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•Reproducibility of harmonized QSM protocol at 3T was tested in a multicentric study.•The traveling brain study yielded optimal structural similarity and ...reproducibility.•ROI-dependent χ quantification errors were 0.001–0.017 ppm for traveling brains.•In healthy subjects, ROI-dependent χ variability of 0.005–0.025 ppm can be expected.•The harmonized protocol yields reliable χ and it is ready for multicentric studies.
Quantitative Susceptibility Mapping (QSM) is an MRI-based technique allowing the non-invasive quantification of iron content and myelination in the brain. The RIN – Neuroimaging Network established an optimized and harmonized protocol for QSM across ten sites with 3T MRI systems from three different vendors to enable multicentric studies. The assessment of the reproducibility of this protocol is crucial to establish susceptibility as a quantitative biomarker. In this work, we evaluated cross-vendor reproducibility in a group of six traveling brains. Then, we recruited fifty-one volunteers and measured the variability of QSM values in a cohort of healthy subjects scanned at different sites, simulating a multicentric study. Both voxelwise and Region of Interest (ROI)-based analysis on cortical and subcortical gray matter were performed.
The traveling brain study yielded high structural similarity (∼0.8) and excellent reproducibility comparing maps acquired on scanners from two different vendors. Depending on the ROI, we reported a quantification error ranging from 0.001 to 0.017 ppm for the traveling brains. In the cohort of fifty-one healthy subjects scanned at nine different sites, the ROI-dependent variability of susceptibility values, of the order of 0.005–0.025 ppm, was comparable to the result of the traveling brain experiment.
The harmonized QSM protocol of the RIN – Neuroimaging Network provides a reliable quantification of susceptibility in both cortical and subcortical gray matter regions and it is ready for multicentric and longitudinal clinical studies in neurological and pychiatric diseases.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent Coronavirus Disease 2019 (COVID-19) pandemic, which has spread all over the world over the past year. ...Comorbidities appear to affect the prognosis of patients with such diseases, but the impact of cancer on the course of SARS-CoV2 has remained largely elusive. The aim of the present study is to analyze the outcome of patients affected by squamous cell carcinoma of the head and neck (SCCHN) and a number of their comorbidities, if infected with SARS-CoV2. The clinical data of 100 patients affected by SCCHN, who were undergoing treatment or who had finished their oncologic treatment in the past 6 months, were retrospectively collected and analysed. For each patient, the Charlson Comorbidity Index (CCI) was calculated to provide a score assessing the real weight of comorbidities on the patient's outcome at the time of diagnosis. It was discovered that these patients, besides the SCCHN, frequently presented at diagnosis with several other comorbidities, including hypertension, type 2 diabetes, cardiac arrhytmia, chronic obstructive pulmonary disease and various forms of vasculopathy (and thus a poor CCI). This feature suggest that, given the high frequency of various comorbidities in patients with SCCHN, additional SARS-CoV2 infection could have particularly devastating consequences.
By increasing the use of daily CBCT, additional delivered imaging dose to the patient became a matter of concern. This can also raise concerns about patients with CIEDs since accumulated dose to ...these devices highly needs to be limited. The aim of this study is to investigate the imaging dose to the CIEDs from Elekta XVI and Varian OBI kV-CBCT systems performed by a multi-institutional study.
Four geographically separated centers with different CBCT imaging systems and three different dosimetric measurement methods including Gafchromic films, metal-oxide-semiconductor field-effect transistor (MOSFET) and thermoluminescence dosimeters (TLDs) participated in this multi-center study. At each center an anthropomorphic phantom (Alderson RANDO phantom) was used and the CIED was placed in the alderson’s left clavicular region using the same setup. The dosimeter was fixed on top of the device over which a 1-cm thick bolus was used to simulate patient’s skin. Different standard CBCT-imaging protocols which are commonly used in clinical practice of each center were applied namely, Head&Neck (HN), Chest, Thorax, Symmetry, Prostate and Pelvis.
The maximum values of imaging doses were found once CIEDs were inside the CBCT field. They were between the following values: HNS20 (XVI):2.57 mGy/100 mAs, Thorax (OBI):2.92 mGy/100 mAs, ChestM15-left (XVI): 1.52 mGy/100 mAs, Symmetry-left (XVI): 5.67 mGy/100 mAs. However, they received much lower dose once the CIEDs were not inside the field.
This study shows that although imaging doses received by CIEDs outside the CBCT field is negligible, a special attention should be paid to this value when CIEDs are inside the CBCT field because daily use of CBCT can make a considerable contribution to the total dose received by CIED. Based on the obtained results, it is possible that in some protocol like symmetry total imaging dose to CIED in a 30-fraction reach as high as 50 cGy. Therefore in such cases, this additional imaging dose should not be ignored when classifying CIED patients into risk groups.
The yeast
Saccharomyces cerevisiae
expresses one member of the metacaspase Cys protease family, encoded by the
YCA1
gene. Combination of proteomics and metabolomics data showed that
YCA1
deletion ...down-regulated glycolysis, the TCA cycle and alcoholic fermentation as compared with WT cells.
Δyca1
cells also showed a down-regulation of the pentose phosphate pathway and accumulation of pyruvate, correlated with higher levels of certain amino acids found in these cells. Accordingly, there is a decrease in protein biosynthesis, and up-regulation of specific stress response proteins like Ahp1p, which possibly provides these cells with a better protection against stress. Moreover, in agreement with the down-regulation of protein biosynthesis machinery in
Δyca1
cells, we have found that regulation of transcription, co-translational protein folding and protein targeting to different subcellular locations were also down-regulated. Metabolomics analysis of the nucleotide content showed a significant reduction in
Δyca1
cells in comparison with the WT, except for GTP content which remained unchanged. Thus, our combined proteome-metabolome approach added a new dimension to the non-apoptotic function of yeast metacaspase, which can specifically affect cell metabolism through as yet unknown mechanisms and possibly stress-response pathways, like HOG and cell wall integrity pathways. Certainly,
YCA1
deletion may induce compensatory changes in stress response proteins offering a better protection against apoptosis to
Δyca1
cells rather than a loss in pro-apoptotic
YCA1
-associated activity.
A combined proteomic and metabolomic approach revealed new non-apoptotic roles of the metacaspase
YCA1
gene in
Saccharomyces cerevisiae
, highlighting its involvement in the cell metabolism and stress response.
Salmonella 4,5,12:i:- is a variant of Salmonella Typhimurium, which lacks the expression of phase-2 flagellar antigen, generally associated with the deletion of the fljB gene. Additional mechanisms ...involving the fljAB operon ( fljA, fljB, and hin genes) lead to the lack of expression of phase-2 flagellar antigens also in Salmonella strains harboring the fljB gene. For 20 S. 4,5,12:i:- strains, defined as "inconsistent" Salmonella Typhimurium variants since they had phenotypically behaved as monophasic, even though the fljB gene was conserved, the fljAB operon was characterized in order to explain the ineffective expression of the phase-2 flagellar antigen. The monophasic phenotype for a first group of strains (9) was likely due to the absence of the hin gene, leading to the inhibited switch between the expression of phase-1 and phase-2 flagellar genes. For a second group of strains (5), the monophasic phenotype could be attributed to nonconservative point mutations identified in fljA and hin genes, which could hamper the proper expression of invertase gene and the fljA, acting as repressor of the phase-1 flagellar gene. Finally, for a last group of inconsistent strains (6), a plausible reason for their monophasic phenotype was not found, since the genes involved in the expression of phase-2 flagellar antigen were fully conserved. Moreover, the collection of inconsistent Salmonella Typhimurium isolates investigated were characterized by distinct molecular profiles, as demonstrated by multiple-locus variable-number tandem repeat analysis, and phenotype variability, as demonstrated by phage-typing. This study highlights the usefulness of investigating the entire fljAB operon when a definitive identification of the monophasic or biphasic status of Salmonella Typhimurium strains is needed (for instance, in the context of epidemiological investigations aimed to identify the relatedness among strains).
Type 2 diabetes mellitus (T2DM) and periodontitis are inflammatory conditions with a bidirectional association. This pilot study aimed to evaluate whether T2DM and glycemic control interfere in ...inflammatory markers profiles in gingival crevicular fluid (GCF) in periodontitis patients.
Fourteen diabetic periodontitis patients were enrolled in this study, seven with adequate glycemic control (glycated hemoglobin HbA1c <8.0%) (DMA + P) and seven with inadequate control (HbA1c ≥8.0%) (DMI + P). Seven chronic periodontitis patients without diabetes formed the control group (P). GCF was obtained from diseased sites (probing depth >6 mm) of an entirely hemiarch, pooled and cytokines levels determined using multiplex beads immunoassay. Clinical periodontal parameters were analyzed by Mann-Whitney test and levels of cytokines by Kruskal-Wallis and Dunn's multiple comparison tests with confidence level of 95% (P < 0.05).
Cytokines profile of GCF obtained from deep periodontal pockets presented high levels of inflammatory cytokines, and there were no statistical differences between levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α according to presence of diabetes or percentage of HbA1c among the groups, despite groups with T2DM and periodontitis exhibit higher levels of PD.
Within the limitations of this study, inflammatory mediators in GCF are dependent to the local response and do not correlate with the diabetic status.
Background Previous evidence demonstrated that restoration of wild type VHL in human renal cancer cells decreased in vitro NK susceptibility. To investigate on the role of tumoral VHL status versus ...NK capability in renal cancer patients, 51 RCC patients were characterized for VHL mutational status and NK function. Methods VHL mutational status was determined by direct DNA sequencing on tumor tissue. NK cytotoxicity was measured against specific target cells K562, VHL-wild type (CAKI-1) and VHL-mutated (A498) human renal cancer cells through externalization of CD107a and IFN-gamma production. Activating NK receptors, NKp30, NKp44, NKp46, NKG2D, DNAM-1, NCAM-1 and FcgammaRIIIa were evaluated through quantitative RT-PCR. RCC tumoral Tregs were characterized as CD4.sup.+CD25.sup.+CD127.sup.lowFoxp3.sup.+ and Treg function was evaluated as inhibition of T-effector proliferation. Results VHL mutations were detected in 26/55 (47%) RCC patients. IL-2 activated whole-blood samples (28 VHL-WT-RCC and 23 VHL-MUT-RCC) were evaluated for NK cytotoxicity toward human renal cancer cells A498, VHL-MUT and CAKI-1, VHL-WT. Efficient NK degranulation and increase in IFN-gamma production was detected when IL-2 activated whole-blood from VHL-MUT-RCC patients were tested toward A498 as compared to CAKI-1 cells (CD107a.sup.+NK: 7 + or - 2% vs 1 + or - 0.41%, p = 0.015; IFN-gamma.sup.+NK: 6.26 + or - 3.4% vs 1.78 + or - 0.9% respectively). In addition, IL-2 activated NKs induced higher CD107a exposure in the presence of RCC autologous tumor cells or A498 as compared to SN12C (average CD107a.sup.+NK: 4.7 and 2.7% vs 0.3% respectively at 10E:1 T ratio). VHL-MUT-RCC tumors were NKp46.sup.+ cells infiltrated and expressed high NKp30 and NKp46 receptors as compared to VHL-WT-RCC tumors. A significant lower number of Tregs was detected in the tumor microenvironment of 13 VHL-MUT-RCC as compared to 13 VHL-WT-RCC tumors (1.84 + or - 0.36% vs 3.79 + or - 0.74% respectively, p = 0.04). Tregs isolated from VHL-MUT-RCC patients were less suppressive of patients T effector proliferation compared to Tregs from VHL-WT-RCC patients (Teff proliferation: 6.7 + or - 3.9% vs 2.8 + or - 1.1%). Conclusions VHL tumoral mutations improve NKs effectiveness in RCC patients and need to be considered in the evaluation of immune response. Moreover therapeutic strategies designed to target NK cells could be beneficial in VHL-mutated-RCCs alone or in association with immune checkpoints inhibitors. Keywords: Von Hippel-Lindau, Natural killer, Renal cell carcinoma, CD107a, Tumor microenvironment
Salmonella enterica subspecies enterica serotype 4,5,12:i:- is an emerging serovar considered as a monophasic variant of Salmonella enterica serotype Typhimurium. The antigenic and genetic similarity ...between Salmonella 4,5,12:i:- and Salmonella Typhimurium suggests that they may behave in a similar way and represent a comparable threat to public health. As serotyping alone does not necessarily provide for identification of Salmonella 4,5,12:i:- and its differentiation from Salmonella Typhimurium, a method that combines traditional serotyping and a multiplex polymerase chain reaction has been tested on 208 strains serotyped as Salmonella 4,5,12:i:-, Salmonella Typhimurium, and similar serovars of serogroup B sharing the same phase-1 antigen "i." For 191 strains, the combined method fully confirmed the results provided by traditional serotyping, whereas for 17 strains of Salmonella 4,5,12:i:- and Salmonella Typhimurium some inconsistencies emerged between the two methods. The combined method resulted in a more accurate and faster identification of these two relevant serovars.
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