Isovaleric acidaemia in two South African children

CITATION: Malan, C., Neethling, A. C. & Shanley, B. C. 1977. Isovaleric acidaemia in two South African children. South African Medical Journal, 51(26):980-983.The original publication is available at http://www.samj.org.zaTwo siblings who were repeatedly admitted to hospital with acute episodes of vomiting, dehydration and coma were found to be suffering from isovaleric acidaemia. This condition is a rare inherited abnormality of leucine metabolism, which is frequently fatal in the early weeks of life and leads to mental retardation in a high proportion of those who survive early attacks. However, both out patients were of normal intelligence. The clinical presentation, biochemical defect, diagnosis and suggested therapies are reviewed.Publisher’s versio

Spatial patterns of soil nitrification and nitrate export from forested headwaters in the northeastern United States

Nitrogen export from small forested watersheds is known to be affected by N deposition but with high regional variability. We studied 10 headwater catchments in the northeastern United States across a gradient of N deposition (5.4 - 9.4 kg ha-1 yr-1) to determine if soil nitrification rates could explain differences in stream water NO 3- export. Average annual export of two years (October 2002 through September 2004) varied from 0.1 kg NO3--N ha-1 yr-1 at Cone Pond watershed in New Hampshire to 5.1 kg ha-1 yr-1 at Buck Creek South in the western Adirondack Mountains of New York. Potential net nitrification rates and relative nitrification (fraction of inorganic N as NO3-) were measured in Oa or A soil horizons at 21-130 sampling points throughout each watershed. Stream NO3- export was positively related to nitrification rates (r2 = 0.34, p = 0.04) and the relative nitrification (r2 = 0.37, p = 0.04). These relationships were much improved by restricting consideration to the 6 watersheds with a higher number of rate measurements (59-130) taken in transects parallel to the streams (r 2 of 0.84 and 0.70 for the nitrification rate and relative nitrification, respectively). Potential nitrification rates were also a better predictor of NO3- export when data were limited to either the 6 sampling points closest to the watershed outlet (r2 = 0.75) or sampling points \u3c250 m from the watershed outlet (r2 = 0.68). The basal area of conifer species at the sampling plots was negatively related to NO3- export. These spatial relationships found here suggest a strong influence of near-stream and near-watershed-outlet soils on measured stream NO3- export. Copyright 2012 by the American Geophysical Union

A novel protamine variant reversal of heparin anticoagulation in human blood in vitro

AbstractPurpose: Protamine reversal of heparin anticoagulation during cardiovascular surgery may cause severe hypotension and pulmonary hypertension. A novel protamine variant, [+18RGD], has been developed that effectively reverses heparin anticoagulation without toxicity in canine experiments. Heretofore, human studies have not been undertaken. This investigation hypothesized that [+18RGD] would effectively reverse heparin anticoagulation of human blood in vitro. Methods: Fifty patients who underwent anticoagulation therapy during vascular surgery had blood sampled at baseline and 30 minutes after receiving heparin (150 IU/kg). Activated clotting times were used to define specific quantities of [+18RGD] or protamine necessary to completely reverse heparin anticoagulation in the blood sample of each patient. These defined amounts of [+18RGD] or protamine were then administered to the heparinized blood samples, and percent reversals of activated partial thromboplastin time, thrombin clotting time, and antifactor Xa/IIa levels were determined. In addition, platelet aggregation assays, as well as platelet and white blood cell counts were performed. Results: [+18RGD] and protamine were equivalent in reversing heparin as assessed by thrombin clotting time, antifactor Xa, antifactor IIa levels, and white blood cell changes. [+18RGD], when compared with protamine, was superior in this regard, as assessed by activated partial thromboplastin time (94.5 ± 1.0 vs 86.5 ± 1.3%δ, respectively; p < 0.001) and platelet declines (–3.9 ± 2.9 vs –12.8 ± 3.4 per mm3, respectively; p = 0.048). Platelet aggregation was also decreased for [+18RGD] compared with protamine (23.6 ± 1.5 vs 28.5 ± 1.9%, respectively; p = 0.048). Conclusions: [+18RGD] was as effective as protamine for in vitro reversal of heparin anticoagulation by most coagulation assays, was statistically more effective at reversal than protamine by aPTT assay, and was associated with lesser platelet reductions than protamine. [+18RGD], if less toxic than protamine in human beings, would allow for effective clinical reversal of heparin anticoagulation. (J Vasc Surg 1997;26:1043-8.

High‐Frequency Dissolved Organic Carbon and Nitrate Measurements Reveal Differences in Storm Hysteresis and Loading in Relation to Land Cover and Seasonality

Storm events dominate riverine loads of dissolved organic carbon (DOC) and nitrate and are expected to increase in frequency and intensity in many regions due to climate change. We deployed three high‐frequency (15 min) in situ absorbance spectrophotometers to monitor DOC and nitrate concentration for 126 storms in three watersheds with agricultural, urban, and forested land use/land cover. We examined intrastorm hysteresis and the influences of seasonality, storm size, and dominant land use/land cover on storm DOC and nitrate loads. DOC hysteresis was generally anticlockwise at all sites, indicating distal and plentiful sources for all three streams despite varied DOC character and sources. Nitrate hysteresis was generally clockwise for urban and forested sites, but anticlockwise for the agricultural site, indicating an exhaustible, proximal source of nitrate in the urban and forested sites, and more distal and plentiful sources of nitrate in the agricultural site. The agricultural site had significantly higher storm nitrate yield per water yield and higher storm DOC yield per water yield than the urban or forested sites. Seasonal effects were important for storm nitrate yield in all three watersheds and farm management practices likely caused complex interactions with seasonality at the agricultural site. Hysteresis indices did not improve predictions of storm nitrate yields at any site. We discuss key lessons from using high‐frequency in situ optical sensors

Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination

Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones

ACKNOWLEDGMENTS This work was funded by The BBSRC (BB/D004659/1) the Wellcome Trust (080980/Z/06/Z) and the Medical Research Council (G0701003).Peer reviewedPublisher PD

Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia1. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse1−7. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorfy understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL)8. We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins

Ambient particulate matter air pollution exposure and mortality in the NIH-AARP diet and health cohort

BACKGROUND: Outdoor fine particulate matter (≤ 2.5 μm; PM2.5) has been identified as a global health threat, but the number of large U.S. prospective cohort studies with individual participant data remains limited, especially at lower recent exposures. OBJECTIVES: We aimed to test the relationship between long-term exposure PM2.5 and death risk from all nonaccidental causes, cardiovascular (CVD), and respiratory diseases in 517,041 men and women enrolled in the National Institutes of Health-AARP cohort. METHODS: Individual participant data were linked with residence PM2.5 exposure estimates across the continental United States for a 2000–2009 follow-up period when matching census tract–level PM2.5 exposure data were available. Participants enrolled ranged from 50 to 71 years of age, residing in six U.S. states and two cities. Cox proportional hazard models yielded hazard ratio (HR) estimates per 10 μg/m3 of PM2.5 exposure. RESULTS: PM2.5 exposure was significantly associated with total mortality (HR = 1.03; 95% CI: 1.00, 1.05) and CVD mortality (HR = 1.10; 95% CI: 1.05, 1.15), but the association with respiratory mortality was not statistically significant (HR = 1.05; 95% CI: 0.98, 1.13). A significant association was found with respiratory mortality only among never smokers (HR = 1.27; 95% CI: 1.03, 1.56). Associations with 10-μg/m3 PM2.5 exposures in yearly participant residential annual mean, or in metropolitan area-wide mean, were consistent with baseline exposure model results. Associations with PM2.5 were similar when adjusted for ozone exposures. Analyses of California residents alone also yielded statistically significant PM2.5 mortality HRs for total and CVD mortality. CONCLUSIONS: Long-term exposure to PM2.5 air pollution was associated with an increased risk of total and CVD mortality, providing an independent test of the PM2.5–mortality relationship in a new large U.S. prospective cohort experiencing lower post-2000 PM2.5 exposure levels. CITATION: Thurston GD, Ahn J, Cromar KR, Shao Y, Reynolds HR, Jerrett M, Lim CC, Shanley R, Park Y, Hayes RB. 2016. Ambient particulate matter air pollution exposure and mortality in the NIH-AARP Diet and Health cohort. Environ Health Perspect 124:484–490; http://dx.doi.org/10.1289/ehp.150967

ECSA's Characteristics of Citizen Science: Explanation Notes

This explanation document provides an interpretation of and explanation for the characteristics document, which was kept short to make it useful to different stakeholders. In this document, the characteristics document is represented, with the original text in blue and an explanation in black

Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Perù