Electronic structure of metal oxide dications with ammonia ligands and their reactivity towards the selective conversion of methane to methanol.

High-level quantum chemical calculations are performed for the (NH)MO and (NH)MO species (M = Ti-Cu), extending our previous work on the bare MO ions. The potential energy curves along the M-O distance are constructed for the ground and multiple excited electronic states of (NH)MO and are compared to those of MO. We see that ammonia stabilizes the oxo states (MO) over the oxyl (MO) ones.

A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant.

Background: To date, the only potential curative treatment for multiple myeloma (MM) remains allogeneic (allo) hematopoietic cell transplant (HCT), although, most patients will eventually relapse. In relapsed patients, donor lymphocyte infusions (DLIs) have been reported to control disease, but the optimal strategy prior to and doses of DLIs remain unclear. With this study (NCT03413800), we aimed to investigate the efficacy and toxicity of lenalidomide and dexamethasome (Len/Dex) followed by escalating pre-determined doses of DLIs in MM patients who relapsed after allo HCT.

Repeatability of Ad Libitum Water Intake during Repeated 1 h Walking/Jogging Exercise Sessions Conducted under Hot Ambient Conditions.

A drinking strategy aiming to replace a given percentage of the sweat losses incurred during exercise should result in reproducible fluid intake volume and, hence, fluid balance from one exercise session to the other performed under similar scenarios. Whether this may also be the case with ad libitum drinking during exercise is unclear. We characterized the repeatability of ad libitum water intake during repeated 1 h exercise sessions and examined its effect over time on fluid balance and selected physiological functions and perceptual sensations.

Optical Genome Mapping Reveals the Complex Genetic Landscape of Myeloma.

Fluorescence in situ hybridization (FISH) on enriched CD138 plasma cells is the standard method for identification of clinically relevant genetic abnormalities in multiple myeloma. However, FISH is a targeted analysis that can be challenging due to the genetic complexity of myeloma. The aim of this study was to evaluate the potential of optical genome mapping (OGM) to detect clinically significant cytogenetic abnormalities in myeloma and to provide larger pangenomic information.

Methane against Methanol: The Tortoise and the Hare of the Oxidation Race.

The selective partial oxidation of methane to methanol has been a major chemistry challenge over the past several decades. The reason for this is that the weaker C-H bond of the desired product (methanol) is readily activated by the same catalyst used to activate the stronger C-H bond of methane. Quantum chemical calculations reveal how hydrogen-bonding interactions with the catalyst as well as other electronic and geometric effects slow the unwanted methanol oxidation reaction.

Real-World Effectiveness of Nirmatrelvir/Ritonavir on Coronavirus Disease 2019-Associated Hospitalization Prevention: A Population-based Cohort Study in the Province of Quebec, Canada.

Background: Nirmatrelvir/ritonavir has shown to reduce COVID-19 hospitalization and death before Omicron, but updated real-world evidence studies are needed. This study aimed to assess whether nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among high-risk outpatients.

Methods: A retrospective cohort study of outpatients with SARS-CoV-2 between March 15 and 15 October 2022, using data from the Quebec clinico-administrative databases.

Transition metal oxide complexes as molecular catalysts for selective methane to methanol transformation: any prospects or time to retire?

Transition metal oxides have been extensively used in the literature for the conversion of methane to methanol. Despite the progress made over the past decades, no method with satisfactory performance or economic viability has been detected. The main bottleneck is that the produced methanol oxidizes further due to its weaker C-H bond than that of methane.

Effect of Pre-Exercise Caffeine Intake on Endurance Performance and Core Temperature Regulation During Exercise in the Heat: A Systematic Review with Meta-Analysis.

Background: Heat is associated with physiological strain and endurance performance (EP) impairments. Studies have investigated the impact of caffeine intake upon EP and core temperature (C) in the heat, but results are conflicting. There is a need to systematically determine the impact of pre-exercise caffeine intake in the heat.

Cognitive Performance Before and Following Habituation to Exercise-Induced Hypohydration of 2 and 4% Body Mass in Physically Active Individuals.

We investigated the effect of repeated exposures to hypohydration upon cognitive performance. In a randomized crossover design, ten physically active adults completed two 4-week training blocks, one where they maintained euhydration (EUH) and the other where they were water-restricted (DEH) during walking/running at 55% V.O2max, 40 °C.

Programmed vs. Thirst-Driven Drinking during Prolonged Cycling in a Warm Environment.

We compared the effect of programmed (PFI) and thirst-driven (TDFI) fluid intake on prolonged cycling performance and exercise associated muscle cramps (EAMC). Eight male endurance athletes (26 ± 6 years) completed two trials consisting of 5 h of cycling at 61% V˙O2peak followed by a 20 km time-trial (TT) in a randomized crossover sequence at 30 °C, 35% relative humidity. EAMC was assessed after the TT with maximal voluntary isometric contractions of the shortened right plantar flexors.

Impact of Repeated Acute Exposures to Low and Moderate Exercise-Induced Hypohydration on Physiological and Subjective Responses and Endurance Performance.

This study aimed to examine whether repeated exposures to low (2%) and moderate (4%) exercise-induced hypohydration may reverse the potentially deleterious effect of hypohydration on endurance performance. Using a randomized crossover protocol, ten volunteers (23 years, V˙O: 54 mL∙kg∙min) completed two 4-week training blocks interspersed by a 5-week washout period. During one block, participants replaced all fluid losses (EUH) while in the other they were fluid restricted (DEH).

Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.

Background: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum.

Management of Pyrexia Associated with the Combination of Dabrafenib and Trametinib: Canadian Consensus Statements.

The combination of dabrafenib and trametinib is a well-established treatment for BRAF-mutated melanoma. However, the effectiveness of this approach may be hindered by the development of treatment-related pyrexia syndrome, which occurs in at least 50% of treated patients. Without appropriate intervention, pyrexia syndrome has the potential to worsen and can result in hypotension secondary to dehydration and associated organ-related complications.

Electronic structure of the dicationic first row transition metal oxides.

Multi-reference electronic structure calculations combined with large basis sets are performed to investigate the electronic structure of the ground and low-lying electronic states of the MO diatomic species with M = Ti-Cu. These systems have shown high efficiency in the activation of the C-H of saturated hydrocarbons. This study is the first systematic and accurate work for these systems and our results and discussion provides insights into the reactivity and stability of MO units.

Provision of instructions to drink ad libitum or according to thirst sensation: impact during 120 km of cycling in the heat in men.

The terms drinking to thirst and ad libitum drinking are used interchangeably, but should they? We investigated the differences in how athletes consumed fluids during exercise when instructed to drink according to thirst or ad libitum. Using a randomized, crossover, and counterbalanced design, 10 males (27 ± 4 y) cycled 120 km (48 ± 4% of peak power, 33 °C, 40% relative humidity) on 2 occasions, while drinking water according to thirst or ad libitum. Participants covered the cycling trials in 222 ± 11 min ( = 0.

Defining the Criteria for Reflex Testing for Mutations in Cutaneous Melanoma Patients.

Targeted therapy has been developed through an in-depth understanding of molecular pathways involved in the pathogenesis of melanoma. Approximately ~50% of patients with melanoma have tumors that harbor a mutation of the oncogene. Certain clinical features have been identified in -mutated melanomas (primary lesions located on the trunk, diagnosed in patients <50, visibly pigmented tumors and, at times, with ulceration or specific dermatoscopic features).

Gymnotic delivery and gene silencing activity of reduction-responsive siRNAs bearing lipophilic disulfide-containing modifications at 2'-position.

Modified oligoribonucleotides used as siRNAs bearing biolabile disulfide-containing groups at some 2'-positions were synthesized following a post-synthesis transformation of solid-supported 2'-O-acetylthiomethyl RNA, previously described. Thus, the reduction-responsive and lipophilic benzyldithiomethyl (BnSSM) modification was introduced at different locations into siRNAs targeting the Ewing sarcoma EWS-Fli1 protein. Thermal stability, serum stability and response to glutathione treatment of modified siRNAs were thoroughly investigated.

Methylmercury effects on migratory behaviour in glass eels (Anguilla anguilla): an experimental study using isotopic tracers.

The effect of methylmercury (MeHg) on glass eels' propensity to migrate, mitochondrial activity and antioxidative defence systems was investigated. Marine glass eels were first sorted in an experimental flume according to their response to dusk. Fish responding to the decrease in light intensity by ascending in the water column and moving with or against the flow were considered as having a high propensity to migrate (migrant).

Detection of Listeria spp. using ACTERO listeria enrichment media.

ACTERO Listeria Enrichment Media (ACTERO Listeria) is a selective medium developed for a single-step recovery and enrichment of Listeria spp. from environmental samples. Robustness testing of the ACTERO Listeria medium demonstrated good performance when minor changes were introduced to the incubation temperature and time.

Broadening the spectrum of β-lactam antibiotics through inhibition of signal peptidase type I.

The resistance of methicillin-resistant Staphylococcus aureus (MRSA) to all β-lactam classes limits treatment options for serious infections involving this organism. Our goal is to discover new agents that restore the activity of β-lactams against MRSA, an approach that has led to the discovery of two classes of natural product antibiotics, a cyclic depsipeptide (krisynomycin) and a lipoglycopeptide (actinocarbasin), which potentiate the activity of imipenem against MRSA strain COL. We report here that these imipenem synergists are inhibitors of the bacterial type I signal peptidase SpsB, a serine protease that is required for the secretion of proteins that are exported through the Sec and Tat systems.

Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population.

Mucolipidosis (ML) II (I-cell disease) is a lysosomal storage disorder caused by a deficiency of UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase. MLII is an autosomal recessive disease with a carrier rate estimated at 1/39 in Saguenay-Lac-Saint-Jean (SLSJ) (Quebec, Canada), which is the highest frequency documented worldwide. To identify the causing mutation, we sequenced GNPTAB exons in 27 parents of 16 MLII-deceased children from the SLSJ region as obligatory and potential carriers.

AZT binding to Na,K-ATPase.

3'-azido-3'-deoxythymidine (AZT) is the first effective drug used clinically for the treatment of human immunodeficiency virus (HIV) infection. The drug interactions with DNA and protein are associated with its mechanism of action in vivo. This study was designed to examine the interaction of AZT with the Na,K-dependent adenosine triphosphatase (Na,K-ATPase) in H2O and D2O solutions at physiological pH using drug concentration of 0.

Interacting influence of light and size on aboveground biomass distribution in sub-boreal conifer saplings with contrasting shade tolerance.

Plant size often influences shade tolerance but relatively few studies have considered the functional response of taller plants to contrasting light environments. Several boreal and sub-boreal Abies, Picea and Pinus species were studied along a light (0-90% full sunlight) and size (30-400-cm high) gradient to examine the interactive influence of tree size and light availability on aboveground biomass distribution. Sampling was conducted in two regions of Canada: (A) British Columbia, for Abies lasiocarpa (Hook.

Basement membrane protein and matrix metalloproteinase deregulation in engineered human oral mucosa following infection with Candida albicans.

A variety of morphological changes in the basement membrane (BM) are known to occur in inflammatory diseases. Modifications of the BM can be associated with significant changes in protein content. Candida albicans (C.

Single-point mutations at the surface of MB-1Trp lead to important changes in its conformational properties.

Protein design is currently used for the creation of new proteins with desirable traits. In our lab we focus on the synthesis of proteins with high essential amino acid content having potential applications in animal nutrition. One of the limitations we face in this endeavour is achieving stable proteins despite a highly biased amino acid content.