Clinical outcomes of hypomethylating agents and venetoclax in newly diagnosed unfit and relapsed/refractory paediatric, adolescent and young adult acute myeloid leukaemia patients.

Venetoclax (VEN) combined with hypomethylating agents (HMA) decitabine or azacitidine is used for adult acute myeloid leukaemia (AML), but its application in paediatric, adolescent and young adult (AYA) AML lacks prospective studies. We performed a retrospective chart review of paediatric and AYA AML patients treated with HMA + VEN at Cincinnati Children's Hospital Medical Centre. Twenty-seven patients received 30 HMA + VEN treatment courses for relapsed/refractory (R/R, n = 21) or newly diagnosed (n = 9) AML due to ineligibility for intensive chemotherapy.

Transglutaminase 2 has higher affinity for relaxed than for stretched fibronectin fibers.

Transglutaminase 2 (TG2) plays a vital role in stabilizing extracellular matrix (ECM) proteins through enzymatic crosslinking during tissue growth, repair, and inflammation. TG2 also binds non-covalently to fibronectin (FN), an essential component of the ECM, facilitating cell adhesion, migration, proliferation, and survival. However, the interaction between TG2 and fibrillar FN remains poorly understood, as most studies have focused on soluble or surface-adsorbed FN or FN fragments, which differ in their conformations from insoluble FN fibers.

The impact of COVID-19 on chronic pain.

A reduced quality of life is often a hefty burden that those with chronic pain are left to bear. This review of literature from PubMed, Google Scholar and other relevant studies focuses on the complex relationship between COVID-19 and chronic pain, which is challenging to study during the COVID-19 pandemic. In this review, we will briefly discuss the epidemiologic facts and risk factors, followed by the proposed pathophysiologic mechanisms.

Combined epigenetic and immunotherapy for blastic and classical mantle cell lymphoma.

Classical MCL (cMCL) constitutes 6-8% of all B cell NHL. Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes.

Distribution and Pathogenicity of Two Cutthroat Trout Virus (CTV) Genotypes in Canada.

The sole member of the genus (family ) is cutthroat trout virus (CTV) but recent metatranscriptomic studies have identified numerous fish hepevirus sequences including CTV-2. In the current study, viruses with sequences resembling both CTV and CTV-2 were isolated from salmonids in eastern and western Canada. Phylogenetic analysis of eight full genomes delineated the Canadian CTV isolates into two genotypes (CTV-1 and CTV-2) within the genus.

Pediatric Patient With Ulcerative Colitis-Associated Bronchiectasis.

We report a unique case of ulcerative colitis-associated bronchiectasis in a pediatric patient 6 years after colectomy. The patient presented with a chronic cough and had a computed tomography demonstrating bronchiectasis. She was treated with sputum expectoration (airway clearance) via chest physiotherapy and pulse-dose steroids with a prolonged oral taper.

Sphingosine kinase-2 is overexpressed in large granular lymphocyte leukaemia and promotes survival through Mcl-1.

Sphingolipid metabolism is increasingly recognised as a therapeutic target in cancer due to its regulation of cell proliferation and apoptosis. The sphingolipid rheostat is proposed to control cell fate through maintaining balance between pro-apoptotic and pro-survival sphingolipids. This balance is regulated by metabolising enzymes involved in sphingolipid production.

Phase 1-2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma.

Altered DNA methylation and histone acetylation in lymphoma provided the rationale for using vorinostat (SAHA), cladribine and rituximab (SCR) in non-Hodgkin lymphomas (NHL) in this phase 1-2 study (NCT00764517). Treatment included cladribine 5 mg/m intravenously (IV) (days 1-5), rituximab 375 mg/m IV (weekly 4× for cycle 1 and 1×/month) and vorinostat orally once daily (days 1-14) every 28 days for up to six cycles. Phase 1 included relapsed patients (n = 10) in a standard 3 + 3 dose escalation design (vorinostat: 200, 300 and 400 mg).

In vivo virulence and genomic comparison of infectious Salmon Anaemia Virus isolates from Atlantic Canada.

The infectious salmon anaemia virus (ISAV) is capable of causing a significant disease in Atlantic salmon, which has resulted in considerable financial losses for salmon farmers around the world. Since the first detection of ISAV in Canada in 1996, it has been a high priority for aquatic animal health management and surveillance programmes have led to the identification of many genetically distinct ISAV isolates of variable virulence. In this study, we evaluated the virulence of three ISAV isolates detected in Atlantic Canada in 2012 by doing in vivo-controlled disease challenges with two sources of Atlantic salmon.

TRAIL mediates and sustains constitutive NF-κB activation in LGL leukemia.

Large granular lymphocyte (LGL) leukemia results from clonal expansion of CD3 cytotoxic T lymphocytes or CD3 natural killer (NK) cells. Chronic antigen stimulation is postulated to promote long-term survival of LGL leukemia cells through constitutive activation of multiple survival pathways, resulting in global dysregulation of apoptosis and resistance to activation-induced cell death. We reported previously that nuclear factor κB (NF-κB) is a central regulator of the survival network for leukemic LGL.

Overview of infectious salmon anaemia virus (ISAV) in Atlantic Canada and first report of an ISAV North American-HPR0 subtype.

The infectious salmon anaemia virus (ISAV) is an important viral disease of farmed Atlantic salmon that has caused considerable financial losses for salmon farmers around the world, including Atlantic Canada. It is listed as a notifiable disease by the World Organization for Animal Health, and to this day, culling of infected cages or farms remains the current practice in many countries to mitigate the spread of the virus. In Atlantic Canada, ISAV was first detected in 1996 and continues to be detected.

_{36}^{96}Kr_{60}-Low-Z Boundary of the Island of Deformation at N=60.

Prompt γ-ray spectroscopy of the neutron-rich ^{96}Kr, produced in transfer- and fusion-induced fission reactions, has been performed using the combination of the Advanced Gamma Tracking Array and the VAMOS++ spectrometer. A second excited state, assigned to J^{π}=4^{+}, is observed for the first time, and a previously reported level energy of the first 2^{+} excited state is confirmed. The measured energy ratio R_{4/2}=E(4^{+})/E(2^{+})=2.

Synthesis, Characterization, and Properties of Weakly Coordinating Anions Based on tris-Perfluoro-tert-Butoxyborane.

A convenient method for the preparation of strongly Lewis acidic tris-perfluoro-tert-butoxyborane B(OR) (1), (OR = OC(CF)) was developed, and its X-ray structure was determined. 1 was used as a precursor, guided by density functional theory (DFT) calculations and volume-based thermodynamics, for the synthesis of [NEt][NCB(OR)] (3) and [NMe][FB(OR)] (5) and the novel large and weakly coordinating anion salts [Li 15-Crown-5][B(OR)] (2) and [NEt][CN{B(OR)}] (4). The stability of [B(OR)] was compared with that of some related known weakly coordinating anions by appropriate DFT calculations.

Optimization of a hot-cavity type resonant ionization laser ion source.

Resonant Ionization Laser Ion Source (RILIS) is nowadays an important technique in many Radioactive Ion Beam (RIB) facilities for its reliability and ability to ionize efficiently and element selectively. Grand Accélérateur National d'Ions Lourds (GANIL) Ion Source using Electron Laser Excitation (GISELE) is an off-line test bench for RILIS developed to study a fully operational resonant laser ion source at GANIL facility. The ion source body has been designed as a modular system to investigate different experimental approaches by varying the design parameters, to develop the future on-line laser ion source.

Manipulation and mobilisation for neck pain contrasted against an inactive control or another active treatment.

Background: Manipulation and mobilisation are commonly used to treat neck pain. This is an update of a Cochrane review first published in 2003, and previously updated in 2010.

Objectives: To assess the effects of manipulation or mobilisation alone compared wiith those of an inactive control or another active treatment on pain, function, disability, patient satisfaction, quality of life and global perceived effect in adults experiencing neck pain with or without radicular symptoms and cervicogenic headache (CGH) at immediate- to long-term follow-up.

Sphingosine kinase inhibitors decrease viability and induce cell death in natural killer-large granular lymphocyte leukemia.

Sphingolipid metabolism has been identified as a potential therapeutic target in cancer. Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid metabolite produced by sphingosine kinases-1 and -2 (SPHK1 and SPHK2). Elevated SPHK1 has been found in numerous cancer types and been shown to contribute to survival, chemotherapeutic resistance and malignancy.

Improving medical communication with patients and families: Skills for a complex (and multilingual) clinical world.

It has been reported that suboptimal communication represents the largest source of preventable error during acute medical care. Because a significant proportion of ongoing care relies heavily on verbal communication, it is incumbent on clinicians to develop, hone and maintain these skills in the interests of their patients and, at the same time, contribute to a more reliable and patient-focused health care system. This review briefly discusses why communication matters, practical strategies from both inside and outside clinical medicine, the implications of poor translation and the state of medical communication in Canada.

The pathogenesis and treatment of large granular lymphocyte leukemia.

Large granular lymphocyte (LGL) leukemia is a spectrum of rare lymphoproliferative diseases of T lymphocytes and natural killer cells. These diseases frequently present with splenomegaly, neutropenia, and autoimmune diseases like rheumatoid arthritis. LGL leukemia is more commonly of a chronic, indolent nature; however, rarely, they have an aggressive course.

An efficient strategy allowed English-speaking reviewers to identify foreign-language articles eligible for a systematic review.

Objective: To assess English-speaking reviewers' accuracy in determining the eligibility of foreign-language articles for a systematic review.

Study Design And Settings: Systematic review of randomized controlled trials of therapy for fibromyalgia. Guided by 10 questions, English-speaking reviewers screened non-English-language articles for eligibility.

Selective hydrosilation of CO2 to a bis(silylacetal) using an anilido bipyridyl-ligated organoscandium catalyst.

A rigid anilido bipyridyl ligand has been designed for use in an organoscandium-based carbon dioxide hydrosilation catalyst. Ligand attachment by alkane elimination results in metalation of an aryl C-H bond in a 3,5-di-tert-butylphenyl group installed on the pyridyl unit, thus rendering the ligand tetradentate. Insertion of CO2 into the newly formed Sc-C bond leads to a κ(1) carboxylate which, when treated with the borane B(C6F5)3, becomes hemilabile.

STAT3 mutations indicate the presence of subclinical T-cell clones in a subset of aplastic anemia and myelodysplastic syndrome patients.

Large granular lymphocyte leukemia (LGL) is often associated with immune cytopenias and can cooccur in the context of aplastic anemia (AA) and myelodysplastic syndromes (MDS). We took advantage of the recent description of signal transducer and activator of transcription 3 (STAT3) mutations in LGL clonal expansions to test, using sensitive methods, for the presence of these mutations in a large cohort of 367 MDS and 140 AA cases. STAT3 clones can be found not only in known LGL concomitant cases, but in a small proportion of unsuspected ones (7% AA and 2.

Systematic review and network meta-analysis of interventions for fibromyalgia: a protocol.

Background: Fibromyalgia is associated with substantial socioeconomic loss and, despite considerable research including numerous randomized controlled trials (RCTs) and systematic reviews, there exists uncertainty regarding what treatments are effective. No review has evaluated all interventional studies for fibromyalgia, which limits attempts to make inferences regarding the relative effectiveness of treatments.

Methods/design: We will conduct a network meta-analysis of all RCTs evaluating therapies for fibromyalgia to determine which therapies show evidence of effectiveness, and the relative effectiveness of these treatments.