We present a novel assay for rapid detection and identification of bacterial urinary tract infections using isotachophoresis (ITP) and molecular beacons. We applied on-chip ITP to extract and focus ...16S rRNA directly from bacterial lysate and used molecular beacons to achieve detection of bacteria specific sequences. We demonstrated detection of E. coli in bacteria cultures as well as in patient urine samples in the clinically relevant range 1E6–1E8 cfu/mL. For bacterial cultures we further demonstrate quantification in this range. The assay requires minimal sample preparation (a single centrifugation and dilution), and can be completed, from beginning of lysing to detection, in under 15 min. We believe that the principles presented here can be used for design of other rapid diagnostics or detection methods for pathogenic diseases.
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IJS, KILJ, NUK, PNG, UL, UM
Purpose The relative effectiveness of partial vs radical nephrectomy remains unclear in light of the recent phase 3 European Organization for the Research and Treatment of Cancer trial. We performed ...a systematic review and meta-analysis of partial vs radical nephrectomy for localized renal tumors, considering all cause and cancer specific mortality, and severe chronic kidney disease. Materials and Methods Cochrane Central Register of Controlled Trials, MEDLINE®, EMBASE®, Scopus and Web of Science® were searched for sporadic renal tumors that were surgically treated with partial or radical nephrectomy. Generic inverse variance with fixed effects models were used to determine the pooled HR for each outcome. Results Data from 21, 21 and 9 studies were pooled for all cause and cancer specific mortality, and severe chronic kidney disease, respectively. Overall 31,729 (77%) and 9,281 patients (23%) underwent radical and partial nephrectomy, respectively. According to pooled estimates partial nephrectomy correlated with a 19% risk reduction in all cause mortality (HR 0.81, p <0.0001), a 29% risk reduction in cancer specific mortality (HR 0.71, p = 0.0002) and a 61% risk reduction in severe chronic kidney disease (HR 0.39, p <0.0001). However, the pooled estimate of cancer specific mortality for partial nephrectomy was limited by the lack of robustness in consistent findings on sensitivity and subgroup analyses. Conclusions Our findings suggest that partial nephrectomy confers a survival advantage and a lower risk of severe chronic kidney disease after surgery for localized renal tumors. However, the results should be evaluated in the context of the low quality of the existing evidence and the significant heterogeneity across studies. Future research should use higher quality evidence to clearly demonstrate that partial nephrectomy confers superior survival and renal function.
Long-term exposure to particulate and gaseous air pollution (AP) may trigger the development of Parkinson disease (PD), but this association remains controversial. The relationship between ...second-hand smoke (SS) and PD risk is also inconclusive. We aimed to systematically review epidemiological studies investigating the association between these AP exposures and PD risk.
This was a systematic review and meta-analysis of studies investigating the relationship of ambient AP and SS with PD risk.
PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases were searched. We used a random-effects model to derive pooled estimates of relative risk (RR) and corresponding 95% confidence intervals (CIs) per increment in pollutant concentration. The studied AP included particulate matter with aerodynamic diameter <2.5 μm (PM2.5), <10 μm (PM10), nitrogen dioxides (NO2, NOx), ozone (O3), and carbon monoxide (CO).
In total, 21 studies with 222,051 patients with PD were eligible for inclusion. We found marginally significant increased risk of PD with per 10-μg/m3 increase in concentration of PM2.5 (RR = 1.08, 95% CI = 0.98–1.19), NO2 (RR = 1.03, 95% CI = 0.99–1.07), and O3 (RR = 1.01, 95% CI = 1.00–1.02). A positive but non-significant association was also detected for CO (RR = 1.32, 95% CI = 0.82–2.11). Furthermore, an inverse PD-SS relationship was noted irrespective of exposure occasions and timing (at home: RR = 0.73, 95% CI = 0.56–0.95; at work: RR = 0.82, 95% CI = 0.57–1.17; in children: RR = 0.91, 95% CI = 0.76–1.08). Both sensitivity and subgroup analyses generated results comparable with those of the overall analyses.
Our study suggested that exposure to PM2.5, NO2, and O3 might contribute to higher risk of PD, whereas SS conferring reduced PD risk. Public and environmental health strategies that aim at reducing outdoor AP levels might reduce the burden of PD. More prospective cohort studies with personal exposure measurements are warranted in the future.
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•PM2.5, NO2, and O3 may contribute to higher risk of Parkinson disease.•Second-hand smoke conferred reduced risk of Parkinson disease, regardless of exposure occasions and timing.•This is the first meta-analysis on the neuroprotective effect of second-hand smoke.•This is the most comprehensive review on the relationship between outdoor air pollution and Parkinson's disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tumor tropism of human bone marrow‐derived mesenchymal stem cells (MSC) has been exploited for the delivery of therapeutic genes for anticancer therapy. However, the exact contribution of these cells ...in the tumor microenvironment remains unknown. In this study, we examined the biological effect of MSC on tumor cells. The results showed that MSC inhibited the growth of human glioma cell lines and patient‐derived primary glioma cells in vitro. Coadministration of MSC and glioma cells resulted in significant reduction in tumor volume and vascular density, which was not observed when glioma was injected with immortalized normal human astrocytes. Using endothelial progenitor cells (EPC) from healthy donors and HUVEC endothelial cells, the extent of EPC recruitment and capacity to form endothelial tubes was significantly impaired in conditioned media derived from MSC/glioma coculture, suggesting that MSC suppressed tumor angiogenesis through the release of antiangiogenic factors. Further studies using antibody array showed reduced expression of platelet‐derived growth factor (PDGF)‐BB and interleukin (IL)‐1β in MSC/glioma coculture when compared with controls. In MSC/glioma coculture, PDGF‐BB mRNA and the corresponding proteins (soluble and membrane bound forms) as well as the receptors were found to be significantly downregulated when compared with that of glioma cocultured with normal human astrocytes or glioma monoculture. Furthermore, IL‐1β, phosphorylated Akt, and cathepsin B proteins were also reduced in MSC/glioma. Taken together, these data indicated that the antitumor effect of MSC may be mediated through downregulation of PDGF/PDGFR axis, which is known to play a key role in glioma angiogenesis. STEM Cells2013;31:146–155
Analysis of regional multi-channel seismic data from the northern Okinawa Trough and adjacent shelf provides some important constraints on the structural development of the area. The sedimentary ...strata in the northern East China Sea shelf basin, separated from the Okinawa Trough by the Taiwan–Sinzi belt, are affected by the Miocene compressional tectonism and truncated by the Late Miocene unconformity. In contrast, those in the western margin of the northern Okinawa Trough are cut by numerous normal faults and the Late Miocene horizon forms a conformable surface. This suggests that the Taiwan–Sinzi belt acted as a buttress for the northern Okinawa Trough against the compressional tectonism. Our data also reveal the Ho Basin in the western margin of the northern Okinawa Trough, previously known only from proprietary industry data. The Longwan Ridge, lying between the Ho Basin and the northern Okinawa Trough, may be the youngest of the relict arcs or buried ridges in the area. The abrupt along-strike change in the fault polarity near the northern margin of the depocenter of the Ho Basin suggests a NW-trending left-lateral transfer zone or fault. The western boundary of the northern Okinawa Trough is characterized by the gently deepening seafloor, whereas that of the southern Okinawa Trough is marked by steep border faults, suggesting more rapid subsidence in the south. This, together with the well-developed symmetric axial faults in the south and the greater width and the lack of well-developed axial zone in the north, may suggest focused rifting/extension in the southern Okinawa Trough and diffuse rifting/extension in the northern Okinawa Trough. We postulate that the diffuse rifting/extension in the northern Okinawa Trough is due to the tectonic perturbation, caused by the convergence or subduction of the topographically high and buoyant Amami Plateau at the northern Ryukyu arc.
► Taiwan–Sinzi belt acted as buttress for Okinawa Trough against Miocene compressional tectonism. ► Southern Okinawa Trough is characterized by focused rifting whereas northern Okinawa Trough by diffuse rifting. ► Diffuse rifting may be caused by convergence and/or subduction of buoyant Amami Plateau at Ryukyu arc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this study, mixed suspensions of large hard polystyrene microspheres and small soft poly(
N
-isopropylacrylamide) microgels are used as model systems to investigate the static and viscoelastic ...properties of suspensions which go through liquid to gel transitions. The microgels cause short-range attraction between microspheres through the bridging and depletion mechanism whose strength can be tuned by the microgel concentration. Rheological measurements are performed on suspensions with the volume fraction (
Φ
) of microspheres ranging from 0.02 to 0.15, and the transitions from liquid-like to solid-like behaviors triggered by the concentration of microgels are carefully identified. Two gel lines due to bridging attraction under unsaturated conditions are obtained. Ultra-small angle neutron scattering is used to probe the thermodynamic properties of suspensions approaching the liquid-solid transition boundaries. Baxter's sticky hard-sphere model is used to extract the effective inter-microsphere interaction introduced by the small soft microgels. It is found that the strength of attraction (characterized by a single stickiness parameter
τ
) on two gel lines formed by bridging is very close to the theoretical value for the spinodal line in the
τ
-
Φ
phase diagram predicted by Baxter's model. This indicates that the nature of the gel state may have the same thermodynamic origins, independent of the detailed mechanism of the short-range attraction. The relationship between the rheological criterion for the liquid-solid transition and the thermodynamic criterion for the equilibrium-nonequilibrium transition is also discussed.
In this study, mixed suspensions of large hard polystyrene microspheres and small soft poly(
N
-isopropylacrylamide) microgels are used as model systems to investigate the static and viscoelastic properties of suspensions which go through liquid to gel transitions.
To perform a quantitative review of the evidence on the diagnostic value of inflammatory markers in maternal serum or umbilical cord blood for the diagnosis of early-onset neonatal sepsis (EONS).
We ...searched multiple databases for studies published through March 2013 that evaluated the diagnostic performance of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and leukocyte count (white blood cell, WBC) in either umbilical cord blood or maternal serum for diagnosis of EONS. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models.
Our search identified 3874 citations, of which 15 studies evaluating 2178 episodes of suspected neonatal infection were included for analysis. IL-6 in cord blood with a pooled-positive likelihood ratio (LR+) of 9.47 (95% confidence interval: 3.86 to 23.3), PCT in cord blood with a LR+ of 5.72 (1.56 to 21.0) and IL-6 in maternal serum with a LR+ of 5.47 (2.10 to 14.2) can be qualified as a valid rule-in test. IL-6 in cord blood with a LR- of 0.10 (0.05 to 0.21) and PCT in cord blood with a LR- of 0.20 (0.12-0.37) can be qualified as a useful rule-out test. Either CRP or WBC was inadequate for diagnosis of EONS.
For cord blood sample, IL-6 or PCT can be used as reliable rule-in and rule-out tool. For maternal serum, only IL-6 appeared to be sufficient for rule-in diagnosis. An interventional study may be needed to answer whether the addition of these tests will improve the outcome of patients with EONS.
Despite preventive human papilloma virus (HPV) vaccination efforts, cervical cancer remains a leading cause of death in women worldwide. Development of therapeutic approaches for cervical cancer are ...hampered by a lack of mechanistic insight during tumorigenesis. The cytoskeletal protein Keratin 17 (KRT17;K17) is robustly expressed in a broad array of carcinomas, including in cervical tumors, where it has both diagnostic and prognostic value. In this study, we have established multiple functional roles for K17 in the promotion of cervical tumorigenesis in vivo using the established HPV16
mouse model for cervical squamous cell carcinoma. In HPV16
;Krt17
relative to HPV16
reference female mice, onset of cervical lesions is delayed and closely paralleled by marked reductions in hyperplasia, dysplasia and vascularization. In addition, loss of Krt17 is associated with a cytokine polarization and recruitment of effector immune cells to lesion-prone cervical epithelia. Further, we observed marked enhancement of terminal differentiation in HPV16
;Krt17
cervical epithelium accompanied by a stimulation and expansion in the expression of p63, a known basal/reserve cell marker in this tissue. Altogether, the data suggest that the loss of Krt17 may foster an overall protective environment for lesion-prone cervical tissue. In addition to providing new insights into the immunomodulatory and cellular mechanisms of cervical tumorigenesis, these findings may help guide the development of future therapies including vaccines.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Gastric cancer is the third most common cause of death from cancer in the world and it remains difficult to cure in Western countries, primarily because most patients present with advanced disease. ...Currently, CEA, CA50 and CA72-4 are commonly used as tumor markers for gastric cancer by immunoassays. However, the drawback and conundrum of immunoassay are the unceasing problem in standardization of quality of antibodies and time/effort for the intensive production. Therefore, there is an urgent need for the development of a standardized assay to detect gastric cancer at the early stage. Aptamers are DNA or RNA oligonucleotides with structural domain which recognize ligands such as proteins with superior affinity and specificity when compared to antibodies. In this study, SELEX (Systematic Evolution of Ligands by Exponential enrichment) technique was adopted to screen a random 30mer RNA library for aptamers targeting CEA, CA50 and CA72-4 respectively. Combined with high-throughput sequencing, we identified 6 aptamers which specifically target for these three biomarkers of gastrointestinal cancer. Intriguingly, the predicted secondary structures of RNA aptamers from each antigen showed significant structural similarity, suggesting the structural recognition between the aptamers and the antigens. Moreover, we determined the dissociation constants of all the aptamers to their corresponding antigens by fluorescence spectroscopy, which further demonstrated high affinities between the aptamers and the antigens. In addition, immunostaining of gastric adenocarcinoma cell line AGS using CEA Aptamer probe showed positive fluorescent signal which proves the potential of the aptamer as a detection tool for gastric cancer. Furthermore, substantially decreased cell viability and growth were observed when human colorectal cell line LS-174T was transfected with each individual aptamers. Taking together, these novel RNA aptamers targeting gastrointestinal cancer biomarker CEA, CA50 and CA72-4 will aid further development and standardization of clinical diagnostic method with better sensitivity and specificity, and potentially future therapeutics development of gastric cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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