Predictors of Very Poor Outcome after Mechanical Thrombectomy for Acute Basilar Artery Occlusion.

Prognosis for patients with acute basilar artery occlusion (BAO) remains poor. Successful revascularization is a main predictor of favorable clinical outcomes after mechanical thrombectomy for BAO. However, even if mechanical thrombectomy is successful, some patients have a poor clinical outcome, including vegetative state and mortality. This study investigated the factors that are predictive of extremely poor clinical outcomes despite successful revascularization after mechanical thrombectomy for BAO. We evaluated 35 consecutive patients who presented with acute ischemic stroke due to BAO and who were successfully treated with mechanical thrombectomy. A very poor outcome was defined as a modified Rankin Scale (mRS) score of 5 or 6 at 3 months after treatment. The associations between the clinical, imaging, procedural factors, and poor outcome were evaluated. Using univariate analyses, there were significant differences in the preoperative National Institute of Health Stroke Scale (NIHSS) score (22.0 ± 9.0 vs. 30.5 ± 4.3, p <0.001), and infarct volume in brain stem (0.11 ± 0.19 cc vs. 2.55 ± 1.56 cc, p <0.001) between the control and very poor outcome groups. In receiver operating characteristic (ROC) curve analysis, the area under ROC curve of infarct volume in brain stem was 0.891 to predict very poor outcome. Preoperative infarct volume in brain stem is strong predictor for very poor outcome. The infarct volume in brain stem is useful for deciding treatment indications.

The rare sugar D-tagatose protects plants from downy mildews and is a safe fungicidal agrochemical.

The rare sugar D-tagatose is a safe natural product used as a commercial food ingredient. Here, we show that D-tagatose controls a wide range of plant diseases and focus on downy mildews to analyze its mode of action. It likely acts directly on the pathogen, rather than as a plant defense activator. Synthesis of mannan and related products of D-mannose metabolism are essential for development of fungi and oomycetes; D-tagatose inhibits the first step of mannose metabolism, the phosphorylation of D-fructose to D-fructose 6-phosphate by fructokinase, and also produces D-tagatose 6-phosphate. D-Tagatose 6-phosphate sequentially inhibits phosphomannose isomerase, causing a reduction in D-glucose 6-phosphate and D-fructose 6-phosphate, common substrates for glycolysis, and in D-mannose 6-phosphate, needed to synthesize mannan and related products. These chain-inhibitory effects on metabolic steps are significant enough to block initial infection and structural development needed for reproduction such as conidiophore and conidiospore formation of downy mildew.

Development of a novel fungicide, tolprocarb.

Tolprocarb developed by Mitsui Chemicals Agro, Inc. (Tokyo, Japan) was discovered as a new oomycete fungicide. However, its antifungal spectrum and action mechanisms against fungi are completely different from those of the original compound, iprovalicarb. Tolprocarb has a potent and highly controlled effect on a rice blast fungus Magnaporthe grisea, and its mode of action was revealed to be the inhibition of polyketide synthase in the melanin biosynthesis pathway. In addition, tolprocarb induced systemic acquired resistance in Arabidopsis thaliana and rice (Oryza sativa L.). Owing to these double modes of action, tolprocarb can effectively control not only rice blast but also bacterial diseases, and has a low risk of developing fungicide-resistant isolates. Tolprocarb also provides long-term residual activity. A meta-analysis was performed in order to demonstrate tolprocarb's superior control against panicle blast in paddy fields. In addition, tolprocarb did not show cross-resistance against the fungi that are resistant to dehydratase inhibitor in melanin biosynthesis (Melanin Biosynthesis Inhibitor-Dehydratase; MBI-D) or respiratory complex III: cytochrome bc 1 at Quinone outside site inhibitor (Quinone outside Inhibitor; QoI). Owing to its stable effects, tolprocarb appears to be a suitable choice for practical use against fungi in the rice production field.

Severe Vasospasm of the Middle Cerebral Artery after Mechanical Thrombectomy Due to Infective Endocarditis: An Autopsy Case.

Untreated infective endocarditis (IE) often produces infective emboli in major cerebral arteries. We describe a case of middle cerebral artery occlusion due to IE, which caused severe vasospasm and reocclusion after mechanical thrombectomy (MT). We present the pathologic findings of the occluded middle cerebral artery and investigate the precautions to be taken while performing MT due to IE. A 72-year-old man with atrial fibrillation treated with dabigatran presented with right hemiparesis and aphasia. A diffusion-weighted image showed a high-intensity area in the left temporoparietal junction, and magnetic resonance angiography revealed a left M2 occlusion. Because of an elevated activated partial thromboplastin time, the thrombolytic therapy was contraindicated; instead, MT was performed. Just after the withdrawal of a stent retriever, the left M2 segment showed severe vasospasm. The next day, the left M2 segment reoccluded. Transthoracic echocardiogram and blood culture findings revealed IE. On the ninth day, the patient died. According to the autopsy report, the cause of death was pulmonary embolism. Pathologic analysis of the occluded M2 segment revealed fibrin thrombi containing vast amounts of neutrophils and invasion of neutrophils into the internal elastic lamina. Severe vasospasm was thought to have occurred because the vascular injury caused by the stent retriever in the vessel had a marked inflammation background. Our findings suggest that devices that are less invasive to the vascular wall are required for performing MT due to IE. The Penumbra aspiration system is thought to be a suitable device.

Synthesis and activities of tolprocarb derivatives against Pyricularia oryzae: relationships among the activities for polyketide synthase, melanin biosynthesis, and rice blast.

The target site of tolprocarb has been reported to be polyketide synthase (PKS). Here, we evaluated the activities for Pyricularia oryzae PKS and melanin biosynthesis as well as the control efficacy of rice blast using a series of tolprocarb derivatives. A comparison of the inhibitory activities of PKS and melanin biosynthesis revealed a linear relationship (r 2=0.90), confirming PKS as the target site of tolprocarb. A compound beyond this relationship was metabolized by P. oryzae to an inactive compound. The control efficacy of rice blast was explained using the melting point and either the inhibitory activity of PKS or melanin biosynthesis. Structure-activity analysis revealed that both end parts of tolprocarb preferred hydrophobic groups, and the chirality of the substituent in the middle part significantly influenced the activities. These relationships will provide useful information for the development of novel PKS inhibitors.

The discovery of dinotefuran: a novel neonicotinoid.

Dinotefuran (MTI-446: (RS)-1-methyl-2-nitro-3-(tetrahydro-3-furylmethyl)guanidine) is a new neonicotinoid commercialized by Mitsui Chemicals. Research led to this novel neonicotinoid by the removal of the chloropyridine or chlorothiazole ring that had been considered as indispensable for neonicotinoides. The research advanced as follows; (1) selection of acetylcholine for the lead compound, (2) recognition of the insecticidal advantages of 3-methoxypropyl compounds, (3) synthesis of (+/-)-tetrahydro-3-furylmethyl compounds by cyclization of the 3-methoxypropyl moiety. It resulted in dinotefuran which has a (+/-)-tetrahydro-3-furylmethyl moiety instead of a halogenated aromatic heterocyclic ring, and belongs to the third-generation neonicotinoids (sub-class: furanicotinyl compounds).