Double Hit

Motor impairments come in different forms. One class of motor impairments, relates to accuracy of tracking a moving object, as, for instance, when chasing in an attempt to catch it. Here we look at neural signals associated with errors in tracking, and the implications for brain-computer-interfaces that target impairment-tailored rehabilitation. As a starting point, we characterized EEG signals evoked by tracking errors during continuous natural motion, in healthy participants. Participants played a virtual 3D, ecologically valid haptic tennis game, and had to track a moving tennis ball in order to hit and send the ball towards the opponent's court...

The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene-signature (adult-mBL), revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24 and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes...

Patients with double-hit or triple-hit lymphoma have a significantly worse prognosis compared to patients with diffuse large B-cell lymphoma without MYC rearrangement. However, the prognostic importance of extra copies of MYC, BCL2, or BCL6 has not been fully explored. We studied 663 patients with de novo diffuse large B-cell lymphoma in whom the status of MYC/8q24, BCL2/18q21, and BCL6/3q27 were assessed by fluorescence in situ hybridization. Cases of double or triple extra copy lymphoma were defined by the presence of increased MYC copies and increased BCL2 and/or BCL6 copies or rearrangement...

Waldenström macroglobulinemia (WM) is a lymphoproliferative lymphoma that is characterized by monoclonal immunoglobulin M (IgM) protein and bone marrow infiltration. Its incidence is rare and rarer still is its ability to transform to a B-cell lymphoma, particularly the aggressive diffuse large B-cell lymphoma, which bodes a poor prognosis. When transformation includes mutations of MYC, BCL-2 and/or BCL-6, it is known as a 'double hit' or 'triple hit' lymphoma respectively. This paper presents a rare case of WM with mutations positive for MYC and BCL2, making it a case of double hit B-cell lymphoplasmacytic lymphoma with plasmatic differentiation without morphological transformation to aggressive histology like DLBCL...

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Double-hit lymphoma (DHL) is a rare aggressive B-cell lymphoma with concomitant c-MYC, BCL2 or BCL6 gene rearrangements, which is characterized by the high frequency of extranodal lesions and by resistance to chemotherapy. The median survival does not exceed 18 months in patients with this disease. The majority of DHL is represented by с-MYC/BCL2 cases. The combination of c-MYC/BCL6 occurs rarely (5-8%). The paper describes a case of DHL with concomitant c-MYC and BCL6 gene rearrangements, which mimics diffuse large B-cell lymphoma, leg-type...

BACKGROUND: OnabotulinumtoxinA has been shown to reduce headache-days among patients with chronic migraine (CM). The objective of this analysis was to determine whether onabotulinumtoxinA has an impact on headache-day severity in patients with CM among those patients who were deemed non-responders based on reduction in the frequency of headache days alone. METHODS: Data from the Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical trial program (a 24-week, 2-treatment cycle, double-blind, randomized, placebo-controlled, parallel-group phase, followed by a 32-week, 3-treatment cycle, open-label phase) were pooled for analysis...

BACKGROUND: The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS: This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy...

PURPOSE: To evaluate the role of infiltrating macrophages in murine models of single and double mutation head and neck tumors using a novel fluorine-19 ((19) F) MRI technology. METHODS: Tumor cell lines single-hit/SCC4 or double-hit/Cal27, with mutations of TP53 and TP53 & FHIT, respectively, were injected bilaterally into the flanks of (n = 10) female mice. With tumors established, perfluorocarbon nanoemulsion was injected intravenously, which labels in situ predominantly monocytes and macrophages...

The update of the 4th edition of the World Health Organization Classification of Haematopoietic and Lymphatic Tissues portends important new findings and concepts in the diagnosis, classification and biology of lymphomas. This review summarizes the basic concepts and cornerstones of the classification of aggressive B-cell lymphomas and details the major changes. Of importance, there is a new concept of High-grade B-cell lymphomas (HGBL), partly replacing the provisional entity of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, the so-called grey zone lymphomas...

Low grade follicular lymphoma (FL1/2) has an annual risk of transformation of approximately 3% which is associated with aberrations in CDKN2A/B, TP53 and MYC. Like in DLBCL high MYC expression in transformed FL (tFL) might predict a MYC breakpoint. We quantified MYC expression by immunohistochemistry and digital analysis in 41 paired biopsies from 20 patients with FL1/2 with subsequent transformation and in 4 isolated biopsies of tFL. As controls 28 biopsies of FL1/2 without transformation (median follow up 105 months) and 9 FL3A/B were analyzed...

OBJECTIVE: To determine the impact of different aortic clamping strategies on the incidence of cerebral embolic events during coronary artery bypass grafting (CABG). METHODS: Between 2012 and 2015, 142 patients with low-grade aortic disease (epiaortic ultrasound grade I/II) undergoing primary isolated CABG were studied. Those undergoing off-pump CABG were randomized to a partial clamp (n = 36) or clampless facilitating device (CFD; n = 36) strategy. Those undergoing on-pump CABG were randomized to a single-clamp (n = 34) or double-clamp (n = 36) strategy...

Recent genetic and molecular discoveries regarding alterations in diffuse large B-cell lymphoma (DLBCL) deeply changed the approach to this lymphoproliferative disorder. Novel additional predictors of outcomes and new therapeutic strategies are being introduced to improve outcomes. Areas covered: This review aims to analyse the recent molecular discoveries in DLBCL, the rationale of novel molecular driven treatments and their impact on DLBCL prognosis, especially in ABC-DLBCL and High Grade B Cell Lymphoma...

Double hit lymphomas (DHLs) are a new category in the World Health Organization newest classification for lymphoid malignancies. DHL encompasses various histologies of lymphomas where the MYC oncogene and either BCL2 or BCL6 oncogenes are present concomitantly. Several observational studies and retrospective series have demonstrated that patients with DHL carry a poor prognosis and respond less and for a shorter duration to standard R-CHOP (rituximab, cyclophosphamide, vincristine, adriamycin, and prednisone)...

Exposure to divalent metals such as iron and manganese is thought to increase the risk for Parkinson's disease (PD). Under normal circumstances, cellular iron and manganese uptake is regulated by the divalent metal transporter 1 (DMT1). Accordingly, alterations in DMT1 levels may underlie the abnormal accumulation of metal ions and thereby disease pathogenesis. Here, we have generated transgenic mice overexpressing DMT1 under the direction of a mouse prion promoter and demonstrated its robust expression in several regions of the brain...

Laser-induced adiabatic alignment and mixed-field orientation of 2,6-difluoroiodobenzene (C6H3F2I) molecules are probed by Coulomb explosion imaging following either near-infrared strong-field ionization or extreme-ultraviolet multi-photon inner-shell ionization using free-electron laser pulses. The resulting photoelectrons and fragment ions are captured by a double-sided velocity map imaging spectrometer and projected onto two position-sensitive detectors. The ion side of the spectrometer is equipped with a pixel imaging mass spectrometry camera, a time-stamping pixelated detector that can record the hit positions and arrival times of up to four ions per pixel per acquisition cycle...

RATIONALE: In a recent systematic review, aging has been identified as the only factor independently associated with mortality during human acute respiratory distress syndrome (ARDS). We explored this age-dependent severity in a clinically relevant double hit murine ARDS model. METHODS: Young adult (Y, 10-12weeks) and middle-old (O, 12-13months) male C57BL6 mice underwent an aspiration of Escherichia coli lipopolysaccharide (LPS) or control saline vehicle. Twenty hours later, four groups of mice were sacrificed [Y(control), O(control), Y(LPS) and O(LPS)]...

The precise etiology of preeclampsia is unknown. Family studies indicate that both genetic and environmental factors influence its development. One of these factors is NFkB, whose activation depends on NEMO (NFkB essential modulator. This is the first study to investigate the association between the existence of single nucleotide variant of the NEMO gene and the appearance of preeclampsia. A total of 151 women (72 preeclamptic women and 79 controls) and their children were examined. Sanger sequencing was performed to identify variants in the NEMO gene in the preeclamptic mothers...

TMPRSS2 and SLC45A3 rearrangements may coexist in the same tumor. ERG rearrangements and PTEN loss are concomitant events in prostate cancer (PrCa), and can cooperate in progression. We have reported that mRNA expression of TMPRSS2-ERG and SLC45A3-ERG rearrangements plus PTEN loss define an aggressive tumor subset. The aim of this study has been to validate these results by immunohistochemistry in a large cohort of tumors. ERG, SLC45A3 and PTEN immunostaining and their association with pathological features and PSA progression-free survival were analyzed in 220 PrCa (PSMAR-Biobank, Barcelona, Spain)...

Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ~30%, while ~70% are aneuploid and senescent cells (AASCs), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...