Mammalian Hippo kinase pathway is downregulated by BCL-2 via protein degradation.

Mammalian ste20-like kinase (MST) signaling pathway plays a significant part in control of cell death and cell cycle. It was originally found as Hippo pathway in Drosophila and composed of MST kinase and Salvador-1 (SAV1), a scaffold protein. In mammalian cells, MST pathway induces cell-cycle exit and apoptosis in response to various signals. BCL-2, an anti-apoptotic protein, inhibits cell death and plays an important part in tumorigenesis. In the present report, we present evidence showing that BCL-2 is a new regulator of MST pathway. First, protein levels of MST2 and SAV1 were reduced significantly by co-expression of BCL-2. Physical interaction of BCL-2 with SAV1 was correlated with proteasomal degradation of SAV1 and MST2 proteins. In SH-SY5Y neuroblastoma cell line expressing a high level of BCL-2 but low levels of MST2 and SAV1, siRNA-induced knockdown of BCL-2 restored the expression of MST2 and SAV1. Inhibition of BCL-2 with BAD or ABT-737, a BCL-2 inhibitor, reversed its effect on MST2 and SAV1 proteins. ABT737 increased HEK293 cell death significantly when both MST2 and SAV1 were co-expressed. These results suggest that cancer cells may avoid cell death through enhanced expression of BCL-2 which down-regulates the pro-apoptotic MST pathway.

Prediction of perioperative complications after robotic-assisted radical hysterectomy for cervical cancer using the modified surgical Apgar score.

BACKGROUND: Although there has been marked development in surgical techniques, there is no easy and fast method of predicting complications in minimally invasive surgeries. We evaluated whether the modified surgical Apgar score (MSAS) could predict perioperative complications in patients undergoing robotic-assisted radical hysterectomy. METHODS: All patients with cervical cancer undergoing robotic-assisted radical hysterectomy at our institution between January 2011 and May 2017 were included. Their clinical characteristics were retrieved from their medical records. The surgical Apgar score (SAS) was calculated from the estimated blood loss, lowest mean arterial pressure, and lowest heart rate during surgery. We modified the SAS considering the lesser blood loss typical of robotic surgeries. Perioperative complications were defined using a previous study and the Clavien-Dindo classification and subdivided into intraoperative and postoperative complications. We analyzed the association of perioperative complications with low MSAS. RESULTS: A total of 138 patients were divided into 2 groups: with (n = 53) and without (n = 85) complications. According to the Clavien-Dindo classification, 49 perioperative complications were classified under Grade I (73.1%); 13, under Grade II (19.4%); and 5, under Grade III (7.5%); 0, under both Grade IV and Grade V. Perioperative complications were significantly associated with surgical time (p = 0.026). The MSAS had a correlation with perioperative complications (p = 0.047). The low MSAS (MSAS, ≤6; n = 52) group had significantly more complications [40 (76.9%), p = 0.01]. Intraoperative complications were more correlated with a low MSAS than were postoperative complications [1 (1.2%) vs. 21 (40.4%); p < 0.001, 13 (15.1%) vs. 25 (48.1%); p = 0.29, respectively]. We also analyzed the risk-stratified MSAS in 3 subgroups: low (MSAS, 7-10), moderate (MSAS 5-6), and high risks (MSAS, 0-4). The prevalence of intraoperative complications significantly increased as the MSAS decreased p = 0.01). CONCLUSIONS: This study was consistent the concept that the intuitive and simple MSAS might be more useful in predicting intraoperative complications than in predicting postoperative complications in minimally invasive surgeries, such as robotic-assisted radical hysterectomy for cervical cancer.

In-bag power morcellation technique in single-port laparoscopic myomectomy.

OBJECTIVE: This study introduces and evaluates the feasibility, safety, and surgical outcomes of the in-bag power morcellation technique during single-port assisted (SPA) laparoscopic myomectomy in comparison with manual scalpel morcellation. METHODS: This is a retrospective review of a total of 58 patients who underwent SPA laparoscopic myomectomy employing in-bag power morcellation (n=27) or manual scalpel morcellation (n=31), performed between December 2014 and December 2016. Surgical outcomes, including total operation time, estimated blood loss, postoperative hemoglobin changes, postoperative hospital stay, postoperative pain (visual analog scale), perioperative and postoperative complications were evaluated. RESULTS: The demographics and patient characteristics were similar between both groups. The median patient age was 34 years and median body mass index was 20.84 kg/m2. The median specimen weight was 110 g. The median operating time was 138 minutes. The median estimated blood loss was 50 mL and the median postoperative hemoglobin change was 2.2 g/dL. The median postoperative hospital stay was 2 days and the median postoperative pain scores were 5 after 6 hours, 3 after 24 hours, and 2 after 48 hours. Occult malignancy was not identified in any patients. There were no intraoperative complications such as LapBag ruptures or gross spillage. CONCLUSION: In-bag power morcellation for SPA laparoscopic myomectomy is feasible and safe, minimizing the risks of open power morcellation. There were also no statistically significant differences in surgical outcomes.

Paradigm for diagnosing mycobacterial disease: direct detection and differentiation of Mycobacterium tuberculosis complex and non-tuberculous mycobacteria in clinical specimens using multiplex real-time PCR.

AIMS: Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) are clinically different, and the rapid detection and differentiation of M. tuberculosis complex (MTBC) and NTM is crucial for patient management and infection control. Given the slow growth of most pathogenic mycobacteria, nucleic acid amplification assays are excellent tools for direct identification of mycobacteria in clinical specimens. Recently, a multiplex real-time PCR assay was developed that can directly detect 20 mycobacterial species in clinical specimens. Here, we evaluated the diagnostic performance of the assay for diagnosing mycobacterial disease under routine laboratory conditions. METHODS: A total of 3334 specimens collected from 1437 patients suspected of tuberculosis infection were subjected to acid-fast bacilli staining, conventional culture and the multiplex real-time PCR assay. To evaluate the sensitivity and specificity of the assay, the overall diagnosis of tuberculosis was defined by positive culture plus medical history, and the 2007 American Thoracic Society and Infectious Disease Society of America diagnostic criteria for NTM disease were applied. RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value were 87.5%, 99.6%, 96.1% and 98.5%, respectively, for the detection of MTBC isolates and 53.3%, 99.9%, 95.2%, and 98.9%, respectively, for detecting NTM isolates. CONCLUSIONS: Thus, the assay can correctly differentiate between MTBC and NTM isolates in clinical specimens and would be a useful tool for the rapid differentiation of tuberculosis and NTM disease, despite its limited sensitivity for the diagnosis of NTM disease.

In vitro fertilization outcome in women with diminished ovarian reserve.

OBJECTIVE: This study aimed to identify factors that affect in vitro fertilization (IVF) outcomes in women with diminished ovarian reserve (DOR). METHODS: We reviewed 99 IVF cycles in 52 women with DOR between September 2010 and January 2015. DOR was defined as serum anti-Müllerian hormone level of <1.1 ng/dL or serum follicle-stimulating hormone level of ≥20 mIU/mL. Total 96 cycles in 50 patients were evaluated after excluding fertility preservation cases. RESULTS: The clinical pregnancy rate was 11.5% per cycle, and the total cancellation rate was 34.4%. Clinical pregnancy rate was significantly associated with the antral follicle count and the cause of the DOR. Age, serum anti-Müllerian hormone and follicle-stimulating hormone levels, antral follicle count, peak estradiol level, and the cause of DOR were significantly associated with cycle cancellation. However, history of previous ovarian surgery remained as a significant factor of clinical pregnancy (model 1: odds ratio [OR] 10.17, 95% confidence interval [CI] 1.46 to 70.84, P=0.019; model 2: OR 10.85, 95% CI 1.05 to 111.71, P=0.045). In cancellation models, idiopathic or previous chemotherapy group showed borderline significance (model 1: OR 3.76, 95% CI 0.83 to 17.04, P=0.086; model 2: OR 3.15, 95% CI 0.84 to 11.84, P=0.09). CONCLUSION: DOR caused by previous ovarian surgery may show better pregnancy outcome, whereas that caused by chemotherapy could significantly increase the cycle cancellation rate. Furthermore, patients with DOR who previously received gonadotoxic agents may show reduced efficacy and increased risk of IVF cycle cancellation.

Direct identification of mycobacteria from liquid media using a triplex real-time PCR coupled with pyrosequencing method.

Culture in enriched broth, as well as on a solid medium, is recommended for primary isolation of mycobacteria. With the introduction of liquid mycobacterial culture methods, a substantial workload regarding the identification of culture-recovered mycobacterial species, particularly Mycobacterium tuberculosis complex (MTC), has been imposed on our laboratory. We thus developed a triplex, real-time PCR coupled with pyrosequencing assay that can directly identify mycobacterial species from liquid media, which can reduce the workload. In this assay, real-time PCR simultaneously detects MTC and Mycobacterium xenopi, and amplifies the region of 16S rRNA gene containing hypervariable region A for pyrosequencing analysis; subsequent, pyrosequencing identifies many other nontuberculous mycobacteria. The assay was evaluated using 333 DNA samples directly prepared from liquid media, including 24 reference strains and 309 clinical isolates. Three hundred and twenty-eight (98.5%) of the 333 samples were correctly identified. The remaining five were determined as indeterminate. In conclusion, this coupled assay would be an alternative method for rapid identification of mycobacteria directly from liquid media in a clinical laboratory with a high workload in regions where tuberculosis is endemic.

The validities and efficiencies of korean ADHD rating scale and korean child behavior checklist for screening children with ADHD in the community.

OBJECTIVE: The purpose of this study is to examine the validity of primary screening tools for attention deficit hyperactivity disorder (ADHD) in a community-based sample of children using the Korean version of the Child Behavior Checklist (K-CBCL) and the Korean version of the ADHD Rating Scale (K-ARS). METHODS: A large-scale community-based study for ADHD screening was conducted in the Jeollabuk province in the Republic of Korea. In 2010-2011, we surveyed a total of 49,088 first- and fourth-grade elementary school students. All of the participants in this study were assessed by the K-ARS-Parent version (K-ARS-P) and the K-ARS-Teacher version (K-ARS-T) as the primary screening instruments. The Diagnostic Interview Schedule for Children Version IV (DISC-IV) was used for confirming the diagnosis of ADHD. DISC-IV was administered to subjects who received top 10% scores in the K-ARS-P or K-ARS-T tests. RESULTS: Of the 3,085 subjects who completed the DISC-IV, 1,215 were diagnosed as having ADHD. A reasonable level of sensitivity, specificity, and negative predictive value were obtained when the total K-ARS-P scores were ≥90th percentile. The positive predictive value and specificity increased significantly when the total K-ARS-P scores were ≥90th percentile, T scores were ≥60 in the attention problems of K-CBCL, and T scores were ≥63 in the total problems of K-CBCL. CONCLUSION: These results suggested that the K-ARS-P could effectively serve as a primary screening tool to identify elementary school children with ADHD in the community. Also, there might be some increment in the effectiveness of K-ARS-P when combined with K-CBCL-A and K-CBCL-T as a secondary screening tool.

Cyberbullying, problematic internet use, and psychopathologic symptoms among Korean youth.

To evaluate the associations between cyberbullying behaviors and problematic internet use, and to compare psychopathologic symptoms in victims, perpetrators, and victims-perpetrators of cyberbullying to those in youths who were not involved in cyberbullying. A total of 4531 youths (11-14 years of age) were recruited from elementary and middle schools. Among 4531 youths, 9.7% were involved in cyberbullying; 3.3% were only victims; 3.4% were only perpetrators; and 3.0% were victims-perpetrators. Cyberbullying behaviors were associated with problematic internet use as well as various psychopathologic symptoms. Depressive symptoms were associated with cyberbullying victimization, and rule-breaking behaviors and aggressive behaviors have relevance to cyberbullying perpetration. Greater attention needs to be paid to identify youths earlier who are involved in cyberbullying and prevent serious adverse consequences in them.

Effects of substrate heating on the photovoltaic characteristics of dye-sensitized solar cells during two-step Ti film deposition by RF magnetron sputtering.

Nanoporous Ti metal film electrodes for use as photoanodes in dye-sensitized solar cells (DSSCs) were deposited directly on the nanoporous TiO2 layer using the two-step RF magnetron sputtering technique. The Ti film electrode replaces the transparent conducting oxide (TCO) layer. The effect of substrate heating during the deposition of the Ti film was studied to improve the porosity and columnar array of the film pores and the resulting cell efficiency. The porous Ti layer (-41 microm) with low sheet resistance (-1.7 omega/sq) was obtained by deposition at 250 degrees C. The porous Ti layer collects electrons from the TiO2 layer and allows the diffusion of I-/I3(-) through the holes. The DSSC efficiency (eta) using porous Ti layers with highly columnar structures was measured with the highest conversion efficiency of -5.77%; the other photovoltaic properties were ff: 0.76, V(oc): 0.72 V, and J(sc): 10.6 mA/cm2.

Multiple Fistula Emptying into the Left Ventricle through the Entire Left Ventricular Wall.

Coronary artery fistulae are usually identified during invasive coronary angiographies. However, in this case, we made the early detection of coronary artery fistulae during non-invasive transthoracic echocardiography, by demonstrating diastolic multiple abnormal color Doppler flows on the entire left ventricular walls including left ventricular free wall, interventricular septum and apex, which were mimicking firecracker on the whole left ventricle. Fistulous communication from the coronary artery to the left ventricle is rare. Moreover, a case of multiple coronary fistulae emptying into the left ventricle through the entire left ventricular walls including left ventricular free wall, interventricular septum and apex is uncommon. We report a case of a 31-year-old woman who was diagnosed with multiple fistula communicating with entire left ventricular wall.

Response to cardiac markers in human serum analyzed by guided-mode resonance biosensor.

Cardiac markers in human serum with concentrations less than 0.1 ng/mL were analyzed by use of a guided-mode resonance (GMR) biosensor. Cardiac troponin I (cTnI), creatine kinase MB (CK-MB), and myoglobin (MYO) were monitored in the serum of both patients and healthy controls. Dose-response curves ranging from 0.05 to 10 ng/mL for cTnI, from 0.1 to 10 ng/mL for CK-MB, and from 0.03 to 1.7 µg/mL for MYO were obtained. The limits of detection (LOD) for cTnI, CK-MB, and MYO were less than 0.05, 0.1, and 35 ng/mL, respectively. Analysis time was 30 min, which is short enough to meet clinical requirements. Antibody immobilization and the hydrophilic properties of the guided-mode resonance filter (GMRF) surface were investigated by X-ray photoelectron spectroscopy (XPS) and by monitoring the peak wavelength shift and water contact angle (CA). Both assays used to evaluate the surface density of the immobilized antibodies, a sandwich enzyme-linked immunosorbent assay (ELISA) and a sandwich immunogold assay, showed that the antibodies were successfully immobilized and sufficiently aligned to detect the low concentration of biomarkers. Our results show that the GMR biosensor will be very useful in developing low-cost portable biosensors that can screen for cardiac diseases.

Detection abnormal pattern in activities of daily living using sequence alignment method.

As the aging is rapidly coming, the necessity of cares for old people increases. As requests for care services for patients requiring help of others increases, various systems for care services have been developed. For care services, recently, there have been developed technologies of tracking and monitoring daily activities of a person and recognizing the daily activities of the person by analyzing tracked data. Particularly, there have been developed systems for taking care of a person whose state should be periodically checked, such as patients or old persons. General care systems are good for tracking what activity the person executes, but limited to detecting what a person's state is, such as a normal or an abnormal state. So it is necessary to develop a new computational method to detect abnormal signs in a life pattern via changes of a sequence of activities of daily living.

Semi-automated clustering of gene expression data sets.

Clustering, as one of key analysis tools for gene expression data sets, attempts to discover groups of genes having similar expression patterns. In order to get a reasonable biological interpretation, it is desirable that a clustering result be accurate enough. However, conventional clustering methods do not always meet this demand since they require the exact tuning of input parameters and cluster centers for an acceptable quality of result. Through an intuitive user interaction, UI-Cluster solves the problem mentioned above, and yields better clustering results.

The Korean research & development program on micro-electro-mechanical systems (MEMS) in medical applications.

Non or minimally invasive approaches for medical applications are very important for the alleviation of patient complaints. The miniaturization of medical devices using micro & nano technologies might be one of the possible solutions. Several national research and development (R&D) programs have been launched by the Korean government to further the development of biological & medical micro/nano devices in this country. This paper gives an overview of the current status of national R&D programs which are related to the development of micro-electro-mechanical systems (MEMS)/Nano technology in biological and medical applications and discusses the main activities of each program.

Finding the evidence for protein-protein interactions from PubMed abstracts.

MOTIVATION: Protein-protein interactions play critical roles in biological processes, and many biologists try to find or to predict crucial information concerning these interactions. Before verifying interactions in biological laboratory work, validating them from previous research is necessary. Although many efforts have been made to create databases that store verified information in a structured form, much interaction information still remains as unstructured text. As the amount of new publications has increased rapidly, a large amount of research has sought to extract interactions from the text automatically. However, there remain various difficulties associated with the process of applying automatically generated results into manually annotated databases. For interactions that are not found in manually stored databases, researchers attempt to search for abstracts or full papers. RESULTS: As a result of a search for two proteins, PubMed frequently returns hundreds of abstracts. In this paper, a method is introduced that validates protein-protein interactions from PubMed abstracts. A query is generated from two given proteins automatically and abstracts are then collected from PubMed. Following this, target proteins and their synonyms are recognized and their interaction information is extracted from the collection. It was found that 67.37% of the interactions from DIP-PPI corpus were found from the PubMed abstracts and 87.37% of interactions were found from the given full texts. AVAILABILITY: Contact authors.

Composite dependency-reflecting model for core promoter recognition in vertebrate genomic DNA sequences.

This paper deals with the development of a predictive probabilistic model, a composite dependency-reflecting model (CDRM), which was designed to detect core promoter regions and transcription start sites (TSS) in vertebrate genomic DNA sequences, an issue of some importance for genome annotation. The model actually represents a combination of first-, second-, third- and much higher order or long-range dependencies obtained using the expanded maximal dependency decomposition (EMDD) procedure, which iteratively decomposes data sets into subsets on the basis of dependency degree and patterns inherent in the target promoter region to be modeled. In addition, decomposed subsets are modeled by using a first-order Markov model, allowing the predictive model to reflect dependency between adjacent positions explicitly. In this way, the CDRM allows for potentially complex dependencies between positions in the core promoter region. Such complex dependencies may be closely related to the biological and structural contexts since promoter elements are present in various combinations separated by various distances in the sequence. Thus, CDRM may be appropriate for recognizing core promoter regions and TSSs in vertebrate genomic contig. To demonstrate the effectiveness of our algorithm, we tested it using standardized data and real core promoters, and compared it with some current representative promoter-finding algorithms. The developed algorithm showed better accuracy in terms of specificity and sensitivity than the promoter-finding ones used in performance comparison.