Immunostimulatory Activities of CpG-Oligodeoxynucleotides in Teleosts: Toll-Like Receptors 9 and 21

Toll-like receptors (TLRs) are pattern-recognition receptors that detect a wide variety of microbial pathogens for the initiation of host defense immunological responses. Thirteen TLRs have been identified in mammals, and teleosts contain 22 mammalian or non-mammalian TLRs. Of these, TLR9 and TLR21 are the cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODNs) recognition TLRs in teleosts. TLR9 is a mammalian TLR expressed in teleost but not in the avian species. TLR21 is a non-mammalian TLR expressed in both teleost and the avian species. Synthetic CpG-ODNs are potent immunostimulants that are being studied for their application against tumors, allergies, and infectious diseases, and as a vaccine adjuvant in humans. The immunostimulatory effects of CpG-ODNs as vaccine adjuvants and their antimicrobial function in domestic animals and teleosts are also being investigated. Most of our current knowledge about the molecular basis for the immunostimulatory activity of CpG-ODNs comes from earlier studies of the interaction between CpG-ODN and TLR9. More recent studies indicate that in addition to TLR9, TLR21 is another receptor for CpG-ODN recognition in teleosts to initiate immune responses. Whether these two receptors have differential functions in mediating the immunostimulatory activity of CpG-ODN in teleost has not been well-studied. Nevertheless, the existence of two recognition TLRs suggests that the molecular basis for the immunostimulatory activity of CpG-ODN in teleosts is different and more complex than in mammals. This article reviews the current knowledge of TLR9 and TLR21 activation by CpG-ODNs. The key points that need to be considered for CpG-ODNs as immunostimulants with maximum effectiveness in activation of immune responses in teleosts are discussed. This includes the structure/activity relationship of CpG-ODN activities for TLR9 and TLR21, the structure/functional relationship of these two TLRs, and differential expression levels and tissue distributions for these two TLRs

Identification of SNP barcode biomarkers for genes associated with facial emotion perception using particle swarm optimization algorithm

BACKGROUND: Facial emotion perception (FEP) can affect social function. We previously reported that parts of five tested single-nucleotide polymorphisms (SNPs) in the MET and AKT1 genes may individually affect FEP performance. However, the effects of SNP-SNP interactions on FEP performance remain unclear. METHODS: This study compared patients with high and low FEP performances (n = 89 and 93, respectively). A particle swarm optimization (PSO) algorithm was used to identify the best SNP barcodes (i.e., the SNP combinations and genotypes that revealed the largest differences between the high and low FEP groups). RESULTS: The analyses of individual SNPs showed no significant differences between the high and low FEP groups. However, comparisons of multiple SNP-SNP interactions involving different combinations of two to five SNPs showed that the best PSO-generated SNP barcodes were significantly associated with high FEP score. The analyses of the joint effects of the best SNP barcodes for two to five interacting SNPs also showed that the best SNP barcodes had significantly higher odds ratios (2.119 to 3.138; P < 0.05) compared to other SNP barcodes. In conclusion, the proposed PSO algorithm effectively identifies the best SNP barcodes that have the strongest associations with FEP performance. CONCLUSIONS: This study also proposes a computational methodology for analyzing complex SNP-SNP interactions in social cognition domains such as recognition of facial emotion

Molecular Imaging, Pharmacokinetics, and Dosimetry of 111In-AMBA in Human Prostate Tumor-Bearing Mice

Molecular imaging with promise of personalized medicine can provide patient-specific information noninvasively, thus enabling treatment to be tailored to the specific biological attributes of both the disease and the patient. This study was to investigate the characterization of DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA) in vitro, MicroSPECT/CT imaging, and biological activities of 111In-AMBA in PC-3 prostate tumor-bearing SCID mice. The uptake of 111In-AMBA reached highest with 3.87 ± 0.65% ID/g at 8 h. MicroSPECT/CT imaging studies suggested that the uptake of 111In-AMBA was clearly visualized between 8 and 48 h postinjection. The distribution half-life (t1/2α) and the elimination half-life (t1/2β) of 111In-AMBA in mice were 1.53 h and 30.7 h, respectively. The Cmax and AUC of 111In-AMBA were 7.57% ID/g and 66.39 h∗% ID/g, respectively. The effective dose appeared to be 0.11 mSv/MBq−1. We demonstrated a good uptake of 111In-AMBA in the GRPR-overexpressed PC-3 tumor-bearing SCID mice. 111In-AMBA is a safe, potential molecular image-guided diagnostic agent for human GRPR-positive tumors, ranging from simple and straightforward biodistribution studies to improve the efficacy of combined modality anticancer therapy

Factors Influencing the Competency of Head Nurses When Assisting With Inhospital Cardiopulmonary Resuscitation

AbstractObjectiveHead nurses in a hospital setting work to maintain the quality of nursing care and ensure that staff nursing skills are up-to-date. Although cardiopulmonary resuscitation (CFR) is most often performed by physicians in a hospital, nurses play crucial assistance roles, including the administration of medication, record-keeping, obtaining intravenous access, and helping with intubation. Patient outcome is therefore related to nurses' skill level in CFR. We hypothesized that the more senior head nurses would be more skillful at assisting with CFR.Materials and MethodsWe conducted an observational study of 55 head nurses, who were asked to perform a 4-minute simulation in which they assisted with CFR using a resuscitation manikin. We collected demographic data, including age and years since becoming a nurse and becoming a head nurse, together with a stress score, which assessed the stress felt by the nurses while taking the test. These measures were analyzed along with the accuracy of the nurses' skills while performing CFR.ResultsTwenty-two skills were evaluated, with each skill graded as either a pass or fail. Only 30/55 (54.5%) of the head nurses passed all 22 skills. There was a significant difference in the numbers of skills with a pass rating (p = 0.043) in relation to the units where the head nurses were employed. Their performance also showed a strong negative correlation with age (p = 0.001), work experience (p = 0.028), and time since becoming head nurse (p<0.001). However, there was no significant difference between the numbers of skills with a pass rating and pre-test stress score (p = 0.129).ConclusionIn our study, the head nurses of surgical wards, medical wards, and intensive care units had better scores than the head nurses of pediatric, obstetrics-gynecology, and other units. In contrast with our original hypothesis, we found that the more senior head nurses' skills when assisting with CFR were poorer than those of their more junior colleagues. This suggests that senior head nurses should undergo frequent refresher courses, not only to help maintain their life-saving abilities, but also so that they can better mentor less experienced nurses in situations requiring CFR

Polycythemia vera as a presentation of renal angiomyolipoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Angiomyolipoma is a common benign renal tumor composed of thick-walled blood vessels, smooth muscle, and adipose tissue. It may be found incidentally during workup for suspected renal disease. Although angiomyolipoma may present as a palpable, tender renal mass with flank pain and gross or microscopic hematuria, many patients are asymptomatic. Erythrocytosis is an unusual presentation, and malignant transformation may be suspected. This report describes a rare case of a woman diagnosed with renal angiomyolipoma and polycythemia vera. The report discusses the differential diagnosis using erythropoietin, erythropoietin-receptor and Janus kinase 2.</p> <p>Case presentation</p> <p>A 79-year-old Chinese woman was diagnosed with erythrocytosis according to World Health Organization criteria. An upper left renal pole angiomyolipoma was successfully ablated after multiple phlebotomy treatments. Red cell count immediately returned to normal, but gradually increased after 4 months. Polycythemia vera was finally diagnosed by positive mutation of Janus kinase 2 and negative erythropoietin protein expression. Her clinical symptoms improved with regular phlebotomy and hydroxyurea treatment.</p> <p>Conclusion</p> <p>Concurrent occurence of angiomyolipoma and polycythemia vera is rare. Polycythemia vera can be easily missed. Polycythemia vera can be confirmed with high specificity and sensitivity by the acquired somatic mutation. Surgical intervention for this renal tumor should be avoided unless malignancy or renal cell carcinoma is suspected or to prevent spontaneous rupture of larger tumors.</p

Clinical characteristics and risk behavior as a function of HIV status among heroin users enrolled in methadone treatment in northern Taiwan

<p>Abstract</p> <p>Background</p> <p>Methadone treatment was introduced in Taiwan in 2006 as a harm-reduction program in response to the human immunodeficiency virus (HIV), which is endemic among Taiwanese heroin users. The present study was aimed at examining the clinical and behavioral characteristics of methadone patients in northern Taiwan according to their HIV status.</p> <p>Methods</p> <p>The study was conducted at four methadone clinics. Participants were patients who had undergone methadone treatment at the clinics and who voluntarily signed a consent form. Between August and November 2008, each participant completed a face-to-face interview that included questions on demographics, risk behavior, quality of life, and psychiatric symptoms. Data on HIV and hepatitis C virus (HCV) infections, methadone dosage, and morphine in the urine were retrieved from patient files on the clinical premises, with permission of the participants.</p> <p>Results</p> <p>Of 576 participants, 71 were HIV positive, and 514 had hepatitis C. There were significant differences between the HIV-positive and HIV-negative groups on source of treatment payment, HCV infection, urine test results, methadone dosage, and treatment duration. The results indicate that HIV-negative heroin users were more likely to have sexual intercourse and not use condoms during the 6 months prior to the study. A substantial percent of the sample reported anxiety (21.0%), depression (27.2%), memory loss (32.7%), attempted suicide (32.7%), and administration of psychiatric medications (16.1%). There were no significant differences between the HIV-positive and HIV-negative patients on psychiatric symptoms or quality of life.</p> <p>Conclusions</p> <p>HIV-positive IDUs were comorbid with HCV, indicating the need to refer both HIV- and HCV-infected individuals for treatment in methadone clinics. Currently, there is a gap between psychiatric/psychosocial services and patient symptoms, and more integrated medical services should be provided to heroin-using populations.</p