The association between the neutrophil lymphocyte ratio and local edema after viper snake envenomation in South Korea.

The role of the inflammatory process in the pathogenesis of local edema-related envenomation has not been explored with endemic venomous snakebites in Korea. Gloydius species are responsible for most snakebites in South Korea. In this study we aimed to investigate whether the neutrophil-lymphocyte ratio is relevant to snake envenomation-induced local edema in South Korea. This retrospective study divided 126 patients into two groups according to local edema severity at presentation. Logistic regression models were used to investigate the association between the neutrophil-lymphocyte ratio and local edema. Sixty-one (48.4%) patients had grade 2 or higher local edema at presentation despite 21 of them being given antivenom before presentation. During hospitalization, local edema progressed in 61 patients 48 (11.5-48) hours after presentation, and 54 patients demonstrated grade 3 or higher local edema. A higher neutrophil-lymphocyte ratio at presentation after adjustment for factors related to envenomation and antivenom administration and factors influencing the neutrophil-lymphocyte ratio were associated with both a higher grade of local edema at presentation and a higher peak local edema grade during hospitalization. The delta neutrophil-lymphocyte ratio during the first 24 h after presentation was related to the local edema progression after presentation. The neutrophil-lymphocyte ratio at presentation is associated with the severity of local edema-related envenomation. Furthermore, the change in the neutrophil-lymphocyte ratio during the first 24 h is related to the risk of local edema progression. Further clinical and experimental research aimed at investigating the role of inflammation on the pathogenesis of local edema should be conducted. This study may suggest the introduction of short-term anti-inflammatory agents considering the failure of antivenom to curb local edema.

Change of Vertebral Left Atrial Size in Dogs With Preclinical Myxomatous Mitral Valve Disease Prior to the Onset of Congestive Heart Failure.

INTRODUCTION/OBJECTIVES: It has been proposed that vertebral left atrial size (VLAS) on thoracic radiographs can be used to assess the left atrial enlargement in dogs with myxomatous mitral valve disease (MMVD). However, it remains unclear whether VLAS can be used to distinguish dogs between pre-clinical MMVD that are at a greater risk of developing congestive heart failure (CHF) from those at a lower risk. We investigated this possibility. ANIMALS, MATERIALS AND METHODS: Forty-one dogs with MMVD were retrospectively classified into one of two groups, a group that developed CHF (group CHF, n = 17) or remained CHF-free (group no-CHF, n = 24). The value of vertebral heart scale (VHS) and VLAS at three time-points, change in VHS and VLAS at a specific time interval (ΔVHS, ΔVLAS) and rate of change in the values per month (ΔVHS/month, ΔVLAS/month) were compared. RESULTS: At the first visit, there were no significant differences in VLAS between the groups. At the median of 105 (interquartile ranges 83-155) days prior to the onset of CHF (group CHF) or the last visit (group no-CHF), VLAS was significantly higher in group CHF (mean, 2.9; standard deviation ± 0.4) than in group no-CHF (2.6 ± 0.3) (p = 0.028). ΔVLAS/month (area under the curve, 0.91; p<0.001) showed high diagnostic accuracy in distinguishing which dogs would develop CHF within 180 days and which would not. CONCLUSIONS: VLAS and ΔVLAS/month in dogs with pre-clinical MMVD may be useful to identify dogs at risk of developing CHF within the next 180 days.

Suspected human intravenous immunoglobulin-induced acute haemolytic anaemia in a dog.

A 2-year-old mixed breed dog presented with a 1-year history of crust and erosion on the nasal planum. Because histopathological examination revealed ruptured intraepidermal pustules and superficial dermal inflammation, the dog was diagnosed with pemphigus foliaceus. Human intravenous immunoglobulin was administered in two consecutive doses of 0.5 g/kg/day due to poor therapeutic response to previous immunosuppressive therapy. From Day 3 after the first dose of human intravenous immunoglobulin, tachypnoea, pale mucous membrane, haemoglobinuria and haemoglobinemia were observed, thus confirming haemolytic anaemia. Other drug-induced haemolytic anaemias were excluded because no additional drugs had been administered before the haemolysis occurred. Immune-mediated haemolytic anaemia was also excluded because the direct antiglobulin test was negative. Two transfusions were performed, and haemolysis was not observed from Day 4 of haemolytic anaemia onset. In conclusion, human intravenous immunoglobulin-induced haemolytic anaemia should be considered in dogs that develop haemolysis following the administration of human intravenous immunoglobulin.

Coagulopathy after snake envenomation in South Korea.

OBJECTIVE: This retrospective study investigated the nature and severity of venom-induced consumption coagulopathy (VICC) and determined the clotting factors involved in VICC in patients after envenomation by South Korea's snakes. Additionally, we studied the effectiveness of antivenom for the treatment of VICC after envenomation. METHODS: Included patients were divided into three groups according to the severity of VICC (no VICC, partial VICC, and complete VICC). Data, including changes in coagulation parameters during hospitalization and clotting factors at presentation, were collected and analyzed. RESULTS: One hundred nineteen patients who presented at our emergency department within 3 h after snake envenomation were included. VICC developed in 34 patients (27 patients with partial VICC and 7 patients with complete VICC). Two of 34 patients with VICC required blood transfusions. Five patients with complete VICC had an undetectable fibrinogen concentration at presentation. Three patients with complete VICC had an unmeasurable INR and aPTT within 24 h. The median times of the most extreme values were 10 h for INR, 12 h for aPTT, and 16 h for fibrinogen after presentation in the VICC group. The D-dimer concentration peaked at a median of 63.5 h after presentation. The activities of factors II and X were significantly reduced in the complete VICC group (factor II: 88 (84-99.3)% in the non-VICC group vs. 69 (49.5-83.5)% in the complete VICC group; factor X:94 (83-102) in the non-VICC group vs. 70 (66.5-79.8)% in the complete VICC group), while there was no difference in factor V activity at presentation. The time from bite to first antivenom administration did not correlate with the time course and most extreme concentrations for fibrinogen and D-dimer within the VICC groups. DISCUSSION AND CONCLUSION: VICC occurs in approximately one-quarter of snakebite patients in South Korea; however, VICC itself does not appear to lead to clinical deterioration. Fibrinogen is an early diagnostic maker for complete VICC. Clotting factors II and X are involved in VICC. Future investigations should explore the mechanism of VICC from Korean snakebites and the effect of antivenom on VICC.

Revisiting straight-line repair in unilateral complete cleft lip: a comparison with rotation-advancement repair.

Rotation-advancement repair (RAR) has been the most widely used technique for unilateral cleft lip repair. We recently used a straight-line repair with medial orbicularis muscle lengthening (SLR-ml) technique, based on the hypothesis that it could minimize the postoperative scar appearance without causing s short-lip deformity when muscle reorientation is performed correctly. A retrospective cohort study was conducted on unilateral complete cleft lip patients who underwent cheiloplasty between 2009 and 2017. Two cheiloplasty techniques were compared: RAR and SLR-ml. Outcomes were evaluated by assessing follow-up photographs using three methods: (1) glance impression on a five-point scale, (2) Manchester Scar Scale, and (3) indirect anthropometry. Seventy-one patients were analysed: 41 in the RAR group (28 male, 13 female) and 30 in the SLR-ml group (15 male, 15 female). The glance impression (P=0.506) and Manchester Scar Scale (P=0.347) scores did not differ between the groups. According to the symmetry ratio (cleft side value/non-cleft side value), vertical lip height (P=0.804), horizontal lip length (P=0.881), and Cupid's bow width (P=0.122) did not differ significantly between the groups. The preoperative lip height discrepancy was not correlated with the postoperative vertical lip height. The SLR-ml method can be regarded as a successful tool for symmetric repair of unilateral cleft lip.

The effect of myocardial injury on the clinical course of snake envenomation in South Korea.

CONTENT: This study investigated the incidence, progression and clinical course of myocardial injury-related snake envenomation in South Korea. In addition, this study evaluated whether antivenom guidelines are appropriate to control envenomation in patients with myocardial injury. METHODS: The study included 198 patients who received antivenom after a snakebite, and they were divided into two groups according to evidence of myocardial injury (defined as elevated troponin I or ischemic change on electrocardiogram) at presentation. Data including serial troponin I, echocardiogram/coronary angiogram findings, the clinical course, and treatment were collected and analyzed. RESULTS: The incidence of myocardial injury at presentation was 15.2%. The troponin I level was 0.11 (0.07-0.56) ng/ml at presentation and tended to decrease over 24 h. Echocardiograms revealed neither regional wall motion abnormalities nor left ventricular dysfunction in 15 of 17 patients, while two patients showed signs of coronary artery stenosis on echocardiograms and coronary angiograms. However, compared with patients without myocardial injury, patients with myocardial injury had a higher frequency of systemic envenomation complications, including bleeding, respiratory failure, hypotension, acute kidney injury, thrombocytopenia and venom-induced consumption coagulopathy (VICC). The patients with myocardial injury at presentation needed significantly more frequent and larger doses of antivenom than indicated by the initial severity of envenomation. Multivariate analysis showed that myocardial injury was associated with the need for additional antivenom administration after initial administration. DISCUSSION AND CONCLUSION: Myocardial injury is not uncommon after snake envenomation in Korea. Although myocardial injury itself seems to be benign, the clinical course of patients with myocardial injury is complicated, and myocardial injury is associated with the need for additional antivenom administration. The optimal use of antivenom to control envenomation in patents with myocardial injury after snake envenomation in South Korea should be established.

Genetic parameters for yearling weight, carcass traits, and primal-cut yields of Hanwoo cattle.

Genetic parameters associated with yearling weight, carcass traits, and primal-cut yields of male Hanwoo cattle were investigated using univariate and bivariate animal models. The mean yearling weight (YWT), carcass weight (CWT), longissimus muscle area (LMA), backfat thickness (BFT), and marbling score (MS) were 352.47 ± 0.40 kg, 337.39 ± 0.64 kg, 78.28 ± 0.13 cm2, 8.45 ± 0.05 mm, and 3.25 ± 0.03, respectively. Total primal-cut yield (TPC) was 78.95 ± 0.10% of CWT, of which 42.3% was contributed by the forequarters (chuck, CHK; shoulder, SLD; ribs, RIB; and brisket and flank, BAF). Loins, top round (TRND), and round (RND) were associated with yields of 13.57%, 5.45 ± 0.01%, and 8.87 ± 0.02%, respectively. The largest cut studied was ribs (15.67 ± 0.03%). The estimated heritabilities (h2) of YWT, CWT, LMA, BFT, and MS were 0.18 ± 0.02, 0.29 ± 0.04, 0.38 ± 0.05, 0.45 ± 0.05, and 0.62 ± 0.07, respectively. Shoulder yield was highly heritable in Hanwoo steers (0.83 ± 0.13), followed by the yields of round (0.66 ± 0.12), striploin (0.64 ± 0.12), top round (0.62 ± 0.12), sirloin (0.60 ± 0.12), and total primal-cut yield (0.52 ± 0.11). The h2 values of CHK, BAF, RIB, and tenderloin (TLN) ranged from 0.19 ± 0.09 to 0.41 ± 0.11. Generally, the genetic CV was low for most traits (2.33%-6.15%), except for CHK, BFT, and MS. The genetic correlation (rg) was strong between YWT and CWT (0.77 ± 0.06). The greatest positive and negative rg among carcass traits were those between LMA and CWT (0.52 ± 0.08) and between LMA and BFT (-0.30 ± 0.09), respectively. The correlation between CHK and SLD (0.81 ± 0.14), and those between SLD, TLN, TRND, and RND, were mostly strong (0.77-0.87), but the rg between RIB and other traits were strongly negative. The TPC yield showed moderate to high rg with most primal cuts. The YWT, CWT, and LMA correlated notably with CHK, SLD, and loin yields, especially LMA. However, BFT and MS were negatively correlated with many primal cuts but RIB. Those rg estimates were also opposite of that of LMA and CWT with primal cuts. Phenotypic correlations (rp) were generally weaker than rg estimates. The rp of YWT, CWT, and LMA were either zero or moderately negative compared to those of the BFT and MS with primal cuts. Most primal cuts yielded positive rp estimates among them, except for RIB. Our results suggest that direct selection for YWT, various carcass traits, and primal-cut yields may increase the carcass value of Hanwoo males.

Performance characteristics of a conformal ultra-wideband multilayer applicator (CUMLA) for hyperthermia in veterinary patients: a pilot evaluation of its use in the adjuvant treatment of non-resectable tumours.

Performance and clinical characteristics of a novel hyperthermia antenna operating at 434 MHz were evaluated for the adjuvant treatment of locally advanced superficial tumours in cats, dogs and horses. Electromagnetic simulations were performed to determine electric field characteristics and compared to simulations for a flat microwave antenna with similar dimensions. Simulation results show a reduced skin surface and backfield irradiation and improved directional irradiation (at broadside) compared to a flat antenna. Radiated power and penetration is notably increased with a penetration depth of 4.59 cm compared to 2.74 cm for the flat antenna. Clinical use of the antenna was then evaluated in six animals with locoregionally advanced solid tumours receiving adjuvant chemotherapy. During clinical applications, therapeutic temperatures were achieved at depths ≥4 cm. Objective responses were seen in all patients; tissue toxicity in one case limited further therapy. This antenna provides compact, efficient, focused and deep-penetrating clinical hyperthermia for the treatment of solid tumours in veterinary patients.

microRNAs in stroke pathogenesis.

Stroke is one of the leading causes of death and disability worldwide. There are two major types of stroke: cerebral ischemia caused by obstruction of blood vessels in the brain and haemorrhagic stroke that is triggered by the disruption of blood vessels. Thrombolytic therapy involving recombinant tissue plasminogen activator (rtPA) has been shown to be beneficial only when used within 4.5 hours of onset of acute ischemic stroke. rtPA treatment beyond this time window has been found to be unsuitable and usually resulting in haemorrhagic transformation. Stroke is a multifactorial disease that forms a possible end state for majority of patients suffering from diabetes, atherosclerosis and hypertension which are known risk factors. Although the biochemistry of stroke and related diseases is quite well understood, the knowledge on the molecular mechanisms underlying these diseases is still at its infancy. microRNAs that form a unique class of endogenous riboregulators of gene function, offer tremendous potential in unraveling the mechanisms underlying stroke pathogenesis. microRNA expression also reflects the response of individuals to drugs and therapy. Several microRNAs and their target genes, known to be involved in endothelial dysfunction, dysregulation of neurovascular integrity, edema formation, pro-apoptosis, inflammation and extra-cellular matrix remodeling contribute to the critical processes in the pathogenesis of stroke. In this review, we will also be discussing the role of microRNAs as possible diagnostic and prognostic biomarkers as well as potential therapeutic targets in stroke pathogenesis.

Central nervous system (CNS) relapse in diffuse large B cell lymphoma (DLBCL): pre- and post-rituximab.

Central nervous system (CNS)-directed prophylactic intrathecal (IT) therapy is indicated in patients with Burkitt and acute lymphoblastic lymphoma. Its role in diffuse large B cell lymphoma (DLBCL), a heterogeneous subtype, is less well defined. While addition of rituximab to standard cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone (CHOP) chemotherapy (R-CHOP) has improved the outcomes of DLBCL patients, its role in reducing CNS relapse is unclear. We aim to (1) evaluate the clinical risk factors predictive of CNS relapse, (2) the role of rituximab in influencing CNS relapse, and (3) role of intrathecal prophylaxis. Four hundred ninety-nine patients with DLBCL from 2000 to 2008 were included (CHOP 179 vs. R-CHOP 320). IT prophylaxis was administered to 82 patients based on our institution's guidelines. Baseline characteristics between CHOP- and R-CHOP-treated patients were similar. Although R-CHOP significantly increased the complete remission rate from 71% to 81% (P < 0.01), CNS relapse rates remained unchanged (R-CHOP 6% vs. CHOP 5.1%). On multivariate analysis, poor performance status (Eastern Cooperative Oncology Group >1; hazard ratio (HR) = 2.01, 95% confidence interval (CI) 1.29-3.14), failure to attain remission (non-complete response (CR) vs. CR: HR = 2.39, 95% CI = 1.03 to 5.51), testicular (HR = 6.67, 95% CI = 1.62 to 27.53), kidney (HR = 20.14, 95% CI = 5.23 to 77.46), and breast involvement (HR = 6.14, 95% CI = 1.61 to 23.37) were each independently predictive of CNS relapse. Use of IT prophylaxis did not appear to decrease CNS relapse. Median survival after CNS relapse was 3.2 months. CNS relapse, a fatal event, remains a challenge in R-CHOP-treated patients. IT prophylaxis may not be sufficient to reduce CNS relapse, and strategies including systemic agents with high CNS penetration should be evaluated in high-risk patients identified in this study.

Functional expression of an insect cathepsin B-like counter-defence protein.

Insects are capable of readjusting their digestive regimes in response to dietary challenge. Cowpea bruchids (Callosobruchus maculatus) strongly induce C. maculatus cathepsin B-like cysteine protease 1 (CmCatB1) transcripts when fed diet containing a soybean cysteine protease inhibitor soyacystatin N (scN). CmCatB1 shares significant sequence similarity with cathepsin B-like cysteine proteases. In this study, we isolated another cDNA, namely CmCatB2 that encodes a protein sequence otherwise identical to CmCatB1, but lacking a 70-amino-acid internal section. CmCatB1 and CmCatB2 probably resulted from alternate splicing events. Only the CmCatB1 transcript, however, exhibited differential expression in response to dietary scN. Further, this expression was only detectable in larvae, which is the developmental stage associated with food ingestion. The scN-activated and developmentally regulated CmCatB1 expression pattern suggests it may have a unique function in insect counter-defence against antinutritional factors. Heterologously expressed recombinant CmCatB1 protein exhibited enzymatic activity in a pH-dependent manner. Activity of the protein was inhibited by both the cysteine protease inhibitor E-64 and the cathepsin B-specific inhibitor CA-074, verifying its cathepsin B-like cysteine protease nature. Interestingly, the enzymatic activity was unaffected by the presence of scN. Together, we have provided functional evidence suggesting that CmCatB1 confers inhibitor-insensitive enzymatic activity to cowpea bruchids, which is crucial for insect survival when challenged by dietary protease inhibitors.

Dysbindin gene variants are associated with bipolar I disorder in a Korean population.

The dysbindin gene (DTNBP1) has been associated with schizophrenia in several populations. Because the clinical characteristics of schizophrenia and bipolar disorder overlap in many respects and findings from genetic studies have suggested common genes between them, we conducted a case control association study of bipolar disorder in Korea to investigate the genetic association between DTNBP1 and bipolar disorder. In total, 163 patients with bipolar disorder and 350 controls were evaluated. We genotyped three single nucleotide polymorphisms of DTNBP1 (SNP A, P1763, and P1320) and analyzed the allele, genotype, and haplotype associations with bipolar disorder. We found significant genotypic associations with P1763 and P1320, but no association with SNP A in the bipolar I group. When we included bipolar II and schizoaffective disorder in the affected phenotype, the significance decreased. A positive association was observed between the SNP A-P1763 haplotype and the bipolar I phenotype. This haplotype association was lost when we either broadened our phenotype or included P1320 in a haplotype. The positive results of the present study lost significance after a Bonferroni correction for multiple testing. These findings are consistent with previous findings that showed a positive association of DTNBP1 with bipolar disorders. Moreover, our results suggest that DTNBP1 may contribute more to bipolar I disorder than bipolar II disorder or schizoaffective disorder. Further comprehensive studies will be required to clarify these association, however, it seems likely that DTNBP1 is a susceptibility gene for bipolar disorder.

Short-term distributions of reduced sulfur compounds in the ambient air surrounding a large landfill facility.

In order to explore the environmental behavior of reduced sulfur compounds (RSC) as malodorous components emitted from diverse source processes, the distribution characteristics of four sulfur (S) compounds - hydrogen sulfide (H2S), methyl mercaptan (CH3SH), dimethyl sulfide (DMS: (CH3)2S), and dimethyl disulfide (DMDS: (CH3)2S2) - were investigated in a municipal landfill area. In the course of this study, their ambient concentration levels were measured during two time periods from 13 individual spots selected as a function of distance from the center of the landfill site. The results generally indicated the absolute dominance of H2S over the other S compounds investigated (up to 5 km radius) such that their mean values were found as 1415 (H2S), 148 (DMS), 20.6 (CH3SH), and 14.4 ppt (DMDS). When our data were compared in terms of either varying distance from the source or relationship with meteorological conditions, the H2S data sets were most evident to reflect the potential effects of strong source processes in the landfill environment, relative to other S gases (or to volatile organic compounds measured concurrently). The results of this study further indicated the relatively good correspondence between the measured H2S concentration level and humans' intuitive sensory of odor and nuisance.

Prognostic significance of glycaemic control in patients with HBV and HCV-related cirrhosis and diabetes mellitus.

AIMS: Diabetes mellitus (DM) is frequently observed in patients with cirrhosis, particularly that due to hepatitis C virus (HCV) infection. However, no studies have focused on the clinical significance of glycaemic control in cirrhotic patients because of their short life expectancy and poor hepatic function. The aim of this study was to evaluate the prognostic impact of glycaemic control in patients with hepatitis B virus (HBV) and HCV-related cirrhosis and DM. METHODS: A total of 434 patients with HCV-related (HCV group, n = 88) or HBV-related (HBV group, n = 346) cirrhosis were studied retrospectively. We determined the prevalence of DM and treatment methods for hyperglycaemia and status of glycaemic control, and the patients' outcome. RESULTS: The prevalence of DM was 43.2% (38/88) in the HCV group and 19.7% (68/346) in the HBV group. Patients in the HCV group were older with a female preponderance. DM was detected before the diagnosis of cirrhosis or simultaneously in 92% and 79% in the HCV and HBV groups, respectively. Most patients were treated with insulin or oral hypoglycaemic agents. However, blood glucose levels were maintained within the normal range in 34.2% of the HCV group and in 23.5% of the HBV group. Forty-six patients died during the observation period in both groups. Hepatic failure was the most common cause of death, and sepsis and variceal bleeding were more frequent in the HCV group than in the HBV group. Multivariate analysis showed that Child-Pugh class was the most important factor for survival in both groups. In the HCV group, the status of glycaemic control was a significant independent factor of survival (P = 0.018). In the HBV group, age and the development of spontaneous bacterial peritonitis were significant. CONCLUSION: DM is more frequent in patients with HCV-related cirrhosis than in patients with HBV. Strict control of blood glucose levels could improve survival in HCV patients. A precise assessment of the risks and benefits of glycaemic control is required to reduce the mortality and morbidity of patients with cirrhosis and DM.