Abstract Background Hyperglycemia occurs frequently after kidney transplantation and may be reversed when the dosage of the immunosuppressive agents is tapered. However, the effect of transient ...post-transplantation hyperglycemia (PTH) on transplantation outcomes is not well described. Methods Kidney transplant recipients without diabetes who underwent kidney transplantation between 2001 and 2012 were enrolled in the study. Transient PTH was defined as recovery from PTH without further antidiabetic therapy and the maintenance of glycated hemoglobin levels <6.5% at 1 year after transplantation. Persistent PTH until 1 year after transplantation was considered to be new-onset diabetes after transplantation (NODAT). The factors associated with increased risk of PTH were analyzed. We compared the development of diabetes mellitus, cardiovascular disease, and other transplantation outcomes among patients with no PTH, transient PTH, and NODAT. Results Among 176 kidney transplant recipients, 106 (60.2%) developed PTH and 58 (54.7%) of 106 patients with PTH had transient PTH. Older age, high body mass index (BMI), and female gender were independent risk factors for transient PTH. The incidence of diabetes was not significantly different between patients with no PTH and those with transient PTH. The incidence of cardiovascular disease was significantly increased in NODAT group compared with that in no PTH and transient PTH groups. However, the incidences of acute rejection, allograft loss, and patient death were comparable among the three groups. Conclusions Transient hyperglycemia after kidney transplantation was found to be associated with older age, high body mass index, and female gender. Transient elevation of blood glucose level did not affect post-transplantation outcomes, including diabetes mellitus and cardiovascular disease. However, patients with NODAT should be carefully monitored for the occurrence of cardiovascular disease.
AMoRE is an international project to search for the neutrinoless double beta decay of
100
Mo
using a detection technology consisting of magnetic microcalorimeters (MMCs) and molybdenum-based ...scintillating crystals. Data collection has begun for the current AMORE-I phase of the project, an upgrade from the previous pilot phase. AMoRE-I employs thirteen
48
depl
.
Ca
100
MoO
4
crystals and five
Li
2
100
MoO
4
crystals for a total crystal mass of 6.2 kg. Each detector module contains a scintillating crystal with two MMC channels for heat and light detection. We report the present status of the experiment and the performance of the detector modules.
Preclinical evidence suggests that MEK inhibition promotes accumulation and survival of intratumoral tumor-specific T cells and can synergize with immune checkpoint inhibition. We investigated the ...safety and clinical activity of combining a MEK inhibitor, cobimetinib, and a programmed cell death 1 ligand 1 (PD-L1) inhibitor, atezolizumab, in patients with solid tumors.
This phase I/Ib study treated PD-L1/PD-1-naive patients with solid tumors in a dose-escalation stage and then in multiple, indication-specific dose-expansion cohorts. In most patients, cobimetinib was dosed once daily orally for 21days on, 7days off. Atezolizumab was dosed at 800mg intravenously every 2weeks. The primary objectives were safety and tolerability. Secondary end points included objective response rate, progression-free survival, and overall survival.
Between 27 December 2013 and 9 May 2016, 152 patients were enrolled. As of 4 September 2017, 150 patients received ≥1 dose of atezolizumab, including 14 in the dose-escalation cohorts and 136 in the dose-expansion cohorts. Patients had metastatic colorectal cancer (mCRC; n=84), melanoma (n=22), non-small-cell lung cancer (NSCLC; n=28), and other solid tumors (n=16). The most common all-grade treatment-related adverse events (AEs) were diarrhea (67%), rash (48%), and fatigue (40%), similar to those with single-agent cobimetinib and atezolizumab. One (<1%) treatment-related grade 5 AE occurred (sepsis). Forty-five (30%) and 23 patients (15%) had AEs that led to discontinuation of cobimetinib and atezolizumab, respectively. Confirmed responses were observed in 7 of 84 patients (8%) with mCRC (6 responders were microsatellite low/stable, 1 was microsatellite instable), 9 of 22 patients (41%) with melanoma, and 5 of 28 patients (18%) with NSCLC. Clinical activity was independent of KRAS/BRAF status across diseases.
Atezolizumab plus cobimetinib had manageable safety and clinical activity irrespective of KRAS/BRAF status. Although potential synergistic activity was seen in mCRC, this was not confirmed in a subsequent phase III study.
NCT01988896 (the investigators in the NCT01988896 study are listed in the supplementary Appendix, available at Annals of Oncology online).
Background
Dietary carbohydrate quality may play an important role in disease development. We evaluated the association between carbohydrate quality index (CQI) and the prevalence of obesity and ...metabolic disorders among adults in South Korea.
Methods
We analysed 12 027 adults aged 19–64 years from the fifth Korea National Health and Nutrition Examination Survey (KNHANES). CQI was based on four criteria: crude fibre intake, dietary glycaemic index (DGI), whole grains/total grains ratio and solid carbohydrates/total carbohydrates ratio.
Results
Participants with a lower CQI were younger, had a lower income and were more likely to be smokers and to drink alcohol. The highest quintile CQI group showed the lowest DGI and the lowest consumption of liquid carbohydrates and refined grains, as well as the highest consumption of solid carbohydrates, crude fibre and whole grains (P < 0.05). A higher CQI was negatively associated with the prevalence of obesity (odds ratio = 0.83; 95% confidence interval = 0.69–0.99) and hypertension (odds ratio = 0.78; 95% confidence interval = 0.61–0.99) but was not associated with other metabolic disorders.
Conclusions
These results suggest that the quality of carbohydrates consumed is associated with the risk of obesity and hypertension. However, the cross‐sectional design does not preclude reverse causality.
Solid-state nanopore (SSN)-based analytical methods have found abundant use in genomics and proteomics with fledgling contributions to virology - a clinically critical field with emphasis on both ...infectious and designer-drug carriers. Here we demonstrate the ability of SSN to successfully discriminate adeno-associated viruses (AAVs) based on their genetic cargo double-stranded DNA (AAV
dsDNA
), single-stranded DNA (AAV
ssDNA
) or none (AAV
empty
), devoid of digestion steps, through nanopore-induced electro-deformation (characterized by relative current change; Δ
I
/
I
0
). The deformation order was found to be AAV
empty
> AAV
ssDNA
> AAV
dsDNA
. A deep learning algorithm was developed by integrating support vector machine with an existing neural network, which successfully classified AAVs from SSN resistive-pulses (characteristic of genetic cargo) with >95% accuracy - a potential tool for clinical and biomedical applications. Subsequently, the presence of AAV
empty
in spiked AAV
dsDNA
was flagged using the Δ
I
/
I
0
distribution characteristics of the two types for mixtures composed of ∼75 : 25% and ∼40 : 60% (in concentration) AAV
empty
: AAV
dsDNA
.
Solid-state nanopore based electro-deformation coupled with deep learning to distinguish AAV particles based on their cargo content.
Several studies have shown physiological functions of interleukin (IL)-32, a novel cytokine. However, the role of IL-32 in cancer development has not been reported. In this study, we showed that ...IL-32γ inhibited tumor growth in IL-32γ-overexpressing transgenic mice inoculated with melanoma as well as colon tumor growth in xenograft nude mice inoculated with IL-32γ-transfected colon cancer cells (SW620). The inhibitory effect of IL-32γ on tumor growth was associated with the inhibition of constitutive activated nuclear transcription factor-κB (NF-κB) and of signal transducer and activator of transcription 3 (STAT3). The expression of antiapoptotic, cell proliferation and tumor-promoting genes (bcl-2, X-chromosome inhibitor of apoptosis protein (IAP), cellular IAP and cellular FADD-like IL-1β-converting enzyme-inhibitory protein, cyclin D), cyclin-dependent kinase 4, cycolooxygenase-2 and inducible nitric oxide synthase was decreased, whereas the expression of apoptotic target genes (caspase-3 and -9, bax) increased. In tumor, spleen and blood, the number of cytotoxic CD8(+) T cells and CD57(+) natural killer cells and the levels of IL-10 increased, but that of tumor necrosis factor-α (TNF-α), IL-1β and IL-6 decreased. We also found that forced overexpression of IL-32γ inhibited colon cancer cell (SW620 and HCT116) growth accompanied with the inhibition of activated NF-κB and STAT3 in vitro. In addition, when IL-32γ was knocked down by small interfering RNA (siRNA) or neutralized with an anti-IL-32γ antibody, IL-32γ-induced colon cancer cell growth inhibition, the IL-32γ-induced decrease of TNF-α, IL-1 and IL-6 production, and the increase of IL-10 production were abolished. However, siRNA of NF-κB and STAT3 augmented IL-32γ-induced colon cancer cell growth inhibition. These findings indicate significant pathophysiological roles of IL-32γ in cancer development.
Please cite this paper as: Kim J‐H, Park J‐Y, Kim D‐Y, Kim Y‐M, Kim Y‐T, Nam J‐H. Fertility‐sparing laparoscopic radical trachelectomy for young women with early stage cervical cancer. BJOG ...2010;117:340–347.
Objective To report the results of laparoscopic radical trachelectomy (LRT) with respect to surgical, oncological and reproductive outcomes.
Design Retrospective analysis.
Setting University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Korea.
Sample Thirty‐two consecutive patients who wish to preserve fertility with early stage cervical cancer.
Methods Demographic, clinicopathologic, surgical, and follow‐up data were obtained from patients’ medical records. All patients agreed to telephone interviews to assess their menstrual and obstetrical outcomes.
Main outcome measures Surgical parameters, perioperative complication, disease‐free survival, overall survival, return and pattern of menstruation and pregnancy rate.
Results Thirty‐two consecutive patients who wish to preserve fertility with early stage cervical cancer were offered LRT. In five patients, the planned LRT procedures were abandoned during the operations because of lymph node metastasis or parametrial involvement on frozen section. The mean age was 29 years (range, 22–37 years). The mean tumour size was 1.7 cm in diameter (range, 0.4–3.5 cm). The mean operating time was 290 min (range, 120–520 min) and the mean estimated blood loss was 332 ml (range, 50–1000 ml). Perioperative transfusion was required in six patients. There were no perioperative complications requiring further management. After a median follow‐up time of 31 months (range, 1–58 months), there was one recurrence and death from disease. Regular menstruation returned in 24 patients. Six patients attempted to conceive, and three succeeded.
Conclusions Laparoscopic radical trachelectomy may be a safe and useful alternative to radical hysterectomy for women with early cervical cancer who want to preserve their fertility.
Two-dimensional (2D) materials are not expected to be metals at low temperature owing to electron localization1. Consistent with this, pioneering studies on thin lms reported only superconducting and ...insulating ground states, with a direct transition between the two as a function of disorder or magnetic eld26. However, more recent works have revealed the presence of an intermediate quantum metallic state occupying a substantial region of the phase diagram710, whose nature is intensely debated1117. Here, we observe such a state in the disorder-free limit of a crystalline 2D superconductor, produced by mechanical co-lamination of NbSe2 in an inert atmosphere. Under a small perpendicular magnetic eld, we induce a transition from superconductor to the quantum metal. We nd a unique power-law scaling with eld in this phase, which is consistent with the Bose-metal model where metallic behaviour arises from strong phase uctuations caused by the magnetic field1114.
Reactor experiment for neutrino oscillation (RENO) began data-taking from August 2011. It successfully observed reactor antineutrino disappearance in April 2012 to measure the smallest mixing angle ...of θ13. Two identical detectors, one at near location and the other at far location, are constructed at the Yonggwang nuclear power plant in South Korea, to compare the observed reactor neutrino fluxes. Each RENO detector is filled with 16 mass tons of Gadolinium loaded liquid scintillator (GdLS) in the neutrino target region, and with 28 mass tons of unloaded liquid scintillator (LS) in the γ-catcher region surrounding the target. LS was developed to satisfy chemical, physical, optical properties, and safety requirements. Linear alkyl benzene (LAB) was chosen as a solvent because of its high flash-point, sufficient light yield, and being environmentally friendly. GdLS is carefully developed to keep a long attenuation length and high light yield for a long time period. In this paper, we report the characteristics and mass production of the RENO LS and GdLS.
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