The rockefeller university

Please cite this paper as: Liang K, Meyers K, Zeng W, Gui X. Predictors of elective pregnancy termination among women diagnosed with HIV during pregnancy in two regions of China, 2004-2010. BJOG 2013;120:1207-1214. Objective To document the rates of abortion among women diagnosed with HIV during pregnancy in two regions of China, and to investigate the sociodemographic factors associated with women's decisions to terminate their pregnancy. Design Prospective cohort study. Setting Three central Chinese provinces (Hubei, Hebei and Shanxi) and Yining, Xinjiang. Population Women diagnosed with HIV during pregnancy, 2004-2010. Methods Of 798 HIV-infected pregnant women identified through routine screening of pregnant women via antenatal care between 2004 and 2010, 499 women made decisions about the outcome of pregnancy. Chi-squared test was used to describe the characteristics of women who chose to terminate their pregnancies. Logistic regression models were used to identify potential predictors for pregnancy outcome for one cohort of women in central China and a second cohort of women in Yining, Xinjiang. Main outcome measures Pregnancy outcome, trends of elective pregnancy termination. Results In the central China cohort, 76 of 161 pregnancies (47.2%) were terminated. In Yining, the proportion was significantly less, at only 61 of 338 (18.0%). Factors associated with pregnancy termination included unmarried marital status, already having one or more children and earlier trimester of pregnancy at the time of diagnosis. Conclusions The rate of pregnancy termination in these cohorts of HIV-infected women appears to be higher than the rate in the general population of women in China. More work needs to be carried out to decrease the social stigma related to HIV and to convey clear messages about the effectiveness of prevention of mother to child transmission to women and their families. The significantly lower rate of pregnancy termination in Yining relative to central China is probably a result of the cultural and religious reservations towards pregnancy termination. Healthcare workers providing services to HIV-infected pregnant women need to be sensitive to cultural factors influencing women's decisions with regard to pregnancy termination.

Previously, we have shown that Dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) knockout mice required significantly more trials to reach criterion than wild-type mice in an operant reversal-learning task. The present study was conducted to examine adult male and female DARPP-32 knockout mice and wild-type controls in a novel object recognition test. Wild-type and knockout mice exhibited comparable behavior during the initial exploration trials. As expected, wild-type mice exhibited preferential exploration of the novel object during the substitution test, demonstrating recognition memory. In contrast, knockout mice did not show preferential exploration of the novel object, instead exhibiting an increase in exploration of all objects during the test trial. Given that the removal of DARPP-32 is an intracellular manipulation, it seemed possible to pharmacologically restore some cellular activity and behavior by stimulating dopamine receptors. Therefore, a second experiment was conducted examining the effect of methylphenidate. The results show that methylphenidate increased horizontal activity in both wild-type and knockout mice, though this increase was blunted in knockout mice. Pretreatment with methylphenidate significantly impaired novel object recognition in wild-type mice. In contrast, pretreatment with methylphenidate restored the behavior of DARPP-32 knockout mice to that observed in wild-type mice given saline. These results provide additional evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory. These results also indicate that the behavioral deficits in DARPP-32 knockout mice may be restored by the administration of methylphenidate. (C) 2013 Elsevier B.V. All rights reserved.

The initiation of the first methadone maintenance treatment program (MMT) in Macao was founded in collaboration between MMT clinics in the USA and Israel. All patients admitted into treatment between October 2005 and October 2008 were prospectively followed through March 2010. Of the 163 patients, 81% were male, the mean age on admission was 39.5 (sd = 10.2). Seventy-three percent (n = 119) were hepatitis C sera positive, and 4.9% (n = 8) were HIV sera positive. One-year treatment retention rate was 59.5%, with 52.6% of the 95 patients who stayed in treatment having an opiate-negative urine test at the 10-month evaluation. Four and a half years of follow-up showed mean long-term retention (Kaplan Meier analyses) of 2.2 years. Higher methadone dose (>= 80mg/day) and hepatitis C sera positive status were predictors for longer treatment retention. This study describes an effective model of MMT that supports the expansion of addiction treatment in other countries.

Purpose To describe diverse medical students' perceptions of and interest in careers in academic medicine. Method In 2010, the authors invited students attending three national medical student conferences to respond to a survey and participate in six focus groups. The authors identified trends in data through bivariate analyses of the quantitative dataset and using a grounded theory approach in their analysis of focus group transcripts. Results The 601 survey respondents represented 103U.S. medical schools. The majority (72%) were in their first or second year; 34% were black and 17% were Hispanic. Many respondents (64%) expressed interest in careers in academic medicine; teaching and research were viewed as positive influences on that interest. However, black and Hispanic respondents felt they would have a harder time succeeding in academia. The 73 focus group participants (25% black, 29% Hispanic) described individual- and institutional-level challenges to academic medicine careers and offered recommendations. They desired deliberate and coordinated exposure to academic career paths, research training, clarification of the promotion process, mentorship, protected time for faculty to provide teaching and research training, and an enhanced infrastructure to support diversity and inclusion. Conclusions Medical students expressed an early interest in academic medicine but lacked clarity about the career path. Black and Hispanic students' perceptions of having greater difficulty succeeding in academia may be an obstacle to engaging them in the prospective pool of academicians. Strategic and dedicated institutional resources are needed to encourage racial and ethnic minority medical students to explore careers in academic medicine.

Background: In Gaucher disease (GD), resulting from mutations in the GBA gene, mutant beta-glucocerebrosidase (GCase) molecules are recognized as misfolded in the endoplasmic reticulum (ER). They are retrotranslocated to the cytoplasm, where they are ubiquitinated and undergo proteasomal degradation in a process known as the ER Associated Degradation (ERAD). We have shown in the past that the degree of ERAD of mutant GCase correlates with GD severity. Persistent presence of mutant, misfolded protein molecules in the ER leads to ER stress and evokes the unfolded protein response (UPR). Methods: We investigated the presence of UPR in several GD models, using molecular and behavioral assays. Results: Our results show the existence of UPR in skin fibroblasts from GD patients and carriers of GD mutations. We could recapitulate UPR in two different Drosophila models for carriers of GD mutations: flies heterozygous for the endogenous mutant GBA orthologs and flies expressing the human N370S or L444P mutant GCase variants. We encountered early death in both fly models, indicating the deleterious effect of mutant GCase during development. The double heterozygous flies, and the transgenic flies, expressing mutant GCase in dopaminergic/serotonergic cells developed locomotion deficit. Conclusion: Our results strongly suggest that mutant GCase induces the UPR in GD patients as well as in carriers of GD mutations and leads to development of locomotion deficit in flies heterozygous for GD mutations.

Taylor's law (TL), a widely verified empirical relationship in ecology, states that the variance of population density is approximately a power-law function of mean density. The growth-rate theorem (GR) states that, in a subdivided population, the rate of change of the overall growth rate is proportional to the variance of the subpopulations' growth rates. We show that continuous-time exponential change implies GR at every time and, asymptotically for large time, TL with power-law exponent 2. We also show why diverse population-dynamic models predict TL in the limit of large time by identifying simple features these models share: If the mean population density and the variance of population density are (exactly or asymptotically) non-constant exponential functions of a parameter (e.g., time), then the variance of density is (exactly or asymptotically) a power-law function of mean density. (C) 2013 Elsevier Inc. All rights reserved.

Dendritic cells (DCs), monocytes, and macrophages are closely related phagocytes that share many phenotypic features and, in some cases, a common developmental origin. Although the requirement for DCs in initiating adaptive immune responses is well appreciated, the role of monocytes and macrophages remains largely undefined, in part because of the lack of genetic tools enabling their specific depletion. Here, we describe a two-gene approach that requires overlapping expression of LysM and Csf1r to define and deplete monocytes and macrophages. The role of monocytes and macrophages in immunity to pathogens was tested by their selective depletion during infection with Citrobacter rodentium. Although neither cell type was required to initiate immunity, monocytes and macrophages contributed to the adaptive immune response by secreting IL-12, which induced Th1 polarization and IFN-gamma secretion. Thus, whereas DCs are indispensable for priming naive CD4(+) T cells, monocytes and macrophages participate in intestinal immunity by producing mediators that direct T cell polarization.

The results of searches for supersymmetry by the CMS experiment are interpreted in the framework of simplified models. The results are based on data corresponding to an integrated luminosity of 4.73 to 4.98 fb(-1). The data were collected at the LHC in proton-proton collisions at a center-of-mass energy of 7 TeV. This paper describes the method of interpretation and provides upper limits on the product of the production cross section and branching fraction as a function of new particle masses for a number of simplified models. These limits and the corresponding experimental acceptance calculations can be used to constrain other theoretical models and to compare different supersymmetry-inspired analyses.

The concentration of ribonucleoside triphosphates (rNTPs) in cells is far greater than the concentration of deoxyribonucleoside triphosphates (dNTPs), and this pool imbalance presents a challenge for DNA polymerases (Pols) to select their proper substrate. This report examines the effect of nucleotide pool imbalance on the rate and fidelity of the Escherichia coli replisome. We find that rNTPs decrease replication fork rate by competing with dNTPs at the active site of the C-family Pol III replicase at a step that does not require correct base-pairing. The effect of rNTPs on Pol rate generalizes to B-family eukaryotic replicases, Pols delta and epsilon. Imbalance of the dNTP pool also slows the replisome and thus is not specific to rNTPs. We observe a measurable frequency of rNMP incorporation that predicts one rNTP incorporated every 2.3 kb during chromosome replication. Given the frequency of rNMP incorporation, the repair of rNMPs is likely rapid. RNase HII nicks DNA at single rNMP residues to initiate replacement with dNMP. Considering that rNMPs will mark the new strand, RNase HII may direct strand-specificity for mismatch repair (MMR). How the newly synthesized strand is recognized for MMR is uncertain in eukaryotes and most bacteria, which lack a methyl-directed nicking system. Here we demonstrate that Bacillus subtilis incorporates rNMPs in vivo, that RNase HII plays a role in their removal, and the RNase HII gene deletion enhances mutagenesis, suggesting a possible role of incorporated rNMPs in MMR.

Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated with enhanced cognition, neuroprotection and neurogenesis in laboratory animals, and has entered phase II clinical trials for both Alzheimer's disease and Huntington's disease (HD). Based on recent indications that latrepirdine protects cells against cytotoxicity associated with expression of aggregatable neurodegeneration-related proteins, including A beta 42 and gamma-synuclein, we sought to determine whether latrepirdine offers protection to Saccharomyces cerevisiae. We utilized separate and parallel expression in yeast of several neurodegeneration-related proteins, including alpha-synuclein (alpha-syn), the amyotrophic lateral sclerosis-associated genes TDP43 and FUS, and the HD-associated protein huntingtin with a 103 copy-polyglutamine expansion (HTT gene; htt-103Q). Latrepirdine effects on alpha-syn clearance and toxicity were also measured following treatment of SH-SY5Y cells or chronic treatment of wildtype mice. Latrepirdine only protected yeast against the cytotoxicity associated with alpha-syn, and this appeared to occur via induction of autophagy. We further report that latrepirdine stimulated the degradation of alpha-syn in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers of autophagic activity. Ongoing experiments will determine the utility of latrepirdine to abrogate alpha-syn accumulation in transgenic mouse models of alpha-syn neuropathology. We propose that latrepirdine may represent a novel scaffold for discovery of robust proautophagic/anti-neurodegeneration compounds, which might yield clinical benefit for synucleinopathies including Parkinson's disease, Lewy body dementia, rapid eye movement (REM) sleep disorder and/or multiple system atrophy, following optimization of its pro-autophagic and pro-neurogenic activities.