Rapid diagnostic test for antenatal syphilis screening in low-income and middle-income countries: a systematic review and meta-analysis

OBJECTIVES: To undertake a systematic review and meta-analysis to evaluate the test performance including sensitivity and specificity of rapid immunochromatographic syphilis (ICS) point-of-care (POC) tests at antenatal clinics compared with reference standard tests (non-treponemal (TP) and TP tests) for active syphilis in pregnant women. METHODS: Five electronic databases were searched (PubMed, EMBASE, CRD, Cochrane Library and LILACS) to March 2016 for diagnostic accuracy studies of ICS test and standard reference tests for syphilis in pregnant women. Methodological quality was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). A bivariate meta-analysis was undertaken to generate pooled estimates of diagnostic parameters. Results were presented using a coupled forest plot of sensitivity and specificity and a scatter plot. RESULTS: The methodological quality of the five included studies with regards to risk of bias and applicability concern judgements was either low or unclear. One study was judged as high risk of bias for patient selection due to exclusion of pregnant women with a previous history of syphilis, and one study was judged at high risk of bias for study flow and timing as not all patients were included in the analysis. Five studies contributed to the meta-analysis, providing a pooled sensitivity and specificity for ICS of 0.85 (95% CrI: 0.73 to 0.92) and 0.98 (95% CrI: 0.95 to 0.99), respectively. CONCLUSIONS: This review and meta-analysis observed that rapid ICS POC tests have a high sensitivity and specificity when performed in pregnant women at antenatal clinics. However, the methodological quality of the existing evidence base should be taken into consideration when interpreting these results. PROSPERO REGISTRATION NUMBER: CRD42016036335

In vivo Tâ cell activation by a monoclonal αCD3ε antibody induces preterm labor and birth

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134074/1/aji12562.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134074/2/aji12562_am.pd

Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

In vivo activation of invariant natural killer T cells induces systemic and local alterations in Tâ cell subsets prior to preterm birth

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137689/1/cei12968.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137689/2/cei12968_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137689/3/cei12968-sup-0001-suppinfo1.pd

Economic Evaluation of Lupus Nephritis in the Systemic Lupus International Collaborating Clinics Inception Cohort Using a Multistate Model Approach.

OBJECTIVE: Little is known about the long-term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling. METHODS: Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. RESULTS: A total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten-year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR)/minute ($310,579 2015 Canadian dollars versus$19,987 if no LN and estimated GFR \u3e60 ml/minute) or with LN and estimated proteinuria \u3e3 gm/day ($84,040 versus$20,499 if no LN and estimated proteinuria CONCLUSION: Patients with estimated GFR/minute incurred 10-year costs 15-fold higher than those with normal estimated GFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future health care costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies

Glaciological Monitoring Using the Sun as a Radio Source for Echo Detection

Funder: NASA Cryospheric SciencesAbstract: Ice‐penetrating radar observations are critical for projecting ice‐sheet contribution to sea‐level rise; however, these prognostic models have significant uncertainties due to an incomplete understanding of glacial subsurface processes. Existing radars that can characterize subsurface conditions are too resource‐intensive to simultaneously monitor ice sheets at both the necessary temporal—daily to multiannual—and spatial—tributary to continental—scales. Here, we investigate using an ambient radio source, instead of transmitting a signal, for glaciological monitoring. We demonstrate, for the first time, passive radio sounding using the Sun to accurately measure ice thickness on Store Glacier, Greenland. Passive radar sounding could provide low‐resource time‐series measurements of the cryosphere, enabling us to observe and understand evolving englacial and subglacial conditions across Greenland and Antarctica with unprecedented coverage and resolution

IQGAP1 and NWASP promote human cancer cell dissemination and metastasis by regulating β1-integrin via FAK and MRTF/SRF

Data and code availability: * All data are available in the main text or the supplementary materials. Original western blot images are in the supplemental material. Blot and imaging data reported in this paper will be shared by the lead contact upon request. * This paper does not report original code. * Any additional information required to reanalyze the data reported in this paper is available from the lead contact, Anne Ridley ([email protected]). upon request.Supplemental information is available online at: https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00317-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124724003176%3Fshowall%3Dtrue#supplementaryMaterial .Summary: Attachment of circulating tumor cells to the endothelial cells (ECs) lining blood vessels is a critical step in cancer metastatic colonization, which leads to metastatic outgrowth. Breast and prostate cancers are common malignancies in women and men, respectively. Here, we observe that β1-integrin is required for human prostate and breast cancer cell adhesion to ECs under shear-stress conditions in vitro and to lung blood vessel ECs in vivo. We identify IQGAP1 and neural Wiskott-Aldrich syndrome protein (NWASP) as regulators of β1-integrin transcription and protein expression in prostate and breast cancer cells. IQGAP1 and NWASP depletion in cancer cells decreases adhesion to ECs in vitro and retention in the lung vasculature and metastatic lung nodule formation in vivo. Mechanistically, NWASP and IQGAP1 act downstream of Cdc42 to increase β1-integrin expression both via extracellular signal-regulated kinase (ERK)/focal adhesion kinase signaling at the protein level and by myocardin-related transcription factor/serum response factor (SRF) transcriptionally. Our results identify IQGAP1 and NWASP as potential therapeutic targets to reduce early metastatic dissemination.This work was funded by a Cancer Research UK grant (C6620/A15961) (A.J.R., C.C., R.G., and N.R.), the University of Bristol School of Cellular and Molecular Medicine (A.J.R. and C.C.), a Cancer Research UK Oxford Center DPhil Prize Studentship (BBRTJW00) (S.L.), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement (no. 655817) MSCA-IF-2014 (S.T.M. and A.R.), a Cancer Research UK grant A1731 (R.M.), and the Biotechnology and Biological Sciences Research Council (grant no. BB/K009184/1) (I.A.R.)

Sexually transmitted infections and factors associated with risky sexual practices among female sex workers: A cross sectional study in a large Andean city.

BACKGROUND: There are limited published data on factors related to risky sexual practices (RSP) affecting sexually transmitted infections (STIs) among female sex workers (FSWs) in Ecuador. METHODS: Cross-sectional study of FSWs presenting for a consultation in a primary health care centre during 2017. A questionnaire was administered to collect information on RSP and potential risk factors including age, membership of an FSW association, self-report of previous STI diagnosis, previous treatment for suspected STI and temporary migration for sex work. Associations between RSP and potential risk factors were estimated by logistic regression. The proportion of STI was estimated from vaginal swabs by real-time PCR for four sexually transmitted pathogens (Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, and Mycoplasma genitalium). RESULTS: Of 249 FSWs recruited, 22.5% had reported RSPs at least once during sex work. Among FSWs reporting unprotected vaginal sex in the previous three months, 25.5% had at least one other RSP type. 17.6% (95%CI 13.3-22.8) had at least one active STI. Prevalence of co-infections was 2.4% (95%CI 1.1-5.2). In multivariable analysis, RSP was associated with age (adjusted OR 1.06; 95%CI 1.02-1.10), membership of an FSWs association (aOR 3.51; 95%CI 1.60-7.72) and self-reported previous STI (aOR 3.43; 95%CI 1.28-9.17). CONCLUSIONS: Among a population of female sex workers with high proportion of STIs, increasing age and belonging to an FSWs association was associated with a higher likelihood of engaging in RSP with clients. Engaging with FSWs organisations may reduce the burden of STI among sex workers

Innate lymphoid cells at the human maternalâ fetal interface in spontaneous preterm labor

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143766/1/aji12820.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143766/2/aji12820_am.pd