Abstract
Introduction/Objective
Lyme disease (LD) is a multisystem infection caused by tick-transmitted spirochete Borrelia burgdorferi. Serologic testing of LD is the primary diagnostic approach, ...and two-tiered testing is required to optimize specificity. The FDA cleared a variation of standard two-tiered testing (STTT) known as modified two-tier testing (MTTT) replacing the second tier immunoblot testing with a second enzyme immunoassay either ELISA or chemiluminescence format that can detect IgM and IgG simultaneously (MTTT-1) or separately (MTTT-2). The objective of this study is to evaluate the MTTT-2 assay performance against the predicate immunoblot method.
Methods/Case Report
Positive and negative quality controls (QC) were used to perform within and between day precision. 96 serum specimens were screened using ZEUS ELISA Borrelia VlsE1/pepC10 IgG/IgM Test System followed by method comparison using ZEUS B. burgdorferi IgG and IgM, separate test systems (ZEUS scientific, Branchburg, NJ) with the predicate MarDX Lyme Western Blot kit on Biotech Trinblot analyzer (Trinity Biotech USA, Jamestown, NY). Interference study was performed using 17 serum samples: 4 HIV positive, 5 ANA positive with high titer, 2 EBV IgG positive, 1 CMV IgG positive, 2 EBV & CMV IgG positive, and 3 reactive syphilis samples. Patient clinical chart was reviewed on results that disagreed.
Results (if a Case Study enter NA)
Within and between day precision studies were acceptable. Method comparison between MTTT-2 vs. immunoblot demonstrated 73% agreement (70/96). The remaining 26 samples showed disagreement either by IgM or IgG alone, or both. Upon clinical chart review, 8/26 samples that disagreed were likely true positive and 3/26 samples were likely false positive by MTTT-2 assay; the remaining 15/26 samples either cannot be confirmed due to lack of clinical history or inappropriately ordered as routine test. No cross-reactivity was observed on the MTTT-2 assay.
Conclusion
Our study demonstrated MTTT-2 assay is equivalent or slightly better than the predicate immunoblot method, if ordered appropriately when clinically indicated.
Multiple myeloma is the second most frequent hematological cancer after lymphoma and remains an incurable disease. The pervasive support provided by the bone marrow microenvironment to myeloma cells ...is crucial for their survival. Here, an unbiased assessment of receptor tyrosine kinases overexpressed in myeloma identified ROR2, a receptor for the WNT noncanonical pathway, as highly expressed in myeloma cells. Its ligand, WNT5A is the most abundant growth factor in the bone marrow of myeloma patients. ROR2 mediates myeloma cells interactions with the surrounding bone marrow and its depletion resulted in detachment of myeloma cells from their niche in an in vivo model, triggering apoptosis and thus markedly delaying disease progression. Using in vitro and ex vivo 3D-culture systems, ROR2 was shown to exert a pivotal role in the adhesion of cancer cells to the microenvironment. Genomic studies revealed that the pathways mostly deregulated by ROR2 overexpression were PI3K/AKT and mTOR. Treatment of cells with specific PI3K inhibitors already used in the clinic reduced myeloma cell adhesion to the bone marrow. Together, our findings support the view that ROR2 and its downstream targets represent a novel therapeutic strategy for the large subgroup of MM patients whose cancer cells show ROR2 overexpression.
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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
Introduction/Objective Lyme disease (LD) is a multisystem infection caused by tick-transmitted spirochete Borrelia burgdorferi. Serologic testing of LD is the primary diagnostic approach, and ...two-tiered testing is required to optimize specificity. The FDA cleared a variation of standard two-tiered testing (STTT) known as modified two-tier testing (MTTT) replacing the second tier immunoblot testing with a second enzyme immunoassay either ELISA or chemiluminescence format that can detect IgM and IgG simultaneously (MTTT-1) or separately (MTTT-2). The objective of this study is to evaluate the MTTT-2 assay performance against the predicate immunoblot method. Methods/Case Report Positive and negative quality controls (QC) were used to perform within and between day precision. 96 serum specimens were screened using ZEUS ELISA Borrelia VlsE1/pepC10 IgG/IgM Test System followed by method comparison using ZEUS B. burgdorferi IgG and IgM, separate test systems (ZEUS scientific, Branchburg, NJ) with the predicate MarDX Lyme Western Blot kit on Biotech Trinblot analyzer (Trinity Biotech USA, Jamestown, NY). Interference study was performed using 17 serum samples: 4 HIV positive, 5 ANA positive with high titer, 2 EBV IgG positive, 1 CMV IgG positive, 2 EBV & CMV IgG positive, and 3 reactive syphilis samples. Patient clinical chart was reviewed on results that disagreed. Results (if a Case Study enter NA) Within and between day precision studies were acceptable. Method comparison between MTTT-2 vs. immunoblot demonstrated 73% agreement (70/96). The remaining 26 samples showed disagreement either by IgM or IgG alone, or both. Upon clinical chart review, 8/26 samples that disagreed were likely true positive and 3/26 samples were likely false positive by MTTT-2 assay; the remaining 15/26 samples either cannot be confirmed due to lack of clinical history or inappropriately ordered as routine test. No cross-reactivity was observed on the MTTT-2 assay. Conclusion Our study demonstrated MTTT-2 assay is equivalent or slightly better than the predicate immunoblot method, if ordered appropriately when clinically indicated.
Murugesan K, Koroth J, Srinivasan PP, et al. Int J Nanomedicine. 2019;14:5257–5270. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns ...were raised regarding the alleged duplication of H&E images in Figure 8. Specifically, * Figure 8, ST06, Tumor image appears to be partly duplicated with the Figure 8, ST06-AgNPs, Tumor image. The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication, nor were they able to provide original data that could adequately verify the findings. The Editor requested to retract the article and the authors agreed with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper
Curcumin is known for its anticancer properties, but its clinical application is limited due to its poor bioavailability and chemical stability. In this study we report the curcumin derivative, ST03 ...(1,2-bis(3E,5E)-3,5-bis(2-chlorophenyl)methylene-4-oxo-1-piperidylethane-1,2-dione) exhibits ∼ 14 fold better bioavailability compared to curcumin and is detectable in plasma up to 12 h. ST03 induces ROS, activates the intrinsic apoptotic pathway as evident by disruption of mitochondrial membrane potential, and induction of proapoptotic proteins in ovarian cancer lines PA1 and A2780. ST03 also blocked the migration of ovarian cancer cells. ST03 exerted its antitumor effect in-vivo in the EAC mouse model by activating the intrinsic apoptotic pathway. Our findings demonstrate ST03, a curcumin derivative, with better bioavailability and stability with no discernable toxicity in vivo to be a promising drug candidate for anticancer therapies.
•Curcumin derivative ST03 induces apoptosis in ovarian cancer cell lines via intrinsic mitochondrial pathway along with induction of ROS.•ST03 inhibits the migration of ovarian cancer cells by altering MMP1.•ST03 treatment reduced tumor growth in EAC induced tumor bearing mouse without any adverse systemic toxicity.•Importantly, ST03 showed better bioavailability compared to its parent compound curcumin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Burkholderia glumae causes bacterial panicle blight of rice and produces major virulence factors, including toxoflavin, under the control of the quorum-sensing (QS) system mediated by the luxI ...homolog, tofI, and the luxR homolog, tofR. In this study, a series of markerless deletion mutants of B. glumae for tofI and tofR were generated using the suicide vector system, pKKSacB, for comprehensive characterization of the QS system of this pathogen. Consistent with the previous studies by other research groups, ΔtofI and ΔtofR strains of B. glumae did not produce toxoflavin in Luria-Bertani (LB) broth. However, these mutants produced high levels of toxoflavin when grown in a highly dense bacterial inoculum (∼ 10(11) CFU/ml) on solid media, including LB agar and King's B (KB) agar media. The ΔtofI/ΔtofR strain of B. glumae, LSUPB201, also produced toxoflavin on LB agar medium. These results indicate the presence of previously unknown regulatory pathways for the production of toxoflavin that are independent of tofI and/or tofR. Notably, the conserved open reading frame (locus tag: bglu_2g14480) located in the intergenic region between tofI and tofR was found to be essential for the production of toxoflavin by tofI and tofR mutants on solid media. This novel regulatory factor of B. glumae was named tofM after its homolog, rsaM, which was recently identified as a novel negative regulatory gene for the QS system of another rice pathogenic bacterium, Pseudomonas fuscovaginae. The ΔtofM strain of B. glumae, LSUPB286, produced a less amount of toxoflavin and showed attenuated virulence when compared with its wild type parental strain, 336gr-1, suggesting that tofM plays a positive role in toxoflavin production and virulence. In addition, the observed growth defect of the ΔtofI strain, LSUPB145, was restored by 1 µM N-octanoyl homoserine lactone (C8-HSL).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The histopathological diagnosis plays a major role in the treatment of diseases. Errors in these reports affect patient care. Hence, it is of utmost importance for all practitioners of this specialty ...to be aware of possible errors in histopathology laboratories and the means to minimize them. As with other disciplines of laboratory medicine, errors can occur in the pre-analytical, analytical and post analytical phase. The concept of quality and its control should be applied to all phases to curb errors. Audit can be used as a tool to generate information about the background level of errors in pathology which in turn can be used to reduce and avoid errors in histopathology laboratory. Furthermore, accreditation is a means to ensure patient safety and best quality assurance.
Potato late blight, caused by the oomycete pathogen Phytophthora infestans, significantly hampers potato production. Recently, a new Resistance to Phytophthora infestans (Rpi) gene, Rpi‐amr1, was ...cloned from a wild Solanum species, Solanum americanum. Identification of the corresponding recognized effector (Avirulence or Avr) genes from P. infestans is key to elucidating their naturally occurring sequence variation, which in turn informs the potential durability of the cognate late blight resistance. To identify the P. infestans effector recognized by Rpi‐amr1, we screened available RXLR effector libraries and used long read and cDNA pathogen‐enrichment sequencing (PenSeq) on four P. infestans isolates to explore the untested effectors. Using single‐molecule real‐time sequencing (SMRT) and cDNA PenSeq, we identified 47 highly expressed effectors from P. infestans, including PITG_07569, which triggers a highly specific cell death response when transiently coexpressed with Rpi‐amr1 in Nicotiana benthamiana, suggesting that PITG_07569 is Avramr1. Here we demonstrate that long read and cDNA PenSeq enables the identification of full‐length RXLR effector families and their expression profile. This study has revealed key insights into the evolution and polymorphism of a complex RXLR effector family that is associated with the recognition by Rpi‐amr1.
Long reads and cDNA pathogen enrichment sequencing (PenSeq) are developed to reveal the RXLR effector repertoires and expression pattern of four Phytophthora infestans isolates and enable to identify a new avirulence gene Avramr1.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Child maltreatment is a global public health problem. There is limited information about this problem in low-income countries. We aimed to document the prevalence and factors associated with physical ...punishment of children less than 14 years of age in Nepal.
Population-based cross-sectional study.
We conducted an in-depth analysis using data from the Nepal Multiple Indicator Cluster Survey, a nationally representative multi-stage-stratified cluster sampling survey. Data were collected from 13,000 households in 520 sample enumeration areas. We assessed prevalence of physical punishment and different child violence related acts on 5081 children aged 3–14 years for whom complete information on all acts and attitude towards violence was available. Logistic regression was used to investigate the association between physical punishment of child and factors such as household and maternal demographics.
Our results suggested violence is common across Nepal, with data showing one in every second child is physically punished. One in every third (33%) of children were spanked, hit or slapped on the bottom, 25% were hit or slapped on the face and approximately 3% were beaten up hard. Odds of facing physical punishment were higher among children aged 3–5 years (odds ratio OR 2.9, 95% confidence interval CI: 2.0–4.3), aged 6–8 years (OR 2.8, 95% CI: 2.2–3.7), engaged in child labour activities (OR 1.4, 95% CI: 1.1–1.7), with mother that accepted wife beating by husband is justified (OR 1.2, 95% CI: 1.1–1.4), whose father is currently abroad (OR 1.5, 95% CI: 1.2–1.9) and whose father is away from home but in the same country (OR 1.60, 95% CI: 1.1–2.3). The risk was also higher among children living in households that believe physical punishment of children is necessary (OR 3.5, 95% CI: 2.9–4.3) and from lower caste/indigenous (dalit/janajati) ethnicity (OR 1.3, 95% CI: 1.1–1.7). Those less likely to experience physical punishment included female children (OR 0.7, 95% CI: 0.6–0.9) and children with an older mother (34–49 years; OR 0.5, 95% CI: 0.3–0.9).
Our results suggest that physical punishment of children is common across Nepal with varying severity. Prevention efforts should focus on designing and promoting interventions that support parents to adapt alternative forms of parenting practices.
•Prevalence and factors associated with child maltreatment in Nepal was assessed.•One out of every second child was physically punished.•Prevalence and risk differed by (sub-national) region.•Young age, absence of father at home and attitude towards violence increased the risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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