Histopathological predictor of the progression from actinic keratosis to squamous cell carcinoma: quantitative computer-aided image analysis.

BACKGROUND: The current histopathological classifications for actinic keratosis (AK) are subjective, and histopathological factors predicting the progression into invasive squamous cell carcinoma (SCC) remain unclear. OBJECTIVES: To quantitatively assess the histopathological findings of AK and to investigate the predisposing factors for malignant transformation of AK. METHODS: A total of 502 AK specimens were retrospectively reviewed. The AK lesions were divided into the atrophic, intermediate, hypertrophic and bowenoid types. Histopathological features were quantitatively analysed using computer-aided image analysis. RESULTS: The epidermal thickness excluding the horny layer increased with statistical significance (P < 0.001) in order of atrophic, intermediate, hypertrophic and bowenoid type. The proportion of keratinocytic atypia was not significantly different among subtypes, except for the bowenoid type. Five of 498 cases were confirmed to develop into SCC. Bowenoid type, epidermal thickening and higher proportion of keratinocytic atypia were significantly associated with progression to invasive SCC in univariate analysis (OR = 12.571, 95% CI: 1.392-113.57; OR = 1.004, 95% CI: 1.001-1.007; OR = 1.069, 95% CI: 1.011-1.130, respectively). In multivariate analysis, only the proportion of keratinocytic atypia was an independent predisposing factor for progression to invasive SCC (OR = 1.069; 95% CI: 1.011-1.130). CONCLUSIONS: Histopathological subtypes based on the essential change of the epidermis well correlated with the actual epidermal thickness excluding the horny layer. The overall severity of keratinocytic atypia might be an independent risk factor for malignant transformation of AK.

Support from superiors reduces depression in Republic of Korea military officers.

BACKGROUND: The prevalence of depression is relatively high in the Korean military. Social support is a protective factor against depression and is classified into four categories: emotional support-having the sense of feeling loved; instrumental support-receiving material assistance; informational support-receiving advice; appraisal support-feeling valued and respected for one's abilities. OBJECTIVE: To investigate the effect of support from one's superior on depression among Republic of Korea (ROK) military officers. METHODS: 2047 participants from the 2015 Military Health Survey were included in the study. The Korean version of the Beck Depression Inventory was used to measure depression, and a self-reported questionnaire was used to assess support from one's superior. A chi-squared test and multiple logistic regression were used to analyse the data. RESULTS: Of the 2047 participants, 177 (8.6%) had depression. Military officers who did not receive support from their superior were more likely to have depression than than those who did receive support (OR=2.09, 95% CI 1.30 to 3.36). Additionally, military personnel who did not receive emotional or appraisal support were more likely to have depression (emotional support: OR=2.37, 95% CI 1.31 to 4.29; appraisal support: OR=1.56, 95% CI 1.48 to 2.75). CONCLUSIONS: Our study found that depression in military officers was associated with lack of support from superiors. In particular, emotional support and appraisal support had a statistically significant effect. Therefore, we suggest that the ROK armed forces consider early intervention and management for high-risk groups. A social support programme and organisational atmosphere are also needed to improve supportive ability and skills of superiors.

Association of preoperative anemia and perioperative allogenic red blood cell transfusion with oncologic outcomes in patients with nonmetastatic colorectal cancer.

Background: We investigated whether preoperative anemia and perioperative blood transfusion (pbt) are associated with overall survival and recurrence-free survival in patients with nonmetastatic colorectal cancer. Methods: From 1 January 2009 to 31 December 2014, 1003 patients with primary colorectal cancer were enrolled in the study. Perioperative clinical and oncologic outcomes were analyzed based on the presence of preoperative anemia and pbt. Results: Preoperative anemia was found in 468 patients (46.7%). In the anemia and no-anemia groups, pbt was performed in 44% and 15% of patients respectively. Independent predictors for pbt were preoperative anemia, higher American Society of Anesthesiologists score, laparotomy, lengthy operative time, advanced TNM stage, T4 stage, and 30-day morbidity. The use of pbt, but not preoperative anemia, was found to be an independent adverse prognostic factor for overall survival. In terms of recurrence-free survival, the presence of preoperative anemia was similarly not a significant prognostic factor, but the use of pbt was an independent factor for an unfavourable prognosis. Conclusions: The use of pbt, but not preoperative anemia, was independently associated with worse overall and recurrence-free survival in nonmetastatic colorectal cancer. For better oncologic outcomes, our findings indicate a need to reduce the use of blood transfusion during the perioperative period.

In Vitro Red Fluorescence as an Indicator of Caries Lesion Activity.

This in vitro study examined the utility of comparing red fluorescence between active and inactive caries lesions and investigated whether changes in red fluorescence and fluorescence loss are influenced by lesion activity following remineralization. Sixty-two noncavitated smooth surface caries lesions on extracted human teeth were classified into active or inactive lesions using the Nyvad system prior to a 12-day pH-cycling procedure. Quantitative light-induced fluorescence-digital images were used to measure fluorescence parameters before and after pH cycling. At baseline, the intensity (ΔR) and area (AΔR) of red fluorescence were 1.5- and 2.2-fold higher in active lesions than in inactive lesions (p<0.05). The ratio of AΔR to lesion area was associated with classification of active lesions (odds ratio = 1.031; 95% confidence interval = 1.005-1.058). After pH cycling, the active lesions showed about 2- and 8-fold greater reductions in the median values of AΔR and fluorescence loss related to lesion volume (ΔQ) compared with inactive lesions (p<0.05). In conclusion, red fluorescence differs depending on lesion activity, and the red fluorescence area and lesion volume change following remineralization. The results suggest that measuring red fluorescence may be a useful way of objectively evaluating lesion activity of smooth surface lesions.

Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial.

Background: Intraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone. Methods: Patients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml-1 remifentanil with 0.05 µg kg-1 h-1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml-1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery. Results: The pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22-3.84) vs 3.84 (3.76-4.00) vs 3.80 (3.69-4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups. Conclusions: The intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain. Clinical trial registration: NCT02856087.

Sterile Neutrino Search at the NEOS Experiment.

An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.

Observation of Energy and Baseline Dependent Reactor Antineutrino Disappearance in the RENO Experiment.

The RENO experiment has analyzed about 500 live days of data to observe an energy dependent disappearance of reactor ν[over ¯]_{e} by comparing their prompt signal spectra measured in two identical near and far detectors. In the period between August of 2011 and January of 2013, the far (near) detector observed 31 541 (290 775) electron antineutrino candidate events with a background fraction of 4.9% (2.8%). The measured prompt spectra show an excess of reactor ν[over ¯]_{e} around 5 MeV relative to the prediction from a most commonly used model. A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the observed number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.082±0.009(stat)±0.006(syst) and |Δm_{ee}^{2}|=[2.62_{-0.23}^{+0.21}(stat)_{-0.13}^{+0.12}(syst)]×10^{-3} eV^{2}.

A cephalic vein drained into one of the double axillary veins through the pectoralis major muscle.

Although the cephalic vein follows a fairly consistent course, numerous variants have been reported. We found a rare anatomical presentation of the cephalic vein in a 43-year-old Korean male cadaver. The cephalic vein had anastomosed with the basilic vein and brachial vein at the level of the elbow, perforated the pectoralis major muscle between the clavicular and sternal heads, and then entered into one of the double axillary veins. Knowledge of the variations on the cephalic vein is important for clinicians as well as anatomists since the approach through the axillary base is favoured in many invasive procedures.

Long-term follow up of HIV-1-infected Korean haemophiliacs, after infection from a common source of virus.

In the early 1990s, 20 haemophiliacs (HPs) were infected with a common source of HIV-1 viruses through the contaminated clotting factor IX. The aim of this study is to review 20 HPs infected with a common source of virus. The enrolled patients have been consecutively treated with Korean red ginseng (KRG), zidovudine (ZDV) or two-drug therapy and highly active antiretroviral therapy (HAART). We determined full-length pol gene over 20 years and human leukocyte antigen (HLA) class I with peripheral blood mononuclear cells and reviewed medical records. Eighteen HPs experienced various opportunistic infections or clinical manifestations. There were significant inverse correlations between the HLA prognostic score and the annual decrease in CD4+ T-cell counts prior to HAART (AD) (P < 0.05) and the amount of KRG and the AD (P < 0.01). From 1998, the HPs had been treated with HAART. Each of the two patients died without and with HAART regimen respectively. At present, 16 HPs have been alive with HAART. Among the 16 HPs, 12 and 4 are on HAART-plus-KRG and HAART only respectively. Eleven HPs including 2 HPs with G-to-A hypermutations had revealed resistance mutations. Ten and two HPs have shown poor adherence and incomplete viral suppres-sion on HAART respectively. Virological failure based on WHO guidelines was not observed on KRG-plus-HAART. Two HPs revealed additional resistance mutations against two classes on KRG-plus-HAART. As a nationwide study, we first report overall features on clinical course of Korean haemophiliacs. Further education on the importance of drug adherence is needed.

Characteristics of subjective recognition and computer-aided image analysis of facial erythematous skin diseases: a cornerstone of automated diagnosis.

BACKGROUND: Rosacea and seborrhoeic dermatitis are common diseases that cause facial erythema. They have common features and are frequently misdiagnosed. OBJECTIVES: To extract characteristic features of erythrotelangiectatic rosacea (ETR), papulopustular rosacea (PPR) and seborrhoeic dermatitis (SEB) through computer-aided image analysis (CAIA) and compare them with subjectively recognized features and to use these findings to construct a decision tree for differential diagnosis. METHODS: Thirty-four clinical photos of patients with facial erythema were assessed: 12 patients were classified as showing ETR, 12 as PPR and 10 as SEB. Five dermatologists blinded to the original diagnosis gave their impressions of each photo. The mean, SD and T-zone to U-zone (T/U) ratios of the erythema parameter a* (a* of the L*a*b* colour space) were calculated for each photo using CAIA. These CAIA parameters were compared between impression groups. The most closely related CAIA parameter for each disease was established using the receiver-operating characteristic curve analysis. A decision tree which predicts the diagnosis from given CAIA parameters was constructed. RESULTS: All the photos classified as PPR generated impressions of PPR. However, approximately 30% of the photos classified as ETR generated impressions of SEB and vice versa. PPR was characterized by a large SD of erythema of the cheek, ETR was characterized by a large mean erythema of the U-zone, and SEB was characterized by a large T/U ratio of mean erythema. Fifteen additional photos were examined: the decision tree predicted the original diagnosis for 14, but incorrectly predicted one case of ETR as SEB. CONCLUSIONS: The CAIA result of facial erythema is well correlated with the actual clinical diagnosis. The accuracy of differential diagnosis using a decision tree with CAIA parameters is as good as that of global examination impressions of dermatologists.

Observation of reactor electron antineutrinos disappearance in the RENO experiment.

The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six 2.8 GW(th) reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is 0.920±0.009(stat)±0.014(syst). From this deficit, we determine sin(2)2θ(13)=0.113±0.013(stat)±0.019(syst) based on a rate-only analysis.

Evaluation of the leukocyte differential on a new automated flow cytometry hematology analyzer.

INTRODUCTION: The Hematoflow (Beckman Coulter, USA) is a new automated hematology analyzer, which provides a 16-part white blood cell count (WBC) differential. METHODS: We evaluated the differential WBC count performance of the Hematoflow. 101 blood samples from patients were selected for comparison analysis. RESULTS: The methodological comparison of the WBC differential parameters of neutrophils, lymphocytes, monocytes and eosinophils showed good correlations among 4 different analyses. More than 1% of blast cells were counted in 30 of 101 samples. A good correlation for blast cell counts obtained by Hematoflow was found with the reference manual method (r=0.9637, P 0.0001). For blast B, Hematoflow shows good correlation with reference method results but did not identify blast T. CONCLUSIONS: These results demonstrate that the Hematoflow has a comparable performance with the Sysmex XE-2100 and indicate that B cell lineage ALL can be identified by the use of the Hematoflow in an initial evaluation of acute leukemia.

Generation of anti-tumour immune response using dendritic cells pulsed with carbonic anhydrase IX-Acinetobacter baumannii outer membrane protein A fusion proteins against renal cell carcinoma.

Carbonic anhydrase IX (CA9), a specific molecular marker for renal cell carcinoma (RCC), serves as a potential target for RCC-specific immunotherapy using dendritic cells (DCs). However, pulsing of DCs with CA9 alone is not sufficient for generation of a therapeutic anti-tumour immune response against RCC. In this study, in order to generate a potent anti-tumour immune response against RCC, we produced recombinant CA9-Acinetobacter baumannii outer membrane protein A (AbOmpA) fusion proteins, designated CA9-AbOmpA, and investigated the ability of DCs pulsed with CA9-AbOmpA fusion proteins in a murine renal cell carcinoma (RENCA) model. A recombinant CA9-AbOmpA fusion protein was composed of a unique proteoglycan-related region of CA9 (1-120 amino acids) fused at the C-terminus with transmembrane domain of AbOmpA (1-200 amino acids). This fusion protein was capable of inducing DC maturation and interleukin (IL)-12 production in DCs. Interaction of DCs pulsed with CA9-AbOmpA fusion proteins with naive T cells stimulated secretion of IL-2, interferon (IFN)-γ and tumour necrosis factor (TNF)-α in T cells. Lymphocytes harvested from mice immunized with DCs pulsed with CA9-AbOmpA fusion proteins secreted IFN-γ and showed a specific cytotoxic activity against CA9-expressing RENCA (RENCA-CA9) cells. Administration of CA9-AbOmpA-pulsed DC vaccine suppressed growth of RENCA-CA9 cells in mice with an established tumour burden. These results suggest that DCs pulsed with CA9-AbOmpA fusion proteins generate a specific anti-tumour immune response against RCC, which can be utilized in immunotherapy of RCC.

Development of a plasma generator for a long pulse ion source for neutral beam injectors.

A plasma generator for a long pulse H(+)/D(+) ion source has been developed. The plasma generator was designed to produce 65 A H(+)/D(+) beams at an energy of 120 keV from an ion extraction area of 12 cm in width and 45 cm in length. Configuration of the plasma generator is a multi-cusp bucket type with SmCo permanent magnets. Dimension of a plasma chamber is 25 cm in width, 59 cm in length, and 32.5 cm in depth. The plasma generator was designed and fabricated at Japan Atomic Energy Agency. Source plasma generation and beam extraction tests for hydrogen coupling with an accelerator of the KSTAR ion source have been performed at the KSTAR neutral beam test stand under the agreement of Japan-Korea collaborative experiment. Spatial uniformity of the source plasma at the extraction region was measured using Langmuir probes and ±7% of the deviation from an averaged ion saturation current density was obtained. A long pulse test of the plasma generation up to 200 s with an arc discharge power of 70 kW has been successfully demonstrated. The arc discharge power satisfies the requirement of the beam production for the KSTAR NBI. A 70 keV, 41 A, 5 s hydrogen ion beam has been extracted with a high arc efficiency of 0.9 -1.1 A/kW at a beam extraction experiment. A deuteron yield of 77% was measured even at a low beam current density of 73 mA/cm(2).

Effects of a cGMP-specific phosphodiesterase inhibitor on expression of endothelial nitric oxide synthase and vascular endothelial growth factor in rats with cyclosporine-induced nephrotoxicity.

BACKGROUND: The mechanism of cyclosporine (CsA)-induced nephrotoxicity has been suggested to be vasoconstriction due to reduced nitric oxide (NO), providing tissue fibrosis by elevation of transforming growth factor beta and vascular endothelial growth factor (VEGF). In this study using a rat model of CsA-induced nephrotoxicity, we administered a phosphodiesterase-5 inhibitor to ameliorate the renal injury and alter the expression of endothelial No synthase (eNOS) and VEGF. METHODS: A right nephrectomy was performed in Sprague-Dawley rats (n = 30; 200-250 g, all male). The Ischemia group (n = 6) underwent ligation of the left renal artery for 45 minutes (IR) before observation for 28 days. After IR, the udenafil group (n = 6) was treated with 10 mg/kg drug orally, the CsA group (n = 6) received 15 mg/kg CsA injected subcutaneously and the CsA plus udenafil group (n = 6) received 15 mg/kg CsA injected subcutaneously together with the oral administration of 10 mg/kg udenafil. RESULTS: Administration of udenafil significantly decreased serum creatinine either alone (0.21 ± 0.04 mg/dL) or in combination with CsA (1.86 ± 0.35 mg/dL) versus the ischemia (0.85 ± 0.22 mg/dL) and the CsA alone (3. 10 ± 0.77 mg/dL) group. (P = .002; P = .002). Comparing the Hematoxylin-eosin staining of the ischemia (0.41 ± 0.09) and CsA (0.44 ± 0.08) groups showed a significantly decreased loss of nuclei in proximal tubules after the administration of udenafil (0.27 ± 0.05 [P = .004] and 0.26 ± 0.02 [P = .002] respectively). Immunohistochemical staining showed strong eNOS staining in the udenafil and CsA plus udenafil groups. Western blots for eNOS showed decreased expression in the CsA group and increased expression in the udenafil group. Western blots for VEGF revealed reduced expression only in the CsA plus udenafil group. eNOS mRNA was decreased in the CsA (0.017 ± 0.010) compared with the ischemia group (0.048 ± 0.015; P = .000). VEGF mRNA which was decreased in the CsA group (2.026 ± 1.109), showed greater tendency after administration of udenafil (0.440 ± 0.449) (P = .003). CONCLUSION: The phosphodiesterase inhibitor ameliorated renal injury in a rat model of CsA-induced nephrotoxicity, possibly related to increased eNOS and reduced VEGF expression.