Validation of the Japanese version of the Social Functioning in Dementia scale and COVID-19 pandemic's impact on social function in mild cognitive impairment and mild dementia.

OBJECTIVES: We aimed to psychometrically evaluate and validate a Japanese version of the Social Functioning in Dementia scale (SF-DEM-J) and investigate changes in social function in people with dementia during the coronavirus disease-19 (COVID-19) pandemic. DESIGN: We interviewed people with mild cognitive impairment (MCI) and mild dementia and their caregivers during June 2020-March 2021 to validate patient- and caregiver-rated SF-DEM-J and compared their scores at baseline (April 2020 to May 2020) and at 6-8 months (January 2021 to March 2021) during a time of tighter COVID-19 restrictions. SETTING: The neuropsychology clinic in the Department of Psychiatry at Osaka University Hospital and outpatient clinic in the Department of Psychiatry and Neurology at Daini Osaka Police Hospital, Japan. PARTICIPANTS: 103 dyads of patients and caregivers. MEASUREMENTS: SF-DEM-J, Mini-Mental State Examination, Neuropsychiatric Inventory, UCLA Loneliness Scale, and Apathy Evaluation Scale. RESULTS: The scale's interrater reliability was excellent and test-retest reliability was substantial. Content validity was confirmed for the caregiver-rated SF-DEM-J, and convergent validity was moderate. Caregiver-rated SF-DEM-J was associated with apathy, irritability, loneliness, and cognitive impairment. The total score of caregiver-rated SF-DEM-J and the score of Section 2, "communication with others," significantly improved at 6-8 months of follow-up. CONCLUSIONS: The SF-DEM-J is acceptable as a measure of social function in MCI and mild dementia. Our results show that the social functioning of people with dementia, especially communicating with others, improved during the COVID-19 pandemic, probably as a result of adaptation to the restrictive life.

Structure-based drug design of novel and highly potent pyruvate dehydrogenase kinase inhibitors.

Pyruvate dehydrogenase kinases (PDHKs) are fascinating drug targets for numerous diseases, including diabetes and cancers. In this report, we describe the result of our structure-based drug design from tricyclic lead compounds that led to the discovery of highly potent PDHK2 and PDHK4 dual inhibitors in enzymatic assay. The C3-position of the tricyclic core was explored, and the PDHK2 X-ray structure with a representative compound revealed a novel ATP lid conformation in which the phenyl ring of Phe326 mediated the interaction of the Arg258 sidechain and the compound. Compounds with amide linkers were designed to release the ATP lid by forming an intramolecular pi-pi interaction, and these compounds showed single-digit nM IC50 values in an enzymatic assay. We also explored the C4-position of the tricyclic core to reproduce the interaction observed with the C3-position substitution, and the pyrrolidine compound showed the same level of IC50 values. By optimizing an interaction with the Asn255 sidechain through a docking simulation, compounds with 2-carboxy pyrrole moiety also showed single-digit nM IC50 values without having a cation-pi interaction with the Arg258 sidechain.

Stereoselective Construction of 2,7-Disubstituted fused-Bis Tetrahydrofuran Skeletons: Biomimetic-Type Synthesis and Biological Evaluation of (±)- and (-)-Aplysiallene and Their Derivatives.

A series of trans/trans and cis/cis fused-bis tetrahydrofuran compounds have been obtained stereoselectively in high yields via a one-pot operation involving the intramolecular haloetherification of (Z,Z)-diene diol 19a and (E,E)-diene disilylether 19d, respectively. This method was subsequently applied to the biomimetic-type synthesis of (±)- and (-)-aplysiallene. The inhibitory activities of these compounds and their bromodiene isomers toward Na(+)/K(+) ATPase were determined in vitro, and gave IC50 values of approximately 15 µM in all cases.

A case report of robot-assisted radical nephrectomy and inferior vena cava thrombectomy in a patient with renal cell carcinoma after pembrolizumab and axitinib combination therapy.

Background: Robot-assisted surgery is widely performed for renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombi. Although many chemotherapeutic options are available for the treatment of unresectable RCC, there are very few reports on robot-assisted radical nephrectomy (RARN) with inferior vena cava thrombectomy (IVCT) after presurgical treatment with immune checkpoint inhibitors and tyrosine kinase inhibitors. We believe that pre-surgical treatment can provide minimally invasive surgical benefits to high-risk patients during the perioperative period. Case Description: A 77-year-old male with right RCC that invaded the IVC (cT3bN0M0, Mayo classification level III) underwent pembrolizumab and axitinib combination therapy because he had high surgical risk due to angina pectoris. The level of the tumor thrombus decreased from level III to II, and RARN with IVCT was then performed. Surgery was performed without complications, and the patient was discharged on postoperative day seven. The pathological diagnosis was clear cell RCC (ypT3b, G2). Adjuvant chemotherapy using pembrolizumab monotherapy is still ongoing. Conclusions: In this report, the inferior vena cave tumor thrombus level was down staged from level III to level II by treatment with pembrolizumab and axitinib. RARN with IVCT was safely performed without complication completely under robotic assistance.

[NONRISING BLADDER PARAGANGLIOMA SUCCESSFULLY TREATED BY THE OPEN BLADDER SURGERY: A CASE REPORT].

The patient is a 47-year-old female. MRI revealed a well-defined submuscular mass in the bladder muscle layer. Bladder paraganglioma was suspected based on MRI findings. Endocrinologic Testing showed no significant elevation. 123I-MIBG scintigraphy of the mass showed a significant uptake, and we made diagnosis of bladder paraganglioma. The mass was nonrising and showed no color differentiation making its location undetectable. Using MRI with a ureteral stent and urethral catheter in place, we were able to determine its location. The possibility of damage to the ureteral or internal urethral opening was feared. We chose open bladder surgery, emphasizing ease of operation and visualization. Although a transient increase in blood pressure was observed during the operation, the mass was resected as a single mass from all layers of the bladder without damaging the ureteral or internal urethral opening. Histopathological examination revealed a paraganglioma.MRI (ureteral stent and urethral catheter placement) and open bladder surgery were useful for identifying the location and resecting this case of this otherwise undetectable bladder paraganglioma.

Normalized Power Variance: A new Field Orthogonal to Power in EEG Analysis.

To date, electroencephalogram (EEG) has been used in the diagnosis of epilepsy, dementia, and disturbance of consciousness via the inspection of EEG waves and identification of abnormal electrical discharges and slowing of basic waves. In addition, EEG power analysis combined with a source estimation method like exact-low-resolution-brain-electromagnetic-tomography (eLORETA), which calculates the power of cortical electrical activity from EEG data, has been widely used to investigate cortical electrical activity in neuropsychiatric diseases. However, the recently developed field of mathematics "information geometry" indicates that EEG has another dimension orthogonal to power dimension - that of normalized power variance (NPV). In addition, by introducing the idea of information geometry, a significantly faster convergent estimator of NPV was obtained. Research into this NPV coordinate has been limited thus far. In this study, we applied this NPV analysis of eLORETA to idiopathic normal pressure hydrocephalus (iNPH) patients prior to a cerebrospinal fluid (CSF) shunt operation, where traditional power analysis could not detect any difference associated with CSF shunt operation outcome. Our NPV analysis of eLORETA detected significantly higher NPV values at the high convexity area in the beta frequency band between 17 shunt responders and 19 non-responders. Considering our present and past research findings about NPV, we also discuss the advantage of this application of NPV representing a sensitive early warning signal of cortical impairment. Overall, our findings demonstrated that EEG has another dimension - that of NPV, which contains a lot of information about cortical electrical activity that can be useful in clinical practice.