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Impact of containment and social distancing on the number of community-acquired Staphylococcus aureus skin infections Panton-valentine Leukocidin-positive staphylococcus aureus strains are associated with follicular skin infections. Community-acquired I Staphylococcus aureus i skin infections (CA-SASI) outbreaks are regularly reported within closed communities suggesting a direct transmission person-to-person.1-3 However, most cases of CA-SASI occur sporadically and are not clearly related to a cross transmission. [Extracted from the article]

Background: Macrophage elastase (MMP-12) is involved in the inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate in mice the effect of MMP-12 inhibition on the inflammatory process induced by cigarette smoke (CS) or by lipopolysaccharide (LPS) exposure of the airways.Experimental Approach: C57BL/6 mice were given, orally, either the selective MMP-12 inhibitor AS111793 (3, 10, 30 and 100 mg kg(-1)), the PDE-4 inhibitor roflumilast (3 mg kg(-1)) or vehicle, then exposed to CS (for 3 days) or to LPS (100 microg mL(-1), 30 min). Subsequent to the last smoke or LPS exposure, bronchoalveolar lavages (BAL) were performed and lungs were removed and homogenized to analyze various markers of inflammation at appropriate times.Key Results: Inhibition of MMP-12 by AS111793 (10 and 30 mg kg(-1)) was associated with a reduction of the increase in neutrophil number in BAL fluids after 4 days and of macrophages after 11 days. On day 4, AS111793 also significantly reduced all the inflammation markers that had increased after CS exposure, including soluble TNF receptors I and II, MIP-1gamma, IL-6 and pro-MMP-9 activity in BAL fluids, and KC/CXCL1, fractalkine/CX3CL1, TIMP-1 and I-TAC/CXCL11 in lung parenchyma. In contrast, inhibition of MMP-12 did not reduce neutrophil influx, pro-MMP-9 activity or KC/CXCL1 release in BAL fluids of mice exposed to LPS.Conclusion: Inhibition of MMP-12 with AS111793, reduced the inflammatory process associated with exposure of mice to CS, strongly suggesting a specific involvement of MMP-12 in lung inflammation following CS exposure. [ABSTRACT FROM AUTHOR]

Background and Purpose: Based on their proven ability, in animal models of stroke, to reduce damage to brain grey matter, many drugs have been tested in clinical trials but without success. Failure to save axons from injury and to protect functional outcome has been proposed as the major reason for this lack of success. We have previously demonstrated in two rodent models of cerebral ischaemia, that AS601245 (1,3-benzothiazol-2-yl (2-([2-(3-pyridinyl) ethyl] amino)-4 pyrimidinyl) acetonitrile), an inhibitor of the c-Jun NH(2)-terminal kinase (JNK), has neuroprotective properties. The aim of the present study was to further investigate if AS601245 in addition to its ability to protect neurons also could protect neurites and preserve memory after cerebral ischaemia, in gerbils.Experimental Approach: Using immunohistochemical techniques and a behavioural test, we studied the effect of the compound AS601245 on neurodegeneration and cognitive deficits after global cerebral ischaemia in gerbils.Key Results: At a dose of 80 mg kg(-1), i.p., AS601245 reduced damage to neurites by 67% (P<0.001 versus controls) and activation of astrocytes by 84% (P<0.001 versus controls). In addition, AS601245 (80 mg kg(-1), i.p.) prevented ischaemia-induced impairment of memory in the inhibitory avoidance task model.Conclusions and Implications: The present results suggest that AS601245 reduced damage to neurites and decreased astrogliosis following global ischaemia and also improved long-term memory, supporting JNK inhibition as a promising therapeutic strategy for ischaemic insults to the CNS. [ABSTRACT FROM AUTHOR]

Background and Objectives The infrastructure established for screening blood donations for hepatitis C virus has enabled large-scale population testing for other viruses which are potentially transmissible by transfusion of blood components and plasma-derived blood products. We have measured the frequency of viraemia of enteroviruses and parechoviruses in 83 600 Scottish blood donors to allow an initial assessment of their risk to blood safety. Materials and Methods Plasma samples collected from blood donors over 7 calendar months were tested anonymously in mini-pools of 95 donations, by polymerase chain reaction (PCR) for human enterovirus and parechovirus sequences. Results A total of 19 mini-pools, from the 880 that were tested, were PCR-positive for enterovirus RNA, predicting a donor prevalence of 0·023%. Enterovirus sequences were not detected in factor VIII or IX clotting factor concentrates. None of the 230 mini-pools or concentrates contained detectable parechovirus RNA. Conclusions The prevalence of enterovirus viraemia detected in this study predicts that at least 1000 enterovirus-contaminated blood components are transfused per year in the UK. The frequency of transmission and clinical outcome after exposure to enterovirus-contaminated blood components in recipients is unknown. [ABSTRACT FROM AUTHOR]

ABSTRACTThe 18O content of CO2 is a powerful tracer of photosynthetic activity at the ecosystem and global scale. Due to oxygen exchange between CO2 and 18O-enriched leaf water and retrodiffusion of most of this CO2 back to the atmosphere, leaves effectively discriminate against 18O during photosynthesis. Discrimination against 18O (Δ18O) is expected to be lower in C4 plants because of low ci and hence low retrodiffusing CO2 flux. C4 plants also generally show lower levels of carbonic anhydrase (CA) activities than C3 plants. Low CA may limit the extent of 18O exchange and further reduce Δ18O. We investigated CO2–H2O isotopic equilibrium in plants with naturally low CA activity, including two C4 (Zea mays, Sorghum bicolor) and one C3 (Phragmites australis) species. The results confirmed experimentally the occurrence of low Δ18O in C4, as well as in some C3, plants. Variations in CA activity and in the extent of CO2–H2O isotopic equilibrium (θeq) estimated from on-line measurements of Δ18O showed large range of 0–100% isotopic equilibrium (θeq = 0–1). This was consistent with direct estimates based on assays of CA activity and measurements of CO2 concentrations and residence times in the leaves. The results demonstrate the potential usefulness of Δ18O as indicator of CA activity in vivo. Sensitivity tests indicated also that the impact of θeq < 1 (incomplete isotopic equilibrium) on 18O of atmospheric CO2 can be similar for C3 and C4 plants and in both cases it increases with natural enrichment of 18O in leaf water. [ABSTRACT FROM AUTHOR]

Circulating food antibodies, intestinal permeability and HLA status were studied in twelve blood donors previously identified as being selectively IgA deficient from screening 10 000 donations by means of a latex agglutination inhibition test, and confirmed by laser nephelometry. Assessment of intestinal function also included clinical history and standard laboratory tests. The donors proved to be healthy with no evidence of autoimmune disease or allergy. Nine donors (75%) had precipitins to food antigens. None had increased intestinal permeability as measured by the cellobiose/mannitol absorption test, HLA-A, B and DR antigen distribution was normal, IgG sub-class distribution was normal with the exception of an IgG2 level slightly below normal in one donor (0.9 g/l). An unexpected finding was a return of IgA levels to normal in four donors (33%) within 6 months. [ABSTRACT FROM AUTHOR]

The contribution which (photo)respiration makes to carbon isotope discrimination (Δ13C) was examined by conducting simultaneous gas exchange measurements and isotopic analysis of carbon dioxide passing over leaves of Triticum aestivum and Phaseolus vulgaris, via manipulations of the carbon isotope composition (δ13C) of source CO2 during growth and measurement. Dark respiration only altered net Δ13C (Δobs) at tow CO2 assimilation, and was sensitive to source CO2 δ13C during measurement. Photorespiration reduced Δobs relative to Δ13C predicted from p[subi]/pa (Δi) over the full range of CO2 assimilation, to a greater degree under elevated oxygen partial pressure (pO2), indicating fractionation during photorespiration (f) in T. aestivum. For P. vulgaris, Δobs was insensitive to elevated pO2 at higher assimilation rates, suggesting that f was minimal. A model was developed to calculate gross discrimination (Δps), independent of (photo)respiration, from which estimates of f were obtained for T. aestivum (3.3‰) and P. vulgaris (0.5‰). Because photorespiratory fractionation varies interspecifically, and influences net Δ13C which is directly reflected in leaf δ13C, consideration of (photo)respiratory fractionation is necessary when interpreting δ13C of leaf material, especially under conditions where (photo)respiratory CO2 losses make a large relative contribution to total plant carbon budgets. [ABSTRACT FROM AUTHOR]

The photosynthetic properties of cyanobiont lichens from contrasting habitats were measured to identify whether the increased assimilation rates which characterized Peltigera membranacea (Ach.) Nyl. from an exposed habitat were correlated with increased carbon-concentrating mechanism (CCM) activity. The results were contrasted with data obtained from two populations of Peltigera praetextata (Flörke ex Sommerf.) Zopf collected from dry and damp microhabitats within a shaded woodland and Peltigera leucophlebia (Nyl.) Gyelnik, which has been shown to lack a carbon-concentrating mechanism. The differences in assimilation rates between the cyanobiont lichens were not accounted for by differences in chlorophyll content. Peltigera membranacea from the exposed habitat which had the highest assimilation rates had the lowest Γ and K0.5 values and accumulated the greatest Ci-pool indicating that increased Ci accumulation contributed towards the higher assimilation rates shown by these species. The convexity of the light response curve for the cyanobiont lichens decreased with increasing assimilation rates. This might have indicated a diversion of electron transport to energize the carbon-concentrating mechanism. The apparent quantum efficiency of CO2 assimilation (ΦCO2) was correlated with the genus of lichen photobiont. All cyanobiont lichens had comparable values for ΦCO2 which were greater than that of the tripartite Peltigera leucophlebia. Light compensation points reflected the exposure of the habitats with higher compensation points characterizing the cyanobiont population from the exposed crag and the tri-partite population from the open grassland. Carbon isotope discrimination values for organic matter and measured instantaneously were the same for all cyanobiont lichens and were comparable with values recorded for species with a carbon-concentrating mechanism. Carbon isotope measurements for P. leucophlebia were typical of those recorded for species without a carbon-concentrating mechanism. Variation in source isotope signature and refixation of respiratory CO2 were considered to be significant factors in determining organic matter and instantaneous carbon-isotope discrimination. These factors might have masked any subtle variation in carbon-isotope discrimination which resulted from variable CCM activity. The functional significance of increased carbon-concentrating mechanism activity in cyanobiont lichens occupying exposed habitats is discussed. [ABSTRACT FROM AUTHOR]

Donor deferral rates continue to rise inexorably. Currently in Scotland more than a third of new donors are deferred, and nearly 20% of all donors attending. This reflects not only some major precautionary measures, e.g. the exclusion of donors with a history of transfusion since 1980, but also the increasing stringency and effectiveness of our selection procedures. The CSD SAC has been working to make the donor selection guidelines more evidence based, but often there is little or no evidence to guide decision making. Donors are frequently upset and angry at what they see as arbitrary decisions. While they are not always right, and cannot be considered to have a right to donate, their reaction may be triggered by the paternalistic nature of our approach to this issue. While accepting that we must do nothing to jeopardise recipient safety, an argument can be constructed for putting our relationship with potential donors on a more ‘modern’ footing, perhaps by defining a ‘contract’ which allows for a definition of, and acceptance of, the risks of donation on a ‘partnership’ basis. It is also fair to say that improvements in recipient safety due to the extreme sensitivity of donation testing have as yet had no impact on donor selection. This is not unreasonable but as and when pathogen inactivation becomes a reality it will perhaps provide an opportunity to review donor selection criteria for which we should be prepared. The threat that testing for vCJD might drastically reduce the available donor base should provide the stimulus for us to begin to contemplate a ‘paradigm shift’ in donor selection. [ABSTRACT FROM AUTHOR]

Peripheral blood stem cell (PBSC) mobilization for autologous transplantation is more difficult in treated patients and those with bone marrow involvement. In 17 pretreated lymphoma patients, cyclophosphamide (4 g/m2) and G-CSF mobilized a median circulating peak of 1959 CFU-GM/ml on day 12.5. PBSC harvesting commenced when WBC was 1 x 10(9)/l at day 10.5 collected a median of 21.2 x 10(4)/CFU-GM/kg. 13/17 (76%) patients exceeded the 10 x 10(4) CFU-GM/kg threshold for engraftment. The CFU-GM yield was significantly higher in patients whose WBC recovered from 1-5 x 10(9)/l in less than 3 days and correlated with the maximum WBC pre and post the cyclophosphamide induced nadir. This regime safely mobilized adequate PBSC in the majority of pretreated lymphoma patients.

The aim of the present work was to determine if noradrenergic neurons of the anterior and the posterior subregions of the locus coeruleus exhibit a difference in reactivity in response to sodium nitroprusside-induced arterial hypotension, and if the pharmacological induction of tyrosine hydroxylase by RU24722 modifies the reactivity of locus coeruleus neurons to this hypotensive stimulus. Previous findings have demonstrated that administration of RU24722 increases the concentration of tyrosine hydroxylase in the rat locus coeruleus by two different mechanisms in the anterior and in the posterior locus coeruleus subregions. The goal of the present study was to measure in vivo the changes in catecholaminergic metabolism in the locus coeruleus after treatment with RU24722 using differential normal pulse voltammetry (DNPV). In vehicle-treated rats, arterial hypotension increased catecholaminergic metabolism with the same pattern in the two locus coeruleus subregions. However, the changes in the magnitude of the catechol oxidation current throughout the recording period were significantly smaller in the posterior subregion (P < 0.001). In the RU24722-pretreated rats, there was a 39% increase in tyrosine hydroxylase and dihydroxyphenylacetic acid in the locus coeruleus. The functional reactivity to hypotension measured by DNPV was significantly decreased (P < 0.001) in both the anterior and posterior locus coeruleus subregions with RU24722 treatment. Therefore, this study suggests that the response of locus coeruleus cells to a hypotensive stimulus depends upon the intracellular tyrosine hydroxylase concentration both in the basal condition and during pharmacological induction of tyrosine hydroxylase gene expression.