Chrysosplenol-C Increases Contraction by Augmentation of Sarcoplasmic Reticulum Ca2+ Loading and Release via Protein Kinase C in Rat Ventricular Myocytes.

Naturally found chrysosplenol-C (4',5,6-trihydroxy-3,3',7-trimethoxyflavone) increases the contractility of cardiac myocytes independent of ß-adrenergic signaling. We investigated the cellular mechanism for chrysosplenol-C-induced positive inotropy. Global and local Ca2+ signals, L-type Ca2+ current (ICa), and contraction were measured from adult rat ventricular myocytes using two-dimensional confocal Ca2+ imaging, the whole-cell patch-clamp technique, and video-edge detection, respectively. Application of chrysosplenol-C reversibly increased Ca2+ transient magnitude with a maximal increase of ∼55% within 2- to 3-minute exposures (EC50 ≅ 21 µM). This chemical did not alter ICa and slightly increased diastolic Ca2+ level. The frequency and size of resting Ca2+ sparks were increased by chrysosplenol-C. Chrysosplenol-C significantly increased sarcoplasmic reticulum (SR) Ca2+ content but not fractional release. Pretreatment of protein kinase C (PKC) inhibitor but not Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor abolished the stimulatory effects of chrysosplenol-C on Ca2+ transients and Ca2+ sparks. Chrysosplenol-C-induced positive inotropy was removed by the inhibition of PKC but not CaMKII or phospholipase C. Western blotting assessment revealed that PKC-δ protein level in the membrane fractions significantly increase within 2 minutes after chrysosplenol-C exposure with a delayed (5-minute) increase in PKC-α levels in insoluble membrane. These results suggest that chrysosplenol-C enhances contractility via PKC (most likely PKC-δ)-dependent enhancement of SR Ca2+ releases in ventricular myocytes. SIGNIFICANCE STATEMENT: Study shows that chrysosplenol-C, a natural flavone showing a positive inotropic effect, increases SR Ca2+ releases on depolarizations and Ca2+ sparks with an increase of SR Ca2+ loading but not L-type Ca2+ current in ventricular myocytes. Chrysosplenol-C-induced enhancement in contraction is eliminated by PKC inhibition, and it is associated with redistributions of PKC to the membrane. These indicate that chrysosplenol-C enhances contraction via PKC-dependent augmentations of SR Ca2+ release and Ca2+ loading during action potentials.

Factors associated with HIV/AIDS-related stigma and discrimination by medical professionals in Korea: A survey of infectious disease specialists in Korea.

OBJECTIVES: This study sought to identify factors associated with this discrimination by medical professionals in Korea. SUBJECTS AND METHODS: This study was a cross-sectional survey. We conducted web-based surveys against infectious disease specialists and infectious disease nurse. We evaluated the frequency of human immunodeficiency virus (HIV)/AIDS-related discrimination by medical professionals by health service type on the 5-point scale. We identified the association between several factors and HIV/AIDS-related stigma and discrimination by medical professionals on the 5-point scale. RESULTS: A total of 81 experts, 57 infectious disease specialists (approximately 27% of all infectious disease specialists in Korea) and 24 infectious disease nurse practitioners, participated in this study. The frequency of stigma and discrimination increased significantly when invasive treatment included both outpatient and inpatient services (both P < 0.05). Medical professional's preconceptions, fear of infection, and lack of knowledge have an association with HIV/AIDS-related stigma and discrimination by medical professionals. CONCLUSION: HIV/AIDS-related stigma and discrimination by medical professionals in Korea might be associated with factors related to the fear of medical professionals.

The accuracies of abdominal computed tomography and the neutrophil-to-lymphocyte ratio used to predict the development of clinically severe acute cholecystitis in elderly patients visiting an emergency department.

BACKGROUND: Mortality in patients with severe acute cholecystitis (AC) remains high, and the prognosis for elderly patients tends to be poor. A comparative analysis of clinical, laboratory, and abdominal computed tomography (CT) parameters was conducted in this study to investigate the effectiveness of each index for predicting clinically severe AC in elderly patients in the emergency department (ED). METHODS: This was a single-center, retrospective study that included 156 patients (≥65 years of age) with AC who were admitted in the ED between January 2012 and December 2014. Parameters including age, gender, initial clinical findings, laboratory findings, and CT findings in the ED were examined for their ability to predict severity. RESULTS: Forty-five patients were diagnosed with clinically severe AC. The white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, erythrocyte sedimentation rate, protein, albumin, and prothrombin time/International Normalized Ratio values were significantly higher in the severe group than in the nonsevere group (P < 0.05). In addition, the CT parameters of increased pericholecystic fat stranding and pericholecystic fluid collection were significantly higher in the severe group than in the nonsevere group (P < 0.001, P < 0.001). Increased pericholecystic fat stranding (odds ratio [OR], 8.17; 95% confidence interval [CI], 2.29-29.22; P = 0.001), pericholecystic fluid collection (OR, 6.55; 95% CI, 1.39-30.92; P = 0.018), and an NLR cutoff value of 9.9 (OR, 4.20; 95% CI, 1.01-17.53; P = 0.049) were independent predictors of severe AC in elderly patients. CONCLUSIONS: The CT parameters of increased pericholecystic fat stranding and pericholecystic fluid collection with an NLR cutoff of 9.9 were useful for predicting the severity of AC in elderly patients in the ED.

Iliacus abscess with radiculopathy mimicking herniated nucleus pulposus: Additional diagnostic value of magnetic resonance imaging.

An iliacus abscess is an extremely rare cause of low back pain. With an iliacus abscess, the classical signs seen with a psoas abscess are frequently absent. Therefore, a timely diagnosis at the initial visit is difficult and inadequate treatment usually results in high mortality. Here, we report the case of 19-year-old man who presented with acute low back pain with radiculopathy and was ultimately diagnosed with an iliacus muscle abscess.

Clinical features of emergency department patients with depression who had attempted to commit suicide by poisoning.

BACKGROUND: Many patients present to the emergency department (ED) complaining of intentional poisoning. Of those, some have major depressive disorder (MDD) in their medical history. The aim of this study was to investigate the prevalence of MDD patients who were treated for poisoning in the ED. MATERIALS AND METHODS: A retrospective review was performed on 268 patients who were treated with poisoning between July 2007 and November 2011. Of these patients, we only included those who were over 18 years of age. Information regarding age, gender, cause, time of ingestion, type of drug, history of attempting suicide, and outcome, among other characteristics, was collected and compared to patients who did not have MDD. RESULTS: A total of 244 patients were included in this study. Of those, 52 patients (21.3%) had a history of MDD. Compared to non-MDD patients, a majority (34.6% vs. 19.8%) of those in the MDD group had a history of suicide attempts (P = 0.027), and 34 (65.4% in the MDD group vs. 34.4% in the non-MDD group) took more than two types of drugs (P < 0.001). There were no differences in age, sex, time of ingestion or disease severity between MDD and non-MDD patients. CONCLUSION: In poisoning patients with MDD, physicians in the ED must consider that they have a higher tendency to show suicidal behavior and to have ingested multiple types of drugs.

Physician and nurse knowledge about patient radiation exposure in the emergency department.

BACKGROUND: Imaging methods that use ionizing radiation in emergency departments (EDs) have increased with advances in radiological diagnostic methods. Physician and nurse awareness of the radiation dose in the ED and the associated cancer risks to which the patients are exposed were surveyed with a questionnaire. METHODS: A total of 191 subjects in six EDs participated in this study. ED physicians and ED nurses were asked about the risks and the radiation doses of imaging methods ordered in the ED. The differences between the two groups were compared using Student's t-test for continuous variables. A Fisher's exact and Chi-squared tests were used for categorical variables. RESULTS: A total of 82 ED physicians and 109 ED nurses completed the questionnaire; 38 (46.3%) physicians and 8 (7.3%) nurses correctly answered the question about the chest X-ray radiation dose. A question about the number of chest X-rays that is equivalent to the dose of a pelvic X-ray was answered correctly by 5 (6.1%) physicians and 9 (8.3%) nurses (P = 0.571). Questions regarding abdominal computed tomography (CT), chest CT, brain CT, abdominal ultrasonography, and brain magnetic resonance imaging were answered correctly more frequently by the physician group than the nurse group (P < 0.05). The risk of developing cancer over a lifetime due to a brain CT was correctly answered by 21 (25.6%) physicians and 30 (27.5%) nurses (P = 0.170). A similar question regarding abdominal CT was correctly answered by 21 (25.6%) physicians and 42 (38.5%) nurses (P = 0.127). CONCLUSIONS: Knowledge of the radiation exposure of radiology examinations was lower in nurses than physicians, but knowledge was poor in both groups. ED physicians and nurses should be educated about radiation exposure and cancer risks associated with various diagnostic radiological methods.

The clinical usefulness of initial serum procalcitonin as an aggravation predictor in a hepatobiliary tract infection at emergency department.

BACKGROUND AND OBJECTIVES: The ability to predict future clinical deterioration early in patients who present to an emergency care center with a hepatobiliary tract infection is difficult. We studied the clinical usefulness of the initial serum levels of procalcitonin in a hepatobiliary tract infection as an indicator for predicting aggravation in the early stages. METHODS: Of the patients who presented with the clinical symptoms of a hepatobiliary tract infection, 99 were diagnosed with a hepatobiliary tract infection by imaging studies and subsequently enrolled in the study. Laboratory tests were obtained in the early stage of disease after presentation to an emergency care center. We assessed and compared the serum levels of many early inflammatory markers (white blood cell [WBC] counts, C-reactive protein and procalcitonin) between patients whose symptoms were initially stable upon arrival to an emergency care center but then deteriorated to, those whose symptoms remained consistently stable. Thus, we examined if the above serum markers are useful in predicting the possibility of future symptom aggravation. RESULTS: Of a total of 99 patients, 27 were assigned to the symptom aggravation group. The serum levels of WBC counts and C-reactive protein in the aggravation group were elevated. However, the median value (interquartile range) of procalcitonin was relatively increased at 2.28 (0.41-7.84 ng/ml), demonstrating a significant difference. CONCLUSIONS: In conclusion, initial serum levels of procalcitonin might be used as an indicator for aggravation in patients with hepatobiliary tract infection at the emergency department, even though there is hemodynamic stability.

Effect of tamsulosin on stone expulsion in proximal ureteral calculi: an open-label randomized controlled trial.

AIM: Medical expulsive therapy (MET) using alpha-blockers is effective for distal ureteral calculi (UC). We aimed to evaluate the efficacy of tamsulosin for proximal UC expulsion. MATERIALS AND METHODS: An open-label randomized controlled trial was conducted with 108 patients who agreed to conservative management for single, radiopaque, proximal UC ≤ 6 mm and were randomized into group A (n = 54, conservative managements only) or B (n = 54, 0.2 mg tamsulosin once a day). The primary end-point was stone passage rates (SPR) in the intention-to-treat population in 4 treatment weeks. The secondary end-points were estimated in per-protocol population and were time to stone passage, post-trial Euro-quality-of-life (EuroQOL) score, oral analgesic requirements, and willingness to undergo conservative treatment again. RESULTS: The two groups were well balanced in terms of baseline patient and stone characteristics. Seventy nine patients (73.2%; 35 of group A and 44 of group B) completed the study protocol. The overall SPR was 60.2% (65/108). Group B had a higher SPR (74.1%; 40/54) than group A (46.3%; 25/54; p = 0.003) and a significantly shorter time to stone passage (mean days, A: 19.6 vs. B: 14.3, p = 0.005). The groups did not differ in post-trial EuroQOL score or oral analgesic requirements, whereas 74.3% (26/35) of group A and 90.9% (40/44) of group B were willing to undergo conservative treatment again (p = 0.048). Univariate logistic regression analysis showed that stone size (OR = 1.447, p = 0.045) and tamsulosin treatment (OR = 3.314, p = 0.004) significantly predicted stone expulsion. On multivariate analysis, only tamsulosin was statistically significant (OR=3.198, p = 0.021). CONCLUSIONS: Tamsulosin was associated with significantly higher stone expulsion rate and shorter expulsion time in proximal UC ≤ 6 mm compared with conservative managements only. Our results indicate that similar to patients with distal UC, MET using tamsulosin is a reasonable treatment option for patients with proximal UC.

Telemetry capsule for measuring contractile motion in the small intestine.

The aim of this study was to develop a capsule which can measure contractions in the small intestine. Currently available methods cause discomfort to the patient while taking measurements; with the development of a telemetry capsule that can measure contractions, patients can avoid pain and continue with ordinary activities while the information is automatically collected from the external receiver. In order to develop the contraction force measuring capsule, various types of silicone transducers were designed and implemented to measure the contraction pressure in the small intestine. The minimum resolution of the implemented transducer was 0.05 mbar, which was small enough to measure contractions. The transducer was assembled with telemetry modules and packaged as a capsule (Φ13 × L25 mm) that had a similar size to a commercial capsule endoscope. In order to verify the function of the capsule, in vitro experiments were conducted and contractile motion was measured as 16.6 cycles per minute (CPM).

Feedback characteristics between implantable microphone and transducer in middle ear cavity.

With the advent of implantable hearing aids, implementation and acoustic sensing strategy of the implantable microphone becomes an important issue; among the many types of implantable microphone, placing the microphone in middle ear cavity (MEC) has advantages including simple operation and insensitive to skin touching or chewing motion. In this paper, an implantable microphone was implemented and researched feedback characteristic when both the implantable microphone and the transducer were placed in the MEC. Analytical and finite element analysis were conducted to design the microphone to have a natural frequency of 7 kHz and showed good characteristics of SNR and sensitivity. For the feedback test, simple analytical and finite element analysis were calculated and compared with in vitro experiments (n = 4). From the experiments, the open-loop gain and feedback factor were measured and the minimum gain margin measured as 14.3 dB.

Primary Osteoma Cutis in the Interscapular Region of a Dog.

A 9-year-old neutered male Shih Tzu was presented with three contiguous firm nodules in the subcutaneous tissue of the interscapular region. Histopathological examination revealed that the nodules consisted of mature lamellar bone with a Haversian system, with no apparent lesion around the bone. Clinical examination revealed that the dog had no underlying disease and no history of trauma at the lesion site. Based on these findings and on the medical history, a diagnosis of primary osteoma cutis was made. Osteoma cutis is rare in both human and veterinary medicine, and most dogs reported to have secondary osteoma cutis. To our knowledge, this case is only the second report of primary osteoma cutis in a dog.

Soil washing using various nonionic surfactants and their recovery by selective adsorption with activated carbon.

The performance of activated carbon in soil washing and subsequent selective adsorption for surfactant recovery from the washed solution was investigated. Sandy loam soil contaminated with phenanthrene at 200 mg kg(-1) was washed with four different nonionic surfactants: Tween 40, Tween 80, Brij 30 and Brij 35. The efficiency of soil washing was highest when using Brij 30 with the highest solubilizing ability for phenanthrene and low adsorption onto soil. In the selective adsorption step, surfactant recovery was quite effective for all surfactants ranging from 85.0 to 89.0% at 1 g L(-1) of activated carbon (Darco 20-40 mesh). Phenanthrene removal from the solution washed with Brij 30 was only 33.9%, even though it was 54.1-56.4% with other surfactants. The selectivity was larger than 7.02 except for Brij 30 (3.60). The overall performance considering both the washing and surfactant recovery step was effective when using Tween 80 and Brij 35. The results suggest that higher solubilizing ability of surfactants is a requirement for soil washing but causes negative effects on phenanthrene removal in the selective adsorption. Therefore, if a surfactant recovery process by selective adsorption is included in soil remediation by washing, the overall performance including the two steps should be considered for properly choosing the surfactant.

Apparatus and method for achieving reproducible measurements of diauxic lag length and anoxic net maximum specific growth rate.

An apparatus for continuous growth of pure bacterial cultures under oxic conditions followed by a switch to anoxic batch conditions was designed. The application of this apparatus gave variability of measured parameters (diauxic lag length, anoxic net maximum specific growth rate) which were significantly lower than the variability of previously reported data. The improvement is attributed to more consistent nitrate reductase levels as a result of achieving steady state under oxic condition prior to switching to anoxic batch conditions.

Cdc5 interacts with the Wee1 kinase in budding yeast.

Development of a multicellular organism requires that mitosis and morphogenesis be coordinated. These processes must also be synchronized during the growth of unicellular organisms. In the yeast Saccharomyces cerevisiae, mitosis is dependent on the prior growth of a daughter cell in the form of a bud. Overexpression of wild-type Polo-like kinase Cdc5 or a catalytically inactive form resulted in the formation of multinucleate cells in budding yeast. Immunofluorescence analysis of these multinulceate cells showed that mitosis and bud formation were no longer linked. Others have shown that Swe1 is required for coupling mitosis to bud formation during a perturbed cell cycle. When the normal pathway of bud formation is perturbed, Swe1 functions to delay mitosis through negative regulation of Clb/Cdk. In cells lacking Swe1, multinucleate cells are formed in response to delays in bud formation. Affinity purification, two-hybrid analysis, and mutant characterization results suggested that Cdc5 and Swe1 interact. From these results, we conclude that multinucleate formation in response to Cdc5 overexpression is linked to titration of Swe1 function. These results also suggest that Cdc5 may be a negative regulator of Swe1.

Intra-oral Sebaceous Gland Tumours in Two Dogs.

A 12-year-old female miniature schnauzer and a 12-year-old neutered female cocker spaniel each had a grey-yellow nodular lesion arising from the gingiva. Microscopical examination showed that both nodules were composed of varied proportions of sebocytes and basal-type reserve cells with few ducts lined by stratified squamous epithelium. Based on the histopathological findings, the cases were diagnosed as sebaceous adenoma and sebaceous epithelioma, respectively. In man, the occurrence of sebaceous neoplasms in the oral cavity has been reported to some extent, but these lesions are very rare in animals. To the best of our knowledge, this is the first report of intra-oral sebaceous neoplasms in dogs. Intra-oral sebaceous epithelioma has never been reported in animals.

Systemic Mycobacterium kansasii Infection in a Domestic Shorthair Cat.

A 1-year-old, female domestic shorthair cat was presented with anorexia, depression and weight loss, accompanied by multifocal nodules affecting the face, pinnae and periarticular tissue. Routine medical treatments were ineffective. The animal's physical condition continued to deteriorate and it finally died. Post-mortem examination revealed multifocal to coalescing firm nodules with occasional ulceration affecting the ears, peri-ocular areas, nasal planum, oral cavity and laryngopharyngeal region. Tan-coloured, firm, nodular lesions were also observed in the periarticular tissue, lungs and tracheobronchial and mediastinal lymph nodes. Impression smears of several of these lesions revealed a myriad of slender rod-shaped organisms, mainly in the cytoplasm of macrophages. Histopathological examination showed severe pyogranulomatous inflammation with or without necrosis in the nodules. Acid-fast staining revealed large numbers of acid-fast bacilli. Mycobacterium kansasii was detected in the tissues using multiplex polymerase chain reaction and DNA sequencing. No protozoal or fungal organisms were detected using special stains. On the basis of these results, the cat was diagnosed with systemic M. kansasii infection. To our knowledge, there have been few reports of M. kansasii infection, especially with systemic spread, in cats.

Cloning and characterization of six highly similar endo-1,3-beta-glucanase genes in hexaploid wheat.

Pathogenesis-related (PR) proteins are often used as a marker of plant defense reactions. Some endo-1,3-beta-glucanase (Gns) genes encode proteins that belong to the PR protein family 2 (PR-2). Although the number of homologous family member genes is significantly greater in hexaploid wheat (Triticum aestivum L.) compared to other model plants, earlier studies did not evaluate the possible contribution of their homologs to hybridization signals in Northern blot analysis. In this study, we have examined whether routine transcriptional analyses of a PR gene is of high reliability or not by isolating six highly similar Gns genes (TaGlb2a, TaGlb2b, TaGlb2c, TaGlb2d, TaGlb2e, and TaGlb2f) and characterizing their expression patterns in detail. While TaGlb2b was shown to be a PR-2 gene, transcription of TaGlb2c and TaGlb2d was not induced upon infection with either powdery mildew (Erysiphe graminis) or head blight (Fusarium graminearum) pathogens; their transcripts were most abundant in healthy spikes (lemmas and in particular paleae). Therefore, in some cases, the conventional analyses do not necessarily provide accurate information on expression pattern of a PR gene in hexaploid wheat. This is also the first report of wheat genes that are specifically expressed in lemma/palea tissues of flowering spikelets.

Orally active antimalarial 3-substituted trioxanes: new synthetic methodology and biological evaluation.

On the basis of a mechanistic understanding of the mode of action of artemisinin-like antimalarials, a series of structurally simple 3-aryl-1,2,4-trioxanes 5 was designed and was prepared in three to five operations from commercial reactants. The 3-aryl group was attached in each case as a nucleophile. In an electronically complementary fashion, 3-(fluoroalkyl)-trioxanes 6 were prepared via attachment of electrophilic fluoroalkyl esters. Both in vitro and in vivo antimalarial evaluations of these new trioxanes showed 12 beta-methoxy-3-aryltrioxanes 5g, 5j, 5k, and 51 to be highly potent, with crystalline fluorobenzyl ether trioxane 5k especially potent even when administered to rodents orally. As shown by rearrangement of hexamethyl Dewar benzene into hexamethylbenzene, iron-induced degradation of some of these 3-aryltrioxanes 5 involves generation of high-valent iron oxo species that might kill malaria parasites.