Effect of 1995 pill scare on rates of venous thromboembolism among women taking combined oral contraceptives: analysis of general practice research database

In October 1995 the UK Committee on Safety of Medicines advised that combined oral contraceptives (OCs) containing either gestodene or desogestrel were associated with twice the risk of venous thromboembolism compared with older products. This study was conducted to compare the incidence of venous thromboembolism among women taking combined OCs before and after the October 1995 pill scare. Using data from the General Practice Research Database, a total of 304 practices were analyzed. Overall, results show that use of third-generation combined OCs fell from 53% during the period of January 1993 to October 1995 to 14% during the period of November 1995 to December 1998. No significant change was noted in the incidence of venous thromboembolism between the two periods after age was adjusted for (incidence ratio, 1.04; 95% confidence interval, 0.78-1.39). Based on these findings, it is concluded that third-generation OCs are not associated with a twofold increase in risk of venous thromboembolism compared with older progestogens.     

Fatty acid ketodienes and fatty acid ketotrienes: Michael addition acceptors that accumulate in wounded and diseased Arabidopsis leaves

Physical damage and disease are known to lead to changes in the oxylipin signature of plants. We searched for oxylipins produced in response to both wounding and pathogenesis in Arabidopsis leaves. Linoleic acid 9- and 13-ketodienes (KODEs) were found to accumulate in wounded leaves as well as in leaves infected with the pathogen Pseudomonas syringae pv. tomato (Pst). Quantification of the compounds showed that they accumulated to higher levels during the hypersensitive response to Pst avrRpm1 than during infection with a Pst strain lacking an avirulence gene. KODEs are Michael addition acceptors, containing a chemically reactive alpha,beta-unsaturated carbonyl group. When infiltrated into leaves, KODEs were found to induce expression of the GST1 gene, but vital staining indicated that these compounds also damaged plant cells. Several molecules typical of lipid oxidation, including malonaldehyde, also contain the alpha,beta-unsaturated carbonyl reactivity feature, and, when delivered in a volatile form, powerfully induced the expression of GST1. The results draw attention to the potential physiological importance of naturally occurring Michael addition acceptors in plants. In particular, these compounds could act directly, or indirectly via cell damage, as powerful gene activators and might also contribute to host cell death.     

Parental Care: The Key to Understanding Endothermy and Other Convergent Features in Birds and Mammals

Birds and mammals share a number of features that are remarkably similar but that have evolved independently. One of these characters, endothermy, has been suggested to have played a cardinal role in avian and mammalian evolution. I hypothesize that it is parental care, rather than endothermy, that is the key to understanding the amazing convergence between mammals and birds. Endothermy may have arisen as a consequence of selection for parental care because endothermy enables a parent to control incubation temperature. The remarkable ability of many birds and mammals to sustain vigorous exercise may also have arisen as a consequence of selection for parental care because provisioning of offspring often requires sustained vigorous exercise. Because extensive parental care encompasses a wide range of behaviors, morphology, and physiology, it may be a key innovation that accounts for the majority of convergent avian and mammalian characters.     

Processing of viral envelope glycoprotein by the endomannosidase pathway: evaluation of host cell specificity

Endo-alpha-D-mannosidase is an enzyme involved in N-linked oligosaccharide processing which through its capacity to cleave the internal linkage between the glucose-substituted mannose and the remainder of the polymannose carbohydrate unit can provide an alternate pathway for achieving deglucosylation and thereby make possible the continued formation of complex oligosaccharides during a glucosidase blockade. In view of the important role which has been attributed to glucose on nascent glycoproteins as a regulator of a number of biological events, we chose to further define the in vivo action of endomannosidase by focusing on the well characterized VSV envelope glycoprotein (G protein) which can be formed by the large array of cell lines susceptible to infection by this pathogen. Through an assessment of the extent to which the G protein was converted to an endo-beta-N- acetylglucosaminidase (endo H)-resistant form during a castanospermine imposed glucosidase blockade, we found that utilization of the endomannosidase-mediated deglucosylation route was clearly host cell specific, ranging from greater than 90% in HepG2 and PtK1 cells to complete absence in CHO, MDCK, and MDBK cells, with intermediate values in BHK, BW5147.3, LLC-PK1, BRL, and NRK cell lines. In some of the latter group the electrophoretic pattern after endo H treatment suggested that only one of the two N-linked oligosaccharides of the G protein was processed by endomannosidase. In the presence of the specific endomannosidase inhibitor, Glcalpha1-->3(1- deoxy)mannojirimycin, the conversion of the G protein into an endo H- resistant form was completely arrested. While the lack of G protein processing by CHO cells was consistent with the absence of in vitro measured endomannosidase activity in this cell line, the failure of MDBK and MDCK cells to convert the G protein into an endo H-resistant form was surprising since these cell lines have substantial levels of the enzyme. Similarly, we observed that influenza virus hemagglutinin was not processed in castanospermine-treated MDCK cells. Our findings suggest that studies which rely on glucosidase inhibition to explore the function of glucose in controlling such critical biological phenomena as intracellular movement or quality control should be carried out in cell lines in which the glycoprotein under study is not a substrate for endomannosidase action.      

Biotherapeutic effects of Bifidobacterium spp. on orogastric and systemic candidiasis in immunodeficient mice

Two commercially available Bifidobacterium spp. (Bifidobacterium infantis and Bifidobacterium lactis) were compared for their capacities to protect immunodeficient bg/bg-nu/nuand bg/bg-nu/+mice from orogastric and lethal candidiasis. Both Bifidobacterium spp. prolonged the survival of Candida albicans-colonized adult and neonatal bg/bg-nu/numice. The bifidobacteria affected the production of antibodies to C. albicans, inhibited disseminated candidiasis, suppressed weight loss associated with C. albicans infection, inhibited the growth of C. albicans in the alimentary tract, inhibited systemic candidiasis of endogenous origin, and decreased the severity of gastric candidiasis in both mouse strains. B. infantis inhibited systemic candidiasis of endogenous origin better than B. lactis; however, B. lactis was significantly more effective at inhibiting C. albicans colonization of the alimentary tract, suppressing gastric candidiasis, and protecting bg/bg-nu/numice from lethal candidiasis than B. infantis. These results show that Bifidobacterium spp. can protect immunodeficient mice from candidiasis but different species manifest quantitative and qualitative differences in their probiotic and biotherapeutic effects.     

Dynamics of Maize Carbon Contribution to Soil Organic Carbon in Association with Soil Type and Fertility Level

Soil type and fertility level influence straw carbon dynamics in the agroecosystems. However, there is a limited understanding of the dynamic processes of straw-derived and soil-derived carbon and the influence of the addition of straw carbon on soil-derived organic carbon in different soils associated with different fertility levels. In this study, we applied the in-situ carborundum tube method and ¹³C-labeled maize straw (with and without maize straw) at two cropland (Phaeozem and Luvisol soils) experimental sites in northeast China to quantify the dynamics of maize-derived and soil-derived carbon in soils associated with high and low fertility, and to examine how the addition of maize carbon influences soil-derived organic carbon and the interactions of soil type and fertility level with maize-derived and soil-derived carbon. We found that, on average, the contributions of maize-derived carbon to total organic carbon in maize-soil systems during the experimental period were differentiated among low fertility Luvisol (from 62.82% to 42.90), high fertility Luvisol (from 53.15% to 30.00%), low fertility Phaeozem (from 58.69% to 36.29%) and high fertility Phaeozem (from 41.06% to 16.60%). Furthermore, the addition of maize carbon significantly decreased the remaining soil-derived organic carbon in low and high fertility Luvisols and low fertility Phaeozem before two months. However, the increasing differences in soil-derived organic carbon between both soils with and without maize straw after two months suggested that maize-derived carbon was incorporated into soil-derived organic carbon, thereby potentially offsetting the loss of soil-derived organic carbon. These results suggested that Phaeozem and high fertility level soils would fix more maize carbon over time and thus were more beneficial for protecting soil-derived organic carbon from maize carbon decomposition.     

High Transmitter CD4+ T-Cell Count Shortly after the Time of Transmission in a Study of African Serodiscordant Couples

Background

2013 WHO guidelines recommend starting ART at CD4+ T-cell counts ≤500 cells/μL. We present the T-cell counts from adult Africans with HIV shortly following transmission to their sexual partners.

Methods

HIV-discordant couples in Zambia, Uganda and Rwanda were followed prospectively and received couples counseling and condoms. HIV uninfected partners were tested for HIV at least quarterly and HIV-infected partners received HIV care and referral for ART per national guidelines. Upon diagnosis of incident HIV infection in the previously HIV-uninfected partner, a blood sample was collected from both partners to measure CD4+ T-cells and perform viral linkage. The estimated date of infection (EDI) of the incident case was calculated based on testing history. EDI was unknown for suspected transmitting partners.

Results

From 2006–2011, 4,705 HIV-discordant couples were enrolled in this cohort, and 443 cases of incident HIV infection were documented. Virus linkage analysis was performed in 374 transmission pairs, and 273 (73%) transmissions were linked genetically. CD4 counts in the transmitting partner were measured a median of 56 days after EDI (mean:90.5, min:10, max:396). The median CD4 count was 339 cells/μl (mean:386.4, min:15, max:1,434), and the proportion of partners with a CD4+ T-cell count above 500/μl was 25% (95% CI:21, 31).

Conclusions

In our cohort of discordant couples, 73% of HIV transmissions occurred within the relationship, and the transmitter CD4+ T cell count shortly after the transmission event was frequently higher than the WHO 2013 ART-initiation guidelines.