Structure-activity relationship of mycoloyl glycolipids derived from Rhodococcus sp. 4306

Novel mycoloyl glycolipids with short carbon chains were isolated and purified from Rhodococcus sp. 4306, a soil origin of Actinomycetales. Their chemical structures were identified as trehalose 6,6'-dimycolate (TDM), trehalose 6-monomycolate, glucose 6-monomycolate, mannose 6-monomycolate and fructose 6-monomycolate. The length of carbon chains and number of double bonds of mycolic acids were C(34), C(36)and C(38)saturated, monoenoic and dienoic molecular species, which were much shorter than those of Mycobacterium tuberculosis (C(78-88)monoenoic and dienoic). Among them, only TDM could induce prominent granulomatous inflammation of the lung and spleen in mice. By contrast, other mycoloyl glycolipids induced mild lesions. The small-sized TDM of Rhodococcus possessed granulomatogenic activity, however, the toxicity was much lower than that of M. tuberculosis. Rhodococcal TDM was composed of mycolic acid with the shortest carbon chains, when compared to granulomatogenic TDM of Mycobacterium, Nocardia and Rhodococcus reported previously. Our results imply that rhodococcal TDM is a pathogenetic factor similar to that of M. tuberculosis, although rhodococcal TDM exhibits low toxicity.     

Control of feeding rhythm in the terrestrial slug Incilaria bilineata

A modulatory neuron of feeding rhythm was newly identified in the buccal ganglia of the isolated central nervous system (CNS) of the terrestrial slug Incilaria bilineata. This neuron was termed the “feeding rhythm modulator” (FRM). Its morphological and electrical properties were compared with those of the MGC (metacerebral giant cell, a cerebral modulatory neuron of feeding rhythm). There was no direct connection between FRM and MGC. In order to investigate the control mechanism of the buccal central pattern generator, feeding rhythm was observed by varying the activities of MGC and FRM simultaneously. At a lower level of activity of MGC, feeding rhythm was not only sensitive to the activity of MGC but also to that of FRM. As the level of activity of MGC increased, feeding rhythm was exclusively controlled by the activity of MGC, and became unaffected by the activity of FRM. This indicates that cerebral neurons such as MGC primarily control feeding rhythm and modulate the contribution of FRM in a hierarchical manner.     

Competition and physician-induced demand in a healthcare market with regulated price: evidence from Ghana

International Journal of Health Economics and Management - Using panel data of administrative claims spanning 36 months (2017–2019) and an instrumental variable method, this study...     

Retrosigmoid Approach in the Supine Position Using ORBEYE: A Consecutive Series of 14 Cases

One of the merits of recently introduced exoscopes, including ORBEYE, is that they are superior to a conventional microscope in terms of ergonomic features. Taking advantage of it, the retrosigmoid approach can be performed in the supine position using ORBEYE. We report a consecutive series of 14 operations through the retrosigmoid approach in the supine position using ORBEYE. Fourteen consecutive patients who underwent surgery through the retrosigmoid approach for cerebellopontine (CP) angle lesions in the supine position using ORBEYE were targeted, and surgical outcomes and complications were examined. We evaluated the posture of the operator and the surgical field during this approach compared with those using a conventional microscope. In all 14 cases, all operative procedures were accomplished only using the ORBEYE. There were no operative complications due to this approach. Using ORBEYE, even when the angle of the operative visual axis was horizontal, the operators could manipulate in a comfortable posture. They were not forced to be in an uncomfortable posture that extended their arms, as is often the case with a conventional microscope. Therefore, they could use shorter surgical instruments. As the cerebellum shifted downward with gravity even using slight retraction during this approach, the working space of the surgical field was easily secured. Through this approach, the operators can perform stable microsurgery of CP angle lesions in a comfortable posture. This approach can reduce the burden on the operator and the patient, leading to a refined surgical procedure.     

Development and Validation of Scoring Indication of Surgical Clipping and Endovascular Coiling for Aneurysmal Subarachnoid Hemorrhage from the Post Hoc Analysis of Japan Stroke Data Bank

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II–V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III–V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model’s scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.     

The effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy: A longitudinal analysis (FRARP-QL Study)

ObjectivesWe aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP).Materials and MethodsWe longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP.ResultsThe median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients’ background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening.ConclusionsFrailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.     

Prognostic significance of the Ki67 index and programmed death-ligand 1 expression after radical cystectomy in patients with muscle-invasive bladder cancer

ObjectivesTo investigate the association between Ki67 index and programmed death-ligand 1 (PD-L1) expression in muscle-invasive bladder cancer (MIBC) patients after RC.Materials and MethodsWe retrospectively evaluated 262 MIBC patients treated with RC between April 2004 and April 2020. The impact of Ki67 index and PD-L1 expression on prognosis was evaluated by univariate Cox regression analysis. In addition, a pathomolecular risk score, including Ki67 and PD-L1, was developed to predict prognosis and pathological factors. We also evaluated the link between the Ki67 index and PD-L1 under the IL-6 stimulation in the bladder cancer cell lines of T24 and 5637 cells.ResultsThe median age and follow-up period was 69 years and 52 months, respectively. Ki67 index and PD-L1 expression were significantly associated with tumor recurrence. Univariate Cox regression analysis showed that pT3–4, mixed histology, lymphovascular invasion positive (LVI+), pN+, Ki67-high (>17%), and PD-L1+ were significantly associated with recurrence-free survival (RFS). The pathomolecular risk score was developed using resection margin+ (1 point), mixed histology (1 point), LVI+ (1 point), pN+ (1 point), and Ki67-high (1 point). RFS and overall survival were significantly shorter in patients with higher pathomolecular risk scores (>1) than in those with lower risk scores (≤1). Cell proliferation was significantly increased in the T24 and 5637 cells under the IL-6 stimulation, while PD-L1 expression was not.ConclusionsA significant effect of Ki67-high and PD-L1 expression on poor prognosis was observed in patients with MIBC. Further studies are necessary to elucidate the precise mechanisms of cell proliferation and PD-L1 expression in patients with MIBC.     

Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUNDPreoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear.AIMTo investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and ^99mTc-galactosyl-human serum albumin (^99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODSThirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and ^99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D ^99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D ^99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV.RESULTSFFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSIONThe functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.