Viral antigen nanoparticles for discriminated and quantitative detection of different subtypes of anti-virus immunoglobulins.

The aim of this study is to develop a novel method for the accurate diagnosis of the infection status of viral diseases, which requires discriminated and quantitative detection of different anti-virus immunoglubulin subtypes. Considering hepatitis A as a representative model disease, viral antigen nanoparticles (vAgNPs) were designed and synthesized by genetically presenting hepatitis A virus (HAV) antigens on the surface of human heavy chain ferritin (hFTH) nanoparticles to detect anti-HAV antibodies with discriminating immunoglobulin subtypes M and G (IgM and IgG, respectively). The vAgNPs also display multi-copies of hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is vital for the autonomous generation of quantitatively meaningful detection signals. The quantitative level of anti-HAV IgM or IgG in 30 patient sera was successfully analyzed using the vAgNPs of HAV, which was performed through label-free one-step-immunoassay based on the self-enhancement of optical signals from gold nanoparticles clustered on the viral antigen nanoparticles. The diagnostic performance was compared with that of enzyme-linked immunosorbent assay (ELISA), which did not enable accurate quantitative assay due to the poor linearity between the antibody concentration and detection signal. Furthermore, these vAgNP-based immunoassays did not produce any false negative/positive signals, indicating 100% sensitivity and 100% specificity.

Predisposition to and effects of methamphetamine use on the adolescent brain.

Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users. Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain. Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents.

Comparison of the optimal effect-site concentrations of remifentanil for preventing cough during emergence from desflurane or sevoflurane anaesthesia.

OBJECTIVE: To compare the effect-site concentrations of remifentanil target-controlled infusion (TCI) that produced 50% and 95% of the maximal effect (EC50 and EC95, respectively) for preventing cough during emergence from desflurane or sevoflurane anaesthesia, in patients undergoing elective thyroidectomy. METHODS: Adults undergoing elective thyroidectomy were randomized to receive anaesthesia with desflurane or sevoflurane. The EC50 and EC95 values for remifentanil TCI were determined using Dixon's up-and-down method and probit analysis with sigmoid curve. RESULTS: In total, 48 patients aged 20-64 years were enrolled in the study. The EC50±SD of remifentanil TCI, determined by Dixon's up-and-down method, were 1.54±0.70 and 1.11±0.24 ng/ml for desflurane and sevoflurane, respectively. The EC95 of remifentanil TCI, analysed by probit analysis, were 2.88 ng/ml and 2.29 ng/ml for desflurane and sevoflurane, respectively. The effect-site concentration of remifentanil TCI for preventing cough during emergence from desflurane anaesthesia was not significantly higher than that observed for sevoflurane. CONCLUSIONS: During emergence from anaesthesia, variations in effect-site concentrations of remifentanil for preventing cough are of limited importance as they do not generate significant differences in results.

Limited maximal flow rate of target-controlled remifentanil infusion and induced cough.

This study evaluated the effect of limiting maximal infusion-pump flow rate on suppression of remifentanil-induced cough during target-controlled infusion. Two hundred and ten patients were randomly assigned to receive remifentanil at an effect-site concentration of 4.0 ng.ml(-1) with maximal flow rate limited to 100 (group R(100)), 200 (group R(200)), or 1200 ml.h(-1) (group R(1200)). The number of episodes of cough were recorded and graded as mild (1-2), moderate (3-4), or severe (5 or more). The incidence of cough was 2.9% in group R(100), 5.7% in group R(200) and 25.7% in group R(1200). Patients in group R(100) and R(200) had a significantly lower incidence of cough than those in group R(1200) (p < 0.05). Zero, two and five patients coughed a moderate amount in groups R(100), R(200) and group R(1200), respectively (p < 0.05). Limiting maximal infusion rate during remifentanil TCI suppressed remifentanil-induced cough.

The incidence of postoperative nausea and vomiting after thyroidectomy using three anaesthetic techniques.

The choice of anaesthetics can affect the incidence of postoperative nausea and vomiting (PONV). This study compared the incidence of PONV in 177 female patients who underwent thyroidectomy, with anaesthesia induced and maintained using one of three regimens: (i) sevoflurane (thiopental sodium 4 - 5 mg/kg and sevoflurane 2.0 - 2.5 vol% in 50% air); (ii) total intravenous anaesthesia (TIVA; propofol-remifentanil [target blood concentrations 2.5 - 3.5 µg/ml and 3.5 - 4.5 ng/ml, respectively]); or (iii) combined inhalation and intravenous anaesthesia (sevoflurane 1.0 vol% in 50% air plus propofol-remifentanil [target blood concentrations 1.5 - 2.5 µg/ml and 2.5 - 3.5 ng/ml, respectively]). The incidence and severity of PONV and the need for rescue antiemetics were assessed at 0 - 24 h postoperatively. Overall, the incidence of PONV was significantly lower in the TIVA and combined groups compared with the sevoflurane group (33.9%, 39.0% and 64.4%, respectively). In conclusion, the maintenance of anaesthesia with propofol-remifentanil or sevoflurane-propofol-remifentanil decreased the incidence of PONV compared with sevoflurane alone.

Haemodynamic changes during left anterior descending artery exposure in off-pump coronary artery bypass: comparison between use of moist laparotomy pads and deep pericardial traction sutures for heart displacement.

Haemodynamic changes occurring during heart displacement, using moist laparotomy pads placed behind the heart (PAD group, n = 26) or deep pericardial traction sutures (DPS group, n = 25) to facilitate exposure of the left anterior descending artery during off-pump coronary artery bypass surgery, were compared. Haemodynamic variables were assessed before and 10 min after displacement of the heart. The central venous pressure, mean pulmonary artery pressure and pulmonary capillary wedge pressure increased in both groups. After heart displacement in the PAD group, the cardiac index, stroke volume index, mixed venous oxygen saturation, right ventricular ejection fraction and left ventricular stroke work index decreased significantly, and the systemic vascular resistance and pulmonary vascular resistance increased significantly; these parameters remained unchanged in the DPS group. It was concluded that displacement of the heart using moist laparotomy pads caused significant haemodynamic derangement compared with that caused by deep pericardial traction sutures.

Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial.

AIMS: Prominent anxiety symptoms are related to poor clinical course and outcome in major depressive disorder (MDD). The aim of this randomised, open-label, controlled study is to compare the efficacy and tolerability of mirtazapine in the form of orally disintegrating tablets against paroxetine in treating MDD patients with anxiety symptoms. METHODS: A total of 60 MDD patients with a score above 18 on the Hamilton Anxiety Rating Scale (HARS) were randomly assigned to 8 weeks of fixed dosing treatment with mirtazapine (15-30 mg/day) and paroxetine (10-20 mg/day). Efficacy was primarily assessed with the HARS and with the 17-item Hamilton Depression Rating Scale (HDRS) at weeks 1, 2, 4 and 8 after treatment. Tolerability was assessed from adverse events. RESULTS: The generalised estimating equations (GEE) models showed that the rates of improvement in HDRS scores from baseline to week 8 were similar between mirtazapine and paroxetine groups. However, patients with mirtazapine exhibited earlier improvement in HARS scores at weeks 1 and 2. Week-by-week GEE models showed that these significant differences in improvement of HARS scores between the two treatment groups were detectable from the first evaluation after the treatment (week 1) and maintained through week 2. There was no difference in the overall frequency of adverse events experienced between the two treatment groups. The most common adverse event in the mirtazapine group was somnolence (n = 8), whereas that in the paroxetine group was gastrointestinal discomfort (n = 9). CONCLUSIONS: Mirtazapine and paroxetine were equally effective and well tolerated for the depressive symptoms in MDD patients with the high level of anxiety symptoms. Mirtazapine was, however, more effective in reducing the anxiety symptoms than paroxetine in the early weeks of treatment, suggesting that mirtazapine may have an earlier-onset action for the anxiety symptoms in MDD patients.

Reduction of microemulsion propofol-induced injection pain via target-controlled remifentanil infusion.

The intravenous injection of microemulsion propofol to induce anaesthesia causes more intense and frequent pain than lipid emulsion propofol. This study investigated whether different target effect-site concentrations of remifentanil could prevent pain due to microemulsion propofol injection. In total, 96 patients were randomly assigned to one of three groups receiving target effect-site concentrations of remifentanil 0 (control group), 4 or 6 ng/ml, followed by injection with microemulsion propofol. Remifentanil pretreatment significantly reduced the incidence and severity of injection pain compared with the control group. Although no difference in pain reduction between the two remifentanil-treated groups was observed, those receiving a target effect-site concentration of 6 ng/ml exhibited an increased rate of complications, compared with those receiving 4 ng/ml. In conclusion, prior administration of remifentanil at a target effect-site concentration of 4 ng/ml is a useful strategy to decrease the injection pain of microemulsion propofol.

Comparison of the incidence and severity of cough after alfentanil and remifentanil injection.

BACKGROUND: Intravenous administration of fentanyl derivatives can induce cough paradoxically. This study examined the incidence and severity of cough after a bolus of alfentanil and remifentanil. METHODS: Four hundred and sixty-five patients, aged 18-70 years, were allocated randomly to three groups to receive alfentanil 10 microg/kg, remifentanil 1 microg/kg or an equal volume of 0.9% saline intravenously over 10 s. Any episode of cough was classified as coughing and graded as mild (1-2), moderate (3-4) or severe (5 or more). RESULTS: The overall incidence of cough was higher in the opioid groups than in the saline group. The remifentanil group [39/150 patients; 26.0% (95% CI, 19.6-33.6%)] showed a higher incidence than the alfentanil group [11/152 patients; 7.2% (95% CI, 0.4-12.6%)] (P<0.001). There was no significant difference in the severity of cough between the alfentanil group and the remifentanil group. CONCLUSION: This study demonstrated that equipotent boluses of alfentanil and remifentanil induced coughing, even though the incidence of cough after alfentanil administration was lower than that after remifentanil administration.

The simultaneous detection of both enteroviruses and adenoviruses in environmental water samples including tap water with an integrated cell culture-multiplex-nested PCR procedure.

AIMS: To evaluate an integrated cell culture (ICC)-multiplex-nested PCR using the buffalo green monkey kidney (BGMK) cells for the simultaneous detection of both enteroviruses and adenoviruses in surface water and tap water samples and optimize the procedure for more sensitive detection of virus showing no apparent cytopathic effect (CPE). METHODS AND RESULTS: A total of 69 surface water and 50 tap water samples were analysed by the ICC-multiplex-nested PCR. All the PCRs were performed five times with a cell lysate from each flask after at least 2 weeks incubation. Forty-six surface water samples (66.7%) and 23 tap water samples (46.0%) exhibited CPE by the cell culture method. By using an ICC-multiplex-nested PCR, 53 surface water samples (76.8%) and 29 tap water samples (58.0%) were determined as containing infectious enteric viral particles. CONCLUSIONS: An ICC-PCR method with a long incubation time using BGMK cells enables the simultaneous detection of enteroviruses and adenoviruses from environmental water samples, including tap water, even with low numbers of viruses. SIGNIFICANCE AND IMPACT OF THE STUDY: A method capable of detecting small numbers of viral particles is necessary.

Detection of adenoviruses and enteroviruses in tap water and river water by reverse transcription multiplex PCR.

A reverse transcription (RT) multiplex polymerase chain reaction (PCR) assay was developed to simultaneously detect adenoviruses and enteroviruses, both of which have attracted much attention as molecular indices of viral pollution in environmental samples. The method involves a reverse transcription step, followed by a multiplex nested PCR in which the combination of primers amplifies cDNA from enteroviruses and adenoviruses. The sensitivity of this assay was found to be similar to that of each monoplex PCR or RT-PCR assay, and to be consistent regardless of relative concentrations of adenoviruses and enteroviruses. To assess suitability and environmental application of the RT multiplex PCR assay, a total of 12 river water samples and 4 tap water samples were analyzed by RT multiplex PCR, each monoplex PCR or RT-PCR, and cell culture assay on the Buffalo Green Monkey kidney cell line. The sensitivity of the RT multiplex PCR was also found to be similar to that of each monoplex PCR in environmental samples. This suggests the RT multiplex PCR assay could be applied to the routine monitoring of viral pollution in environmental waters.

Heavy contamination of a subsurface aquifer and a stream by livestock wastewater in a stock farming area, Wonju, Korea.

A survey of groundwater and stream water quality was undertaken in a stock farming area where livestock wastewater infiltrates into sandy unsaturated zones and saturated bedrock aquifers containing fractures. To determine the degree of contamination and track the effect of livestock wastewater on groundwater and stream water quality, the population of indicator bacteria (total coliforms, fecal coliforms, fecal streptococci, Staphylococcus spp., and sulfite-reducing clostridia) together with relevant physicochemical parameters were monitored along the wastewater flow-pathways over a 19-month period. The stream water was severely contaminated with livestock wastewater. Nearly all physicochemical and bacteriological parameters in the stream water were much greater than those in the groundwater. Nitrate-N concentrations ranged from 10.0 to 20.0 mg l(-1) in boreholes located downstream (site C) from the livestock waste disposal site, while those in the background borehole (W2) were below 1.0 mg l(-1). Densities of indicator bacteria in boreholes at site C were two or three orders of magnitude higher than those in W2 borehole. In boreholes located downstream from the livestock waste disposal site, the concentration of ammonium-N, nitrate-N, and pollution indicator bacteria increased as groundwater level rose due to infiltration of rainwater. In W2 borehole, however, physicochemical parameters and the number of pollution indicator bacteria had no correlation with the groundwater level. Collectively, these results suggest that the deep aquifers were heavily contaminated with infiltrated livestock wastewater, which consequently must be adequately treated to minimize groundwater pollution.