Turicibacter faecis sp. nov., isolated from faeces of heart failure mouse model.

Strain TC023T, a Gram-positive, long, rod-shaped, spore-forming anaerobe, was isolated from the faeces of a heart failure mouse model. The strain formed greyish-white coloured colonies with a convex elevation on brain-heart infusion medium supplemented with 0.1 % sodium taurocholate, incubated at 37 °C for 2 days. Taxonomic analysis based on the 16S rRNA gene sequence showed that TC023T belonged to the genus Turicibacter, and was closely related to Turicibacter bilis MMM721T (97.6 %) and Turicibacter sanguinis MOL361T (97.4 %). The whole genome of the strain has a G+C content of 37.3 mol%. The average nucleotide identity and genome-to-genome distance between TC023T and Turicibacter bilis MMM721T were 77.6 % and 24.3 %, respectively, and those with Turicibacter sanguinis MOL361T were 75.4 % and 24.3 %, respectively. These genotypic, phenotypic, and biochemical analyses indicated that the isolate represents a novel species in the genus Turicibacter, and the name Turicibacter faecis sp. nov. is proposed. The type strain is TC023T (RIMD 2002001T=TSD 372T).

Rationale and Design of Prospective, Multicenter, Double-Arm Clinical Trial to Investigate the Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus (TOP-HFPEF Trial).

BACKGROUND: Recent large clinical trials have revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes not only in patients with heart failure with reduced ejection fraction, but also in patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF). However, the effect of SGLT2 inhibitors on left ventricular (LV) diastolic function is still controversial. METHODS AND RESULTS: The TOP-HFPEF trial (Efficacy of Tofogliflozin on Left Ventricular Diastolic Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes Mellitus) is a multicenter, double-arm, open-label, confirmatory, investigator-initiated clinical study to investigate the effect of SGLT2 inhibitor on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus. The participants are randomly assigned (1:1) to the tofogliflozin group (20 mg once daily) or the control group (administration or continuation of antidiabetic drugs other than SGLT2 inhibitors). The estimated number of patients to be enrolled in this trial is 90 in total (45 in each group). The participants are followed up for 52 weeks with tofogliflozin or control drugs. The primary endpoint is the change in E/e' assessed by echocardiography from the baseline to the end of this study (52 weeks). This trial will also evaluate the effects of tofogliflozin on cardiovascular events, biomarkers, other echocardiographic parameters, the occurrence of atrial fibrillation, and renal function. CONCLUSIONS: The TOP-HFPEF trial will clarify the efficacy of an SGLT2 inhibitor, tofogliflozin, on LV diastolic function in patients with HFpEF and type 2 diabetes mellitus.

Relative B-Type Natriuretic Peptide Deficiency May Exist in Diastolic Dysfunction in Subclinical Population.

Background: Heart failure patients are deficient in B-type natriuretic peptide (BNP) but the significance of subclinical BNP deficiency is unclear. Methods and Results: A total of 1,398 subjects without cardiovascular disease, with left ventricular ejection fraction (LVEF) ≥50% and BNP level <100 pg/mL, were selected from a 2005-2008 health checkup in Arita-cho, Japan, and divided into 2 groups: with and without LV diastolic dysfunction (DD+ or DD-). We performed propensity score matching on non-cardiac factors affecting BNP levels and analyzed 470 subjects in each group (372/940 men; median age, 66 years). The DD(+) group showed higher lateral E/e', an index of estimated left ventricular filling pressure, and greater prevalence of concentric hypertrophy (CH) despite similar BNP levels, suggesting a relative deficiency of BNP in DD(+) compared with DD(-). Multivariable logistic regression analysis revealed an increase in BNP correlated with decreased odds of CH (adjusted odds ratio [aOR] 0.663, 95% confidence interval (CI) 0.484-0.909, P=0.011), whereas an increase in lateral E/e' was associated with increased odds of CH (aOR, 2.881; 95% CI, 1.390-5.973; P=0.004). Furthermore, CH in combination with diastolic dysfunction independently predicted major adverse cardiovascular events (hazard ratio 3.272, 95% CI 1.215-8.809; P=0.019). Conclusions: Relative BNP deficiency was associated with CH, which had a poor prognosis in patients with diastolic dysfunction.

Effects of flusulfamide on spore germination of Plasmodiophora brassicae.

Flusulfamide inhibits germination of Plasmodiophora brassicae resting spores to suppress clubroot disease, but its mechanism of action on the germination of P. brassicae resting spores remains unclear. In this study, P. brassicae resting spores were treated with flusulfamide and visualized using transmission electron microscopy (TEM). The gene expression of P. brassicae resting spores was analyzed using RT-PCR, followed by immunoblotting analysis. TEM results revealed that flusulfamide suppressed the primary zoosporogenesis of P. brassicae resting spores during the early phase, and RT-PCR results revealed that flusulfamide affected the gene expression during the germination of the resting spores. Immunoblot and RT-qPCR analyses revealed that PbCyp3, an immunophilin (peptidyl-prolyl-isomerase) gene, was highly expressed, resulting in the unusual accumulation of PbCYP3 protein in P. brassicae resting spores immediately after treatment with flusulfamide. This suggests that flusulfamide may cause aberrant folding of proteins involved in primary zoosporogenesis, thereby inhibiting germination.

Electrolytic Hydrogen Release from Hydrogen Boride Sheets.

Solid-state hydrogen storage materials are safe and lightweight hydrogen carriers. Among the various solid-state hydrogen carriers, hydrogen boride (HB) sheets possess a high gravimetric hydrogen capacity (8.5 wt%). However, heating at high temperatures and/or strong ultraviolet illumination is required to release hydrogen (H2 ) from HB sheets. In this study, the electrochemical H2 release from HB sheets using a dispersion system in an organic solvent without other proton sources is investigated. H2 molecules are released from the HB sheets under the application of a cathodic potential. The Faradaic efficiency for H2 release from HB sheets reached >90%, and the onset potential for H2 release is -0.445 V versus Ag/Ag+ , which is more positive than those from other proton sources, such as water or formic acid, under the same electrochemical conditions. The total electrochemically released H2 in a long-time experiment reached ≈100% of the hydrogen capacity of HB sheets. The H2 release from HB sheets is driven by a small bias; thus, they can be applied as safe and lightweight hydrogen carriers with economical hydrogen release properties.

Third nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2020 and 2021: Antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum ß-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan.

Metabolic syndrome is linked to the incidence of pancreatic cancer.

Background: Although previous studies have showed that metabolic syndrome is one of the contributors of pancreatic cancer, there is no clear consensus that early stages of metabolic syndrome are linked to increased incidence of pancreatic cancer. Therefore, we confirmed the linkage between metabolic syndrome and pancreatic cancer, and shown that even early stage of metabolic syndrome is linked to pancreatic cancer in the retrospective observational study. Methods: We recruited approximately 4.6 million Japanese in 2005 and followed up these subjects for more than 10 years. At the time of the enrollment, after obtaining clinical data with prescribed drugs and examining the presence or absence of metabolic syndrome (MetS), we followed up on these subjects with and without MetS to examine the incidence of pancreatic cancer. The modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) were used to define MetS. Findings: During the 40.7-month average follow-up period for 2,707,296 subjects with complete data for identifying MetS and important risk factors without pancreatic cancer before the enrollment, 87,857 suffered from pancreatic cancer. Pancreatic cancers occurred in 16,154 of 331,229 subjects (4.9%) in the MetS group and 71,703 of 2,376,067 patients (3.0%) in the non-MetS group (hazard ratio (HR), 1.37; 95% confidence interval [CI], 1.34-1.39; p < 0.0001 after the adjustment with age, smoking and sex). As the number of the constituent factors of MetS increased from one to five, the incidence of pancreatic cancer correspondingly increased (HR: 1.11, 1.23, 1.42, 1.66 and 2.03 using Cox proportional hazard models, p < 0.0001 each). When we defined MetS using the Japanese criteria, the results are in accord with the results using NCEP/ATPIII. Especially pre-metabolic syndrome (pre-MetS) in the Japanese criteria was tightly linked to the incidence of pancreatic cancers. Interpretation: MetS is confirmed to be linked to pancreatic cancer. Although we cannot conclude causality. We also demonstrated the link between pre-MetS and pancreatic cancer. Funding: The sponsors of the study were Japanese Heart Foundation and Japan Cardiovascular Research Foundation. This is also partially supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and Grants-in-Aid from the Japan Agency for Medical Research and Development.

Pathogenicity chromosome of Fusarium oxysporum f. sp. cepae.

Fusarium oxysporum f. sp. cepae (Foc) is the causative agent of Fusarium basal rot disease in onions, which leads to catastrophic global crop production losses. Therefore, the interaction of Foc with its host has been actively investigated, and the pathogen-specific (PS) regions of the British strain Foc_FUS2 have been identified. However, it has not been experimentally determined whether the identified PS region plays a role in pathogenicity. To identify the pathogenicity chromosome in the Japanese strain Foc_TA, we initially screened effector candidates, defined as small proteins with a signal peptide that contain two or more cysteines, from genome sequence data. Twenty-one candidate effectors were identified, five of which were expressed during infection. Of the expressed effector candidates, four were located on the 4-Mb-sized chromosome in Foc_TA. To clarify the relationship between pathogenicity and the 4-Mb-sized chromosome in Foc_TA, nine putative 4-Mb-sized chromosome loss strains were generated by treatment with benomyl (a mitotic inhibitor drug). A pathogenicity test with putative 4-Mb-sized chromosome loss strains showed that these strains were impaired in their pathogenicity toward onions. Genome analysis of three putative 4-Mb-sized chromosome loss strains revealed that two strains lost a 4-Mb-sized chromosome in common, and another strain maintained a 0.9-Mb region of the 4-Mb-sized chromosome. Our findings show that the 4-Mb-sized chromosome is the pathogenicity chromosome in Foc_TA, and the 3.1-Mb region within the 4-Mb-sized chromosome is required for full pathogenicity toward onion.

The SIX5 Protein in Fusarium oxysporum f. sp. cepae Acts as an Avirulence Effector toward Shallot (Allium cepa L. Aggregatum Group).

Fusarium oxysporum f. sp. cepae (Foc) causes basal rot disease in Allium species, including onions (Allium cepa L.) and shallots (A. cepa L. Aggregatum group). Among Allium species, shallots can be crossbred with onions and are relatively more resistant to Foc than onions. Thus, shallots are considered a potential disease-resistant resource for onions. However, the mechanisms underlying the molecular interactions between shallots and Foc remain unclear. This study demonstrated that SIX5, an effector derived from Foc (FocSIX5), acts as an avirulence effector in shallots. We achieved this by generating a FocSIX5 gene knockout mutant in Foc, for which experiments which revealed that it caused more severe wilt symptoms in Foc-resistant shallots than the wild-type Foc and FocSIX5 gene complementation mutants. Moreover, we demonstrated that a single amino acid substitution (R67K) in FocSIX5 was insufficient to overcome shallot resistance to Foc.

Multi-gene Liquid Biopsy to Detect Resistance to First-line Osimertinib in Patients With EGFR-mutated Lung Adenocarcinoma.

BACKGROUND/AIM: Osimertinib is currently used as a first-line treatment for EGFR-mutated non-small cell lung cancer, and the emergence of drug resistance poses a substantial challenge. Liquid biopsy with a multi-gene panel can examine both the molecular mechanisms and possibility of early resistance diagnosis. PATIENTS AND METHODS: We used a molecular barcode library construction kit (Archer® LiquidPlex™) that allowed the analysis of multiple cancer-related genes using cell-free DNA from the plasma samples of patients. We collected plasma from 17 consecutive patients with lung adenocarcinoma at our hospital at various time points and cell-free DNA was extracted and subjected to LiquidPlex analysis. RESULTS: Plasma DNA concentration was not associated with the presence or absence of resistance to osimertinib. The pathological mutations detected using next-generation sequencing in the resistant specimens were in MAP2K1, PIK3CA, TP53, BRAF, and EGFR. Among the recurrent cases, EGFR mutations identified at the initial diagnosis were detected within 6 months before relapse confirmation in four cases (average 88 days). Many of the recurrent cases without detection of known EGFR mutations in the liquid biopsy showed a longer interval between the detection of relapse and the last blood draw for the liquid biopsy (average 255 days). CONCLUSION: Frequent liquid biopsies are useful for identifying known EGFR mutations as markers for early detection of relapse. Several cancer driver mutations were observed, suggesting a variety of mechanisms of resistance in first-line osimertinib-treated lung adenocarcinoma.

A Rare Case of Sinonasal Seromucinous Hamartoma Developing from the Nasal Septum.

A 45-year-old man presented with a history of chronic left nasal congestion. Nasal endoscopy revealed a pedunculated polypoid mass with glandular epithelium surface on the posterior nasal septum. Computed tomography revealed a 25-mm mass-like growth in the left posterior nasal cavity attached to the nasal septum with a stalk. The patient underwent transnasal endoscopic surgery, and the tumor was removed under a block with safety margin. The final pathological diagnosis was sinonasal seromucinous hamartoma (SH). Sinonasal SH is a rare tumor with only 31 reported cases. Transnasal endoscopic surgery is currently the first-line treatment for sinonasal SH. Differential diagnoses of this lesion include inflammatory polyps, respiratory epithelial adenomatoid hamartoma, and adenocarcinoma. Although SH is a benign tumor, its progression to adenocarcinoma has been reported. Therefore, unilateral posterior nasal tumors must be diagnosed precisely.

Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial.

Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.

The third nationwide surveillance of antimicrobial susceptibility against Neisseria gonorrhoeae from male urethritis in Japan, 2016-2017.

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were ß-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan.

Effective treatment of hydrogen boride sheets for long-term stabilization.

Two-dimensional hydrogen boride (HB) sheets prepared via the ion-exchange reaction from magnesium diboride (MgB2) are known to possess several intriguing properties for a wide range of applications; however, previous reports have shown that the sheets prepared using this method contain small amounts of reactive components, making them unsuitable for certain applications. Therefore, developing a method for preparing HB sheets that exhibit long-term stability and do not contain reactive species is essential. In this study, we developed an effective treatment method for achieving long-term stabilization of HB sheets. We found that by pre-treating the HB sheets with water and then filtering the dried product from an acetonitrile dispersion, we could achieve excellent long-term stability over nine months. This stability was maintained even outside of a glovebox, with no H2 released by the decomposition and/or reaction. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) absorption spectroscopy measurements revealed that the sample exhibited pure HB characteristics with negatively charged boron and B-H-B and terminal B-H bonds, even after nine months of storage. Furthermore, based on thermal desorption spectroscopy (TDS) measurements, the presence of reactive species in the as-prepared HB sheets is attributed to fluctuating B-H bonds with relatively weak binding energies that can be removed using the method developed in this study.

Genome-Wide Characterization of Effector Protein-Encoding Genes in Sclerospora graminicola and Its Validation in Response to Pearl Millet Downy Mildew Disease Stress.

Pearl millet [Pennisetum glaucum (L.) R. Br.] is the essential food crop for over ninety million people living in drier parts of India and South Africa. Pearl millet crop production is harshly hindered by numerous biotic stresses. Sclerospora graminicola causes downy mildew disease in pearl millet. Effectors are the proteins secreted by several fungi and bacteria that manipulate the host cell structure and function. This current study aims to identify genes encoding effector proteins from the S. graminicola genome and validate them through molecular techniques. In silico analyses were employed for candidate effector prediction. A total of 845 secretory transmembrane proteins were predicted, out of which 35 proteins carrying LxLFLAK (Leucine-any amino acid-Phenylalanine-Leucine-Alanine-Lysine) motif were crinkler, 52 RxLR (Arginine, any amino acid, Leucine, Arginine), and 17 RxLR-dEER putative effector proteins. Gene validation analysis of 17 RxLR-dEER effector protein-producing genes was carried out, of which 5genes were amplified on the gel. These novel gene sequences were submitted to NCBI. This study is the first report on the identification and characterization of effector genes in Sclerospora graminicola. This dataset will aid in the integration of effector classes that act independently, paving the way to investigate how pearl millet responds to effector protein interactions. These results will assist in identifying functional effector proteins involving the omic approach using newer bioinformatics tools to protect pearl millet plants against downy mildew stress. Considered together, the identified effector protein-encoding functional genes can be utilized in screening oomycetes downy mildew diseases in other crops across the globe.

Clinical and genomic features of non-small cell lung cancer occurring in families.

BACKGROUND: Exposure to environmental carcinogens, such as through smoking, is a major factor in the carcinogenesis of non-small cell lung cancer (NSCLC). However, genetic factors may also contribute. METHODS: To identify candidate tumor suppressor genes for NSCLC, we included 23 patients (10 related pairs and 3 individuals) with NSCLC who had other NSCLC-affected first-degree relatives in a local hospital. Exome analyses for both germline and somatic (NSCLC specimens) DNA were performed for 17 cases. Germline exome data of these 17 cases revealed that most of the short variants were identical to the variants in 14KJPN (a Japanese reference genome panel of more than 14 000 individuals) and only a nonsynonymous variant in the DHODH gene, p.A347T, was shared between a pair of NSCLC patients in the same family. This variant is a known pathogenic variant of the gene for Miller syndrome. RESULTS: Somatic genetic alterations in the exome data of our samples showed frequent mutations in the EGFR and TP53 genes. Principal component analysis of the patterns of 96 types of single nucleotide variants (SNVs) suggested the existence of unique mechanisms inducing somatic SNVs in each family. Delineation of mutational signatures of the somatic SNVs with deconstructSigs for the pair of germline pathogenic DHODH variant-positive cases showed that the mutational signatures of these cases included SBS3 (homologous recombination repair defect), SBS6, 15 (DNA mismatch repair), and SBS7 (ultraviolet exposure), suggesting that disordered pyrimidine production causes increased errors in DNA repair systems in these cases. CONCLUSION: Our results suggest the importance of the detailed collection of data on environmental exposure along with genetic information on NSCLC patients to identify the unique combinations that cause lung tumorigenesis in a particular family.

Molecular Analysis of MgO Nanoparticle-Induced Immunity against Fusarium Wilt in Tomato.

Fusarium wilt, caused by Fusarium oxysporum f. sp. lycopersici (FOL), is a devastating soilborne disease in tomatoes. Magnesium oxide nanoparticles (MgO NPs) induce strong immunity against Fusarium wilt in tomatoes. However, the mechanisms underlying this immunity remain poorly understood. Comparative transcriptome analysis and microscopy of tomato roots were performed to determine the mechanism of MgO NP-induced immunity against FOL. Eight transcriptomes were prepared from tomato roots treated under eight different conditions. Differentially expressed genes were compared among the transcriptomes. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that in tomato roots pretreated with MgO NPs, Rcr3 encoding apoplastic protease and RbohD encoding NADPH oxidase were upregulated when challenge-inoculated with FOL. The gene encoding glycine-rich protein 4 (SlGRP4) was chosen for further analysis. SlGRP4 was rapidly transcribed in roots pretreated with MgO NPs and inoculated with FOL. Immunomicroscopy analysis showed that SlGRP4 accumulated in the cell walls of epidermal and vascular vessel cells of roots pretreated with MgO NPs, but upon FOL inoculation, SlGRP4 further accumulated in the cell walls of cortical tissues within 48 h. The results provide new insights into the probable mechanisms of MgO NP-induced tomato immunity against Fusarium wilt.

A Rare Case of Scalp Metastasis from Encapsulated Angioinvasive Follicular Thyroid Carcinoma.

Cutaneous metastases from thyroid carcinomas are extremely rare; however, the scalp is a common site for cutaneous metastases from follicular thyroid carcinomas (FTCs). We report the case of a 77-year-old male patient with a blood-rich scalp lesion. Histopathological tests of punch biopsy specimens revealed subcutaneous well-formed follicular structures that were similar to those found in the thyroid gland. Immunohistochemistry using thyroid transcription factor-1 (TTF-1) and paired-box gene family 8 (PAX8) revealed an FTC metastasis. We performed total thyroidectomy and resection of the scalp lesion at the same time and administered postoperative radioactive iodine treatment. The primary thyroid lesion was diagnosed as an FTC based on extracapsular extension and vessel invasion. The patient has not experienced disease recurrence since the treatment. When scalp metastasis of thyroid carcinoma is suspected, we recommend total extirpation, including the primary tumor and scalp metastasis, for an improved prognosis.

Effect of eplerenone on clinical stability of Japanese patients with acute heart failure.

BACKGROUND: In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients' clinical stability is warranted. METHODS: The EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months. Cox proportional hazards and mixed-effects models were used for analyses. RESULTS: Three hundred patients were included (mean age, 67 ± 13 years; 73% males). The median furosemide equivalent dose was 40 (20-62) mg at randomization. Patients with higher furosemide-equivalent doses had more severe signs and symptoms of congestion and a higher risk of all-cause mortality or HF hospitalization during 6-month follow-up (adjusted-hazard ratio per 10 mg/day increase = 1.25, 95% confidence interval: 1.05-1.49). Eplerenone significantly decreased furosemide-equivalent diuretic doses and b-type natriuretic levels throughout the follow-up (overall-joint-p < 0.05 for both) and reduced E/e' and inferior vena cava diameter at 4 weeks (both p < 0.05). Additionally, eplerenone significantly reduced left ventricular (LV) end-diastolic diameter at 24 weeks (p < 0.05). CONCLUSIONS: Eplerenone treatment improved the clinical stability particularly during short period following hospitalization for AHF, translated by lower diuretic doses, natriuretic peptide levels, indirect markers of filling pressure and venous congestion, and a smaller LV volume.