Inactivation of airborne porcine reproductive and respiratory syndrome virus (PRRSv) by a packed bed dielectric barrier discharge non-thermal plasma.

Porcine reproductive and respiratory syndrome virus (PRRSv) is one of the most significant airborne viruses impacting the pork industry in the US. Non-thermal plasmas (NTPs) are electrical discharges comprised of reactive radicals and excited species that inactivate viruses and bacteria. Our previous experiments using a packed bed NTP reactor demonstrated effective inactivation of bacteriophage MS2 as a function of applied voltage and power. The present study examined the effectiveness of the same reactor in inactivating aerosolized PRRSv. A PRRSv solution containing ∼105 TCID50/ml of PRRSv VR2332 strain was aerosolized at 3 ml/min by an air-jet nebulizer and introduced into 5 or 12 cfm air flow followed by NTP exposure in the reactor. Twin impingers upstream and downstream of the reactor collected samples of the virus-laden air flow for subsequent TCID50 assay and qPCR analyses. An optical particle sizer measured upstream and downstream aerosol size distributions, giving estimates of aerosol filtration by the reactor. The results showed that PRRSv was inactivated to a similar degree as MS2 at the same conditions, with the maximum 1.3-log inactivation of PRRSv achieved at 20 kV and 12 cfm air flow rate. The results demonstrate the potential of properly optimized NTPs in controlling PRRSv transmission.

Inter-relationships among psychopathology, premorbid adjustment, cognition and psychosocial functioning in first-episode psychosis: a network analysis approach.

BACKGROUND: Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP. METHOD: This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses. RESULTS: Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength. CONCLUSION: Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.

Inactivation of airborne viruses using a packed bed non-thermal plasma reactor.

Outbreaks of airborne infectious diseases such as measles or severe acute respiratory syndrome can cause significant public alarm. Where ventilation systems facilitate disease transmission to humans or animals, there exists a need for control measures that provide effective protection while imposing minimal pressure differential. In the present study, viral aerosols in an airstream were subjected to non-thermal plasma (NTP) exposure within a packed-bed dielectric barrier discharge reactor. Comparisons of plaque assays before and after NTP treatment found exponentially increasing inactivation of aerosolized MS2 phage with increasing applied voltage. At 30 kV and an air flow rate of 170 standard liters per minute, a greater than 2.3 log reduction of infective virus was achieved across the reactor. This reduction represented ~2 log of the MS2 inactivated and ~0.35 log physically removed in the packed bed. Increasing the air flow rate from 170 to 330 liters per minute did not significantly impact virus inactivation effectiveness. Activated carbon-based ozone filters greatly reduced residual ozone, in some cases down to background levels, while adding less than 20 Pa pressure differential to the 45 Pa differential pressure across the packed bed at the flow rate of 170 standard liters per minute.

Targeting of acute myeloid leukemia in vitro and in vivo with an anti-CD123 mAb engineered for optimal ADCC.

Acute myeloid leukemia (AML) is a biologically heterogeneous group of related diseases in urgent need of better therapeutic options. Despite this heterogeneity, overexpression of the interleukin (IL)-3 receptor α-chain (IL-3 Rα/CD123) on both the blast and leukemic stem cell (LSC) populations is a common occurrence, a finding that has generated wide interest in devising new therapeutic approaches that target CD123 in AML patients. We report here the development of CSL362, a monoclonal antibody to CD123 that has been humanized, affinity-matured and Fc-engineered for increased affinity for human CD16 (FcγRIIIa). In vitro studies demonstrated that CSL362 potently induces antibody-dependent cell-mediated cytotoxicity of both AML blasts and CD34(+)CD38(-)CD123(+) LSC by NK cells. Importantly, CSL362 was highly effective in vivo reducing leukemic cell growth in AML xenograft mouse models and potently depleting plasmacytoid dendritic cells and basophils in cynomolgus monkeys. Significantly, we demonstrated CSL362-dependent autologous depletion of AML blasts ex vivo, indicating that CSL362 enables the efficient killing of AML cells by the patient's own NK cells. These studies offer a new therapeutic option for AML patients with adequate NK-cell function and warrant the clinical development of CSL362 for the treatment of AML.

Association of hypertension with small, dense low-density lipoprotein in patients without metabolic syndrome.

A higher proportion of small, dense low-density lipoprotein (sdLDL) is known to be associated with a high prevalence of cardiovascular disease in association with metabolic syndrome (MS). Hypertension (HTN) is one of the known risk factors for MS. However, whether HTN is associated with sdLDL in patients without MS is not yet clear. The lipid profiles, including low-density-lipoprotein (LDL) subfractions, of 383 consecutive subjects were evaluated. The patients without MS consisted of 198 hypertensive patients (non-MS/HTN group) and 108 normotensive subjects (non-MS/non-HTN group). The peak and mean particle diameter of LDL were measured by gradient gel electrophoresis. Plasma total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), HDL cholesterol/Apo A1, LDL-C/ApoB and Apo(A1, B, CII and E) levels did not differ between the non-MS/non-HTN and non-MS/HTN groups. When analyzing LDL subfraction, the absolute amount of patterns A and B was not different between the non-MS/non-HTN and non-MS/HTN groups. Compared with the non-MS/non-HTN groups, the proportion of sdLDL was higher in the non-MS/HTN group (37.7% versus 39.9%, P=0.046), but not significant after adjustment of waist circumference, serum TG, age and statin usage. The proportion of sdLDL to total LDL was higher in hypertensive subjects, even those without MS, than in normotensive subjects. However, this difference of LDL subfraction in hypertensive patients is associated with higher waist circumference, higher serum TG, older age and more statin usage. This result suggests that HTN may contribute to atherosclerosis and endothelial dysfunction with associated risk factors that influence LDL size.

Glass-type wireless PPG measuring system.

This paper is about a glass-type wireless bio-signal transmitter that can monitor the user's health state in daily life. The device implemented in this study consists of the transmission part and the receiving part. The transmission part includes a photoplethysmography(PPG) sensor for detecting pulse wave signals, accelerometer for detecting kinetic signals, and a wireless controller for transmitting acquired bio-information. The receiving part is designed to check and process transmitted data through interoperation with a PC. In the experiments, we collected data during a sitting posture and repeated sit-to-stand motion in laboratory environment, and analyzed the data. As to accuracy, the correlation between the peak-to-peak intervals in the signals of the Biopac equipment and the developed device measured in a sitting posture was 97.5%, and that measured in sit-to-stand motion was 87%. In addition, when bio-signals were transmitted through wireless communication, the transmission was successful 100% without any error. When pulse wave signals and kinetic signals were obtained and compared, the results proved the accuracy and daily applicability of the developed device, and the glass-type wireless bio-signal transmission system is expected to be applicable to unobtrusive health monitoring for the user.

Effects of a modified live CSFV vaccine on the development of PMWS in pigs infected experimentally with PCV-2.

The objective of this study was to determine the effect of vaccination against classical swine fever virus (CSFV) on the development of postweaning multisystemic wasting syndrome (PMWS) in conventional pigs infected experimentally with porcine circovirus type 2 (PCV-2). The pigs infected with PCV-2 and immunised with modified live CSFV developed mild to moderate PMWS, whereas none of the pigs infected with PCV-2 alone or immunised with modified live CSFV alone developed PMWS. Lesions histologically characteristic of PMWS were observed in lymph nodes from the pigs infected with PCV-2 and immunised with modified live CSFV vaccine, and extensive replication of PCV-2 was detected in the nodes by in situ hybridisation.

Respiratory rate detection algorithms by photoplethysmography signal processing.

Photoplethysmography (PPG) offers the clinically meaningful parameters, such as, heart rate, and respiratory rate. In this study, we presented three respiratory signal detection algorithms using photoplethysmography raw data generated from commercial PPG sensor: (1)Min-Max (2)Peak-to-Peak (3)Pulse Shape. As reference signal, nasal sensor signal was acquired simultaneously and compared and analyzed. We used two types of moving average filtering technique to process three PPG parameters. In laboratory experiment, 6 subjects' PPG signals were measured when they respire ten and fifteen, and arbitrary times per minute. From the results, following conclusions were drawn. Min-Max and Peak-to-Peak algorithms perform better than Pulse shape algorithm. They can be used to detect respiratory rate. But, Pulse Shape algorithm was accurate for subject 4 only. More experimental data is necessary to improve the accuracy and reliability.

The mitochondrial genome of the Korean hairstreak, Coreana raphaelis (Lepidoptera: Lycaenidae).

We determined the complete nucleotide sequences of the mitochondrial genome (mitogenome) of the Korean hairstreak, Coreana raphaelis (Lepidoptera: Lycaenidae). The entire mitochondrial DNA (mtDNA) molecule was 15,314 bp long. The C. raphaelis genes were in the same order and orientation as the completely sequenced mitogenomes of other lepidopteran species, except for the presence of an extra copy of tRNA(Ser)(AGN). High similarity in primary sequence and secondary structure between the two tandemly located copies of the tRNA(Ser)(AGN) suggest a recent duplication of an original single tRNA(Ser)(AGN). The DHU arm of the two copies of tRNA(Ser)(AGN) formed a simple loop as seen in many other metazoan mt tRNA(Ser)(AGN). The putative initiation codon for the C. raphaelis COI gene appears to be a tetranucleotide, TTAG, found commonly in the sequenced lepidopterans. ATPase8, ATPase6, ND4L and ND6 genes, which are next to another protein-coding gene at their 3' end all had the sequences potential to form a hairpin structure, suggesting the importance of such a structure for precise cleavage of the mature protein-coding genes.

Investigation of occupational radiation exposures to NORM at an Irish peat-fired power station and potential use of peat fly ash by the construction industry.

Annually, approximately 15% of Ireland's electricity requirement is provided through the combustion of 3 x 10(6) tonnes of peat. While the literature on coal-fired power generation is quite abundant, studies on the peat-fired power generation industry from a radiological point of view are scarce. A study of the largest Irish peat-fired power plant was initiated to review the potential occupational radiation exposures arising from the occurrence of naturally occurring radioactive material (NORM) at different stages of the industrial process and to investigate any radiological health consequences that may arise should peat fly ash be used as a component of building materials. Ambient gamma dose rate measurements, radon measurements, quantification of the occupational exposure from inhalation of airborne particles (personal air sampling) and gamma spectrometry analysis of peat, peat ash and effluent samples from the ash ponds were undertaken. The results indicate that the radiation dose received by any worker involved in the processing of the peat and the handling of the ash resulting from peat combustion does not exceed 150 microSv per annum. Regulatory control of the peat-fired power generation is therefore unnecessary according to the Irish legislation with regards to NORM. The potential use of peat fly ash as a by-product in the building industry was also found to have a negligible radiological impact for construction workers and for members of the public.

The prevalence of abnormal cervical cytology in a sexually transmitted diseases clinic.

Women seeking sexually transmitted disease (STD) services are at high risk of human papillomavirus infections. Cervical cytological screening with Papanicolau staining (Pap smear) is not consistently offered at public STD clinics. We reviewed Pap smear results on a series of 1000 female STD clinic attendees, abstracted demographics, risk behaviours and STD diagnosis from the clinical record and tested for associations with abnormal Pap smear. In all, 5.7% of the satisfactory specimens (56/993) were abnormal; increasing age category, genital warts, and chlamydia infections were independently associated with an abnormal Pap smear in multivariate analysis. Routine Pap smear screening provided satisfactory results in the STD clinic and, where population-based programmes are not available, should be fully integrated into public STD care, (particularly in settings serving younger women).

Natural radioactivity in building materials in the Republic of Ireland.

This paper presents the findings of a study undertaken to determine the natural radioactivity present in building materials in the Republic of Ireland. A total of 70 samples of commonly used building materials were collected from various manufacturers and suppliers throughout the country and analyzed using a HPGe gamma ray spectrometer. The specific activities of 226Ra, 232Th, and 40K were measured in all samples, and results ranged from minimum values of <1, <1, and 4 Bq kg(-1) to maximum values of 139, 57, and 1,977 Bq kg(-1), with mean values of 32, 18, and 353 Bq kg(-1), respectively. Results obtained were compared with relevant national, EU, and international legislation and guidance, and with the results of similar studies undertaken in other countries. These activities would suggest that the use of such building materials in the construction of domestic dwellings or workplaces in Ireland is unlikely to give rise to any significant radiation exposure to the occupants. In general, these activities were comparable to the results of similar studies undertaken in other countries. 137Cs activity was also detected in some samples.

Liposome-complexed adenoviral gene transfer in cancer cells expressing various levels of coxsackievirus and adenovirus receptor.

PURPOSE: Loss of coxsackievirus and adenovirus receptor (CAR) is frequently observed in malignant cancer, hampering adenoviral gene therapy approaches. Complexing adenovirus with cationic liposomes can increase adenoviral transgene expression, particularly in cells with CAR-deficiency. We investigated whether other factors such as lipid composition might be involved in determining the efficiency of liposome-complexed adenoviral gene transfer in cancer cells. MATERIAL AND METHODS: Human cancer cell lines with different expression levels of CAR were infected with a GFP transgene. The efficiency of transgene expression was assessed by determining GFP expression using FACS analysis. RESULTS: The efficiency of liposome-complexed adenoviral gene transfer was dependent on the lipid composition constituting liposomes. Polyethylene glycol (PEG)-containing liposomes were most effective in increasing liposome-complexed adenoviral gene transfer. In CAR-deficient cells, use of PEG-containing liposomes enhanced adenoviral gene transfer, whereas in CAR-expressing cells enhancement varied depending on cell type. In some CAR-expressing cells, the effect of liposome complexing was even comparable to that in CAR-deficient cells. Increased adenoviral transgene expression following complexing with PEG-containing liposomes correlated with liposome uptake in cancer cells. CONCLUSIONS: Liposome-complexed adenoviral gene transfer appears to depend on lipid composition and the level of liposome uptake by cancer cells, in addition to CAR levels. Our study suggest that these multiple factors should be considered in designing liposome-complexed adenoviral vectors to improve outcomes of current adenoviral cancer gene therapies.

Effects of pathophysiological concentrations of albumin on NHE3 activity and cell proliferation in primary cultures of human proximal tubule cells.

The progression of renal disease correlates strongly with hypertension and the degree of proteinuria, suggesting a link between excessive Na+ reabsorption and exposure of the proximal tubule to protein. The present study investigated the effects of albumin on cell growth and Na+ uptake in primary cultures of human proximal tubule cells (PTC). Albumin (1.0 mg/ml) increased cell proliferation to 134.1 +/- 11.8% (P < 0.001) of control levels with no change in levels of apoptosis. Exposure to 0.1 and 1.0 mg/ml albumin increased total 22Na+ uptake to 119.1 +/- 6.3% (P = 0.005) and 115.6 +/- 5.3% (P < 0.006) of control levels, respectively, because of an increase in Na+/H+ exchanger isoform 3 (NHE3) activity. This was associated with an increase in NHE3 mRNA to 161.1 +/- 15.1% (P < 0.005) of control levels in response to 0.1 mg/ml albumin. Using confocal microscopy with a novel antibody raised against the predicted extracellular NH2 terminus of human NHE3, we observed in nonpermeabilized cells that exposure of PTC to albumin (0.1 and 1.0 mg/ml) increased NHE3 at the cell surface to 115.4 +/- 2.7% (P < 0.0005) and 122.4 +/- 3.7% (P < 0.0001) of control levels, respectively. This effect was paralleled by significant increases in NHE3 in the subplasmalemmal region as measured in permeabilized cells. These albumin-induced increases in expression and activity of NHE3 in PTC suggest a possible mechanism for Na+ retention in response to proteinuria.

Polymorphisms in the TNF-alpha and TNF-receptor genes in patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is both multifactorial and polygenic in nature. Atheroma formation, the pathological hallmark of CAD, is an inflammatory process, with pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), having a major role in its pathogenesis. We have therefore investigated whether polymorphisms in the TNF-alpha (- 238 and - 308), TNF receptor 1 (position - 609 and + 10, intron 6) and TNF receptor 2 (position + 422, codon 198) genes show an association with CAD. MATERIALS AND METHODS: Patients with angiographically proven single vessel (n = 58) and multivessel (n = 122) CAD were compared to patients with angiographically proven normal coronary arteries (n = 79) and volunteers without clinical evidence of CAD (n = 250). Genotyping was performed by PCR-RFLP analysis. For the TNF-alpha polymorphisms, a meta-analysis of all published studies was also undertaken. RESULTS: No significant differences in allele or genotype frequencies were found between the normal coronary artery group or healthy volunteers and patients with CAD for any of the polymorphisms. There was also no difference in allele frequency between patients with single- and multivessel disease. For the - 308 and - 238 TNRalpha gene polymorphisms, a meta-analysis of our data and previously published studies failed to demonstrate any significant association with CAD. CONCLUSIONS: Polymorphisms in the TNF-alpha promoter region and TNF-receptor genes are not associated with the development of CAD.