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.     

Determination of the depth of 50% of maximum ionization, I50, for electron beams by the divided difference method

A new characterization of depth-ionization parameters for electron beams is empirically deduced from our data analysis based on the divided difference method (the DD method), which employs the numerical differential of an ionization curve. The important feature of the present method is that it does not necessarily require normalized percent depth-ionization (NPDI) data. The depth of 50% of maximum ionization, I50, which is an important parameter for electron beam dosimetry, can be deduced from the analysis of an unnormalized (or partial) depth-ionization (UDI) curve obtained over a short interval of depth. The values of I50 determined by the DD method are in agreement to within 0.1 mm for energies of 4, 6, and 9 MeV, compared with the ones determined by the TG-51 protocol method (or the conventional method), and the difference was 0.9 mm for 12 and 15 MeV. The dose at the reference depth, dref, calculated from I50 by the DD method, is found to be in agreement with TG-51 to within 0.1%. The field size dependence of the DD method using UDI data was studied for three field sizes: 6 x 6, 10 x 10, and 20 x 20 cm2. For all energies, the discrepancies of I50 as determined by both methods were 0.9 mm on average for the 6 x 6 cm2 fields and 0.6 mm for the other two field sizes. This dependence was remarkable for 6 x 6 cm2 fields for 12 and 15 MeV, and the discrepancies shown by the DD method were 1.2 mm for 12 MeV and 1.8 mm for 15 MeV, respectively. Since the reference field size in clinical dosimetry is usually 10 x 10 cm2, this dependence will not affect clinical dosimetry. The DD method could be an alternative option for checking beam quality in dose calibration.     

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.     

Lessons learned from lower urinary tract complications of anorectoplasty for imperforate anus with rectourethral/rectovesical fistula: Laparoscopy-assisted versus posterior sagittal approaches

PurposeTo report the sequelae of and preventive strategies for selected lower urinary tract (LUT) complications, i.e., posterior urethral diverticulum (PUD), intraoperative LUT injuries, postoperative dysuria, and fistula recurrence in male imperforate anus (IA) with rectourethral/rectovesical (RU/RV) fistula after laparoscopy-assisted anorectoplasty (LAARP) or posterior sagittal anorectoplasty (PSARP).Methods153 boys with IA and RU/RV fistula treated 1986–2019 by LAARP (n = 56) or PSARP (n = 97) at two unrelated institutes were studied retrospectively.ResultsAfter mean follow-up of 17.0 years (range: 36.5 days-32.0 years), the overall incidences of LUT complications were: LAARP (6/56; 10.7%); PSARP (7/97; 7.2%); p = 0.55, comprising PUD: LAARP (n = 5), PSARP (n = 0); p = 0.006; injuries: LAARP (n = 0), PSARP (n = 5); p = 0.16; dysuria: LAARP (n = 1), PSARP (n = 1); p>0.999; and recurrence: LAARP (n = 0), PSARP (n = 1); p>0.999. Mean onset of PUD was 5.1 years (range: 1.0–15.1 years). Treatment: PUD: surgery (n = 2/5), conservative (n = 3/5); injuries: intraoperative repair (n = 5/5); dysuria: conservative (n = 2/2), and recurrence: redo PSARP (n = 1/1).ConclusionsStrategies devised to improve dissection accuracy resolved the specific technical issues causing LUT complications (remnant RU fistula dissection in LAARP and blind posterior access in PSARP). Currently, the incidence of new cases of PUD and LUT injuries is zero.Level of Evidence: Level III     

Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma

BackgroundExtrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection.MethodsThe participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping.ResultsExtrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively.ConclusionWe have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.     

Developing network adequacy standards for VA Community Care

ObjectivesTo inform how the VA should develop and implement network adequacy standards, we convened an expert panel to discuss Community Care Network (CCN) adequacy and how VA might implement network adequacy standards for community care.Data Sources/Study settingData were generated from expert panel ratings and from an audio‐recorded expert panel meeting conducted in Arlington, Virginia, in October 2017.Study DesignWe used a modified Delphi panel process involving one round of expert panel ratings provided by nine experts in network adequacy standards. Expert panel members received a list of network adequacy standard measures used in commercial and government market and were provided a rating form listing a total of 11 measures and characteristics to rate.Data Collection MethodsItems on the rating form were individually discussed during an expert panel meeting between the nine expert panel members and VA Office of Community Care leaders. Attendees addressed discordant views and generated revised or new standards accordingly. Recorded audio data were transcribed to facilitate thematic analysis regarding opportunities and challenges with implementing network adequacy standards in VA Community Care.Principal FindingsThe five highest ranked standards were network directories for Veterans, regular reporting of network adequacy data to VA, maximum wait time/distance standards, minimum ratio of providers to enrolled population, and qualitative assessments of network adequacy. During the expert panel discussion with VA Community Care leaders, opportunities and challenges implementing network adequacy standards were highlighted.ConclusionsOur expert panel shed light on priorities for network adequacy to be implemented under CCN contracts, such as developing comprehensive provider directories for Veterans to use when selecting community providers. Remaining questions focus on whether the VA could reasonably develop and implement network adequacy standards given current Congressional restraints on VA reimbursement to community providers.     

Prevention of postischemic reperfusion injury: The improvement of myocardial tissue blood flow after ischemia by terminal Nicorandil-Mg cardioplegia

We evaluated the preventive effect of postischemic reperfusion injury by Nicorandil-Mg cardioplegia given just prior to reperfusion as terminal cardioplegia. Twenty seven dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 90 min under hypothermic (17–19°C) cardioplegic arrest. The canine hearts were divided into three groups: in group A (n=10) the hearts were reperfused without any treatment; in group B (n=9) the hearts received coronary perfusion with Nicorandil-Mg solution (Nic, 8 mg/l; Mg, 20 mEq/l; glucose, 50 g/l) for 2 min just prior to reperfusion; and in group C (n=8) the hearts received coronary perfusion with Nicorandil-Mg free solution (glucose, 50g/l). During and after ischemia, the myocardial tissue PCO₂ (t-PCO₂) was continuously monitored by an ion-sensitive field effective transistor (ISFET) sensor. In addition, the myocardial tissue blood flow (TBF), oxygen consumption, and lactate flux were then calculated at 5, 10, 20, and 40 min of reperfusion. In the initial reperfusion period, Group B showed an improved TBF compared to group A and C (at 5 min, group B was 42.7±11.9; group A was 29.4±11.2, P<0.025; and group C was 33.9±9.2% of the preischemic control level, P<0.05). T-PCO₂ in group B was significantly decreased at 5 min of reperfusion (group B, 127.5±22.5 42.5±9.7; group A, 117.5±23.0 85.2±17.4, P<0.001; group C, 122.3 mmHg 68.2±18.7 mmHg, P<0.01), and group B had a better metabolic recovery. These results suggest that terminal Nicorandil-Mg cardioplegia might reduce the rate of postischemic reperfusion injury.     

Confluent BALB/c 3T3 cells monolayer provides selective and efficient growth of neoplastic cells

In an attempt to further characterize non-irradiated contact-inhibited confluent monolayer of BALB/c 3T3 cells (= Contact-Sensitive Plates; CSP) as substrata for in vitro drug sensitivity testing, we compared the efficiency of colony formation with panels of cell lines on CSP with that on plastic dishes or in agar. Tumorigenicity in athymic nude mice was also examined. We found that: (1) HeLa cells, 2 esophageal cancer lines, rat 3Y1 fibroblasts transformed by either adenovirus type 12, mouse polyoma virus, Rous avian sarcoma virus, or plasmid DNA carrying v-Ha-ras oncogene all formed colonies on CSP and in agar and at the same time was tumorigenic. The efficiency of colony formation on CSP proved always to be higher than that in agar. (2) None of the 4 "normal" fibroplastic cell lines formed colonies on CSP or in agar and were tumorigenic. (3) Simian virus 40 and adenovirus E1A gene transformed rat 3Y1 fibroblasts formed colonies on CSP but not in agar, and were not tumorigenic. Therefore, CSP was found to provide selective and efficient growth of neoplastic cells when compared to other substrata and is also helpful in detecting incompletely transformed cells.