title: Contribution of a winged phlebotomy device design to blood splatter.

text: BACKGROUND Despite a proliferation of phlebotomy devices with engineered sharps injury protection (ESIP), the impact of various winged device designs on blood splatter occurring during venipuncture procedures has not been explored. OBJECTIVES To evaluate the potential for blood splatter of 6 designs of winged phlebotomy devices. DESIGN A laboratory-based device evaluation without human subjects, using a simulated patient venous system. METHODS We evaluated 18 winged phlebotomy devices of 6 device designs by Terumo, BD Vacutainer (2 designs), Greiner, Smith Medical, and Kendall (designated A-F, respectively). Scientific filters were positioned around the devices and weighed before and after venipuncture was performed. Visible blood on filters, exam gloves, and devices and measurable blood splatter were the primary units of analysis. RESULTS The percentages of devices and gloves with visible blood on them and filters with measurable blood splatter ranged from 0% to 20%. There was a statistically significant association between device design and visible blood on devices ([Formula: see text]) and between device design and filters with measurable blood splatter ([Formula: see text]), but not between device design and visible blood on gloves. A wide range of associations were demonstrated between device design and visible blood on gloves or devices and incidence of blood splatter. CONCLUSIONS The results of this evaluation suggest that winged phlebotomy devices with ESIP may produce blood splatter during venipuncture. Reinforcing the importance of eye protection and developing a methodology to assess ocular exposure to blood splatter are major implications for healthcare personnel who use these devices. Future studies should focus on evaluating different designs of intravascular devices (intravenous catheters, other phlebotomy devices) for blood splatter.


Two more cases of novel coronavirus are confirmed in UK.


title: The crystal structure of porcine reproductive and respiratory syndrome virus nonstructural protein Nsp1beta reveals a novel metal-dependent nuclease.

text: Porcine reproductive and respiratory syndrome virus (PRRSV), a member of the Arteriviridae family of Nidovirales, is the causative agent of porcine reproductive and respiratory syndrome, which results in enormous economic losses in the swine industry. As the second protein encoded by the PRRSV genome, nsp1beta cleaves itself from the downstream nsp2 protein via a C-terminal papain-like cysteine protease (PCP) domain. Although nsp1beta is known to be involved in virulence, its precise role in the process of viral infection remains unclear. In this work, we describe the homodimeric crystal structure of PRRSV nsp1beta in its natural, self-processed form. We show that the architecture of its N-terminal domain (NTD) adopts a fold closely resembling that of several known nucleases and has intrinsic nuclease activity that is strongly activated by manganese ions in vitro. Key features, however, distinguish nsp1beta from characterized nucleases, including the C-terminal PCP domain (which is responsible for the self-release of nsp1beta from nsp2), a linker domain (LKD) that connects the NTD and the PCP domain, and a C-terminal extension (CTE) that binds to and is stabilized by the putative substrate binding site of the PCPbeta domain. Combined with the reported nuclear localization of this protein, these results shed light on the self-processing mode and precise biological function of nsp1beta and thus offer a multitarget template for future drug discovery.


title: A feasibility study of cerebral oximetry during in-hospital mechanical and manual cardiopulmonary resuscitation*.

text: OBJECTIVE A major hurdle limiting the ability to improve the quality of resuscitation has been the lack of a noninvasive real-time detection system capable of monitoring the quality of cerebral and other organ perfusion, as well as oxygen delivery during cardiopulmonary resuscitation. Here, we report on a novel system of cerebral perfusion targeted resuscitation. DESIGN An observational study evaluating the role of cerebral oximetry (Equanox; Nonin, Plymouth, MI, and Invos; Covidien, Mansfield, MA) as a real-time marker of cerebral perfusion and oxygen delivery together with the impact of an automated mechanical chest compression system (Life Stat; Michigan Instruments, Grand Rapids, MI) on oxygen delivery and return of spontaneous circulation following in-hospital cardiac arrest. SETTING Tertiary medical center. PATIENTS In-hospital cardiac arrest patients (n = 34). MAIN RESULTS Cerebral oximetry provided real-time information regarding the quality of perfusion and oxygen delivery. The use of automated mechanical chest compression device (n = 12) was associated with higher regional cerebral oxygen saturation compared with manual chest compression device (n = 22) (53.1% ± 23.4% vs 24% ± 25%, p = 0.002). There was a significant difference in mean regional cerebral oxygen saturation (median % ± interquartile range) in patients who achieved return of spontaneous circulation (n = 15) compared with those without return of spontaneous circulation (n = 19) (47.4% ± 21.4% vs 23% ± 18.42%, p < 0.001). After controlling for patients achieving return of spontaneous circulation or not, significantly higher mean regional cerebral oxygen saturation levels during cardiopulmonary resuscitation were observed in patients who were resuscitated using automated mechanical chest compression device (p < 0.001). CONCLUSIONS The integration of cerebral oximetry into cardiac arrest resuscitation provides a novel noninvasive method to determine the quality of cerebral perfusion and oxygen delivery to the brain. The use of automated mechanical chest compression device during in-hospital cardiac arrest may lead to improved oxygen delivery and organ perfusion.


title: Face coverings for the public: Laying straw men to rest.

text: Background This article responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on face coverings for the lay public in the Covid-19 pandemic. Their paper reflects criticisms that have been made of face coverings policies more generally. Method Narrative rebuttal. Results I address charges that my coauthors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms But before that, I remind my critics that the evidence on face coverings goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies, and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly framed objections. I challenge my critics' apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. Conclusion I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and embrace the full range of evidence in the context of the perilous threat the world is now facing.


title: Factors associated with the willingness of health care personnel to work during an influenza public health emergency: an integrative review.

text: INTRODUCTION The first decade of the 21st century has witnessed three major influenza public health emergencies: (1) the severe acute respiratory syndrome of 2002-2003; (2) the avian flu of 2006; and (3) the 2009 H1N1 pandemic influenza. An effective public health response to an influenza public health emergency depends on the majority of uninfected health care personnel (HCP) continuing to report to work. The purposes of this study were to determine the state of the evidence concerning the willingness of HCP to work during an influenza public health emergency, to identify the gaps for future investigation, and to facilitate evidence-based influenza public health emergency planning. METHODS A systemic literature review of relevant, peer-reviewed, quantitative, English language studies published from January 1, 2001 through June 30, 2010 was conducted. Search strategies included the Cochrane Library, PubMed, PubMed Central, EBSCO Psychological and Behavioral Sciences Collection, Google Scholar, ancestry searching of citations in relevant publications, and information from individuals with a known interest in the topic. RESULTS Thirty-two studies met the inclusion criteria. Factors associated with a willingness to work during an influenza public health emergency include: being male, being a doctor or nurse, working in a clinical or emergency department, working full-time, prior influenza education and training, prior experience working during an influenza emergency, the perception of value in response, the belief in duty, the availability of personal protective equipment (PPE), and confidence in one's employer. Factors found to be associated with less willingness were: being female, being in a supportive staff position, working part-time, the peak phase of the influenza emergency, concern for family and loved ones, and personal obligations. Interventions that resulted in the greatest increase in the HCP's willingness to work were preferential access to Tamiflu for the HCP and his/her family, and the provision of a vaccine for the individual and his/her family. CONCLUSIONS Understanding the factors that contribute to the willingness of HCP to report to work during an influenza public health emergency is critical to emergency planning and preparedness. Information from this review can guide emergency policy makers, planners, and implementers in both understanding and influencing the willingness of HCP to work during an influenza public health emergency.


title: Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an angiotensin II type I receptor-dependent mechanism.

text: Angiotensin-converting enzyme type 2 (ACE2) is a pivotal component of the renin-angiotensin system, promoting the conversion of angiotensin II (Ang-II) to Ang-(1-7). We previously reported that decreased ACE2 expression and activity contributes to the development of Ang-II-mediated hypertension in mice. The present study aimed to investigate the mechanisms involved in ACE2 downregulation during neurogenic hypertension. In ACE2-transfected Neuro-2A cells, Ang-II treatment resulted in a significant attenuation of ACE2 enzymatic activity. Examination of the subcellular localization of ACE2 revealed that Ang-II treatment leads to ACE2 internalization and degradation into lysosomes. These effects were prevented by both the Ang-II type 1 receptor (AT1R) blocker losartan and the lysosomal inhibitor leupeptin. In contrast, in HEK293T cells, which lack endogenous AT1R, Ang-II failed to promote ACE2 internalization. Moreover, this effect could be induced after AT1R transfection. Furthermore, coimmunoprecipitation experiments demonstrated that AT1R and ACE2 form complexes, and these interactions were decreased by Ang-II treatment, which also enhanced ACE2 ubiquitination. In contrast, ACE2 activity was not changed by transfection of AT2 or Mas receptors. In vivo, Ang-II-mediated hypertension was blunted by chronic infusion of leupeptin in wildtype C57Bl/6, but not in ACE2 knockout mice. Overall, this is the first demonstration that elevated Ang-II levels reduce ACE2 expression and activity by stimulation of lysosomal degradation through an AT1R-dependent mechanism.


title: Noninvasive autoregulation monitoring in a swine model of pediatric cardiac arrest.

text: BACKGROUND Cerebrovascular autoregulation after resuscitation has not been well studied in an experimental model of pediatric cardiac arrest. Furthermore, developing noninvasive methods of monitoring autoregulation using near-infrared spectroscopy (NIRS) would be clinically useful in guiding neuroprotective hemodynamic management after pediatric cardiac arrest. We tested the hypotheses that the lower limit of autoregulation (LLA) would shift to a higher arterial blood pressure between 1 and 2 days of recovery after cardiac arrest and that the LLA would be detected by NIRS-derived indices of autoregulation in a swine model of pediatric cardiac arrest. We also tested the hypothesis that autoregulation with hypertension would be impaired after cardiac arrest. METHODS Data on LLA were obtained from neonatal piglets that had undergone hypoxic-asphyxic cardiac arrest and recovery for 1 day (n = 8) or 2 days (n = 8), or that had undergone sham surgery with 2 days of recovery (n = 8). Autoregulation with hypertension was examined in a separate cohort of piglets that underwent hypoxic-asphyxic cardiac arrest (n = 5) or sham surgery (n = 5) with 2 days of recovery. After the recovery period, piglets were reanesthetized, and autoregulation was monitored by standard laser-Doppler flowmetry and autoregulation indices derived from NIRS (the cerebral oximetry [COx] and hemoglobin volume [HVx] indices). The LLA was determined by decreasing blood pressure through inflation of a balloon catheter in the inferior vena cava. Autoregulation during hypertension was evaluated by inflation of an aortic balloon catheter. RESULTS The LLAs were similar between sham-operated piglets and piglets that recovered for 1 or 2 days after arrest. The NIRS-derived indices accurately detected the LLA determined by laser-Doppler flowmetry. The area under the curve of the receiver operator characteristic curve for cerebral oximetry index was 0.91 at 1 day and 0.92 at 2 days after arrest. The area under the curve for hemoglobin volume index was 0.92 and 0.89 at the respective time points. During induced hypertension, the static rate of autoregulation, defined as the percentage change in cerebrovascular resistance divided by the percentage change in cerebral perfusion pressure, was not different between postarrest and sham-operated piglets. At 2 days recovery from arrest, piglets exhibited neurobehavioral deficits and histologic neuronal injury. CONCLUSIONS In a swine model of pediatric hypoxic-asphyxic cardiac arrest with confirmed brain damage, the LLA did not differ 1 and 2 days after resuscitation. The NIRS-derived indices accurately detected the LLA in comparison with laser-Doppler flow measurements at those time points. Autoregulation remained functional during hypertension.


Reply to comment to "update with level 1 studies of the European Hernia Society guidelines on the treatment of inguinal hernia in adult patients" W.J. Bökkerink, C.J. van Laarhoven, G.G. Koning. DOI 10.1007/s10029-014-1266-0.


title: Long-term Outcomes of Laparoscopic Versus Open Transhiatal Approach for the Treatment of Esophagogastric Junction Cancer.

text: Purpose The laparoscopic transhiatal approach (LA) for adenocarcinoma of the esophagogastric junction (AEJ) is advantageous since it allows better visualization of the surgical field than the open approach (OA). We compared the surgical outcomes of the 2 approaches. Materials and Methods We analyzed 108 patients with AEJ who underwent transhiatal distal esophagectomy and gastrectomy with curative intent between 2003 and 2015. Surgical outcomes were reviewed using electronic medical records. Results The LA and OA were performed in 37 and 71 patients, respectively. Compared to the OA, the LA was associated with significantly shorter duration of postoperative hospital stay (9 vs. 11 days, P=0.001), shorter proximal resection margins (3 vs. 7 mm, P=0.004), and extended operative times (240 vs. 191 min, P=0.001). No significant difference was observed between the LA and OA for intraoperative blood loss (100 vs. 100 mL, P=0.392) or surgical morbidity rate (grade≥II) for complications (8.1% vs. 23.9%, P=0.080). Two cases of anastomotic leakage occurred in the OA group. The number of harvested lymph nodes was not significantly different between the LA and OA groups (54 vs. 51, P=0.889). The 5-year overall and 3-year relapse-free survival rates were 81.8% and 50.7% (P=0.024) and 77.3% and 46.4% (P=0.009) for the LA and OA groups, respectively. Multivariable analyses revealed no independent factors associated with overall survival. Conclusions The LA is feasible and safe with short- and long-term oncologic outcomes similar to those of the OA.


title: Linking aerosol characteristics of size distributions, core potential pathogens and toxic metal(loid)s to wastewater treatment process.

text: Wastewater treatment plants (WWTPs) play important roles in water purification but are also important source of aerosols. However, the relationship between aerosol characteristics and wastewater treatment process remains poorly understood. In this study, aerosols were collected over a 24-month period from a WWTP using a modified anaerobic-anoxic-oxic process. The aerated tank (AerT) was characterized by the highest respiratory fraction (RF) concentrations (861-1525 CFU/m3) and proportions (50.76%-65.96%) of aerosol particles. Fourteen core potential pathogens and 15 toxic metal(loid)s were identified in aerosols. Mycobacterium was the genus that aerosolized most easily in fine grid, pre-anoxic tank, and AerT. High wastewater treatment efficiency may increase the emission of RF and core potential pathogens. The median size of activated sludge, richness of core potential pathogens in wastewater, and total suspended particulates were the most influential factors directly related to the RF proportions, core community of potential pathogens, and composition of toxic metal(loid)s in WWTP aerosols, respectively. Relative humidity, temperature, input and removal of biochemical oxygen demand, dissolved oxygen, and mixed liquor suspended solids could also directly or indirectly affect the aerosol characteristics. This study enhances the mechanistic understanding of linking aerosol characteristics to treatment processes and has important implications for targeted manipulation.


Public health and biosecurity. Restricted data on influenza H5N1 virus transmission.


title: Stroke severity in patients with preceding direct oral anticoagulant therapy as compared to vitamin K antagonists.

text: BACKGROUND Although direct oral anticoagulants (DOAC) have proven at least equally effective in the prevention of acute ischemic stroke (AIS) in patients with atrial fibrillation as compared to the vitamin K antagonists (VKA), no reliable data on the severity of AIS of DOAC patients as compared to VKA is available. METHODS Using a prospectively collected cohort of AIS patients, we performed univariate and multivariate (displayed as adjusted Odds Ratios, OR and 95% confidence intervals, 95% CI) analyses regarding the severity of AIS in patients with preceding DOAC (N = 210) versus VKA (N = 173) therapy. Additionally, we provide a sensitivity analysis considering only patients with warranted therapeutic anticoagulation activity. FINDINGS In a comprehensive stroke center population, the frequency of AIS under DOAC was multiple times higher than previously reported at around 6% of all AIS and steadily increasing. National Institute of Health Stroke Scale (NIHSS) in VKA patients (median 7, IQR 2-14) was equal to DOAC (median 5, IQR 2-16) on univariate analysis (P = 0.229). According to the multivariable linear logistic regression analysis adjusting for confounders of severe stroke, VKA was not significantly associated with higher NIHSS scores (β - 0.165, 95% CI - 1.874 to 1.545, P = 0.850) as compared to DOAC. Also in the sensitivity analysis considering only patients with warranted therapeutic OAC therapy, VKA was not significantly associated with higher NIHSS scores (β - 1.392, 95% CI - 3.506 to 0.721, P = 0.195) as compared to DOAC. However, VKA as compared to DOAC was significantly associated with lower rates of good functional outcome at three months (0.527, 95% CI 0.300-0.928), but not with increased mortality (aOR 1.825, 95% CI 0.780-4.273). INTERPRETATION Ischemic stroke in patients taking DOAC is an important and frequent scenario. Stroke severity in our real world population dataset is equal in patients taking VKA and DOAC, also in the case of warranted anticoagulation therapy. Preceding VKA as compared to DOAC was associated with lower rates of good functional outcome without excess mortality, but a causal relationship cannot be proven by our study design.


title: Fetal articular cartilage regeneration versus adult fibrocartilaginous repair: secretome proteomics unravels molecular mechanisms in an ovine model.

text: Osteoarthritis (OA), a degenerative joint disease characterized by progressive cartilage degeneration, is one of the leading causes of disability worldwide owing to the limited regenerative capacity of adult articular cartilage. Currently, there are no disease-modifying pharmacological or surgical therapies for OA. Fetal mammals, in contrast to adults, are capable of regenerating injured cartilage in the first two trimesters of gestation. A deeper understanding of the properties intrinsic to the response of fetal tissue to injury would allow us to modulate the way in which adult tissue responds to injury. In this study, we employed secretome proteomics to compare fetal and adult protein regulation in response to cartilage injury using an ovine cartilage defect model. The most relevant events comprised proteins associated with the immune response and inflammation, proteins specific for cartilage tissue and cartilage development, and proteins involved in cell growth and proliferation. Alarmins S100A8, S100A9 and S100A12 and coiled-coil domain containing 88A (CCDC88A), which are associated with inflammatory processes, were found to be significantly upregulated following injury in adult, but not in fetal animals. By contrast, cartilage-specific proteins like proteoglycan 4 were upregulated in response to injury only in fetal sheep postinjury. Our results demonstrate the power and relevance of the ovine fetal cartilage regeneration model presented here for the first time. The identification of previously unrecognized modulatory proteins that plausibly affect the healing process holds great promise for potential therapeutic interventions.


title: Emerging and Future Therapeutic Options for Femoropopliteal and Infrapopliteal Endovascular Intervention.

text: Despite recent advances in endovascular therapy for peripheral artery disease, current technologies remain limited by rates of long-term restenosis and application to complex lesion subsets. This article presents data on upcoming therapies, including novel drug-coated balloons, drug-eluting stents, bioresorbable scaffolds, novel drug delivery therapies to target arteries, techniques to limit postangioplasty dissection, and treatment of severely calcified lesions.


title: Impact of lockdown following COVID-19 on the gaming behavior of college students.

text: Background The uncertainty about the impact of the lockdown in wake of COVID-19 on their future academic and carrier prospects, besides other concerns; makes college students, particularly vulnerable to stress during the COVID-19 pandemic. Gaming has been recognized as a coping mechanism against stress in the previously published literature. Objectives The current study aimed to assess the gaming behavior of college students during the lockdown following COVID-19. Methods Data were collected from a cohort of students that constituted the sampling frame of an ongoing project. A total of 393 college students were enrolled. All the eligible students were subsequently contacted through E-mail and WhatsApp messenger and invited to share the details. Results About half (50.8%) of the participants reported that their gaming behavior had increased, whereas 14.6% reported a decrease in their gaming during the lockdown period. In binary logistic regression analysis, hours of gaming per day (odds ratio [OR] 1.75 [1.29-2.36]), increase in gaming due to examination related stress (OR 4.96 [1.12-21.98]), and belief that gaming helps managing stress (OR 4.27 [1.65-11.04]), were found to be independently associated with gaming behavior during lockdown period. Conclusion In the lockdown period following COVID-19 pandemic, the increase in gaming behavior was associated with examination-related stress and the belief that gaming helps combat stress. These observations highlight the need to focus on the coping style of the students to ascertain the likelihood of them engaging in gaming behavior as a coping mechanism against stress.


title: Medical mask or N95 respirator: When and how to use?

text: COVID-19 pandemic is now a global threat on human health reaching up to 2 million infected people all around the World. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipments and especially masks were among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty; is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.


title: Outcome of Infants with Therapeutic Hypothermia after Perinatal Asphyxia and Early-Onset Sepsis.

text: BACKGROUND Animal models suggest that neuroprotective effects of therapeutic hypothermia (TH) after perinatal asphyxia are reduced in infants with early-onset sepsis. OBJECTIVES To assess the outcome of infants with perinatal asphyxia, neonatal encephalopathy, and TH in the presence of early-onset sepsis. METHODS In a retrospective cohort of 1,084 infants with perinatal asphyxia and TH, the outcome of 42 infants (gestational age 36.1-42.6 weeks and birth weight 2,280-5,240 g) with proven sepsis (n = 14) and probable sepsis (n = 28) was analyzed. Death, cerebral palsy, or a delayed development at 2 years was considered an adverse outcome. RESULTS Sepsis was caused mostly by group B streptococci (n = 17), other Gram-positive bacteria (n = 5), and Candida albicans (n = 1). Of the 42 infants, 9 (21.4%) died, and 5 (11.9%) showed impairments on follow-up. The outcome is comparable to the previously reported outcome of infants with TH without early-onset sepsis. CONCLUSION A good outcome was reported in the majority of infants with perinatal asphyxia, TH, and early-onset sepsis. Cooling should not be withheld from these infants.


title: Do Omega-3/6 Fatty Acids Have a Therapeutic Role in Children and Young People with ADHD?

text: BACKGROUND Attention deficit hyperactivity disorder (ADHD) is a debilitating behavioural disorder affecting daily ability to function, learn, and interact with peers. This publication assesses the role of omega-3/6 fatty acids in the treatment and management of ADHD. METHODS A systematic review of 16 randomised controlled trials was undertaken. Trials included a total of 1,514 children and young people with ADHD who were allocated to take an omega-3/6 intervention, or a placebo. RESULTS Of the studies identified, 13 reported favourable benefits on ADHD symptoms including improvements in hyperactivity, impulsivity, attention, visual learning, word reading, and working/short-term memory. Four studies used supplements containing a 9 : 3 : 1 ratio of eicosapentaenoic acid : docosahexaenoic acid : gamma linolenic acid which appeared effective at improving erythrocyte levels. Supplementation with this ratio of fatty acids also showed promise as an adjunctive therapy to traditional medications, lowering the dose and improving the compliance with medications such as methylphenidate. CONCLUSION ADHD is a frequent and debilitating childhood condition. Given disparaging feelings towards psychostimulant medications, omega-3/6 fatty acids offer great promise as a suitable adjunctive therapy for ADHD.


title: Mental health ramifications of the COVID-19 pandemic for Black Americans: Clinical and research recommendations.

text: Mental health clinicians and researchers must be prepared to address the unique needs of Black Americans who have been disproportionately affected by the COVID-19 pandemic. Race-conscious and culturally competent interventions that consider factors such as discrimination, distrust of health care providers, and historical and racial trauma as well as protective factors including social support and culturally sanctioned coping strategies are needed. Research to accurately assess and design treatments for the mental health consequences of COVID-19 among Black Americans is warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Health risks and potential remedies during prolonged lockdowns for coronavirus disease 2019 (COVID-19).

text: As coronavirus disease 2019 (COVID-19) pandemic continues, an increasing number of countries and territories are adopting restrictive measures based on physical ("social") distancing, aimed at preventing human-to-human transmission and thereby limiting virus propagation. Nationwide lockdowns, encompassing mass quarantine under stay-at-home ordinances, have already been proven effective to contain the COVID-19 outbreak in some countries. Nevertheless, a prolonged homestay may also be associated with potential side effects, which may jeopardize people's health and thus must be recognized and mitigated in a way without violating local ordinances. Some of the most important undesirable consequences of prolonged homestay such as physical inactivity, weight gain, behavioral addiction disorders, insufficient sunlight exposure and social isolation will be critically addressed in this article, which also aims to provide some tentative recommendations for the alleviation of side effects.


title: Progressive Deconstruction of a Distal Posterior Cerebral Artery Aneurysm Using Competitive Flow Diversion.

text: Progressive deconstruction is an endovascular technique for aneurysm treatment that utilizes flow diverting stents to promote progressive thrombosis by diverting blood flow away from the aneurysm's parent vessel. While the aneurysm thromboses, collateral blood vessels develop over time to avoid infarction that can often accompany acute parent vessel occlusion. We report a 37-year-old woman with a left distal posterior cerebral artery aneurysm that was successfully treated with this strategy. The concept and rationale of progressive deconstruction are discussed in detail.


title: Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection.

text: Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics.


title: Discovery of a novel coronavirus, China Rattus coronavirus HKU24, from Norway rats supports the murine origin of Betacoronavirus 1 and has implications for the ancestor of Betacoronavirus lineage A.

text: UNLABELLED We discovered a novel Betacoronavirus lineage A coronavirus, China Rattus coronavirus (ChRCoV) HKU24, from Norway rats in China. ChRCoV HKU24 occupied a deep branch at the root of members of Betacoronavirus 1, being distinct from murine coronavirus and human coronavirus HKU1. Its unique putative cleavage sites between nonstructural proteins 1 and 2 and in the spike (S) protein and low sequence identities to other lineage A betacoronaviruses (βCoVs) in conserved replicase domains support ChRCoV HKU24 as a separate species. ChRCoV HKU24 possessed genome features that resemble those of both Betacoronavirus 1 and murine coronavirus, being closer to Betacoronavirus 1 in most predicted proteins but closer to murine coronavirus by G+C content, the presence of a single nonstructural protein (NS4), and an absent transcription regulatory sequence for the envelope (E) protein. Its N-terminal domain (NTD) demonstrated higher sequence identity to the bovine coronavirus (BCoV) NTD than to the mouse hepatitis virus (MHV) NTD, with 3 of 4 critical sugar-binding residues in BCoV and 2 of 14 contact residues at the MHV NTD/murine CEACAM1a interface being conserved. Molecular clock analysis dated the time of the most recent common ancestor of ChRCoV HKU24, Betacoronavirus 1, and rabbit coronavirus HKU14 to about the year 1400. Cross-reactivities between other lineage A and B βCoVs and ChRCoV HKU24 nucleocapsid but not spike polypeptide were demonstrated. Using the spike polypeptide-based Western blot assay, we showed that only Norway rats and two oriental house rats from Guangzhou, China, were infected by ChRCoV HKU24. Other rats, including Norway rats from Hong Kong, possessed antibodies only against N protein and not against the spike polypeptide, suggesting infection by βCoVs different from ChRCoV HKU24. ChRCoV HKU24 may represent the murine origin of Betacoronavirus 1, and rodents are likely an important reservoir for ancestors of lineage A βCoVs. IMPORTANCE While bats and birds are hosts for ancestors of most coronaviruses (CoVs), lineage A βCoVs have never been found in these animals and the origin of Betacoronavirus lineage A remains obscure. We discovered a novel lineage A βCoV, China Rattus coronavirus HKU24 (ChRCoV HKU24), from Norway rats in China with a high seroprevalence. The unique genome features and phylogenetic analysis supported the suggestion that ChRCoV HKU24 represents a novel CoV species, occupying a deep branch at the root of members of Betacoronavirus 1 and being distinct from murine coronavirus. Nevertheless, ChRCoV HKU24 possessed genome characteristics that resemble those of both Betacoronavirus 1 and murine coronavirus. Our data suggest that ChRCoV HKU24 represents the murine origin of Betacoronavirus 1, with interspecies transmission from rodents to other mammals having occurred centuries ago, before the emergence of human coronavirus (HCoV) OC43 in the late 1800s. Rodents are likely an important reservoir for ancestors of lineage A βCoVs.


title: Intraoperatively self-made bovine pericardial graft for portomesenteric reconstruction in pancreatic surgery.

text: PURPOSE Vascular encasement or infiltration of the portomesenteric veins can compromise resectability and local tumour control in pancreatic resections. So far, there is no consensus on how vascular reconstruction should be performed. Bovine pericardium has shown promising results, particularly in infected arterial vascular reconstructions. The aim of this study is to evaluate the feasibility and technical success of portomesenteric venous vascular reconstruction using bovine pericardium in pancreatic resections. METHODS Retrospective analysis of portomesenteric reconstruction using bovine pericardium (patches, self-made tube grafts) in pancreatic resections between 2014 and 2019. The primary endpoint examined was the technical success rate and short-term patency of vascular reconstruction. In addition to clinical surveillance and laboratory routine testing, patency was tested with duplex scans (4 h postoperatively) and computed tomography imaging in case of an abnormal clinical course and as part of the oncological follow-up. RESULTS In 15 surgical procedures (pancreaticoduodenectomy (12, 80%), pancreatic left resection (3, 20%)), vascular reconstruction was performed with superior mesenteric vein (6/15), portal vein (7/15) and the junction between superior mesenteric and splenic vein (2/15). Eighty percent of the reconstructions were tube grafts (12/15), and the remaining were patch plasties. In 13/15 (87%) of the cases, the vascular reconstruction was patent; in 2/15 (13%), there was one stenosis without reintervention need and one graft failure with complete thrombosis. Out of 15 patients, 4 major complications according to Clavien-Dindo classification (IIIa n = 2, 13%; IIIb n = 1, 7%; V n = 1, 7%) were documented. Latest re-imaging after surgery among the 10 patients with imaging follow-up more than 1 month postoperatively was after 6.5 months ((median, interquartile range 4-12 months), and clinical follow-up was at 6.7 months (median, 3.3-13 months)). CONCLUSION Due to its off-the-shelf availability, portomesenteric reconstruction using bovine pericardium seems to be a feasible and safe method in pancreatic resection with vascular encasement. Xenopericardial grafts can be crafted to any size and are applicable in potentially infected environment.


Challenges and adaptations in training during pandemic COVID-19: observations by an orthopedic resident in Singapore.


title: Comparison of quality of recovery from anaesthesia in cats induced with propofol or alfaxalone.

text: OBJECTIVE To assess the quality and length of recovery from anaesthesia induced with either propofol or alfaxalone and maintained with isoflurane, in cats undergoing short procedures in private veterinary practice. STUDY DESIGN Prospective, blinded, randomized study. ANIMALS Ninety-three healthy mixed breed cats. METHODS After premedication with intramuscular acepromazine (0.05 mg kg(-1)) and buprenorphine (0.01 mg kg(-1)), cats were randomly allocated to receive either propofol (Group P) or alfaxalone (Group A) for induction of anaesthesia. Following endotracheal intubation, anaesthesia was maintained with isoflurane vaporized in oxygen. The quality of induction, physiological parameters throughout anaesthesia and the duration of both surgery and anaesthesia were recorded. The level of ambient noise, recovery times, number of attempts to stand, reaction of the cat to touch 15 minutes after extubation, and other relevant characteristics of the recovery period were noted and a video recording of the recovery was made. The videos were assessed by a second, blinded anaesthetist, using simple descriptive and visual analogue scales. RESULTS No statistically significant differences between groups with respect to preoperative data, premedication, surgery, anaesthesia and recovery times and scores were observed. There was a statistically significant difference in the number of patients paddling and trembling on recovery in Group A (p = 0.032) even though there was no statistically significant difference in the level of ambient noise in the recovery ward or in the overall quality of recovery. CONCLUSIONS Both propofol and alfaxalone provide good recovery characteristics in premedicated cats undergoing short procedures in clinical settings. Alfaxalone induction was associated with more episodes of paddling and trembling during recovery. CLINICAL RELEVANCE Both agents would appear appropriate for induction of anaesthesia in cats for short procedures.


Clinical characteristics and outcomes of patients with COVID-19 and rheumatic disease in China 'hot pot' versus in US 'hot pot': similarity and difference.


title: Efficacy and tolerability of long-acting octreotide in the treatment of thymic tumors: results of a pilot trial.

text: OBJECTIVES Octreotide is a somatostatin analog, long-acting formulations of which have been used experimentally for the treatment of patients with invasive tumors and/or residual disease after conventional therapies. The objective of this retrospective study was to evaluate the efficacy of long-acting octreotide (Sandostatin LAR) for the treatment of thymic tumors, with a primary efficacy end point of progression-free survival. METHODS Between 1994 and 2010, 44 patients with thymic malignancies were evaluated. Twenty-seven patients underwent an OctreoScan, and 12 OctreoScan-positive patients were treated with long-acting octreotide at a dose of 20 mg, given as an intramuscular injection, every 2 weeks. RESULTS Treatment with long-acting octreotide gave the following results: 3 cases of partial response (25%), 5 cases of stable disease (42%), and 4 cases of progressive disease (33%), with an average progression-free survival of 8 months (range, 3 to 21). Treatment compliance and tolerability were good for all evaluated patients. CONCLUSIONS The results of this study confirm the somatostatin receptor as a valid target for the treatment of thymic malignancies. Overall, therapy with long-acting somatostatin analogs seems to be safe and effective.


title: Severe viral respiratory infections in children with IFIH1 loss-of-function mutations.

text: Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. Using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in IFIH1, which encodes an RIG-I-like receptor involved in the sensing of viral RNA. Functional testing of the variants IFIH1 alleles demonstrated that the resulting proteins are unable to induce IFN-β, are intrinsically less stable than wild-type IFIH1, and lack ATPase activity. In vitro assays showed that IFIH1 effectively restricts replication of human respiratory syncytial virus and rhinoviruses. We conclude that IFIH1 deficiency causes a primary immunodeficiency manifested in extreme susceptibility to common respiratory RNA viruses.


title: Current status of minimally invasive radical cystectomy: an outcome-based comparison.

text: Minimally invasive approaches to radical cystectomy are 20 years old. Available data suggest that minimally invasive radical cystectomy can provide comparable outcomes to open radical cystectomy despite the scarcity of level 1-2 evidence. Perioperative, functional and early oncologic outcomes seem comparable between the two surgical approaches. Robotic technology has allowed more surgeons to perform minimally invasive radical cystectomy and has simplified technically demanding steps that posed problems in conventional laparoscopy. This is evident by the rapid dissemination of robotics in many bladder cancer centers worldwide and by the numerous emerging series of robot-assisted intracorporeal urinary diversion. Until more data are available regarding the oncologic performance of minimally invasive radical cystectomy, open radical cystectomy remains the gold standard procedure for now.


title: Are we missing the target? Are we aiming too low? What are the aerobic exercise prescriptions and their effects on markers of cardiovascular health and systemic inflammation in patients with knee osteoarthritis? A systematic review and meta-analysis.

text: OBJECTIVES We systemically reviewed published studies that evaluated aerobic exercise interventions in patients with knee osteoarthritis (OA) to: (1) report the frequency, intensity, type and time (FITT) of exercise prescriptions and (2) quantify the changes in markers of cardiovascular health and systemic inflammation. DATA SOURCES PubMed, CINAHL, Scopus; inception to January 2019. ELIGIBILITY CRITERIA Randomised clinical trials (RCT), cohort studies, case series. DESIGN We summarised exercise prescriptions for all studies and calculated effect sizes with 95% CIs for between-group (RCTs that compared exercise and control groups) and within-group (pre-post exercise) differences in aerobic capacity (VO2), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and inflammatory markers (interleukin-6 (IL-6), tumour necrosis factor-alpha). We pooled results where possible using random effects models. RESULTS Interventions from 49 studies were summarised; 8% (4/49) met all FITT guidelines; 16% (8/49) met all or most FITT guidelines. Fourteen studies (10 RCTs) reported at least one marker of cardiovascular health or systemic inflammation. Mean differences (95% CI) indicated a small to moderate increase in VO2 (0.84 mL/min/kg; 95% CI 0.37 to 1.31), decrease in HR (-3.56 beats per minute; 95% CI -5.60 to -1.52) and DBP (-4.10 mm Hg; 95% CI -4.82 to -3.38) and no change in SBP (-0.36 mm Hg; 95% CI -3.88 to 3.16) and IL-6 (0.37 pg/mL; 95% CI -0.11 to 0.85). Within-group differences were also small to moderate. CONCLUSIONS In studies of aerobic exercise in patients with knee OA, very few interventions met guideline-recommended dose; there were small to moderate changes in markers of cardiovascular health and no decrease in markers of systemic inflammation. These findings question whether aerobic exercise is being used to its full potential in patients with knee OA. PROSPERO REGISTRATION NUMBER CRD42018087859.


title: Phenotyping and outcomes of hospitalized COPD patients using rapid molecular diagnostics on sputum samples.

text: Background Etiologies of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous. We phenotyped severe AECOPD based on molecular pathogen detection of sputum samples collected at hospitalization of COPD patients and determined their outcomes. Methods We phenotyped 72 sputum samples of COPD patients who were hospitalized with a primary diagnosis of AECOPD using a molecular array that detected common bacterial and viral respiratory pathogens. Based on these results, the patients were classified into positive or negative pathogen groups. The pathogen-positive group was further divided into virus or bacteria subgroups. Admission day 1 blood samples were assayed for N-terminal prohormone brain natriuretic peptide, CRP, and complete blood counts. Results A total of 52 patients had a positive result on the array, while 20 patients had no pathogens detected. The most common bacterial pathogen detected was Haemophilus influenzae and the most common virus was rhinovirus. The pathogen-negative group had the worse outcomes with longer hospital stays (median 6.5 vs 5 days for bacteria-positive group, P=0.02) and a trend toward increased 1-year mortality (P=0.052). The bacteria-positive group had the best prognosis, whereas the virus-positive group had outcomes somewhere in between the bacteria-positive and pathogen-negative groups. Conclusion Molecular diagnostics on sputum can rapidly phenotype serious AECOPD into bacteria-, virus-, or pathogen-negative groups. The bacteria-positive group appears to have the best prognosis, while pathogen-negative group has the worst. These data suggest that AECOPD is a heterogeneous event and that accurate phenotyping of AECOPD may lead to novel management strategies that are personalized and more precise.


title: Molecular farming of antimicrobial peptides: available platforms and strategies for improving protein biosynthesis using modified virus vectors.

text: The constant demand for new antibiotic drugs has driven efforts by the scientific community to prospect for peptides with a broad spectrum of action. In this context, antimicrobial peptides (AMPs) have acquired great scientific importance in recent years due to their ability to possess antimicrobial and immunomodulatory activity. In the last two decades, plants have attracted the interest of the scientific community and industry as regards their potential as biofactories of heterologous proteins. One of the most promising approaches is the use of viral vectors to maximize the transient expression of drugs in the leaves of the plant Nicotiana benthamiana. Recently, the MagnifectionTM expression system was launched. This sophisticated commercial platform allows the assembly of the viral particle in leaf cells and the systemic spread of heterologous protein biosynthesis in green tissues caused by Agrobacterium tumefaciens "gene delivery method". The system also presents increased gene expression levels mediated by potent viral expression machinery. These characteristics allow the mass recovery of heterologous proteins in the leaves of N. benthamiana in 8 to 10 days. This system was highly efficient for the synthesis of different classes of pharmacological proteins and contains enormous potential for the rapid and abundant biosynthesis of AMPs.


title: Does the length of uniportal video-assisted thoracoscopic lobectomy affect postoperative pain? Results of a randomized controlled trial.

text: BACKGROUND Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy has become a common approach for the treatment of early stage lung cancer. Here, we aimed to establish whether the length of uniportal incision could affect postoperative pain and surgical outcomes in consecutive patients undergoing uniportal VATS lobectomy for early stage lung cancer. METHODS This was a unicenter Randomized Control Trial (NCT03218098). Consecutive patients undergoing uniportal VATS lobectomy for Stage I lung cancer were randomly assigned to a Small Incision group or Long Incision group in 1:1 ratio based on whether patients received a 4 cm or 8 cm incision. The endpoints were to compare the intergroup difference regarding (i) postoperative pain measured by brief pain inventory (BPI) questionnaire (first endpoint); (ii) operative time; (iii) length of chest drainage; (iv) length of hospital stay; (v) postoperative complications; and (vi) pulmonary functional status (secondary endpoints). RESULTS A total of 48 patients were eligible for the study. Four patients were excluded; the study population included 44 patients: 23 within the Small Incision group, and 21 within the Long Incision group. The 11 BPI scores between the two groups showed no significant difference. Small Incision group presented higher operative time than Long Incision group (138.69 vs. 112.14 minutes; P = 0.0001) while no significant differences were found regarding length of hospital stay (P = 0.95); respiratory complications (P = 0.92); FEV1% (P = 0.63), and 6-Minute Walking Test (P = 0.77). CONCLUSIONS A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. KEY POINTS A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. To perform a larger incision could be a valuable strategy, particularly in nonexpert hands or when the patient's anatomy or tumor size make exposure of anatomic structures through smaller incisions difficult.


Let's not forget our female front line.


title: [Epidemiological investigation of a family clustering of COVID-19].

text: Objective: To investigate the epidemiological characteristics of a family clustering of COVID-19. Methods: Field epidemiological survey was conducted. Result: Case 1 of the long-term residents from Hubei province was the source of infection of this family clustering. There were 6 cases (from case 2 to case 7) infected in the whole incubation period. The incubation period was more than 14 days for 3 of the second-generation cases. Routes of transmission include respiratory droplets (from case 1 transmitted to case 6, from case 1 to her family members) and closecontact (from case 1 to other cases in her family). All the age groups were generally susceptible, while elderly were easier to progress to critically ill. Besides respiratory symptoms, there were also gastrointestinal symptoms, of which diarrhea was the most common one. Conclusion: Family clustering had been an important part for COVID-19 cases.


title: Rapid Synthesis of 68Ga-labeled macroaggregated human serum albumin (MAA) for routine application in perfusion imaging using PET/CT.

text: 99mTc-labeled MAA is commonly used for single photon emission computed tomography SPECT. In contrast, positron emission tomography/CT (PET/CT) delivers images with significantly higher resolution. The generator produced radionuclide 68Ga is widely used for PET/CT imaging agents and 68Ga-labeled MAA represents an attractive alternative to 99mTc-labeled MAA. We report a simple and rapid NaCl based labeling procedure for the labeling of MAA with 68Ga using a commercially available MAA labeling kit for 99mTc. The procedure delivers 68Ga-labeled MAA with a high specific activity and a high labeling efficiency (>99%). The synthesis does not require a final step of separation or the use of organic solvents.


title: Inactivation of murine norovirus on a range of copper alloy surfaces is accompanied by loss of capsid integrity.

text: Norovirus is one of the most common causes of acute viral gastroenteritis. The virus is spread via the fecal-oral route, most commonly from infected food and water, but several outbreaks have originated from contamination of surfaces with infectious virus. In this study, a close surrogate of human norovirus causing gastrointestinal disease in mice, murine norovirus type 1 (MNV-1), retained infectivity for more than 2 weeks following contact with a range of surface materials, including Teflon (polytetrafluoroethylene [PTFE]), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. Persistence was slightly prolonged on ceramic surfaces. A previous study in our laboratory observed that dry copper and copper alloy surfaces rapidly inactivated MNV-1 and destroyed the viral genome. In this new study, we have observed that a relatively small change in the percentage of copper, between 70 and 80% in copper nickels and 60 and 70% in brasses, had a significant influence on the ability of the alloy to inactivate norovirus. Nickel alone did not affect virus, but zinc did have some antiviral effect, which was synergistic with copper and resulted in an increased efficacy of brasses with lower percentages of copper. Electron microscopy of purified MNV-1 that had been exposed to copper and stainless steel surfaces suggested that a massive breakdown of the viral capsid had occurred on copper. In addition, MNV-1 that had been exposed to copper and treated with RNase demonstrated a reduction in viral gene copy number. This suggests that capsid integrity is compromised upon contact with copper, allowing copper ion access to the viral genome.


title: Transcarotid Mechanical Thrombectomy for Embolic Intracranial Large Vessel Occlusion after Endovascular Deconstructice Embolization for Carotid Blowout Syndrome.

text: Carotid blowout syndrome (CBS) is a fatal complication of head and neck cancer. Endovascular treatment, particularly deconstructive embolization, is effective for CBS, but it might result in thromboembolic events. We report the case of a 57-year-old man with underlying recurrent head and neck cancer who had CBS. The patient received endovascular embolization of the right internal, external, and common carotid arteries. Right internal carotid artery to middle cerebral artery embolic occlusion was noted immediately after the procedure, and left-sided weakness and facial palsy were found. Ipsilateral suprabulbar cervical internal carotid artery puncture was performed under fluoroscopic guidance, and rescue suction thrombectomy was successful. The patient had no significant neurological sequela. Transcarotid intraarterial thrombectomy is a reasonable method for managing postembolization large vessel occlusion, even in the neck, after irradiation.


title: A randomized comparison of the Ambu AuraGain versus the LMA supreme in patients undergoing gynaecologic laparoscopic surgery.

text: Second generation supraglottic airway devices providing high seal airway pressures are suitable for patients undergoing gynecologic laparoscopy. We compared the seal pressure achieved by the new Ambu AuraGain™ versus LMA Supreme™ following pneumoperitoneum in the Trendelenburg position. Sixty female patients were randomly allocated to ventilation with either the AuraGain or the Supreme. A target-controlled system was used to administer total intravenous anesthesia. Intracuff pressure was maintained below 60 cm H2O. The following parameters were registered: Time, number of attempts and manoeuvres required for insertion; seal pressure and peak inspiratory pressure at four time points; ease of gastric tube insertion, flexible scope view, complications and postoperative morbidity. Both devices were quick and easily inserted, although the Supreme required less rotation manoeuvres (16 in AuraGain vs. 6 in LMA Supreme; p = 0.01). The AuraGain achieved higher seal pressures (34 ± 5 in AuraGain vs. 29 ± 5 in LMA Supreme; p = 0.0002). Following pneumoperitoneum in head-down position, peak airway pressure increased 9 ± 3 cm H2O in both groups, exceeding seal pressure in 3 patients in the Supreme group (p = 0.06). The vocal cords were seen through all AuraGain and 90% of the Supreme devices; epiglottis was often visible inside the tube (68%). No differences were found in the incidence of traces of blood on the mask or postoperative symptoms. Both devices allowed effective ventilation in patients undergoing gynaecologic laparoscopic surgery with a low rate of complications. The Ambu AuraGain provided higher seal pressures and a clear view of glottic inlet in all patients offering the possibility to guide direct tracheal intubation if required.


title: RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade.

text: The Raf/MEK/ERK signal transduction cascade belongs to the mitogen-activated protein kinase (MAPK) cascades. Raf/MEK/ERK signaling leads to stimulus-specific changes in gene expression, alterations in cell metabolism or induction of programmed cell death (apoptosis), and thus controls cell differentiation and proliferation. It is induced by extracellular agents, including pathogens such as RNA viruses. Many DNA viruses are known to induce cellular signaling via this pathway. As these pathogens partly use the DNA synthesis machinery for their replication, they aim to drive cells into a proliferative state. In contrast, the consequences of RNA virus-induced Raf/MEK/ERK signaling were less clear for a long time, but since the turn of the century the number of publications on this topic has rapidly increased. Research on this virus/host-interaction will broaden our understanding of its relevance in viral replication. This important control center of cellular responses is differently employed to support the replication of several important human pathogenic RNA viruses including influenza, Ebola, hepatitis C and SARS corona viruses.


title: Lifetime Prevalence of Self-Reported Work-Related Health Problems Among U.S. Workers - United States, 2018.

text: Approximately 2.8 million nonfatal workplace illnesses and injuries were reported in the United States in 2018 (1). Current surveillance methods might underestimate the prevalence of occupational injuries and illnesses (2,3). One way to obtain more information on occupational morbidity is to assess workers' perceptions about whether they have ever experienced health problems related to work (4). Occupational exposures might directly cause, contribute to, exacerbate, or predispose workers to various health problems (work-related health problems). CDC's National Institute for Occupational Safety and Health estimated the lifetime prevalence of self-reported, work-related health problems for the currently employed population overall and stratified by various demographic and job characteristics using data from the 2018 version of the SummerStyles survey. Overall, 35.1% of employed respondents had ever experienced a work-related health problem (95% confidence interval [CI] = 33.0%-37.3%). The most commonly reported work-related health problem was back pain (19.4%, 95% CI = 17.6%-21.2%). Among industries, construction (48.6%, 95% CI = 36.54%-60.58%) had the highest prevalence of any work-related health problems. Workplace injury and illness prevention programs are needed to reduce the prevalence of work-related health problems, especially in higher-risk industries.


title: Transanal total mesorectal excision: a pure NOTES approach for selected patients.

text: BACKGROUND The concept of natural orifice transluminal endoscopic surgery (NOTES) has stimulated the development of various "incisionless" procedures. One of the most popular is the transanal approach for rectal lesions. The aims of this study were to report how we standardized NOTES technique for transanal mesorectal excision without abdominal assistance, discuss the difficulties and surgical outcomes of this technique and report its feasibility in a small group of selected patients. METHODS Three consecutive female patients underwent transanal NOTES rectal resection without transabdominal laparoscopic assistance for rectal lesions. Functional results were assessed with the Fecal Incontinence Quality of Life scale and the Wexner score. RESULTS The technical steps are described in details and complemented with a video. All procedures were completed without transabdominal laparoscopic help. The mesorectal plane was entirely dissected without any disruption, and distal and circumferential margins were tumor-free. No major complications were observed. Functional results show a significant impairment after surgery with improvement at 6 months to levels near those of the preoperative period. CONCLUSIONS The performance and publication of NOTES procedures are subject to much discussion. Despite the small number of patients, this procedure appears feasible and can be accomplished maintaining fecal continence and respecting oncologic principles.


Thoughts on Adaptive Leadership in a Challenging Time.


title: Minimal invasive lung support via umbilical vein with a double-lumen cannula in a neonatal lamb model: a proof of principle.

text: PURPOSE Acute respiratory distress syndrome, with the need for invasive mechanical ventilation (MV) remains a major cause of neonatal mortality and morbidity. Although venovenous extracorporeal lung support (VV-ECLS) has become a standard of care procedure in neonatal patients with acute pulmonary failure there are no reports regarding the use of a double-lumen cannula for extracorporeal minimal invasive lung support via the umbilical vein. METHODS A neonatal lamb model was used (n = 3). Umbilical vein was cannulated with a double-lumen catheter allowing venovenous extracorporeal gas exchange. Cannula was positioned with its tip in the right atrium. VV-ECLS was started and ventilation was stopped. Providing oxygenation and CO2 removal solely through VV-ECLS hemodynamics, blood gases were measured. RESULTS Total VV-ECLS without MV was applied to all three neonatal lambs. Time on venovenous ECLS was 60, 120 and 120 min. Initial pCO2 was 60, 56 and 65 mmHg compared to 31, 32 and 32 mmHg at the end of VV-ECLS. Initial pO2 was 30, 27 and 26 mmHg compared to 22, 19 and 23 mmHg. Initial lactate was 5, 10 and 3.7 mmol/l compared to 13.3, 12.6 and 11.3 mmol/l at the end of VV-ECLS. MAP at baseline was 51, 52 and 65 mmHg compared to 36, 38 and 41 mmHg at the end of VV-ECLS. In all three lambs inotropes were admitted to maintain MAD >35 mmHg. CONCLUSION Even without mechanical ventilation we were able to sufficiently remove pCO2 with our new minimal invasive VV-ECLS using a double-lumen catheter via the umbilical vein, supporting the idea of a lung protective strategy in neonatal acute respiratory failure. pO2 was measured 22, 19 and 23 mmHg, respectively, at the end of VV-ECLS, at least partially caused by recirculation phenomenon, which could possibly be improved by different cannula design. Inotropic support was necessary during VV-ECLS to achieve targeted MAD > 35 mmHg. While technically feasible, this new approach might allow further research in the field of extracorporeal lung support and therefore will follow the concept of a lung protective strategy in acute neonatal respiratory failure.


title: [Retrieval of embolized coronary stent: combination of various approaches].

text: Device embolization is a potentially serious complication of percutaneous vascular interventions. Various devices and techniques can be used for the retrieval procedure. Herein, we report the retrieval of a stent that slipped off the balloon in the left main coronary artery and then embolized to the right femoral artery in a 77-year-old male. The stent could not be retrieved by snare, but was removed from the coronary tree via a balloon advanced inside it. The stent then embolized into the right femoral artery. Using a balloon catheter advanced through the stent and then via a biopsy forceps advanced over a femoro-femoral wire loop, we were able to remove the stent from the patient. In conclusion, there is no proven standard method for the retrieval of embolized material. Different techniques and devices can be used depending on the creativity of the operator as well as the individual situation of the case.


Public Health Urgency Created by the Success of Mechanical Thrombectomy Studies in Stroke.


title: COVID-19: The Endocrine opportunity in a pandemic.

text: The 2019 Coronavirus disease (COVID-19) pandemic has disrupted the social, economical and medical system worldwide. Although it is strictly an infectious disease, its intricate bidirectional relationship with various non-communicable metabolic diseases and endocrinological factors has been observed. While diabetes, hypertension, obesity have been found to be independent risk factors for COVID-19 disease severity and mortality, more inclination towards sedentary lifestyle, psychosocial stress at this critical time may be the harbingers of metabolic syndrome. Thus, endocrinologists have a great opportunity to play their role to combat this pandemic. This paper examines how various endocrinological disorders influence the dynamics of COVID-19 and vice versa. Moreover, it also intends to review the clinical guidelines to be adopted in practice of endocrinology in this trying time.


title: Simulation-based training for thoracoscopy.

text: INTRODUCTION An increasing proportion of thoracic procedures are performed using video-assisted thoracic surgery. This minimally invasive technique places special demands on the surgeons. Using simulation-based training on artificial models or animals has been proposed to overcome the initial part of the learning curve. This study aimed to investigate the effect of simulation-based training and to compare self-guided and educator-guided training. METHODS The study included a surgeon group (n = 10) and 30 randomized novices in 3 groups. A control group (n = 10) and the group of surgeons (n = 10) were tested with no previous simulator training. A self-guided training group (n = 10) and an educator-guided training group (n = 10) trained for 3 hours on 3 scenarios of increasing fidelity and difficulty before taking a standardized test consisting of performing a wedge resection on a porcine lung, which was recorded and assessed blindly and independently by 2 thoracoscopic experts using a modified version of a validated assessment tool. RESULTS Interrater reliability was acceptable (Spearman ρ = 0.73, P < 0.001). The control group and the self-guided training group performed significantly worse than the experienced surgeons (P = 0.012 and P = 0.010, respectively). There was no significant difference between the educator-guided training group and the experienced surgeons (P = 0.271). CONCLUSIONS This randomized study concerning simulation-based training for thoracoscopy showed that 3 hours of intensive simulator training with a dedicated educator enables novices to perform an acceptable wedge resection in a simple, simulated model. Although not significant, it seemed that having an educator present during training had a beneficiary effect. Transfer studies are required for further conclusions.


title: Multisociety consensus quality improvement guidelines for intraarterial catheter-directed treatment of acute ischemic stroke, from the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society for Card

text: PURPOSE In this international multispecialty document, quality benchmarks for processes of care and clinical outcomes are defined. It is intended that these benchmarks be used in a quality assurance program to assess and improve processes and outcomes in acute stroke revascularization. MATERIALS AND METHODS Members of the writing group were appointed by the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society of Cardiac Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, European Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology. The writing group reviewed the relevant literature from 1986 through February 2012 to create an evidence table summarizing processes and outcomes of care. Performance metrics and thresholds were then created by consensus. The guideline was approved by the sponsoring societies. It is intended that this guideline be fully updated in 3 years. RESULTS In this international multispecialty document, quality benchmarks for processes of care and clinical outcomes are defined. These include process measures of time to imaging, arterial puncture, and revascularization and measures of clinical outcome up to 90 days. CONCLUSIONS Quality improvement guidelines are provided for endovascular acute ischemic stroke revascularization procedures.


title: Grape juice increases the BDNF levels but not alter the S100B levels in hippocampus and frontal cortex from male Wistar Rats.

text: Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.


title: Can single-incision thoracoscopic surgery using a wound protector be used as a first-line approach for the surgical treatment of primary spontaneous pneumothorax? A comparison with three-port video-assisted thoracoscopic surgery.

text: OBJECTIVE In this study, we compared single-incision thoracoscopic surgery (SITS) using a wound protector, with three-port video-assisted thoracoscopic surgery (VATS) to investigate whether it can be used as a first-line approach for primary spontaneous pneumothorax (PSP). METHODS We retrospectively reviewed and analyzed the medical records of patients who were diagnosed with PSP in our hospital between March 2013 and January 2014 who underwent SITS (n = 37) or three-port VATS (n = 23). RESULTS There was no significant difference between the patients who underwent SITS and those who underwent three-port VATS in terms of their age, gender, number of episodes, pneumothorax laterality, operation time, number of wedge resection, duration of post-operative hospital stay and post-operative drainage, and complications. The post-operative pain score was significantly lower in the SITS group compared to the three-port group at both 24 and 72 h (3.9 ± 1.2 vs. 5.2 ± 1.3, p = 0.022, 2.5 ± 1.5 vs. 3.9 ± 1.8, p = 0.03). There was no statistically significant difference in the use of additional intramuscular analgesia between the two groups, but it was lower in the SITS group. CONCLUSIONS We consider that SITS using a wound protector is an appropriate first-line surgical approach for PSP.


title: Leucine-rich repeat-containing G-protein-coupled receptor 5 is associated with invasion, metastasis, and could be a potential therapeutic target in human gastric cancer.

text: BACKGROUND Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), which is identified as a novel intestinal stem cell marker, is overexpressed in various tumours. In this study, we explore Lgr5 expression in gastric carcinoma and analyse its role in invasion, metastasis, and prognosis in carcinoma. METHODS A combination of immunohistochemistry, western blotting, and quantitative reverse transcription-polymerase chain reaction were used to detect mRNA and protein expression levels of Lgr5 and matrix metalloproteinase 2 (MMP2). Small interfering RNA against Lgr5 was designed, synthesised, and transfected into AGS cells. The effects of Lgr5 siRNA on cell invasion were detected by transwell invasion chamber assay and wound healing assay. RESULTS Leucine-rich repeat-containing G-protein-coupled receptor 5 expression was significantly higher in gastric carcinomas than in normal mucosa. Leucine-rich repeat-containing G-protein-coupled receptor 5 expression positively correlated with the depth of invasion, lymph node metastasis, distance of metastasis, and MMP2 expression levels. Multivariate analysis showed that Lgr5 had an independent effect on survival, and that it positively correlated with MMP2. Leucine-rich repeat-containing G-protein-coupled receptor 5 siRNAs inhibited Lgr5 mRNA and protein expression. Transwell assays indicated that these siRNAs resulted in significantly fewer cells migrating through the polycarbonate membrane, and wound healing assay also indicated that siRNAs decreased the migration of cells. Inhibition of Lgr5 resulted in a significant decrease in MMP2 and β-catenin levels compared with those in controls. CONCLUSIONS Leucine-rich repeat-containing G-protein-coupled receptor 5 was correlated with invasion and metastasis. Leucine-rich repeat-containing G-protein-coupled receptor 5 inhibition could serve as a novel therapeutic approach.


title: SARS-COV-2 and Male Reproductive Health.

text: Critical challenges for the public and private health, research, and medical communities have been posed by the COVID-19 outbreak. Some of these challenges are related to the possible adverse effects of SARS-CoV-2 on male reproductive health, and whether other potential modes of transmission may occur, such as sexual transmission. Moreover, concerns have been raised in terms of whether the COVID-19 outbreak may have an impact on fertility worldwide. In this study, we will discuss the origins of SARS-CoV-2. We will further describe its mechanism of action, diagnosis, symptoms, and potential effects on the male reproductive system.


title: US CDC Real-Time Reverse Transcription PCR Panel for Detection of Severe Acute Respiratory Syndrome Coronavirus 2.

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent associated with coronavirus disease, which emerged in late 2019. In response, we developed a diagnostic panel consisting of 3 real-time reverse transcription PCR assays targeting the nucleocapsid gene and evaluated use of these assays for detecting SARS-CoV-2 infection. All assays demonstrated a linear dynamic range of 8 orders of magnitude and an analytical limit of detection of 5 copies/reaction of quantified RNA transcripts and 1 x 10-1.5 50% tissue culture infectious dose/mL of cell-cultured SARS-CoV-2. All assays performed comparably with nasopharyngeal and oropharyngeal secretions, serum, and fecal specimens spiked with cultured virus. We obtained no false-positive amplifications with other human coronaviruses or common respiratory pathogens. Results from all 3 assays were highly correlated during clinical specimen testing. On February 4, 2020, the Food and Drug Administration issued an Emergency Use Authorization to enable emergency use of this panel.


title: The use of specialised preterm birth clinics for women at high risk of spontaneous preterm birth: a systematic review.

text: BACKGROUND Specialised preterm birth clinics care for women at high risk of spontaneous preterm birth. This systematic review assesses current practice within preterm birth clinics globally. METHODS A comprehensive search strategy was used to identify all studies on preterm birth clinics on the MEDLINE, Embase, PsycINFO, CENTRAL and CINAHL databases. There were no restrictions to study design. Studies were limited to the English language and publications from 1998 onwards. Two reviewers assessed studies for inclusion, performed data extraction and reviewed methodological quality. Primary outcomes were referral criteria, investigations and interventions offered in preterm birth clinics. Secondary outcomes were the timing of planned first and last appointments and frequency of review. RESULTS Thirty-two records fulfilled eligibility criteria and 20 studies were included in the main analysis following grouping of records describing the same study or clinic. Studies were of mixed study design and methodological quality. A total of 39 clinics were described; outcome data was not available for all clinics. Referral criteria included previous spontaneous preterm birth (38/38, 100%), previous mid-trimester loss (34/38, 89%) and previous cervical surgery (33/38, 87%). All clinics offered transvaginal cervical length scans. Additional investigations varied, including urogenital swabs (16/28, 57%) and fetal fibronectin (8/28, 29%). The primary treatment of choice for a sonographic short cervix was cervical cerclage in 10/33 (30%) clinics and vaginal progesterone in 6/33 (18%), with 10/33 (30%) using multiple first-line options and 6/33 (18%) using a combination of treatments. The majority of clinics planned timing of first review for 12-16 weeks (30/35, 86%) and the frequency of review was usually determined by clinical findings (18/24, 75%). There was a wide variation in gestational age at clinic discharge between 24 and 37 weeks. CONCLUSIONS There is variation in the referral criteria, investigations and interventions offered in preterm birth clinics and in the timing and frequency of review. Consistency in practice may improve with the introduction of consensus guidelines and national preterm birth prevention programmes. TRIAL REGISTRATION Systematic review registration number: CRD42019131470.


title: Prediction of adverse outcomes by blood glucose level after endovascular therapy for acute ischemic stroke.

text: OBJECT The authors evaluated the prognostic significance of blood glucose level at admission (BGA) and change in blood glucose at 48 hours from the baseline value (CG48) in nondiabetic and diabetic patients before and after endovascular therapy for acute ischemic stroke (AIS). METHODS The BGA and CG48 data were analyzed in 614 patients with AIS who received endovascular therapy at 7 US centers between 2006 and 2009. Data reviewed included demographics, stroke risk factors, diabetic status, National Institutes of Health Stroke Scale (NIHSS) score at presentation, recanalization grade, intracranial hemorrhage (ICH) rate, and 90-day outcomes (mortality rate and modified Rankin Scale score of 3-6 [defined as poor outcome]). Variables with p values < 0.2 in univariate analysis were included in a binary logistic regression model for independent predictors of 90-day outcomes. RESULTS The mean patient age was 67.3 years, the median NIHSS score was 16, and 27% of patients had diabetes. In nondiabetic patients, BGA ≥ 116 mg/dl (≥ 6.4 mmol/L) and failure of glucose level to drop > 30 mg/dl (> 1.7 mmol/L) from the admission value were both significant predictors of 90-day poor outcome and death (p < 0.001). In patients with diabetes, BGA ≥ 116 mg/dl (≥ 6.4 mmol/L) was an independent predictor of poor outcome (p = 0.001). The CG48 was not a predictor of outcome in diabetic patients. A simplified 6-point scale including BGA, Thrombolysis in Myocardial Infarction (TIMI) Grade 2-3 Reperfusion, Age, presentation NIHSS score, CG48, and symptomatic ICH (BRANCH) corresponded with poor outcomes at 90 days; the area under the curve value was > 0.79. CONCLUSIONS Failure of blood glucose values to decrease in the first 48 hours after AIS intervention correlated with poor 90-day outcomes in nondiabetic patients. The BRANCH scale shows promise as a simple prognostication tool after endovascular therapy for AIS, and it merits prospective validation.


title: In-bag morcellation.

text: In-bag morcellation seems to be a viable alternative to open power morcellation and offers the advantage of minimal to no spillage of tissue or fluids during morcellation. We report our initial experience and technique using this approach.


title: Novel coronavirus and central nervous system.

text: An outbreak of a novel coronavirus (2019-nCoV) that emerged in Wuhan has rapidly spread throughout China and has now become a global public health concern. As of the early March, a total of 100,000 cases have been confirmed in multiple countries. Clinical characteristics of 2019-nCoV that respiratory symptoms, such as cough, are the most common.[1] This is consistent with the finding that the majority of patients are virus-positive in nasopharyngeal and oropharyngeal swabs suggesting it mainly invades and infects the respiratory system, a hypothesis supported by pathological data.[2] In addition, it has been reported that patients' stool has tested positive for 2019-nCoV, indicating that the virus could spread from the respiratory tract to the digestive tract, or that individuals could be infected via the faecal-oral route. However, the neuroinvasive potential of 2019-nCoV remains poorly understood.


title: Beyond autophagy: New roles for ULK1 in immune signaling and interferon responses.

text: The human serine/threonine kinase ULK1 is the human homolog of the Caenorhabditis elegans Unc-51 kinase and of the Saccharomyces cerevisiae autophagy-related protein kinase Atg1. As Unc-51 and Atg1, ULK1 regulates both axon growth and autophagy, respectively, in mammalian cells. However, a novel immunoregulatory role of ULK1 has been recently described. This kinase was shown to be required for regulation of both type I interferon (IFN) production and induction of type I IFN signaling. Optimal regulation of IFN production is crucial for generation of effective IFN-immune responses, and defects in such networks can be detrimental for the host leading to uncontrolled pathogen infection, tumor growth, or autoimmune diseases. Thus, ULK1 plays a central role in IFN-dependent immunity. Here we review the diverse roles of ULK1, with special focus on its importance to type I IFN signaling, and highlight important future study questions.


title: The Valeo stent: a pre-mounted, open-cell, large stent for use in small children with CHD.

text: OBJECTIVES The aim of the present study was to determine the outcomes of using the Valeo stent (Bard Peripheral Vascular, Tempe, Arizona, United States of America) in small children with CHD. BACKGROUND Stenting vascular stenoses is safe and effective in adults and older children with CHD but is limited in smaller children. The design of the Valeo stent addresses these limitations but has not been extensively described. METHODS Bench testing was conducted to determine the maximum diameter of the stent, foreshortening, and side-cell diameter. A retrospective analysis of Valeo stents implanted between October, 2012 and October, 2014 was performed. Patient profile, pre-implant/post-implant catheterization data, and stent geometry were reviewed. RESULTS Bench testing: medium and large Valeo stents can be dilated up to 13 mm and 20 mm diameters, respectively. Side-cells are dilatable up to 12 mm. Valeo stents are of low profile - delivered through 6- or 7-Fr sheaths - and show minimal foreshortening. Retrospective analysis: a total of 81 stents were implanted in 61 patients with CHD. The median weight was 15.3 kg, and the median age was 58.9 months. Stents were implanted in the pulmonary artery, systemic vein, aorta, and pulmonary vein. Overall, mean vessel diameters increased from 4.1 to 7.7 mm (121.7%). There was effective mean gradient reduction: 3.7-0.5 mmHg (63%) in the venous systems, 28.2-12.5 mmHg (63.7%) in the pulmonary arteries, and 17.4-4 mmHg (77.1%) in the aorta. The mean stent foreshortening was 2.5%, and the mean recoil was 5.9%. Side-cells that crossed other vessels were dilated in four cases, and stents were re-mounted onto different-sized balloons in seven cases. CONCLUSIONS The features of the Valeo stent, such as low profile, large maximum diameter, open-cell design, minimal foreshortening, and recoil, make it suitable for treating vascular stenoses in small children with CHD.


title: Interaction of novel fluorescent nanoscale ionic silicate platelets with biomaterials for biosensors.

text: The nano silicate platelets (NSPs) of 100 × 100 × 1 nm(3) in dimension were previously derived from the exfoliation of naturally occurring sodium montmorillonite clay, and their affinity to the surface of bacteria was revealed. The unique characteristics of ionic charges (≡Si-O-Na(+)) and the presence of siloxanol functionalities (≡Si-OH) allowed the organic modification of NSP to form NSP-tethering poly(hydroxyethyl methacrylate) (PHEMA) pendants through a sol-gel and living polymerization. By attaching nathphalimide-type fluorescence onto NSP-PHEMA, a new class of fluorescent organic-inorganic hybrid (NSP-PHEMA-HA), was prepared and its photoluminescence (PL) and bacterial trapping properties were characterized. The investigation of PL emission revealed that the fluorescent NSP hybrids could be used to detect bacteria and possess the potential for the biosensor applications.


title: Implementation science: the laboratory as a command centre.

text: PURPOSE OF REVIEW Recent advances in point-of-care technologies to ensure universal access to affordable quality-assured diagnostics have the potential to transform patient management, surveillance programmes, and control of infectious diseases. Decentralization of testing can put tremendous stresses on fragile health systems if the laboratory is not involved in the planning, introduction, and scale-up strategies. RECENT FINDINGS The impact of investments in novel technologies can only be realized if these tests are evaluated, adopted, and scaled up within the healthcare system with appropriate planning and understanding of the local contexts in which these technologies will be used. SUMMARY In this digital age, the laboratory needs to take on the role of the Command Centre for technology introduction and implementation. Implementation science is needed to understand the political, cultural, economic, and behavioural context for technology introduction. The new paradigm should include: building a comprehensive system of laboratories and point-of-care testing sites to provide quality-assured diagnostic services with good laboratory-clinic interface to build trust in test results and linkage to care; building and coordinating a comprehensive national surveillance and communication system for disease control and global health emergencies; conducting research to monitor the impact of new tools and interventions on improving patient care.


Fast, portable tests come online to curb coronavirus pandemic.


title: Infectious complications in dialysis--epidemiology and outcomes.

text: This Review focuses on the changing epidemiology of infections among patients with end-stage renal disease who are undergoing dialysis. In particular, bloodstream infections related to vascular access in patients undergoing hemodialysis, and peritonitis in patients undergoing peritoneal dialysis, are highlighted. Gram-positive (staphylococcal and enterococcal) bloodstream infections and Gram-negative peritonitis (especially extended-spectrum β-lactamase-producing organisms) contribute substantially to excess health-care use owing to infection caused by dialysis access. Although the management of peritoneal-dialysis-related peritonitis has been hampered by a dearth of randomized, controlled studies, epidemiological data have provided useful information. To overcome the problem of differing methods used to monitor infections within various dialysis centers, uniform reporting systems for vascular-access-related infection and peritoneal-dialysis-related peritonitis, as recommended by the Centers for Disease Control and Prevention and the International Society for Peritoneal Dialysis, respectively, are discussed. Infections unrelated to the port of entry for dialysis are also examined, namely hepatitis and respiratory infection. To address the disease burden, we examine the infection-related mortality as well as the implications for subsequent cardiovascular mortality.


title: Functional dissection of an IFN-alpha/beta receptor 1 promoter variant that confers higher risk to chronic hepatitis B virus infection.

text: BACKGROUND/AIMS We previously demonstrated that two linked single nucleotide polymorphisms (SNPs) at -408 and -3 of type I interferon receptor 1 (IFNAR1) promoter are associated with susceptibility to chronic HBV infection. We aimed to elucidate the mechanism by which -3 and/or -408 C/T SNPs had such profound effects. METHODS A functional SNP in IFNAR1 promoter was defined by reporter gene assay, mutational analysis, flow cytometry analysis and gel shift assay. The nuclear protein binding to the essential polymorphic site was identified and its effect on transcriptional regulation of IFNAR1 was further demonstrated in a series of ex vivo and in vivo experiments. RESULTS We found C>T change at the -3 locus reduced the transcriptional activity of IFNAR1 promoter. High mobility group B protein 1 (HMGB1) and PARP-1 were co-recruited to the IFNAR1 promoter to regulate its transcription. We demonstrated HMGB1-binding affinity to IFNAR1 promoter was reduced in the -3T variant. Additionally, PARP-1, a cofactor for IFNAR1 transcription activation, was significantly suppressed by HBV. CONCLUSION Upon HBV infection, decreased binding affinity of HMGB1 to the IFNAR1 promoter -3T variant is aggravated by the suppressed PARP-1 expression caused by HBV, resulting in a further attenuated IFNAR1 expression. This compromises the antiviral and immuno-regulatory effects of IFN-alpha/beta, which may in turn affect the clinical outcome of HBV infection.


Response to Elmaraghi et al. re: "Maxillofacial Trauma Management During COVID-19: Multidisciplinary Recommendations".


title: Complications of microwave and radiofrequency lung ablation: personal experience and review of the literature.

text: PURPOSE Complications correlated with percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA) of lung tumours were retrospectively reviewed to compare them with data from the literature and to assess risk factors related with the procedures. MATERIALS AND METHODS From January 2003 to January 2009, 29 patients (36 lung lesions) were treated with RFA; from January 2007 to January 2009, 16 patients (17 lung lesions) were treated with MWA. Complications recorded at our institution are reported following the Society of Interventional Radiology guidelines. A systematic review of the literature was performed. RESULTS Any major complication of RFA or MWA was recorded. In agreement with the literature, pneumothorax was the most frequent complication, even though the incidence in our series was lower than reported in the literature (3.5% vs. 4.3-18%). Other complications of RFA were pleural effusion and subcutaneous emphysema. No massive haemorrhages, haemoptysis, abscesses, pneumonia, infections or tumour seeding were recorded in our series. The most common complication of MWA was pneumothorax (25% vs. 39% reported in the literature). Pleural effusion was a common reaction, but therapeutic drainage was never required. CONCLUSIONS Pneumothorax is the most common complication of both techniques. RFA and MWA are both excellent choices in terms of safety and tolerance.


title: Immune checkpoint inhibition in the era of COVID-19.

text: The worldwide Coronavirus pandemic continues to result in significant morbidity and mortality, with almost 9 million confirmed cases to date. Approximately 80% of patients have mild disease and do not require hospitalization. A key challenge facing the medical community is predicting which patients are at risk of developing severe disease in order to initiate early supportive treatment and to facilitate enrollment into much needed prospective clinical trials; crucial for developing effective treatment strategies.


Collaboration, simplicity and transparency (CoSiTra): the European Society of Anaesthesiology's guidelines initiative.


title: The Characteristics of 50 Hospitalized COVID-19 Patients With and Without ARDS.

text: BACKGROUND The type of pneumonia (coronavirus disease 2019, COVID-19) that is caused by the new coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) is now spreading across the world in a pandemic. Many patients with COVID-19 were admitted to the University Hospital Aachen during an outbreak that first struck the Heinsberg district in February 2020. METHODS A comparative presentation of the clinical features of the first 50 COVID-19 patients with and without acute respiratory distress syndrome (ARDS) who were hospitalized in the University Hospital Aachen. RESULTS 24 intubated patients were treated in the intensive care unit for ARDS of varying degrees of severity, while 26 patients who were breathing spontaneously without ARDS, but nevertheless needed supplemental oxygen, were treated in a separate isolation ward. The median age of the patients was 65 (IQR 58-76). The median latency from symptom onset to hospitalization was four days (IQR 1-8). Patients with ARDS had preexisting respiratory diseases more commonly than patients without ARDS (58% [95% confidence interval: 39; 76] versus 42% [26; 61]) and were more commonly overweight or obese (83% [64; 93] versus 42% [26; 61]). The two groups did not differ in viral burden but displayed significant differences in laboratory findings: ARDS patients had persistently elevated values for leukocytes, interleukin-6, lactate dehydrogenase, creatine kinase, and D-dimers over the period of observation. Patients without ARDS had persistently elevated inflammatory parameters and fever for at least one week, with an accompanying need for supplemental oxygen. Three of the patients with ARDS died of multiorgan failure, while four in the non-ARDS group died of respiratory insufficiency. CONCLUSION This initial description of a cohort of COVID-19 patients with and without ARDS in Germany reveals that those with ARDS more commonly have preexisting respiratory diseases and obesity, as well as persistently elevated inflammatory markers. COVID-19 patients without ARDS may likewise require prolonged hospitalization because of persistently elevated inflammatory values with a simultaneous need for supplemental oxygen.


title: Prognostic Accuracy of the HEART Score for Prediction of Major Adverse Cardiac Events in Patients Presenting With Chest Pain: A Systematic Review and Meta-analysis.

text: OBJECTIVE The HEART score has been proposed for emergency department (ED) prediction of major adverse cardiac events (MACE). We sought to summarize all studies assessing the prognostic accuracy of the HEART score for prediction of MACE in adult ED patients presenting with chest pain. METHODS We searched MEDLINE, PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews from inception through May 2018 and included studies using the HEART score for the prediction of short-term MACE in adult patients presenting to the ED with chest pain. The main outcome was short-term (i.e., 30-day or 6-week) incidence of MACE. We secondarily evaluated the prognostic accuracy of the HEART score for prediction of mortality and myocardial infarction (MI). Where available, accuracy of the Thrombolysis in Myocardial Infarction (TIMI) score was determined. RESULTS We included 30 studies (n = 44,202) in analysis. A HEART score above the low-risk threshold (≥4) had a sensitivity of 95.9% (95% confidence interval [CI] = 93.3%-97.5%) and specificity of 44.6% (95% CI = 38.8%-50.5%) for MACE. A high-risk HEART score (≥7) had a sensitivity of 39.5% (95% CI = 31.6%-48.1%) and specificity of 95.0% (95% CI = 92.6%-96.6%) for MACE, whereas a TIMI score above the low-risk threshold (≥2) had a sensitivity of 87.8% (95% CI = 80.2%-92.8%) and specificity of 48.1% (95% CI = 38.9%-57.5%) for MACE. A high-risk TIMI score (≥6) was 2.8% sensitive (95% CI = 0.8%-9.6%), but 99.6% (95% CI = 98.5%-99.9%) specific for MACE. A HEART score ≥ 4 had a sensitivity of 95.0% (95% CI = 87.2%-98.2%) for prediction of mortality and 97.5% (95% CI = 93.7%-99.0%) for prediction of MI. CONCLUSIONS The HEART score has excellent performance for prediction of MACE (particularly mortality and MI) in chest pain patients and should be the primary clinical decision instrument used for the risk stratification of this patient population.


Retained anvil after laparoscopic gastric bypass.