Interlaboratory Study on Zebrafish in Toxicology: Systematic Evaluation of the Application of Zebrafish in Toxicology's (SEAZIT's) Evaluation of Developmental Toxicity.

Embryonic zebrafish represent a useful test system to screen substances for their ability to perturb development. The exposure scenarios, endpoints captured, and data analysis vary among the laboratories who conduct screening. A lack of harmonization impedes the comparison of the substance potency and toxicity outcomes across laboratories and may hinder the broader adoption of this model for regulatory use.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations-IBD in Seniors.

Approximately one out of every 88 seniors has inflammatory bowel disease (IBD), and this is expected to increase in the future. They are more likely to have left-sided disease in ulcerative colitis, and isolated colonic disease in Crohn's disease; perianal disease is less common. Other common diagnoses in the elderly must also be considered when they initially present to a healthcare provider.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Cancer and IBD.

Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Treatment Landscape.

The therapeutic landscape for inflammatory bowel disease (IBD) has changed considerably over the past two decades, owing to the development and widespread penetration of targeted therapies, including biologics and small molecules. While some conventional treatments continue to have an important role in the management of IBD, treatment of IBD is increasingly moving towards targeted therapies given their greater efficacy and safety in comparison to conventional agents. Early introduction of these therapies-particularly in persons with Crohn's disease-combining targeted therapies with traditional anti-metabolite immunomodulators and targeting objective markers of disease activity (in addition to symptoms), have been shown to improve health outcomes and will be increasingly adopted over time.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Mental Health and Inflammatory Bowel Disease.

Psychiatric disorders are 1.5 to 2 times more prevalent in persons with inflammatory bowel disease (IBD) than in the general population, with pooled prevalence estimates of 21% for clinical anxiety and 15% for depression. Rates are even higher when considering mental health symptoms, as nearly one-third of persons with IBD experience elevated anxiety symptoms and one-quarter experience depression symptoms.

The 2023 Impact of Inflammatory Bowel Disease in Canada: The Influence of Sex and Gender on Canadians Living With Inflammatory Bowel Disease.

Sex (the physical and physiologic effects resulting from having specific combinations of sex chromosomes) and gender (sex-associated behaviours, expectations, identities, and roles) significantly affect the course of inflammatory bowel disease (IBD) and the experience of living with IBD. Sex-influenced physiologic states, like puberty, the menstrual cycle, pregnancy, and andropause/menopause may also impact and be impacted by IBD. While neither Crohn's disease nor ulcerative colitis is commonly considered sex-determined illnesses, the relative incidence of Crohn's disease and ulcerative colitis between males and females varies over the life cycle.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations-Children and Adolescents with IBD.

Rates of inflammatory bowel disease (IBD) in Canadian children and adolescents are among the highest in the world, and the incidence is rising most rapidly in children under five years of age. These young children may have either a typical form of IBD with multi-factorial aetiology, or they may have a monogenic form. Despite the growing number of children in Canada living with this important chronic disease, there are few available medical therapies approved by Health Canada due to the omission of children from most clinical trials of newly developed biologics.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Access to and Models of Care.

Rising compounding prevalence of inflammatory bowel disease (IBD) (Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Direct Health System and Medication Costs.

Healthcare utilization among people living with inflammatory bowel disease (IBD) in Canada has shifted from inpatient management to outpatient management; fewer people with IBD are admitted to hospitals or undergo surgery, but outpatient visits have become more frequent. Although the frequency of emergency department (ED) visits among adults and seniors with IBD decreased, the frequency of ED visits among children with IBD increased. Additionally, there is variation in the utilization of IBD health services within and between provinces and across ethnocultural and sociodemographic groups.

Adverse Events and Serological Responses After SARS-CoV-2 Vaccination in Individuals With Inflammatory Bowel Disease.

Introduction: We determined adverse events after 4 doses of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in those with inflammatory bowel disease (IBD), associations between antibodies and injection site reactions (ISR), and risk of IBD flare.

Methods: Individuals with IBD were interviewed for adverse events to SARS-CoV-2 vaccine. Multivariable linear regression assessed the association between antibody titers and ISR.

Utilizing paralogues for phylogenetic reconstruction has the potential to increase species tree support and reduce gene tree discordance in target enrichment data.

The analysis of target enrichment data in phylogenetics lacks optimization toward using paralogues for phylogenetic reconstruction. We developed a novel approach of detecting paralogues and utilizing them for phylogenetic tree inference, by retrieving both ortho- and paralogous copies and creating orthologous alignments, from which the gene trees are built. We implemented this approach in ParalogWizard and demonstrate its performance in plant groups that underwent a whole genome duplication relatively recently: the subtribe Malinae (family Rosaceae), using Angiosperms353 as well as Malinae481 probes, the genus Oritrophium (family Asteraceae), using Compositae1061 probes, and the genus Amomum (family Zingiberaceae), using Zingiberaceae1180 probes.

A state-of-the-art implementation of a binaural cochlear-implant sound coding strategy inspired by the medial olivocochlear reflex.

Cochlear implant (CI) users find it hard and effortful to understand speech in noise with current devices. Binaural CI sound processing inspired by the contralateral medial olivocochlear (MOC) reflex (an approach termed the 'MOC strategy') can improve speech-in-noise recognition for CI users. All reported evaluations of this strategy, however, disregarded automatic gain control (AGC) and fine-structure (FS) processing, two standard features in some current CI devices.

A Generalization Performance Study Using Deep Learning Networks in Embedded Systems.

Deep learning techniques are being increasingly used in the scientific community as a consequence of the high computational capacity of current systems and the increase in the amount of data available as a result of the digitalisation of society in general and the industrial world in particular. In addition, the immersion of the field of edge computing, which focuses on integrating artificial intelligence as close as possible to the client, makes it possible to implement systems that act in real time without the need to transfer all of the data to centralised servers. The combination of these two concepts can lead to systems with the capacity to make correct decisions and act based on them immediately and in situ.

Speech-in-Noise Recognition With More Realistic Implementations of a Binaural Cochlear-Implant Sound Coding Strategy Inspired by the Medial Olivocochlear Reflex.

Objectives: Cochlear implant (CI) users continue to struggle understanding speech in noisy environments with current clinical devices. We have previously shown that this outcome can be improved by using binaural sound processors inspired by the medial olivocochlear (MOC) reflex, which involve dynamic (contralaterally controlled) rather than fixed compressive acoustic-to-electric maps. The present study aimed at investigating the potential additional benefits of using more realistic implementations of MOC processing.

Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes.

A 5-day in vivo rat model was evaluated as an approach to estimate chemical exposures that may pose minimal risk by comparing benchmark dose (BMD) values for transcriptional changes in the liver and kidney to BMD values for toxicological endpoints from traditional toxicity studies. Eighteen chemicals, most having been tested by the National Toxicology Program in 2-year bioassays, were evaluated. Some of these chemicals are potent hepatotoxicants (eg, DE71, PFOA, and furan) in rodents, some exhibit toxicity but have minimal hepatic effects (eg, acrylamide and α,β-thujone), and some exhibit little overt toxicity (eg, ginseng and milk thistle extract) based on traditional toxicological evaluations.

Preclinical toxicity evaluation of JD5037, a peripherally restricted CB receptor inverse agonist, in rats and dogs for treatment of nonalcoholic steatohepatitis.

JD5037 is a novel peripherally restricted CB receptor (CBR) inverse agonist being developed for the treatment of visceral obesity and its metabolic complications, including nonalcoholic fatty liver disease and dyslipidemia. JD5037 was administered by oral gavage at 10, 40, and 150 mg/kg/day dose levels for up to 34 days to Sprague Dawley rats, and at 5, 20, and 75 mg/kg/day dose levels for 28 consecutive days to Beagle dogs. In rats, higher incidences of stereotypic behaviors were observed in 10 mg/kg females and 40 mg/kg males, and slower responses for reflex and sensory tests were observed only in males at 10 and 40 mg/kg during neurobehavioral testing.

Lateralization of virtual sound sources with a binaural cochlear-implant sound coding strategy inspired by the medial olivocochlear reflex.

Many users of bilateral cochlear implants (BiCIs) localize sound sources less accurately than do people with normal hearing. This may be partly due to using two independently functioning CIs with fixed compression, which distorts and/or reduces interaural level differences (ILDs). Here, we investigate the potential benefits of using binaurally coupled, dynamic compression inspired by the medial olivocochlear reflex; an approach termed "the MOC strategy" (Lopez-Poveda et al.

Adaptation to noise in amplitude modulation detection without the medial olivocochlear reflex.

The detection of amplitude modulation (AM) in quiet or in noise improves when the AM carrier is preceded by noise, an effect that has been attributed to the medial olivocochlear reflex (MOCR). We investigate whether this improvement can occur without the MOCR by measuring AM sensitivity for cochlear implant (CI) users, whose MOCR effects are circumvented as a result of the electrical stimulation provided by the CI. AM detection thresholds were measured monaurally for short (50 ms) AM probes presented at the onset (early condition) or delayed by 300 ms (late condition) from the onset of a broadband noise.

Intelligibility in speech maskers with a binaural cochlear implant sound coding strategy inspired by the contralateral medial olivocochlear reflex.

We have recently proposed a binaural cochlear implant (CI) sound processing strategy inspired by the contralateral medial olivocochlear reflex (the MOC strategy) and shown that it improves intelligibility in steady-state noise (Lopez-Poveda et al., 2016, Ear Hear 37:e138-e148). The aim here was to evaluate possible speech-reception benefits of the MOC strategy for speech maskers, a more natural type of interferer.

GFAP mutations, age at onset, and clinical subtypes in Alexander disease.

Objective: To characterize Alexander disease (AxD) phenotypes and determine correlations with age at onset (AAO) and genetic mutation. AxD is an astrogliopathy usually characterized on MRI by leukodystrophy and caused by glial fibrillary acidic protein (GFAP) mutations.

Methods: We present 30 new cases of AxD and reviewed 185 previously reported cases.