Search

Background: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic for more than 2 years. Autopsy examination is an invaluable tool to understand the pathogenesis of emerging infections and their consequent mortalities. The aim of the current study was to present the lung and heart pathological findings of COVID-19–positive autopsies performed in Jordan. Methods: The study involved medicolegal cases, where the cause of death was unclear and autopsy examination was mandated by law. We included the clinical and pathologic findings of routine gross and microscopic examination of cases that were positive for COVID-19 at time of death. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed through molecular detection by real-time polymerase chain reaction, serologic testing for IgM and electron microscope examination of lung samples. Results: Seventeen autopsies were included, with male predominance (76.5%), Jordanians (70.6%), and 50 years as the mean age at time of death. Nine out of 16 cases (56.3%) had co-morbidities, with one case lacking such data. Histologic examination of lung tissue revealed diffuse alveolar damage in 13/17 cases (76.5%), and pulmonary microthrombi in 8/17 cases (47.1%). Microscopic cardiac findings were scarcely detected. Two patients died as a direct result of acute cardiac disease with limited pulmonary findings. Conclusions: The detection of SARS-CoV-2 in postmortem examination can be an incidental or contributory finding which highlights the value of autopsy examination to determine the exact cause of death in controversial cases.

Background: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. Objectives: The aim of this systematic review is to better understand the various aspects of the cardio-vascular complications of COVID-19 by pooling data from a large number of autopsy studies. Data sources: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published be-tween database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. Study eligibility criteria: Articles were considered eligible for inclusion if they reported human post-mortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. Participants: Confirmed COVID-19 patients with post-mortem cardiovascular findings. Interventions: None. Methods: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). Results: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-10 0%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median re-ported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). Conclusions: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19. (C) 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The resistance spot welding (RSW) method was used to join aluminum alloy AA 1050 and copper alloy UNS C50100 sheets. Mechanical properties of the joints were examined. The influence of welding process parameters on tensile shear force of the joints was discussed. The design of experiments (DOE) method was used to analyze the influence of welding parameters on the mechanical properties of the joints. Three RSW parameters were used: welding current, squeeze time, and welding time. The results showed that the joint shear stress increased with increasing the welding current until a value of 12000 Amp. Then the shear stress decreased. The tensile shear stress increased with increasing the welding and squeeze time. As a consequence, it can be possible to weld copper with aluminum by RSW.

Background\ud\udPost-acute COVID-19 syndrome (PACS) is an important healthcare burden. We examined persistent symptoms in COVID-19 patients at least four weeks after the onset of infection, participants’ return to pre-COVID-19 health status and associated risk factors.\udMethods\ud\udCross-sectional study was conducted (December 2020 to January 2021). A validated online questionnaire was sent to randomly selected individuals aged more than 14 years from a total of 1397,386 people confirmed to have COVID-19 at least 4 weeks prior to the start of this survey. This sample was drawn from the Saudi ministry of health COVID-19 testing registry system.\udResults\ud\udOut of the 9507 COVID-19 patients who responded to the survey, 5946 (62.5%) of them adequately completed it. 2895 patients (48.7%) were aged 35–44 years, 64.4% were males, and 91.5% were Middle Eastern or North African. 79.4% experienced unresolved symptoms for at least 4 weeks after the disease onset. 9.3% were hospitalized with 42.7% visiting healthcare facility after discharge and 14.3% requiring readmission. The rates of main reported persistent symptoms in descending order were fatigue 53.5%, muscle and body ache 38.2%, loss of smell 35.0%, joint pain 30.5%, and loss of taste 29.1%. There was moderate correlation between the number of symptoms at the onset and post-four weeks of COVID-19 infection. Female sex, pre-existing comorbidities, increased number of baseline symptoms, longer hospital-stay, and hospital readmission were predictors of delayed return to baseline health state (p < 0.05).\udConclusion\ud\udThe symptoms of PACS are prevalent after contracting COVID-19 disease. Several risk factors could predict delayed return to baseline health state.

Introduction: Virgin coconut oil (VCO) is an edible oil extracted from the meat of mature coconuts. It is also known for its health and therapeutic benefits, mainly attributed to its polyphenols and medium-chain fatty acid contents The immunomodulatory effects of VCO have not been extensively investigated. The aim of the present study was to investigate the effects of VCO on cyclophosphamide (CY)-induced immunotoxicity of peripheral lymphoid tissues. Methods: Forty Wistar rats were divided into five groups of eight rats each. Group 1 served as the normal control, while the other groups were all given 10 mg/kg of CY orally once daily for 4 weeks. Group 2 received CY served as the negative control. Group 3 rats were treated with levamisole (LMS) for 6 weeks, while Groups 4A and 4B were given VCO at 10 mL/kg and 15 mL/kg, respectively, for 6 weeks. The spleen and ileum sections were subjected to routine histological examination and immunohistochemical evaluation for T and B lymphocytes. Results: Histologically, the spleen and Peyer’s patches (PPs) of the ileum exhibited a significant reduction in the lymphoid cellularity following daily administration of 10 mg/kg CY for 4 weeks.

Preoperative variables can predict short term left ventricular assist device (LVAD) survival, but predictors of extended survival remain insufficiently characterized.Patients undergoing LVAD implant (2012-2018) in the Intermacs registry were grouped according to time on support: short-term (1 year, n = 7,483), mid-term (MT, 1-3 years, n = 5,976) and long-term (LT, ≥3 years, n = 3,015). Landmarked hazard analyses (adjusted hazard ratio, HR) were performed to identify correlates of survival after 1 and 3 years of support.After surviving 1 year of support, additional LVAD survival was less likely in older (HR 1.15 per decade), Caucasian (HR 1.22) and unmarried (HR 1.16) patients (p0.05). After 3 years of support, only 3 preoperative characteristics (age, race, and history of bypass surgery, p0.05) correlated with extended survival. Postoperative events most negatively influenced achieving LT survival. In those alive at 1 year or 3 years, the occurrence of postoperative renal (creatinine HR MT = 1.09; LT HR = 1.10 per mg/dl) and hepatic dysfunction (AST HR MT = 1.29; LT HR = 1.34 per 100 IU), stroke (MT HR = 1.24; LT HR = 1.42), infection (MT HR = 1.13; LT HR = 1.10), and/or device malfunction (MT HR = 1.22; LT HR = 1.46) reduced extended survival (all p ≤ 0.03).Success with LVAD therapy hinges on achieving long term survival in more recipients. After 1 year, extended survival is heavily constrained by the occurrence of adverse events and postoperative end-organ dysfunction. The growth of destination therapy intent mandates that future LVAD studies be designed with follow up sufficient for capturing outcomes beyond 24 months.

Fifteen albino mice were subjected to three days dehydration and fifteen albino mice were given 1% NaCl in their drinking water. Control animals were given drinking water All animals were sacrificed and kidneys were fixed in different fixatives and processed for light microscopy Section were stained for juxtaglomerular cells demonstration and the juxtaglomerular index (GI) and percentage of granulated nephron(%GN) were calculated. Kidneys from dehydrated and sodium-loaded animals showed significant decrease in both JGI and % GN and was discussed in relation to renin secretion and release.

Hydranencephaly is a central nervous system disorder at birth in which brain's cerebral hemispheres are absent and replaced by sacks filled with CSF. The prevalence of hydranencephaly is less than 1 in 10,000 births, with 0.2 percent of children autopsies showing the condition.

Literature regarding outcomes and predictors of complications secondary to infective endocarditis (IE) is limited. We aimed to study the outcomes and predictors of complications of IE. Data from a national emergency department sample, which constitutes 20% sample of hospital-owned emergency departments in the USA, were analyzed for hospital visits for IE. Complications of endocarditis were obtained by using ICD codes. Multivariable generalized linear method was used to evaluate predictors of in-hospital mortality and complications. Out of 255,838 adult IE patients (mean age 60.3 ± 20.1 years, 48.5% females), 97,803 (38.2%) patients developed one or more major complications. The major complications were cardiovascular system complications [57,900 (22.6%)], neurologic [42,851 (16.7%)] complications, and renal [16,236 (6.4%)] complications. These included cardiogenic shock [3873 (1.5%)], septic shock [25,798 (10.1%)], acute heart failure [35,602 (14%)], systemic thromboembolism (STE) [21,390 (8.36%)], heart block [11,430 (4.47%)], in-hospital dialysis [2880 (1.1%)], and disseminated intravascular coagulation (DIC) [2704 (1.1%)]. Patients with complicated IE had risk of mortality (adjusted RR 1.12, 95% CI 1.11–1.13, p

Rising prices of novel cancer medications are increasing the economic burden from cancer in Jordan, risking the ability of cancer patients to access lifesaving and life-extending treatments. Furthermore, in the absence of a national health technology assessment (HTA) framework, medication prices in Jordan are set based on manufacturers’ pricing considerations and not a value proposition. In response to these challenges, King Hussein Cancer Center (KHCC), the de facto national cancer institute, developed a first-in-country, cancer-specific, cost-effectiveness threshold (CET) to aid institutional decision makers in approving only cost-effective medications. Over the past 10 years, cost-effectiveness analyses based on this CET have led to the introduction of > 70% of requested novel cancer medications after manufacturers agreed to lower prices, beyond registration prices, to meet the CET. Future work is warranted to empirically derive a CET for Jordan to better guide reimbursement decisions.

Memory dysfunction is prevalent in temporal lobe epilepsy (TLE), but little is known about the underlying molecular etiologies. Single-nucleus RNA sequencing technology was used to examine differences in cellular heterogeneity among left (language-dominant) temporal neocortical tissues from patients with TLE with (n = 4) or without (n = 2) impairment in verbal episodic memory. We observed marked cell heterogeneity between memory phenotypes and identified numerous differentially expressed genes across all brain cell types. The most notable differences were observed in glutamatergic (excitatory) and GABAergic (inhibitory) neurons with an overrepresentation of genes associated with long-term potentiation, long-term depression, and MAPK signaling, processes known to be essential for episodic memory formation.

Memory dysfunction is prevalent in temporal lobe epilepsy, but little is known about the underlying pathophysiological etiologies. Here, we use spatial quantitation to examine differential expression of targeted proteins and transcripts in four brain regions essential for episodic memory (dentate gyrus, CA3, CA1, neocortex) between temporal lobe epilepsy patients with and without episodic memory impairment. Brain tissues were obtained from dominant temporal lobectomies in 16 adults with pharmacoresistant temporal lobe epilepsy associated with hippocampal sclerosis. Verbal memory tests from routine pre-operative clinical care were used to classify episodic memory as impaired or intact. Digital spatial profiling of a targeted protein panel and the whole transcriptome was performed using tissue sections from the temporal neocortex and hippocampus. We performed differential expression and pathway enrichment analysis between the memory groups within each temporal lobe region. Several proteins associated with neurodegenerative disease were overexpressed in the neocortex of patients with impaired memory, corroborating our prior findings using bulk transcriptomics. Spatial transcriptomics identified numerous differentially expressed transcripts in both neocortical and hippocampal subregions between memory groups, with little overlap across subregions. The strongest molecular signal was observed in the CA3 hippocampal subregion, known to play an essential role in memory encoding. Enrichment analyses revealed BDNF as a central hub in CA3-related networks regulating phenotype-relevant processes such as cognition, memory, long-term potentiation and neuritogenesis (Padj < 0.05). Results suggest memory impairment in temporal lobe epilepsy with hippocampal sclerosis is associated with molecular alterations within temporal lobe subregions that are independent from hippocampal cell loss, demographic variables and disease characteristics. Importantly, each temporal subregion shows a unique molecular signature associated with memory impairment. While many differentially expressed transcripts and proteins in the neocortex have been associated with neurodegenerative disorders/processes, differentially expressed transcripts in hippocampal subregions involve genes associated with neuritogenesis and long-term potentiation, processes essential for new memory formation.

PID control is commonly utilized in an active suspension system to achieve desirable chassis attitude, where, due to delays, feedback information has much difficulty regulating the roll and pitch behavior, and stabilizing the chassis attitude, which may result in roll over when the vehicle steers at a large longitudinal velocity. To address the problem of the feedback delays in chassis attitude stabilization, in this paper, a feedforward control strategy is proposed to combine with a previously developed PID control scheme in the recently introduced Parallel Active Link Suspension (PALS). Numerical simulations with a nonlinear multi-body vehicle model are performed, where a set of ISO driving maneuvers are tested. Results demonstrate the feedforward-based control scheme has improved suspension performance as compared to the conventional PID control, with faster speed of convergence in brake in a turn and step steer maneuvers, and surviving the fishhook maneuver (although displaying two-wheel lift-off) with 50 mph maneuver entrance speed at which conventional PID control rolls over., 8 pages, 17 figures, CCTA conference

This paper investigates the problem of robust model predictive control (RMPC) of linear-time-invariant (LTI) discrete-time systems subject to structured uncertainty and bounded disturbances. Typically, the constrained RMPC problem with state-feedback parameterizations is nonlinear (and nonconvex) with a prohibitively high computational burden for online implementation. To remedy this, a novel approach is proposed to linearize the state-feedback RMPC problem, with minimal conservatism, through the use of semidefinite relaxation techniques. The proposed algorithm computes the state-feedback gain and perturbation online by solving a linear matrix inequality (LMI) optimization that, in comparison to other schemes in the literature is shown to have a substantially reduced computational burden without adversely affecting the tracking performance of the controller. Additionally, an offline strategy that provides initial feasibility on the RMPC problem is presented. The effectiveness of the proposed scheme is demonstrated through numerical examples from the literature., Comment: IEEE TRANSACTIONS ON AUTOMATIC CONTROL

ImportanceThe antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as a potential treatment for COVID-19 due their effect on several cellular processes that impact viral replication. Although more than 100 ongoing trials are testing their efficacy, CQ and HCQ are being used widely in clinical practice, exposing COVID-19 patients to potentially significant cardiac adverse effects.ObjectiveTo systematically review the literature and estimate the risk of cardiac toxicity in patients receiving CQ or HCQ for COVID-19.Data SourcesA systematic search was conducted on May 27, 2020 of Ovid EBM Reviews, Ovid Embase (1974+), Ovid Medline (1946+ including epub ahead of print, in-process & other non-indexed citations), Scopus (1970+) and Web of Science (1975+) and preprint servers (Medrvix and ResearchSquare) and manual search of references lists.Study SelectionStudies that included COVID-19 patients treated with CQ or HCQ, with or without azithromycin, were included as follows: (1) COVID-19 patient population, (2) the study included more than 10 patients receiving either one of the medications, (3) reported electrocardiographic changes and/or cardiac arrhythmias.Data Extraction and SynthesisStudy characteristics and endpoints incidence were extracted. Due to the very low incidence of torsades de pointes (TdP) and other endpoints (rare events), the arcsine transformation was used to obtain a pooled estimate of the different incidences using a random-effects meta-analysis. Meta-regression analyses were used to assess whether the incidence of different endpoints significantly varied by multiple study-level variables specified a priori.Main Outcomes and MeasuresPooled Incidence of: (1) change in QTc value from baseline ≥ 60 ms, (2) QTc ≥ 500 ms, (3) the composite of endpoint 1 and 2, (4) TdP arrhythmia or ventricular tachycardia (VT) or cardiac arrest, (5) discontinuation of treatment due to drug-induced QT prolongation or arrhythmias.ResultsA total of 19 studies with a total of 5652 patients were included. All included studies were of high methodological quality in terms of exposure ascertainment or outcome assessment. Among 2719 patients treated with CQ or HCQ, only two episodes of TdP were reported; the pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I2=96%, 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5%, 95% CI (1-11), I2=98%. The pooled incidence of change in QTc from baseline of ≥ 60 ms was 7%, 95% CI (3-14), I2=94% (12 studies of 2008 patients). The pooled incidence of QTc ≥ 500 ms was 6%, 95% CI (2-12), I2=95% (16 studies of 2317 patients). Among 11 studies of 3127 patients, the pooled incidence of change in QTc from baseline of ≥ 60 ms or QTc ≥ 500 ms was 9%, 95% CI (3-17), I2=97%. Mean/median age, coronary artery disease, hypertension, diabetes, concomitant QT prolonging medications, ICU care, and severity of illness in the study populations explained between-studies heterogeneity.Conclusions and RelevanceTreatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation, which is a harbinger for drug-induced TdP/VT or cardiac arrest. CQ/HCQ use resulted in a relatively higher incidence of TdP as compared to drugs withdrawn from the market for this particular adverse effect. Therefore, these agents should be used only in the context of randomized clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.Key PointsQuestionWhat are the risks of different cardiac toxicities in patients receiving chloroquine (CQ) or hydroxychloroquine (HCQ) for COVID-19.FindingsIn this systematic review, treatment of COVID-19 patients with CQ or HCQ is associated with a clinically significant risk of drug-induced QT prolongation, and torsades de pointes (TdP) arrhythmia/ventricular tachycardia/cardiac arrest in a relatively higher incidence compared to drugs withdrawn from the market for such adverse effects.MeaningThese agents should be used only in the context of clinical trials, in patients at low risk for drug-induced QT prolongation, with adequate safety monitoring.

Objectives Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients. Methods Data sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach. Results Of 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80–1.49, I2 = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52–0.96, I2 = 0%), with a corresponding number needed to treat of 17 (95%CI 9–100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51–0.66, I2 = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38–1.06, five RCTs) and 0.83 (95%CI 0.55–1.24, five RCTs), respectively. Conclusions Cumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.

© 2022 International Federation of Clinical NeurophysiologyObjective: The significance of ictal magnetoencephalography (MEG) is not well appreciated. We evaluated the relationships between ictal MEG, MRI, intracranial electroencephalography (ICEEG), surgery and postoperative seizure outcome. Methods: A total of 45 patients (46 cases) with ictal MEG who underwent epilepsy surgery was included. We examined the localization of each modality, surgical resection area and seizure freedom after surgery. Results: Twenty-one (45.7%) out of 46 cases were seizure-free at more than 6 months follow-up. Median duration of postoperative follow-up was 16.5 months. The patients in whom ictal, interictal single equivalent current dipole (SECD) and MRI lesion localization were completely included in the resection had a higher chance of being seizure-free significantly (p < 0.05). Concordance between ictal and interictal SECD localizations was significantly associated with seizure-freedom. Concordance between MRI lesion and ictal SECD, concordance between ictal ICEEG and ictal and interictal SECD, as well as concordance between ictal ICEEG and MRI lesion were significantly associated with seizure freedom. Conclusions: Ictal MEG can contribute useful information for delineating the resection area in epilepsy surgery. Significance: Resection should include ictal, interictal SECDs and MRI lesion localization, when feasible. Concordant ictal and interictal SECDs on MEG can be a favorable predictor of seizure freedom.

The glucocorticoid receptor (GR) at the blood–brain barrier (BBB) is involved in the pathogenesis of drug-resistant epilepsy with focal cortical dysplasia (FCD); however, the roles of GR isoforms GRα and GRβ in the dysplastic brain have not been revealed. We utilized dysplastic/epileptic and non-dysplastic brain tissue from patients who underwent resective epilepsy surgery to identify the GRα and GRβ levels, subcellular localization, and cellular specificity. BBB endothelial cells isolated from the dysplastic brain tissue (EPI-ECs) were used to decipher the key BBB proteins related to drug regulation and BBB integrity compared to control and transfected GRβ-overexpressed BBB endothelial cells. GRβ was upregulated in dysplastic compared to non-dysplastic tissues, and an imbalance of the GRα/GRβ ratio was significant in females vs. males and in patients > 45 years old. In EPI-ECs, the subcellular localization and expression patterns of GRβ, Hsp90, CYP3A4, and CYP2C9 were consistent with GRβ+ brain endothelial cells. Active matrix metalloproteinase levels and activity increased, whereas claudin-5 levels decreased in both EPI-ECs and GRβ+ endothelial cells. In conclusion, the GRβ has a major effect on dysplastic BBB functional proteins and is age and gender-dependent, suggesting a critical role of brain GRβ in dysplasia as a potential biomarker and therapeutic target in epilepsy.

Background SARS-CoV-2 infects its target cells via angiotensin converting enzyme 2 receptor, a membrane-bound protein found on the surface of many human cells. Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptors blockers (ARB) has been shown to increase angiotensin converting enzyme 2 expression by up to 5-fold. Areas of uncertainty These findings coupled with observations of the high prevalence and mortality among SARS-CoV-2-infected patients with underlying cardiovascular disease have led to a speculation that ACEIs/ARBs may predispose to higher risk of being infected with SARS-CoV-2. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and the risk of SARS-CoV-2 infection or hospitalization due to COVID-19 disease. Data sources We searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Medrxiv.org preprint server until June 18, 2020. Therapeutic advances Ten studies (6 cohorts and 4 case control) that enrolled a total of 23,892 patients and 853,369 controls were eligible for inclusion in our meta-analysis. One study was excluded from the analysis because of high risk of bias. Prior use of ACEIs was not associated with an increased risk of acquiring SARS-CoV-2 or hospitalization due to COVID-19 disease, odds ratio 0.98, 95% confidence interval (0.91-1.05), I2 = 15%. Similarly, prior use of ARBs was not associated with an increased risk of acquiring SARS-CoV-2, odds ratio 1.04, 95% confidence interval (0.98-1.10), I2 = 0%. Conclusion Cumulative evidence suggests that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19 or hospitalization due to COVID-19 disease. Our results provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs because of fear of COVID-19.

BackgroundChloroquine (CQ) and hydroxychloroquine (HCQ) show anti-SARS-CoV-2 activity in vitro; however, clinical studies have reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin (AZ) on outcomes of COVID-19 patients.MethodsWe searched Medline, Embase, EBM Reviews, Scopus, Web of Science, preprints and grey literature up to July 7, 2020. We included studies that assessed COVID-19 patients treated with CQ or HCQ, with or without AZ. We pooled only adjusted effect estimates of mortality using a random effect model. We summarized the effect of CQ or HCQ on viral clearance and ICU admission/ mechanical ventilation.ResultsOut of 1463 citations screened for eligibility, five RCTs and 14 cohort studies were included (20,263 hospitalized patients). Thirteen studies (1 RCT and 12 cohorts) with 15,938 patients examined the effect of HCQ on short term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2=0 %, p=0.647). Six cohort studies examined the effect of HCQ and AZ combination among 14,016 patients. The pooled adjusted OR was 0.93 (95% CI 0.79-1.11, I2=59.3%, p=0.003). Two cohort studies and three RCTs found no significant effect of HCQ on viral clearance. One RCT with 48 patients demonstrated improved viral clearance in patients treated with CQ and HCQ. Three cohort studies found that HCQ with or without AZ had no significant effect on mechanical ventilation/ ICU admission.ConclusionModerate certainty evidence suggests that HCQ, with or without AZ, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19.SummaryThis systematic review and meta-analysis showed that in-hospital treatment of COVID-19 patients with antimalarials medications failed to reduce short-term mortality and morbidity with potential harm if used in combination with azithromycin.

Background: Direct anterior hip replacement is a slightly aggressive surgical procedure but potentially widespread. It involves opening on the front of the hip to allow the joint to be substituted by moving muscles aside along their ordinary tissue planes without removing any tendons. Nevertheless, there is diminutive consent concerning the threats and profits of this method compared to the posterior approach (PA) regarding the rates of dislocation and infection. Methods: This research is a prospective study conducted in Erbil city from September 2015 to September 2017 on 57 patients, including 28 females and 29 males, with primary total hip arthroplasty (THA). Twenty-nine patients were enrolled in the direct anterior approach (DAA: First group), and 28 patients were registered in the PA group (PA: Second group). Their age ranged between 49 and 80 years, and the regular follow-up was 12 months for all patients. Results: It was found that using the DAA, there was a significantly (P ≤ 0.05) lower incidence rate of dislocation in patients undergoing THA than the PA. No significant difference in the rates of infection was noticed between both groups. However, slightly shorter operational time and extent of the incision were noticed in the DAA group, and less blood loss was found in the PA group (non-significant). Conclusion: We realized that DAA has a clear advantage over PA regarding the lower incidence in the dislocation risk and without variance in the infection rates.

This paper presents a practical solution for two existing problems in traditional electrical energy measurements. The first problem is the manual electrical billing system; so far, some countries are still adopting a manual technique with a high percentage of human errors and much complains from the consumers’ side and a lot of work from the authorities’ side. The second problem is having a low power factor at most of the domestic loads and some main commercial ones. Low power factor causes more current to flow in the network leading to an overheating of transformers and cables, and an increase of the core losses of transformers; in addition, less power factor means more burned fuel and more environment pollution. In This study, an automated solution for both problems is introduced, where two control units are added to the already existing three phase energy meters. The first unit solves the problem of manual billing by automatically calculating the monthly bill and sending monthly SMS messages to the consumers as well as authorities. The second unit solves the problem of low power factor by injecting reactive power using capacitor bank at the end load points to maintain a power factor of 0.95 at all load cases. A penalty will be added to the monthly calculated bill once the above value is violated. A prototype was implemented proving the capability of introducing both solutions using existing meters with a reasonable added cost

This paper presents an algorithm to calculate tightened invariant tubes for output feedback model predictive controllers (MPC). We consider discrete-time linear time-invariant (DLTI) systems with bounded state and input constraints and subject to bounded disturbances. In contrast to existing approaches which either use pre-defined control and observer gains or compute the control and observer gains that optimize the volume of the invariant sets for the estimation and control errors separately, we consider the problem of optimizing the volume of these sets simultaneously. The nonlinearities associated with computing the control and observer gains are circumvented by the application of Farkas’ Theorem and an extended Elimination Lemma, to convert the nonconvex optimization problem into a convex semidefinite program. An update algorithm is then used to reduce the volume of the invariant tube through a finite number of iterations. Numerical examples are provided to illustrate the effectiveness of the proposed algorithm.

Linear robust control schemes, for example the H∞ control, are commonly utilized in the control design of an active suspension system, with a linearized and time-invariant state-space model of the system adopted. However, the vehicle parameter uncertainties are mainly ignored and their effect on the control robustness is not investigated. In this paper, a µ-synthesis-based control scheme is synthesized for a full car with the recently introduced Series Active Variable Geometry Suspension (SAVGS), to mainly enhance the ride comfort and road holding performance, with two significant practical uncertainties in the sprung mass and the suspension damping taken into account. Numerical simulations with a high fidelity nonlinear vehicle model are performed, with the cases of the fixed and swept values of the sprung mass tested, to assess the control robustness and performance of the developed scheme against the passive suspension as well as the H∞ -controlled SAVGS. The proposed µ-synthesis control scheme is proved to be more effective for realistic applications as it is capable of maintaining the suspension performance improvement regardless of variations of system parameters associated with the uncertainties, while the H∞ control performance tends to deteriorate when a notable deviation from the nominal values occurs.

The recent advancement in vehicular networking technology provides novel solutions for designing intelligent and sustainable vehicle motion controllers. This work addresses a car-following task, where the feedback linearisation method is combined with a robust model predictive control (RMPC) scheme to safely, optimally and efficiently control a connected electric vehicle. In particular, the nonlinear dynamics are linearised through a feedback linearisation method to maintain an efficient computational speed and to guarantee global optimality. At the same time, the inevitable model mismatch is dealt with by the RMPC design. The control objective of the RMPC is to optimise the electric energy efficiency of the ego vehicle with consideration of a bounded model mismatch disturbance subject to satisfaction of physical and safety constraints. Numerical results first verify the validity and robustness through a comparison between the proposed RMPC and a nominal MPC. Further investigation into the performance of the proposed method reveals a higher energy efficiency and passenger comfort level as compared to a recently proposed benchmark method using the space-domain modelling approach., Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessible

The International Narcotics Control Board's (INCB) opioids consumption data are often cited in the literature and by policy makers to benchmark the adequacy of pain management among different countries. This practice may be inaccurate as INCB data does not account for variations in disease burden and use of other pain medications and only controls for population sizes differences among countries.To demonstrate that INCB consumption data may not be an accurate/sensitive indicator for pain management adequacy due to significant inter-country variations in disease burden and in the use of pain medications that are not reported by INCB.We compared opioid consumption data between 2012 and 2016 for Jordan and King Hussein Cancer Center vs five high-income countries (United States of America, United Kingdom, France, Sweden, and Japan) taking into consideration the cancer burden in those countries. In addition, we examined the significance of tramadol utilization in the setting of cancer pain management.Jordan's INCB-reported opioid consumption is ostensibly low at a median of 291 sDDD/million inhabitants/day. Compared to Jordan, the median consumption in the five HICs is 34 (range 4-172) times that of Jordan. However, when consumption is adjusted to cancer burden data, the gap is significantly reduced to a median of 2 (range 0.2-24) times that of Jordan and in the case of one institution's experience, the gap is eliminated. Furthermore, Jordan's tramadol's median consumption between 2012-2016 of 176 kg is equivalent to 127% of morphine consumption on an equianalgesic basis.INCB data should not be utilized to benchmark the adequacy of pain management among different countries without taking into consideration variations in disease burden and the use of tramadol and other pain drugs.

This research paper studies the use of an environmentally and not expensive method to degrade Orange G dye (OG) from the aqueous solution, where the extract of ficus leaves has been used to fabricate the green bimetallic iron/copper nanoparticles (G-Fe/Cu-NPs). The fabricated G‑Fe/Cu-NPs were characterized utilizing scanning electron microscopy, BET, atomic force microscopy, energy dispersive spectroscopy, Fourier-transform infrared spectroscopy and zeta potential. The rounded and shaped as like spherical nanoparticles were found for G-Fe/Cu‑NPs with the size ranged 32-59 nm and the surface area was 4.452 m2/g. Then the resultant nanoparticles were utilized as a Fenton-like oxidation catalyst. The degradation efficiency of OG dye highly depends on H2O2 concentration (1.7-5.28 mM), catalyst dose (0.4-1.6 g/L), pH (2-7), initial OG concentration (25-75 mg/L), and temperature (20-50 ℃). Batch experiments showed that 94.8 % of 50 mg/L of OG dye was removed within the optimum peroxide concentration, dose, pH and temperature which were 3.52 mM, 1 g/L, 3, and 40℃ respectively along with 30 min contact time. The results of kinetic models showed that OG removal followed the second-order model. Finally, the thermodynamic study of reaction was also examined and concluded to endothermic reaction with 29.725 kJ/mol activation energy.

Background The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America. Methods A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included. Results Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%. Conclusions The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE.

Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.Objective: We investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan.Methods: Febrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden.Results: Of 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9–40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30–44 × 103 copies/PCR run [12 × 103 – 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%.Conclusion: Among children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.

Literature regarding outcomes and predictors of complications secondary to infective endocarditis (IE) is limited. We aimed to study the outcomes and predictors of complications of IE.Data from a national emergency department sample, which constitutes 20% sample of hospital-owned emergency departments in the USA, were analyzed for hospital visits for IE. Complications of endocarditis were obtained by using ICD codes. Multivariable generalized linear method was used to evaluate predictors of in-hospital mortality and complications.Out of 255,838 adult IE patients (mean age 60.3 ± 20.1 years, 48.5% females), 97,803 (38.2%) patients developed one or more major complications. The major complications were cardiovascular system complications [57,900 (22.6%)], neurologic [42,851 (16.7%)] complications, and renal [16,236 (6.4%)] complications. These included cardiogenic shock [3873 (1.5%)], septic shock [25,798 (10.1%)], acute heart failure [35,602 (14%)], systemic thromboembolism (STE) [21,390 (8.36%)], heart block [11,430 (4.47%)], in-hospital dialysis [2880 (1.1%)], and disseminated intravascular coagulation (DIC) [2704 (1.1%)]. Patients with complicated IE had risk of mortality (adjusted RR 1.12, 95% CI 1.11-1.13, p 0.001). The complications strongly associated with mortality were septic shock (RR 1.29, 95% CI 1.27-1.30, p 0.001), cardiogenic shock (RR 1.24, 95% CI 1.20-1.29, p 0.001), DIC (RR 1.4, 95% CI 1.35-1.46, p 0.001), and STE (RR 1.07, 95% CI 1.05-1.08, p 0.001). Staphylococci were the predominant causative organisms (30.8%) among the complicated IE subgroups with higher associated mortality (42.8%). The main predictors of complications from IE were congenital heart disease, history of congestive heart failure, high Elixhauser comorbidity profile, staphylococcal infection, and fungal infections. The prevalence of cardiogenic shock increased over the study years from 1.13 to 1.98% (p-trend 0.04).Complicated IE is not uncommon and is associated with significant mortality. Staphylococcal infections were associated with high mortality rates. There has been an increasing trend of cardiogenic shock among IE patients across the US. Further research is needed to improve the outcomes of complicated endocarditis.

Background and ObjectivesWe aim to provide detailed imaging-electroclinicopathologic characterization of the black line sign, a novel MRI marker for focal cortical dysplasia (FCD) IIB.Methods7T T2*-weighted gradient-echo (T2*w-GRE) images were retrospectively reviewed in a consecutive cohort of patients with medically intractable epilepsy with pathology-proven FCD II, for the occurrence of the black line sign. We examined the overlap between the black line region and the seizure-onset zone (SOZ) defined by intracranial EEG (ICEEG) and additionally assessed whether complete inclusion of the black line region in the surgical resection was associated with postoperative seizure freedom. The histopathologic specimen was aligned with the MRI to investigate the pathologic underpinning of the black line sign. Region-of-interest–based quantitative MRI (qMRI) analysis on the 7T T1 map was performed in the black line region, entire lesional gray matter (GM), and contralateral/ipsilateral normal gray and white matter (WM).ResultsWe included 20 patients with FCD II (14 IIB and 6 IIA). The black line sign was identified in 12/14 (85.7%) of FCD IIB and 0/6 of FCD IIA on 7T T2*w-GRE. The black line region was highly concordant with the ICEEG-defined SOZ (5/7 complete and 2/7 partial overlap). Seizure freedom was seen in 8/8 patients whose black line region was completely included in the surgical resection; in the 2 patients whose resection did not completely include the black line region, both had recurring seizures. Inclusion of the black line region in the surgical resection was significantly associated with seizure freedom (p= 0.02). QMRI analyses showed that the T1 mean value of the black line region was significantly different from the WM (p< 0.001), but similar to the GM. Well-matched histopathologic slices in one case revealed accumulated dysmorphic neurons and balloon cells in the black line region.DiscussionThe black line sign may serve as a noninvasive marker for FCD IIB. Both MRI-pathology and qMRI analyses suggest that the black line region was an abnormal GM component within the FCD. Being highly concordant with ICEEG-defined SOZ and significantly associated with seizure freedom when included in resection, the black line sign may contribute to the planning of ICEEG/surgery of patients with medically intractable epilepsy with FCD IIB.Classification of EvidenceThis study provides Class II evidence that in individuals with intractable focal epilepsy undergoing resection who have a 7T MRI with adequate image quality, the presence of the black line sign may suggest FCD IIB, be concordant with SOZ from ICEEG, and be associated with more seizure freedom if fully included in resection.