Incidence of perioperative hypotension in patients undergoing transurethral resection of bladder tumor after oral 5-aminolevulinic acid administration: a retrospective multicenter cohort study.

PURPOSE: Tumors can be visualized using 5-Aminolevulinic acid hydrochloride (5-ALA) during transurethral resection of bladder tumors (TURBT). Hypotension is an adverse effect of 5-ALA; however, its incidence and morbidity rates are unknown. This study aimed to describe the incidence of perioperative hypotension and identify risk factors for hypotension among patients after 5-ALA administration in TURBT. METHODS: This retrospective multicenter cohort study was conducted at three general hospitals in Japan. Adult patients who underwent elective TURBT after 5-ALA administration between April 2018 and August 2020 were included. The primary outcome was the incidence of perioperative hypotension (mean blood pressure < 65 mmHg). The secondary outcomes were the use of vasoactive agents and adverse events, including urgent intensive care unit (ICU) admission. Multivariate logistic regression analysis was performed to investigate risk factors of the incidence of intraoperative hypotension. RESULTS: The median age of 261 patients was 73 years. General anesthesia was induced in 252 patients. The intraoperative hypotension was observed in 246 (94.3%) patients. Three patients (1.1%) were urgently admitted to the ICU for continued vasoactive agent use after surgery. All three patients had renal dysfunction. Multivariate logistic regression analysis revealed that general anesthesia was significantly associated with intraoperative hypotension (adjusted odds ratio, 17.94; 95% confidence interval, 3.21-100.81). CONCLUSION: The incidence of hypotension in patients undergoing TURBT after 5-ALA administration was 94.3%. The incidence of urgent ICU admission with prolonged hypotension was 1.1% in all patients with renal dysfunction. General anesthesia was significantly associated with intraoperative hypotension.

A novel mutant allele at the Cleistogamy 1 locus in barley.

KEY MESSAGE: A chasmogamous mutant was induced by exposing a cleistogamous cultivar to sodium azide. The altered cly1 sequence in the mutant was not in the miR172 binding site, as is the case in other known cleistogamous alleles, but rather in a region encoding one of the gene product's two AP2 domains. The genetic basis of cleistogamy (in which pollination occurs before the flower opens) in barley is centered on the Cleistogamy 1 locus (cly1). The sequence of the microRNA (miR172)-targeting site in the gene, which belongs to the APETALA2 family, differs between cleistogamous and chasmogamous cultivars at a single nucleotide position, resulting in the differential ability of the lodicules to swell. Here, mutagenesis of the barley cultivar 'Misato Golden' (which carries the cly1.b allele), achieved using sodium azide, was used to induce a change from cleistogamy to chasmogamy (non-cleistogamous flowering). The cly1 coding sequence in the selected mutant differed from that of cly1.b by two non-synonymous mutations, one of which was responsible for an altered residue in one of the AP2 domains present in the Cly1 protein. Although there was no difference in the miR172 targeting site between cly1.b and the novel allele (designated cly1.b3), the mutant's lodicules' ability to swell was indistinguishable from that observed in cultivars carrying the chasmogamous allele Cly1.a. The phenotype of cly1.b3/cly1.b, cly1.b3/cly1.b2 and cly1.b3/cly1.c heterozygotes indicated that cly1.b3 is recessive or incompletely dominant with respect to these alleles.

New dot-blot method for evaluating the effect of inactivators on mite and Japanese cedar pollen allergens.

As a method of evaluating the effect of inactivators on allergens while suppressing the effect of inactivator on the assay, we developed new dot-blot method that combines immunostaining and protein detection methods. This method is useful for evaluating whether the inactivator can inactivate allergens rather than removing them from the assay.

Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells.

The classical view of neural plate development held that it arises from the ectoderm, after its separation from the mesodermal and endodermal lineages. However, recent cell-lineage-tracing experiments indicate that the caudal neural plate and paraxial mesoderm are generated from common bipotential axial stem cells originating from the caudal lateral epiblast. Tbx6 null mutant mouse embryos which produce ectopic neural tubes at the expense of paraxial mesoderm must provide a clue to the regulatory mechanism underlying this neural versus mesodermal fate choice. Here we demonstrate that Tbx6-dependent regulation of Sox2 determines the fate of axial stem cells. In wild-type embryos, enhancer N1 of the neural primordial gene Sox2 is activated in the caudal lateral epiblast, and the cells staying in the superficial layer sustain N1 activity and activate Sox2 expression in the neural plate. In contrast, the cells destined to become mesoderm activate Tbx6 and turn off enhancer N1 before migrating into the paraxial mesoderm compartment. In Tbx6 mutant embryos, however, enhancer N1 activity persists in the paraxial mesoderm compartment, eliciting ectopic Sox2 activation and transforming the paraxial mesoderm into neural tubes. An enhancer-N1-specific deletion mutation introduced into Tbx6 mutant embryos prevented this Sox2 activation in the mesodermal compartment and subsequent development of ectopic neural tubes, indicating that Tbx6 regulates Sox2 via enhancer N1. Tbx6-dependent repression of Wnt3a in the paraxial mesodermal compartment is implicated in this regulatory process. Paraxial mesoderm-specific misexpression of a Sox2 transgene in wild-type embryos resulted in ectopic neural tube development. Thus, Tbx6 represses Sox2 by inactivating enhancer N1 to inhibit neural development, and this is an essential step for the specification of paraxial mesoderm from the axial stem cells.

Sarcopenia is a Negative Prognostic Factor After Curative Resection of Colorectal Cancer.

BACKGROUND: Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study was performed to evaluate the prognostic significance of skeletal muscle depletion in patients with resectable stage I-III colorectal cancer (CRC). METHODS: We conducted a retrospective analysis of 220 consecutive patients with stage I-III CRC who underwent curative resection. The skeletal muscle cross-sectional area was measured by preoperative computed tomography. The lowest sex-specific quartile of skeletal muscle mass was classified as sarcopenia. Factors contributing to recurrence-free survival (RFS) were analyzed by univariate and multivariate Cox proportional hazard models. RESULTS: Of 220 patients who met our inclusion criteria, 55 (25 %) had sarcopenia. The median follow-up duration was 41.4 months. Patients with sarcopenia were younger and had higher carcinoembryonic antigen levels than patients without sarcopenia. RFS and overall survival (OS) were significantly shorter in patients with sarcopenia than those without (5-year RFS, 56 vs. 79 %, log-rank p = 0.006; 5-year OS, 68 vs. 85 %, log-rank p = 0.015). Multivariate Cox regression analysis revealed that sarcopenia was independently associated with shorter RFS (hazard ratio [HR] 2.176; 95 % confidence interval [CI] 1.200-3.943; p = 0.010) and OS (HR 2.270; 95 % CI 1.147-4.494; p = 0.019). The influence of sarcopenia on patient outcome was modified by age at surgery (p value for interaction = 0.026); sarcopenia was associated with a poor prognosis, especially in young patients (log-rank p < 0.001). CONCLUSIONS: Sarcopenia negatively impacts survival in patients undergoing curative resection for stage I-III CRC.

Micronodular thymoma with lymphoid stroma: an immunohistochemical study of the distribution of Langerhans cells and mature dendritic cells in six patients.

AIMS: Micronodular thymoma with lymphoid stroma (MNT) is an uncommon variant of thymoma, characterized by multiple small nodules consisting of type A thymoma-like cells, which are separated by abundant B lymphocytes. The aim of the study was to elucidate the pathogenesis of the stromal lymphoid hyperplasia, which is currently unclear. METHODS AND RESULTS: We retrieved six cases of MNT, and immunohistochemically examined the number and distribution of Langerhans cells (LCs) and mature dendritic cells (DCs), and compared them with those in type A and type AB thymomas. Many LCs were present within the small tumour nests, but LCs were rarely seen in the stroma (75.5/HPF versus 6.1/HPF, P < 0.0001). In contrast, mature DCs were present mainly in the surrounding stroma rather than within the tumour nodules (63.5/HPF versus 6.0/HPF, P < 0.0001), forming clusters with mature T lymphocytes adjacent to lymphoid follicles. In large nodules, as well as in type A and type AB thymomas, a few scattered LCs and DCs were identified. All patients were still alive and well. CONCLUSIONS: Our results suggest that LCs take up tumour antigens and migrate to the stroma, where they mature and form clusters with T lymphocytes to activate them, resulting in lymphoid follicle formation. The favourable clinical behaviour may be attributable to the immune response induced by LCs.

Predictors of long-term survival in patients with stage IV colorectal cancer with multi-organ metastases: a single-center retrospective analysis.

BACKGROUND: The prognosis for most patients with stage IV colorectal cancer (CRC) and multi-organ metastases is poor. However, little information is currently available on prognostic factors in these patients. The aim of this study was to identify predictors of a good prognosis in this patient group. METHODS: This was a single-center retrospective study in which we examined the relationship between patient characteristics and prognosis in 161 stage IV CRC patients with indications for first-line systemic chemotherapy. Cox proportional-hazards models were used to compute hazard ratios (HR) for death, adjusted for clinical and pathological characteristics. RESULTS: Of the 161 patients recruited to the study, 83 had single-organ and 78 had multi-organ metastases. Median survival time was significantly shorter in patients with multi-organ metastases than in those with single-organ metastases (19.2 vs. 42.0 months, respectively; log-rank, P < 0.001). There was no significant difference in survival between patients with metastases in two versus three or more organs (log-rank; P = 0.368). According to univariate analysis, primary tumor sites in the left side of the colon and in the rectum, a pretreatment carcinoembryonic antigen concentration of >50 ng/mL, a well-/moderately differentiated tumor, and R0 resection of metastatic lesions were associated with better overall survival. According to multivariate analysis, left-sided location of the primary tumor [HR 0.414, 95 % confidence interval (CI) 0.216-0.815; P = 0.011] and R0 resection of metastatic lesions (HR 0.247, 95 % CI 0.04 0-0.834; P = 0.021) were independently associated with good prognosis. CONCLUSIONS: Our results indicate that the site of the primary tumor in the left side of the colon and in the rectum and R0 resection of metastatic lesions are predictors of a good prognosis in patients with stage IV CRC and multi-organ metastases.

Temperature-dependent augmentation of ciliary motility by the TRP2 channel in Chlamydomonas reinhardtii.

Temperature is a critical factor for living organisms. Many microorganisms migrate toward preferable temperatures, and this behavior is called thermotaxis. In this study, the molecular and physiological bases for thermotaxis are examined in Chlamydomonas reinhardtii. A mutant with knockout of a transient receptor potential (TRP) channel, trp2-3, showed defective thermotaxis. The swimming velocity and ciliary beat frequency of wild-type Chlamydomonas increase with temperature; however, this temperature-dependent enhancement of motility was almost absent in the trp2-3 mutant. Wild-type Chlamydomonas showed negative thermotaxis, but mutants deficient in the outer or inner dynein arm showed positive thermotaxis and a defect in temperature-dependent increase in swimming velocity, suggesting involvement of both dynein arms in thermotaxis.

A Case of Adult-onset Still's Disease (AOSD) with Gastrointestinal Lesions.

A 51-year-old woman with fever was admitted to our hospital. A computed tomography (CT) scan showed thickened colonic walls. Colonoscopy revealed erosion in the ileum and colon. Adult-onset Still's disease (AOSD) was diagnosed due to a subsequent sore throat and skin rash. Following AOSD treatment, methylprednisolone pulse therapy, followed by prednisolone and cyclosporine, was initiated. Despite achieving a temporary improvement, relapse occurred with fever, abdominal pain, with worsening CT and endoscopic findings. The reappearance of a skin rash confirmed an exacerbation of AOSD. Tocilizumab treatment alleviated the symptoms and improved the endoscopic findings. Considering their correlation with the symptoms and endoscopic findings, the observed gastrointestinal lesions may be linked to AOSD.

Characteristic features of statistical models and machine learning methods derived from pest and disease monitoring datasets.

While many studies have used traditional statistical methods when analysing monitoring data to predict future population dynamics of crop pests and diseases, increasing studies have used machine learning methods. The characteristic features of these methods have not been fully elucidated and arranged. We compared the prediction performance between two statistical and seven machine learning methods using 203 monitoring datasets recorded over several decades on four major crops in Japan and meteorological and geographical information as the explanatory variables. The decision tree and random forest of machine learning were found to be most efficient, while regression models of statistical and machine learning methods were relatively inferior. The best two methods were better for biased and scarce data, while the statistical Bayesian model was better for larger dataset sizes. Therefore, researchers should consider data characteristics when selecting the most appropriate method.

Mechanoresponses mediated by the TRP11 channel in cilia of Chlamydomonas reinhardtii.

Cilia are organelles involved in motility and sensory transduction, but how these two functions coexist has not been elucidated in depth. Here, the involvement of the ciliary transient receptor potential (TRP) channel TRP11 in mechanoresponses is studied in Chlamydomonas reinhardtii using a TRP11-knockout mutant. The mutant has defects in the conversion of the bending mode of the cilium from forward to reverse when tapped with a glass rod, the detachment of cilia when shear is applied, the increase in ciliary beat frequency upon application of mechanical agitation by vortex mixing, and the initiation of gliding while both cilia are attached in opposite directions to a glass surface. These observations indicate that TRP11 can perceive mechanical stimuli with distinct intensities and durations and induce various types of ciliary responses.

Effect of the Timing of Fungicide Application on Fusarium Head Blight and Mycotoxin Contamination in Wheat.

Fungicide application to control Fusarium head blight (FHB) and accompanying mycotoxin contamination in wheat is generally performed at anthesis because wheat is most susceptible to FHB around this stage. In this study, we evaluated the effect of the timing of fungicide application on FHB and mycotoxin (deoxynivalenol and nivalenol) accumulation in wheat based on our previous finding that the late period of grain development (beyond 20 days after anthesis [DAA]) is important to determine the final toxin contamination level in wheat. Thiophanate-methyl fungicide was tested under artificial inoculation conditions in which moisture and inoculum spores were provided throughout the testing period. Eight treatments differing in application timing (anthesis, 10, 20, and 30 DAA) and in the number of applications (0 to 2) were tested for 2 years. The results indicated that fungicide application timing differentially affects FHB (disease) and mycotoxin concentration. Fungicide application at 20 DAA reduced mycotoxin concentration in matured grain without reducing FHB severity, whereas application at anthesis was crucial for reducing FHB. These results and our previous findings suggest that around 20 DAA (late milk stage) is a potentially critical timing for mycotoxin control in wheat.

Anaphylaxis after vaccination for cats in Japan.

Severe adverse reactions in cats after vaccination were examined from 316 cases reported to the Ministry of Agriculture, Forestry and Fisheries (MAFF) in Japan during 15-year period from April 2004 to March 2019. We found that 130 (41%) showed anaphylaxis, and 99 (76%) of the 130 cases of anaphylaxis resulted in death. Veterinarians should be well prepared to deal with vaccine-associated anaphylaxis in cats. Bovine serum albumin (BSA) as indicator of purification was detected at high levels in commercially available feline vaccines. BSA might derive from fetal calf serum in culture media. This study provides useful information about anaphylaxis including critical details of the potential clinical signs associated with adverse events to feline vaccination.

B1 and B2 Sox gene expression during neural plate development in chicken and mouse embryos: universal versus species-dependent features.

Cumulative evidence now indicates pivotal roles for the group B1 Sox genes, Sox1, Sox2 and Sox3 in the genesis and development of neural primordia. Shared functions for the Sox1, Sox2 and Sox3 protein products have also been indicated. This emphasizes the importance and integral role of the group B1 Sox genes in regulating the neural primordia. We here review what is currently known about the expression patterns of both the group B1 Sox genes and the related group B2 Sox21 gene during the embryonic stages when the neural plate develops. These expression profiles are compared between the chicken and mouse embryos, both representatives of amniote species. This comparison indicates a gross conservation of the regulation of individual Sox genes, yet also demonstrates the existence of species-dependent variations, which should be taken into account when data from different species are being compared. To link the expression patterns and transcriptional regulation of these genes, contribution of gene-specific enhancers are discussed. The regulation of B1 Sox genes in the axial stem cells, the common precursors to the posterior neural plate and paraxial mesoderm and located at the posterior end of developing neural plate, is also highlighted in this review. This article thus provides a guide to performing readouts of B1/B2 Sox expression data during neural plate development in amniotes.

Anesthetic Care During Tracheostomy in a Patient with Generalized Tetanus: A Case Report.

Tetanus is a potentially fatal infectious disease caused by the toxins produced by the anaerobic bacterium, Clostridium tetani. Of major concern during the perioperative care of these patients is control of muscle spasms, skeletal rigidity, and autonomic dysfunction. Several of the modern sedative and opioid agents including remifentanil have not been fully evaluated in managing tetanus. We present the intraoperative use of remifentanil in a 75-year-old woman with generalized tetanus who required anesthetic care during placement of a tracheostomy. The end-organ involvement of tetanus is presented, previous reports of anesthetic care reviewed, and the potential utility of remifentanil explored.

Anaphylaxis after rabies vaccination for dogs in Japan.

Severe adverse reactions after rabies vaccination in dogs were examined from 317 cases reported to the Ministry of Agriculture, Forestry and Fisheries (MAFF) in Japan during 15-year period from April 2004 to March 2019. We found that 109 of the 317 dogs showed anaphylaxis (0.15/100,000 vaccinated dogs), and 71 of the 109 cases of anaphylaxis resulted in death (0.10/100,000 vaccinated dogs). We measured bovine serum albumin (BSA) in four commercially available rabies vaccines and found the levels ranged from 0.1 to 16.6 µg/dose. Our survey showed that the rate of anaphylaxis to rabies vaccines in dogs is rare, although some cases of anaphylaxis resulted in death. Veterinarians should be well prepared to deal with vaccine-associated anaphylaxis.

Deoxynivalenol and nivalenol accumulation in wheat infected with Fusarium graminearum during grain development.

The manner in which deoxynivalenol (DON) and nivalenol (NIV) accumulation progresses in wheat grain infected with Fusarium graminearum and the influence of the time of infection on the accumulation of toxins were investigated. Four cultivars were tested in a greenhouse environment, where the plants were spray inoculated at three different stages with a mixture of DON and NIV chemotypes of F. graminearum. The results indicate that high levels of DON and NIV can be produced beyond 20 days after anthesis (DAA), even by early infection. The results of field experiments performed on seven cultivars, where inoculation was conducted using colonized maize kernel inoculum, were consistent with the greenhouse results. In addition, in the greenhouse experiments, late infection, at least as late as 20 DAA, caused grain contamination with these toxins even without clear disease symptoms on the spike. These results indicate the importance of the late stage in grain development in DON and NIV contamination, suggesting that control strategies that cover the late as well as the early stage of grain development should be established to effectively reduce the risk of these toxins' contaminating wheat.

Transgenic Chlamydomonas Expressing Human Transient Receptor Potential Ankyrin 1 (TRPA1) Channels to Assess the Effect of Agonists and Antagonists.

Transient receptor potential ankyrin 1 (TRPA1) channel is an ion channel whose gating is controlled by agonists, such as allyl isothiocyanate (AITC), and temperature. Since TRPA1 is associated with various disease symptoms and chemotherapeutic side effects, it is a frequent target of drug development. To facilitate the screening of TRPA1 agonists and antagonists, this study aimed to develop a simple bioassay for TRPA1 activity. To this end, transgenic Chlamydomonas reinhardtii expressing human TRPA1 was constructed. The transformants exhibited positive phototaxis at high temperatures (≥20°C) but negative phototaxis at low temperatures (≤15°C); wild-type cells showed positive phototaxis at all temperatures examined. In the transgenic cells, negative phototaxis was inhibited by TRPA1 antagonists, such as HC030031, A-967079, and AP18, at low temperatures. Negative phototaxis was induced by TRPA1 agonists, such as icilin and AITC, at high temperatures. The effects of these agonists were blocked by TRPA1 antagonists. In wild-type cells, none of these substances had any effects on phototaxis. These results indicate that the action of TRPA1 agonists and antagonists can be readily assessed using the behavior of C. reinhardtii expressing human TRPA1 as an assessment tool.

Temperature-sensitive mutants of MscL mechanosensitive channel.

MscL is a mechanosensitive channel that undergoes a global conformational change upon application of membrane stretching. To elucidate how the structural stability and flexibility occur, we isolated temperature-sensitive (Ts) mutants of Escherichia coli MscL that allowed cell growth at 32°C but not at 42°C. Two Ts mutants, L86P and D127V, were identified. The L86P mutation occurred in the second transmembrane helix, TM2. Substitution of residues neighbouring L86 with proline also led to a Ts mutation, but the substitution of L86 with other amino acids did not result in a Ts phenotype, indicating that the Ts phenotype was due to a structural change of TM2 helix by the introduction of a proline residue. The D127V mutation was localized in the electrostatic belt of the bundle of cytoplasmic helices, indicating that stability of the pentameric bundle of the cytoplasmic helix affects MscL structure. Together, this study described a novel class of MscL mutations that were correlated with the thermodynamic stability of the MscL structure.

New otonecine-type pyrrolizidine alkaloid from Petasites japonicus.

One new otonecine-type pyrrolizidine alkaloid secopetasitenine (1), along with petasitenine (fukinotoxine, 2), neopetasitenine (3), and senkirkine (4), was isolated from the whole plant of Petasites japonicus. The structure of 1 was determined by spectroscopic analyses and chemical conversion from the known alkaloid petasitenine (2).