Update on copper and selenium in Canadian cow-calf herds: regional differences and estimation of serum reference values.

Trace mineral supplementation of beef cattle is essential for efficient reproduction and herd health. Understanding regional differences in cow trace mineral status could inform decisions about risks of deficiencies and supplementation management. Cow-calf surveillance projects provided three opportunities to evaluate the trace mineral status of Canadian beef cow herds. Blood samples were collected at pregnancy testing in 2014 from 102 cow-calf herds and in 2016 from 86 cow-calf herds in Western Canada. In 2019, blood samples were collected at pregnancy testing from cows in 163 cow-calf herds from Eastern and Western Canada. Serum samples were analyzed for copper, selenium, and molybdenum concentrations using a plasma mass spectrometer. The prevalence of copper deficient cows sampled from the Western provinces ranged from 24% to 43% across the three periods, and was 20% from Eastern Canada in 2019. The prevalence of selenium deficient cows ranged from 0.2% to 0.4% across the three projects in Western Canada, but was higher in Eastern Canada at 4.6% in 2019. High serum molybdenum was identified in 9.4% to 14% of cows across the three periods in Western Canada and in 15% of cows sampled in Eastern Canada in 2019. Serum copper, selenium, and molybdenum concentrations varied by cow age and month of sample collection. Serum selenium and molybdenum concentrations, but not copper, varied by soil type associated with the location of the farm. A subsample of samples from cows from Western Canadian herds provided body condition score (BCS) data, pregnancy status, and calf survival data and were used to estimate updated serum reference values for adequate concentrations. Age-specific values were required for selenium and molybdenum. Reference intervals (80%) were estimated from 2,406 pregnant beef cows from 99 herds with each cow having a BCS ≥ 2.5/5 and a live calf at 3 wk with no retained placenta: copper for all cows (0.379 to 0.717 ppm), selenium for cows <4 yr (0.052 to 0.152 ppm), and selenium for cows ≥4 yr (0.064 to 0.184 ppm). Upper 90% reference limits were also estimated for serum molybdenum for cows <4 yr (>0.104 ppm) and cows ≥4 yr (>0.110 ppm). The lower limits for the reference intervals for adequate copper and selenium are below those previously reported; nevertheless, they represent a large sample that was specifically applicable to extensively managed beef animals in western Canada.

Time for a Change: Considering Vancomycin Alternatives for Pediatric Methicillin-Resistant Staphylococcus aureus Bacteremia.

Vancomycin remains the standard of care for treating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in pediatrics largely because no alternative antibiotic is definitively superior. Long-standing historical precedent and S. aureus' notable lack of vancomycin resistance are clear benefits, but vancomycin's use remains plagued by nephrotoxicity and the need for therapeutic drug monitoring, with inadequate consensus on how best to dose or monitor vancomycin in pediatrics. Daptomycin, ceftaroline, and linezolid are all promising alternatives, with improved safety relative to vancomycin. However, inadequate and variable efficacy data limit confidence in their use. Despite this, we contend that it is time for clinicians to reconsider vancomycin's place in clinical use. In this review, we summarize the supporting data for using vancomycin versus these other anti-MRSA antibiotics, present a framework for antibiotic decision-making that considers patient-specific factors, and discuss approaches to antibiotic selection for various etiologies of MRSA bacteremia. This review aims to help pediatric clinicians choose among the various treatment options for MRSA bacteremia, acknowledging that the optimal antibiotic choice is sometimes uncertain.

How to not revert to type: Complexity-informed learnings from the pandemic response for health system reform and universal access to integrated care.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Background: COVID-19 has highlighted existing health inequalities and health system deficiencies both in Ireland and internationally; however, understanding of the critical opportunities for health system change that have arisen during the pandemic is still emerging and largely descriptive. This research is situated in the Irish health reform context of Sláintecare, the reform programme which aims to deliver universal healthcare by strengthening public health, primary and community healthcare functions as well as tackling system and societal health inequities. Aims and objectives: This study set out to advance understanding of how and to what extent COVID-19 has highlighted opportunities for change that enabled better access to universal, integrated care in Ireland, with a view to informing universal health system reform and implementation. Methods: The study, which is qualitative, was underpinned by a co-production approach with Irish health system leadership. Semi-structured interviews were conducted with sixteen health system professionals (including managers and frontline workers) from a range of responses to explore their experiences and interpretations of social processes of change that enabled (or hindered) better access to universal integrated care during the pandemic. A complexity-informed approach was mobilized to theorize the processes that impacted on access to universal, integrated care in Ireland in the COVID-19 context. Findings: A range of circumstances, strategies and mechanisms that created favorable system conditions in which new integrated care trajectories emerged during the crisis. Three key learnings from the pandemic response are presented: (1) nurturing whole-system thinking through a clear, common goal and shared information base; (2) harnessing, sharing and supporting innovation; and (3) prioritizing trust and relationship-building in a social, human-centered health system. Policy and practice implications for health reform are discussed.

Results of exploratory investigation into adherence to auditory coping instructions during an acutely stressful task.

Healthcare providers often perform under significant stress, during which their performance must be optimal, but is known to suffer. Stress management interventions in this context can provide cognitive support to rescue performance. This exploratory study sought to evaluate the effect of stress intervention components on stress and performance while clinicians engaged in two versions of a computer-based task, differing in overall level of demand: one high-stress and one low-stress. Participants (N = 45) were assigned to one of five groups (N = 9 per group), where they each completed both versions of the task, under different conditions of cognitive support. Group 1 received no intervention; Group 2 received biofeedback; and Group 3 received biofeedback and explicit coping instructions. Group 4 received emotional intelligence training, and Group 5 received emotional intelligence training and biofeedback. We hypothesized that Group 3 participants would present the lowest self-reported and physiological measures of stress, and the highest performance. Results reveal that the high-stress task induced significantly higher self-reported and physiological stress/anxiety, and lower task performance. No significant main effects of experimental condition or interaction effects were detected, indicating that intervention components had minimal effect on stress and performance. However, ultra-short term physiological analysis, analyzing <5 min of HRV data, revealed significantly decreased stress (SDNN, the standard deviation of normal-to-normal peaks) following auditory coping instructions. Exploratory study results suggest that although cognitive intervention components had minimal effect on stress and performance, physiological stress may be significantly reduced immediately following adherence to a coping instruction intervention. Future work is needed.Lay summaryThis exploratory study evaluated the potential benefit of providing healthcare practitioners with various stress management components during an acutely stressful task. Our results support the positive effect of following behavioral coping instructions on immediate physiological measures of stress.

Engaging Youth (Adolescents and Young Adults) to Change Frequent Marijuana Use: Motivational Enhancement Therapy (MET) in Primary Care.

PURPOSE: To characterize information elicited from adolescent/young adults with frequent cannabis use in Motivational Enhancement Therapy (MET), and determine whether differences exist across stages of change (SOC) for reducing use. DESIGN AND METHODS: Primary care patients 15-24 years old using cannabis ≥3 times/week enrolled in a pilot randomized intervention trial. All youth were offered two 1-hour MET sessions. Content analysis was used to code and categorize main reasons for use, alternative behaviors, goals, values, pros and cons of change, and compared results between youth in Pre-Contemplation vs. Contemplation SOC. RESULTS: Fifty-six youth completed MET session 1, 46 completed session 2. Most reported their main reason for use was related to emotional coping, negative feelings were a top-3 trigger, and distraction was an alternative way to meet their needs. Youth most frequently described progress in education or career/job as 1-year goals. More than half identified family as a very important value. They most frequently reported pros of using less related to achieving goals, self-improving, and saving money, and a con related to stress/coping. Compared to youth in Pre-Contemplation SOC, those in Contemplation were more likely to identify relationships as both a pro and con of using less cannabis. CONCLUSIONS: MET can reveal developmentally appropriate goals, healthy values, and ambivalence about cannabis use that can be used to facilitate movement along the stages of behavior change toward reduction/cessation. PRACTICE IMPLICATIONS: Brief motivational therapy can be used in primary care to gather information important in helping youth to reduce cannabis use.

Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and Antimicrobial Stewardship.

New rapid molecular diagnostic technologies for infectious diseases enable expedited accurate microbiological diagnoses. However, diagnostic stewardship and antimicrobial stewardship are necessary to ensure that these technologies conserve, rather than consume, additional health care resources and optimally affect patient care. Diagnostic stewardship is needed to implement appropriate tests for the clinical setting and to direct testing toward appropriate patients. Antimicrobial stewardship is needed to ensure prompt appropriate clinical action to translate faster diagnostic test results in the laboratory into improved outcomes at the bedside. This minireview outlines the roles of diagnostic stewardship and antimicrobial stewardship in the implementation of rapid molecular infectious disease diagnostics.

Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach.

For nearly a century, aluminum salts have been the most widely used vaccine adjuvant formulation, and have thus established a history of safety and efficacy. Nevertheless, for extremely challenging disease targets such as tuberculosis or HIV, the adjuvant activity of aluminum salts may not be potent enough to achieve protective efficacy. Adsorption of TLR ligands to aluminum salts facilitates enhanced adjuvant activity, such as in the human papilloma virus vaccine Cervarix®. However, some TLR ligands such as TLR7/8 agonist imidazoquinolines do not efficiently adsorb to aluminum salts. The present report describes a formulation approach to solving this challenge by developing a lipid-based nanosuspension of a synthetic TLR7/8 ligand (3M-052) that facilitates adsorption to aluminum oxyhydroxide via the structural properties of the helper lipid employed. In immunized mice, the aluminum oxyhydroxide-adsorbed formulation of 3M-052 enhanced antibody and TH1-type cellular immune responses to vaccine antigens for tuberculosis and HIV.

Kinase Inhibitor Screening Identifies Cyclin-Dependent Kinases and Glycogen Synthase Kinase 3 as Potential Modulators of TDP-43 Cytosolic Accumulation during Cell Stress.

Abnormal processing of TAR DNA binding protein 43 (TDP-43) has been identified as a major factor in neuronal degeneration during amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD). It is unclear how changes to TDP-43, including nuclear to cytosolic translocation and subsequent accumulation, are controlled in these diseases. TDP-43 is a member of the heterogeneous ribonucleoprotein (hnRNP) RNA binding protein family and is known to associate with cytosolic RNA stress granule proteins in ALS and FTLD. hnRNP trafficking and accumulation is controlled by the action of specific kinases including members of the mitogen-activated protein kinase (MAPK) pathway. However, little is known about how kinase pathways control TDP-43 movement and accumulation. In this study, we used an in vitro model of TDP-43-positve stress granule formation to screen for the effect of kinase inhibitors on TDP-43 accumulation. We found that while a number of kinase inhibitors, particularly of the MAPK pathways modulated both TDP-43 and the global stress granule marker, human antigen R (HuR), multiple inhibitors were more specific to TDP-43 accumulation, including inhibitors of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3 (GSK3). Close correlation was observed between effects of these inhibitors on TDP-43, hnRNP K and TIAR, but often with different effects on HuR accumulation. This may indicate a potential interaction between TDP-43, hnRNP K and TIAR. CDK inhibitors were also found to reverse pre-formed TDP-43-positive stress granules and both CDK and GSK3 inhibitors abrogated the accumulation of C-terminal TDP-43 (219-414) in transfected cells. Further studies are required to confirm the specific kinases involved and whether their action is through phosphorylation of the TDP-43 binding partner hnRNP K. This knowledge provides a valuable insight into the mechanisms controlling abnormal cytoplasmic TDP-43 accumulation and may herald new opportunities for kinase modulation-based therapeutic intervention in ALS and FTLD.