Characterisation of invasive group B streptococci based on investigation of surface proteins and genes encoding surface proteins

ABSTRACTThe joint distributions of the six genes bca, bac, ɛ/alp1, alp2, alp3 and rib (encoding α-C-protein, β-C-protein, ɛ/Alp1, Alp2, Alp3, and Rib, respectively) and the proteins α-C-protein, β-C-protein and Rib were investigated in invasive isolates of group B streptococcus (GBS). In total, 297 invasive isolates (123 from neonates, 174 from adults) from south-west Sweden were collected during a 13-year period. Genes were detected using multiplex and specific PCRs, and expression of the surface proteins was demonstrated using monoclonal antibodies. The genes studied were found alone or in combinations in 294 (99%) of the invasive isolates. The most common genes were rib (n = 127 isolates, 43%), alp3 (n = 78, 26%) and ɛ/alp1 (n = 42, 14%). The bac gene was never found alone, but was found in combination with one other gene in 36 isolates. The surface proteins studied were detected alone or in combinations in 152 (51%) isolates, with the most common being Rib (n = 80, 27%), α-C-protein (n = 68, 23%) and β-C-protein (n = 24, 8%). Several genes were associated significantly with particular serotypes (e.g., ɛ/alp1 with serotype Ia; bca and bac with serotypes Ib and II; rib with serotype III; alp3 with serotype V). Overall, it was concluded that demonstration of different genes and surface proteins of GBS strains can be useful in epidemiological studies and in formulation of vaccines, but disappointingly, no single gene or surface protein included in the study was sufficiently common for it to be considered as the basis for a successful GBS vaccine

Metabolic mapping by use of high-resolution magic angle spinning1H MR spectroscopy for assessment of apoptosis in cervical carcinomas

Background High-resolution magic angle proton magnetic resonance spectroscopy (HR1H MAS MRS) provides a broad metabolic mapping of intact tumor samples and allows for microscopy investigations of the samples after spectra acquisition. Experimental studies have suggested that the method can be used for detection of apoptosis, but this has not been investigated in a clinical setting so far. We have explored this hypothesis in cervical cancers by searching for metabolites associated with apoptosis that were not influenced by other histopathological parameters like tumor load and tumor cell density. Methods Biopsies (n = 44) taken before and during radiotherapy in 23 patients were subjected to HR MAS MRS. A standard pulse-acquire spectrum provided information about lipids, and a spin-echo spectrum enabled detection of non-lipid metabolites in the lipid region of the spectra. Apoptotic cell density, tumor cell fraction, and tumor cell density were determined by histopathological analysis after spectra acquisition. Results The apoptotic cell density correlated with the standard pulse-acquire spectra (p < 0.001), but not with the spin-echo spectra, showing that the lipid metabolites were most important. The combined information of all lipids contributed to the correlation, with a major contribution from the ratio of fatty acid -CH2 to CH3 (p = 0.02). In contrast, the spin-echo spectra contained the main information on tumor cell fraction and tumor cell density (p < 0.001), for which cholines, creatine, taurine, glucose, and lactate were most important. Significant correlations were found between tumor cell fraction and glucose concentration (p = 0.001) and between tumor cell density and glycerophosphocholine (GPC) concentration (p = 0.024) and ratio of GPC to choline (p < 0.001). Conclusion Our findings indicate that the apoptotic activity of cervical cancers can be assessed from the lipid metabolites in HR MAS MR spectra and that the HR MAS data may reveal novel information on the metabolic changes characteristic of apoptosis. These changes differed from those associated with tumor load and tumor cell density, suggesting an application of the method to explore the role of apoptosis in the course of the disease

Silicon microcantilever sensors to detect the reversible conformational change of a molecular switch, Spiropyan

The high sensitivity of silicon microcantilever sensors has expanded their use in areas ranging from gas sensing to bio-medical applications. Photochromic molecules also represent promising candidates for a large variety of sensing applications. In this work, the operating principles of these two sensing methods are combined in order to detect the reversible conformational change of a molecular switch, spiropyran. Thus, arrays of silicon microcantilever sensors were functionalized with spiropyran on the gold covered side and used as test microcantilevers. The microcantilever deflection response was observed, in five sequential cycles, as the transition from the spiropyran (SP) (CLOSED) to the merocyanine (MC) (OPEN) state and vice-versa when induced by UV and white light LED sources, respectively, proving the reversibility capabilities of this type of sensor. The microcantilever deflection direction was observed to be in one direction when changing to the MC state and in the opposite direction when changing back to the SP state. A tensile stress was induced in the microcantilever when the SP to MC transition took place, while a compressive stress was observed for the reverse transition. These different type of stresses are believed to be related to the spatial conformational changes induced in the photochromic molecule upon photo-isomerisation

The Potential of Biobanked Liquid Based Cytology Samples for Cervical Cancer Screening Using Raman Spectroscopy.

Patient samples are unique and often irreplaceable. This allows biobanks to be a valuable source of material. The aim of this study was to assess the ability of Raman spectroscopy to screen for histologically confirmed cases of Cervical Intraepithelial neoplasia (CIN) using biobanked liquid based cytology (LBC) samples. Two temperatures for long term storage were assessed; 80°C and -25°C. The utility of Raman spectroscopy for the detection of CIN was compared for fresh LBC samples and biobanked LBC samples. Two groups of samples were used for the study with one group associated with disease (CIN 3) and the other associated with no disease (cytology negative). The data indicates that samples stored at -80°C are not suitable for assessment by Raman spectroscopy due to a lack of cellular material and the presence of cellular debris. However, the technology can be applied to fresh LBC samples and those stored at -25°C and is, moreover, effective in the discrimination of negative samples from those where CIN 3 has been confirmed. Pooled fresh and biobanked samples are also amenable to the technology and achieve a similar sensitivity and specificity for CIN 3. This study demonstrates that cervical cytology samples stored within biobanks at temperatures that preclude cell lysis can act as a useful resource for Raman spectroscopy and will facilitate research and translational studies in this area

Cardiac Vagal Tone Impairment is Associated with Reduced Cerebral Blood Flow in Collegiate Athletes Following Concussion

Reduced cerebral blood flow (CBF) is linked to functional disturbances following concussion. Since cardiac vagal tone (an index of cardiac health) is associated with disturbances in the autonomic nervous system, deficits in CBF are likely associated with cardiac vagal tone impairment post-concussion. PURPOSE: The current study examined cardiac vagal tone and CBF on days 3, 21 and 90 following concussion in comparison to non-injured control athletes. The association between these two variables was also evaluated. METHODS: Concussed male and female collegiate athletes were evaluated day-3 (N=29), day-21 (N=25) and day-90 (N=17) post concussion and matched controls were enrolled (N=29). A 3-lead electrocardiogram was used to assess cardiac vagal tone in the high frequency domain (HF; 0.15-0.4 Hz). Beat-to-beat mean arterial pressure (MAP) was obtained via finger photoplethysmography and transcranial Doppler ultrasonography (TCD) was used to assess middle cerebral blood flow velocity (MCAV). To measure vascular tone, cerebrovascular conductance index (CVCi) was estimated by dividing MCAV with MAP. Symptom severity and cognition were assessed using the Sports Concussion Assessment Tool-3rd Edition (SCAT-3) and executive function was assessed with the Trails test A & B. RESULTS: On day-3, concussed athletes had lower cognition (SAC 28±1vs.26±2,P=0.0005; Trails B 48±8vs.58±15sec,P=0.006) and HF power (52±12vs.36±14,P=0.006) compared to controls. On days 21 and 90, values were comparable to the controls. However, concussed participants were also categorized based on day-3 MCAV (divided at the median), into low and high MCAV groups. On day-3, the group with lower MCAV exhibited lower HF power (29±13vs.42±11.P=0.006) and lower CVCi (0.60±0.13vs.0.88±0.13,PCONCLUSION:Cardiac vagal tone was impaired 3 days following concussion compared to controls. Lower CBF was also associated with higher cerebrovascular tone. Additionally, lower CBF was linked to blunted cardiac vagal tone and functional outcome on day-21. On day-90, CBF recovered with normalization of functional outcome. Future studies with large sample are recommended to validate these findings

ISEC2006-99159 IMPLEMENTING SOLAR ENERGY IN THE COLORADO PRODUCTION HOME MARKET

ABSTRACT A standardized deployment of solar electric systems in the Colorado production home market is crucial to the success of the renewable portfolio standard recently adopted by Colorado voters. This research uses the Built Green ® program as a context for investigating energy conservation measures (ECMs), viable within the production home market, for their efficacy in curtailing new home annual energy consumption and peak electrical demand loads. The research examines the cost effectiveness and impact of residential solar systems compared to the energy conservation measures. Colorado is a state with good solar resources and considerable production-scale residential development. However, most production homes built in the state today are not highly energy efficient. It is generally believed that improvements to energy efficiency -more insulation, better windows, more efficient appliances -are more cost-effective than solar production systems given current costs. In other words, most production homes in Colorado are not ready to don a solar home system (SHS). The analysis uses extensive energy simulation to determine energy savings of selected energy-saving home features relative to the baseline Building America Benchmark for Denver, CO. This optimization process seeks to identify the least-cost combinations of improvements, assuming present day component costs, with the greatest annual energy savings, with the ultimate goal of implementing solar energy in the Colorado production home market. The results of the analysis suggest that optimal characteristics of production home, designed to minimize total costs, are readily achievable in today&apos;s market. Moreover, when these optimal ECMs are implemented, the marginal cost of a SHS is found to be less than additional energy efficiency. With further energy efficiency improvements, site-based solar electric systems can compete economically given current state and federal incentive programs. The results also indicate that a solar system oriented west of due south can offer significant reductions in peak demand relative to both the household and utility load profiles

Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

Background: Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC. Methods: Using mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI. Results: Compared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density ( VD), and vessel area fraction ( VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores ( AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve ( AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size ( VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after pharmacokinetic modeling. Interestingly, such modeling also detected tumor necrosis very strongly. Conclusions: DCE MRI reliably allows non-invasive assessment of tumors’ vascular function. The findings of increased tumor vascularization after ADT encourage further studies into whether these changes are beneficial for combined RT, or if treatment with anti-angiogenic therapy may be a strategy to improve the therapeutic efficacy of ADT in advanced PC.publishedVersio

Edging your bets: advantage play, gambling, crime and victimisation

Consumerism, industrial development and regulatory liberalisation have underpinned the ascendance of gambling to a mainstream consumption practice. In particular, the online gambling environment has been marketed as a site of ‘safe risks’ where citizens can engage in a multitude of different forms of aleatory consumption. This paper offers a virtual ethnography of an online ‘advantage play’ subculture. It demonstrates how advantage players have reinterpreted the online gambling landscape as an environment saturated with crime and victimisation. In this virtual world, advantage play is no longer simply an instrumental act concerned with profit accumulation to finance consumer desires. Rather, it acts as an opportunity for individuals to engage in a unique form of edgework, whereby the threat to one’s well-being is tested through an ability to avoid crime and victimisation. This paper demonstrates how mediated environments may act as sites for edgeworking and how the potential for victimisation can be something that is actively engaged with