Başkent University

Castell’s book is the first part of his milstone “The Information Age: Economy Society, and Culture” work. The author states that, the triology was prepared to be a single book, but then with the contributions of the editor, it was divided into three books by making each part of the study a separate book. In this particular book, Castells presents an easily understandable and comprehensive analysis by examining the economic, social, and cultural changes that caused by the Network Society. He does this by being as realistic as possible and reaching a clear conclusion by supporting all of his claims with various statistics and examples.

We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance ( p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion ( p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely high-powered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.

International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer. SIGNIFICANCE: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.

AIMS: This European Association Cardiovascular Imaging (EACVI) Expert Consensus document aims at defining the main quantitative information on cardiac structure and function that needs to be included in standard echocardiographic report following recent ASE/EACVI chamber quantification, diastolic function, and heart valve disease recommendations. The document focuses on general reporting and specific pathological conditions such as heart failure, coronary artery and valvular heart disease, cardiomyopathies, and systemic diseases. METHODS AND RESULTS: Demographic data (age, body surface area, blood pressure, and heart rhythm and rate), type (vendor and model) of ultrasound system used and image quality need to be reported. In addition, measurements should be normalized for body size. Reference normal values, derived by ASE/EACVI recommendations, shall always be reported to differentiate normal from pathological conditions. This Expert Consensus document suggests avoiding the surveillance of specific variable using different ultrasound techniques (e.g. in echo labs with high expertise in left ventricular ejection fraction by 3D and not by 2D echocardiography). The report should be also tailored in relation with different cardiac pathologies, quality of images, and needs of the caregivers. CONCLUSION: The conclusion should be concise reflecting the status of left ventricular structure and function, the presence of left atrial and/or aortic dilation, right ventricular dysfunction, and pulmonary hypertension, leading to an objective communication with the patient health caregiver. Variation over time should be considered carefully, taking always into account the consistency of the parameters used for comparison.

Biomaterials currently used in cardiac tissue engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating cardiac cell behavior. Here, the myocardial tissue constructs are engineered based on reduced graphene oxide (rGO)-incorporated gelatin methacryloyl (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhances the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO-GelMA scaffolds exhibit better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes show stronger contractility and faster spontaneous beating rate on rGO-GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO-GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial designs to improve tissue engineering outcomes. The engineered cardiac tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high-fidelity tissue models for drug studies and the investigations of cardiac tissue development and/or disease processes in vitro.

BACKGROUND: Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are increasing in frequency and are associated with high mortality rates. Circulation of CTX-M-type ESBLs in the community is of particular concern, because it may confound standard infection-control measures. METHODS: We analyzed the results of epidemiologic studies of infection caused by ESBL-producing Enterobacteriaceae in nonhospitalized patients from 6 centers in Europe, Asia, and North America. Risk factors for infection with an ESBL-producing organism were identified by univariate and multivariate analyses. RESULTS: A total of 983 patient-specific isolates were reviewed (890 [90.5%] of which were Escherichia coli, 68 [6.9%] of which were Klebsiella species, and 25 [2.5%] of which were Proteus mirabilis); 339 [34.5%] of the isolates produced ESBLs. CTX-M types were the most frequent ESBLs (accounting for 65%). Rates of co-resistance to ciprofloxacin among ESBL-producing isolates were high (>70%), but significant variation was seen among centers with respect to rates of resistance to gentamicin, amoxicillin-clavulanate, and trimethoprim-sulfamethoxazole. Similar risk factors for infection with an ESBL-producing organism were found in the different participating centers. Significant risk factors, identified by multivariate analysis, were recent antibiotic use, residence in a long-term care facility, recent hospitalization, age 65 years, and male sex (area under the receiver-operator characteristic [ROC] curve, 0.80). However, 34% of ESBL-producing isolates (115 of 336 isolates) were obtained from patients with no recent health care contact; the area under the ROC curve for the multivariate model for this group of patients was only 0.70, which indicated poorer predictive value. CONCLUSIONS: Community-acquired ESBL-producing Enterobacteriaceae are now prevalent worldwide, necessitating international collaboration. Novel approaches are required to adequately address issues such as empirical treatment for severe community-acquired infection and infection control.

AIMS: To describe the cardiac abnormalities in patients with COVID-19 and identify the characteristics of patients who would benefit most from echocardiography. METHODS AND RESULTS: In a prospective international survey, we captured echocardiography findings in patients with presumed or confirmed COVID-19 between 3 and 20 April 2020. Patient characteristics, indications, findings, and impact of echocardiography on management were recorded. Multivariable logistic regression identified predictors of echocardiographic abnormalities. A total of 1216 patients [62 (52-71) years, 70% male] from 69 countries across six continents were included. Overall, 667 (55%) patients had an abnormal echocardiogram. Left and right ventricular abnormalities were reported in 479 (39%) and 397 (33%) patients, respectively, with evidence of new myocardial infarction in 36 (3%), myocarditis in 35 (3%), and takotsubo cardiomyopathy in 19 (2%). Severe cardiac disease (severe ventricular dysfunction or tamponade) was observed in 182 (15%) patients. In those without pre-existing cardiac disease (n = 901), the echocardiogram was abnormal in 46%, and 13% had severe disease. Independent predictors of left and right ventricular abnormalities were distinct, including elevated natriuretic peptides [adjusted odds ratio (OR) 2.96, 95% confidence interval (CI) 1.75-5.05) and cardiac troponin (OR 1.69, 95% CI 1.13-2.53) for the former, and severity of COVID-19 symptoms (OR 3.19, 95% CI 1.73-6.10) for the latter. Echocardiography changed management in 33% of patients. CONCLUSION: In this global survey, cardiac abnormalities were observed in half of all COVID-19 patients undergoing echocardiography. Abnormalities were often unheralded or severe, and imaging changed management in one-third of patients.

Cyber-attacks represent a potential threat to information security. As rates of data usage and internet consumption continue to increase, cyber awareness turned to be increasingly urgent. This study focuses on the relationships between cyber security awareness, knowledge and behavior with protection tools among individuals in general and across four countries: Israel, Slovenia, Poland and Turkey in particular. Results show that internet users possess adequate cyber threat awareness but apply only minimal protective measures usually relatively common and simple ones. The study findings also show that higher cyber knowledge is connected to the level of cyber awareness, beyond the differences in respondent country or gender. In addition, awareness is also connected to protection tools, but not to information they were willing to disclose. Lastly, findings exhibit differences between the explored countries that affect the interaction between awareness, knowledge, and behaviors. Results, implications, and recommendations for effective based cyber security training programs are presented and discussed.

BACKGROUND: High-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF). MATERIALS AND METHODOLOGY: The European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF. RESULTS: The task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF. CONCLUSIONS: HFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings.

Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC)--or "neonatal hepatitis" suggesting PFIC--that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or "neonatal hepatitis" suggesting PFIC. Archival liver were retrieved and immunostained for BSEP. Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents. Among the 11 nonrelated children studied aged 13-52 months at diagnosis of HCC, 9 (and a full sibling, with neonatal hepatitis suggesting PFIC, of a tenth from whom liver was not available) had immunohistochemical evidence of BSEP deficiency; the eleventh child did not. Mutations in ABCB11 were demonstrated in all patients with BSEP deficiency in whom leukocyte DNA could be studied (n = 7). These mutations were confirmed in the parents (n = 14). With respect to the other 3 children with BSEP deficiency, mutations in ABCB11 were demonstrated in all 5 parents in whom leukocyte DNA could be studied. Thirteen different mutations were found. In conclusion, PFIC associated with BSEP deficiency represents a previously unrecognized risk for HCC in young children. Immunohistochemical evidence of BSEP deficiency correlates well with demonstrable mutation in ABCB11.

We drop the complexification procedure from the Newman-Janis algorithm and introduce more physical arguments and symmetry properties, and we show how one can generate regular and singular rotating black hole and non-black-hole solutions in Boyer-Lindquist coordinates. We focus on generic rotating regular black holes and show that they are regular on the Kerr-like ring, but physical entities are undefined there. We show that rotating regular black holes have much smaller electric charges, and, with increasing charge, they turn into regular non-black-hole solutions well before their Kerr-Newman counterparts become naked singularities. No causality violations occur in the region inside a rotating regular black hole. The separability of the Hamilton-Jacobi equation for neutral particles is also carried out in the generic case, and the innermost boundaries of circular orbits for particles are briefly discussed. Other, but special, properties pertaining to the rotating regular counterpart of the Ay\'on-Beato--Garc\'{\i}a regular static black hole are also investigated.

AIM: This paper is a report of a study conducted to describe the prevalence and risk factors for lower back pain amongst a variety of Turkish hospital workers including nurses, physicians, physical therapists, technicians, secretaries and hospital aides. BACKGROUND: Hospital workers experience more low back pain than many other groups, the incidence varies among countries. Work activities involving bending, twisting, frequent heavy lifting, awkward static posture and psychological stress are regarded as causal factors for many back injuries. METHOD: A 44-item questionnaire was completed by 1600 employees in six hospitals associated with one Turkish university using a cross-sectional survey design. Data were collected over nine months from December 2005 to August 2006 and analysed using Chi square and multivariate logistic regression techniques. FINDINGS: Most respondents (65.8%) had experienced low back pain, with 61.3% reporting an occurrence within the last 12 months. The highest prevalence was reported by nurses (77.1%) and the lowest amongst secretaries (54.1%) and hospital aides (53.5%). In the majority of cases (78.3%), low back pain began after respondents started working in the hospital, 33.3% of respondents seeking medical care for 'moderate' low back pain while 53.8% (n = 143) had been diagnosed with a herniated lumbar disc. Age, female gender, smoking, occupation, perceived work stress and heavy lifting were statistically significant risk-factors when multivariate logistic regression techniques were conducted (P < 0.05). CONCLUSION: Preventive measures should be taken to reduce the risk of lower back pain, such as arranging proper rest periods, educational programmes to teach the proper use of body mechanics and smoking cessation programmes.

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

OBJECT: Hydatidosis is both a medical and an economic problem in Turkey. The aim of this study was to analyze central nervous system (CNS) involvement in this disease, the related problems the disease causes, and its diagnostic and therapeutic aspects. METHODS: The authors conducted an extensive literature survey of the subject, in which papers published by Turkish authors in international and domestic journals were carefully analyzed. In addition, the authors conducted a cooperative study in which data were gathered from 47 neurosurgery departments across the country. The purpose was to determine the current status of the disease in Turkey; thus, each unit was questioned about their experience over the past 5 years. Contrary to common belief, the incidence of hydatidosis has not decreased significantly in Turkey. However, computerized tomography and magnetic resonance imaging have tremendously increased diagnostic specificity. Incidences of morbidity and mortality have improved over time, according to the results of the cooperative study, although these changes are not statistically significant. This may be attributed to experience that has been gained and to more frequent use of chemotherapy, as reflected by the cooperative study data. The two statistically significant findings of that study were expanded use of chemotherapy in the management of hydatidosis, and a higher rate of extraneural involvement in the disease. The cooperative study revealed that chemotherapy was being used more often and that there was a wider range of indications for this treatment than previously reported. The higher rate of extraneural involvement was predictable because lesions in the CNS are typically secondary in this disease. With regard to the studies' findings on cases of spinal hydatid cysts, the authors found that administration of chemotherapeutic drugs was the only statistically significant parameter (t = 3.78, p < 0.05), with the rate of chemotherapy higher in the cooperative study. CONCLUSIONS: Morbidity, mortality, and recurrence rates of hydatidosis uncovered by the cooperative study and the literature survey were not statistically significant.

OBJECTIVE: To assess the efficacy and tolerability of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, for the treatment of acute gouty arthritis. METHODS: In this 8-week, single-blind, double-dummy, dose-ranging study, patients with acute gouty arthritis whose disease was refractory to or who had contraindications to nonsteroidal antiinflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg; n = 143) or an intramuscular dose of triamcinolone acetonide (40 mg; n = 57). Patients assessed pain using a 100-mm visual analog scale. RESULTS: Seventy-two hours after treatment, a statistically significant dose response was observed for canakinumab. All canakinumab doses were associated with numerically less pain than triamcinolone acetonide; thus, a dose with equivalent efficacy to triamcinolone acetonide 72 hours after treatment could not be determined. The reduction from baseline in pain intensity with canakinumab 150 mg was greater than with triamcinolone acetonide 24, 48, and 72 hours after treatment (differences of -11.5 mm [P = 0.04], -18.2 mm [P = 0.002], and -19.2 mm [P < 0.001], respectively), and 4, 5, and 7 days after treatment (all P < 0.05). Canakinumab significantly reduced the risk of recurrent flares versus triamcinolone acetonide (P ≤ 0.01 for all doses) (relative risk reduction 94% for canakinumab 150 mg versus triamcinolone acetonide). The overall incidence of adverse events was similar for canakinumab (41%) and triamcinolone acetonide (42%); most were mild or moderate in severity. CONCLUSION: Our findings indicate that canakinumab 150 mg provides rapid and sustained pain relief in patients with acute gouty arthritis, and significantly reduces the risk of recurrent flares compared with triamcinolone acetonide.

The coronavirus disease 2019 (COVID-19) pandemic has created new and unpredictable challenges for modern medicine and healthcare systems. Preliminary reports have demonstrated that older age, previous cardiovascular disease, diabetes, and hypertension are risk factors for increased mortality.1 Data on the cardiac affinity of the virus and its potential to harm the cardiovascular system and the mechanisms by which this occurs are sparse.2,3A systemic infection generally increases demand on the heart, and can exacerbate underlying cardiac conditions. When the lungs are heavily involved, as seen in COVID-19 patients, this may have a major impact on cardiac function, particularly that of the right ventricle. Finally, COVID-19 may have direct effects on the heart, as may some drugs being used in its treatment. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and is transmitted by droplets from person to person.4 Echocardiographers in particular, and cardiac imagers more generally, are in close contact with patients and therefore likely to have a high risk of being infected. To decrease the risk of patient to patient, patient to imager, and imager to patient contamination, the indication for any cardiac imaging test should be carefully considered, and only those tests considered essential to patient care performed. Cardiologists and cardiology departments are heavily affected by this rapidly changing situation.5 The COVID-19 pandemic also increases the burden on cardiac imaging services generally. However, given its wide availability and key role as a bedside test, echocardiography is the most affected cardiac imaging modality. Common challenges faced by all cardiac imaging modalities during the pandemic include limited expert staff availability [sickness or redeployment in prioritized areas, such as intensive care units (ICUs)] and the risk of peri-procedural transmission of SARS-CoV-2 between patients and staff. The scope of these EACVI recommendations is to summarize how these challenges may be addressed during the pandemic. In particular, we focus upon bold prioritization and provide specific indications and recommendations on how to perform an echocardiogram during the pandemic whilst safeguarding both patient and staff. Some of our recommendations relating to the appropriate use of imaging modalities in the COVID-19 pandemic must be considered only as expert advice due to the lack of evidence-based scientific data and the rapidly changing global situation. For all modalities, the main question is: ‘Will undertaking this study substantially change patient management or be lifesaving?’ If the answer is yes, use the imaging modality with the best capability to meet the request, but also consider the safety of medical staff regarding exposure. It is very important that every cardiac imaging study is performed appropriately to minimize the risk of further dissemination of the disease (Key point 1 and Figure 1). This question needs to be considered in detail for each echocardiogram requested given the risk of cross-infection and the consumption of personal protective equipment. However, computed tomography (CT) and cardiac magnetic resonance (CMR) may also have a significant potential for contamination of personnel and patients, especially linked to transportation, but also via direct contamination during the scan. In parallel with echocardiography and other imaging modalities, CMR and CT should only be performed if the expected information is critical for clinical management and can be justified in the face of the following considerations: (i) risk of transportation of critically ill or high-risk patients; (ii) time duration of CMR; (iii) possible/significant risk of infection for professionals (technicians, physicians, nurses, and other personnel); (iv) possible/significant risk of contamination of equipment and facilities, leading to the need for full disinfection; and (v) whether the test is necessary to confirm the diagnosis, or whether this can be achieved based simply upon the clinical probability. In many countries, imaging exams for elective non-urgent patients have been cancelled or postponed. However, cardiac imaging is still being widely requested for inpatients or those presenting to the Emergency Department (Key point 2). The chest radiograph is the most commonly used imaging test in COVID-19 patients, but CT is frequently used to confirm COVID-19 pneumonia. Whilst this might conceivably provide some possible synergies and opportunities to gain information about the cardiovascular system, this requires bespoke protocols that are not widely employed. Dedicated coronary CT angiography is therefore usually required. One emerging clinical issue is that numerous patients with pneumonia caused by COVID-19 experience elevated troponins with and without signs of obstructive coronary artery disease. In this situation, coronary CT angiography can be of great help in excluding or confirming an acute coronary syndrome if the clinical picture is uncertain, substituting for an invasive coronary angiogram and the associated exposure of all the members of the cardiac catheterization laboratory team.6 Coronary CT angiography is also increasingly used to assess patients with chronic coronary syndromes, and can be considered in the COVID-19 pandemic in patients with severe symptoms. Another important and emerging role for CT in the pandemic is as a replacement for transoesophageal echocardiography (TOE) to rule out the presence of thrombus in the left atrial appendage before direct current (DC) cardioversion, thereby limiting operator exposure (Key point 3). Echocardiography should not routinely be performed in patients with typical signs of COVID-19 disease. Indeed, it should be restricted to those patients in whom it is likely to result in a change in management. Nevertheless, many COVID-19 patients will develop a range of different cardiovascular manifestations which will require a bedside echocardiographic study.7 Moreover, there are reasons to believe that the need for echocardiography might expand further as we understand more about COVID-19, with early reports indicating that patients with established cardiovascular disease and cardiovascular risk factors have worse prognosis than others, and are more likely to be admitted to hospital and need respiratory support.1 Dyspnoea is a typical finding in patients with cardiac disease, and echocardiography may be indicated in the diagnostic work-up, particularly in patients with subacute onset of dyspnoea, oedema, or cardiac murmurs and elevated cardiac biomarkers. Conversely, a normal pro-BNP test can frequently be used to exclude the need for an echocardiogram in patients with dyspnoea or oedema. In the ICU, echocardiography has sometimes been used to routinely monitor the progress of certain patients.7 This should not be routinely performed in the COVID-19 pandemic. Instead, echocardiography should be restricted to patients with cardiovascular instability or signs of right ventricular dysfunction or pulmonary hypertension. Lung ultrasound to detect COVID-19 pneumonia is also useful.8 Thickening of the pleurae, the appearance of B-lines, and lung consolidation indicate pneumonia, with pleural effusions rarely reported. Due to its bedside availability, scanning of the lungs by ultrasound can be performed as a quick diagnostic tool. If transthoracic echocardiography (TTE) is required to change patient management, we recommend a focused cardiac ultrasound study (FoCUS) as described below. The aim is to reduce the time of exposure with the patient and to decrease the risk of contamination.9 Hand-held or smaller lap-top-based scanners may have an advantage as they are easier to cover, clean, and disinfect than larger machines with higher capability.10 At a minimum, such a focused echocardiographic study in patients with verified or suspected COVID-19 should include the following. Left ventricle: systolic global function (ejection fraction), signs of regional dysfunction, end-diastolic cavity dimension. Right ventricle: global function [right ventricular fractional area change (RVFAC) or tricuspid annular plane systolic excursion (TAPSE)], end-diastolic cavity dimension, tricuspid regurgitation pressure gradient (TRP) (if possible). Valves: gross signs of valvar disease, but only in cases of critical clinical importance should an in-depth evaluation be considered. Pericardium: thickening or effusion. ECG monitoring during imaging can be omitted and measurements should be performed offline to reduce exposure and contamination. If a curtailed echocardiogram is performed because of the COVID-19 situation, this should be stated in the report. Due to increased metabolic and haemodynamic demands, infection and concomitant fever act as a cardiac stress test potentially aggravating the effects of pre-existing valve disease, heart muscle disease, coronary artery disease, and congenital heart disease. Similar and additional effects can be caused by reduced oxygenation of the blood due to respiratory failure. This may help explain why co-existing cardiovascular disease is a negative predictor in COVID-19 patients.1 Clinical decision-making may be complicated in these critically ill patients, and cardiac imaging may be decisive. However, unnecessary examinations should be avoided to reduce risk of contamination of personnel and misuse of resources. Indeed, careful consideration should be given to whether echocardiography and cardiac imaging will change management, including whether patients would be candidates for more advanced treatment strategies on the basis of the results of an echocardiogram. If not, the scan may be futile. Clinical priorities and procedures will change during this pandemic. Echocardiography should therefore generally be reserved for patients with symptomatic heart disease (NYHA III–IV) in this phase. Routine follow-up echocardiographic studies of patients with non-severe symptoms or those not eligible for invasive or surgical treatment should be postponed or cancelled. This includes patients with stable congenital heart disease. Patients with acute heart failure and patients with valvular heart disease with severe symptoms such as chest pain, syncope, and dyspnoea during daily activity should be prioritized and receive adequate treatment. Their prognosis without treatment is probably worse than that of most COVID-19 patients. Acute endocarditis, with no relationship to COVID-19, will also continue to appear, and the number of patients may even increase as visits to the dentist are cancelled. Endocarditis has a high mortality, and these patients should continue to have a high priority for echocardiography and treatment according to state of the art recommendations.11 If the patient has concomitant COVID-19, an individualized approach is necessary. In ST-segment elevation myocardial infarction (STEMI) we recommend an LV angiogram for LV function in patients having an invasive revascularization procedure. Echocardiography can then be avoided in these patients, with the exception of those that become haemodynamically unstable or develop potential post-STEMI complications. In unstable non-STEMI patients with positive troponins and clinical signs of heart failure, echocardiography may be of importance to justify a faster invasive revascularization procedure. Patients with murmurs should undergo echocardiography to rule out valve disease as the cause of their presentation with chest pain. TOE might be stressful to our patients and should be avoided in most patients with ongoing COVID-19. The risk of contamination of equipment and personnel is also very high during the procedure due to droplets and aerosols containing virus. The incremental role of TOE over TTE should be carefully considered. This procedure should therefore be reserved for patients where the suspected findings are of crucial importance to confirm or exclude a diagnosis or to guide treatment. Suggested considerations and precautions before and during cardiac imaging. Indications for stress echocardiography, as well as for other stress imaging techniques, seem very limited in the COVID-19 pandemic, and should be avoided in patients with acute infection. Coronary CT angiography should be the preferred method if patients are being investigated for chronic coronary syndromes.6 Ultrasonic contrast agent may be useful in some patients, but should not be used in circulatory unstable or critically ill patients.12 It is currently unclear whether maternal infection affects the foetus, by causing either structural heart disease or foetal myocarditis, and therefore routine foetal echocardiography in infected mothers is not recommended for the indication of COVID-19 infection alone. However, the indications for foetal echocardiography remain the same during the pandemic, in that pregnancies judged to be at high risk for foetal cardiac disease need to continue to be referred according to local guidelines, and assessed within the appropriate time frame.13 Counselling may be undertaken using video conferencing or other technology in order to reduce time in physical proximity to the patient, and the minimum number of healthcare professionals should attend scanning and counselling. Given the acute nature of the disease, and restrictions of hospital facilities for chronic patients, there are probably few defined indications for coronary CT angiography, CMR, or nuclear cardiology in patients with COVID-19 infection during the acute phase. Similar to the situation for echocardiography, patients scheduled for CMR, CT, and nuclear cardiology, with non-severe symptoms or not eligible for invasive or surgical treatment, should be postponed. Routine follow-up scans should be re-scheduled. A possible indication for CMR is the suspicion of COVID-19 myocarditis, but the clinical implication of detecting myocarditis in these patients is not determined. We suggest that positive troponins and myocardial dysfunction or severe arrhythmia not explained by other methods may be an indication for acute CMR if of crucial importance for the treatment and the patient is stable enough to be scanned. All equipment used in close contact with patients has the potential to carry droplets containing the virus. This includes ECG leads which should therefore be avoided when performing echocardiographic studies in COVID-19 patients. Moderately warm water and a mild detergent constitute the basis of equipment cleaning in all cardiac imaging machines, including the echocardiographic probe. An ordinary water-soluble disinfectant should also be added, but not on the membrane. A non-alcoholic disinfectant should be used on the echocardiographic probe (please confirm with recommendations for each vendor). Dedicated wipes may also be used in this process. Protecting the echocardiographic machines with custom-made covers may be possible if available, but, if not, other protective equipment can be fashioned using local entrepreneurs and ingenuity. It is, however, important not to cover the screen in a way that reduces the view for the echocardiographer. This may reduce the quality of the study and increase scan duration. Similarly, the keyboard should be fully operative during the investigation. To facilitate the cleaning of the scanner, all additional 3-D and single-Doppler probes should be removed before the scanning starts, if they are not needed for proper diagnosis. ECG leads should also be removed, although this may make the recordings of loops more difficult and potentially more time consuming. In high-volume centres, one can consider dedicating separate scanners to be used exclusively for COVID-19-positive patients, that remain within designated COVID-19 areas. No additional disinfection procedure is necessary for a TOE probe as every location should have proper routines for cleaning and disinfection of these probes. A protective coat on the TOE probe might also be considered. The positioning of the patient vs. the echocardiographer and the scanner may be of importance. Patients placed in the left lateral position with the scanner positioned on the right side of the bench will result in the longest possible distance between the faces of the patient and the echocardiographer. The contamination of the scanner by airborne droplets from the patient will also probably be minimized. However, the preferred patient position is different among echocardiographers, and these recommendations should not be a hindrance to performing high-quality fast echocardiograms. A surgical mask on the patient will also reduce contamination by air droplets. The echocardiographic study will usually be performed in the ICU or in emergency rooms in critically ill patients. Less critical patients are usually examined in their ward rooms. Dedicated room(s) may be prepared in the echocardiographic lab, where unnecessary equipment can be removed to make the cleaning of the room as easy as possible. However, there is less risk of virus spread if the echocardiographer brings the echocardiographic machine to the patient, and the patient can remain in their isolation. Local factors must be considered with dedicated COVID-19 areas respected, ensuring COVID-19 ‘clean’ and ‘dirty’ areas are not mixed. Reading and conference rooms where echocardiograms are presented on small PC screens may prevent the recommended 2 m distance between the experts. Thus, larger rooms, with projectors that can present the images on large screens are recommended. Virtual communication technology that allows several colleagues to simultaneously visualise images on geographically remote screens is the preferred solution for multidisciplinary team meetings. All advice regarding personal protective equipment (PPE) should follow the internal rules in each institution. This will vary according to the local nature of the pandemic and the availability of PPE. We here offer some general advice. Repeated and thorough handwashing is the basis of virus protection for everyone, including patients and health professionals. In addition to handwashing after every examination, disinfecting agents should be used on the hands. When examining a patient with confirmed or suspected COVID-19, protective clothing, gloves, headcovers, specific facemasks, and eye shields must be used (Table 1). Patients should wear a surgical mask during imaging (Table 2). During TOE, medical protective masks must be used due to risk of aerosols and airborne spread (Table 3). How to adequately dress and undress is described in several publications and is not further described here. Recommendations during TTE and foetal echo Lower risk, patients with no no increased risk a negative virus test, or in areas with risk of COVID-19. risk, patients with symptoms or patients without symptoms in an area with or high risk of COVID-19. risk, patients with typical symptoms or confirmed COVID-19. 2 to to Recommendations for patients during all imaging modalities Recommendations during TOE For of of contamination, and disinfection of the TOE probe and its leads are not further described as procedures should include virus When performing an echocardiogram in patients without confirmed COVID-19, surgical should be used in where the risk of virus spread is high or should also be used and between every patient the of the virus on is If the patient has risk of infection due to risk in the or has no this may be especially if there is of face masks or in the for all the other imaging modalities are and should wear protective clothing, gloves, and and patients should wear a surgical mask during imaging. The scanner, and ECG are for cardiac CMR and CT scans but need to be after imaging (Table 1). of the scanners after imaging patients with COVID-19 infection is also An important to reduce contamination is to one scanner for infected patients and for and patients. The COVID-19 pandemic has to how best to perform cardiac imaging in the right patients at the right time and how to minimize the risk of cross-infection for imagers and patients recommendations are as to guide clinical during is a in our and one that is rapidly changing both the and for cardiac imaging. We our of how best to patients during the COVID-19 pandemic to change rapidly and will our of considerations in patients with suspected or confirmed COVID-19 imaging should be performed if appropriate and only if it is likely to substantially change patient management or be the imaging modality with the best capability to meet the request, but consider also the safety of medical staff regarding exposure non-urgent and routine follow-up exams may be postponed or even cancelled of contamination in patients with suspected or confirmed COVID-19 include risk of infection for professionals (technicians, physicians, nurses, other risk of contamination of equipment and facilities of contamination due to transportation of critically ill or high-risk echo machine should be to the patient duration of a cardiac imaging study will increase the of contamination for cardiac imaging Echocardiography should not routinely be performed in patients with COVID-19 disease A range of different cardiovascular manifestations can be in COVID-19 which may require cardiac including a bedside echocardiographic study A focused cardiac ultrasound study (FoCUS) is recommended to reduce the duration of exposure The risk of contamination of equipment and personnel is very high during CT or CMR as CT is frequently used to confirm COVID-19 pneumonia and might provide possible synergies and opportunities of cardiac imaging Coronary CT angiography can exclude or confirm an acute coronary syndrome in COVID-19 pneumonia where elevated troponins are LV function can be assessed by LV angiogram in patients with acute coronary during the invasive revascularization procedure troponins and myocardial dysfunction or severe arrhythmia of or myocarditis may be an indication for acute CMR if of importance for treatment, and patient can be for imaging Indications for foetal echocardiography remain the same as the COVID-19 pandemic

OBJECTIVE: To evaluate trunk muscle strength in unihemispheric stroke patients and to assess how it relates to body balance and functional disability in this patient group. DESIGN: This prospective case-comparison study investigated isometric and isokinetic reciprocal trunk flexion and extension strength at angular velocities in 38 unihemispheric stroke patients and 40 healthy volunteers. The Berg balance scale was used to assess balance and stability, and the FIM instrument was used to evaluate functional disability in the patient group. Patients were evaluated as soon as they were able to stand long enough for testing. RESULTS: Peak torque values for trunk flexion and extension were lower in the stroke patients than in the controls. The differences were significant for trunk flexion and for trunk extension. In both groups, peak torque values for trunk flexors were greater than peak torque values for trunk extensors. There was a significant positive correlation between trunk muscle strength and Berg balance scale score at discharge. Trunk muscle strength was not correlated with FIM total score or FIM motor score, but the locomotion-transfers FIM subscore at discharge was positively correlated with trunk muscle torque values, except for isometric extension. CONCLUSION: The findings indicate trunk flexion and extension muscle weakness in unihemispheric stroke patients, which can interfere with balance, stability, and functional disability.

PURPOSE: To determine angiographically the origins and variations of renal arteries. MATERIALS AND METHODS: The study included 855 consecutive patients (163 females, 692 males; mean age, 61 years) living in the Cukurova region of Turkey, who underwent either aortofemoropopliteal (AFP) angiography for the investigation of peripheral arterial disease, or renal angiography for renovascular hypertension, and were prospectively evaluated. Renal arteries were visualized by non-selective catheterization during AFP angiography and by selective or non-selective catheterization during renal angiography. Locations of renal artery origins and renal artery variations, including the presence of extra renal arteries and division patterns were analyzed on angiograms. RESULTS: The origin of main renal arteries off the aorta was between the upper margin of L1 and lower margin of L2 vertebra in 98% of the patients, and in 74%, this was the origin of extra renal arteries. The most common location for renal artery origin was the L1-L2 intervertebral disc level. A single renal artery was present in both kidneys in 76% of patients. Renal artery variations included multiple arteries in 24%, bilateral multiple arteries in 5%, and early division in 8% of the cases. Additional renal arteries on the right side were found in 16% and on the left side in 13% of cases. Of all the extra renal arteries, the percentage of accessory and aberrant renal arteries were 49% and 51%, respectively. CONCLUSION: Renal arteries originated between the first and the second lumbar vertebral levels in most patients. Extra renal arteries were quite frequent. These results should be kept in mind when a non-invasive diagnostic search is performed for renal artery stenosis, or when renal surgery related to renal arteries is performed.

The orphan nuclear receptor steroidogenic factor-1 (SF-1, NR5A1) regulates the transcription of multiple genes involved in steroidogenesis, reproduction, and male sexual differentiation. A heterozygous loss-of-function SF-1 mutation (G35E) has been described in a patient with adrenal failure and complete 46XY sex-reversal, indicating that haploinsufficiency of this factor is sufficient to cause a severe clinical phenotype. This mutation in the P-box region of the DNA-binding domain markedly impairs SF-1 binding to most response elements. In an infant with a similar clinical phenotype, we identified an SF-1 mutation (R92Q) in a highly conserved residue of the A-box, a region that functions as a secondary DNA-binding domain. Strikingly, the affected infant was homozygous for the R92Q mutation, but three relatives (parents, sister) were phenotypically normal despite being heterozygous for the mutation. In functional assays, the R92Q mutant exhibited partial loss of DNA binding and transcriptional activity when compared with the G35E P-box change, consistent with its phenotypic expression only when transmitted as a homozygous trait. Taken together, these two naturally-occurring SF-1 mutations reveal the relative functional importance of the P-box and A-box regions for monomeric binding by nuclear receptors. In addition, these patients reveal the exquisite sensitivity of SF-1-dependent developmental pathways to gene dosage and function in humans.

The Injury Hypothesis, first published in 1994 and modified several times between 1996 and 2002, holds that the reactive oxygen species-mediated reperfusion injury to allografts initiates and induces the alloimmune response and contributes to alloatherogenesis. Recent experimental and clinical evidence in support of the concept is presented suggesting that (1) reactive oxygen species-mediated allograft injury activates the innate immune system of the donor and recipient; (2) injury-induced putative endogenous ligands of Toll-like receptors (TLRs) of host origin such as heat shock proteins interact with and activate TLR4-bearing dendritic cells that mature and induce the adaptive alloimmune response (acute rejection), and interact with and activate TLR4-bearing vascular cells contributing to the development of alloatherosclerosis (chronic rejection); and (3) TLR4-triggered signaling, involved in the establishment of a reperfusion injury, seems to use myeloid differentiation marker 88-independent, Toll/interleukin-1 receptor domain containing adaptor inducing interferon-beta-dependent pathways that are associated with the maturation of dendritic cells and induction of interferon-inducible genes.