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AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation [Research Article]

Microtubule-associated serine/threonine kinase like (MASTL), also known as Greatwall (Gwl) kinase, has an important role in the regulation of mitosis. By inhibiting protein phosphatase 2A (PP2A), it plays a crucial role in activating one of the most important mitotic kinases, known as cyclin-dependent kinase 1 (CDK1). MASTL has been seen to be upregulated in various types of cancers and is also involved in tumor recurrence. It is activated by CDK1 through phosphorylations in the activation/T-loop, but the complete mechanism of its activation is still unclear. Here, we report that AKT phosphorylates MASTL at residue T299, which plays a critical role in its activation. Our results suggest that AKT increases CDK1-mediated phosphorylation and hence the activity of MASTL, which, in turn, promotes mitotic progression through PP2A inhibition. We also show that the oncogenic potential of AKT is augmented by MASTL activation, since AKT-mediated proliferation in colorectal cell lines can be attenuated by inhibiting and/or silencing MASTL. In brief, we report that AKT plays an important role in the progression of mitosis in mammalian cells and that it does so through the phosphorylation and activation of MASTL.




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Editorial Board [Masthead]




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Effect of Low-Sodium versus Conventional Sodium Dialysate on Left Ventricular Mass in Home and Self-Care Satellite Facility Hemodialysis Patients: A Randomized Clinical Trial

Background

Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload.

Methods

To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging.

Results

The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake.

Conclusions

Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status.

Clinical Trial registry name and registration number:

The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.




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Risks of N95 Face Mask Use in Subjects With COPD

BACKGROUND:The N95 filtering facepiece respirator (FFR) is the most popular individual protective device to reduce exposure to particulate matter. However, concerns have been raised with regard to its use because it can increase respiratory resistance and dead space. Therefore, this study assessed the safety of N95 use in patients with COPD and air-flow limitation.METHODS:This prospective study was performed at a tertiary hospital and enrolled 97 subjects with COPD. The subjects were monitored for symptoms and physiologic variables during a 10-min rest period and 6-min walking test while wearing an N95.RESULTS:Of the 97 subjects, 7 with COPD did not wear the N95 for the entire test duration. This mask-failure group showed higher British modified Medical Research Council dyspnea scale scores and lower FEV1 percent of predicted values than did the successful mask use group. A modified Medical Research Council dyspnea scale score ≥ 3 (odds ratio 167, 95% CI 8.4 to >999.9; P = .008) or a FEV1 < 30% predicted (odds ratio 163, 95% CI 7.4 to >999.9; P = .001) was associated with a risk of failure to wear the N95. Breathing frequency, blood oxygen saturation, and exhaled carbon dioxide levels also showed significant differences before and after N95 use.CONCLUSIONS:This study demonstrated that subjects with COPD who had modified Medical Research Council dyspnea scale scores ≥ 3 or FEV1 < 30% predicted wear N95s only with care.




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Editorial Board [Masthead]




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Photo Quiz: A 55-Year-Old-Man with Rectal Bleeding and a Rectal Mass [Photo Quiz]




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Genomic Investigation Reveals Contaminated Detergent as the Source of an Extended-Spectrum-{beta}-Lactamase-Producing Klebsiella michiganensis Outbreak in a Neonatal Unit [Bacteriology]

Klebsiella species are problematic pathogens in neonatal units and may cause outbreaks, for which the sources of transmission may be challenging to elucidate. We describe the use of whole-genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-β-lactamase (ESBL)-producing Klebsiella michiganensis colonizing neonates. Ceftriaxone-resistant Klebsiella spp. isolated from neonates (or their mothers) and the hospital environment were included. Short-read sequencing (Illumina) and long-read sequencing (MinION; Oxford Nanopore Technologies) were used to confirm species taxonomy, to identify antimicrobial resistance genes, and to determine phylogenetic relationships using single-nucleotide polymorphism profiling. A total of 21 organisms (10 patient-derived isolates and 11 environmental isolates) were sequenced. Standard laboratory methods identified the outbreak strain as an ESBL-producing Klebsiella oxytoca, but taxonomic assignment from WGS data suggested closer identity to Klebsiella michiganensis. Strains isolated from multiple detergent-dispensing bottles were either identical or closely related by single-nucleotide polymorphism comparison. Detergent bottles contaminated by K. michiganensis had been used for washing milk expression equipment. No new cases were identified once the detergent bottles were removed. Environmental reservoirs may be an important source in outbreaks of multidrug-resistant organisms. WGS, in conjunction with traditional epidemiological investigation, can be instrumental in revealing routes of transmission and guiding infection control responses.




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Multicenter Evaluation of the BD Phoenix CPO Detect Test for Detection and Classification of Carbapenemase-Producing Organisms in Clinical Isolates [Bacteriology]

Limited treatment options contribute to high morbidity/mortality rates with carbapenem-resistant, Gram-negative bacterial infections. New approaches for carbapenemase-producing organism (CPO) detection may help inform clinician decision-making on patient treatment and infection control. BD Phoenix CPO detect (CPO detect) detects and classifies carbapenemases in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa during susceptibility testing. The clinical performance of CPO detect is reported here. Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa isolates were evaluated across three sites using CPO detect and a composite reference method (RM); the latter was comprised of the modified carbapenem inactivation method and a MIC screen for ertapenem, imipenem, and meropenem. Multiplex PCR testing was also utilized for Ambler class determination. Positive and negative percentages of agreement (PPA and NPA, respectively) between CPO detect and the RM were determined. The PPA and NPA for Enterobacterales were 98.5% (confidence intervals, 96.6%, 99.4%) and 97.2% (95.8%, 98.2%), respectively. The A. baumannii PPA and NPA, respectively, were 97.1% (90.2%, 99.2%) and 97.1% (89.9%, 99.2%). The P. aeruginosa PPA and NPA, respectively, were 95.9% (88.6%, 98.6%) and 92.3% (86.7%, 95.6%). The PPA values for carbapenemase class designations for all organisms combined and Enterobacterales alone, respectively, were 95.3% (90.2%, 97.8%) and 94.6% (88.8%, 97.5%) for class A, 94.0% (88.7%, 96.6%) and 96.4% (90.0%, 98.8%) for class B, and 95.0% (90.1%, 97.6%) and 99.0% (94.4%, 99.8%) for class D carbapenemases. NPA values for all organisms and Enterobacterales alone ranged from 98.5% to 100%. CPO detect provided accurate detection and classification of CPOs for the majority of isolates of Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa tested.




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Fourier Transform Infrared Spectroscopy Is a New Option for Outbreak Investigation: a Retrospective Analysis of an Extended-Spectrum-Beta-Lactamase-Producing Klebsiella pneumoniae Outbreak in a Neonatal Intensive Care Unit [Epidemiology]

The IR Biotyper is a new automated typing system based on Fourier-transform infrared (FT-IR) spectroscopy that gives results within 4 h. We aimed (i) to use the IR Biotyper to retrospectively analyze an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) in a neonatal intensive care unit and to compare results to BOX-PCR and whole-genome sequencing (WGS) results as the gold standard and (ii) to assess how the cutoff values used to define clusters affect the discriminatory power of the IR Biotyper. The sample consisted of 18 isolates from 14 patients. Specimens were analyzed in the IR Biotyper using the default analysis settings, and spectra were analyzed using OPUS 7.5 software. The software contains a feature that automatically proposes a cutoff value to define clusters; the cutoff value defines up to which distance the spectra are considered to be in the same cluster. Based on FT-IR, the outbreak represented 1 dominant clone, 1 secondary clone, and several unrelated clones. FT-IR results, using the cutoff value generated by the accompanying software after 4 replicates, were concordant with WGS for all but 1 isolate. BOX-PCR was underdiscriminatory compared to the other two methods. Using the cutoff value generated after 12 replicates, the results of FT-IR and WGS were completely concordant. The IR Biotyper can achieve the same typeability and discriminatory power as genome-based methods. However, to attain this high performance requires either previous, strain-dependent knowledge about the optimal technical parameters to be used or validation by a second method.




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Editorial Board [Masthead]




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Editorial Board [Masthead]




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CXCR4 upregulation is an indicator of sensitivity to B-cell receptor/PI3K blockade and a potential resistance mechanism in B-cell receptor-dependent diffuse large B-cell lymphomas

B-cell receptor (BCR) signaling pathway components represent promising treatment targets in multiple B-cell malignancies including diffuse large B-cell lymphoma (DLBCL). In in vitro and in vivo model systems, a subset of DLBCLs depend upon BCR survival signals and respond to proximal BCR/phosphoinositide 3 kinase (PI3K) blockade. However, single-agent BCR pathway inhibitors have had more limited activity in patients with DLBCL, underscoring the need for indicators of sensitivity to BCR blockade and insights into potential resistance mechanisms. Here, we report highly significant transcriptional upregulation of C-X-C chemokine receptor 4 (CXCR4) in BCR-dependent DLBCL cell lines and primary tumors following chemical spleen tyrosine kinase (SYK) inhibition, molecular SYK depletion or chemical PI3K blockade. SYK or PI3K inhibition also selectively upregulated cell surface CXCR4 protein expression in BCR-dependent DLBCLs. CXCR4 expression was directly modulated by fork-head box O1 via the PI3K/protein kinase B/forkhead box O1 signaling axis. Following chemical SYK inhibition, all BCR-dependent DLBCLs exhibited significantly increased stromal cell-derived factor-1α (SDF-1α) induced chemotaxis, consistent with the role of CXCR4 signaling in B-cell migration. Select PI3K isoform inhibitors also augmented SDF-1α induced chemotaxis. These data define CXCR4 upregulation as an indicator of sensitivity to BCR/PI3K blockade and identify CXCR4 signaling as a potential resistance mechanism in BCR-dependent DLBCLs.




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Prevalent and Diverse Intratumoral Oncoprotein-Specific CD8+ T Cells within Polyomavirus-Driven Merkel Cell Carcinomas

Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AA). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to T-Ag–specific T cells. Strategies to increase CD8+ T-cell number, breadth, or function could augment checkpoint inhibition, but vaccines to augment immunity must avoid delivery of oncogenic T-antigen domains. We probed MCC tumor-infiltrating lymphocytes (TIL) with an artificial antigen-presenting cell (aAPC) system and confirmed T-Ag recognition with synthetic peptides, HLA-peptide tetramers, and dendritic cells (DC). TILs from 9 of 12 (75%) subjects contained CD8+ T cells recognizing 1–8 MCPyV epitopes per person. Analysis of 16 MCPyV CD8+ TIL epitopes and prior TIL data indicated that 97% of patients with MCPyV+ MCC had HLA alleles with the genetic potential that restrict CD8+ T-cell responses to MCPyV T-Ag. The LT AA 70–110 region was epitope rich, whereas the oncogenic domains of T-Ag were not commonly recognized. Specific recognition of T-Ag–expressing DCs was documented. Recovery of MCPyV oncoprotein–specific CD8+ TILs from most tumors indicated that antigen indifference was unlikely to be a major cause of checkpoint inhibition failure. The myriad of epitopes restricted by diverse HLA alleles indicates that vaccination can be a rational component of immunotherapy if tumor immune suppression can be overcome, and the oncogenic regions of T-Ag can be modified without impacting immunogenicity.




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Editorial Board [Masthead]




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Correction: EGFR Exon 20 Insertion Mutations Display Sensitivity to Hsp90 Inhibition in Preclinical Models and Lung Adenocarcinomas




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Novel Insights into the Classification of Staphylococcal {beta}-Lactamases in Relation to the Cefazolin Inoculum Effect [Mechanisms of Resistance]

Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal β-lactamases. Four variants of staphylococcal β-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal β-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the β-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for β-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant β-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal β-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.




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Genomic Epidemiology of Complex, Multispecies, Plasmid-Borne blaKPC Carbapenemase in Enterobacterales in the United Kingdom from 2009 to 2014 [Epidemiology and Surveillance]

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the blaKPC family) is one of the most common transmissible carbapenem resistance mechanisms worldwide. The dissemination of blaKPC historically has been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the United Kingdom, blaKPC has represented a large-scale, persistent management challenge for some hospitals, particularly in North West England. The dissemination of blaKPC has evolved to be polyclonal and polyspecies, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole-genome sequencing of 604 blaKPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterization. We observed the dissemination of blaKPC (predominantly blaKPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 [97%] isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), blaKPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments among plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates), and IncR (252/604 isolates) replicons. The subset of reconstructed plasmid sequences (21 isolates, 77 plasmids) also highlighted modular exchange among non-blaKPC and blaKPC plasmids and the common presence of multiple replicons within blaKPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales for the implementation of adequate surveillance approaches and for control.




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Safety and Pharmacokinetic Characterization of Nacubactam, a Novel {beta}-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers [Clinical Therapeutics]

Nacubactam is a novel β-lactamase inhibitor with dual mechanisms of action as an inhibitor of serine β-lactamases (classes A and C and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae. The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single- and multiple-ascending-dose, placebo-controlled studies. Healthy participants received single ascending doses of nacubactam of 50 to 8,000 mg, multiple ascending doses of nacubactam of 1,000 to 4,000 mg every 8 h (q8h) for up to 7 days, or nacubactam of 2,000 mg plus meropenem of 2,000 mg q8h for 6 days after a 3-day lead-in period. Nacubactam was generally well tolerated, with the most frequently reported adverse events (AEs) being mild to moderate complications associated with intravenous access and headache. There was no apparent relationship between drug dose and the pattern, incidence, or severity of AEs. No clinically relevant dose-related trends were observed in laboratory safety test results. No serious AEs, dose-limiting AEs, or deaths were reported. After single or multiple doses, nacubactam pharmacokinetics appeared linear, and exposure increased in an approximately dose-proportional manner across the dose range investigated. Nacubactam was excreted largely unchanged into urine. Coadministration of nacubactam with meropenem did not significantly alter the pharmacokinetics of either drug. These findings support the continued clinical development of nacubactam and demonstrate the suitability of meropenem as a potential β-lactam partner for nacubactam. (The studies described in this paper have been registered at ClinicalTrials.gov under NCT02134834 [single ascending dose study] and NCT02972255 [multiple ascending dose study].)




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Distinct Mechanisms of Dissemination of NDM-1 Metallo-{beta}-Lactamase in Acinetobacter Species in Argentina [Epidemiology and Surveillance]

A 4-year surveillance of carbapenem-resistant Acinetobacter spp. isolates in Argentina identified 40 strains carrying blaNDM-1. Genome sequencing revealed that most were Acinetobacter baumannii, whereas seven represented other Acinetobacter spp. The A. baumannii genomes were closely related, suggesting recent spread. blaNDM-1 was located in the chromosome of A. baumannii strains and on a plasmid in non-A. baumannii strains. A resistance gene island carrying blaPER-7 and other resistance determinants was found on a plasmid in some A. baumannii strains.




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Predominant Distribution of OXA-48-Like Carbapenemase in Fecal Colonization [Letters]




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Unorthodox Parenteral {beta}-Lactam and {beta}-Lactamase Inhibitor Combinations: Flouting Antimicrobial Stewardship and Compromising Patient Care [Commentary]

In India and China, indigenous drug manufacturers market arbitrarily combined parenteral β-lactam and β-lactamase inhibitors (BL-BLIs). In these fixed-dose combinations, sulbactam or tazobactam is indiscriminately combined with parenteral cephalosporins, with BLI doses kept in ratios similar to those for the approved BL-BLIs. Such combinations have been introduced into clinical practice without mandatory drug development studies involving pharmacokinetic/pharmacodynamic, safety, and efficacy assessments being undertaken. Such unorthodox combinations compromise clinical outcomes and also potentially contribute to resistance development.




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ARGONAUT II Study of the In Vitro Activity of Plazomicin against Carbapenemase-Producing Klebsiella pneumoniae [Mechanisms of Resistance]

Plazomicin was tested against 697 recently acquired carbapenem-resistant Klebsiella pneumoniae isolates from the Great Lakes region of the United States. Plazomicin MIC50 and MIC90 values were 0.25 and 1 mg/liter, respectively; 680 isolates (97.6%) were susceptible (MICs of ≤2 mg/liter), 9 (1.3%) intermediate (MICs of 4 mg/liter), and 8 (1.1%) resistant (MICs of >32 mg/liter). Resistance was associated with rmtF-, rmtB-, or armA-encoded 16S rRNA methyltransferases in all except 1 isolate.




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Editorial Board [Masthead]




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Pemigatinib Is Active in Some FGFR2-Altered Cholangiocarcinomas [Clinical Trials]

Pemigatinib was effective in patients with cholangiocarcinomas with FGFR2 fusions or rearrangements.




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[Cell Biology] Recent Insights on Inflammasomes, Gasdermin Pores, and Pyroptosis

Inflammasomes assemble in the cytosol of myeloid and epithelial cells on sensing of cellular stress and pathogen-associated molecular patterns and serve as scaffolds for recruitment and activation of inflammatory caspases. Inflammasomes play beneficial roles in host and immune responses against diverse pathogens but may also promote inflammatory tissue damage if uncontrolled. Gasdermin D (GSDMD) is a recently identified substrate of murine caspase-1 and caspase-11, and human caspases-1, -4, and -5 that mediates a regulated lytic cell death mode termed pyroptosis. Recent studies have identified pyroptosis as a critical inflammasome effector mechanism that controls inflammasome-dependent cytokine secretion and contributes to antimicrobial defense and inflammasome-mediated autoinflammatory diseases. Here, we review recent developments on inflammasome-associated effector functions with an emphasis on the emerging roles of gasdermin pores and pyroptosis.




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Associations of Abdominal Skeletal Muscle Mass, Fat Mass, and Mortality among Men and Women with Stage I-III Colorectal Cancer

Background:

The associations of abdominal skeletal muscle mass index (SMI), visceral and subcutaneous adipose tissue (VAT and SAT, respectively), and mortality among patients with stage I–III colorectal cancer may differ for men and women, but only few studies stratified their data into men and women. We investigated associations of abdominal SMI, VAT, and SAT with overall mortality among men and among women with stage I–III colorectal cancer.

Methods:

SMI, VAT, and SAT were assessed from abdominal CT images for 1,998 patients with stage I–III colorectal cancer diagnosed between 2006 and 2015. Restricted cubic splines (RCS) were used to investigate associations of SMI, VAT, and SAT with overall mortality.

Results:

Average age of the participants was 67.9 ± 10.6 years and 58% were men. During a median follow-up of 4.3 years, 546 (27%) patients died. Among men, the association of SMI and mortality was statistically significant in a nonlinear way in the RCS analyses, with lower SMI levels associated with higher mortality. SMI was not associated with mortality among women. SAT was associated with mortality in a nonlinear way for men and for women, with lower SAT levels being associated with higher mortality. VAT was not significantly associated with mortality in men or women.

Conclusion:

Associations of abdominal skeletal muscle mass with mortality among patients with colorectal cancer were not the same for men and for women.

Impact:

This study stresses the importance for more attention on sex-related differences in body composition and cancer outcomes.




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Thalamic Massa Intermedia in Children with and without Midline Brain Malformations [PEDIATRICS]

BACKGROUND AND PURPOSE:

The massa intermedia is a normal midline transventricular thalamic connection. Massa intermedia aberrations are common in schizophrenia, Chiari II malformation, X-linked hydrocephalus, Cornelia de Lange syndrome, and diencephalic-mesencephalic junction dysplasia, among others. We have noticed that massa intermedia abnormalities often accompany other midline malformations. The massa intermedia has never been formally evaluated in a group of exclusively pediatric patients, to our knowledge. We sought to compare and contrast the prevalence, size, and location of the massa intermedia in pediatric patients with and without congenital midline brain abnormalities.

MATERIALS AND METHODS:

Successive 3T brain MR imaging examinations from pediatric patients with and without midline malformations were procured from the imaging data base at a pediatric hospital. Massa intermedia presence, size, morphology, and position were determined using 3D-TIWI with 1-mm isotropic resolution. The brain commissures, septum pellucidum, hypothalamus, hippocampus, vermis, and brain stem were evaluated to determine whether alterations were related to or predictive of massa intermedia abnormalities.

RESULTS:

The massa intermedia was more frequently absent, dysmorphic, and/or displaced in patients with additional midline abnormalities than in those without. The massa intermedia was absent in 40% of patients with midline malformations versus 12% of patients with normal findings (P < .001). Massa intermedia absence, surface area, and morphology were predictable by various attributes and alterations of the commissures, hippocampus, hypothalamus, vermis, brain stem, and third ventricle.

CONCLUSIONS:

Most pediatric patients have a thalamic massa intermedia centered in the anterior/superior third ventricle. Massa intermedia abnormalities are commonly associated with other midline malformations. Normal-variant massa intermedia absence is a diagnosis of exclusion.




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Involvement of the Olfactory Apparatus by Gliomas [HEAD & NECK]

SUMMARY:

The olfactory bulbs and tracts are central nervous system white matter tracts maintained by central neuroglia. Although rare, gliomas can originate from and progress to involve the olfactory apparatus. Through a Health Insurance Portability and Accountability Act–compliant retrospective review of the institutional teaching files and brain MR imaging reports spanning 10 years, we identified 12 cases of gliomas involving the olfactory bulbs and tracts, including 6 cases of glioblastoma, 2 cases of anaplastic oligodendroglioma, and 1 case each of pilocytic astrocytoma, diffuse (grade II) astrocytoma, anaplastic astrocytoma (grade III), and diffuse midline glioma. All except the pilocytic astrocytoma occurred in patients with known primary glial tumors elsewhere. Imaging findings of olfactory tumor involvement ranged from well-demarcated enhancing masses to ill-defined enhancing infiltrative lesions to nonenhancing masslike FLAIR signal abnormality within the olfactory tracts. Familiarity with the imaging findings of glioma involvement of the olfactory nerves is important for timely diagnosis and treatment of recurrent gliomas and to distinguish them from other disease processes.




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Polymorphous Low-Grade Neuroepithelial Tumor of the Young as a Partially Calcified Intra-Axial Mass in an Adult [RADIOLOGY-PATHOLOGY CORRELATION]

SUMMARY:

Polymorphous low-grade neuroepithelial tumors of the young (PLNTYs) are recently described CNS tumors. Classically, PLNTYs are epileptogenic and are a subtype of a heterogeneous group of low-grade neuroepithelial tumors that cause refractory epilepsy, such as angiocentric gliomas, oligodendrogliomas, gangliogliomas, and pleomorphic xanthoastrocytomas. Although they are a relatively new entity, a number of imaging and histologic characteristics of PLNTYs are already known. We present the imaging and pathologic findings of such a tumor as well as the surgical approach and clinical management.




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Chuyên cho thuê căn hộ cao cấp Masteri Millennium 1PN 16tr, 2PN 18tr, 3PN 26 triệu Lh 0901756869

Chuyên cho thuê căn hộ cao cấp Masteri Millennium giá tốt* Nhận kí gửi căn hộ cho thuê và sang nhượng từ chủ nhà* Cập nhật giá thuê Masteri Millennium hiện tại -1PN diện tích 54m2 giá NTCB 13,5-15 triệu Full nọii thất đẹp giá 16-17 triệu -2PN diện tích 65-77m2 giá NTCB 16 triệ...




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CHUYÊN chuyển nhượng Masteri giá thật đang có 2PN view hồ bơi giá chỉ 3,3 tỷ. LH em Ni 0901381558

Em chuyên giỏ hàng Masteri Thảo Điền và Masteri An Phú. Giá và vị trí căn hộ nào cũng có hàng. * Có mặt ở Masteri 24/7 để dẫn khách hàng đi xem thực tế căn hộ đã bàn giao, những căn hộ đã có nội thất đầy đủ. * Sổ hồng pháp lý rõ ràng, hỗ trợ vay ngân hàng lên tới 80% giá trị căn hộ. * Cam kết tư vấn đúng nhu cầu, đúng sự thật. Trước khi mua Masteri, muốn tìm hiểu tốt n...




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Chuyên chuyển nhượng CH Masteri Thảo Điền giá rẻ nhất thị trường hỗ trợ vay 80%. LH 0906574444 Dung

Liên hệ ngay để được hướng dẫn chọn căn nhà vừa ý nhất 0906.57.4444 gặp Dung (24/7). Ở đâu giá rẻ, em có giá rẻ hơn. Hỗ trợ tư vấn nhiệt tình + tận tâm + lấy uy tín làm đầu + không mua cũng không sao. Bên em cam kết: Giá rẻ hơn thị trường, trả sát giá chủ nhà. Miễn sao k...




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The Millennium Masteri - Selling luxury shophouse A

Shophouse A11 for sale: Court A. Align the residential corner and front of Ben Van Don. Area: 74m2 Price:VND 16 billion. Hotline: 0919462121 - 0933235111 Yan Lin (English, )...




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Cho thuê căn hộ Masteri Thảo Điền 1 - 3PN, cam kết giá tốt, hỗ trợ xem nhà 24/7

Bảng giá tham khảo cho thuê căn hộ Masteri Thảo Điền.1. Căn hộ 1 phòng ngủ: Diện tích: 45 - 52m2, giá thuê từ 12 - 16 triệu/tháng.2. Căn hộ 2 phòng ngủ: Diện tích: 59 - 72m2, giá thuê từ 15 - 22 triệu/tháng.3. Căn hộ 3 phòng ngủ: Diện tích: 86 - 90m2, giá thuê từ 23 - 33 triệu/th...




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Chuyên cho thuê căn hộ Masteri Thảo Điền Quận 2 1, 2, 3 phòng ngủ giá tốt nhất 0901692239

Sau đây là các căn hộ đang cho thuê tại Masteri Thảo Điền. Anh chị quan tâm xin vui lòng gọi số điện thoại 0901692239 để được tư vấn và hỗ trợ. Xin chân thành cảm ơn!Diện tích: 50m2, 1 phòng khách, 1 phòng ngủ, 1 phòng tắm, nội thất dính tường. Giá: 10 triệu/tháng.Diện tích: 50m2, 1 phòng khách, 1 phòng ngủ, 1 phòng tắm, nội thất đầy đủ. Giá: 12 triệu/tháng.Diện tích: 70m2, 1 p...




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Donald Trump can't mask his message to Indian country: 'Live and let die'

The COVID-19 pandemic has hit the Diné/Navajo people hard, inflicting the highest per capita infection rate in the country after New York, New Jersey, Connecticut and Massachusetts. The Navajo Nation is the largest reservation in the country, larger than West Virginia, straddling Arizona, New Mexico, Colorado and Utah. Half of the over 300,000 enrolled members reside on the reservation. Navajo President Jonathan Nez has issued some of the strongest stay-at-home measures in the country, including a weekday evening curfew and a complete, stay-at-home curfew for the entire weekend. Nearby Gallup, New Mexico, with a large Diné population, has enacted a complete lockdown, with the National Guard prohibiting entry.

As of May 5, despite these efforts, there were 2,559 confirmed COVID-19 cases on the Navajo Nation and 79 deaths. Among the victims, 28-year-old Valentina Blackhorse, a beloved champion of Navajo culture and a community leader. She left behind her partner, Robby Jones, and their one-year-old daughter, Poet.

"She really loved her family -- her parents, her sisters, her nieces and nephews. She loved her elderly. She loved children," Jones said Tuesday on the Democracy Now! news hour. "She was a kind and hardworking lady, and she was warmhearted. She would do anything for her family."

Jones is a detention officer with the Navajo Department of Corrections, and contracted COVID-19 at work. "When she was taking care of me, I guess she contracted it," he said. "She started showing symptoms -- shortness of breath, body aches, loss of taste and smell. By the time I started feeling better … that's when she started feeling sick."

Valentina Blackhorse tested positive for COVID-19 on April 22. She died the next day. She had won numerous pageants, being named Miss Western Navajo and Miss Diné College, among others, and hoped to run for office in the Navajo Nation government one day.

Dr. Michelle Tom, a member of the Navajo Nation, is a family physician in Winslow, Arizona, just across the Navajo reservation line. She spoke about Valentina's death on Democracy Now!: "It's a reflection of what we're going through as a people, and it correlates with what this virus can do to our young and someone who was very motivated, loved our culture, spread our rich and strong culture, and our language. That's what we're trying to fight for," she said, adding, "She was going to lead our next generation. It was a hard loss for our community."

The Navajo Nation, along with the nearby Hopi, Pueblo, Zuni and Gila River Indigenous communities, have endured despite centuries of genocide, oppression and systemic racism and poverty. The novel coronavirus pandemic is afflicting them disproportionately, as it has African American and Latinx populations across the U.S. Access to water is challenging on the Navajo reservation.

"That's from a long state of histories with treaties and our relationship with the [federal] government," Dr. Michelle Tom explained. "Our infrastructure for water has never been at the capacity where we can provide water for everyone on the reservation. So, you're telling people to wash your hands for 20 seconds, and yet people are trying just to get water just to drink and to cook with."

President Donald Trump made a rare trip Tuesday, visiting an Arizona N95 mask factory, where he ignored factory rules by not wearing a mask. Guns 'N Roses blared from a factory sound system, playing the song Live and Let Die. It's not clear if it was a coincidental music choice or not.

Trump also met with elected officials, including Navajo Nation Vice President Myron Lizer. The Navajo Nation joined a lawsuit filed by numerous native tribes against Treasury Secretary Steven Mnuchin, for his abject failure in disbursing $8 billion promised to Native American tribes in the CARES Act.

"The amount of money that’s being sent to 'Indian country,' as we call it, is the largest amount in the history of the U.S. And you deserve it. And you've been through a lot," Trump said to VP Lizer. "The Navajo Nation will soon receive over $600 million. That's a lot. Should I renegotiate that? Can we renegotiate that?" (Laughter.)

There was no laughter back on the Navajo Nation. "Today, the federal government announced that they intend to release a portion of funds appropriated by Congress over one month ago to tribes to help fight COVID-19, but I'll believe it when I see it," President Jonathan Nez, who himself tested positive for the virus, replied. "We couldn't sit around and wait for those dollars, so we've had boots on the ground in nearly 20 communities giving out food, water, firewood, protective masks and other supplies … We lost many of our beloved relatives and family members to this virus, but our teachings also tell us to move forward. We will and we are."

Amy Goodman is the host of Democracy Now!, a daily international TV/radio news hour airing on more than 1,300 stations. She is the co-author, with Denis Moynihan, of The Silenced Majority, a New York Times bestseller. This column originally appeared on Democracy Now!

Image: Shealah Craighead/The White House/Flickr

May 7, 2020




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Halo 2: Anniversary for Halo: The Master Chief Collection for PC Launches May 12

Publisher Microsoft and developer 343 Industries announced Halo 2: Anniversary will launch for the Windows PC version of Halo: The Master Chief Collection via Steam and Microsoft Store on Tuesday, May 12.

Earth will never be the same.

Halo 2: Anniversary arrives on PC as part of Halo: The Master Chief Collection on May 12! https://t.co/y5NHDTiQ1E pic.twitter.com/HVzgxIuY8V

— Halo (@Halo) May 5, 2020

Here is an overview of the game:

Halo 2: Anniversary comes to PC as the next installment in Halo: The Master Chief Collection. Now optimized for PC, experience the impeccably remastered edition of the original Halo 2 game. Following the destruction of Halo, humankind experiences a short-lived victory. Eager for revenge, the Covenant launches a surprise attack on Earth, but they find themselves ill-prepared to defeat the UNSC’s home fleet and are forced to flee into slipspace. When the Master Chief pursues his overzealous enemies, they discover yet another Halo ring, uncovering long-buried secrets, including an unlikely ally, that will dramatically alter the course of the Human-Covenant Conflict forever.

Key Features:

  • PC Settings/Optimizations: Halo 2: Anniversary is now optimized for PC and looking better than ever at up to 4k UHD and at 60+ FPS.* Other PC native settings include customizable mouse and keyboard support, ultrawide support, FOV customization, and more.
  • Campaign: Experience the next chapter in the Halo saga and fight your way through 15 unforgettable missions. Play as both Spartan-117, the Master Chief, and for the first time, the Covenant Elite, known as the Arbiter, and experience the Human-Covenant Conflict in a whole new way.
  • Anniversary Edition/Update: Toggle between the remastered graphics in the Anniversary edition and the graphics from the original Halo 2 campaign. In the Anniversary edition, view Blur Studio’s spectacularly remastered cutscenes from the original Halo 2 game.
  • Multiplayer: Continue your Halo adventure with 7 remastered multiplayer maps from Halo 2: Anniversary and 25 multiplayer maps from the original Halo 2, featuring a completely updated progression system.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443396/halo-2-anniversary-for-halo-the-master-chief-collection-for-pc-launches-may-12/




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Vampire: The Masquerade - Bloodlines 2 Confirmed for Xbox Series X

It was confirmed at the Inside Xbox event today Vampire: The Masquerade - Bloodlines 2 will be getting a next generation release on the Xbox Series X. It was already confirmed the game will release on the PlayStation 4, Xbox One and Windows PC.

View the latest trailer below:

Here is an overview of the game:

Enter the World of Darkness and rise through vampire society. Experience Seattle - a city full of alluring, dangerous, characters and factions. You are dead now but stronger, quicker, more alluring and with potential for so much more. Choose to be brutal and unflinching or cultured and seductive. Use charm, cunning, terror and sheer will to rise through vampire society. What monster will you be?

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443424/vampire-the-masquerade-bloodlines-2-confirmed-for-xbox-series-x/




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Rumor: Mass Effect Trilogy HD Remaster to Launch by March 31, 2021

Electronic Arts in their fiscal year Q4 2020 results said they plan to release 14 titles in the 2021 fiscal year, which ends on March 31, 2021. Electronic Arts labeled one of the game as "an HD remake of an EA game."

VentureBeat is reporting this HD remake is an HD remaster of the Mass Effect Trilogy.

"We are planning to launch 14 new titles to players this fiscal year," said EA CEO Andrew Wilson. "hat includes four new EA Sports titles — FIFA, Madden, NHL, and one more unannounced sports game — all of which deliver on the mix of creativity, authenticity, and quality that sets EA Sports apart.

"Our FY21 plans also include four more games drawing on the breadth of our IP, from Command & Conquer Remastered to unannounced games for our console and PC players. We’ll have more games from indie developers launching this year through EA Partners, and two new mobile titles leveraging top IP that we’ll bring to players worldwide."

Read EA's full lineup for the 2021 fiscal year below:

  1. Burnout Paradise Remastered (Nintendo Switch)
  2. Command & Conquer Remastered (PC)
  3. Medal of Honor VR
  4. FIFA 21
  5. Madden NFL 21
  6. NHL 21
  7. Unannounced sports game
  8. An HD remake of an EA game
  9. EA Partner game
  10. EA Partner game
  11. EA Partner game
  12. EA Partner game
  13. EA Mobile game
  14. EA Mobile game

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443409/rumor-mass-effect-trilogy-hd-remaster-to-launch-by-march-31-2021/




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China is using mass surveillance tech to fight new coronavirus spread

QR codes, tracking apps and drones at toll booths are just some of the tech tools China is deploying to monitor the spread of the new coronavirus




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Disneyland in China to Reopen 11 May With Temperature Checks and Masks Required

This could be a trial run for the rest of Disney’s parks in the US, Japan, France, and Hong Kong.




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Unemployment fears mount in UK holiday hotspots with mass job cuts predicted



BRITAIN'S summer holiday destinations will face some of the biggest economic hits of the coronavirus pandemic with fears of massive job losses in coastal communities, a study has claimed.




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Mysteriously bright supernova may have smashed up a huge gas cloud

A strange supernova that’s 100 times brighter than it should be has long been a mystery, but it may be explained by the explosion slamming into a cloud of gas




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Inside the mission to stop killer asteroids from smashing into Earth

When asteroid Armageddon is upon us, we can't just call Bruce Willis. Meet the people who really do watch the skies – and make detailed plans for our survival




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Supermassive stars may have formed by repeatedly eating their siblings

Some black holes are way bigger than we can explain, and they may have come from supermassive stars that formed by devouring the other stars around them




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ETH Zurich Demonstrates PuppetMaster Robot

Robots that can control puppets could one day learn to manipulate complex physical objects like clothing and flexible sheets