Lead-Dust Contamination on Radiation Protection Apparel.

PURPOSE: To evaluate the prevalence of surface lead-dust contamination on radiation protection apparel (RPAs) in the radiology department and compare findings with those from other studies of RPA lead-dust contamination. MATERIALS AND METHODS: A survey of RPAs was conducted between June and December 2021 in radiology departments at a tertiary-care university hospital. A convenience sample of RPAs located on wall-mounted racks outside the angiography suite and emergency department was surveyed. Surface lead dust on RPAs was detected using a rapid qualitative test. RESULTS: A total of 69 RPAs included full-length frontal lead aprons (n = 11), full-length frontal lead aprons (n = 25) with thyroid collars (n = 25), and thyroid collars alone (n = 8). Garments consisted mainly of a lead/antimony composite core with a 0.5-mm lead equivalency. One RPA failed radiologic quality inspection, and 8 garments were in poor or worn condition. The overall prevalence of surface lead-dust contamination on RPAs was 60.9% (95% CI, 49.1%-71.5%) and was significantly (P = .0035) higher on thyroid collars (78.8% [95% CI, 62.2%-89.3%]) than on lead aprons (44.4% [95% CI, 29.5%-60.4%]). CONCLUSIONS: A high prevalence of surface lead-dust contamination was detected on RPAs using a rapid qualitative test. There is currently no established safe level of lead, and these findings suggest RPAs be monitored frequently not only for physical defects limiting radiation protection but also for lead-dust contamination.

Cardiac Investigation Trends Among Primary Care Physicians: A Paradigm Shift.

OBJECTIVE: While numerous recent guidelines support coronary computed tomography angiography (CTA) as a first-line test for stable chest pain, it remains underutilized by primary care physicians (PCPs). We aimed to evaluate cardiac investigation ordering practices following education sessions, as well as the total number of downstream tests and time to diagnosis for patients presenting with stable chest pain. METHODS: A retrospective chart review was completed for eligible patients assessed at the Women's College Hospital Family Practice Health Centre between 2017 and 2019 following the education sessions. The outcome measures were first-choice cardiac investigation, additional downstream testing, time from presentation to first investigation, and time to final diagnosis. RESULTS: 419 patients were included in the final analysis (74.70% female; mean age 61 ± 11 years). Coronary CTA requests by PCPs increased between 2017 and 2019 (18 vs 72 tests; P < .0001). When coronary CTA was the first-line test, patients were less likely to receive additional downstream testing when compared to those receiving other first-line investigations (P < .0001). Coronary CTA was associated with longer time to diagnosis than stress echocardiography (47 ± 45 vs 27 ± 36 days; P = .0068) due to limited availability of coronary CTA appointment times. There was no significant difference in time to final diagnosis among the cardiac imaging modalities observed in the cohort (P = .0623). CONCLUSION: Utilization of coronary CTA as the first-line test for stable chest pain increased following our education sessions targeting PCPs. Coronary CTA was associated with less downstream testing compared to other non-invasive cardiac investigations.

The role of miR-711 in cardiac cells in response to oxidative stress and its biogenesis: a study on H9C2 cells.

BACKGROUND: Oxidative stress results in cell apoptosis/death and plays a detrimental role in disease development and progression. Stressors alter the miRNA expression profile and miRNAs play a role in the cell response to stress. We previously showed that miR-711 is significantly over-expressed in extended cold ischemia reperfusion injured hearts in heart transplant. In this study, we aimed to investigate the role of miR-711 in cardiac cell damage in response to oxidative stress and how miR-711 is regulated. METHODS: Rat cardiac cell line H9c2 cells were cultured and exposed to oxidative conditions (Antimycin A (AA), H2O2, CoCl2, or cold hypoxia/reoxygenation (H/R)) in vitro. H9c2 cells were transfected with miR-711 mimics, miR-711 inhibitors, or small interference RNA, using transfection reagents. The expression of miR-711 was measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell apoptosis/death was detected by flow cytometry and an IncuCyte system. Mitochondrial damage was detected by measuring the mitochondria membrane potential by flow cytometry. Gene expression was detected by qRT-PCR at the mRNA level and Western blotting and immunocytochemistry staining at the protein level. RESULTS: We found that miR-711 was significantly up-regulated in cells treated with H2O2, AA, CoCl2, and cold H/R. Over-expression of miR-711 increased cell apoptosis/death induced by AA and H/R whereas cell death was reduced by miR-711 inhibitors. MiR-711 induced cell death through negative regulation of angiopoietin 1 (Ang-1), fibroblast growth factor 14 (FGF14) and calcium voltage-gated channel subunit alpha1C (Cacna1c) genes. Both knockdown of hypoxia inducible factor 1α (HIF-1α) and inactivation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFКB) pathway inhibited over-expression of miR-711. CONCLUSION: Oxidative stress increases the expression of miR-711. Over-expression of miR-711 induces cell apoptosis/death. HIF-1α and NFКB regulate miR-711 in H9c2 cells during oxidative stress. miR-711 is a new target for preventing oxidative stress.

Circular RNA in cardiovascular disease.

Circular RNA (circRNA) are endogenous transcripts that display differential expression across species, developmental stages, and pathologies. Their lack of free ends confers increased stability when compared with linear transcripts, making them ideal candidates for future diagnostic biomarkers and therapeutic interventions. Increasing evidence has implicated circRNA in the pathogenesis of multiple cardiovascular diseases. In this paper, we summarize current understanding of circRNA biogenesis, properties, expression profiles, detection methods, functions, and their implication in cardiac pathologies including/ischemia reperfusion injury, myocardial infarction, cardiac senescence, cardiac fibrosis, cardiomyopathy, cardiac hypertrophy and heart failure, atherosclerosis, coronary artery disease, and aneurysm.

Approach to Imaging of Patients Presenting With Acute Coronary Syndrome With No Culprit Lesion Identified at Angiography.

Chest pain is a common chief complaint among patients presenting to the emergency department. However, in the scenario where the clinical presentation is consistent with acute coronary syndrome and no culprit lesions are identified on angiography, clinicians and cardiac imagers should be informed of the differential diagnosis and appropriate imaging modalities used to investigate the potential causes. This review describes an imaging-based algorithm that highlights the diagnostic possibilities, their differentiating imaging features, and the important role of cardiovascular magnetic resonance imaging for narrowing the differential diagnosis.

In vitro analysis of tantalum-containing mesoporous bioactive glass fibres for haemostasis.

Haemorrhage is the leading cause of battlefield deaths and second most common cause for civilian mortality worldwide. Biomaterials-based haemostatic agents are used to aid in bleeding stoppage; mesoporous bioactive glasses (MBGs) are candidates for haemostasis. Previously made Tantalum-containing MBG (Ta-MBG) powders' compositions were fabricated as electrospun fibres for haemostatic applications in the present study. The fibres were fabricated to address the challenges associated with the powder form: difficult to compress without gauze, getting washed away in profuse bleeding, generating dust in the surgical environment, and forming thick callus-difficult to remove for surgeons and painful for patients. Ta-MBGs were based on (80-x)SiO2-15CaO-5P2O5-xTa2O5 mol% compositions with x = 0 (0Ta), 0.5 (0.5Ta), 1 (1Ta), and 5 (5Ta) mol%. The present study details the fibres' in vitro analyses, elucidating their cytotoxic effects, and haemostatic capabilities and relating these observations to fibre chemistry and previously fabricated powders of the same glasses. As expected, when Ta addition is increased at the expense of silica, a new FTIR peak (non-bridging oxygen-silicon, Si-NBO) develops and Si-O-Si peaks become wider. Compared to 0Ta and 1Ta fibres, 0.5Ta show Si-O peaks with reduced intensity. The fibres had a weaker intensity of Si-NBO peaks and release fewer ions than powders. A reduced ion profile provides fibres with a stable matrix for clot formation. The ion release profile for 1Ta and 5Ta fibres was significantly lower than 0Ta and 0.5Ta fibres. Ta-MBGs were not found to be cytotoxic to primary rat fibroblasts using a methyl thiazolyl tetrazolium (MTT) assay. Furthermore, a modified activated partial thromboplastin time assay analysing the fibrin absorbance showed that the absorption increases from physiological clotting < 0Ta < 0.5Ta < 5Ta < commercial haemostat, Surgical SNoWTM, Ethicon, USA < 1Ta. Higher absorption signifies a stronger clot. It is concluded that Ta-MBG fibres can provide stable matrix for clot formation and 1Ta can potentially enhance clotting best among other Ta-MBGs.

Association of SARS-CoV-2 infection with neurological impairments in pediatric population: A systematic review.

Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population. A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged <18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches. A total of 843 no-duplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6985 individuals were included, where 12.8% (n = 892) of hospitalized patients experienced neurocognitive impairments which includes: 1) neurological symptoms (n = 294 of 892, 33.0%), 2) neurological syndromes and neuroimaging abnormalities (n = 223 of 892, 25.0%), and 3) other phenomena (n = 233 of 892, 26.1%). Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%). Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice. Further investigation revealed the RBD could bind platelets, cause platelet activation, and potentiate platelet aggregation, which was exacerbated in the Delta and Kappa variants. The RBD-platelet interaction was partially dependent on the ß3 integrin as binding was significantly reduced in ß3-/- mice. Furthermore, RBD binding to human and mouse platelets was significantly reduced with related αIIbß3 antagonists and mutation of the RGD (arginine-glycine-aspartate) integrin binding motif to RGE (arginine-glycine-glutamate). We developed anti-RBD polyclonal and several monoclonal antibodies (mAbs) and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation, aggregation, and clearance in vivo, and SARS-CoV-2 infection and replication in Vero E6 cells. Our data show that the RBD can bind platelets partially though αIIbß3 and induce platelet activation and clearance, which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT. Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.

Association of SARS-CoV-2 Infection with Neurological Symptoms and Neuroimaging Manifestations in the Pediatric Population: A Systematic Review.

Background: Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population. Methods: A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged < 18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches. Results: A total of 843 nonduplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6,985 individuals were included, where 12.8% of hospitalized patients experienced neurocognitive impairments: MIS-C (24.2%), neuroinflammation (10.1%), and encephalopathy (8.1%) were the most common disorders; headaches (16.8%) and seizures (3.8%) were the most common symptoms. Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%). Conclusion: Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.

Small Particle DEBIRI TACE as Salvage Therapy in Patients with Liver Dominant Colorectal Cancer Metastasis: Retrospective Analysis of Safety and Outcomes.

The aim of this study was to examine the safety and efficacy of 40 µm and 75 µm calibrated irinotecan-eluting beads (DEBIRI-TACE) for the treatment of colorectal cancer metastases. We conducted a retrospective review of 36 patients with unresectable liver metastases from colorectal cancer who were treated with DEBIRI-TACE between 2017 to 2020. Patients who received at least one session of DEBIRI were included in our analysis. A total of 105 DEBIRI sessions were completed. 86% of patients (n = 31) underwent one round of treatment, 14% of patients (n = 5) underwent two distinct rounds of treatment. The majority of patients were discharged the next day (92%, n = 33 patients) with no 30-day post-DEBIRI mortality. Five high-grade adverse events occurred, including longer stay for pain management (n = 2), postembolization syndrome requiring readmission (n = 2), and liver abscess (n = 1). The average survival from diagnosis of metastatic disease was 33.3 months (range 11-95, median 28). Nine of 36 patients are still alive (December 2020) and have an average follow-up time of 36.8 months from T0 (range 12-63, median 39). Small particle DEBIRI is safe and well-tolerated in the salvage setting, with outcomes comparable to that of larger bead sizes.

In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα.

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation.Trial registration: Clinicaltrials.gov NCT01588132.

Updated Understanding of Platelets in Thrombosis and Hemostasis: The Roles of Integrin PSI Domains and their Potential as Therapeutic Targets.

Platelets are small blood cells known primarily for their ability to adhere and aggregate at injured vessels to arrest bleeding. However, when triggered under pathological conditions, the same adaptive mechanism of platelet adhesion and aggregation may cause thrombosis, a primary cause of heart attack and stroke. Over recent decades, research has made considerable progress in uncovering the intricate and dynamic interactions that regulate these processes. Integrins are heterodimeric cell surface receptors expressed on all metazoan cells that facilitate cell adhesion, movement, and signaling, to drive biological and pathological processes such as thrombosis and hemostasis. Recently, our group discovered that the plexin-semaphorin-integrin (PSI) domains of the integrin ß subunits exert endogenous thiol isomerase activity derived from their two highly conserved CXXC active site motifs. Given the importance of redox reactions in integrin activation and its location in the knee region, this PSI domain activity may be critically involved in facilitating the interconversions between integrin conformations. Our monoclonal antibodies against the ß3 PSI domain inhibited its thiol isomerase activity and proportionally attenuated fibrinogen binding and platelet aggregation. Notably, these antibodies inhibited thrombosis without significantly impairing hemostasis or causing platelet clearance. In this review, we will update mechanisms of thrombosis and hemostasis, including platelet versatilities and immune-mediated thrombocytopenia, discuss critical contributions of the newly discovered PSI domain thiol isomerase activity, and its potential as a novel target for anti-thrombotic therapies and beyond.