The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma

AbstractTo test the hypothesis that the non-enzymatic reaction of quinones with thiols in plasma can generate reactive oxygens (ROS), thereby leading to potentiated cellular toxicity, we have studied the effect of a representative quinone compound, menadione, on plasma isolated from rats. The experimental results are as follows: (1) menadione generated ROS via non-enzymatic reaction with protein thiols in plasma; (2) the presence of plasma increased menadione-induced cytotoxicity to platelets; (3) pretreatment of plasma with a thiol-depleting agent significantly suppressed menadione-induced ROS and cytotoxicity. These results suggest that the non-enzymatic reaction of menadione with plasma thiols could be an important process in quinone-induced cellular toxicity

Construction of the Nursing Diagnosis Ontology in Obstetric and Gynecologic Nursing Unit using Nursing Process and SNOMED CT

PURPOSE: This study was performed to propose an ontology methodology based on standardized nursing process as framework in obstetric and gynecologic nursing practice. METHODS: The instrument used in this study was based on the nursing diagnosis classification established by North American Nursing Diagnosis Association (NANDA) (2009-2011), fifth edition of the Nursing Interventions Classification (NIC) (2008), forth edition of the Nursing Outcomes Classification (NOC) (2008) developed by Iowa State University and systematized nomenclature of medicine clinical terms (SNOMED CT). The nursing records data were collected from electronic medical records of one hospital from August to October 2010. RESULTS: One hundred and forty-one nursing diagnosis statements used in obstetric and gynecologic nursing unit were linked standardized nursing classifications and constructed nursing diagnosis ontology including interoperability. CONCLUSION: Not only will this result be helpful to complete nurse's lack of knowledge and experience, it will also help to determine nursing diagnosis logically by using standardized nursing process. It will be utilized as the method to construct ontology including interoperability in other nursing units. It will be presented nursing interventions according to nursing diagnosis and thus will be easier to establish nursing planning. This can provide immediate feedback of the nursing process application

The squeeze film effect on micro-electromechanical resonators

The air squeeze film damping effect on the dynamic responses of clamped micro- electromechanical resonators is investigated in this study. A dynamic model for a clamped micro-electromechanical resonator with the damping consideration is derived using Lagrange’s equation. The corresponding resonator eigen solutions are formulated and solved by employing the assumed-mode method. The effect of different parameters; i.e. the resonator size, ambient temperature and pressure on the squeeze film damping characteristics were simulated and investigated. The results indicate that the squeeze film damping effect may significantly affect the dynamic responses of micro-scale electromechanical resonator

A comprehensive functional map of the hepatitis C virus genome provides a resource for probing viral proteins.

UnlabelledPairing high-throughput sequencing technologies with high-throughput mutagenesis enables genome-wide investigations of pathogenic organisms. Knowledge of the specific functions of protein domains encoded by the genome of the hepatitis C virus (HCV), a major human pathogen that contributes to liver disease worldwide, remains limited to insight from small-scale studies. To enhance the capabilities of HCV researchers, we have obtained a high-resolution functional map of the entire viral genome by combining transposon-based insertional mutagenesis with next-generation sequencing. We generated a library of 8,398 mutagenized HCV clones, each containing one 15-nucleotide sequence inserted at a unique genomic position. We passaged this library in hepatic cells, recovered virus pools, and simultaneously assayed the abundance of mutant viruses in each pool by next-generation sequencing. To illustrate the validity of the functional profile, we compared the genetic footprints of viral proteins with previously solved protein structures. Moreover, we show the utility of these genetic footprints in the identification of candidate regions for epitope tag insertion. In a second application, we screened the genetic footprints for phenotypes that reflected defects in later steps of the viral life cycle. We confirmed that viruses with insertions in a region of the nonstructural protein NS4B had a defect in infectivity while maintaining genome replication. Overall, our genome-wide HCV mutant library and the genetic footprints obtained by high-resolution profiling represent valuable new resources for the research community that can direct the attention of investigators toward unidentified roles of individual protein domains.ImportanceOur insertional mutagenesis library provides a resource that illustrates the effects of relatively small insertions on local protein structure and HCV viability. We have also generated complementary resources, including a website (http://hangfei.bol.ucla.edu) and a panel of epitope-tagged mutant viruses that should enhance the research capabilities of investigators studying HCV. Researchers can now detect epitope-tagged viral proteins by established antibodies, which will allow biochemical studies of HCV proteins for which antibodies are not readily available. Furthermore, researchers can now quickly look up genotype-phenotype relationships and base further mechanistic studies on the residue-by-residue information from the functional profile. More broadly, this approach offers a general strategy for the systematic functional characterization of viruses on the genome scale

Effects of Early Surgical Exploration in Suspected Barotraumatic Perilymph Fistulas

ObjectivesTreatment of traumatic perilymph fistula (PLF) remains controversial between surgical repair and conservative therapy. The aim of this study is to analyze the outcomes of early surgical exploration in suspected barotraumatic PLF.MethodsNine patients (10 cases) who developed sudden sensorineural hearing loss and dizziness following barotrauma and underwent surgical exploration with the clinical impression of PLF were enrolled. Types of antecedent trauma, operative findings, control of dizziness after surgery, postoperative hearing outcomes, and relations to the time interval between traumatic event and surgery were assessed retrospectively.ResultsAll patients had sudden or progressive hearing loss and dizziness following trauma. Types of barotrauma were classified by the origin of the trauma: 4 external (car accident, slap injury) and 6 internal traumas (lifting, nasal blowing, straining). Surgical exploration was performed whenever PLF was suspected with the time interval of 2 to 47 days after the trauma. The possible evidence of PLF was found during surgery in 9 cases: a fibrous web around the oval window (n=3), fluid collection in the round window (RW; n=6) and bulging of the RW pseudomembrane (n=1). In every patient, vestibular symptoms disappeared immediately after surgery. The hearing was improved with a mean gain of 27.0±14.9 dB. When the surgical exploration was performed as early as less than 10 days after the trauma, serviceable hearing (≤40 dB) was obtained in 4 out of 7 cases (57.1%).ConclusionSudden or progressive sensorineural hearing loss accompanied by dizziness following barotrauma should prompt consideration of PLF. Early surgical exploration is recommended to improve hearing and vestibular symptoms

A Case of Cushing's Syndrome Presenting as Endometrial Hyperplasia

We describe here the case of a 39-year-old woman with a cortisol-producing adrenal adenoma and she presented with endometrial hyperplasia and hypertension without the specific characteristics of Cushing's syndrome. The patient had consulted a gynecologist for menometrorrhagia 2 years prior to her referral and she was diagnosed with endometrial hyperplasia and hypertension. Her blood pressure and the endometrial lesion were refractory despite taking multiple antihypertensives and repetitive dilation and curettage and progestin treatment. On admission, the clinical examination revealed mild central obesity (a body mass index of 22.9 kg/m2, a waist circumference of 85 cm and a hip circumference of 94cm), but there was no hirsutism and myopathy. She showed impaired glucose tolerance on an oral glucose tolerance test. The biochemical hypercortisolemia together with the prolactin and androgen levels were evaluated to explore the cause of her anovulation. Adrenal Cushing's syndrome was confirmed on the basis of the elevated urinary free cortisol (454 µg/24h, normal range: 20-70) with a suppressed ACTH level (2.0 pg/mL, normal range: 6.0-76.0) and the loss of circadian cortisol secretion. A CT scan revealed a 3.1 cm, hyperechoic, well-marginated mass in the left adrenal gland. Ten months post-adrenalectomy, the patient had unintentionally lost 9 kg of body weight, had regained a regular menstrual cycle and had normal thickness of her endometrium

A Case of Familial Comedonal Darier's Disease

Darier's disease is a genetic disorder of keratinization with autosomal dominant inheritance. Its appearance is usually in the form of greasy, crusted, keratotic yellow-brown papules and plaques found particularly on seborrheic areas of the body. However, there are some clinical variants showing atypical skin lesions. Here we report an unusual case of Darier's disease, which mainly showed prominent comedonal papules over the face