Aims
To evaluate and compare the reductions of human viruses and F‐specific coliphages in a full‐scale wastewater treatment plant based on the quantitative PCR (qPCR) and plate count assays.
Methods ...and Results
A total of 24 water samples were collected from four locations at the plant, and the relative abundance of human viruses and F‐RNA phage genogroups were determined by qPCR. Of the 10 types of viruses tested, enteric adenoviruses were the most prevalent in both influent and effluent wastewater samples. Of the different treatment steps, the activated sludge process was most effective in reducing the microbial loads. Viruses and F‐RNA phages showed variable reduction; among them, GI and GIII F‐RNA phages showed the lowest and the highest reduction, respectively.
Conclusions
Ten types of viruses were present in wastewater that is discharged into public water bodies after treatment. The variability in reduction for the different virus types demonstrates that selection of adequate viral indicators is important for evaluating the efficacy of wastewater treatment and ensuring the water safety.
Significance and Impact of the Study
Our comprehensive analyses of the occurrence and reduction of viruses and indicators can contribute to the future establishment of appropriate viral indicators to evaluate the efficacy of wastewater treatment.
Mechanisms of control of microRNA biogenesis Davis-Dusenbery, Brandi N; Hata, Akiko
Journal of Biochemistry/The journal of biochemistry,
10/2010, Letnik:
148, Številka:
4
Journal Article
Recenzirano
Odprti dostop
MicroRNAs (miRNAs) are a class of ~22 nt non-coding RNAs that control diverse biological functions in animals, plants and unicellular eukaryotes by promoting degradation or inhibition of translation ...of target mRNAs. miRNA expression is often tissue specific and developmentally regulated. Aberrant expression of miRNAs has been linked to developmental abnormalities and human diseases, including cancer and cardiovascular disorders. The recent identification of mechanisms of miRNA biogenesis regulation uncovers that various factors or growth factor signalling pathways control every step of the miRNA biogenesis pathway. Here, we review the mechanisms that control the regulation of miRNA biogenesis discovered in human cells. Further understanding of the mechanisms that control of miRNA biogenesis may allow the development of tools to modulate the expression of specific miRNAs, which is crucial for the development of novel therapies for human disorders derived from aberrant expression of miRNAs.
Rearranged during transfection (RET) gene fusions are a validated target in non-small-cell lung cancer (NSCLC). RET-selective inhibitors selpercatinib (LOXO-292) and pralsetinib (BLU-667) recently ...demonstrated favorable antitumor activity and safety profiles in advanced RET fusion-positive NSCLC, and both have received approval by the US Food and Drug Administration for this indication. Insights into mechanisms of resistance to selective RET inhibitors remain limited.
This study was performed at five institutions. Tissue and/or cell-free DNA was obtained from patients with RET fusion-positive NSCLC after treatment with selpercatinib or pralsetinib and assessed by next-generation sequencing (NGS) or MET FISH.
We analyzed a total of 23 post-treatment tissue and/or plasma biopsies from 18 RET fusion-positive patients who received an RET-selective inhibitor (selpercatinib, n = 10; pralsetinib, n = 7; pralsetinib followed by selpercatinib, n = 1, with biopsy after each inhibitor). Three cases had paired tissue and plasma samples, of which one also had two serial resistant tissue specimens. The median progression-free survival on RET inhibitors was 6.3 months 95% confidence interval 3.6–10.8 months. Acquired RET mutations were identified in two cases (10%), both affecting the RET G810 residue in the kinase solvent front. Three resistant cases (15%) harbored acquired MET amplification without concurrent RET resistance mutations, and one specimen had acquired KRAS amplification. No other canonical driver alterations were identified by NGS. Among 16 resistant tumor specimens, none had evidence of squamous or small-cell histologic transformation.
RET solvent front mutations are a recurrent mechanism of RET inhibitor resistance, although they occurred at a relatively low frequency. The majority of resistance to selective RET inhibition may be driven by RET-independent resistance such as acquired MET or KRAS amplification. Next-generation RET inhibitors with potency against RET resistance mutations and combination strategies are needed to effectively overcome resistance in these patients.
•Resistance is a major challenge in RET fusion-positive lung cancer treated with RET tyrosine kinase inhibitors (TKIs).•RET mutations involving the solvent front residue G810 are a recurrent yet infrequent mechanism of resistance to RET TKIs.•The majority of resistance to selective RET inhibition is driven by RET-independent resistance, such as MET amplification.•RET TKIs with potency against RET solvent front mutations and combination strategies are needed to overcome resistance.
Aims
Early studies have shown that magnesium intake decreases the risk of Type 2 diabetes, but the results are still inconsistent. We prospectively examined the association between magnesium intake ...and incidence of Type 2 diabetes in a general Japanese population.
Methods
A total of 1999 subjects without diabetes aged 40–79 years who underwent a 75‐g oral glucose tolerance test were followed up prospectively for a mean of 15.6 years.
Results
During the follow‐up, 417 subjects developed Type 2 diabetes. The age‐ and sex‐adjusted incidence of Type 2 diabetes significantly decreased with increasing magnesium intake quartile levels (≤ 148.5, 148.6–171.5, 171.6–195.5 and ≥ 195.6 mg/day, P for trend = 0.01). In multivariate analyses, after adjusting for comprehensive risk factors and other dietary factors, the hazard ratio of Type 2 diabetes was 0.67 (95% CI 0.49–0.92; P = 0.01) in the third quartile and 0.63 (95% CI 0.44–0.90; P = 0.01) in the highest quartile compared with the first quartile. In addition, the risk of Type 2 diabetes was 14% lower (P = 0.04) for a 1‐sd increment of log‐transformed magnesium intake in the multivariate‐adjusted model. In stratified analysis, there were statistically significant interactions between magnesium intake and levels of homeostasis model assessment of insulin resistance, high‐sensitivity C‐reactive protein or alcohol intake on the risk of Type 2 diabetes (all P < 0.05).
Conclusions
Our findings suggest that increased magnesium intake was a significant protective factor for the incidence of Type 2 diabetes in the general Japanese population, especially among subjects with insulin resistance, low‐grade inflammation and a drinking habit.
What's new?
A number of prospective cohort studies and meta‐analyses have suggested that magnesium intake reduces the risk of diabetes, but the results are still inconsistent. In addition, most cohort studies have been derived from Caucasian populations, and thus the effect of magnesium intake on diabetes risk in Asians remains to be fully elucidated. In this paper, we demonstrate that higher intake of magnesium reduces the risk of Type 2 diabetes in Japanese.
To the best of our knowledge, this is the first prospective study showing the effect modification by insulin resistance and low‐grade inflammation on the association between magnesium intake and the development of Type 2 diabetes.
To assess the image quality of deep-learning image reconstruction (DLIR) of chest computed tomography (CT) images on a mediastinal window setting in comparison to an adaptive statistical iterative ...reconstruction (ASiR-V).
Thirty-six patients were evaluated retrospectively. All patients underwent contrast-enhanced chest CT and thin-section images were reconstructed using filtered back projection (FBP); ASiR-V (60% and 100% blending setting); and DLIR (low, medium, and high settings). Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were evaluated objectively. Two independent radiologists evaluated ASiR-V 60% and DLIR subjectively, in comparison with FBP, on a five-point scale in terms of noise, streak artefact, lymph nodes, small vessels, and overall image quality on a mediastinal window setting (width 400 HU, level 60 HU). In addition, image texture of ASiR-Vs (60% and 100%) and DLIR-high was analysed subjectively.
Compared with ASiR-V 60%, DLIR-med and DLIR-high showed significantly less noise, higher SNR, and higher CNR (p<0.0001). DLIR-high and ASiR-V 100% were not significantly different regarding noise (p=0.2918) and CNR (p=0.0642). At a higher DLIR setting, noise was lower and SNR and CNR were higher (p<0.0001). DLIR-high showed the best subjective scores for noise, streak artefact, and overall image quality (p<0.0001). Compared with ASiR-V 60%, DLIR-med and DLIR-high scored worse in the assessment of small vessels (p<0.0001). The image texture of DLIR-high was significantly finer than that of ASIR-Vs (p<0.0001).
DLIR-high improved the objective parameters and subjective image quality by reducing noise and streak artefacts and providing finer image texture.
•DLIR-med and DLIR-high showed less noise and higher SNR and CNR than ASiR-V 60%.•DLIR-high showed the best subjective score for overall image quality.•The visualization of small vessels was deteriorated in DLIR-med and DLIR-high.•DLIR-high showed finer image texture compared with ASiR-V 60% and 100%.
Purpose
To determine the incidence of Herpes zoster in patients with one of 17 specific underlying diseases compared with that in patients with other underlying diseases.
Methods
We conducted a ...retrospective hospital-based cohort study using data from patients’ electronic medical records for the period 2001–2007 of the Kitano Hospital Research Database. These analyses included 55,492 patients with one of 17 underlying diseases, which were those reported as related to the contraction of Herpes zoster. Of these, 769 patients contracted Herpes zoster. The main outcome measure was the clinical diagnosis of Herpes zoster.
Results
The adjusted hazard ratios (95% confidence interval) for Herpes zoster in patients with the 17 diseases were compared with other patients, with the following results: brain tumor 3.84 (2.51–5.88), lung cancer 2.28 (1.61–3.22), breast cancer 2.41 (1.52–3.82), esophageal cancer 4.19 (2.16–8.11), gastric cancer 1.95 (1.39–2.72), colorectal cancer 1.85 (1.33–2.56), gynecologic cancer 3.45 (2.08–5.70), malignant lymphoma 8.23 (6.53–10.38), systemic lupus erythematosus 3.90 (2.66–5.70), rheumatoid arthritis 2.00 (1.60–2.50), diabetes mellitus 2.44 (2.10–2.85), hypertension 2.04 (1.75–2.38), renal failure 2.14 (1.65–2.79), and disk hernia 2.18 (1.52–3.13).
Conclusions
Patients with diabetes mellitus, renal failure, and malignancies have a 1.8–8.4-fold higher risk of a Herpes zoster event than patients with other diseases. Future studies should investigate alteration of the immune system in the underlying diseases and approaches for Herpes zoster prevention.
MicroRNAs (miRNAs) are small, noncoding RNAs that influence diverse biological outcomes through the repression of target genes during normal development and pathological responses. In particular, the ...alteration of miRNA expression has dramatic consequences for the progression of tumorigenesis. miRNAs undergo two processing steps that transform a long primary transcript into the mature miRNA. Although the general miRNA biogenesis pathway is well established, it is clear that not all miRNAs are created equally. Recent studies show that miRNA expression is controlled by diverse mechanisms in response to cellular stimuli. In this review, we discuss the mechanisms that govern the regulation of miRNA biogenesis with particular focus on how these mechanisms are perturbed in cancer.
Summary
This study aimed to determine the incidence and risk factors for hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) undergoing immunosuppressive therapy. The ...National Database of Japan, in which insurance claim data have been comprehensively accumulated, was utilized. The subjects were 76 641 RA patients who were plausibly initiated on immunosuppressive therapy from April 2013 to March 2014. Laboratory tests of the hepatitis B surface antigen, anti‐hepatitis B virus surface antibody, and anti‐hepatitis B virus core antibody were performed in 28.23%, 12.52% and 14.63% of patients, respectively, when the therapy was initiated. We found that HBV reactivation and fulminant hepatitis occurred in both the patients with and without HBV DNA monitoring, indicating insufficient monitoring in Japan during the study. The cumulative incidence of HBV reactivation over 24 months was 1.57% (95% confidence interval CI = 1.28%‐1.92%) in the monitoring group, which consisted of those with resolved HBV infection. Glucocorticoid administration was a potent risk factor for HBV reactivation (hazard ratio HR = 1.70, 95% CI = 1.26‐2.29, P = .001 in all subjects, and HR = 1.82, 95% CI = 1.18‐2.81, P = .007 in the nonmonitoring group), although it was not statistically significant in the monitoring group (HR = 1.49, 95% CI = 0.99‐2.26 and P = .057). No significant risk difference was observed between single administration of methotrexate and biological drugs.
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