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Bacterial infection and antimicrobial resistance are important constraints in the production and sustainability of farmed salmonids. This retrospective study aimed to describe the frequency of bacterial isolates and antimicrobial resistance profiles in salmonid aquaculture in Atlantic Canada. Bacterial isolates and antimicrobial susceptibility testing (AST) results assessed by disk diffusion testing were summarized for 18,776 Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) samples from 2291 unique cases submitted to the Atlantic Veterinary College, Aquatic Diagnostic Services Bacteriology Laboratory from 2000 to 2021. Kidney was the most commonly submitted tissue (60.29%, n = 11,320), and these specimens were mostly submitted as swabs (63.68%, n = 11,957). The most prevalent pathogens detected in these cases were Yersinia ruckeri type 1 (5.54%, n = 127), Renibacterium salmoninarum (2.10%, n = 48), Aeromonas salmonicida (atypical) (1.66%, n = 38), and Pseudomonas fluorescens (1.22%, n = 28). Most bacterial isolates tested (n = 918) showed resistance to florfenicol, oxytetracycline, ormetoprim-sulfadimethoxine, and trimethoprim-sulfamethoxazole, but not to enrofloxacin. This report provides baseline data for antimicrobial surveillance programs that investigate emerging antimicrobial resistance trends in salmonid aquaculture in Atlantic Canada.

Background Eight out of ten adults use social media, yet its efficacy in recruitment in clinical trials remains under-explored. The purpose of this SWAT was to determine which recruitment method, X, Facebook or QR code via posters, was more efficient and cost effective for recruiting participants to the host trial. Methods A cluster randomised cross-over design evaluated three recruitment strategies, X, Facebook and QR code. Seven Gaelic Athletic Association (GAA) clubs were randomised to receive either X, Facebook, or QR code. The seven clubs were re-randomised twice more, two weeks apart. There were two primary outcomes: 1. proportion of participants who consent to participate, relative to the number of players contacted; and 2. proportion of participants who consent to participate, relative to the number of players who clicked the link to register their interest. Results Fifty participants were randomised to three recruitment methods, and 47 were retained in the host trial. Participants mainly heard about the study through friends, with some engagement via social media platforms Facebook and X, and little to no engagement with the QR code. Primary outcomes were hindered by the inability to disaggregate data by GAA club. Economic outcomes revealed QR code as the costliest strategy, and while X was cheaper than Facebook in terms of the number of clicks, Facebook demonstrated better recruitment and retention and thus reduced the costs per participant. Conclusions While the inability to disaggregate data by club was a limitation, the study revealed that Facebook outperformed X and QR codes in terms of recruitment and participant retention and was thus considered to be more cost effective. The findings emphasise the importance of considering engagement patterns and cost-effectiveness in designing recruitment strategies for clinical trials, especially within the dynamic landscape of social media use.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows rapid and reliable identification of microorganisms. The accuracy of bacterial identification using MALDI-TOF MS depends on main spectral profiles (MSPs) provided in a quality-assured commercial reference library, which requires ongoing improvement. This study aimed to develop and validate an in-house MALDI-TOF MS MSP to rapidly identify Yersinia ruckeri isolated from Atlantic salmon (Salmo salar). The novel MSP was prepared using an isolate of Y. ruckeri recovered from Atlantic salmon and confirmed by 16S rRNA gene sequencing. Subsequently, a validation set which comprises 29 isolates of Y. ruckeri were examined from three fishes: Atlantic salmon (Salmo salar) (n = 26), American eel (Anguilla rostrata) (n = 1), and Atlantic cod (Gadus morhua) (n = 2). These isolates were randomly selected from the Atlantic Veterinary College, Aquatic Diagnostic Services Bacteriology Laboratorys culture collection to validate the novel MSP. Analytical sensitivity of MALDI-TOF MS using the novel MSP to identify the validation set was 86.2%. Repeatability was assessed by acquiring spectra from 30 different spots of a randomly-selected isolate of Y. ruckeri, and analyzed spectra from each spot were compared against the novel MSP. The coefficient of variation was 3.3%. The novel MSP clustered with Bruker MSPs (n = 3) of Y. ruckeri in the reference library and did not falsely identify any closely related bacteria to Y. ruckeri. This study reports the development of a novel MSP of high analytical sensitivity and specificity for rapid identification of Y. ruckeri using MALDI-TOF MS.

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

Introduction: During the COVID-19 pandemic, screening asymptomatic admitted patients for COVID-19 became routine in order to minimize the potential risk of these individuals as silent but infectious hosts in the propagation of this pandemic. However, testing is costly and the value of this indiscriminate testing was not studied. Hence, our study aimed to determine the rates of positive COVID-19 PCR results in patients presenting to the emergency department (ED) with no suspicion for a COVID-19 infection at different times during the pandemic.Methods: This was a retrospective cohort study of asymptomatic patients presenting to the ED with no COVID infection risk factors, in an urban, tertiary care hospital in Lebanon, from March 2020 to January 2021, representing periods with different national incidence rates of COVID-19. We included patients of all ages, from the last 15 days of each month, who were tested for COVID-19 by PCR in the ED and who fulfilled the following “screening group” criteria: no travel within the last 14 days; no known COVID-19 exposure within the last 14 days; and no symptoms or physical exam findings that could be associated with a COVID-19 infection. We collected data on age, and PCR result.Results: We identified 3,853 patients who underwent COVID-19 PCR test during the above time intervals in our ED. The rate of test positivity in the community during this study period ranged from 1.1% to 21.8%. Out of the 743 (19.3%) patients that fit our inclusion criteria, none had a positive COVID-19 test.Conclusion: Even during high countrywide incidence rates of COVID-19, all patients in the screening group had a negative PCR. Algorithms identifying this group can be used to minimize a costly test, to avoid delaying inpatient care or surgeries and to reduce patient’s length of stay in already overwhelmed EDs.

The present study aims to provide a systematic understanding of how perspective-taking ability contributes to primary-school students' cooperative behaviours and learning outcomes. The present study is frontline as we combined person-oriented (e.g., describing patterns of behaviours based on individual characteristics), process-oriented (e.g., examining factors affecting the quality of cooperative behaviours), and effect-oriented (e.g., examining the effect of cooperative learning on individual learning outcomes) analytical approaches within one research framework. In addition, we adhered to the multi-dimensional nature of perspective-taking ability and differentiated between social and cognitive perspective-taking ability while taking into account the contribution of perspective-taking ability at both the individual level and group level (i.e., heterogeneous and homogeneous perspective-taking ability groups) to cooperative behaviour profiles and learning outcomes of primary-school children. Based on transcribed episodes of interaction of 115 fifth-grade students, four different profiles of cooperative behaviours were discerned: captains, hard workers, switchers, and passive participants. We found that these profiles are related to perspective taking conceptualized at the group level, but not to individual-level perspective-taking ability. Profile membership, cognitive perspective-taking ability, and group-level perspective-taking ability could not predict students' learning outcomes. Social perspective-taking ability and reading comprehension did positively predict learning outcomes. Our findings add to existing knowledge as they suggest that the influence of perspective-taking ability on cooperative behaviours and learning outcomes is susceptible to the conceptualization (i.e., cognitive vs. social) and measurement level (i.e., individual vs. group level) of perspective-taking ability.

Liposomal irinotecan is a liposomal formulation of irinotecan, which prolongs circulation of irinotecan and its active metabolite SN-38. A population pharmacokinetic (PK) model was developed based on data from seven studies (N = 440). Adequacy of the model was assessed using multiple methods, including visual predictive check. Associations between PK exposure and the incidence of diarrhea (grade ≥3) and neutropenia adverse events (AEs) (grade ≥3) at first event in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) were investigated using logistic regression based on data from two studies (the phase III NAPOLI-1 [N = 260] and phase I/II NCT02551991 [N = 56] trials). The PKs of total irinotecan was described by a two-compartment model with first-order elimination, with SN-38 formed directly by a first-order constant from the central compartment of irinotecan or after using a transit compartment. Clearance was 17.9 L/week (0.107 L/h) and 19,800 L/week (118 L/h) for total irinotecan and SN-38, respectively. The UGT1A1*28 7/7 homozygous genotype had no significant impact on SN-38 clearance. Model evaluation was satisfactory for both irinotecan and SN-38. The incidence of diarrhea (grade ≥3) at first event was significantly higher with increasing average concentrations of total irinotecan and SN-38; there was no significant association between an increased risk of neutropenia AEs (grade ≥3) at first event and average SN-38 concentrations. In summary, the PKs of total irinotecan and SN-38 after administration of liposomal irinotecan were well-described by the model. The UGT1A1*28 status had no significant impact on the PKs of liposomal irinotecan.

ObjectiveTo determine whether metformin or lifestyle modification can lower rates of all-cause and cause-specific mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.Research design and methodsFrom 1996 to 1999, 3,234 adults at high risk for type 2 diabetes were randomized to an intensive lifestyle intervention, masked metformin, or placebo. Placebo and lifestyle interventions stopped in 2001, and a modified lifestyle program was offered to everyone, but unmasked study metformin continued in those originally randomized. Causes of deaths through 31 December 2018 were adjudicated by blinded reviews. All-cause and cause-specific mortality hazard ratios (HRs) were estimated from Cox proportional hazards regression models and Fine-Gray models, respectively.ResultsOver a median of 21 years (interquartile range 20-21), 453 participants died. Cancer was the leading cause of death (n = 170), followed by cardiovascular disease (n = 131). Compared with placebo, metformin did not influence mortality from all causes (HR 0.99 [95% CI 0.79, 1.25]), cancer (HR 1.04 [95% CI 0.72, 1.52]), or cardiovascular disease (HR 1.08 [95% CI 0.70, 1.66]). Similarly, lifestyle modification did not impact all-cause (HR 1.02 [95% CI 0.81, 1.28]), cancer (HR 1.07 [95% CI 0.74, 1.55]), or cardiovascular disease (HR 1.18 [95% CI 0.77, 1.81]) mortality. Analyses adjusted for diabetes status and duration, BMI, cumulative glycemic exposure, and cardiovascular risks yielded results similar to those for all-cause mortality.ConclusionsCancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.

BackgroundNonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and cirrhosis. NAFLD is mediated by changes in lipid metabolism and known risk factors include obesity, metabolic syndrome, and diabetes. The aim of this study was to better understand differences in the lipid composition of individuals with NAFLD compared to controls, by performing direct infusion lipidomics on serum biospecimens from a cohort study of adults in Mexico.MethodsA nested case-control study was conducted with a sample of 98 NAFLD cases and 100 healthy controls who are participating in an on-going, longitudinal study in Mexico. NAFLD cases were clinically confirmed using elevated liver enzyme tests and liver ultrasound or liver ultrasound elastography, after excluding alcohol abuse, and 100 controls were identified as having at least two consecutive normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (

Brain circuits are comprised of distinct interconnected neurons that are assembled by synaptic recognition molecules presented by defined pre- and post-synaptic neurons. This cell-cell recognition process is mediated by varying cellular adhesion molecules, including the latrophilin family of adhesion G-protein-coupled receptors. Focusing on parahippocampal circuitry, we find that latrophilin-2 (Lphn2; gene symbol ADGRL2) is specifically enriched in interconnected subregions of the medial entorhinal cortex (MEC), presubiculum (PrS), and parasubiculum (PaS). Retrograde viral tracing from the Lphn2-enriched region of the MEC reveals unique topographical patterning of inputs arising from the PrS and PaS that mirrors Lphn2 expression. Using a Lphn2 conditional knockout mouse model, we find that deletion of MEC Lphn2 expression selectively impairs retrograde viral labeling of inputs arising from the ipsilateral PrS. Combined with analysis of Lphn2 expression within the MEC, this study reveals Lphn2 to be selectively expressed by defined cell types and essential for MEC-PrS circuit connectivity.

Commitment to teaching is a recurring topic in both research and policy discussions on teaching and the teaching profession. We investigated factors explaining differences in student-teachers' commitment to the teaching profession and to student learning, and their intentions to enter the teaching profession. Student-teachers (n = 3,246) from one University College in Tanzania completed a Commitment-to-Teaching questionnaire. Bandura's Social-Cognitive Theory was used to explain the findings. Differences in student-teachers' commitment were explained by personal characteristics (i.e., student-teachers' sense of self-efficacy), environmental factors (i.e., perceived influence of significant others and school conditions), and learning experiences (i.e., student-teachers' attitudes towards the teaching profession, their teaching subjects, and satisfaction with the teacher education programme). Implications for practice and for research on student-teachers' commitment to teaching are discussed.

Nimy John,1 Brittney Ibrahim,2 Mark Ebaid,2 Sammy Saab1,2 1Department of Medicine, University of California, Los Angeles, CA, USA; 2Department of Surgery, University of California, Los Angeles, CA, USACorrespondence: Sammy Saab, Departments of Medicine and Surgery, 200 Medical Plaza, Suite 214, Los Angeles, CA, 90095, USA, Tel +1 310 206 6705, Fax +1 310-206-4197, Email Ssaab@mednet.ucla.eduAim: Since 2019, the COVID-19 pandemic wreaked havoc all over the world. Early in the course of the pandemic, multiple hepatic manifestations of COVID-19 were noted. We aim to categorize hepatic dysfunction and its outcome in COVID-19 infection.Methods: This is a review article based on a literature search in PubMed and Medline databases for articles detailing short-term and long-term outcomes of COVID-19 related liver dysfunction.Results: The most common hepatic manifestation of COVID-19 was aspartate amino transferase (AST) predominant transaminase elevation. Transaminases improve once the COVID-19 infection resolves. In addition, COVID-19 cholangiopathy, autoimmune hepatitis associated COVID-19, and splanchnic venous thrombosis triggered by COVID-19 are other manifestations. Patients with preexisting liver disease, especially those with cirrhosis, have poor prognosis with COVID-19 infections compared to the general population. Elevations in liver tests were associated with severe COVID-19 infections. Patients with chronic liver disease have a higher risk of morbidity and mortality from COVID-19 infection. Among patients with chronic liver disease, decompensated liver cirrhosis, hepatocellular carcinoma and alcohol-associated liver disease were associated with an increased risk of severity and mortality from COVID-19 infection. Interactions between antiviral therapy for COVID-19 and hepatitis B/hepatitis C medications must be considered in patients with chronic viral hepatitis and COVID-19 infection. COVID-19 vaccination-related hepatic dysfunction has been reported.Conclusion: COVID-19 is here to stay. Hepatic dysfunction in COVID-19 signals severe COVID-19 infections. Patients with chronic liver disease have higher mortality from COVID-19 than general population. It is important to remember the lessons learned throughout the covid pandemic to take care of patients with COVID-19 now and in the future. Further studies are needed to document long-term outcomes in patients with COVID-19 who developed hepatic dysfunction.Keywords: COVID-19, liver injury, cirrhosis, thrombosis, cholangiopathy

Background Sjogren-Larsson syndrome (SLS) is a neurocutaneous disease with an autosomal recessive inheritance, caused by mutations in the gene that encodes fatty aldehyde dehydrogenase (ALDH3A2), clinically characterized by ichthyosis, spastic diplegia, and cognitive impairment. Brain imaging plays an essential role in the diagnosis, demonstrating a nonspecific leukoencephalopathy. Data regarding brain atrophy and grey matter involvement is scarce and discordant.

Insect humoral immune responses are regulated in part by protease cascades, whose components circulate as zymogens in the hemolymph. In mosquitoes, these cascades consist of clip-domain serine proteases (cSPs) and/or their non-catalytic homologs, which form a complex network, whose molecular make-up is not fully understood. Using a systems biology approach, based on a co-expression network of gene family members that function in melanization and co-immunoprecipitation using the serine protease inhibitor (SRPN)2, a key negative regulator of the melanization response in mosquitoes, we identify the cSP CLIPB4 from the African malaria mosquito Anopheles gambiae as a central node in this protease network. CLIPB4 is tightly co-expressed with SRPN2 and forms protein complexes with SRPN2 in the hemolymph of immune-challenged female mosquitoes. Genetic and biochemical approaches validate our network analysis and show that CLIPB4 is required for melanization and antibacterial immunity, acting as a prophenoloxidase (proPO)-activating protease, which is inhibited by SRPN2. In addition, we provide novel insight into the structural organization of the cSP network in An. gambiae, by demonstrating that CLIPB4 is able to activate proCLIPB8, a cSP upstream of the proPO-activating protease CLIPB9. These data provide the first evidence that, in mosquitoes, cSPs provide branching points in immune protease networks and deliver positive reinforcement in proPO activation cascades.