Microwave-assisted C-C bond formation of diarylacetylenes and aromatic hydrocarbons on carbon beads under continuous-flow conditions.

The synthesis of polycyclic aromatic compounds generally requires stoichiometric oxidants or homogeneous metal catalysts, however, the risk of contamination of inorganic residues can affect their properties. Here we present a microwave (MW)-assisted platinum on beaded activated carbon (Pt/CB)-catalyzed C-C bond formation of diarylacetylenes and aromatic hydrocarbons under continuous-flow conditions. Various fused aromatic compounds were continuously synthesized via dehydrogenative C(sp2)-C(sp2) and C(sp2)-C(sp3) bond formation with yields of up to 87% without the use of oxidants and bases. An activated, local reaction site on Pt/CB in the flow reaction channel reaching temperatures of more than three hundred degrees Celsius was generated in the catalyst cartridge by selective microwave absorption in CB with an absorption efficiency of > 90%. Mechanistic experiments of the transformation reaction indicated that a constant hydrogen gas supply was essential for activating Pt. This is an ideal reaction with minimal input energy and no waste production.

Microwave Flow: A Perspective on Reactor and Microwave Configurations and the Emergence of Tunable Single-Mode Heating Toward Large-Scale Applications.

Microwave heating in chemical reactions was first reported in 1986. There have since been many reports employing microwave heating in organic chemistry, where microwave heating has afforded higher yields of products in shorter time periods. However, such reactions are challenging to scale in batch due to the limited penetration depth of microwaves as well as the wave propagation dependence on cavity size. Continuous flow has addressed both these issues, enabling scalability of microwave processes. As such, a host of reports employing microwave flow chemistry have emerged, employing various microwave heating and reactor configurations in the context of either custom-built or commercial apparatus. The focus of this review is to present the benefits of microwave heating in the context of continuous flow and to characterize the different types of microwave flow apparatus by their design (oscillator, cavity type and reactor vessel). We advocate the adoption of tunable, solid-state oscillator single-mode microwave flow reactors which are more versatile heaters, impart better process control and energy efficiency toward laboratory and larger-scale synthetic chemistry applications.

Intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute cerebral infarction in a patient with ANCA-associated vasculitis.

We report the case of a 68-year-old man who suddenly developed right hemiparesis. MRI of the brain revealed a new infarction in the left corona radiata, and intravenous rt-PA was administered 100 minutes after the onset of symptoms. After the rt-PA infusion was started, his consciousness declined and the CT revealed bilateral intracerebral hemorrhage. His consciousness did not improve thereafter. He was diagnosed with ANCA-associated vasculitis owing to the high levels of MPO-ANCA and urinary protein and the presence of erythrocytes without any other cause of renal damage. Although ANCA-associated vasculitis rarely involves the central nervous system, intracerebral hemorrhage as well as cerebral infarction may occur. This case provides an important opportunity to explore the implications of intravenous rt-PA therapy for acute cerebral infarction in patients with ANCA-associated vasculitis.

Clinical characteristics of atrial fibrillation-related cardioembolic stroke in patients aged 80 years or older.

AIM: Atrial fibrillation (AF)-related cardioembolic stroke is a serious problem in the aging society. The present study examined the clinical characteristics and outcomes of AF-related cardioembolic stroke in patients aged ≥80 years. METHODS: Between September 2011 and April 2014, consecutive patients with ischemic stroke and AF were retrospectively extracted from the multicenter database. Clinical characteristics were compared between patients aged ≥80 years and <80 years. Multivariate cox proportional hazard models were used to estimate hazard ratios and 95% confidential intervals on 90-day mortality for age of ≥80 years. RESULTS: A total of 253 patients aged ≥80 years (87 men, 86.4 ± 5.0 years) and 196 patients aged <80 years (134 men, 70.4 ± 7.1 years) were included. Patients aged ≥80 years were more frequently female, and more likely to have higher premorbid modified Rankin Scale score (mRS), lower body mass index, previous history of stroke, prior antiplatelet therapy, congestive heart failure, and persistent AF. Patients aged ≥80 years had higher initial National Institutes of Health Stroke Scale score and were more likely to have occlusion of the cervicocephalic arteries, but less likely to receive thrombolysis. Patients aged ≥80 years had a higher mRS and mortality after 3 months. Age of ≥80 years was a significant predictor of 90-day mortality after adjustment for sex (hazard ratio 2.20, 95% confidential interval 1.25-4.09), but was no longer significant after further adjustment for other clinical characteristics and stroke severity. CONCLUSIONS: In AF-related cardioembolic stroke, patients aged ≥80 years had different clinical characteristics and poorer outcome compared with patients aged <80 years. Geriatr Gerontol Int 2017; 17: 708-713.

Predictive Factors for Excellent or Extremely Poor Functional Outcome in Initial Atrial Fibrillation-Related Cardioembolic Stroke.

BACKGROUND: We aimed to determine the predictive factors for excellent or extremely poor functional outcome in patients with first-ever atrial fibrillation (AF)-related cardioembolic stroke. METHODS: Retrospective observational study from a database. Patients with AF-related cardioembolic stroke with a premorbid modified Rankin Scale (mRS) score of 0 or 1 and without a previous history of stroke were included. RESULTS: Factors associated with excellent functional outcome (mRS scores of 0 or 1; n = 77; 30.4% of patients) included age >78 years (OR 0.31, 95% CI 0.15-0.61), male sex (OR 2.16, 95% CI 1.04-4.60), absence of hypertension (OR 0.46, 95% CI 0.22-0.94) and initial National Institutes of Health Stroke Scale (NIHSS) score of >9 (OR 0.08, 95% CI 0.03-0.16). Factors associated with extremely poor functional outcome (mRS scores of 5 or 6; n = 63; 24.9%) included age >78 years (OR 3.30, 95% CI 1.54-7.39), initial NIHSS score of >9 (OR 12.38, 95% CI 5.40-32.56), congestive heart failure (OR 4.82, 95% CI 2.00-12.19) and ischemic heart disease (OR 4.02, 95% CI 1.18-14.69). CONCLUSIONS: Predictive factors exist to delineate excellent and extremely poor functional outcomes after a first-time stroke associated with AF.

Pure dysarthria and dysarthria-facial paresis syndrome due to internal capsule and/or corona radiata infarction.

BACKGROUND: Pure dysarthria (PD) and dysarthria-facial paresis syndrome (DFP) mainly result from lenticulostriate artery territory infarction. PD and DFP are rare clinical entities, often grouped without distinction. The purpose of this study was to examine clinical and radiographic differences between PD and DFP due to unilateral internal capsule and/or corona radiata infarction. METHODS: Using a database that included consecutive patients with ischemic stroke admitted to the neurological stroke units of three hospitals within 7 days from onset between September 2011 and April 2014, we retrospectively extracted first-ever stroke patient data, who presented with PD or DFP with a single ischemic lesion localized in the internal capsule and/or corona radiata. Patients with weakness, ataxia, sensory deficit, or cortical symptoms were excluded. Ischemic lesion volume was calculated by the ABC/2 method on diffusion-weighted imaging (DWI). DWI images were normalized and superimposed to the template for PD and DFP. We compared patients' characteristics between PD and DFP. RESULTS: A total of 2126 patients, including 65 patients (3.1%) with PD or DFP, were registered. Of these, 13 PD patients and 18 patients with DFP due to unilateral internal capsule and/or corona radiata infarction were included for analysis. Compared with DFP patients, PD patients had longer onset-to-door time (median 37.5 vs. 10.8 h, p = 0.031), shorter vertical length (C component) of ischemic lesions (median 12.0 vs. 18.8 mm, p = 0.007), and smaller ischemic lesion volume (median 285 vs. 828 mm(3), p = 0.023). Ischemic lesions causing PD were located more frequently in the left hemisphere than DFP (92% vs. 56%, p = 0.045). The superimposed lesion pattern indicated that DFP had lesions more medial and involving posterior portions of the putamen and the caudate body, as well as more of the genu and posterior limb of the internal capsule, than PD. Ninety days after onset, symptoms disappeared in 21 (72%) out of 29 patients. CONCLUSIONS: In cerebral infarction limited to the internal capsule and/or corona radiata, PD is derived from smaller and left-sided lesions with delay in diagnosis compared with DFP. The clinical course of those with PD and DFP might be benign.

Controlled Microwave Heating Accelerates Rolling Circle Amplification.

Rolling circle amplification (RCA) generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms. Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity. The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect. The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions. Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA. Furthermore, the temperatures of the individual buffer components were specifically influenced by microwave heating. We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same.

Pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 Scores on Severity and Functional Outcome in Acute Ischemic Stroke with Atrial Fibrillation.

BACKGROUND: We examined the association between pre-admission risk scores and severity on admission and functional outcome in acute ischemic stroke with atrial fibrillation (AF). METHODS: Between September 2011 and April 2014, we retrospectively extracted consecutive ischemic stroke patients with AF whose pre-admission modified Rankin Scale (mRS) score was 2 or less from our prospective database. Pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were calculated in each patient, and their association with the National Institutes of Health Stroke Scale (NIHSS) score on admission or unfavorable outcome (mRS ≥ 3 at 3 months from the onset) was assessed. RESULTS: A total of 344 patients (189 were men; age, 77.7 ± 10.0 years) were included in the analysis. The median pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were 2, 4, and 4, respectively. NIHSS score on admission was positively correlated with pre-admission CHADS2 (ρ = .116, P = .031), CHA2DS2-VASc (ρ = .166, P = .020), and R2CHADS2 scores (ρ = .106, P = .049). Receiver operating characteristic (ROC) curve analysis revealed that pre-admission CHADS2 score of 2 or more (sensitivity, 80%; specificity, 45%; area under the ROC curve [AUC], .654), CHA2DS2-VASc score of 3 or more (sensitivity, 86%; specificity, 44%; AUC, .683), and R2CHADS2 score of 4 or more (sensitivity, 61%; specificity, 62%; AUC, .657) were associated with unfavorable outcome. The pre-admission CHA2DS2-VASc score was better than the pre-admission CHADS2 score in estimating unfavorable outcome (P = .017). In multivariate analysis, cutoffs of these scores, female sex, higher NIHSS score, and internal carotid artery occlusion were associated with unfavorable outcome. CONCLUSIONS: Pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were associated with onset severity and functional outcome in acute ischemic stroke with AF.

[Case of cerebellar and spinal cord infarction presenting with acute brachial diplegia due to right vertebral artery occlusion].

A 73-year-old man was admitted for evaluation of sudden onset of dizziness, bilateral shoulder pain, and brachial diplegia. Neurological examination revealed severe bilateral weakness of the triceps brachii, wrist flexor, and wrist extensor muscles. There was no paresis of the lower limbs. His gait was ataxic. Pinprick and temperature sensations were diminished at the bilateral C6-C8 dermatomes. Vibration and position senses were intact. An MRI of the head revealed a right cerebellar infarction and occlusion of the right vertebral artery. An MRI of the cervical spine on T2 weighted imaging (T2WI) showed cord compression at the C3/4-C5/6 level secondary to spondylotic degeneration without any intramedullary signal changes of the cord. On the following day, however, high-signal lesions on T2WI appeared in the C5-C6 spinal cord, suggesting cord infarction. Unilateral vertebral artery occlusion does not usually result in cervical cord infarction because of anastomosis of arteries. Because of the long-term mechanical compression in our case, it was likely that cervical cord ischemia was present before the onset of symptoms. On the basis of chronic cord compression, our case suggests that occlusion of a unilateral vertebral artery could cause cervical cord infarction.

[A case of subacute necrotizing lymphadenitis with recurrent aseptic meningitis associated with persistent high titer of anti-nuclear antibody occurring over a short period of time].

A 35-year-old woman developed recurrent aseptic meningitis three times over a period of 16 months. Each episode followed swelling of her cervical lymph nodes. During the third episode, microscopic findings of biopsied specimens from a cervical lymph node indicated subacute necrotizing lymphadenitis (SNL). While she responded poorly to NSAIDs, steroids rapidly improved her fever, headache and swollen lymph nodes. Since the first episode, anti-nuclear antibody (ANA) and anti-SS-A antibody was positive and the titer of ANA increased with each episode. SNL is a benign and self-limited disease, and the appearance of autoantibodies is usually transient. It is possible that a persistent immune abnormality is related to recurrences of aseptic meningitis with SNL.

[Elderly hereditary hemorrhagic telangiectasia female with portosystemic encephalopathy].

We present a 71-year-old woman with hereditary hemorrhagic telangiectasia (HHT) who at age 69, had undergone total gastrectomy because of repeated upper gastrointestinal bleeding. A day prior to admission she began to demonstrate abnormal behavior. Examination showed she was restless and had higher brain dysfunction. Triphasic waves were seen on EEG, and a high signal in the globus pallidus on T1-weighted MRI. Plasma NH3 level was increased after a meal. Abdominal CT scan showed vascular anomalies including a portohepatic vein shunt. She was diagnosed with portosystemic encephalopathy. After treatment with a low-protein diet, lactitol, and branched chain-amino acids, her clinical condition, plasma NH3 level after a meal, and EEG returned to normal. Because portosystemic shunt is rare in HHT, there have been few reports of portosystemic encephalopathy with this condition. However, with aging, the possibility of portosystemic encephalopathy increases because of age-related increases in portosystemic shunt volume.

Estimation of DNA polymerase for improvement of rolling circle amplification.

Rolling Circle Amplification (RCA) is a technique to amplify the oligoncleotides containing tandemly repetitive sequence motif. Various repetitive sequences of which the motif unit is the circular template can be synthesized by extending the primer. Additionally, RCA need not change the temperature regulatory processes like PCR, but RCA has the gene amplification efficiency similar to PCR. Although, it contains the problem of the sequence confirmation and the activity of polymerase as the DNA polymerase I. We comparatively estimated of the various polymerases for the improvement of the RCA. Five DNA polymerases were estimated for RCA.

Microwave assisted rolling circle amplification.

The Rolling Circle Amplification is an effective method of DNA amplification having tandem repeated sequences. Firstly, the template sequence is designed to form a circular structure by the annealing with the primer. The thermostable polymerase is catalyzed to primer and circular template DNA. As a result, tandem repetitive olignucleotide of circular template sequence can be obtained. In our recent study, Bst DNA polymerase catalyzed RCA reaction had been elucidated that the oligonucleotides with tandem repeated sequence were obtained as the ladder band and amplified the enough amounts of DNA within short time. On the other hand, we also focused on the microwave technology for advance to the various chemical and biological reactions. In this study, the microwave was irradiated to RCA reaction on controlling the temperature.

[MRI and SPECT findings in a case of metronidazole-induced reversible acute cerebellar ataxia].

A 69-year-old man was referred to our department because of acute onset nausea, vomiting, dysphagia, dysarthria and gait disturbance. He had a 50-day-history of amebic dysentery and had been treated with 1,500 mg metronidazole per day. Neurological examination revealed dysphagia, ataxic speech, ataxia of the left extremities and the trunk, and hyperactive deep tendon reflexes in all extremities. Sensory impairment of all modalities was apparent in a glove and stocking pattern, with mild paresthesia. Brain MRI showed T2 high signal lesions in the bilateral cerebellar dentate nuclei, more markedly on the left. On brain SPECT, obvious low blood perfusion was observed in the left cerebellar hemisphere. These findings well explained the ataxia of the left limbs. One month after discontinuing metronidazole, the cerebellar ataxia, dysphagia and MRI abnormalities completely cleared. Therefore, central nervous system damage induced by metronidazole is considered reversible. In spite of the presence of the MRI lesion in the right dentate nucleus, the patient had no ataxia of the right extremities and there was no hypoperfusion in the right cerebellar hemisphere. Thus, metronidazole does not appear to have a direct neurotoxic effect on the central nervous system. On the other hand, nerve conduction studies showed axonal polyneuropathy, which was not improved one month after cessation of the drug; thus metronidazole seems to exert more damage on peripheral nerves.

[Primary progressive multiple sclerosis as a differential diagnosis of ALS: a case report].

A 44-year-old man was admitted to our hospital because of a five year history of chronic progressive gait disturbance. Neurological examination revealed mild weakness and atrophy of the upper extremities, but severe of the lower ones, and without sphincter disturbance or apparent sensory impairment. Hyperreflexia and positive pathological reflexes of the lower extremities were apparent. EMG showed a reinnervation pattern and decreased number of motor units in the extremities, suggesting ALS. However, multiple plaques on the head and spinal MRI, a prolonged central conduction time of MEP and SEP, a delayed P100 latency of VEP, and a increased IgG index in the CSF indicated primary progressive type multiple sclerosis. After receiving steroid pulse therapy, the weakness of the lower extremities showed slight improvement. Diffuse inflammation in the spinal cord involving not only the pyramidal tract but also the anterior horn cells/intramedullary ventral roots explained the ALS-like clinical picture.