Long-term clinical outcomes of total mesorectal excision and selective lateral pelvic lymph node dissection for advanced low rectal cancer: a comparative study of a robotic versus laparoscopic approach.

BACKGROUND: The long-term outcomes of minimally invasive lateral pelvic lymph node dissection (LPND) are not completely known. The aim of this study was to compare long-term outcomes between robotic and laparoscopic LPND in low rectal cancer patients with suspected lymph node metastasis in the pelvic sidewall. METHODS: We retrospectively reviewed the records of all rectal cancer patients who had laparoscopic or robotic total mesorectal excision (TME) with LPND between March 2006 and June 2016. Stage IV patients were excluded. The outcomes of patients who had laparoscopic and robotic TME with LPND were compared. RESULTS: Twenty-nine patients had laparoscopic LPND and 70 had robotic LPND. No significant differences in patient characteristics were observed between the two groups. The urinary retention rate was lower in the robotic group than in the laparoscopic group (7.1% vs. 24.1%; p = 0.043). During a median follow-up of 44.3 months, the overall recurrence rates were 48.3% and 31.4% in the laparoscopic and robotic groups, respectively (p = 0.175). The 5-year disease-free survival rates were 50.4% and 67.0% in the laparoscopic and robotic groups, respectively (p = 0.227). The 5-year overall survival rates were 65.0% and 92.2% in the laparoscopic and robotic groups, respectively (p = 0.017). CONCLUSIONS: Robotic TME with LPND is safe and feasible. In particular, it is associated with lower urinary retention. Robotic TME with LPND might yield a similar local recurrence rate and 5-year disease-free survival, but favorable long-term overall survival as compared to the laparoscopic approach. However, considering the retrospective nature and both major variables of TME and LPND involved together, this should be cautiously interpreted.

Nonsurgical Rhinoplasty With Polydioxanone Threads and Fillers.

BACKGROUND: Absorbable wedge-shaped polydioxanone (PDO) sutures are currently available for facial rejuvenation, and they are extremely popular in the aesthetic clinics in Korea. Other than face lifting, threads also can be used for nonsurgical rhinoplasty. The Asian nose is typified by a flat nasal bridge, indistinct nasal dorsum, underprojected and broad nasal tip, and a short columella. In the past, Asian rhinoplasty mainly focused on dorsal augmentation. At present, augmentation of the nasal tip is very popular and is considered an important aspect of achieving a natural and balanced nose. OBJECTIVE: To describe a novel technique with PDO threads in nonsurgical rhinoplasty. In addition, the authors aimed to assess the overall safety and efficacy of nonsurgical rhinoplasty combining both fillers and threads. METHODS: A retrospective analysis was performed on Korean patients who received rhinoplasty with PDO threads and fillers. All participants underwent a single treatment session. The results were assessed objectively by 2 independent dermatologists using serial photography and subjectively based on the patients' satisfaction scores at 6-month follow-up. RESULTS: A total of 31 patients were evaluated, and 93.5% considered the results satisfactory. Consensus ratings at the 6-month follow-up were largely categorized as very much improved (38.7%), much improved (35.5%), and improved (25.8%). An average increase of 6.3° (percentage increase by 7.6) in the nasolabial angle (p < .05) was measured at follow-up. The incidence of the complications was low, and the ones reported were minor. CONCLUSION: Nonsurgical rhinoplasty combining PDO threads and fillers can be safe and effective, maintaining good results at 6 months after the procedure. Threads are especially useful for lifting-up the nasal tip, contributing to a more harmonious and pleasing nasal appearance by modifying the columella-labial angle.

Evaluation of a diagnostic 18F-FDG PET/CT strategy for differentiating benign from malignant retroperitoneal soft-tissue masses.

AIM: To investigate the optimal combined 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) diagnostic criteria for distinguishing between benign and malignant retroperitoneal soft-tissue masses (RPMs). MATERIALS AND METHODS: A total of 74 patients (M:F=34:40; age, 53±13.2 years) who underwent FDG PET/CT for the initial work-up of RPMs were included. The maximum standardised uptake value (SUVmax), tumour size, presence of fat or calcifications and separated hypermetabolic lesions were included as PET/CT diagnostic parameters. Receiver-operating characteristic (ROC) curves were used to compare the diagnostic performance. RESULTS: The final pathological diagnoses included 52 malignant and 22 benign tumours. High SUVmax (>4.8) and large size (>13 cm) favoured malignancy, and yielded a diagnostic accuracy and AUC of 64.9%, 0.820±0.059, and 68.9%, 0.738±0.061, respectively. In a subgroup of RPMs with a fat component, both SUVmax and size were significantly different between benign and malignant RPM, which yielded a diagnostic accuracy and AUC of 91%, 0.977±0.024 (cut-off, 1.9 cm) and 87.9%, 0.865±0.072 (cut-off, 13 cm), respectively. In a subgroup without a fat component, only SUVmax was significantly different with an accuracy of 90.2% and AUC of 0.919±0.043. The optimal diagnostic flow by combining SUVmax and tumour size after dividing patients into two groups according to the presence of fat showed a sensitivity of 90.4%, a specificity of 95.5%, and an accuracy of 91.9%. CONCLUSIONS: The combination of SUVmax and size according to the presence of a fat component may be the optimal PET/CT diagnostic criteria for distinguishing benign and malignant RPMs.

Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior.

Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1f/f; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.

Age-dependent prognostic value of body mass index for non-metastatic clear cell renal cell carcinoma: A large multicenter retrospective analysis.

BACKGROUND AND OBJECTIVES: The prognostic value of obesity is unestablished for renal cell carcinoma. We assessed the age-dependent prognostic value of body mass index (BMI) in a large multicenter cohort of patients with non-metastatic clear cell renal cell carcinoma (nm-cRCC). METHODS: This study evaluated 2092 patients with nm-cRCC who underwent surgery with curative intent at five Korean institutions between 2001 and 2014. RESULTS: There was no significant difference in BMI between the young (<45 years) and older patients (≥45 years) (P = 0.398). Among older patients, high BMI (≥25 kg/m2 ) was associated with better 5-year rates of recurrence-free survival (RFS) and cancer-specific survival (CSS) (P = 0.003 and 0.004, respectively), and multivariate analysis confirmed that high BMI was independently associated with better RFS and CSS (RFS hazard ratio [HR]: 0.617, P = 0.005; CSS HR: 0.588, P = 0.024). However, among young patients, there were no significant BMI-related differences in the 5-year RFS and CSS rates (P = 0.457 and 0.420, respectively), and high BMI was not independently associated with RFS or CSS (P = 0.822 and 0.749, respectively). CONCLUSIONS: Among patients with nm-cRCC, high BMI was associated with a favorable prognosis among older patients but not among young patients. Therefore, the relationship between obesity and nm-cRCC prognosis might vary according to age.

Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests.

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used 'days post onset of illness (dpoi)' and 'days post exposure (dpex)' assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.

A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitor targeting MEP isoprenoid precursor biosynthesis.

The apicoplast is an essential plastid organelle found in Plasmodium parasites which contains several clinically validated antimalarial-drug targets. A chemical rescue screen identified MMV-08138 from the "Malaria Box" library of growth-inhibitory antimalarial compounds as having specific activity against the apicoplast. MMV-08138 inhibition of blood-stage Plasmodium falciparum growth is stereospecific and potent, with the most active diastereomer demonstrating a 50% effective concentration (EC50) of 110 nM. Whole-genome sequencing of 3 drug-resistant parasite populations from two independent selections revealed E688Q and L244I mutations in P. falciparum IspD, an enzyme in the MEP (methyl-d-erythritol-4-phosphate) isoprenoid precursor biosynthesis pathway in the apicoplast. The active diastereomer of MMV-08138 directly inhibited PfIspD activity in vitro with a 50% inhibitory concentration (IC50) of 7.0 nM. MMV-08138 is the first PfIspD inhibitor to be identified and, together with heterologously expressed PfIspD, provides the foundation for further development of this promising antimalarial drug candidate lead. Furthermore, this report validates the use of the apicoplast chemical rescue screen coupled with target elucidation as a discovery tool to identify specific apicoplast-targeting compounds with new mechanisms of action.

High-finesse sub-GHz-resolution spectrometer employing VIPA etalons of different dispersion.

We report a novel configuration of a two-stage virtually imaged phased array spectrometer that enables high-throughput sub-GHz spectroscopy at a high finesse (>750). Two etalons with different free spectral range and different dispersion are arranged in an orthogonal direction and spread the spectrum across two dimensions, with a greatly improved rejection ratio of white-light background noise. A proof-of-concept application for Brillouin spectroscopy is demonstrated.

Perspectives of mid-infrared optical coherence tomography for inspection and micrometrology of industrial ceramics.

Optical coherence tomography (OCT) is a promising tool for detecting micro channels, metal prints, defects and delaminations embedded in alumina and zirconia ceramic layers at hundreds of micrometers beneath surfaces. The effect of surface roughness and scattering of probing radiation within sample on OCT inspection is analyzed from the experimental and simulated OCT images of the ceramic samples with varying surface roughnesses and operating wavelengths. By Monte Carlo simulations of the OCT images in the mid-IR the optimal operating wavelength is found to be 4 µm for the alumina samples and 2 µm for the zirconia samples for achieving sufficient probing depth of about 1 mm. The effects of rough surfaces and dispersion on the detection of the embedded boundaries are discussed. Two types of image artefacts are found in OCT images due to multiple reflections between neighboring boundaries and inhomogeneity of refractive index.

Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism.

Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. Heparin inhibited hMSC adhesion to PS-MBP-FGF2 but not to FN-coated surface. The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. hMSCs that were expanded on FN-coated surface differentiated into osteogenic and adipogenic cells more readily than those that were expanded on PS-MBP-FGF2. Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. Elucidation of the glycan structure on the cell membrane may help characterise hMSC function.

Trends in renal function after radical nephrectomy: a multicentre analysis.

OBJECTIVE: To evaluate serial changes in renal function by investigating various clinical factors after radical nephrectomy (RN). PATIENTS AND METHODS: The study population consisted of 2068 consecutive patients who were treated at multiple institutions by RN for renal cortical tumour without metastasis between 1999 and 2011. We measured the serial change in estimated glomerular filtration rate (eGFR) and clinical factors during a 60-month follow-up period. The changes in eGFR over time were analysed according to baseline eGFR (eGFR ≥60 and 15-59 mL/min/1.73m(2) ) using a linear mixed model. The independent prognostic value of various clinical factors on the increase in eGFR was ascertained by multivariate mixed regression model. RESULTS: Overall, there was a subsequent restoration of renal function over the 60 months. The slope for the relationship between the eGFR and the time since RN was 0.082 (95% confidence interval [CI] 0.039-0.104; P < 0.001) and 0.053 (95% CI 0.006-0.100; P = 0.038) in each baseline group, indicating that each month after RN was associated with an increase in eGFR of 0.082 and 0.053 mL/min/1.73m(2) , respectively. When we analysed renal function based on various factors, postoperative eGFR of patients with diabetes mellitus, old age (≥70 years) or a preoperative eGFR of <30 mL/min/1.73 m(2) , was decreased or maintained at a certain level without any improvement in renal function. Preoperative predictors of an increase in eGFR after RN were young age, no DM, no hypertension, a preoperative eGFR of ≥30 mL/min/1.73m(2) and time after surgery (≥36 months). CONCLUSIONS: Renal function recovered continuously during the 60-month follow-up period after RN. However, the trends in functional recovery change were different according to various clinical factors and such information should be discussed with patients when being counselled about their treatment for renal cell carcinoma (RCC).

Restoration of cone vision in a mouse model of achromatopsia.

Loss of cone function in the central retina is a pivotal event in the development of severe vision impairment for many prevalent blinding diseases. Complete achromatopsia is a genetic defect resulting in cone vision loss in 1 in 30,000 individuals. Using adeno-associated virus (AAV) gene therapy, we show that it is possible to target cones and rescue both the cone-mediated electroretinogram response and visual acuity in the Gnat2 ( cpfl3 ) mouse model of achromatopsia.

In vivo wide-area cellular imaging by side-view endomicroscopy.

In vivo imaging of small animals offers several possibilities for studying normal and disease biology, but visualizing organs with single-cell resolution is challenging. We describe rotational side-view confocal endomicroscopy, which enables cellular imaging of gastrointestinal and respiratory tracts in mice and may be extensible to imaging organ parenchyma such as cerebral cortex. We monitored cell infiltration, vascular changes and tumor progression during inflammation and tumorigenesis in colon over several months.

Clinical characteristics and insulin independence of Koreans with new-onset type 2 diabetes presenting with diabetic ketoacidosis.

BACKGROUND: We evaluated the incidence, characteristics and insulin independence of Koreans with new-onset type 2 diabetes (T2D) initially presenting with diabetic ketoacidosis (DKA). METHODS: We analysed clinical and biochemical data from diabetic patients presenting with DKA. They were classified into ketosis-prone diabetes (KPD) type 1A (KPD-T1A) (A+ß-), type 1B (KPD-T1B) (A-ß-), type 2A (KPD-T2A) (A+ß+) or type 2B (KPD-T2B) (A-ß+) according to the presence or absence of an autoantibody and ß-cell reserve. Changes in therapy after insulin discontinuation were evaluated for up to 4 years. We also compared clinical and biochemical characteristics between newly diagnosed T2D patients presenting with DKA and previously diagnosed T2D patients presenting with DKA. RESULTS: Among 60 newly diagnosed KPD patients, 18, 21 and 21 patients were classified as KPD-T1A, KPD-T1B and KPD-T2B, respectively. In the KPD-T2B group, both fasting and stimulated C-peptide were recovered over 6 months. After 4 years of DKA development, 75% of KPD-T2B subjects no longer required insulin. Compared with previously diagnosed T2D patients presenting with DKA, newly diagnosed KPD-T2B patients tended to be younger, more obese and showed better insulin secretory function after recovery from DKA. CONCLUSIONS: New-onset T2D patients presenting with DKA was not uncommon among the Korean population. In contrast to previously diagnosed T2D patients presenting with DKA, who showed a progressive decrease in insulin secretory function, new-onset KPD-T2B patients recovered insulin secretory function over time, and insulin independence could be expected.

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

Control of Tire Wear Particulate Matter through Tire Tread Prescription.

This study aims to analyze tire wear particulate matter (TWP) from tread rubber with different formulations and to compare the concentration of TWP with different wear devices. The TWP generated during the abrasion of truck and bus radial (TBR) tires were examined, and the effect of using different types of rubber and carbon black (CB) were investigated. When natural rubber (NR) was solely used as the tire tread rubber material, there was a higher concentration of 5-10 µm TWP. However, when the tread formulation consisted of NR mixed with butadiene rubber, the TWP concentration decreased. Changing the type of CB also reduced the amount of TWP in the 2.5 µm size range. The TWP concentration in the specimens increased with increasing speed and vertical load. The TWP generated during the abrasion tests using wear testers and tire simulators exhibited similar trends. These findings suggest that modifying tire tread formulations can effectively control the distribution and amount of TWP generation.

Subnanometer optical coherence tomographic vibrography.

The ability to quantify and visualize submicrometer-scale oscillatory motions of objects in three dimensions has a wide range of application in acoustics, materials sciences, and medical imaging. Here we demonstrate that volumetric snapshots of rapid periodic motion can be captured using optical coherence tomography (OCT) with subnanometer-scale motion sensitivity and microsecond-scale temporal resolution. This technique, termed OCT vibrography, was applied to generate time-resolved volumetric vibrographs of a miniature drum driven acoustically at several kilohertz.

Acute arsenic toxicity alters cytochrome P450 and soluble epoxide hydrolase and their associated arachidonic acid metabolism in C57Bl/6 mouse heart.

Acute arsenic (As(III)) exposure has been reported to cause cardiac toxicity, however this toxicity was never linked to the disturbance in cytochrome P450 (P450)-mediated arachidonic acid metabolism. Therefore, we investigated the effect of acute As(III) toxicity on the expression of P450 and soluble epoxide hydrolase (sEH) and their associated arachidonic acid metabolism in mice hearts. As(III) toxicity was induced by a single intraperitoneal injection of 12.5 mg/kg of As(III). Our results showed that As(III) treatment caused a significant induction of the cardiac hypertrophic markers in addition to Cyp1b1, Cyp2b, Cyp2c, Cyp4f, and sEH gene expression in mice hearts. Furthermore, As(III) increased sEH protein expression and activity in hearts with a consequent decrease in 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs) formation. Whereas the formation of 8,9-, 11,12-, 14,15-dihydroxyeicosatrienoic acids (DHETs) was significantly increased. As(III) also increased sEH mRNA and protein expression levels in addition to the hypertrophic markers which was reversed by knockdown of sEH in H9c2 cells. In conclusion, acute As(III) toxicity alters the expression of several P450s and sEH enzymes with a consequent decrease in the cardioprotective EETs which may represent a novel mechanism by which As(III) causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent As(III)-induced hypertrophy.

Influence of molybdenum layer on the laser plasma generated from interfacing copper layer.

The results for laser-induced breakdown spectroscopy (LIBS) measurement of thin Cu films (1 µm) on soda-lime glass (SLG) substrates with and without a supporting thin Mo layer (1 µm) are reported. The ablation was carried out using a nanosecond Q-switched Nd:YAG laser (λ=1064 nm, τ=4 ns, spot diameter=50 µm, top-hat profile) in the laser fluence range of 19.16-65.97 J/cm(2). It was found that, under the same laser irradiance conditions, the depth and morphology of ablation craters produced with and without the Mo layer were completely different. The electron number densities of the plasma from the two samples calculated from the measured LIBS spectra differed by a factor of 4 as 4.1×10(17) cm(-3) (Cu/Mo/SLG) and 17.7×10(17) cm(-3) (Cu/SLG), which was attributed to the matrix effects resulting from ionization of Na atoms diffused into the Mo layer. It is demonstrated that a nanosecond-laser-based LIBS is applicable for the characterization and composition analysis of thin film layers of a few micrometer thickness on glass substrates, especially for the measurement of Na contents of each layer.

Analysis of the absorption layer of CIGS solar cell by laser-induced breakdown spectroscopy.

Laser induced breakdown spectroscopy (LIBS) was applied for the elemental analysis of the thin copper indium gallium diselenide (CuIn(1-x)Ga(x)Se(2) [CIGS]) absorption layer deposited on Mo-coated soda-lime glass by the co-evaporation technique. The optimal laser and detection parameters for LIBS measurement of the CIGS absorption layer (1.23 µm) were investigated. The calibration results of Ga/In ratio with respect to the concentration ratios measured by x-ray fluorescence and inductively coupled plasma optical emission spectroscopy showed good linearity.