Sensing of Metal Ions by Hybrid Systems of a Chiral Schiff Base Zn(II) Complex and Spiropyran

We have constructed three (hybrid) systems for quantitative fluorescence sensing of metal ions by using chiral Schiff base Zn(II) complexes. System 1 is a hybrid system composed of a trans-type chiral Schiff base Zn(II) complex and merocyanine (Mc), which is open-form of spiropyran (Sp) after photoisomerization. Depending on intermolecular interactions and quenching, increase (Zn2+) or decrease (Cu2+ and Gd3+) of fluorescence intensity of Zn(II) complex could be observed as functions of concentration of metal ions. System 2 is a sole component of a salen-type chiral Schiff base Zn(II) complex which can coordinate metal ions. After coordination of Zn2+, Cu2+, and Gd3+ ions, decreasing of fluorescence intensity could be found for all the cases for system 2 under the same condition to system 1. System 3 is a hybrid system being consisted of a salen-type chiral Schiff base Zn(II) complex and Mc. Decrease or increase of fluorescence intensity is in agreement with intermolecular interactions, namely affinity for the Zn(II) complex is Zn2+ > Cu2+ > Gd3+, whereas it is reverse order for Mc. The quantitative spectroscopic nature (detected as absorption, CD, and fluorescence) of these systems is predominantly attributed to both organic ligands and Zn(II) center in a probe comple

びまん性血管損傷 磁化率強調画像を用いた重症頭部外傷での収束性出血

INTRODUCTION:Susceptibility-weighted image (SWI) is one of the most sensitive methods for detect microbleeding and useful for evaluation of traumatic brain damage. The purpose of this study is to delineate the characteristics and importance of supratentorial deep white matter hemorrhages detected by SWI in cases of traumatic brain damage. METHODS:Twenty-one consecutive cases with severe traumatic head injury were included in the current study. MRI examinations were made within 1 month after injury. We evaluated the degree and distribution of the supratentorial hemorrhages on SWI retrospectively. We classified the degree of bleeding into four grades: "small hemorrhage," "single bead-like hemorrhage," "convergent-type hemorrhage," and "massive hemorrhage." We then correlated the degree and distribution of the hemorrhage to clinical outcomes. We also evaluated the apparent diffusion coefficient (ADC) image of lobes with "convergent-type hemorrhage." RESULTS:Existence of "massive hemorrhage" correlated with a poor outcome, that is, worse than "severely disabled" on the Glasgow Outcome Scale. The number of lobes affected by "convergent-type hemorrhage" also correlated with poor outcome. There were 45 lobes with "convergent-type hemorrhage" and 27 of them showed increased diffusivity on ADC images. CONCLUSION:Supratentorial massive hemorrhages and supratentorial convergent-type multiple hemorrhages were associated with poor prognosis after traumatic brain injury. The increased diffusivity in lobes with convergent-type hemorrhages may indicate that congestion of the proximal medullary vein may play some role for these hemorrhages.博士（医学）・甲第594号・平成25年3月15日© Springer International Publishing AG,201

The relationship between baseline diastolic dysfunction and postimplantation invasive hemodynamics with transcatheter aortic valve replacement.

BACKGROUND Abnormal invasive hemodynamics after transcatheter aortic valve replacement (TAVR) is associated with poor survival; however, the mechanism is unknown. HYPOTHESIS Diastolic dysfunction will modify the association between invasive hemodynamics postTAVR and mortality. METHODS Patients with echocardiographic assessment of diastolic function and postTAVR invasive hemodynamic assessment were eligible for the present analysis. Diastology was classified as normal or abnormal (Stages 1 to 3). The aorto-ventricular index (AVi) was calculated as the difference between the aortic diastolic and the left ventricular end-diastolic pressure divided by the heart rate. AVi was categorized as abnormal (AVi < 0.5 mmHg/beats per minute) or normal (≥ 0.5 mmHg/beats per minute). RESULTS From 1339 TAVR patients, 390 were included in the final analysis. The mean follow-up was 3.3 ± 1.7 years. Diastolic dysfunction was present in 70.9% of the abnormal vs 55.1% of the normal AVi group (P < .001). All-cause mortality was 46% in the abnormal vs 31% in the normal AVi group (P < .001). Adjusted hazard ratio (HR) for AVi < 0.5 mmHg/beats per minute vs AVi ≥0.5 mmHg/beats per minute for intermediate-term mortality was (HR = 1.5, 95% confidence interval [CI] 1.1 to 2.1, P = .017). This association was the same among those with normal diastolic function and those with diastolic dysfunction (P for interaction = .35). CONCLUSION Diastolic dysfunction is prevalent among TAVR patients. Low AVi is an independent predictor for poor intermediate-term survival, irrespective of co-morbid diastolic dysfunction

The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission

SummaryEndocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase α (DGLα) and β (DGLβ). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLα knockout mice, whereas the retrograde suppression was intact in DGLβ knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLα knockout brains, whereas the 2-AG content was normal in DGLβ knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLα, but not by DGLβ, mediates retrograde suppression at central synapses

Assessment of New Onset Arrhythmias After Transcatheter Aortic Valve Implantation Using an Implantable Cardiac Monitor.

Background Transcatheter aortic valve implantation (TAVI) is associated with new onset brady- and tachyarrhythmias which may impact clinical outcome. Aims To investigate the true incidence of new onset arrhythmias within 12 months after TAVI using an implantable cardiac monitor (ICM). Methods One hundred patients undergoing TAVI received an ICM within 3 months before or up to 5 days after TAVI. Patients were followed-up for 12 months after discharge from TAVI for the occurrence of atrial fibrillation (AF), bradycardia (≤30 bpm), advanced atrioventricular (AV) block, sustained ventricular and supraventricular tachycardia. Results A previously undiagnosed arrhythmia was observed in 31 patients (31%) and comprised AF in 19 patients (19%), advanced AV block in 3 patients (3%), and sustained supraventricular and ventricular tachycardia in 10 (10%) and 2 patients (2%), respectively. Three patients had a clinical diagnosis of sick-sinus-syndrome. A permanent pacemaker (PPM) was implanted in six patients (6%). The prevalence of pre-existing AF was 28%, and 47% of the patients had AF at the end of the study period. AF burden was significantly higher in patients with pre-existing [26.7% (IQR 0.3%; 100%)] compared to patients with new-onset AF [0.0% (IQR 0.0%; 0.06%); p = 0.001]. Three patients died after TAVI without evidence of an arrhythmic cause according to the available ICM recordings. Conclusions Rhythm monitoring for 12 months after TAVI revealed new arrhythmias, mainly AF, in almost one third of patients. Atrial fibrillation burden was higher in patients with prevalent compared to incident AF. Selected patients may benefit from short-term remote monitoring. Trial Registration https://clinicaltrials.gov/: NCT02559011

Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders

Intracellular trafficking of receptor proteins is essential for neurons to detect various extracellular factors during the formation and refinement of neural circuits. However, the precise mechanisms underlying the trafficking of neurotrophin receptors to synapses remain elusive. Here, we demonstrate that a brain-enriched sorting nexin, ARHGAP33, is a new type of regulator for the intracellular trafficking of TrkB, a high-affinity receptor for brain-derived neurotrophic factor. ARHGAP33 knockout (KO) mice exhibit reduced expression of synaptic TrkB, impaired spine development and neuropsychiatric disorder-related behavioural abnormalities. These deficits are rescued by specific pharmacological enhancement of TrkB signalling in ARHGAP33 KO mice. Mechanistically, ARHGAP33 interacts with SORT1 to cooperatively regulate TrkB trafficking. Human ARHGAP33 is associated with brain phenotypes and reduced SORT1 expression is found in patients with schizophrenia. We propose that ARHGAP33/SORT1-mediated TrkB trafficking is essential for synapse development and that the dysfunction of this mechanism may be a new molecular pathology of neuropsychiatric disorders

Rupture and Rhythm: A Phenomenology of National Experiences

This article investigates how people make sense of ruptures in the flow of everyday life as they enter new experiential domains. Shifts in being-in-time create breaks in the natural attitude that offer the opportunity to register national—or, for example, religious, gender, or class—experiences. People interpret ruptures in perception and proprioception by drawing connections with domains in which similar or contrasting kinds of disruption are evident. Normalizing the transition, rhythm—as both cadence and overall flow—helps people adjust to new circumstances, align action, and smooth subsequent ruptures. Based on extensive qualitative fieldwork, I examine the specific case of how novice and experienced tea ceremony practitioners in Japan move into, interpret, and normalize action within tea spaces

Case report of simultaneous transcatheter mitral valve-in-valve implantation and percutaneous closure of two paravalvular leaks.

Background Concomitant structural degeneration of surgical mitral bioprostheses and paravalvular leak (PVL) is rare but potentially fatal. Data pertaining to simultaneous transcatheter mitral valve implantation (TMVI) and percutaneous PVL closure are limited, and the optimal treatment strategy remains undetermined. We report a case of simultaneous TMVI and double percutaneous PVL closure in a patient with a degenerated bioprosthetic mitral valve and associated medial and lateral PVLs. Case summary A 75-year-old woman who underwent combined aortic (Edwards Perimount Magna 19 mm) and mitral (Edwards Perimount Magna 25 mm) surgical valve replacement 6 years ago was referred for treatment of new-onset orthopnoea and severely reduced exercise capacity. Transoesophageal echocardiography revealed severe mitral stenosis and concomitant moderate to severe mitral regurgitation, originating from two PVLs located medial and lateral from the surgical bioprosthesis. Due to high surgical risk, we performed successful transseptal mitral valve-in-valve (ViV) implantation combined with the closure of two PVLs during the same procedure. Discussion Although surgery should be considered as a first-line treatment in this setting, most patients have extremely high or prohibitive surgical risk inherent to repeat open heart surgery. Mitral ViV implantation appears a reasonable treatment option for patients with failed mitral bioprostheses. Furthermore, a recent study of percutaneous PVL closure showed no significant difference in long-term all-cause mortality compared with redo open-heart surgery. Simultaneous TMVI and percutaneous PVL closure appears feasible in selected high-risk patients

Progress of Diabetic Macular Edema after Loading Injection of Anti-Vascular Endothelial Growth Factor Agents in Real-World Cases

Background and Objectives: To evaluate the recurrence of diabetic macular edema (DME) after loading an injection of anti-VEGF agents by a pro re nata (PRN) protocol using central retinal thickness (CRT) as a re-injection criterion. Materials and Methods: This is a retrospective, observational single-center study. DME patients with a central retinal thickness (CRT) over 350 &mu;m received a PRN injection of anti-VEGF agents following one to three consecutive monthly loading injections (bevacizumab, ranibizumab, and aflibercept) for 6 months from January 2012 to June 2019. Results: We enrolled a total of 72 eyes for loading injections and the mean CRT improved from 434.04 &plusmn; 139.4 &mu;m (before treatment) to 362.9 &plusmn; 125.0 &mu;m after the loading injection. One week after injection, 36 eyes (50%) obtained a CRT of &le;350 &mu;m. Fourteen eyes (19.4%) remained with a CRT of &le;350 &mu;m for 6 months without additional injections. A total of 22 eyes (30.6%) had a CRT of &gt;350 &mu;m at 6 months. Fifteen eyes did not receive additional injections because of visual improvement. Conclusions: About 20% of DME patients can be maintained at a CRT of &le;350 &mu;m for 6 months with only a loading injection. However, there is a tendency to delay additional injections for patients with recurrences using PRN protocol