In hematological malignancies, leukemias or myelomas, malignant cells present bone marrow (BM) homing, in which the niche contributes to tumor development and drug resistance. BM architecture, cellular and molecular composition and interactions define differential microenvironments that govern cell fate under physiological and pathological conditions and serve as a reference for the native biological landscape to be replicated in engineered platforms attempting to reproduce blood cancer behavior. This review summarizes the different models used to efficiently reproduce certain aspects of BM in vitro; however, they still lack the complexity of this tissue, which is relevant for fundamental aspects such as drug resistance development in multiple myeloma. Extracellular matrix composition, material topography, vascularization, cellular composition or stemness vs. differentiation balance are discussed as variables that could be rationally defined in tissue engineering approaches for achieving more relevant in vitro models. Fully humanized platforms closely resembling natural interactions still remain challenging and the question of to what extent accurate tissue complexity reproduction is essential to reliably predict drug responses is controversial. However, the contributions of these approaches to the fundamental knowledge of non-solid tumor biology, its regulation by niches, and the advance of personalized medicine are unquestionable.

Background: This study aims to provide information on the success rate of CPR in COVID-19 patients and some probable risk factors of mortality in these cases. Methods: In this historical cohort design, the CPR success rate probable risk factors of 737 critically ill patients during the COVID-19 pandemic in 17 hospitals in the catchment area of Iran University of Medical Sciences, Tehran, Iran, was evaluated between Feb and Apr 2020. Data were extracted from a database that is a part of a national integrated care electronic health record system and analyzed with logistic and Cox regression models. Results: COVID-19 cases were 341 (46.3%). The mean age in COVID-19 cases and non-COVID-19 patients were 70.014.6 and 63.019.3 years, respectively (P<0.001). The mortality was significantly higher in COVID-19 patients (99.1% vs. 74%, OR: 39.6, 95%CI: 12.4, 126.2). Cardiovascular diseases were the most frequent underlying disease (46.3% of COVID-19 cases and 35.1% of non-COVID-19 patients). Being a COVID-19 case (OR: 29.0, 95%CI: 8.9, 93.2), Intensive care unit admission (OR: 2.6, 95%CI: 1.5, 4.6) and age for each ten-year increase (OR: 1.2, 95%CI: 1.1, 1.4) were observed to be independent risk factors of mortality following CPR. The hazard ratio of being a COVID-19 patient was HR= 1.8 (95%CI: 1.5, 2.1). Conclusion: Critically ill COVID-19 patients who undergo CPR have a decreased chance of survival in comparison to non-COVID-19 patients. ? Iran University of Medical Sciences

Socioeconomic disadvantages are amplified by the COVID-19 pandemic all over the world. Public actions and omissions severely affect the poor, alongside their precarious living, health and working conditions. As we slowly prepare for the aftermath of the pandemic, thanks to the progression of vaccination, especially in developed countries, certain measures taken in this context, more specifically the "vaccination certificates", are likely particularly to affect the poor, who usually also belong to other vulnerable groups such as ethnic minorities or single parents, and could eventually constitute for them a state of permanent quarantine. In this contribution, I argue that COVID-19 vaccination certificates are a slippery slope towards exclusion and stigmatisation of the poor through a bureaucratic system based on privileges that raises important questions in light of the fundamental rights of the people who reside at society's margins, struggling to conform to the "phantom of normalcy". ? 2021 The Author(s). Published by Cambridge University Press.

[Image: see text] The urgent need for a cure for early phase COVID-19 infected patients critically underlines drug repositioning strategies able to efficiently identify new and reliable treatments by merging computational, experimental, and pharmacokinetic expertise. Here we report new potential therapeutics for COVID-19 identified with a combined virtual and experimental screening strategy and selected among already approved drugs. We used hydroxychloroquine (HCQ), one of the most studied drugs in current clinical trials, as a reference template to screen for structural similarity against a library of almost 4000 approved drugs. The top-ranked drugs, based on structural similarity to HCQ, were selected for in vitro antiviral assessment. Among the selected drugs, both zuclopenthixol and nebivolol efficiently block SARS-CoV-2 infection with EC(50) values in the low micromolar range, as confirmed by independent experiments. The anti-SARS-CoV-2 potential of ambroxol, amodiaquine, and its active metabolite (N-monodesethyl amodiaquine) is also discussed. In trying to understand the hydroxychloroquine mechanism of action, both pK(a) and the HCQ aromatic core may play a role. Further, we show that the amodiaquine metabolite and, to a lesser extent, zuclopenthixol and nebivolol are active in a SARS-CoV-2 titer reduction assay. Given the need for improved efficacy and safety, we propose zuclopenthixol, nebivolol, and amodiaquine as potential candidates for clinical trials against the early phase of the SARS-CoV-2 infection and discuss their potential use as adjuvant to the current (i.e., remdesivir and favipiravir) COVID-19 therapeutics.

BACKGROUND Hemorrhage is the second leading cause of death in civilian trauma and the leading cause of preventable death in military trauma. The purpose of this study was to examine the effectiveness of three hemostatic agents: BleedArrest, TraumaDex, and Celox. MATERIALS AND METHODS This was a prospective, experimental study using male Yorkshire swine. The pigs (n = 5 per group) were randomly assigned to one of the following: BleedArrest, TraumaDex, Celox, or control. To simulate a trauma injury, the investigators generated a complex groin injury with transection of the femoral artery and vein in all pigs. After 1 min of uncontrolled hemorrhage, one of the hemostatic agents was poured into the wound, followed by standard wound packing. The control group underwent the same procedures with the exception of the hemostatic agents. In all groups, 5 min of direct manual pressure was applied to the wound followed by a standard pressure dressing. After 30 min, dressings were removed, and the amount of bleeding was determined. RESULTS There were significant differences between the BleedArrest (mean = 21.2, SD 36.6 mL) TraumaDex (mean = 68, SD 103.5 mL) and Celox (mean = 18.l6, SD 41.6 mL) groups compared with Control group (mean = 230, SD 154 mL) (P < 0.05). However, there were no statistically significant difference between BleedArrest, TraumaDex, and Celox groups (P = 0.478). CONCLUSIONS BleedArrest, Celox, and TraumaDex were statistically and clinically superior at controlling hemorrhage compared with the standard pressure dressing in the control group.

In this work, we analyze the growth of the cumulative number of confirmed infected cases by a novel coronavirus (COVID-19) until March 27, 2020, from countries of Asia, Europe, North America, and South America. Our results show that (i) power-law growth is observed in all countries; (ii) by using the distance correlation, the power-law curves between countries are statistically highly correlated, suggesting the universality of such curves around the world; and (iii) soft quarantine strategies are inefficient to flatten the growth curves. Furthermore, we present a model and strategies that allow the government to reach the flattening of the power-law curves. We found that besides the social distancing of individuals, of well known relevance, the strategy of identifying and isolating infected individuals in a large daily rate can help to flatten the power-laws. These are the essential strategies followed in the Republic of Korea. The high correlation between the power-law curves of different countries strongly indicates that the government containment measures can be applied with success around the whole world. These measures are scathing and to be applied as soon as possible.

Coronavirus disease 2019 (COVID-19) was initially recognized in late December 2019 and has quickly spread globally with over 114 million reported cases worldwide at the time of this publication For the majority of patients infected with COVID-19, the clinical manifestations are absent or mild In more advanced cases, severe respiratory dysfunction is the leading cause of morbidity and mortality However, increasingly, there have been reports of increased thrombotic complications including pulmonary embolism and deep vein thrombosis seen in these patients We present herein a series of cases of concomitant COVID-19 pneumonia and venous thromboembolism These cases highlight the importance of clinical and radiologic vigilance to ensure this often clinically silent complication is not missed

The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use.

BACKGROUND: The Skilled Nursing Facility Value-based Purchasing Program (SNF-VBP) incentivizes facilities to coordinate care, improve quality, and lower hospital readmissions. However, SNF-VBP may unintentionally punish facilities with lower profit margins struggling to invest resources to lower readmissions. OBJECTIVE: The objective of this study was to estimate the SNF-VBP penalty amounts by skilled nursing facility (SNF) profit margin quintiles and examine whether facilities with lower profit margins are more likely to be penalized by SNF-VBP. RESEARCH DESIGN: We combined the first round of SNF-VBP performance data with SNF profit margins and characteristics data. Our outcome variables included estimated penalty amount and a binary measure for whether facilities were penalized by the SNF-VBP. We categorized SNFs into 5 profit margin quintiles and examined the relationship between profit margins and SNF-VBP performance using descriptive and regression analysis. RESULTS: The average profit margins for SNFs in the lowest profit margin quintile was -14.4% compared with the average profit margin of 11.1% for SNFs in the highest profit margin quintile. In adjusted regressions, SNFs in the lowest profit margin quintile had 17% higher odds of being penalized under SNF-VBP compared with facilities in the highest profit margin quintile. The average penalty for SNFs in the lowest profit margin quintile was $22,312. CONCLUSIONS: SNFs in the lowest profit margins are more likely to be penalized by the SNF-VBP, and these losses can exacerbate quality problems in SNFs with lower quality. Alternative approaches to measuring and rewarding SNFs under SNF-VBP or programs to assist struggling SNFs is warranted, particularly considering the coronavirus disease 2019 pandemic, which requires resources for prevention and management.

INTRODUCTION: Endoscopic full-thickness resection (eFTR) using the full-thickness resection device (FTRD?) is a novel minimally invasive procedure that allows the resection of various lesions in the gastrointestinal tract including the colorectum. Real-world data outside of published studies are limited. The aim of this study was a detailed analysis of the outcomes of colonoscopic eFTR in different hospitals from different care levels in correlation with the number of endoscopists performing eFTR. MATERIAL AND METHODS: In this case series, the data of all patients who underwent eFTR between November 2014 and June 2019 (performed by a total of 22 endoscopists) in 7 hospitals were analyzed retrospectively regarding rates of technical success, R0 resection, and procedure-related complications. RESULTS: Colonoscopic eFTR was performed in 229 patients (64.6% men; average age 69.3 10.3 years) mainly on the basis of the following indication: 69.9% difficult adenomas, 21.0% gastrointestinal adenocarcinomas, and 7.9% subepithelial tumors. The average size of the lesions was 16.3 mm. Technical success rate of eFTR was achieved in 83.8% (binominal confidence interval 78.4-88.4%). Overall, histologically complete resection (R0) was achieved in 77.2% (CI 69.8-83.6%) while histologically proven full-wall excidate was confirmed in 90.0% (CI 85.1-93.7%). Of the resectates obtained (n = 210), 190 were resected en bloc (90.5%). We did not observe a clear improvement of technical success and R0 resection rate over time by the performing endoscopists. Altogether, procedure-related complications were observed in 17.5% (mostly moderate) including 2 cases of acute gangrenous appendicitis requiring operation. DISCUSSION: In this pooled analysis, eFTR represents a feasible, effective, and safe minimally invasive endoscopic technique.

It is widely accepted that overcoming the social-ecological crises we face requires major changes to the food system. However, opinions diverge on the question whether those great efforts towards sustainability require systemic changes or merely systematic ones. Drawing upon Brand and Wissens concept of imperial modes of living (Rev Int Polit Econ 20:687C711, 2013; The imperial mode of living: everyday life and the ecological crisis of capitalism, Verso, London/New York, 2021), we ask whether the lively debates about sustainability and ethical consumption among producers and consumers in Germany are far reaching enough to sufficiently reduce the imperial weight on the environment and other human and nonhuman animals. By combining discourse analysis of agri-food businesses sustainability reports with narrative consumer interviews, we examine understandings of sustainability in discourses concerning responsible food provision and shed light on how those discourses are inscribed in consumers everyday food practices. We adopt Ehgartners discursive frames of consumer sovereignty, economic rationality, and stewardship to illustrate our findings, and add a fourth one of legitimacy. Constituting the conditions under which food-related themes become sustainability issues, these frames help businesses to (1) individualise the responsibility to enact changes, (2) tie efforts towards sustainability to financial profits, (3) subject people and nature to the combination of care and control, and (4) convey legitimacy through scientific authority. We discuss how these frames, mirrored in some consumer narratives, work to sideline deeper engagement with ecological sustainability and social justice, and how they brush aside the desires of some ostensibly sovereign consumers to overcome imperial modes of food provision through much more far reaching, systemic changes. Finally, we reflect on possible paths towards a de-imperialised food system.

A review of the literature on psychological disorders aming the pediatric population during the Covid 19 pandemic. [ FROM AUTHOR] Copyright of Middle East Journal of Family Medicine is the property of Medi+WORLD International Pty. Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

OBJECTIVE To evaluate the ability of small interfering RNAs (siRNAs) to inhibit in vitro viral replication and gene expression of feline coronavirus (FCoV). SAMPLE Cell cultures of Crandell-Rees feline kidney cells. PROCEDURES 5 synthetic siRNAs that each targeted a different region of the FCoV genome were tested individually and in various combinations for their antiviral effects against 2 strains of FCoV (feline infectious peritonitis virus WSU 79-1146 and feline enteric coronavirus WSU 79-1683) in cell cultures. Tested combinations targeted the FCoV leader and 3' untranslated region, FCoV leader region and nucleocapsid gene, and FCoV leader region, 3' untranslated region, and nucleocapsid gene. For each test condition, assessments included relative quantification of the inhibition of intracellular viral genomic RNA synthesis by means of real-time, reverse-transcription PCR analysis; flow cytometric evaluation of the reduction of viral protein expression in infected cells; and assessment of virus replication inhibition via titration of extracellular virus with a TCID?? infectivity assay. RESULTS The 5 siRNAs had variable inhibitory effects on FCoV when used singly. Combinations of siRNAs that targeted different regions of the viral genome resulted in more effective viral inhibition than did individual siRNAs that targeted a single gene. The tested siRNA combinations resulted in approximately 95% reduction in viral replication (based on virus titration results), compared with findings in negative control, nontargeting siRNA-treated, FCoV-infected cells. CONCLUSIONS AND CLINICAL RELEVANCE In vitro replication of FCoV was specifically inhibited by siRNAs that targeted coding and noncoding regions of the viral genome, suggesting a potential therapeutic application of RNA interference in treatment of feline infectious peritonitis.

AIMS: In three days at the beginning of the COVID-19 pandemic, the Copenhagen Emergency Medical Services developed a digital diagnostic device. The purpose was to assess and triage potential COVID-19 symptoms and to reduce the number of calls to public health-care helplines. The device was used almost 150,000 times in a few weeks and was described by politicians and administrators as a solution and success. However, high usage cannot serve as the sole criterion of success. What might be adequate criteria? And should digital triage for citizens by default be considered low risk? METHODS: This paper reflects on the uncertain aspects of the performance, risks and issues of accountability pertaining to the digital diagnostic device in order to draw lessons for future improvements. The analysis is based on the principles of evidence-based medicine (EBM), the EU and US regulations of medical devices and the taxonomy of uncertainty in health care by Han et al. RESULTS: Lessons for future digital devices are (a) the need for clear criteria of success, (b) the importance of awareness of other severe diseases when triaging, (c) the priority of designing the device to collect data for evaluation and (d) clear allocation of responsibilities. CONCLUSIONS: A device meant to substitute triage for citizens according to its own criteria of success should not by default be considered as low risk. In a pandemic age dependent on digitalisation, it is therefore important not to abandon the ethos of EBM, but instead to prepare the ground for new ways of building evidence of effect.

PURPOSE OF REVIEW Children are at risk of severe hypoxemia in the perioperative period owing to their unique anatomy and physiology. Safe and effective airway management strategies are therefore key to the practice of pediatric anesthesia. The goal of this review is to highlight recent publications (2019-2021) aimed to advance pediatric airway safety and to highlight a proposed simple, pediatric-specific, universal framework to guide clinical practice. RECENT FINDINGS Recent investigations demonstrate that infants with normal and difficult airways experience high incidences of multiple laryngoscopy attempts and resulting hypoxemia. Video laryngoscopy may improve tracheal intubation first attempt success rate in infants with normal airways. In infants with difficult airways, standard blade video laryngoscopy is associated with higher first attempt success rates over non-standard blade video laryngoscopy. Recent studies in children with Pierre Robin sequence and mucopolysaccharidoses help guide airway equipment and technique selection. Department airway leads and hospital difficult airway services are necessary to disseminate knowledge, lead quality improvement initiatives, and promote evidence-based practice guidelines. SUMMARY Pediatric airway management morbidity is a common problem in pediatric anesthesia. Improvements in individual practitioner preparation and management strategies as well as systems-based policies are required. A simple, pediatric-specific, universal airway management framework can be adopted for safe pediatric anesthesia practice.

Due to the COVID\19 pandemic and the exponential increase in cases, educational institutions worldwide were forced to close, making way for digital learning. After a period of confinement and an online teaching methodology, a new school year has begun. However, this new school year included the application of a wide range of measures that transformed the educative setting. The present study aimed to understand the health consequences for adolescents and young adults (AYA) during the back to school period after the COVID\19 lockdown. This mixed\method study included 304 participants between 16 and 24 years old (M = 18.4, SD = 2.12), female (71.1%), Portuguese (90.8%) and students (85.2%). In general, it was with a pessimistic perspective that young people in general, particularly girls and university students, understood the new school reality postconfinement, the effects on friendship relations, leisure activities and physical activity. By demonstrating AYA's ability and competence to identify and expose their problems, this study intends to raise awareness of the need for their involvement in the issues that affect them.

[Figure: see text].

By March 31, 2020, COVID-19 had spread to more than 200 countries. Over 750,000 confirmed cases were reported, leading to more than 36,000 deaths. In this study, we analysed the efficiency of various intervention strategies to prevent infection by the virus, SARS-CoV-2, using an agent-based SEIIR model, in the fully urbanised city of Shenzhen, Guangdong Province, China. Shortening the duration from symptom onset to hospital admission, quarantining recent arrivals from Hubei Province, and letting symptomatic individuals stay at home were found to be the three most important interventions to reduce the risk of infection in Shenzhen. The ideal time window for a mandatory quarantine of arrivals from Hubei Province was between 10 January and January 17, 2020, while the ideal time window for local intervention strategies was between 15 and 22 January. The risk of infection could have been reduced by 50% if all symptomatic individuals had immediately gone to hospital for isolation, and by 35% if a 14-day quarantine for arrivals from Hubei Province had been introduced one week earlier. Intervention strategies implemented in Shenzhen were effective, and the spread of infection would be controlled even if the initial basic reproduction number had doubled. Our results may be useful for other cities when choosing their intervention strategies to prevent outbreaks of COVID-19.

The global coronavirus pandemic overwhelmed many health care systems, enforcing lockdown and encouraged work from home to control the spread of the virus and prevent overrunning of hospitalized patients. This prompted a sharp widespread use of telehealth to provide low-risk care for patients. Nevertheless, a continuous mutation into new variants and widespread unavailability of test kits, especially in developing countries, possess the challenge to control future potential waves of infection. In this paper, we propose a novel Smartphone application-based platform for early diagnosis of possible Covid-19 infected patients. The application provides three modes of diagnosis from possible symptoms, cough sound, and specific blood biomarkers. When a user chooses a particular setting and provides the necessary information, it sends the data to a trained machine learning (ML) model deployed in a remote server using the internet. The ML algorithm then predicts the possibility of contracting Covid-19 and sends the feedback to the user. The entire procedure takes place in real-time. Our machine learning models can identify Covid-19 patients with an accuracy of 100%, 95.65%, and 77.59% from blood parameters, cough sound, and symptoms respectively. Moreover, the ML sensitivity for blood and sound is 100%, which indicates correct identification of Covid positive patients. This is significant in limiting the spread of the virus. The multimodality offers multiplex diagnostic methods to better classify possible infectees and together with the instantaneous nature of our technique, demonstrates the power of telehealthcare as an easy and widespread low-cost scalable diagnostic solution for future pandemics.

The Nordic countries have differed in their approach as to how much priority for COVID19 vaccine access should be given to health care workers. Two countries decided not to give health care workers highest priority, raising some controversy. The rationale was that those at highest risk of dying needed to come first. However, when it comes to protecting those at the highest risk of dying from COVID19, their needs and vulnerabilities need to be considered more broadly than just in terms of the individual protection that vaccination will afford them. Likewise, when considering whether to prioritize health care workers for the vaccine, their crucial role in keeping the health care system operational, and right to a safe work environment need to be factored in. Below we review several ethical arguments for why frontline health care workers and first responders should receive priority access to the COVID19 vaccine.