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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

Silencing of Twist1 sensitizes NSCLC cells to cisplatin via AMPK-activated mTOR inhibition.

Twist1 is highly expressed in primary and metastatic non-small cell lung cancer (NSCLC), and thus acts as a critical target for lung cancer chemotherapy. In the current study, we investigated the underlying mechanism initiated by silencing of Twist1 that sensitizes NSCLC cells to cisplatin. Silencing of Twist1 triggered ATP depletion, leading to AMP-activated protein kinase (AMPK)-activated mammalian target of rapamycin (mTOR) inhibition in NSCLC cells. AMPK-induced mTOR inhibition, in turn, resulted in downregulation of ribosome protein S6 kinase 1 (S6K1) activity. Downregulation of mTOR/S6K1 reduced Mcl-1 protein expression, consequently promoting sensitization to cisplatin. Overexpression of Mcl-1 reduced PARP cleavage induced by cisplatin and Twist1 siRNA, suggesting that this sensitization is controlled through Mcl-1 expression. Interestingly, cells treated with Twist1 siRNA displayed upregulation of p21(Waf1/CIP1), and suppression of p21(Waf1/CIP1) with specific siRNA further enhanced the cell death response to cisplatin/Twist1 siRNA. In conclusion, silencing of Twist1 sensitizes lung cancer cells to cisplatin via stimulating AMPK-induced mTOR inhibition, leading to a reduction in Mcl-1 protein. To our knowledge, this is the first report to provide a rationale for the implication of cross-linking between Twist1 and mTOR signaling in resistance of NSCLC to anticancer drugs.

TXNIP potentiates Redd1-induced mTOR suppression through stabilization of Redd1.

The mammalian target of rapamycin (mTOR) is a highly conserved serine-threonine kinase activated in response to growth factors and nutrients. Because of frequent dysregulation of the mTOR signaling pathway in diverse human cancers, this kinase is a key therapeutic target. Redd1 is a negative regulator of mTOR, mediating dissociation of 14-3-3 from tuberous sclerosis complex (TSC)2, which allows formation of a TSC-TSC2 complex. In the present study, we identify TXNIP that inhibits mTOR activity by binding to and stabilizing Redd1 protein. Redd1 and TXNIP expression was induced by a synthetic glucose analog, 2-deoxyglucose (2-DG). Moreover, Redd1 expression in response to 2-DG was regulated by activating transcription factor 4 (ATF4). Overexpression of TXNIP was associated with reduced mTOR activity mediated by an increase in Redd1 level, whereas knockdown of TXNIP using small interfering RNA resulted in recovery of mTOR activity via downregulation of Redd1 during treatment with 2-DG. Interestingly, Redd1 was additionally stabilized via interactions with N-terminal-truncated TXNIP, leading to suppression of mTOR activity. Our results collectively demonstrate that TXNIP stabilizes Redd1 protein induced by ATF4 in response to 2-DG, resulting in potentiation of mTOR suppression. To the best of our knowledge, this is the first study to identify TXNIP as a novel member of the mTOR upstream that acts as a negative regulator in response to stress signals.

High speed receiver for capsule endoscope.

In this study, a high-speed receiver for a capsule endoscope was proposed and implemented. The proposed receiver could receive 20 Mbps data that was sufficient to receive images with a higher resolution than conventional receivers. The receiver used a 1.2 GHz band to receive radio frequency (RF) signal, and demodulated the signal to an intermediate frequency (IF) stage (150 MHz). The demodulated signal was amplified, filtered, and under-sampled by a high-speed analog-to-digital converter (ADC). In order to decode the under-sampled data in real time, a simple frequency detection algorithm was selected and was implemented by using a FPGA. The implemented system could receive 20 Mbps data.

Telemetry system for slow wave measurement from the small bowel.

A telemetry capsule system was designed and implemented to measure the slow wave activity of the small bowel, which is an important parameter for the diagnosis of gastric diseases. The capsule amplified the slow wave signal from the intraluminal electrodes, and transmitted the digitally sampled data by means of a radio frequency transmitter. The implemented capsule (11 x 21 mm(2)) was smaller than a commercially available capsule endoscope, and it can remain active for more than 18 h. The feasibility of using this capsule was investigated by conducting in vitro experiments, and the average motility signals of the ileum, jejunum, and colon were measured as 6.1, 10.2, and 1.5 cycles per minute, respectively.

A dual anteroposterior approach to the Bernese periacetabular osteotomy.

When the Bernese periacetabular osteotomy is performed through an anterior approach, the ischial and retroacetabular osteotomies and manual fracture of the incompletely osteotomized ischium are conducted with an incomplete view resulting in increased risk and morbidity. We have assessed the dual anteroposterior approach which appears to address this deficiency. We compared the results of the Bernese periacetabular osteotomy performed in 11 patients (13 osteotomies) through a single anterior approach with those in 12 patients (13 osteotomies) in whom the procedure was carried out through a dual anteroposterior approach. The estimated blood loss, the length of anaesthesia, duration of surgery and radiological parameters were measured. The mean operative time and length of anaesthesia were not significantly different in the two groups (p = 0.781 and p = 0.698, respectively). The radiological parameters improved to a similar extent in both groups after the operation but there was significantly less blood loss in the dual osteotomy group (p = 0.034). The dual anteroposterior approach provides a direct view of the retroacetabular and ischial parts of the osteotomy, within a reasonable operating time and with minimal blood loss and gives a satisfactory outcome.