Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth patterns in the first year of life differ in infants born to perinatally vs. nonperinatally HIV-infected women

Objective:To compare the growth patterns in the first year of life between children born to perinatally HIV-infected (PHIV) vs. nonperinatally HIV-infected (NPHIV) women in the United States. Design:Retrospective cohort study of HIV-infected pregnant women who received care and delivered a live-born at two urban tertiary centers from January 2004 to March 2012. Methods:We collected data via chart review on demographics, behavioral risk factors, HIV clinical markers, combination antiretroviral therapy (cART), mode of HIV acquisition, pregnancy outcomes, and infant anthropometrics on study participants. Mixed-effects models were used to assess the association between maternal mode of HIV acquisition and weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and weight-for-length z-score (WLZ). Results:Of the 152 pregnancies evaluated, 32 and 120 infants were born to 25 PHIV and 99 NPHIV women, respectively. Infants of PHIV women exhibited lower mean WAZ and LAZ throughout the first year of life in unadjusted analyses. After adjusting for potential confounders, the relationship between PHIV women and LAZ persisted (&bgr; = −0.54, P = 0.026). Small-for-gestational age for each birth anthropometric parameter (birth length, birth weight, and both birth length and weight) was associated with decreased LAZ (&bgr; = −0.48, P = 0.007), WAZ (&bgr; = −0.99, P < 0.001), and WLZ (&bgr; = −0.36, P = 0.027), respectively. A delivery HIV RNA level below 400 copies/ml was associated with increased WAZ and WLZ (&bgr; = 0.43, P = 0.015 and &bgr; = 0.38, P = 0.021, respectively). Conclusions:Infants of PHIV women may remain at persistently decreased lengths throughout the first year of life. Further studies aimed at understanding intrauterine and environmental factors in PHIV women are warranted.
X-ray Structure of 4,4′-Dihydroxybenzophenone Mimicking Sterol Substrate in the Active Site of Sterol 14α-Demethylase (CYP51)*♦

A universal step in the biosynthesis of membrane sterols and steroid hormones is the oxidative removal of the 14α-methyl group from sterol precursors by sterol 14α-demethylase (CYP51). This enzyme is a primary target in treatment of fungal infections in organisms ranging from humans to plants, and development of more potent and selective CYP51 inhibitors is an important biological objective. Our continuing interest in structural aspects of substrate and inhibitor recognition in CYP51 led us to determine (to a resolution of 1.95Å) the structure of CYP51 from Mycobacterium tuberculosis (CYP51Mt) co-crystallized with 4,4′-dihydroxybenzophenone (DHBP), a small organic molecule previously identified among top type I binding hits in a library screened against CYP51Mt. The newly determined CYP51Mt-DHBP structure is the most complete to date and is an improved template for three-dimensional modeling of CYP51 enzymes from fungal and prokaryotic pathogens. The structure demonstrates the induction of conformational fit of the flexible protein regions and the interactions of conserved Phe-89 essential for both fungal drug resistance and catalytic function, which were obscure in the previously characterized CYP51Mt-estriol complex. DHBP represents a benzophenone scaffold binding in the CYP51 active site via a type I mechanism, suggesting (i) a possible new class of CYP51 inhibitors targeting flexible regions, (ii) an alternative catalytic function for bacterial CYP51 enzymes, and (iii) a potential for hydroxybenzophenones, widely distributed in the environment, to interfere with sterol biosynthesis. Finally, we show the inhibition of M. tuberculosis growth by DHBP in a mouse macrophage model.
Current concepts in vulvodynia with a focus on pathogenesis and pain mechanisms

Vulvodynia is a common and debilitating chronic pain syndrome characterised by neuropathic‐type pain. Localised provoked vulvodynia is the most common type, followed by generalised unprovoked vulvodynia. Vulvodynia is a diagnosis of exclusion. The cause is unknown but current research suggests an underlying predisposition to increased sensitivity to pain and peripheral and central neural sensitisation. Musculoskeletal factors also play an important role. Vulvodynia has a significant impact on the quality of life, mood, functional ability and relationships of patients and their partners. It is highly associated with anxiety and depression. Treatment needs to follow a biopsychosocial model and be tailored to the patient. A multimodal and multidisciplinary approach is often most effective. We have suggested a therapeutic ladder.
Comparison of antimicrobial, antioxidant activities and total phenolic content of Antidesma thwaitesianum fruit extracts by different methods.

BACKGROUND Antidesma thwaitesianum Mull. Arg. is a tropical fruit in Northeast Thailand and its fruits are used for soft drink and healthy food. The biological activities of extracts from Antidesma thwaitesianum using different extraction methods have not been reported. OBJECTIVE Extracts from Antidesma thwaitesianum using different extraction methods were tested for antibacterial and antioxidant activities as well as were determined for total phenolic content. Ten extracts were tested for antimicrobial activity by disc diffusion, MIC, and MBC methods. DPPH assay was used to test antioxidant activity and Folin-Ciocalteu 's reagent was used to determine total phenolic content. RESULTS The extract obtained by decocting residue after maceration process of dried marc (MRW) exhibited stronger antioxidative power (EC50 = 11.73 microg/ml) than BHT (EC50 = 13.36 microg/ml). This antioxidant activity was related to total phenolic content of 85.77 +/- 0.34 mg GAE/g. This extract also exhibited antimicrobial activity against Staphylococcus aureus (inhibition zone = 8 mm, MIC = 2.5 mg/ml). Moreover the extract obtained by macerating dried marc (MME) exhibited antimicrobial activity against Bacillus subtilis with the same MIC value of 10 mg/ml. CONCLUSION All of the extracts of Antidesma thwaitesianum had less potential for antimicrobial activity than Gentamicin and Amphotericin B. On the other hand, the water extract especially obtained by decocting residue after maceration of dry marc had good antioxidant power and the highest total phenolic content. Thus, such water extract should be recommended for a good source of natural antioxidants for commercial uses.
Caries risk assessment in young adults using Public Dental Service guidelines and the Cariogram—a comparative study

Abstract Objectives. To investigate the caries risk profiles in young adults and to compare the risk classification using the Public Dental Service (PDS) guidelines with a risk assessment program, the Cariogram. Materials and methods. All 19-year-old patients registered at eight public dental clinics were invited to participate (n = 1699). The study group who completed the baseline examination consisted of 1295 subjects representing 10% of all 19 year-olds attending dental care at the PDS in Skåne, Sweden. A risk classification of each patient was made by the patient's regular team according to the PDS guidelines. A research team collected whole saliva samples and information from a questionnaire and a structured interview in order to calculate risk according to the Cariogram model. Results. The mean DFS value was 4.9 and 23% of the patients were registered as caries-free (DFS = 0). The PDS risk classification was predominantly based on past caries and/or present caries activity. The majority was classified as ‘some risk', while 16.7% were assessed as being of ‘high' or ‘very high risk'. The corresponding value for the two highest risk groups in the Cariogram model was 17.4%. The agreement between the two models was found acceptable (77.5%) for those assessed as low risk, while discrepancies were disclosed among those classified with higher risks. Conclusions. Although the proportion of subjects assessed with high or very high risk was similar using the PDS guidelines and the Cariogram model, the agreement between the models was fair. An acceptable agreement was only disclosed for the low risk category.
Canine transmissible venereal tumour: a morphological and immunohistochemical study of 11 tumours in growth phase and during regression after chemotherapy.

Eleven dogs with canine transmissible venereal tumour (CTVT) were given vincristine sulphate chemotherapy to induce tumour regression. Biopsy specimens were collected from tumours during the growth phase, before chemotherapy, and again from the same dogs during the regression induced by chemotherapy. Laboratory assessment included cytology, histology, the number of tumour cells in relation to the number of intratumoral leucocytes, proliferative and apoptotic fractions of tumour cells, intratumoral vessel density, and fibrosis. The results revealed that during regression, tumour cell proliferation ceased, apoptosis increased, leucocytes increased (with increased proportion of T lymphocytes), tumour parenchyma collapsed around intratumoral vessels, and fibrosis increased. These results, which were similar to findings in dogs with spontaneous regression of CTVT, suggest that tumour immunity plays a role in tumour regression after modest chemotherapy.
Susceptibility Baseline and Chlorantraniliprole Resistance Monitoring in Chilo suppressalis (Lepidoptera: Pyralidae)

ABSTRACT Chlorantraniliprole, a new anthranilic diamide insecticide, has been commercialized in China since 2008 for controlling of several lepidopterans, including rice stem borer, Chilo suppressalis Walker. Chemical control of this pest has become difficult because of its resistance development to many conventional insecticides. To facilitate chlorantraniliprole-resistance monitoring, seedling dip bioassays were conducted in 2011 and 2012 to assess the susceptibility of 30 populations of C. suppressalis from seven provinces in China. The assays established a larval susceptibility baseline with LC50 at 1.393 mg a.i/liter. The toxicity (LC50) of chlorantraniliprole against second-instar larvae of field populations ranged from 0.568 (SL12) to 13.547 (RA12) mg a.i/liter. Substantial variations of the susceptibility to chlorantraniliprole were detected among different geographic populations, but no significant difference was observed between years for most populations except for populations from Dong'an, Cangnan, and Lujiang. Resistance ratios to the chemical ranged from 1.0 to 9.7, indicating that most colonies remained susceptible or showed certain decrease in susceptibility. Approximately, 13.3% of the populations exhibited low levels of resistance to chlorantraniliprole. These data are useful in future monitoring program for detecting any changes in susceptibility as a result of use of the insecticide.
MicroRNAs Are Stored in Human MII Oocyte and Their Expression Profile Changes in Reproductive Aging1

ABSTRACT Maternal RNAs are synthesized by the oocyte during its growth; some of them are utilized for oocyte-specific processes and metabolism, others are stored and used during early development before embryonic genome activation. The appropriate expression of complex sets of genes is needed for oocyte maturation and early embryo development. In spite of the basic role of noncoding RNAs in the regulation of gene expression, few studies have analyzed their role in human oocytes. In this study, we identified the microRNAs (miRNAs) expressed in human metaphase II stage oocytes, and found that some of them are able to control pluripotency, chromatin remodeling, and early embryo development. We demonstrated that 12 miRNAs are differentially expressed in women of advanced reproductive age and, by bioinformatics analysis, we identified their mRNA targets, expressed in human oocytes and involved in the regulation of pathways altered in reproductive aging. Finally, we found the upregulation of miR-29a-3p, miR-203a-3p, and miR-494-3p, evolutionarily conserved miRNAs, also in aged mouse oocytes, and demonstrated that their overexpression is antithetically correlated with the downregulation of DNA methyltransferase 3A (Dnmt3a), DNA methyltransferase 3B (Dnmt3b), phosphatase and tensin homolog (Pten), and mitochondrial transcription factor A (Tfam). We propose that oocyte miRNAs perform an important regulatory function in human female germ cells, and their altered regulation could explain the changes occurring in oocyte aging.
Characterization of Endothelium- Dependent Relaxation in Guinea Pig Basilar Artery – Effect of Hypoxia and Role of Cytochrome P450 Mono-Oxygenase

In the guinea pig basilar artery, acetylcholine and the calcium ionophore A23187 induced endothelium-dependent relaxations, which were not significantly affected by the nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine (L-NOARG; 0.3 mM) or the guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one; 1-10 µM), or by these inhibitors combined. However, acetylcholine (10 µM) and A23187 (3 µM) each significantly increased the tissue level of cGMP in the absence but not in the presence of L-NOARG, suggesting that NO is released from the vascular endothelium in this blood vessel. Treatment with the potassium (K) channel inhibitors charybdotoxin (0.1 µM) plus apamin (0.1 µM), a toxin mixture previously shown to inhibit relaxations mediated by endothelium-derived hyperpolarizing factor (EDHF) in this artery, had no effect on the A23187-induced relaxation but slightly inhibited the response to acetylcholine (Emax was reduced by 24%). When the action of EDHF was prevented by these K channel inhibitors, the remaining relaxation was abolished by either ODQ (1 µM) or L-NOARG (0.3 mM), indicating that NO, apart from EDHF, contributes to the endothelium-dependent relaxations. Furthermore, ODQ (10 µM) abolished the relaxation induced by the NO donor S-nitroso-N-acetylpenicillamine. Thus, activation of soluble guanylate cyclase seems to be the only mechanism through which NO causes relaxation in this artery. When vessels were exposed to grave hypoxia (pO2 = 6 mm Hg), the NO-mediated relaxation (induced by acetylcholine in the presence of charybdotoxin plus apamin) disappeared. In contrast, EDHF-mediated responses (elicited by acetylcholine in the presence of L-NOARG) were only marginally affected by hypoxia (Emax was reduced by 16%). 17-Octadecynoic acid (50 µM) and 5,8,11,14-eicosatetraynoic acid (10 µM), inhibitors of cytochrome P450-dependent oxidation of arachidonic acid, failed to inhibit the acetylcholine-induced relaxation in the presence of L-NOARG. The cytochrome P450-dependent arachidonic acid metabolite 11,12-epoxyecosatrienoic acid (0.3–3.0 µM) had no relaxant effect per se. In conclusion, EDHF and NO are both mediators of endothelium-dependent relaxations in the guinea pig basilar artery. However, during grave hypoxia, EDHF alone mediates acetylcholine-induced relaxation. The results further suggest that EDHF is not a metabolite of arachidonic acid formed by cytochrome P450 mono-oxygenase or generated by another oxygen-dependent enzyme in this artery.
Costs, Impacts, and Benefits of CO2 Mitigation

This volume presents the proceedings of the first international workshop on "Costs, Impacts, and Possible Benefits of CO2 Mitigation" held at IIASA in October 1992. The workshop was co-organized by the Japanese Central Research Institute of the Electric Power Industry (CRIEPI), IIASA, the National Science Foundation (NSF), Yale University, and the Intergovernmental Panel on Climate Change (IPCC). The workshop was held to review current research and analysis of economic costs and possible benefits of measures for responding to global climate change, and to critically evaluate knowledge gaps and future research activities. Technological and economic measures for achieving environmentally compatible development have been and continue to be studied. There are a few studies on the comparative assessment of mitigation and adaptation costs, and the potential benefits of these measures. Since these are long-term issues ranging into the next century, their assessment also requires a degree of understanding of possible development paths the world may take in the absence of global warming. The workshop covered the economics of climate change, its impacts, mitigation costs, policy instruments, and modeling issues. This volume summarizes these proceedings and presents the papers from the workshop.
Impact of Intermediate Goods Trade on Income Distribution between Skilled and Unskilled Labor: Empirical Analysis Based on 31 Segmented Industries

With the deepening of the global trade, the intermediate goods trade develops rapidly which has an impact on income distribution between the skilled and unskilled labor. Based on the data of the 31 segmented industries of industrial department, the dynamic panel model (first-difference GMM) is employed to analyze the impact of the intermediate goods trade on the income distribution between the skilled and unskilled labor. The result shows that,compared with the negative effect of final goods trade on the relative income of the skilled labor, the intermediate goods trade has a positive effect on the relative income of the skilled labor. In addition, the effect of the intermediate goods trade is greater than the final goods trade. With the development of the intermediate goods trade, the growth of the proportion of the intermediate goods trade will widening the wage gap between the skilled and unskilled labor. Finally, some valuable propositions are presented.
Mortgage Debt and Social Externalities

In an attempt to keep up with the social standards defined by their peer group, households can use long-term collateralized lending to finance purchases of goods that signal social value â€“ most notably, real estate. Because in the social status game somebody's advance is always somebody else's regress, this behavior can lead to inefficient allocations, making the economy as a whole more financially vulnerable. In this paper, we show that prudential policy taking the form of collateral constraints can mitigate the negative consequences of social arms races, and potentially improve household welfare. We introduce preferences for social status in a calibrated life cycle framework with heterogeneous agents, and find that positional concerns lead to a higher build-up of debt and a net loss of resources. In equilibrium, the optimal collateral policy results from the trade-off between a usual purely distortionary effect, and the negative social externalities of over-borrowing. (Copyright: Elsevier)
Use of Dried Serum Spots for Serological and Molecular Detection of Hepatitis A Virus

ABSTRACT We assessed the feasibility of using dried serum spots (DSS) for the serological and molecular diagnosis of hepatitis A virus (HAV) infection. Sixty-eight sera spotted onto filter papers (Whatman International Ltd., United Kingdom) were used for detection of total anti-HAV antibodies, and 64 sera were used for detection of immunoglobulin M antibody to HAV. DSS were stored at 4°C, room temperature, and 37°C for 1, 2, and 4 weeks. Sensitivity and specificity of the serological assays were 100% regardless of temperature and storage duration. To assess the stability of HAV RNA, we performed qualitative and quantitative reverse transcription-PCRs (RT-PCRs) with human plasma spiked with serial dilutions of cultured HAV spotted on Flinders Technology Associates filter paper cards (Whatman International Ltd.). Filter papers were stored at room temperature and processed for RT-PCR assays. No reduction of viral load was observed after 5, 15, and 30 days of storage. The ∼10-fold reduction of sensitivity from DSS was attributable to a smaller sample input in DSS samples. This method was further evaluated using 35 frozen sera. HAV RNA amplification showed 100% specificity and 92.3% sensitivity, and sequence analysis from DSS and sera provided identical results. HAV RNA can be accurately recovered from DSS for molecular epidemiology purposes, and we confirm the reliability of blotted samples in the serological diagnosis of HAV infection. The DSS method facilitates storage and shipment of samples from routine laboratories to reference centers for further investigations and large epidemiological studies.
Initial Cleavage of the Human Immunodeficiency Virus Type 1 GagPol Precursor by Its Activated Protease Occurs by an Intramolecular Mechanism

ABSTRACT Processing of the GagPol polyprotein precursor of human immunodeficiency virus type 1 (HIV-1) is a critical step in viral assembly and replication. The HIV-1 protease (PR) is translated as part of GagPol and is both necessary and sufficient for precursor processing. The PR is active only as a dimer; enzyme activation is initiated when the PR domains in two GagPol precursors dimerize. The precise mechanism by which the PR becomes activated and the subsequent initial steps in precursor processing are not well understood. However, it is clear that processing is initiated by the PR domain that is embedded within the precursor itself. We have examined the earliest events in precursor processing using an in vitro assay in which full-length GagPol is cleaved by its embedded PR. We demonstrate that the embedded, immature PR is as much as 10,000-fold less sensitive to inhibition by an active-site PR inhibitor than is the mature, free enzyme. Further, we find that different concentrations of the active-site inhibitor are required to inhibit the processing of different cleavage sites within GagPol. Finally, our results indicate that the first cleavages carried out by the activated PR within GagPol are intramolecular. Overall, our data support a model of virus assembly in which the first cleavages occur in GagPol upstream of the PR. These intramolecular cleavages produce an extended form of PR that completes the final processing steps accompanying the final stages of particle assembly by an intermolecular mechanism.
A chemiluminescent, magnetic particle‐based immunoassay for the detection of hepatitis C virus core antigen in human serum or plasma

Hepatitis C virus (HCV) exposure in blood donors is determined serologically by the detection of anti‐HCV antibodies in serum or plasma. However, a “window” period of 30–70 days after exposure exists where specific antibodies to HCV antigens are not detected. The use of nucleic acid testing for the detection of HCV RNA or antigen testing for the detection of HCV core protein have resulted in dramatic reductions in the pre‐seroconversion window period. In this study, an automated HCV core antigen detection test was developed. This magnetic microparticle‐based assay utilizes anti‐HCV core monoclonal antibody to capture antigen present in human serum or plasma. Captured antigen is then detected using an anti‐HCV core monoclonal antibody conjugated with a chemiluminescent compound. The specificity of this assay was established at 99% upon testing a population of normal volunteer blood donors. Sensitivity was determined by testing 16 commercially available HCV seroconversion panels representing genotypes 1a, 1b, 2b, and 3a. In each panel tested, HCV core antigen was detected prior to anti‐HCV antibody, resulting in a reduction of the window period by greater than 23 days on average, and greater than 34 days on panels initially NAT negative. In addition, HCV core antigen was detected in >97% of HCV RNA positive/antibody negative specimens, exhibiting sensitivity nearly equivalent to nucleic acid testing in the pre‐seroconversion window period for the panels examined. J. Med. Virol. 78:1436–1440, 2006. © 2006 Wiley‐Liss, Inc.