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Background When performing lymphovenous anastomosis, it is sometimes difficult to find venules in the proximity of an ideal lymphatic vessel that have a similar diameter to that of the lymphatic vessel. In this situation, larger venules can be used. Methods The authors evaluated the efficacy of and patient satisfaction with lymphovenous bypass with sleeve-in anastomosis. Between January 2014 and December 2016, we performed this procedure in 18 patients (eight upper extremities and 10 lower extremities) with secondary lymphedema. Lymphovenous bypass with sleeve-in anastomosis was performed under microscopy after injecting indocyanine green dye. The circumferential diameter was measured before lymphovenous bypass and at 1, 2, and 6 months after the procedure. An outcomes survey that included patients’ qualitative satisfaction with lymphovenous bypass was conducted at 6 months postoperatively. Results Almost all patients showed quantitative improvements after surgery. The circumferential reduction rate in patients with stage II lymphedema of both the upper and lower extremities was significantly greater than in their counterparts with stage III/IV lymphedema. The circumferential reduction rate was lower in lower-extremity patients than in upper-extremity patients. Conclusions Lymphovenous bypass surgery with sleeve-in anastomosis in lymphedema patients is beneficial, and appears to be effective, when adequately-sized venules cannot be found in the proximity of an ideal lymphatic vessel.

Type 1 diabetic Akita mice develop severe cardiac parasympathetic dysfunction that we have previously demonstrated is due at least in part to an abnormality in the response of the end organ to parasympathetic stimulation. Specifically, we had shown that hypoinsulinemia in the diabetic heart results in attenuation of the G-protein coupled inward rectifying K channel (GIRK) which mediates the negative chronotropic response to parasympathetic stimulation due at least in part to decreased expression of the GIRK1 and GIRK4 subunits of the channel. We further demonstrated that the expression of GIRK1 and GIRK4 is under the control of the Sterol Regulatory element Binding Protein (SREBP-1), which is also decreased in response to hypoinsulinemia. Finally, given that hyperactivity of Glycogen Synthase Kinase (GSK)3β, had been demonstrated in the diabetic heart, we demonstrated that treatment of Akita mice with Li+, an inhibitor of GSK3β, increased parasympathetic responsiveness and SREBP-1 levels consistent with the conclusion that GSK3β might regulate IKACh via an effect on SREBP-1. However, inhibitor studies were complicated by lack of specificity for GSK3β. Here we generated an Akita mouse with cardiac specific inducible knockout of GSK3β. Using this mouse, we demonstrate that attenuation of GSK3β expression is associated with an increase in parasympathetic responsiveness measured as an increase in the heart rate response to atropine from 17.3 ± 3.5% (n = 8) prior to 41.2 ± 5.4% (n = 8, P = 0.017), an increase in the duration of carbamylcholine mediated bradycardia from 8.43 ± 1.60 min (n = 7) to 12.71 ± 2.26 min (n = 7, P = 0.028) and an increase in HRV as measured by an increase in the high frequency fraction from 40.78 ± 3.86% to 65.04 ± 5.64 (n = 10, P = 0.005). Furthermore, patch clamp measurements demonstrated a 3-fold increase in acetylcholine stimulated peak IKACh in atrial myocytes from GSK3β deficiency mice compared with control. Finally, western blot analysis of atrial extracts from knockout mice demonstrated increased levels of SREBP-1, GIRK1 and GIRK4 compared with control. Taken together with our prior observations, these data establish a role of increased GSK3β activity in the pathogenesis of parasympathetic dysfunction in type 1 diabetes via the regulation of IKACh and GIRK1/4 expression.

In this study, a skewness estimation method (SEM) and kurtosis estimation method (KEM) are introduced to determine the number of inactive cycles in Monte Carlo eigenvalue calculations. The SEM and KEM can determine the number of inactive cycles on the basis that fully converged fission source distributions may follow normal distributions without asymmetry or outliers. Two convergence criteria values and a minimum cycle length for the SEM and KEM were determined from skewness and kurtosis analyses of the AGN-201K benchmark and 1D slab problems. The SEM and KEM were then applied to two OECD/NEA slow convergence benchmark problems to evaluate the performance and reliability of the developed methods. Results confirmed that the SEM and KEM provide appropriate and effective convergence cycles when compared to other methods and fission source density fraction trends. Also, the determined criterion value of 0.5 for both ε1 and ε2 was concluded to be reasonable. The SEM and KEM can be utilized as a new approach for determining the number of inactive cycles and judging whether Monte Carlo tally values are fully converged. In the near future, the methods will be applied to various practical problems to further examine their performance and reliability, and optimization will be performed for the convergence criteria and other parameters as well as for improvement of the methodology for practical usage.

Hepatic metabolism is an important process for evaluate the potential activity and toxicity of endocrine disrupting chemicals (EDCs) metabolites. Organization for Economic Co-operation and Development (OECD) has advocated the development of in vitro assays that mimic in vivo hepatic metabolism to eventually replace classical animal tests. In response to this need, we established a 3D mouse liver organoid (mLO) platform that mimics the animal model and is distinct from existing models. We evaluated the effects the activity of EDC metabolites generated through mLOs based on human cell-based reporter gene assays in addition to existing models. This study emphasizes the importance of hepatic ex-vivo and suggests the need a new metabolic model through a 3D mLOs platform. These results indicate that mLOs provides a novel biological method to screen for potential endocrine-disrupting activities of EDC metabolites.

In this study, a similarity coefficient generation code system was established using the Monte Carlo Code for Advanced Reactor Design (McCARD) transport code and the MIG multi-correlated input sampling code. We considered the adjoint-based sensitivity and uncertainty (S/U) and stochastic sampling (S.S.) approaches to the generation of the ck similarity coefficient. To examine the code system, the ck similarity coefficients of 23 relevant critical experiments and the System-Integrated Modular Advanced Reactor (SMART) small modular reactor (SMR) target system were generated using ENDF/B-VII.1 covariance data with the Los Alamos National Laboratory (LANL) 30-group energy group structure. Our results show that the similarity coefficients between the 16 LEU thermal-spectrum-based critical experiments and SMART are more than 0.90, which is the recommended criterion of the U.S. Nuclear Regulatory Commission (NRC). These results are very helpful for licensees and can be used to justify the determination of critical experiment benchmarks for computational bias estimations of the SMART target system. To examine the discrepancy in the similarity coefficient, ck, due to the covariance data, similarity analyses for a 24 × 24 benchmark matrix were performed using ENDF-VIII.0, JENDL-5.0, and JEFF-3.3 covariance data. The results show that the selection of the covariance data used for ck generation significantly impacts the similarity coefficient. Moreover, it was observed that the current results for the SCALE 6.1 covariance data show a consistent trend with the results reported in earlier studies.

Abstract Background Successful chemoprevention or chemotherapy is achieved through targeted delivery of prophylactic agents during initial phases of carcinogenesis or therapeutic agents to malignant tumors. Bacteria can be used as anticancer agents, but efforts to utilize attenuated pathogenic bacteria suffer from the risk of toxicity or infection. Lactic acid bacteria are safe to eat and often confer health benefits, making them ideal candidates for live vehicles engineered to deliver anticancer drugs. Results In this study, we developed an effective bacterial drug delivery system for colorectal cancer (CRC) therapy using the lactic acid bacterium Pediococcus pentosaceus. It is equipped with dual gene cassettes driven by a strong inducible promoter that encode the therapeutic protein P8 fused to a secretion signal peptide and a complementation system. In an inducible CRC cell-derived xenograft mouse model, our synthetic probiotic significantly reduced tumor volume and inhibited tumor growth relative to the control. Mice with colitis-associated CRC induced by azoxymethane and dextran sodium sulfate exhibited polyp regression and recovered taxonomic diversity when the engineered bacterium was orally administered. Further, the synthetic probiotic modulated gut microbiota and alleviated the chemically induced dysbiosis. Correlation analysis demonstrated that specific bacterial taxa potentially associated with eubiosis or dysbiosis, such as Akkermansia or Turicibacter, have positive or negative relationships with other microbial members. Conclusions Taken together, our work illustrates that an effective and stable synthetic probiotic composed of P. pentosaceus and the P8 therapeutic protein can reduce CRC and contribute to rebiosis, and the validity and feasibility of cell-based designer biopharmaceuticals for both treating CRC and ameliorating impaired microbiota. Video abstract

International Criticality Safety Benchmark Evaluation Project (ICSBEP) criticality analyses were conducted using the McCARD Monte Carlo code for 85 selected benchmark problems with 7 evaluated nuclear data libraries (ENDLs): ENDF/B-VII.1, ENDF/B-VIII.0, JENDL-4.0, JENDL-5.0, JEFF-3.3, TENDL-2021, and CENDL-3.2. Regarding the analyses, it was confirmed that the keff results are sensitive to the ENDL. It is noted that the new-version ENDLs show better performance in the fast benchmark cases, while on the other hand, there are no significant differences in keff among the different ENDLs in the thermal benchmark cases. The sensitivity of the keff results depending on the ENDL may impact nuclear core design parameters such as the shutdown margin, critical boron concentration, and power defects. This study and keff results will be a good reference in the development of new types of nuclear cores or new design codes.

The Korea Atomic Energy Research Institute (KAERI) has developed the DeCART2D 2-dimensional (2D) method of characteristics (MOC) transport code and the MASTER nodal diffusion code and has established its own two-step procedure. For design code licensing, KAERI prepared a critical experiment on the verification and validation (V&V) of the DeCART2D code. DeCART2D is able to perform the MOC calculation only for 2D nuclear fuel systems, such as the fuel assembly. Therefore, critical buckling in the vertical direction is essential for comparison between the results of experiments and DeCART2D. In this study, the B1 theory-augmented Monte Carlo (MC) method was adopted for the generation of critical buckling. To examine critical buckling using the B1 theory-augmented MC method, TCA critical experiment benchmark problems were considered. Based on the TCA benchmark results, it was confirmed that the DeCART2D code with the newly-generated critical buckling predicts the criticality very well. In addition, the critical buckling generated by the B1 theory-augmented MC method was bound to uncertainties. Therefore, utilizing basic equations (e.g., SNU S/U formulation) linking input uncertainties to output uncertainties, a new formulation to estimate the uncertainties of the newly generated critical buckling was derived. This was then used to compute the uncertainties of the critical buckling for a TCA critical experiment, under the assumption that nuclear cross-section data have uncertainties.

The ultimate goal of cleft palate repair is to achieve an intact palate with the separation of the oral and nasal cavities. However, some patients develop an oronasal fistula in the secondary palate after palatoplasty. Postoperatively, a secondary palatal oronasal fistula may develop, leading to functional problems. In this study, we describe a patient with recurrent oronasal fistula and alveolar cleft with multiple failed previous reconstructions at another clinic. The oronasal fistula and alveolar cleft were repaired using a tongue flap and an iliac bone graft, respectively. The patient demonstrated excellent clinical progress with no recurrence of the oronasal fistula at the 1-year follow-up. [ABSTRACT FROM AUTHOR]

This paper concerns estimating uncertainties of the core neutronics design parameters of power reactors by direct sampling method (DSM) calculations based on the two-step McCARD/MASTER design system in which McCARD is used to generate the fuel assembly (FA) homogenized few group constants (FGCs) while MASTER is used to conduct the core neutronics design computation. It presents an extended application of the uncertainty propagation analysis method originally designed for uncertainty quantification of the FA FGCs as a way to produce the covariances between the FGCs of any pair of FAs comprising the core, or the covariance matrix of the FA FGCs required for random sampling of the FA FGCs input sets into direct sampling core calculations by MASTER. For illustrative purposes, the uncertainties of core design parameters such as the effective multiplication factor (keff), normalized FA power densities, power peaking factors, etc. for the beginning of life (BOL) core of Yonggwang nuclear unit 4 (YGN4) at the hot zero power and all rods out are estimated by the McCARD/MASTER-based DSM computations. The results are compared with those from the uncertainty propagation analysis method based on the McCARD-predicted sensitivity coefficients of nuclear design parameters and the cross section covariance data.