Objective: The arterial switch operation is the standard treatment for the transposition of the great arteries. The timely variation in the residual pressure gradient across the pulmonary arteries is ill-defined. This work is aimed to study the progressive changes in the pressure gradient across the pulmonary valve and pulmonary arteries after arterial switch operation (ASO). Methods: All eligible patients for this study who underwent arterial switch operation between 2000 and 2019 were reviewed. Transthoracic echocardiography (TTE), was used to estimate the peak pressure gradient across the pulmonary artery and its branches. The primary outcome was the total peak pressure gradient (TPG) which is the sum of peak pressure gradients across the main pulmonary artery and pulmonary artery branches. Furthermore, a longitudinal data analyses with mixed effect modeling were used to determine the independent predictors for the changes in pressure gradient. Results: 309 patients were included in the study. Over 17-year follow up, the freedom from pulmonary stenosis reintervention was 95% (16 out of the 309 patients underwent reintervention = 5%). the Longitudinal data analyses of serial 1844 echocardiographic studies for the included patients revealed that the TPG recorded in the first postoperative echocardiogram across pulmonary valve, right and left pulmonary artery branches was the most significant predictor for reintervention. Conclusion: The total peak gradient measured in the first postoperative echocardiogram is the most important predictor for reintervention. We propose that a total peak gradient in the first postoperative echocardiography of 55 mmHg or more is a predictor for reintervention

Since its first emergence in 2012, cases of infection with Middle East respiratory syndrome coronavirus (MERS-CoV) have continued to occur. In this study, we present two nucleic acid visualization assays that target the MERS-CoV UpE and N genes as a panel that combines reverse transcription recombinase polymerase amplification with a closed vertical flow visualization strip (RT-RPA-VF). The limit of detection was 1.2×10^1 copies/μl for the UpE assay and 1.2 copies/μl for the N assay. The two assays exhibited no cross-reactivity with multiple CoVs, including the bat severe acute respiratory syndrome related coronavirus (SARSr-CoV), the bat coronavirus HKU4, and the human coronaviruses 229E, OC43, HKU1 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The RT-RPA-VF assay does not require sophisticated equipment and provides rapid detection within 30 min, so it has potential for use in surveillance and detection of MERS-CoV in low-resource settings.

In this study, we unveiled the lumped effects at the reach spatial scale over three decades in one of the braided rivers in the Qinghai-Tibet Plateau of China, the Upper Lancang River (ULR). Using Landsat images obtained in 13 years between 1989 and 2018, we extracted flowing and non-flowing channels, active channel widths (unvegetated bars and flowing channels), and calculated lateral shifting rates of the main channel for the 13 periods. We also developed an empirical equation between vegetation area (Av) calculated from the high-resolution ortho-photo derived from an Unmanned Aerial Vehicle survey and Normalized Difference Vegetation Index for pixels of the Landsat image obtained at the same time. This relationship allowed us to estimate Av for other 12 selected years. We found that (1) braiding intensity increases with low discharges, indicating that the ULR is a very well-connected braided system with groundwater providing a large set of aquatic habitats, (2) this braided system is very well-supplied and actively shifting in relation to peak flow and flood duration, and (3) The ULR supports a progressive vegetation encroachment, which seems to be linked to temperature rising. Our study showed several similar morphological patterns to those in other braided rivers, such as the ones observed in the European Alps but much more active, well-supplied and highly connected. These similarities suggest that similar morphodynamic processes might take effect in the braided rivers with very high elevations and potentially high spots of biodiversity, indicating the ULR may be a reference for this region similarly to the Tagliamento in the Alps, but it seems that this system can be very sensitive to global change due to vegetation encroachment following temperature rising and decreases of low flows.

The space debris management and alleviation in the microgravity environment is a dynamic research theme of contemporary interest. Herein, we provide a theoretical proof of the concept of a lucrative energy conversion system that is capable for changing the space debris into useful powders in the international space station (ISS) for various bids. A specially designed broom is adapted to collect the space debris of various sizes. An optical sorting method is proposed for the debris segregation in the ISS by creating an artificial gravitational field using frame-dragging or gravitomagnetism. An induction furnace is facilitated for converting the segregated metal-scrap into liquid metal. A fuel-cell aided water atomization method is proposed for transforming the liquid debris into metal powder. The high-energetic metal powders obtained from the space debris could be employed for producing propellants for useful aerospace applications, and the silicon powder obtained could be used for making soil for fostering the pharmaceutical-flora in the space lab in the future aiming for the scarce-drug discoveries for high-endurance health care management. The proposed energy conversion system is a possible alternative for the space debris extenuation, and its real applications in orbiting laboratories through the international collaboration for the benefits to humanity.

Rationale Assessing the performance of diagnostic tests requires evaluation of the amount of diagnostic uncertainty the test reduces (i.e. 0% - useless test, 100% - perfect test). Statistical measures currently dominating the evidence-based medicine (EBM) field and particularly meta-analysis (e.g. sensitivity and specificity), cannot explicitly measure this uncertainty reduction. Mutual information (MI), an information theory statistic, is a more appropriate metric for evaluating diagnostic tests as it explicitly quantifies uncertainty and, therefore, facilitates natural interpretation of a test’s value. In this paper, we propose the use of MI as a single measure to express diagnostic test performance and demonstrate how it can be used in meta-analysis of diagnostic test studies. Methods We use two cases from the literature to demonstrate the applicability of MI meta-analysis in assessing diagnostic performance. These cases are: 1) Meta-analysis of studies evaluating ultrasonography (US) to detect endometrial cancer and 2) meta-analysis of studies evaluating magnetic resonance angiography to detect arterial stenosis. Results Results produced by the MI meta-analyses are comparable to the results of meta-analyses based on traditionally used statistical measures. However, the results of MI are easier to understand as it relates directly to the extent of uncertainty a diagnostic test can reduce. For example, a US test diagnosing endometrial cancer is 40% specific and 94% sensitive. The combination of these values is difficult to interpret and may lead to inappropriate assessment (e.g. one could favour the test due to its high sensitivity, ignoring its low specificity). In terms of MI however, the test reduces diagnostic uncertainty by 10%, which is marginal and thus the test is clearly not very useful. Conclusions We have demonstrated the suitability of MI in assessing the performance of diagnostic tests, which can facilitate easier interpretation of the true utility of diagnostic tests.

Objectives: To assess a newly developed educational video about lumbar puncture (LP), in the parents’ native language, tailored to their social background, and whether it facilitates their consent for LP. Methods: The randomized, controlled trial was conducted at outpatient pediatric clinics at a teaching hospital, Riyadh, Saudi Arabia. The conventional arm used LP verbal explanation. The second group utilized a standardized video with similar information. Parents’ knowledge, perceived LP risks, and willingness to consent were measured, before and after the intervention. Results: We enrolled 201 parents, with similar baseline characteristics. Both groups had an increase in knowledge scores, with Wilcoxon signed-rank test showing significant knowledge gains (Verbal Explanation: W=2693, n=83, P<0.001, and Video: W=5538, n=117, P< 0.001). However, the conventional verbal counseling resulted in more consistent knowledge gain (SD=14.5) as compared to the video group (SD= 18.94). The video group reported higher perceived risk (Mean 8.2, SD 3.59) than the verbal group (mean 7.12, SD 2.51). The less-educated parents perceived higher LP risk after watching the video (P< 0.001). Conclusions: LP video education in parents’ native language is as effective as conventional verbal education for the informed consent, with the additional advantage of reproducibility and more illustrations. While videos could facillitate remote procedural consenting process during infectious disease outbreaks; however, this should be followed by direct verbal interaction with parents, to ensure their full understanding and address any further concerns.

This paper examined the ability of √area△ using the material fatigue-life curves in estimating high-cycle fatigue life considering micro scratch. Ultrasonic fatigue tensile experiment were reported in determining the fatigue life model for micro scratches, where fatigue failure of all the specimens occurred from surface in the lab study. A high cycle fatigue (HCF) life model of TC17 based on micro scratches is established with the synthesis of surface condition fatigue strength modified by √area△ and the three-parameter power function. Reasonable agreements are observed between the model predictions and the experimental values. What is more, according to the application of √area△ from current papers, it can be suggested that the proposed √area△ is suitable for being used in fatigue strength and fatigue life analysis.

Gross primary production (GPP) determines the amounts of carbon and energy that enter terrestrial ecosystems. However, the tremendous uncertainty of the GPP still hinders the reliability of the GPP estimates and therefore understanding of the global carbon cycle. In this study, using observations from global eddy covariance (EC) flux towers, we appraised the performance of 22 widely used GPP models and quality of major spatial data layers that drive the models. Results show that the global GPP products generated by the 22 models varied greatly in the means (from 92.7 to 178.9 Pg C yr-1), trends (from -0.25 to 0.84 Pg C yr-1). Model structures (i.e., light use efficiency models, machine learning models, and process-based biophysical models) are an important aspect contributing to the large uncertainty. In addition, various biases in currently available spatial datasets have found (e.g., only 57% of the observed variation in photosynthetically active radiation was explained by the spatial dataset), which contributed greatly affects global GPP estimates. Our analysis indicates that the model development did not converge GPP simulations with the advance of time. Moving forward, research into efficacy of model structures and the precision of input data may be more important than the development of new models for global GPP estimation.

We introduce a new pattern of population genetic structure in a host-parasite system that can arise after secondary contact of previously isolated populations. Due to different generation time and therefore different tempo of molecular evolution the host and parasite populations reach different degrees of genetic differentiation during their separation (e.g. in refugia). Consequently, during the secondary contact the host populations are able to re-establish a single panmictic population across the area of contact, while the parasite populations stop their dispersal at the secondary contact zone and create a narrow hybrid zone. From the host’s perspective, the parasite’s hybrid zone functions on a microevolutionary scale as a “parasite turnover zone”: while the hosts are passing from area A to area B, their parasites turn genetically from the area A genotypes to the area B genotypes. We demonstrate this novel pattern on a model composed of Apodemus mice and Polyplax lice by comparing maternally inherited markers (complete mitochondrial genomes, and complete genomes of vertically transmitted symbiont Legionella polyplacis) with SNPs derived from the louse genomic data. We discuss circumstances that may lead to this pattern and possible reasons why it has been overlooked in the studies on host-parasite population genetics.

Abstract Prescription medicine misuse, especially misuse of opioids has become a major public healthcare issue in many developed countries such as the United States of America and Australia where this is associated with significant morbidity (Emergency Department visits due to acute toxicity) and mortality. In this review, we looked at the available data obtained from peer-reviewed articles and population surveys to gain an insight into the current situation in the Asia Pacific region. There is currently limited information available, but data from subpopulation surveys in a number of countries suggests that prescription medicine misuse is likely to be an issue of concern from a public health perspective in the Asia Pacific region. The available data suggest that misuse prevalence rates and the medicines that are commonly misused are similar to countries such as the USA and United Kingdom. Further studies are required to determine the overall prevalence of misuse, the harms associated with this and the sources of drugs being misused so that appropriate interventions can be implemented to tackle issues related to prescription medicine misuse in this region. Keywords: Prescription medicine misuse, drug abuse, opioids, benzodiazepines, GABA analogues

This spring, instructors moved their courses online in an emergency fashion as campuses were closed due to the pandemic. As colleges prepare for the next academic year, there is a need to provide flexible instruction that is more intentional for quality online learning. We taught two undergraduate courses online for the first time this spring and surveyed our students’ reactions to the course experiences. From our experiences and student feedback we identified design elements and activities that were beneficial in promoting student engagement, sense of connectivity, and learning. We describe four qualities for a successful transition to online learning: 1) big questions and core concepts; 2) peer groups including reflective writing; 3) outreach to broader scientific community; and 4) instructor’s social presence in the class. Our experience gives us confidence that courses can be redesigned for online without compromising rigor or essential learning goals.

Hypertrophic cardiomyopathy is a common heritable cardiomyopathy with various clinical phenotypes. A rare spiral variant has been recently reported that has been associated with adverse outcomes and has traditionally been diagnosed using cardiac magnetic resonance. We report a case of the rare variant spiral hypertrophic cardiomyopathy where we used transthoracic echocardiography with an ultrasound enhancing agent to demonstrate the geometry of spiral hypertrophic cardiomyopathy and compared to simultaneous cardiac MRI images. The use of echocardiography with ultrasound enhancing agents may prove to be a valuable tool in identifying the geometry of hypertrophic cardiomyopathy variants in selected patients.

Introduction:To retrospectively evaluate Doppler ultrasound findings for patients with popliteal vascular entrapment syndrome (PVES).Methods:Twenty-four patients (30legs) who underwent surgical intervention for PVES were included in this study.The popliteal artery, popliteal vein, and surrounding musculotendinous structures were explored in all symptomatic lower extremities using ultrasound. Intraoperative findings served as the gold standard. In the absence of popliteal artery occlusion, popliteal arteries were examined using Doppler ultrasound at rest and during a provocative maneuver.Results:Ultrasonography in 25 cases (25/30,83%) showed that gastrocnemius medial head or popliteal vascular anomalies were consistent with surgical photography results.The classic type I was found in five limbs, type II in twelve limbs, type III in seven limbs, and type V in one limb.In the remaining five cases (5/30,17%), no anatomical abnormalities of the popliteal fossa were discovered by the ultrasound examination.Among these, two cases (2/30,7%) were misdiagnosed as lower extremity atherosclerosis and popliteal vascular depression was not found. In addition, increasing blood flow velocity was found in three cases (3/30,10%) of compressed popliteal arteries using Duplex scanning during active plantar flexion, with decreasing flow at the distal end.Color Doppler ultrasound of the affected popliteal vessels showed varied degrees of vascular structure pathology, including arterial stenosis in ten limbs, occlusion in fifteen limbs, and aneurysm in two limbs.Conclusion:Conclusion: Doppler ultrasound may have a high diagnostic rate in PVES. Due to its simplicity, repeatability, functional evaluation of blood flow, and non-invasiveness, it can be used as a primary screening examination modality in PVES.Provocative maneuvers could help clinicians diagnose PVES

Background: Leukemia in children has a good prognosis with an overall cure rate of 85% in pediatric patients with acute lymphoblastic leukemia and 50-60% in pediatric patients with acute myeloid leukemia. Nevertheless in patients with refractory or relapsed leukemia the prognosis is limited and can only be cured by a salvage chemotherapy, in most cases followed by an allogeneic hematopoietic stem cell transplantation. Methods: In this retrospective case cohort ananlysis we investigated the outcome of eight patients with relapsed or refractory acute myeloid (n=2), lymphoblastic (n=4), biphenotypic (n=1) leukemia or T-lymphoblastic lymphoma (n=1) who failed to respond to standard salvage regimens. They received a salvage therapy with melphalan and cytarabine at our institution between 2015 and 2019. Results: After salvage chemotherapy with melphalan and cytarabine 63% of the patients achieved a remission of the disease and qualified for subsequent allogeneic hematopoietic stem cell transplantation. The one year overall survival rate was 50%, the three year overall survival rate was 29%. 25% of patients experienced a temporary period of fever and SIRS. Conclusions: The reported results of our case cohort analysis indicate that a salvage therapy with melphalan and cytarabine in relapsed or refractory leukemia could represent a curative approach with the possibility of achieving remission and subsequent allogeneic hematopoietic stem cell transplantation. Future multicentre studies are needed to verify the here presented results.

To the Editor, The coronavirus disease 2019 (COVID-19) pandemic is a significant, global threat to human life1. Because there is no established prevention or treatment protocol for COVID-19, all potential therapeutics and prevention strategies, which may reduce the severity of infection, are of vital importance. Nutritional therapy may be considered as one possible tool. Fermented foods have been a well-established part of the human diet for thousands of years. The health benefits associated with the fermentation process may be the result of direct interactions between the ingested live microorganisms and the host (probiotic effect), or indirectly as a result of ingestion of microbial metabolites produced during the fermentation process (biogenic effect)2.The presence of several comorbidities, such as hypertension, diabetes, hypercholesterolemia, and cardiovascular diseases severely influence the mortality rate reported in COVID-19 patients1. Fermented foods contain angiotensin converting enzyme (ACE) inhibitor peptides and they are recommended as a non-pharmacological strategy for the management of hypertension3. Angiotensin-converting enzyme 2 (ACE2) was identified as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. ACE inhibitors have the capacity to upregulate the expression and activity of ACE2 in the lungs. The higher level of ACE2 might increase the susceptibility of cells to SARS-CoV-2 viral host entry and propagation. On the other hand, the activation of ACE2 might ameliorate the acute lung injury. 4,5. ACE inhibitor peptides in fermented foods may have similar dual effects. Although it was previously thought that ACE inhibitors would increase susceptibility to SARS-CoV-2 infection, the available evidence does not seem to support the hypothesis4,5. After all, hypertension is a risk factor for severe COVID-19, and the hypertension-preventing diet can be one strategy to prevent and/or alleviate severe COVID-19. Moreover, fermented foods can lower the serum LDL-cholesterol values, hypertension, coronary heart disease and insulin resistance, which are other risk factors for severe COVID-193.It was shown that fermented foods and probiotics clinically effective in reducing the incidence, severity and duration of upper respiratory tract infections6. While none of these effects or mechanisms have been tested on the new SARS-CoV-2 virus, the effects of probiotics against other coronavirus strains have been reported6. Furthermore, secondary bacterial infections during COVID-19 infection are important causes of morbidity and mortality. Many species of LAB isolated from fermented vegetable and milk products have antibacterial activities due to the production of antimicrobial compounds such as bacteriocin and pediocin. It stands to reason that fermented foods may offer COVID-19 patients some protection against secondary bacterial infections.Fermented foods may modulate the gut microbiota with the probiotic bacteria they contain, and their biological ingredients, such as fiber and short chain fatty acids3. The gut microbiota and lung microbiota interact, which is called the Gut Lung Axis (GLA)6. GLA can shape immune responses and interfere with the course of respiratory diseases6. As reports from China indicate that COVID-19 might be associated with intestinal dysbiosis which causes inflammation and weakened response to pathogens. It is feasible that consumption of fermented foods could further influence and restore gut homeostasis and GLA6. Two randomized controlled trials showed that modulating gut microbiota can reduce ventilator-associated pneumonia (NOT specifically COVID-19) which can be evidence of gut-lung axis7. During the COVID-19 pandemic, 2–47% of infected patients required invasive mechanical ventilation7. Accordingly, we can speculate that COVID-19-related pneumonia may be alleviated in the same manner. Furthermore, aging is associated with a significant reduction in microbiome diversity. This may explain, at least partially, the different impacts of viral infections in elderly individuals.The inflammatory response plays a crucial role in the clinical manifestations of COVID-19. Post SARS-CoV-2 entry, host factors trigger an immune response against the virus. It left uncontrolled, this response may result in pulmonary tissue damage. This extremely high level of inflammatory response is called the cytokine storm5. Subsequently, there is the activation of transcription factors NF-κB, pathway that induce the expression of inflammatory factors5. It is important to determine the optimal of reducing inflammation. Fermented foods have anti-inflammatory properties, and may suppress pro-inflammatory cytokine production and increase Treg cells. Chen et al. showed that treatment with kefir peptides decreased the particulate matter-induced inflammatory cell infiltration and the expression of the inflammatory mediators IL-lβ, IL-4 and TNF-α in lung tissue by inactivating NF-κB signaling8. Reactive oxygen species also play a crucial role in the inflammatory response. As such, utilizing compounds with antioxidant properties may also be considered as a way to reduce the cytokine storm5. Fermented foods contain high amounts of antioxidants, such as proline, conjugated linoleic acid and phenolic compounds. These antioxidants also contribute to their anti-inflammatory effects3. Cytokine storm syndrome could be strictly linked with coagulopathy, generating acute pulmonary embolism caused by in-situ thrombosis. A 20% reduction in mortality was observed when patients with D-dimer exceeding 3.0 μg/mL were treated with prophylactic doses of heparin9. Some fermented food products have antithrombic or fibrinolytic activity which have the potential to reduce mortality in COVID-19 patients.Mortality is one of the most important ways of measuring the burden of COVID-19, and it differs between countries4. Among many factors, diet differs considerably between low and high mortality countries. Traditional dietary habits may be associated with these different mortality rates. Fermented cabbage is largely consumed in low-death rate European countries, Korea and Taiwan. It might be considered as one factor in the lower death rates. Consumption of fermented milk is common in Greece and Bulgaria, and they have very low death rates across European countries4. Fermented milk and cabbage are common in Turkey2 and Turkey is another low-death rate country4.In summary, based on the current evidence and clinical observations, we speculate that it is plausible to assume that these anti-inflammatory, antithrombotic, antioxidant, and antimicrobial effects could potentially contribute, at least partially, or in combination with other medications, in the prevention and/or alleviation of COVID-19-related symptoms. There is a need for well-designed, randomized controlled clinical trials to measure the effects of fermented foods in COVID-19.1. Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020.2. Celik V, Beken B, Yazicioglu M, Ozdemir PG, Sut N. Do traditional fermented foods protect against infantile atopic dermatitis.Pediatr Allergy Immunol. 2019;30(5):540-546.3. Melini F, Melini V, Luziatelli F, Ficca AG, Ruzzi M. Health-Promoting Components in Fermented Foods: An Up-to-Date Systematic Review.Nutrients. 2019;11(5).4. Bousquet J, Anto JM, Iaccarino G, et al. Is diet partly responsible for differences in COVID-19 death rates between and within countries?Clin Transl Allergy. 2020;10:16.5. Zabetakis I, Lordan R, Norton C, Tsoupras A. COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation.Nutrients. 2020;12(5).6. Baud D DAV, Gibson GR, Reid G, Giannoni E. . Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic. . 2020;8:186. Published 2020 May 8. doi:10.3389/fpubh.2020.00186.Front Public Health. 2020;8(186):1-5.7. Mak JWY, Chan FKL, Ng SC. Probiotics and COVID-19: one size does not fit all. Lancet Gastroenterol Hepatol. 2020;5(7):644-645.8. Chen HL, Hung KF, Yen CC, et al. Kefir peptides alleviate particulate matter <4 mum (PM4.0)-induced pulmonary inflammation by inhibiting the NF-kappaB pathway using luciferase transgenic mice.Sci Rep. 2019;9(1):11529.9. Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033-2040.Velat Celik, M.D. Trakya University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Edirne, TurkeyMuserref Celik, Trakya University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Edirne, TurkeyThe authors have no conflict of interest.There is no funding.All authors read, corrected and approved the final manuscript.

Nanotechnology is science, engineering, and technology conducted at the nanoscale, which is about 1 to 100 nanometers. It has led to the development of nanomaterials, which behave very differently compared with materials with larger scales and can be applied in a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition, and functionalisation of the system. Nanoparticles, carbon nanotubes, liposomes, polymers, dendrimers, nanogels, among others, can be nanoengineeried for controlling all parameters, including their functionalisation with ligands, which provide the desired interaction with the immunological system. However, undesired issues related to their toxicity and hypersensitivity responses have impeded more rapid health applications. Through interactions with the immune system, some of these nanostructures show promising applications as vaccines and diagnostics tools. Dendrimeric Antigens, Nanoallergens, and nanoparticles are potential tools for the in vitro diagnosis of allergic reactions. Glycodendrimers, liposomes, polymers, and nanoparticles have shown interesting applications in immunotherapy. There are wide panels of structures accessible, and controlling their physico-chemical properties would allow the obtainment of safer and more efficient compounds for clinical applications goals, either in diagnosis or treatment.

Severe bronchospasm during cardiopulmonary bypass is an unusual but potentially fatal event. No literature has previously reported such an event observed during surgery for type A aortic dissection. Herein, we report on a case of severe bronchospasm following cardiopulmonary bypass during aortic surgery for type A aortic dissection. Bronchospasm did not respond to any conventional therapy, necessitating extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation thus serves as an alternative and effective therapy for refractory bronchospasm.

The number of cases and mortality from COVID-19 is changing rapidly worldwide. We analyzed the case fatality rate (CFR) and recovery rate (RR) from COVID-19 using recent data. By using the information of CFR and RR, we made a comparison between high and middle or low-income countries to understand the current global outbreak. We further ranked the countries based on their CFR and RR from higher to lower.

Background: Open living donor hepatectomy (OLDH) is a highly painful procedure. Advanced strategies for enhancing perioperative analgesia and accelerating recovery are needed for patients undergoing OLDH. This study evaluated the effects of intravenous infusion of dexmedetomidine (DEX) during OLDH on postoperative analgesia and recovery. Methods: This prospective, randomized, double-blinded, and placebo-controlled study included 34 patients randomized to a control group (group C) and a DEX group (group D). Utilization of intravenous patient-controlled analgesia (IV-PCA) pump, pain intensity, and postoperative recovery variables were recorded. Moreover, intraoperative anesthetic consumption, hemodynamic parameters, and fluid status were also recorded. Results: During the first 24 hours after surgery, patients in group D had a lower pain intensity. The cumulative numbers of IV-PCA pump presses and fentanyl consumption within 24 and 48 hours postoperatively in group C were significantly higher than in group D. The time to first IV-PCA attempt was prolonged in group D. In addition, faster flatus passage was observed in group D. Intraoperatively, fewer anesthetic agents were required in group D. Less fluctuation in hemodynamics and reduced bleeding were also found in group D. Conclusions: The present study revealed that the addition of intravenous infusion of DEX during OLDH provided several benefits in relieving postoperative pain and promoting recovery. Therefore, we concluded that intraoperative DEX infusion may play an important role in enhancing recovery of patients undergoing OLDH.

Abstract: Coronavirus disease 2019 (COVID-19), has affected many regions and countries. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has a powerful ability to spread and is highly lethal. SARS-CoV-2 belongs to CoVs, together with the SARS-CoV and middle east respiratory syndrome-CoV. SARS-CoV-2 damages the lungs and some other organs in humans by infecting cells via binding to the ACE2 receptor. The infection with SARS-CoV-2 results in varying degrees of clinical manifestations. Although the amount of the evidence in favor of the impact of COVID-19 on the clinical manifestations of myocardial injury and the onset of cardiovascular disease (CVD) is increasing, myocardial cell damage caused by viruses not identified in biopsies and autopsies. Therefore, it has been suggested that viruses might affect cardiac function by mechanisms other than direct infection of cardiomyocytes, and several plausible conjectures have been proposed. Based on the fact that the viruses can exert influence on multiple systems in an organism, this article describes and proposes, for the first time, the possible impact of the interaction between the brain and the heart on the cardiovascular system in COVID-19 patients.

Background and Purpose: Andrographolide (AG) is a labdane diterpenoid herb, which is isolated from the leaves of Andrographis paniculate, and widely used for its potential medical properties. However, there are no reports on the effects of AG on the human suprapatellar fat pad of osteoarthritis patients. In the present study, our goal was to evaluate the innovative effects of AG on viability and Tri-lineage differentiation of human mesenchymal stem cells from suprapatellar fat pad tissues. Experimental approach: The effects of Andrographolide on viability and differentiation of human primary mesenchymal stem cells obtained from human suprapatellar fat pad tissues were evaluated by staining assay. Moreover, the effects on molecular expression were quantitatively measured by mRNA expression in real time PCR. Key Results: The results revealed that AG had no cytotoxic effects when the concentration was less than 12.5 µg/mL. Interestingly, AG had significantly enhanced, dose dependent, osteogenesis and chondrogenesis as evidenced by a significantly intensified stain for Alizarin Red S, Toluidine Blue and Alcian Blue. Moreover, AG can upregulate the expression of genes related to osteogenic and chondrogenic differentiation, including Runx2, OPN, Sox9, and Aggrecan in mesenchymal stem cells from human suprapatellar fat pad tissues. In contrast, AG suppressed adipogenic differentiation as evidenced by significantly diminished Oil Red O staining and expression levels for adipogenic-specific genes for PPAR-γ2 and LPL. Conclusions and Implications: These findings confirm that AG can specifically enhance osteogenesis and chondrogenesis of mesenchymal stem cells from human suprapatellar fat pad tissues. It has potential as a therapeutic agent derived from natural sources for regenerative medicine.

Nowadays, COVID-19 represents the most serious inflammatory respiratory disease worldwide. Despite of many proposed therapies, no effective medication has been approved yet. Neutrophils appear to be the key mediator for COVID-19-associated inflammatory immunopathologic, thromboembolic and fibrotic complications. Thus, for any therapeutic agent to be more appropriate, it should greatly block the neutrophilic component of COVID-19. One of the effective therapeutic approaches investigated to reduce neutrophils-associated inflammatory lung diseases with less adverse effects was Roflumilast. Being a highly selective PDE4i, roflumilast acts by enhancing cAMP level, that probably potentiates its anti-inflammatory action via increasing NEP activity. Because activating NEP was previously reported to mitigate several airway inflammatory ailments; this review deeply discusses the proposed NEP-based therapeutic properties of roflumilast, which may be of great importance in curing COVID-19. However, further clinical studies are required to confirm this strategy and to evaluate its in-vivo preventive and therapeutic efficacy against COVID-19.

Background: We described the QTc interval prolongation and related adverse cardiac events during the administration of hydroxychloroquine (HCQ) and its combinations for treatment of COVID-19. Methods: The hospitalized patients who were infected with SARS-CoV-2 and received HCQ with initial and follow up ECGs from March 10th to May 30th were included. The critical QTc prolongation was accepted as QTc >500 ms if QRS<120ms and >550 ms if QRS >120 ms or ∆QTc levels >60 ms when compared with the initial ECG. Primary outcomes were critical QTc prolongation, ventricular tachyarrhythmia, and sudden cardiac arrest. Results: Out of 336 hospitalized patients with suspected or confirmed COVID-19, 297 received HCQ, and 94 met the inclusion criteria, and 66 cases were included in final analysis. The mean baseline QTc was 444.5 (sd= 39.5) ms. In total, 63% of the patients’ QTc levels increased under HCQ treatment and critical QTc prolongation occurred in 8 cases (12%) all of whom were male. The male gender (p=0.033), DM (p=0.035) and oseltamivir use (p=0.047) were significantly associated with critical QTc prolongation. In multivariate analysis, DM (OR:5.8, %95 Cl:1.11-30.32, p:0.037), and concomitant use of oseltamivir (OR:5.3, %95 Cl:1,02-28, p:0.047) were found to be associated with critical QTc prolongation. Conclusion: Critical QTc prolongation was detected in 12% of the patients. The DM and concomitant oseltamivir use were associated with critical QTc prolongation. The use of concurrent drugs that have potential to enhance QTc interval should be kept in mind and special attention should be paid for ECG monitoring.

Aim: Polypharmacy (PP) is a common problem among the older adults and has a potential effect on health-related problems. However, the significance of PP in older advanced non–small cell lung cancer (NSCLC) patients and those on oral molecular-targeted anticancer agents is unclear. Methods: This retrospective study reviewed the records of 334 advanced NSCLC patients who underwent epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. PP was defined as >=5 concomitant medications. Potentially inappropriate medication (PIM) use was measured using the updated screening tool of older people’s prescriptions (STOPP) ver. 2 criteria. We also estimated survival distributions using the Kaplan–Meier method, compared between–group differences using the log-rank test, explored potential predictors of survival using Cox regression, and performed cluster analysis to identify factors affecting multiple-medication use. Results: The PP and PIM use prevalence was 38.4% and 31.9%, respectively. The median overall survival (OS) for PP(+) and PP(–) patients was 19.4 months (95% CI = 14.1–24.8) and 27.3 months (95% CI = 22.6–36.4), respectively (P < 0.001). Multivariate analysis revealed a significant correlation between PP and OS. The frequency of unexpected hospitalization during EGFR-TKI treatment was higher in PP(+) compared to PP(–) patients (49.4% vs. 29.4%; P = 0.0032; OR = 2.34; 95% CI = 1.31–4.23). Conclusion: PP is an independent prognostic factor in older NSCLC patients taking EGFR-TKIs. PP can be used as a simple indicator of such patients’ comorbidities and symptoms or as a predictive marker of unexpected hospitalization during treatment.