Evaluation of Heparin-Induced Thrombocytopenia Antibody Laboratory Use and Anticoagulation Prescribing Patterns

Introduction Heparin-induced thrombocytopenia (HIT) is a rare adverse reaction Calculating a 4T score prior to ordering a heparin-PF4 immunoassay is recommended. For a score \u3c 4, HIT probability is low and an assay is not advised If high suspicion of HIT (4T greater than or equal to 4), an assay should be ordered, all heparin products discontinued, and a non-heparin anticoagulant initiated. Purpose Determine if heparin immunoassay ordering was indicted according to retrospective 4T score Assess anticoagulation prescribing depending on the result of the assay Serve as a pre-group for a planned perverse post-HIT order set implementation analysishttps://digitalcommons.centracare.com/pharmacy_posters/1007/thumbnail.jp

Post-Pandemic Predictors of Anxiety in College Students

Rates of anxiety among college students have increased significantly during the COVID-19 pandemic and have remained high (Elharake et al., 2023), placing students at risk for diminished academic performance, depression, and academic burnout (Rassaby et al., 2022). The goal of this study was to examine possible predictors of anxiety in a diverse group of undergraduate students post-pandemic, with the goal of informing future preventive intervention efforts. Maladaptive perfectionism, passive procrastination, active procrastination, cognitive flexibility, and social well-being were assessed as potential predictors of state and trait anxiety in a sample of 297 currently enrolled college students. Results showed that perfectionism and passive procrastination were the strongest predictors of anxiety; cognitive flexibility and social well-being were also significant correlates. These results suggest that anxiety in college students could be ameliorated by: (1) reducing the unrealistic expectations that often accompany perfectionism; (2) preventing students from developing habits of academic procrastination; (3) increasing students’ ability to respond flexibly to changing circumstances; and (4) helping students develop strategies to approach their social world more positively

Paleomagnetism and Geochemistry of similar to 1144-Ma Lamprophyre Dikes, Northwestern Ontario : Implications for the North American Polar Wander and Plate Velocities

We present new paleomagnetic and geochemical data from a suite of the similar to 1144-Ma ultramafic lamprophyre dikes that outcrop in the Canadian Shield northeast of Lake Superior (Ontario, Canada). Nineteen of 22 sampled dikes yielded consistent characteristic remanent magnetization directions of normal (n = 5) and reversed (n = 14) polarity. The primary origin of characteristic remanent magnetization is bolstered by positive baked contact tests and a reversal test. The group mean direction (D = 306.4 degrees, I = 72.1 degrees, alpha(95) = 5.5 degrees, N = 19) obtained from the lamprophyre dikes is statistically indistinguishable from the group mean direction (D = 297.4 degrees, I = 65.5 degrees, alpha(95) = 8.3 degrees, N = 8) previously reported for the nearly coeval similar to 1142-Ma Abitibi dikes. The geochemistry of the lamprophyre dikes suggests strong affinity with magmas derived from ocean island basalt-type mantle sources, consistent with the mantle plume hypothesis for the formation of the similar to 1.1-Ga North American Midcontinent Rift. The similarity in age, trend, paleomagnetism, and geochemistry indicates that the lamprophyre and Abitibi dike suites represent the earliest magmatic event associated with the commencement of rifting. The combined mean direction (D = 303.1 degrees, I = 70.2 degrees, alpha(95) = 4.5 degrees, N = 27) corresponds to a paleomagnetic pole at P-lat = 55.8 degrees N, P-long = 220.0 degrees E (A(95) = 7.3 degrees). The new pole merits the highest classification on the Q-scale of paleomagnetic reliability and represents a key pole defining the North American apparent polar wander path during the late Mesoproterozoic. Combined with high-quality data from the similar to 1108-Ma Coldwell Complex, our data indicate an equatorward motion of Laurentia at 3.8 +/- 1.4 cm/year, comparable with the present-day velocities of continental plates, before switching to extremely rapid motion between similar to 1108 and similar to 1099 Ma. Plain Language Summary Similar to a magnetic tape, rocks can retain the direction of ancient Earth's magnetic field. Scientists use this record (known as paleomagnetism) to reconstruct past positions of continents and to decipher the geological history of our planet. We investigated paleomagnetism and chemical composition of the similar to 1.14 Ga-old intrusive rocks called lamprophyres exposed in Northwestern Ontario (Canada). We found that the paleomagnetic field directions recorded in lamprophyres are indistinguishable from those recorded by another similar age suite of basaltic intrusions called the Abitibi dikes, from the same area. The combined data from these rocks allowed us to constrain the position of an ancient supercontinent called Laurentia at similar to 1.14 billions of years ago more accurately than it was possible before. Our results convincingly show that, during that time, Laurentia moved with a velocity comparable to present-day plate velocities, before switching to an extremely rapid motion approximately 35 millions of years later. The lamprophyre and Abitibi rocks also share similar chemical signatures, close to those observed for ocean island basalts (e.g., Hawaii). These observations support the hypothesis that a failed ocean opening attempt called the North American Midcontinent Rift was instigated by the arrival of a hot mantle material upwelling to the Earth surface.Peer reviewe

Understanding resilience capitals, agency and habitus in household experiences of water scarcity, floods and fire in marginalized settlements in the Cape Flats, South Africa

A significant percentage of the urban population in most low- and middle-income countries live in informal settlements. Due to poor quality housing, dense settlement patterns and lack of risk reducing infrastructure, informal settlements are least prepared and at higher risk for climate change issues. Marginalized communities in settlements in the Cape Flats region of South Africa face a range of environmental hazards and risks including recurrent large-scale fires, localised flooding and inconsistent access to water. This paper presents findings from a household survey with 600 participants from three economically marginalised settlements in this region. The paper explores how different forms of capital come into play in the shaping of these experiences and responses and uses these to consider power structures and the creation of particular types of habitus amongst settlement residents. Results show that cultural (knowledge) capital is one of the most important capitals enabling resilience and adaptive capacities across all three sites. Findings show the complex interplay of forms of capital and the importance of recognizing ownership, control and power structures. Our findings also illustrate how repeated exposure to risk can shape a habitus of risk acceptance and a focus on coping rather than change. Insights from this study further enhance knowledge of community resilience that could potentially inform policy development and institutional disaster risk reduction strategies for climate change resilience of cities in low- and middle-income countries

Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats

<p>Abstract</p> <p>Background</p> <p>Many studies have focused on the implication of the serotonin and dopamine systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine (MDMA). Less attention has been given to the major excitatory neurotransmitter glutamate known to be implicated in schizophrenia and drug addiction. The aim of the present study was to investigate the effect of repeated intermittent MDMA administration upon gene-transcript expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2), the glutamate receptor subunits of AMPA (GluR1, GluR2, GluR3), the glutamate receptor subunits of NMDA (NR1, NR2A and NR2B), as well as metabotropic glutamate receptors (mGluR1, mGluR2, mGluR3, mGluR5) in six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of 3 × 1 and 3 × 5 mg/kg/day, or 3× vehicle 3 hours apart, every 7^thday for 4 weeks. The gene-transcript levels were assessed using real-time PCR validated with a range of housekeeping genes.</p> <p>Results</p> <p>The findings showed pronounced enhancements in gene-transcript expression of GluR2, mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus. In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 gene-transcript expressions.</p> <p>Conclusion</p> <p>Repeated intermittent MDMA administration induces neuroadaptive changes in gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic receptors and transporters in regions of the brain regulating reward-related associative learning, cognition, and memory and neuro-endocrine functions.</p

‘It Means We are Not Safe’: Understanding and Learning from Household Experiences of Water Scarcity, Flood and Fire in Marginalized Settlements in the Cape Flats, South Africa

As climate change-related extreme weather events such as flooding and droughts increase in frequency and severity in most cities worldwide, there is a need to deepen understanding of disaster risks and adaptive capacities. A significant percentage of the urban population in most low- and middle-income countries live in informal settlements. Due to poor quality housing, dense settlement patterns and lack of risk reducing infrastructure e.g., drainage systems, informal settlements have been identified as being least prepared and at higher risk for climate change issues and therefore serve as important sites for understanding these risks and capacities. Marginalized communities in settlements in the Cape Flats region of South Africa face a range of environmental hazards including recurrent large-scale fires, localised flooding and water supply shortages. This paper presents findings from a household survey with 600 participants from three economically marginalised township settlements in this region. The aim of the survey was to understand the lived experiences, coping mechanisms and resilience attributes of the residents faced with localised flooding, fires and water shortages – locally salient environmental risks and hazards. The paper explores how different forms of capital come into play in the shaping of these experiences and responses and uses these to consider power structures and the creation of particular types of habitus amongst settlement residents. Insights from this study further enhance knowledge of community resilience that could potentially inform policy development and institutional disaster risk reduction strategies for climate change resilience of cities in low- and middle-income countries

Co-localization and functional cross-talk between A1 and P2Y1 purine receptors in rat hippocampus

Adenosine and ATP, via their specific P1 and P2 receptors, modulate a wide variety of cellular and tissue functions, playing a neuroprotective or neurodegenerative role in brain damage conditions. Although, in general, adenosine inhibits excitability and ATP functions as an excitatory transmitter in the central nervous system, recent data suggest the existence of a heterodimerization and a functional interaction between P1 and P2 receptors in the brain. In particular, interactions of adenosine A1 and P2Y1 receptors may play important roles in the purinergic signalling cascade. In the present work, we investigated the subcellular localization/co-localization of the receptors and their functional cross-talk at the membrane level in Wistar rat hippocampus. This is a particularly vulnerable brain area, which is sensitive to adenosine- and ATP-mediated control of glutamatergic transmission. The postembedding immunogold electron microscopy technique showed that the two receptors are co-localized at the synaptic membranes and surrounding astroglial membranes of glutamatergic synapses. To investigate the functional cross-talk between the two types of purinergic receptors, we evaluated the reciprocal effects of their activation on their G protein coupling. P2Y1 receptor stimulation impaired the potency of A1 receptor coupling to G protein, whereas the stimulation of A1 receptors increased the functional responsiveness of P2Y1 receptors. The results demonstrated an A1–P2Y1 receptor co-localization at glutamatergic synapses and surrounding astrocytes and a functional interaction between these receptors in hippocampus, suggesting ATP and adenosine can interact in purine-mediated signalling. This may be particularly important during pathological conditions, when large amounts of these mediators are released

Mepolizumab versus placebo for asthma

Background Mepolizumab is a human monoclonal antibody against interleukin-5 (IL-5), the main cytokine involved in the activation of eosinophils, which in turn causes airway inflammation. Recent studies have suggested these agents may have a role in reducing exacerbations and improving health-related quality of life (HRQoL). There are no recommendations for the use of mepolizumab in adults or children in the recent update of the BTS/SIGN guidelines (BTS/SIGN 2014). Objectives To compare the effects of mepolizumab with placebo on exacerbations and HRQoL in adults and children with chronic asthma. Search methods We searched the Cochrane Airways Group Register (CAGR) of trials, clinical trial registries, manufacturers' websites and the reference lists of included studies. Searches were conducted in November 2013 and updated in November 2014. Selection criteria We included randomised controlled trials comparing mepolizumab versus placebo in adults and children with asthma. Data collection and analysis Two authors independently extracted data and analysed outcomes using a random-effects model. We used standard methods expected by The Cochrane Collaboration. Main results Eight studies on 1707 participants met the inclusion criteria. Only two studies included children (over 12 years of age), but they did not report separate findings for the adolescents. Seven studies involved intravenous mepolizumab alone; one included a subcutaneous arm. There was heterogeneity in the severity and clinical pattern of asthma among the participants in the eight studies, varying from mild to moderate atopic asthma, to persistent asthma and eosinophilic asthma with recurrent exacerbations. Selection bias was a concern in several of the studies included in this review. Four trials compared intravenous mepolizumab to placebo in relation to HRQoL. Two studies measured scores from the Asthma Quality of Life Questionnaire (AQLQ), which showed a non-significant difference between mepolizumab and placebo (mean difference (MD) 0.21, 95% confidence interval (CI) − 0.01 to 0.44; participants = 682), in the direction favouring mepolizumab. The third study used the St. George's Respiratory Questionnaire (SGRQ) and found a significant difference between mepolizumab and placebo (MD 6.40, 95% CI 3.15 to 9.65; participants = 576), which indicated a clinically important benefit favouring mepolizumab. A fourth study noted that there was no significant difference but did not provide any data. The two studies in people with eosinophilic asthma showed a reduction in clinically significant exacerbation rates (Risk Ratio 0.52, 95% CI 0.43 to 0.64; participants = 690). However, an analysis of four studies that were not confined to people with eosinophilic asthma indicated considerable heterogeneity and no significant difference in people with one or more exacerbations between mepolizumab and placebo using a random-effects model (Risk Ratio 0.67, 95% CI 0.34 to 1.31; participants = 468; I2 = 59%).The analysis of serious adverse events indicated a significant difference favouring mepolizumab (Risk ratio 0.49, 95% CI 0.30 to 0.80; participants = 1441; studies = 5; I2 = 0%). It was not possible to combine the results for adverse events, and we deemed the quality of this evidence to be low. A single study compared subcutaneous mepolizumab to placebo in 385 adults with severe eosinophilic asthma and found an improvement in HRQoL scores and a reduction in asthma exacerbations, including exacerbations requiring admission to hospital. Authors' conclusions It is not possible to draw firm conclusions from this review with respect to the role of mepolizumab in patients with asthma. Our confidence in the results of this review are limited by the fact that the intravenous route is not currently licensed for mepolizumab, and the evidence for the currently licenced subcutaneous route is limited to a single study in participants with severe eosinophilic asthma. The currently available studies provide evidence that mepolizumab can lead to an improvement in health-related quality of life scores and reduce asthma exacerbations in people with severe eosinophilic asthma. Further research is needed to clarify which subgroups of patients with asthma could potentially benefit from this treatment. Dosage, ideal dosing regimens and duration of treatment need to be clarified, as the studies included in this review differed in their protocols. There are no studies reporting results from children, so we cannot comment on treatment for this age group. At the present time, larger studies using licenced treatment regimens are required to establish the role of mepolizumab in the treatment of severe asthma

Quality control for unfolded proteins at the plasma membrane

A temperature-sensitive chimeric transmembrane protein reveals a mechanism for disposing misfolded proteins that make it to the plasma membrane

ENaC-mediated sodium influx exacerbates NLRP3-dependent inflammation in Cystic Fibrosis.

Cystic Fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective CFTR-mediated chloride and bicarbonate transport, with dysregulation of epithelial sodium channels (ENaC). These changes alter fluid and electrolyte homeostasis and result in an exaggerated proinflammatory response driven, in part, by infection. We tested the hypothesis that NLRP3 inflammasome activation and ENaC upregulation drives exaggerated innate-immune responses in this multisystem disease. We identify an enhanced proinflammatory signature, as evidenced by increased levels of IL-18, IL-1β, caspase-1 activity and ASC-speck release in monocytes, epithelia and serum with CF-associated mutations; these differences were reversed by pretreatment with NLRP3 inflammasome inhibitors and notably, inhibition of amiloride-sensitive sodium (Na+) channels. Overexpression of β-ENaC, in the absence of CFTR dysfunction, increased NLRP3-mediated inflammation, indicating that dysregulated, ENaC-dependent signalling may drive exaggerated inflammatory responses in CF. These data support a role for sodium in modulating NLRP3 inflammasome activation