Active learning strategies such as formative assessment through clinical cases may help to get a deeper learning. We have studied the effect of this kind of online formative assessment in ...pathophysiology teaching.
Seven brief clinical cases were used to give formative assessment in the first semester of a pathophysiology course. To evaluate its effect on learning, we analyzed the proportion of students that passed the end of semester exam with a score above 60 over 100. We also analyzed the effect of the intervention according to the students' previous academic performance.
Ninety-six students participated in the study and sat the exam. Sixty-five of them passed it. Students that passed the exam had a higher previous academic performance and had done a higher number of exercises of formative assessment, both in univariate and multivariate analysis. The participants were divided in three groups, according to their previous academic performance. In the intermediate group, the number of cases done by the students who passed the exam was significantly higher than in those who did not pass it (median: 4 versus 0; P = 0.009).
Formative assessment through web-based clinical cases was followed by an improvement of the academic results in pathophysiology, mainly in students with intermediate performance.
Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 ...patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset.
Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022.
All patients recruited completed the trial (median age, 26 IQR 19–36 in the ivermectin and 21–44 in the controls years; 12 50% women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77–1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001).
Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials.
ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra.
Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This ...large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients.
The physical implementation of quantum information processing relies on individual modules-qubits-and operations that modify such modules either individually or in groups-quantum gates. Two examples ...of gates that entangle pairs of qubits are the controlled NOT-gate (CNOT) gate, which flips the state of one qubit depending on the state of another, and the gate that brings a two-qubit product state into a superposition involving partially swapping the qubit states. Here we show that through supramolecular chemistry a single simple module, molecular {Cr7Ni} rings, which act as the qubits, can be assembled into structures suitable for either the CNOT or gate by choice of linker, and we characterize these structures by electron spin resonance spectroscopy. We introduce two schemes for implementing such gates with these supramolecular assemblies and perform detailed simulations, based on the measured parameters including decoherence, to demonstrate how the gates would operate.
Quantum information processing (QIP) would require that the individual units involved--qubits--communicate to other qubits while retaining their identity. In many ways this resembles the way ...supramolecular chemistry brings together individual molecules into interlocked structures, where the assembly has one identity but where the individual components are still recognizable. Here a fully modular supramolecular strategy has been to link hybrid organic-inorganic 2- and 3-rotaxanes into still larger 4-, 5- and 7-rotaxanes. The ring components are heterometallic octanuclear Cr7NiF8(O2C(t)Bu)16(-) coordination cages and the thread components template the formation of the ring about the organic axle, and are further functionalized to act as a ligand, which leads to large supramolecular arrays of these heterometallic rings. As the rings have been proposed as qubits for QIP, the strategy provides a possible route towards scalable molecular electron spin devices for QIP. Double electron-electron resonance experiments demonstrate inter-qubit interactions suitable for mediating two-qubit quantum logic gates.
Controlled Synthesis of Nanoscopic Metal Cages Ferrando-Soria, Jesùs; Fernandez, Antonio; Moreno Pineda, Eufemio ...
Journal of the American Chemical Society,
06/2015, Volume:
137, Issue:
24
Journal Article
Peer reviewed
Open access
Here we show an elegant and general route to the assembly of a giant {M12C24} cage from 12 palladium ions (M) and 24 heterometallic octanuclear coordination cages (C = {Cr7Ni-Py2}). The molecule is 8 ...nm in size, and the methods for its synthesis and characterization provide a basis for future developments at this scale.
Background:
Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, ...dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA.
Methods:
A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity.
Results:
A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score–C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 beta coefficient 0.3 (95% confidence interval (CI) 0.1–0.5), p = 0.001 and ⩾2 beta coefficient 0.5 (95% CI 0.3–0.7), p = 0.000 CV risk factors compared with those without CV risk factors. Similarly, patients with 1 OR 2.00 (95%CI 0.99–4.02), p = 0.053 and ⩾2 OR 3.39 (95%CI 1.82–6.31), p = 0.000 CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ⩾2 over 1 CV risk factor.
Conclusion:
Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner.
To determine the potential impact of extra-articular manifestations (EAMs) on disease characteristics and cardiovascular (CV) risk in patients with axial spondylarthritis (axSpA).
This is a ...cross-sectional study from the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Data on the history of CV events, subclinical carotid atherosclerosis, and disease-related features, including EAMs, were collected.
888 axSpA patients were recruited. Concomitant acute anterior uveitis (AAU), psoriasis (PSO), and inflammatory bowel disease (IBD) were present in 177 (19.9%), 96 (10.8%), and 57 (6.4%) patients, respectively. When compared with axSpA patients without EAMs, a significant increase in past CV events was observed in patients with PSO (9% versus 4%, p = 0.048) and in those with at least one EAM (7% versus 4%, p = 0.032) or with more than one EAM (11% versus 4%, p = 0.022). The frequency of carotid plaques and the values of cIMT were higher in patients with EAMs than in those without EAMs, although only the univariable analysis for carotid plaques in patients with PSO (39% versus 30%, p = 0.038) and for cIMT in patients with AAU (665 ± 156 µm versus 637 ± 139 µm, p = 0.042) and those with at least one EAM (661 ± 155 µm versus 637 ± 139 µm, p = 0.024) showed significant results. In addition, patients with PSO or IBD were found to have specific disease-related features, such as higher ESR at diagnosis, and more frequent use of glucocorticoids and TNF inhibitors than those without EAMs. Also, PSO patients had more commonly peripheral involvement and those with AAU more severe radiographic damage than those without EAMs. The frequency of HLA B27 was higher in patients with AAU and lower in those with PSO or IBD compared to those without EAMs.
Patients with axSpA and EAMs, in addition to displaying their own disease-related features, are likely to have an increased CV risk that appears proportional to the number of EAMs and could be related to proatherogenic factors other than traditional CV risk factors, such as the inflammatory load and the use of glucocorticoids.
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To determine the potential impact of sex-specific disease-related characteristics on cardiovascular (CV) disease in axial spondyloarthritis (axSpA).
Cross-sectional study of the Spanish AtheSpAin ...cohort to study CV disease in axSpA. Data on carotid ultrasound and CV disease and disease-related features were collected.
611 men and 301 women were recruited. Classic CV risk factors were significantly less prevalent in women, who also showed a lower frequency of carotid plaques (p = 0.001), lower carotid intima-media thickness (IMT) values (p<0.001) and CV events (p = 0.008). However, after adjustment for classic CV risk factors, only the differences with respect to carotid IMT remained statistically significant. Women showed higher ESR at diagnosis (p = 0.038), and more active disease (ASDAS, p = 0.012, and BASDAI, p<0.001). They had shorter disease duration (p<0.001), lower prevalence of psoriasis (p = 0.008), less structural damage (mSASSS, p<0.001), and less mobility limitation (BASMI, p = 0.033). To establish whether these findings could lead to sex differences in CV disease burden, we compared the prevalence of carotid plaques in men and women with the same level of CV risk stratified according to the Systematic Coronary Risk Evaluation (SCORE). Men included in the low-moderate CV risk SCORE category had more carotid plaques (p = 0.050), along with longer disease duration (p = 0.004), higher mSASSS (p = 0.001) and psoriasis (p = 0.023). In contrast, in the high-very high-risk SCORE category, carotid plaques were observed more frequently in women (p = 0.028), who were characterized as having worse BASFI (p = 0.011), BASDAI (p<0.001) and ASDAS (p = 0.027).
Disease-related features may influence the expression of atherosclerosis in patients with axSpA. This may be especially applicable to women at high CV risk, characterized by greater disease severity and more severe subclinical atherosclerosis than men, suggesting a stronger interaction between disease activity and atherosclerosis in women with axSpA.
•Identifying pro-atherogenic factors in rheumatic diseases can help prevent cardiovascular events.•Axial spondyloarthritis features associated with atherosclerosis remain unclear.•Inflammation and ...disease severity are associated with atherosclerosis in axial spondyloarthritis.
To identify disease-related factors associated with subclinical atherosclerosis and cardiovascular (CV) events in a large series of patients with axial spondyloarthritis (axSpA) and to identify possible differences in the effect of the potential pro-atherogenic factors between ankylosing spondylitis (AS) non-radiographic axSpA (nr-axSpA).
This is a cross-sectional observational study of the AtheSpAin cohort, a Spanish multicenter cohort to study atherosclerosis in axSpA. Subclinical atherosclerosis determined by carotid ultrasound included assessment of carotid intima-media thickness (cIMT) and plaque detection.
639 AS and 167 nr-axSpA patients were recruited. CV risk factors (CRF) and several disease-related factors showed a statistically significant association with subclinical atherosclerosis in the crude analysis. After adjustment for age, sex, and smoking (model 1), associations remained statistically significant for spinal mobility, inflammatory bowel disease, use of prednisone, and Disease-modifying antirheumatic drugs (DMARD) when assessing carotid plaques and for acute phase reactants (APR) at diagnosis, use of prednisone, DMARD, and TNF-inhibitors when measuring cIMT. In model 2, which also included classic CRF as confounding factors to identify axSpA features with a potential independent pro-atherogenic effect, the functional status was the only variable significantly associated with plaques and the use of prednisone and APR at diagnosis with cIMT. No association differences were found between both subtypes of patients. Besides, APR at diagnosis were also associated with subsequent development of CV events that had occurred in 33 patients.
Apart from CRF, atherosclerotic disease in AxSpA is associated with disease-related factors such as inflammatory response and disease severity, with no differences between AS and nr-axSpA.
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