Изготовление изделий сложной формы из металлических порошков методом квазиизостатического прессования

Работа посвящена изучению влияния параметров эластичной оболочки (жесткость,объем внутренней полости) на деформацию металлических порошковых материалов в процессе квазиизостатического прессования.The work is devoted to the study of the influence of the parameters of the elastic shell (stiffness, volume of the internal cavity) on the deformation of metal powder materials in the process of quasi-isostatic pressing

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment

In this Policy Forum piece, Aditya Narayan and colleagues discuss the challenges and opportunities for tuberculosis preventive treatment in carceral settings

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment

Persons deprived of liberty (PDLs) are disproportionately impacted by tuberculosis, with high incidence rates and often limited access to diagnostics, treatment, and preventive measures. The World Health Organization (WHO) expanded its recommendations for tuberculosis preventive treatment (TPT) to many high-risk populations, but their guidance does not include PDL, and most low- and middle-income countries do not routinely provide edforthoseusedthroughoutthetext TPT in prisons. :Pleaseverifythatallentriesarecorrectlyabbreviated: Recent studies demonstrate high acceptability and completion rates of short-course TPT regimens in jails and prisons; costs of these regimens have been markedly reduced through international agreements, making this an opportune for further expanding their use. We argue that PDL should be a priority group for TPT in national guidelines and discuss implementation considerations and resource needs for TPT programs in carceral facilities. Scaling access to TPT for PDL is important for reducing disease and transmission in this population; it is also critical to advancing an equitable response to tuberculosis

Monocyte metabolic transcriptional programs associate with resistance to tuberculin skin test/interferon-γ release assay conversion.

After extensive exposure to Mycobacterium tuberculosis (Mtb), most individuals acquire latent Mtb infection (LTBI) defined by a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA). To identify mechanisms of resistance to Mtb infection, we compared transcriptional profiles from highly exposed contacts who resist TST/IGRA conversion (resisters, RSTRs) and controls with LTBI using RNAseq. Gene sets related to carbon metabolism and free fatty acid (FFA) transcriptional responses enriched across 2 independent cohorts suggesting RSTR and LTBI monocytes have distinct activation states. We compared intracellular Mtb replication in macrophages treated with FFAs and found that palmitic acid (PA), but not oleic acid (OA), enhanced Mtb intracellular growth. This PA activity correlated with its inhibition of proinflammatory cytokines in Mtb-infected cells. Mtb growth restriction in PA-treated macrophages was restored by activation of AMP kinase (AMPK), a central host metabolic regulator known to be inhibited by PA. Finally, we genotyped AMPK variants and found 7 SNPs in PRKAG2, which encodes the AMPK-γ subunit, that strongly associated with RSTR status. Taken together, RSTR and LTBI phenotypes are distinguished by FFA transcriptional programs and by genetic variation in a central metabolic regulator, which suggests immunometabolic pathways regulate TST/IGRA conversion

Cholesterol side-chain cleavage gene expression in theca cells: augmented transcriptional regulation and mRNA stability in polycystic ovary syndrome.

Hyperandrogenism is characteristic of women with polycystic ovary syndrome (PCOS). Ovarian theca cells isolated from PCOS follicles and maintained in long-term culture produce elevated levels of progestins and androgens compared to normal theca cells. Augmented steroid production in PCOS theca cells is associated with changes in the expression of genes for several steroidogenic enzymes, including CYP11A1, which encodes cytochrome P450 cholesterol side-chain cleavage. Here, we further examined CYP11A1 gene expression, at both the transcriptional and post-transcriptional level in normal and PCOS theca cells propagated in long-term culture utilizing quantitative RT-PCR, functional promoter analyses, and mRNA degradation studies. The minimal element(s) that conferred increased basal and cAMP-dependent CYP11A1 promoter function were determined. CYP11A1 mRNA half-life in normal and PCOS theca cells was compared. Results of these cumulative studies showed that basal and forskolin stimulated steady state CYP11A1 mRNA abundance and CYP11A1 promoter activity were increased in PCOS theca cells. Deletion analysis of the CYP11A1 promoter demonstrated that augmented promoter function in PCOS theca cells results from increased basal regulation conferred by a minimal sequence between -160 and -90 bp of the transcriptional start site. The transcription factor, nuclear factor 1C2, was observed to regulate basal activity of this minimal CYP11A1 element. Examination of mRNA stability in normal and PCOS theca cells demonstrated that CYP11A1 mRNA half-life increased >2-fold, from approximately 9.22+/-1.62 h in normal cells, to 22.38+/-0.92 h in PCOS cells. Forskolin treatment did not prolong CYP11A1 mRNA stability in either normal or PCOS theca cells. The 5'-UTR of CYP11A1 mRNA confers increased basal mRNA stability in PCOS cells. In conclusion, these studies show that elevated steady state CYP11A1 mRNA abundance in PCOS cells results from increased transactivation of the CYP11A1 promoter and increased CYP11A1 mRNA stability

Quantification of <i>CYP11A1</i> mRNA abundance in normal and PCOS theca cells.

<p>The time course of CYP11A1 mRNA accumulation was examined in <b>A)</b> normal or <b>B)</b> PCOS theca cells treated in serum free medium for 0, 4, 8, 16, 24, or 48 h in the presence and absence of 20 µM forskolin. <b>C)</b> CYP11A1 mRNA accumulation in normal and PCOS theca cells following 24 h treatment with and without 20 µM forskolin serum free medium. CYP11A1 mRNA was measured using quantitative real-time PCR as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048963#s2" target="_blank">Materials and Methods</a>. The data presented in <b>Panel A</b> and <b>Panel B</b> are data obtained from two normal and two PCOS patients, that are representative of data collected from theca cells from 5 normal and 5 PCOS patients. The data presented in <b>Panel C</b> are the results from independent analyses of theca cells isolated from 5 normal and 5 PCOS women. CYP11A1 mRNA accumulation was increased in PCOS theca cells as compared to normal theca cells under both control (<i>a</i>, <i>P</i><0.01) and forskolin-stimulated conditions (<i>b</i>, <i>P</i><0.01). Forskolin- treatment significantly increased CYP11A1 mRNA accumulation in both normal and PCOS theca cells (*, <i>P<0.01</i>).</p

Deletion analysis of the <i>CYP11A1</i> promoter in normal and PCOS theca cells.

<p><b>A)</b> Theca cells were transiently transfected with pGL3 luciferase constructs containing −2327, −1676, −660, −160, or −90 to +49 bp of the 5′-flanking sequence of the <i>CYP11A1</i> gene. All constructs contain the endogenous TATA box and transcriptional start site. <b>B)</b> Normal and PCOS theca cells were transiently transfected with the above constructs described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048963#s2" target="_blank">Materials and Methods</a>. Following transfection, cells were cultured in transfection medium alone or with forskolin (20 µM) for 48 h. Data are presented as relative luciferase (LUC) activity that was normalized with β-galactosidase activity, and represent the mean ± SEM of independent experiments in five normal and five PCOS theca cell cultures. <i>CYP11A1</i> promoter activity was increased in PCOS theca cells, under basal (<i>a</i>, <i>P</i><0.01) and forskolin-stimulated conditions (<i>b</i>, <i>P</i><0.01), as compared to normal theca cells for individual promoter constructs.</p

Levofloxacin versus placebo for the treatment of latent tuberculosis among contacts of patients with multidrug-resistant tuberculosis (the VQUIN MDR trial): A protocol for a randomised controlled trial

Introduction Treatment of latent tuberculosis infection (LTBI) plays a substantial role in the prevention of drug-susceptible tuberculosis (TB). However, clinical trials to evaluate the efficacy of preventive therapy for presumed multidrug-resistant (MDR) LTBI are lacking. This trial aims to evaluate the efficacy of the antibiotic levofloxacin in preventing the development of active TB among latently infected contacts of index patients with MDR-TB. Methods and analysis A double-blind placebo-controlled parallel group randomised controlled trial will be conducted in 10 provinces of Vietnam. Household contacts living with patients with bacteriologically confirmed rifampicin-resistant or MDR-TB will be eligible for recruitment if they have a positive tuberculin skin test or are known to be immunosuppressed, and do not have active TB. Participants will be randomised to receive either levofloxacin or placebo tablets once per day for 6 months. Screening for incident TB will be performed at 6 months intervals. The primary study outcome is the incidence of bacteriologically confirmed TB within 30 months after randomisation. Analysis will be by intention to treat, using Poisson regression. Ethics Ethical approval from the University of Sydney Human Research Ethics Committee was obtained on 29 April 2015 (2014/929), and from the Vietnam Ministry of Health Institutional Review Board on 30 September 2015 (4040/QD-BYT). Dissemination Findings of the study will be published in peer-reviewed publications and conference presentations. Trial registration number ACTRN12616000215426