title: Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.

text: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis.


title: Seasonal invasive pneumococcal disease in children: role of preceding respiratory viral infection.

text: OBJECTIVE Our objective was to demonstrate correlations between invasive pneumococcal disease in children and circulating respiratory viruses. METHODS This retrospective study included 6 winter respiratory viral seasons (2001-2007) in Intermountain Healthcare, an integrated health system in the Intermountain West, including Primary Children's Medical Center in Salt Lake City, Utah. Children <18 years of age who were hospitalized with either invasive pneumococcal disease in any Intermountain Healthcare facility or culture-confirmed invasive pneumococcal disease at Primary Children's Medical Center were included. We analyzed the correlation between invasive pneumococcal disease and circulating respiratory viruses. RESULTS A total of 435 children with invasive pneumococcal disease and 203 with culture-confirmed invasive pneumococcal disease were hospitalized in an Intermountain Healthcare facility or Primary Children's Medical Center during the study period. During the same period, 6963 children with respiratory syncytial virus, 1860 with influenza virus, 1459 with parainfluenza virus, and 818 with adenoviruses were evaluated at Primary Children's Medical Center. A total of 253 children with human metapneumovirus were identified during the last 5 months of the study. There were correlations between invasive pneumococcal disease and seasonal respiratory syncytial virus, influenza virus, and human metapneumovirus activity. The correlation with invasive pneumococcal disease was strong up to 4 weeks after respiratory syncytial virus activity. For influenza virus and human metapneumovirus, the correlations were strong at 2 weeks after activity of these viruses. Pneumonia was the most common clinical disease associated with culture-confirmed invasive pneumococcal disease, mostly attributable to serotypes 1, 19A, 3, and 7F. CONCLUSIONS In the post-pneumococcal conjugate vaccine era, seasonal increases in respiratory syncytial virus, influenza virus, and human metapneumovirus infections in children were associated with increased pediatric admissions with invasive pneumococcal disease, especially pneumonia caused by nonvaccine serotypes.


title: Candidemia in critically ill immunocompromised patients: report of a retrospective multicenter cohort study.

text: BACKGROUND Immunocompromised critically ill patients constitute a population with the high risk of candidemia. This retrospective study aimed to assess the outcome of immunocompromised critically ill patients with candidemia. Secondary objectives were to describe clinical phenotypes of these patients, Candida ecology, and factors associated with mortality. RESULTS Overall, 121 patients were included in this study. Median delay from candidemia to first antifungal therapy was 3 days, in line with the observed delay of blood culture positivity. Candia albicans was the main Candida specie identified (54%), and susceptibility of Candida to fluconazole and echinocandins was of, respectively, 70% and 92%. Hospital mortality was of 60%. After adjustment for confounders, severity as assessed by the need for vasopressors (HR 1.8, CI95% 1.1-3.1), need for mechanical ventilation (HR 2.0, CI95% 1.1-3.8) and allogenic stem cell transplantation (HR 2.5, CI95% 1.1-6.0) were independently associated with poor outcome. Candida specie, susceptibility and treatment strategies were not associated with outcome. CONCLUSIONS Candidemia in immunocompromised critically ill patients is associated with a grim outcome. Despite the high prevalence of Candida non-albicans species, neither C. species nor its susceptibility was associated with outcome. Conversely, severity and preexisting allogeneic stem cell transplantation were independently associated with poor outcome. Despite antifungal prophylaxis and use of preemptive antifungal therapy in neutropenic patients, antifungal therapy was initiated three days after symptoms onset suggesting needs for specific strategies aiming to reduce this delay.


title: Prepare to adapt: Blood supply and transfusion support during the first 2 weeks of the 2019 Novel Coronavirus (COVID-19) pandemic affecting Washington State.

text: BACKGROUND The first coronavirus (COVID-19) case was reported in United States (US), in the state of Washington, approximately three months after the outbreak in Wuhan, China. Three weeks later, the US federal government declared the pandemic a national emergency. The number of confirmed COVID-19 positive cases increased rather rapidly and changed routine daily activities of the community. STUDY DESIGN AND METHODS This brief report describes the response from the hospital, the regional blood center, and the hospital-based transfusion services to the events that took place in the community during the initial phases of the pandemic. RESULTS In Washington State, the first week of March started with 4 confirmed cases and ended with 150; by the end of the second week of March there were more than 700 cases of confirmed COVID-19. During the first week, blood donations dropped significantly. Blood units provided from blood centers of non-affected areas of the country helped keep inventory stable and allow for routine hospital operations. The hospital-based transfusion service began prospective triaging of blood orders to monitor and prioritize blood utilization. In the second week, blood donations recovered, and the hospital postponed elective procedures to ensure staff and personal protective equipment were appropriate for the care of critical patients. CONCLUSION As community activities are disrupted and hospital activities switch from routine operations to pandemic-focused and urgent care-oriented, the blood supply and utilization requires a number of transformations.


Is post-operative radiotherapy of any benefit after R0 resection for N2 disease?


Repeated lumbar puncture in adults with pneumococcal meningitis: an observational study.


title: Multi-center colonoscopy quality measurement utilizing natural language processing.

text: BACKGROUND An accurate system for tracking of colonoscopy quality and surveillance intervals could improve the effectiveness and cost-effectiveness of colorectal cancer (CRC) screening and surveillance. The purpose of this study was to create and test such a system across multiple institutions utilizing natural language processing (NLP). METHODS From 42,569 colonoscopies with pathology records from 13 centers, we randomly sampled 750 paired reports. We trained (n=250) and tested (n=500) an NLP-based program with 19 measurements that encompass colonoscopy quality measures and surveillance interval determination, using blinded, paired, annotated expert manual review as the reference standard. The remaining 41,819 nonannotated documents were processed through the NLP system without manual review to assess performance consistency. The primary outcome was system accuracy across the 19 measures. RESULTS A total of 176 (23.5%) documents with 252 (1.8%) discrepant content points resulted from paired annotation. Error rate within the 500 test documents was 31.2% for NLP and 25.4% for the paired annotators (P=0.001). At the content point level within the test set, the error rate was 3.5% for NLP and 1.9% for the paired annotators (P=0.04). When eight vaguely worded documents were removed, 125 of 492 (25.4%) were incorrect by NLP and 104 of 492 (21.1%) by the initial annotator (P=0.07). Rates of pathologic findings calculated from NLP were similar to those calculated by annotation for the majority of measurements. Test set accuracy was 99.6% for CRC, 95% for advanced adenoma, 94.6% for nonadvanced adenoma, 99.8% for advanced sessile serrated polyps, 99.2% for nonadvanced sessile serrated polyps, 96.8% for large hyperplastic polyps, and 96.0% for small hyperplastic polyps. Lesion location showed high accuracy (87.0-99.8%). Accuracy for number of adenomas was 92%. CONCLUSIONS NLP can accurately report adenoma detection rate and the components for determining guideline-adherent colonoscopy surveillance intervals across multiple sites that utilize different methods for reporting colonoscopy findings.


title: Platelets Endocytose Viral Particles and Are Activated via TLR (Toll-Like Receptor) Signaling.

text: OBJECTIVE Thrombocytopenia is associated with many viral infections suggesting virions interact with and affect platelets. Consistently, viral particles are seen inside platelets, and platelet activation markers are detected in viremic patients. In this article, we sought mechanistic insights into these virion/platelet interactions by examining how platelets endocytose, traffic, and are activated by a model virion. Approach and Results: Using fluorescently tagged HIV-1 pseudovirions, 3-dimensional structured illumination microscopy, and transgenic mouse models, we probed the interactions between platelets and virions. Mouse platelets used known endocytic machinery, that is, dynamin, VAMP (vesicle-associated membrane protein)-3, and Arf6 (ADP-ribosylation factor 6), to take up and traffic HIV-1 pseudovirions. Endocytosed HIV-1 pseudovirions trafficked through early (Rab4+) and late endosomes (Rab7+), and then to an LC3+ (microtubule-associated protein 1A/1B-light chain 3) compartment. Incubation with virions induced IRAK4 (interleukin 1 receptor-associated kinase 4), Akt (protein kinase B), and IKK (IκB kinase) activation, granule secretion, and platelet-leukocyte aggregate formation. This activation required TLRs (Toll-like receptors) and MyD88 (myeloid differentiation primary response protein 88) but was less extensive and slower than activation with thrombin. In vivo, HIV-1 pseudovirions injection led to virion uptake and platelet activation, as measured by IKK activation, platelet-leukocyte aggregate formation, and mild thrombocytopenia. All were decreased in VAMP-3-/- and, megakaryocyte/platelet-specific, Arf6-/- mice. Similar platelet activation profiles (increased platelet-leukocyte aggregates, plasma platelet factor 4, and phospho-IκBα) were detected in newly diagnosed and antiretroviral therapy-controlled HIV-1+ patients. CONCLUSIONS Collectively, our data provide mechanistic insights into the cell biology of how platelets endocytose and process virions. We propose a mechanism by which platelets sample the circulation and respond to potential pathogens that they take up.


title: Clinical, radiographic, ultrasonographic and computed tomographic features of nonseptic osteitis of the axial border of the proximal sesamoid bones.

text: REASONS FOR PERFORMING STUDY Lysis of the axial aspect of equine proximal sesamoid bones (PSBs) is a rare condition reported to have septic or traumatic origins. Limited information exists regarding imaging of nonseptic axial osteitis of a PSB. OBJECTIVES To report the clinical, radiographic, ultrasonographic, computed tomographic and intra-arterial contrast-enhanced computed tomographic abnormalities in horses with axial nonseptic osteitis of a PSB. STUDY DESIGN Retrospective clinical study. METHODS Eighteen horses diagnosed with nonseptic osteitis of the axial border of a PSB between 2007 and 2012 were reviewed retrospectively. Case details, clinical examination, radiographic, ultrasonographic, computed tomographic and intra-arterial/intra-articular contrast-enhanced computed tomographic features were recorded, when available. Radiographic, ultrasonographic and computed tomographic evaluations of the fetlock region had been performed on 18, 15 and 9 horses, respectively. The effect of the degree of lysis on the grade and duration of lameness was determined. RESULTS All horses had chronic unilateral lameness, 4 with forelimb and 14 with hindlimb signs. On radiographs, lysis was identified in both PSBs in 14 horses, one PSB in 3 horses and in one horse no lysis was identified. The degree of osteolysis was variable. Ultrasonography identified variably sized irregularities of the bone surface and alteration in echogenicity of the palmar/plantar ligament (PL). All horses undergoing computed tomographic examination (n = 9) had biaxial lysis. The lesions were significantly longer and deeper on computed tomographic images compared with radiographic images. Intra-arterial contrast-enhanced computed tomography may reveal moderate to marked contrast enhancement of the PL. There was no significant effect of the degree of lysis on the grade and duration of lameness. CONCLUSIONS Lesions of nonseptic axial osteitis of a PSB can be identified using a combination of radiography and ultrasonography. Computed tomography provides additional information regarding the extent of the pathology.


COVID-19 mental-health responses neglect social realities.


title: Viral RNA Load in Mildly Symptomatic and Asymptomatic Children with COVID-19, Seoul.

text: Along with positive SARS-CoV-2 RNA in nasopharyngeal swabs, viral RNA was detectable at high concentration for >3 weeks in fecal samples from 12 mildly symptomatic and asymptomatic children with COVID-19. Saliva also tested positive during the early phase of infection. If proven infectious, feces and saliva could serve as transmission sources.


title: Wavelet-based reconstruction of dynamic susceptibility MR-perfusion: a new method to visualize hypervascular brain tumors.

text: OBJECTIVES Parameter maps based on wavelet-transform post-processing of dynamic perfusion data offer an innovative way of visualizing blood vessels in a fully automated, user-independent way. The aims of this study were (i) a proof of concept regarding wavelet-based analysis of dynamic susceptibility contrast (DSC) MRI data and (ii) to demonstrate advantages of wavelet-based measures compared to standard cerebral blood volume (CBV) maps in patients with the initial diagnosis of glioblastoma (GBM). METHODS Consecutive 3-T DSC MRI datasets of 46 subjects with GBM (mean age 63.0 ± 13.1 years, 28 m) were retrospectively included in this feasibility study. Vessel-specific wavelet magnetic resonance perfusion (wavelet-MRP) maps were calculated using the wavelet transform (Paul wavelet, order 1) of each voxel time course. Five different aspects of image quality and tumor delineation were each qualitatively rated on a 5-point Likert scale. Quantitative analysis included image contrast and contrast-to-noise ratio. RESULTS Vessel-specific wavelet-MRP maps could be calculated within a mean time of 2:27 min. Wavelet-MRP achieved higher scores compared to CBV in all qualitative ratings: tumor depiction (4.02 vs. 2.33), contrast enhancement (3.93 vs. 2.23), central necrosis (3.86 vs. 2.40), morphologic correlation (3.87 vs. 2.24), and overall impression (4.00 vs. 2.41); all p < .001. Quantitative image analysis showed a better image contrast and higher contrast-to-noise ratios for wavelet-MRP compared to conventional perfusion maps (all p < .001). CONCLUSIONS wavelet-MRP is a fast and fully automated post-processing technique that yields reproducible perfusion maps with a clearer vascular depiction of GBM compared to standard CBV maps. KEY POINTS • Wavelet-MRP offers high-contrast perfusion maps with a clear delineation of focal perfusion alterations. • Both image contrast and visual image quality were beneficial for wavelet-MRP compared to standard perfusion maps like CBV. • Wavelet-MRP can be automatically calculated from existing dynamic susceptibility contrast (DSC) perfusion data.


title: Laparoscopic hepatic resection for metastatic liver tumor of colorectal cancer: comparative analysis of short- and long-term results.

text: BACKGROUND With the progress of surgical techniques and devices, laparoscopic hepatectomy (Lap-Hx) became a realizable option for patients with liver tumors. However, the feasibility of Lap-Hx for metastatic liver tumor of colorectal cancer also should be guaranteed oncologically. This study evaluated the short- and long-term outcomes of Lap-Hx compared with open hepatectomy (Open-Hx) for patients with colorectal liver metastasis (CLM) by matched-pair analysis. METHODS This study enrolled 21 patients who underwent Lap-Hx and compared them with 21 matched patients who underwent Open-Hx. The following parameters were matched between the two cohorts: tumor size, tumor location, and operative procedures. Both short- and long-term outcomes of Lap-Hx were compared with those of Open-Hx. RESULTS No difference was observed between the two groups in terms of age, gender, tumor size, or operative procedures. With regard to short-term outcomes, the operative time for Lap-Hx (377 ± 29 min) was similar to that for Open-Hx (369 ± 31 min), whereas the blood loss for the patients who underwent a Lap-Hx (198 ± 39 ml) was significantly less than for those who underwent an Open-Hx (326 ± 50 ml). The incidence of postoperative complications among the patients who underwent Lap-Hx tended to be lower than for the patients who underwent Open-Hx, and intraabdominal abscess was observed only in the Open-Hx group. The hospital stay for Lap-Hx (average, 18.3 days) tended to be shorter than for Open-Hx (27 days). With respect to long-term outcomes, the two groups did not differ significantly in terms of 5-year overall and disease-free survival rates. CONCLUSIONS Lap-Hx is a safe and feasible option for selected patients with CLM. The short- and long-term outcomes of Lap-Hx also are considered to be acceptable.


title: Port-Site Metastases After Robotic Radical Cystectomy: A Systematic Review and Management Options.

text: BACKGROUND Port-site metastases (PSMs) are a rare occurrence after robotic surgery. For robot-assisted radical cystectomy (RARC), isolated cases have been reported but management has not been previously described. We present a case of PSM that occurred after RARC and report the results of our systematic review of previously reported PSMs and describe the treatment options. Search Criteria and Methods: We describe a case of a PSM in a 55-year-old man who had undergone intracorporeal RARC. We performed a systematic review of MEDLINE and Embase databases for previously reported PSMs, detailing the stage and grade of the primary tumor, time to presentation of PSM, treatment offered, and outcomes for the identified cases. RESULTS We identified 4 cases of PSMs after RARC in published studies and also included our case for analysis. All 5 patients had muscle-invasive bladder cancer at cystectomy (stage ≥ T2) and 3 had local lymph node-positive disease. Our aggressive treatment of chemotherapy, wide surgical excision of PSM, and radiotherapy provided our patient with a 2-year disease-free status. CONCLUSION PSMs are a rare event in RARC, with only 4 other cases reported in published studies. The outcomes have not been well reported for these cases. We propose that multimodality treatment consisting of salvage chemotherapy, surgery, and radiotherapy should be considered, although concessions could be needed after consideration of patient factors.


Covid-19 worldwide: we need precise data by age group and sex urgently.


title: Incidence of Interstitial Pregnancy After In Vitro Fertilization/Embryo Transfer and the Outcome of a Consecutive Series of 38 Cases Managed by Laparoscopic Cornuostomy or Cornual Repair.

text: STUDY OBJECTIVE To determine the incidence of interstitial pregnancy after in vitro fertilization/embryo transfer (ET) treatment and report on our experience of laparoscopic cornuostomy or cornual repair for interstitial pregnancy. DESIGN Single-center, retrospective review (Canadian Task Force classification II-3). SETTING University hospital. PATIENTS Thirty-eight women diagnosed with interstitial pregnancy, which developed after 10,143 ET cycles, managed in our center between April 2011 and April 2014. INTERVENTIONS All 38 cases of interstitial pregnancy were managed by laparoscopic cornuostomy or cornual repair. No patient was converted to laparotomy. MEASUREMENTS AND MAIN RESULTS Of 43 cases of interstitial pregnancy, 38 were managed in our department. The overall incidence of interstitial pregnancy was .4% per ET cycle (43/10 143), or .8% per pregnancy (43/5297), but comprising 35.5% of all ectopic pregnancy cases. The risk factors for interstitial pregnancy included tubal infertility, cleavage ET, and frozen ET. Twenty-seven subjects (71.1%) had undergone bilateral salpingectomy. Among the 38 cases, 27 were intact, with no persistent ectopic pregnancy after surgery, but there were 3 cases (28.3%) of persistent pregnancy in the 11 ruptured cases. Among the 38 subjects, 15 conceived again with 14 live births and 1 ongoing pregnancy, without uterine rupture. CONCLUSION Laparoscopic cornuostomy or cornual repair appears to be an effective treatment in intact cases, although it sometimes needs to be combined with methotrexate therapy in ruptured cases complicated by persistent disease.


title: An international comparison analysis of reserve and supply system for emergency medical supplies between China, the United States, Australia, and Canada.

text: Coronavirus disease 19 (COVID-19) has become a pandemic around the world. With the explosive growth of confirmed cases, emergency medical supplies are facing global shortage, which restricts the treatment of seriously ill patients and protection of medical staff. Taking China, the United States, Australia, and Canada as examples, this study compares and analyzes the reserve and supply systems of emergency medical supplies and problems exposed in response to the COVID-19 epidemic. Some common problems were found, such as insufficient types and quantities of emergency medical supplies in reserve, insufficient emergency production capacity, and imperfect command mechanism for emergency supplies deployment and transportation. A sound reserve system of emergency medical supplies is the basis and guarantee for dealing with public health emergencies such as major outbreaks. Based on the comparison of systems and practical experience, countries around the world should further improve the reserve and supply system of emergency medical supplies, and improve the coordination and cooperation mechanism for emergency supplies for international public health emergencies, so as to cope with increasingly severe public health emergencies in the context of globalization.


title: Persistent effects on bovine granulosa cell transcriptome after resolution of uterine disease.

text: Metritis is associated with reduced fertility in dairy cows, but the mechanisms are unclear because the disease resolves several weeks before insemination. One hypothesis is that metritis causes persistent changes in granulosa cells during follicle development, which might be evident in the transcriptome of granulosa cells from dominant follicles weeks after parturition. To test this hypothesis we collected follicular fluid and granulosa cells from dominant follicles 63 days post partum from cows previously diagnosed with metritis, at least 6 weeks after resolution of the disease, and from cows not diagnosed with metritis (control cows). Bacterial lipopolysaccharide was detected in follicular fluid, and concentrations were associated with follicular fluid IL-8 and glucose concentrations. Transcriptome analysis using RNAseq revealed 177 differentially expressed genes in granulosa cells collected from cows that had metritis compared with control cows. The most upregulated genes were ITLN1, NCF2, CLRN3, FSIP2 and ANKRD17, and the most downregulated genes were ACSM1, NR4A2, GHITM, CBARP and NR1I3. Pathway analysis indicated that the differentially expressed genes were involved with immune function, cell-cell communication, cell cycle and cellular metabolism. Predicted upstream regulators of the differentially expressed genes included NFκB, IL-21 and lipopolysaccharide, which are associated with infection and immunity. Our data provide evidence for a persistent effect of metritis on the transcriptome of granulosa cells in ovarian follicles after the resolution of disease.


title: Structural Changes In Cells Imaged by Soft X-ray Cryo-Tomography During Hepatitis C Virus Infection.

text: Chronic hepatitis C virus (HCV) infection causes severe liver disease in millions of humans worldwide. Pathogenesis of HCV infection is strongly driven by a deficient immune response of the host, although intersection of different aspects of the virus life cycle with cellular homeostasis is emerging as an important player in the pathogenesis and progression of the disease. Cryo soft X-ray tomography (cryo-SXT) was performed to investigate the ultrastructural alterations induced by the interference of HCV replication with cellular homeostasis. Native, whole cell, three-dimensional (3D) maps were obtained in HCV replicon-harboring cells and in a surrogate model of HCV infection. Tomograms from HCV-replicating cells show blind-ended endoplasmic reticulum tubules with pseudospherical extrusions and marked alterations of mitochondrial morphology that correlated spatially with the presence of endoplasmic reticulum alterations, suggesting a short-range influence of the viral machinery on mitochondrial homeostasis. Both mitochondrial and endoplasmic reticulum alterations could be reverted by a combination of sofosbuvir/daclatasvir, which are clinically approved direct-acting antivirals for the treatment of chronic HCV infection. In addition to providing structural insight into cellular aspects of HCV pathogenesis, our study illustrates how cryo-SXT is a powerful 3D wide-field imaging tool for the assessment and understanding of complex cellular processes in a setting of near-native whole hydrated cells. Our results also constitute a proof of concept for the use of cryo-SXT as a platform that enables determining the potential impact of candidate compounds on the ultrastructure of the cell that may assist drug development at a preclinical level.


The robot recruits in China's health-care system.


title: Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine.

text: The target of neutralizing antibodies that protect against influenza virus infection is the viral protein HA. Genetic and antigenic variation in HA has been used to classify influenza viruses into subtypes (H1-H16). The neutralizing antibody response to influenza virus is thought to be specific for a few antigenically related isolates within a given subtype. However, while heterosubtypic antibodies capable of neutralizing multiple influenza virus subtypes have been recently isolated from phage display libraries, it is not known whether such antibodies are produced in the course of an immune response to influenza virus infection or vaccine. Here we report that, following vaccination with seasonal influenza vaccine containing H1 and H3 influenza virus subtypes, some individuals produce antibodies that cross-react with H5 HA. By immortalizing IgG-expressing B cells from 4 individuals, we isolated 20 heterosubtypic mAbs that bound and neutralized viruses belonging to several HA subtypes (H1, H2, H5, H6, and H9), including the pandemic A/California/07/09 H1N1 isolate. The mAbs used different VH genes and carried a high frequency of somatic mutations. With the exception of a mAb that bound to the HA globular head, all heterosubtypic mAbs bound to acid-sensitive epitopes in the HA stem region. Four mAbs were evaluated in vivo and protected mice from challenge with influenza viruses representative of different subtypes. These findings reveal that seasonal influenza vaccination can induce polyclonal heterosubtypic neutralizing antibodies that cross-react with the swine-origin pandemic H1N1 influenza virus and with the highly pathogenic H5N1 virus.


title: Survey for the amphibian chytrid Batrachochytrium dendrobatidis in Hong Kong in native amphibians and in the international amphibian trade.

text: Chytridiomycosis, caused by the pathogen Batrachochytrium dendrobatidis, is responsible for many amphibian declines and has been identified in wild amphibian populations on all continents where they exist, except for Asia. In order to assess whether B. dendrobatidis is present on the native amphibians of Hong Kong, we sampled wild populations of Amolops hongkongensis, Paa exilispinosa, P. spinosa and Rana chloronota during 2005-2006. Amphibians infected with B. dendrobatidis have been found in the international trade, so we also examined the extent and nature of the amphibian trade in Hong Kong during 2005-2006, and assessed whether B. dendrobatidis was present in imported amphibians. All 274 individuals of 4 native amphibian species sampled tested negative for B. dendrobatidis, giving an upper 95% confidence limit for prevalence of 1.3%. Approximately 4.3 million amphibians of 45 species from 11 countries were imported into Hong Kong via air over 12 mo; we did not detect B. dendrobatidis on any of 137 imported amphibians sampled. As B. dendrobatidis generally occurs at greater than 5% prevalence in infected populations during favorable environmental conditions, native amphibians in Hong Kong appear free of B. dendrobatidis, and may be at severe risk of impact if it is introduced. Until it is established that the pathogen is present in Hong Kong, management strategies should focus on preventing it from being imported and decreasing the risk of it escaping into the wild amphibian populations if imported. Further research is needed to determine the status of B. dendrobatidis in Hong Kong with greater certainty.


title: Evaluation of transanal hemorrhoidal dearterialization: a single surgeon experience.

text: BACKGROUND There is an increasing, though still limited, amount of evidence describing the use of the transanal hemorrhoidal dearterialization (THD) device for the treatment of hemorrhoidal disease. This study assesses postoperative outcomes from a single surgeon experience with the THD device. METHODS From January 2009 to December 2011, 108 THD procedures were performed. With Doppler guidance, the THD device makes possible precise ligation of the branches of the superior hemorrhoidal artery. Patients were seen postoperatively at 3 weeks and 6 months. They underwent physical examination to determine whether there was recurrence of hemorrhoidal prolapse. They were asked to describe any bleeding, to rate pain using the visual analog scale, and to rate their level of satisfaction on a scale of 1-5 (with 5 = highly satisfied). A phone interview was used for follow-up at 1 year to determine the rate of recurrent prolapse. RESULTS Of the 108 patients who underwent THD, two were lost to follow-up and excluded. All of the remaining 106 patients completed follow-up at 3 weeks and 6 months. At 3 weeks, 92% of patients had no pain and 88% were highly satisfied with the procedure at 3 weeks. This increased to 92% satisfaction at 1 year. Prolapse recurrence was 7.5% at 6 months and 10.3% at 1 year. Bleeding was the most common complication, but did not require re-intervention or transfusion. CONCLUSIONS THD is a same-day procedure for the treatment of hemorrhoidal disease that is safe and effective, and offers the potential for immediate return to normal activity.


title: Litsea Species as Potential Antiviral Plant Sources.

text: Litsea verticillata Hance (Lauraceae), a Chinese medicine used to treat swelling caused by injury or by snake bites, was the first plant identified by our National Institutes of Health (NIH)-funded International Cooperative Biodiversity Group (ICBG) project to exhibit anti-HIV activities. From this plant, we discovered a class of 8 novel litseane compounds, prototypic sesquiterpenes, all of which demonstrated anti-HIV activities. In subsequent studies, 26 additional compounds of different structural types were identified. During our continuing investigation of this plant species, we identified two new litseanes, litseaverticillols L and M, and a new sesquiterpene butenolide, litseasesquibutenolide. Litseaverticillols L and M were found to inhibit HIV-1 replication, with an IC[Formula: see text] value of 49.6[Formula: see text][Formula: see text]M. To further determine the antiviral properties of this plant, several relatively abundant isolates, including a litseane compound, two eudesmane sesquiterpenes and three lignans, were evaluated against an additional 21 viral targets. Lignans 8 and 9 were shown to be active against the Epstein-Barr Virus (EBV), with EC[Formula: see text] values of 22.0[Formula: see text][Formula: see text]M ([Formula: see text]) and 16.2[Formula: see text][Formula: see text]M ([Formula: see text]), respectively. Since many antiviral compounds have been discovered in L. verticillata, we further prepared 38 plant extracts made from the different plant parts of 9 additional Litsea species. These extracts were evaluated for their anti-HIV and cytotoxic activities, and four of the extracts, which ranged across three different species, displayed 97-100% inhibitory effects against HIV replication without showing cytotoxicity to a panel of human cell lines at a concentration of 20 μg/mL.


title: How is the lockdown affecting vet students?

text: Like most other professions in the UK, the veterinary profession has been hit hard by Covid-19. But how has it impacted on students? Alexia Yiannouli investigates.


title: Effect of Implant Duration, Anatomical Location and Electrode Orientation on Bandwidth Recorded with a Chronically Implanted Endovascular Stent-Electrode Array.

text: Access to the brain to implant recording electrodes has conventionally required a craniotomy. To mitigate risks of open brain surgery, we previously developed a stent-electrode array that can be delivered to the cortex via cerebral vessels. Following implantation of a stent-electrode array (Stentrode) in a large animal model, we investigated the longevity of highquality signals, by measuring bandwidth in animals implanted for up to six months; no signal degradation was observed. We also investigated whether bandwidth was influenced by implant location with respect to the superior sagittal sinus and branching cortical veins; it was not. Finally, we assessed whether electrode orientation had an impact on recording quality. There was no significant difference in bandwidths from electrodes facing different orientations. Interestingly, electrodes facing the skull (180°) were still able to record neural information with high fidelity. Consequently, a minimally invasive surgical approach combined with a stent-electrode array is a safe and efficacious technique to acquire neural signals over a chronic duration.


title: Cross-Linked Protein Nanofilter with Antibacterial Properties for Multifunctional Air Filtration.

text: Development of high-performance nanomaterials with not only strong ability to trap the pollutants but also good structure stability under varying environmental conditions is a critical need for air-filtration applications. However, it has been very challenging for a filtering material to simultaneously realize multifunctional air filtration and good environmental stability. Here, based on our previous studies on protein-based nanofilters, we report a cross-linked protein nanofabric to address this challenging issue. It is found that cross-linked protein nanofabrics can significantly improve the structure stability against different moisture levels and temperatures, while maintaining the multifunctional filtration performance. Moreover, it is demonstrated that the cross-linked protein nanomaterials also possess antibacterial properties, such as Shewanella oneidensis bacteria, further improving the environmental stability. The effects of cross-linking with different loadings of cross-linking agent on the structure stability and filtration performance are further investigated at different humidity levels and temperatures. This study provides a cost-effective solution for advanced "green" nanomaterials with excellent performance in both filtration functions and structure stability under varying environment.


title: Ethical allocation of scarce health care resources in the context of the COVID-19 crisis.

text: The current COVID-19 pandemic has the potential to overwhelm the capacity of hospitals and Intensive Care Units in Chile and Latin America. Thus local authorities have an ethical obligation to be prepared by implementing pertinent measures to prevent a situation of rationing of scarce healthcare resources, and by defining ethically acceptable and socially legitimate criteria for the allocation of these resources. This paper responds to recent ethical guidelines issued by a Chilean academic institution and discusses the main moral principles for the ethical foundations of criteria for rationing during the present crisis. It argues that under exceptional circumstances such as the current pandemic, the traditional patient-centered morality of medicine needs to be balanced with ethical principles formulated from a public health perspective, including the principles of social utility, social justice and equity, among others. The paper concludes with some recommendations regarding how to reach an agreement about rationing criteria and about their implementation in clinical practice.


title: Does the stapler for en bloc resection of renal pedicles during kidney removal surgery increase the risk of arteriovenous fistula?

text: BACKGROUND It was previously thought that renal hilum en bloc ligation during kidney removal may increase the risk of renal arteriovenous fistula (AVF) formation. We evaluated the safety and effectiveness of en bloc ligation of the renal pedicle using a stapler during laparoscopic nephrectomy and nephroureterectomy. METHODS Ninety patients underwent en bloc renal hilar ligation using 45-mm endo-gastrointestinal anastomosis stapler and 2.5-mm staples during laparoscopic nephrectomy and nephroureterectomy from 2002 to 2015. Perioperative outcomes including estimated blood loss, operative time, and perioperative complications were documented. RESULTS Twenty-seven patients underwent nephrectomy and 63 patients underwent nephroureterectomy. Thirty patients (33.3%) had perioperative complications. The majority of complications were of Clavien grade II. Six patients had Clavien Dindo grade III and none of the patients had grade IV complications. There were no significant differences in complication rates between right- and left-sided procedures (p = 0.233). Median blood loss was 190.1 ml and mean operative time was 227.1 minutes in nephrectomy and 256.6 minutes in nephroureterectomy. None of the patients had evidence of AVF formation on postoperative computerized tomography scan. Only three patients had a new diagnosis of heart failure. One of them was eventually lost to follow up. The remaining two patients had no evidence of AVF formation in imaging studies and physical examination. CONCLUSION En bloc ligation of the renal pedicle during laparoscopic nephrectomy and nephroureterectomy using a stapler is safe. None of our patients developed an AVF during follow up.


title: The comparison of single incision laparoscopic cholecystectomy and three port laparoscopic cholecystectomy: prospective randomized study.

text: PURPOSE Laparoscopic techniques have allowed surgeons to perform complicated intra-abdominal surgery with minimal trauma. Single incision laparoscopic surgery (SILS) was developed with the aim of reducing the invasiveness of conventional laparoscopy. In this study we aimed to compare results of SILS cholecystectomy and three port conventional laparoscopic (TPCL) cholecystectomy prospectively. METHODS In this prospective study, 100 patients who underwent laparoscopic cholecystectomy for gallbladder disease were randomly allocated to SILS cholecystectomy (group 1) or TPCL cholecystectomy (group 2). Demographics, pathologic diagnosis, operating time, blood loss, length of hospital stay, complications, pain score, conversion rate, and satisfaction of cosmetic outcome were recorded. RESULTS Forty-four SILS cholesystectomies (88%) and 42 TPCL cholecystectomies (84%) were completed successfully. Conversion to open surgery was required for 4 cases in group 1 and 6 cases in group 2. Operating time was significantly longer in group 1 compared with group 2 (73 minutes vs. 48 minutes; P < 0.05). Higher pain scores were observed in group 1 versus group 2 in postoperative day 1 (P < 0.05). There was higher cosmetic satisfaction in group 1 (P < 0.05). CONCLUSION SILS cholecystectomy performed by experienced surgeons is at least as successful, feasible, effective and safe as a TPCL cholecystectomy. Surgeons performing SILS should have a firm foundation of advanced minimal access surgical skills and a cautious, gradated approach to attempt the various procedures. Prospective randomized studies comparing single access versus conventional multiport laparoscopic cholecystectomy, with large volumes and long-term follow-up, are needed to confirm our initial experience. (ClinicalTrials.gov Identifier: NCT01772745.).


title: COVID-19 and the role of imaging: early experiences in Central Switzerland.

text: The SARS-CoV-2 virus (COVID-19) was initially observed in a group of Chinese patients with unclear pneumonia in Wuhan, Hubei [1] in late December 2019. The first positive case in Switzerland was confirmed on 25 February 2020 in a patient from canton Tessin, who most likely caught the virus during a visit to Milan, Italy [2]. The country has since been preparing for an imminent public health emergency caused by the pandemic. As of 14 May 2020, the Swiss healthcare system is facing a total of 30,463 corona virus-positive people [3]. With numbers of new infections decreasing after the first pandemic wave, the continuing endemic situation will continue to be a major challenge for the Swiss healthcare system. It remains crucial to separate the clinically low-symptomatic from the severely affected patients in order to offer a specific therapeutic strategy to every SARS-CoV-2 patient. Reports from Chinese cohorts describe an increasing role of imaging strategies in the detection and surveillance of COVID-19 patients because of insufficient testing sensitivity of real-time reverse transcription polymerase chain reaction (RT-PCR) tests [4]. Chest computed tomography (CT), with a reported sensitivity of up to 97% [5, 6], gained importance particularly in patients with false negative RT-PCR results. In this short communication, we describe our first clinical experiences with 55 COVID-19 patients in Central Switzerland, who were either imaged with a standard chest x-ray, chest CT, or both. We provide an illustrative and schematic description of typical COVID-19 imaging features and suggest that imaging plays an important role in the clinical work-up of suspected or confirmed COVID-19 patients. This study was approved by the national ethics review committee (EKNZ, Switzerland) and patients’ informed consent was waived.


title: Influenza virus activating host proteases: Identification, localization and inhibitors as potential therapeutics.

text: Cellular proteases are reponsible for activation of influenza virus hemagglutinin (HA) in epithelial tissues of the respiratory tract. The trans-Golgi network (TGN) is the main subcellular compartment where HA cleavage occurs during its biosynthesis. The proteolytic HA cleavage is an indispensable prerequisite for the fusion of viral with endosomal membrane and the delivery of the virus genome into the cell. Both, the structure and accessibility of the HA cleavage site determine the responsible host protease(s) for cutting. Most influenza virus strains contain a HA sequence with a single arginine at the cleavage site suitable for processing by the trypsin-like serine proteases human airway trypsin-like protease (HAT) and transmembrane protease serine 2 (TMPRSS2), albeit a minority of viruses possesses HA cleavage site motifs that are processed by other proteases. TMPRSS2-deficient mice demonstrated the relevance of TMPRSS2 for pneumotropism and pathogenicity of H1N1 and H7N9 virus infections. In contrast, H3N2 virus infections are promoted by an additional not yet identified protease. Highly pathogenic avian H5 and H7 viruses are characterized by an enlarged cleavage site loop containing a multibasic amino acid motif, where the eukaryotic subtilases furin or PC5/6 cleave. Their ubiquitous presence in the organism allows a systemic virus infection. Peptidomimetic inhibitors derived from the HA cleavage site inhibit the HA-activating proteases and thus virus propagation.


title: A pressure-based bioassay for the rapid, portable and quantitative detection of C-reactive protein.

text: A portable method for the rapid detection of the disease biomarker C-reactive protein (CRP) with a hand-held pressuremeter was developed. The method allows an ultrasensitive quantitation of CRP within the entire clinical range. The pressure-based method could facilitate CRP measurements in point-of-care testing (POCT) scenarios, such as clinical offices, emergency departments, and community service centers.


title: Bridging therapy for achalasia in a second trimester pregnant patient.

text: We present the case of a 28-year-old female who presented for primary care at 22-week gestation with type II achalasia and worsening solid/liquid dysphagia leading to pregnancy weight loss. Considering that durable therapies such as surgical myotomy and pneumatic dilatation have considerable risk, botulinum A toxin injection was selected as a temporizing bridging therapy. She had an uncomplicated post procedure course and had significant rapid improvement in dysphagia symptoms, which enabled her to progress to normal peripartum weight. This case highlights the need for early recognition of achalasia and an unique niche for use of botulinum toxin A as a temporizing therapy in this risk averse population.


title: Incidence of delivery wire recapture failure with the Pipeline Flex device.

text: BACKGROUND The Pipeline Flex embolization device has several advantages over the first-generation Pipeline embolization device (Covidien, Dublin, Republic of Ireland). Despite these advantages, we have observed frequent difficulty in recapturing the device's delivery wire. OBJECTIVE To prospectively document the incidence of failure to recapture the delivery wire. METHODS We tracked our experience in patients undergoing endovascular treatment with a flow-diverting stent for cerebral aneurysms between 1 May and 30 September 2016. Patient and lesion characteristics, device dimensions, and technical outcomes of delivery wire recapture were prospectively recorded for each device. RESULTS Eighteen devices were deployed in 15 patients by the senior author (FCA) during this period. Failure to recapture the delivery wire occurred in 10 of 18 (56%) cases. No adverse outcomes of delivery wire recapture failure were encountered in this series. CONCLUSIONS The incidence of delivery wire recapture failure with the Pipeline Flex device is high. Failure to recapture the delivery wire carries a theoretical risk of stent displacement when re-navigating across the device, and endovascular surgeons should be aware of this limitation. Authors are encouraged to report delivery wire recapture failure rates in future clinical series in which the Pipeline Flex device is used.


title: Intraoperative near-infrared fluorescence tumor imaging with vascular endothelial growth factor and human epidermal growth factor receptor 2 targeting antibodies.

text: UNLABELLED Fluorescence imaging is currently attracting much interest as a method for intraoperative tumor detection, but most current tracers lack tumor specificity. Therefore, this technique can be further improved by tumor-specific detection. With tumor-targeted antibodies bound to a radioactive label, tumor-specific SPECT or PET is feasible in the clinical setting. The aim of the present study was to apply antibody-based tumor detection to intraoperative optical imaging, using preclinical in vivo mouse models. METHODS Anti-vascular endothelial growth factor (VEGF) antibody bevacizumab and anti-human epidermal growth factor receptor (HER) 2 antibody trastuzumab were labeled with the near-infrared (NIR) fluorescence dye IRDye 800CW. Tumor uptake of the fluorescent tracers and their (89)Zr-labeled radioactive counterparts for PET was determined in human xenograft-bearing athymic mice during 1 wk after tracer injection, followed by ex vivo biodistribution and pathologic examination. Intraoperative imaging of fluorescent VEGF- or HER2-positive tumor lesions was performed in subcutaneous tumors and in intraperitoneal dissemination tumor models. RESULTS Tumor-to-background ratios, with fluorescent imaging, were 1.93 ± 0.40 for bevacizumab and 2.92 ± 0.29 for trastuzumab on day 6 after tracer injection. Real-time intraoperative imaging detected tumor lesions at even the submillimeter level in intraperitoneal dissemination tumor models. These results were supported by standard histology, immunohistochemistry, and fluorescence microscopy analyses. CONCLUSION NIR fluorescence-labeled antibodies targeting VEGF or HER2 can be used for highly specific and sensitive detection of tumor lesions in vivo. These preclinical findings encourage future clinical studies with NIR fluorescence-labeled tumor-specific antibodies for intraoperative-guided surgery in cancer patients.


title: Vogt-Koyanagi-Harada disease: recurrence rates after initial-onset disease differ according to treatment modality and geographic area.

text: Background/Purpose Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis producing a spill-over panuveitis. For initial-onset VKH disease, it is increasingly thought that corticosteroid therapy is not sufficient and additional non-steroidal immunosuppressive therapy is needed. At the 11th workshop on VKH, the disease was said to be well controlled with corticosteroids alone in Japanese patients. The aim of this study was to review the literature to determine whether different levels of severity exist in different geographical areas. METHODS Literature was reviewed for studies on the evolution of initial-onset VKH disease, looking at treatment modalities and proportion of cases with chronic evolution and/or sunset-glow fundus (SGF). RESULTS PubMed search yielded 1249 references containing the term of Vogt-Koyanagi-Harada. Twenty references (15 from outside of Japan and 5 from Japan) contained information on the evolution of treated initial-onset disease. For the "international" group, percentage of chronic evolution after systemic corticosteroid monotherapy was 61%, and after combined steroidal and non-steroidal therapy it fell to 2% (0% in 3/4 studies). In the Japanese studies where all patients received systemic corticosteroids alone, chronic evolution was reported in 25%; however, SGF amounted to 61%. CONCLUSION In the world at large, chronic evolution of initial-onset VKH disease treated with corticosteroids alone concerned two-thirds of patients. Japanese studies showed that chronic evolution was substantially less frequent, indicating possibly less severe disease in Japan. This proportion fell to almost zero when dual steroidal and non-steroidal immunosuppression was given at onset.


title: Foreign Body Emboli following Cerebrovascular Interventions: Clinical, Radiographic, and Histopathologic Features.

text: Foreign material emboli following cerebral, cardiac, and peripheral catheterizations have been reported since the mid-1990s. Catheter coatings have been frequently implicated. The most recent surge of interest in this phenomenon within the neurointerventional community is associated with procedures using flow-diversion devices for the treatment of cerebral aneurysms. Following coil-supported Pipeline embolization in 4 cases and stent-supported coiling in 1, 5 patients developed multiple subcentimeter enhancing lesions, usually with surrounding edema and variable magnetic susceptibility in the vascular territories of the treated aneurysms. Conventional angiography findings were unrevealing. Laboratory work-up showed mild CSF protein elevation with no leukocytosis. Brain biopsy in 2 cases revealed granulomatous angiitis encasing foreign material, identical in stain appearance to a polyvinylpyrrolidone catheter coating. Corticosteroid administration typically produced clinical improvement. A heterogeneous radiographic and clinical course was noted, with rise and fall in the number of enhancing lesions in 2 patients and persistence in others. The etiology may be related to widespread adoption of increasingly sophisticated catheterization techniques.


title: Health Sensors, Smart Home Devices, and the Internet of Medical Things: An Opportunity for Dramatic Improvement in Care for the Lower Extremity Complications of Diabetes.

text: OBJECTIVE The prevalent and long-neglected diabetic foot ulcer (DFU) and its related complications rank among the most debilitating and costly sequelae of diabetes. With the rise of the Internet of medical things (IoMT), along with smart devices, the med-tech industry is on the cusp of a home-care revolution, which could also create opportunity for developing effective solutions with significant potential to reduce DFU-associated costs and saving limbs. This article discusses potential applications of IoMT to the DFU patient population and beyond. METHODS To better understand potential opportunities and challenges associated with implementing IoMT for management of DFU, the authors reviewed recent relevant literatures and included their own expert opinions from a multidisciplinary point of view including podiatry, engineering, and data security. RESULTS The IoMT has opened digital transformation of home-based diabetic foot care, as it enables promoting patient engagement, personalized care and smart management of chronic and noncommunicable diseases through individual data-driven treatment regimens, telecommunication, data mining, and comprehensive feedback tailored to individual requirements. In particular, with recent advances in voice-activated commands technology and its integration as a part of IoMT, new opportunities have emerged to improve the patient's central role and responsibility in enabling an optimized health care ecosystem. CONCLUSIONS The IoMT has opened new opportunities in health care from remote monitoring to smart sensors and medical device integration. While it is at its early stage of development, ultimately we envisage a connected home that, using voice-controlled technology and Bluetooth-radio-connected add-ons, may augment much of what home health does today.


title: Brief Report: Incubation Period Duration and Severity of Clinical Disease Following Severe Acute Respiratory Syndrome Coronavirus Infection.

text: BACKGROUND Few previous studies have investigated the association between the severity of an infectious disease and the length of incubation period. METHODS We estimated the association between the length of the incubation period and the severity of infection with the severe acute respiratory syndrome coronavirus, using data from the epidemic in 2003 in Hong Kong. RESULTS We estimated the incubation period of severe acute respiratory syndrome based on a subset of patients with available data on exposure periods and a separate subset of patients in a putative common source outbreak, and we found associations between shorter incubation period and greater severity in both groups after adjusting for potential confounders. CONCLUSIONS Our findings suggest that patients with a shorter incubation period went on to have more severe disease. Further studies are needed to investigate potential biological mechanisms for this association.


COVID-19 and Keeping Clean: A Narrative Review to Ascertain the Efficacy of Personal Protective Equipment to Safeguard Healthcare Workers Against SARS-CoV-2.


title: Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity.

text: The coronavirus disease COVID-19, caused by emerging SARS-CoV-2, has posed serious threats to global public health, economic and social stabilities, calling for the prompt development of therapeutics and prophylactics. In this study, we firstly verified that SARS-CoV-2 uses human ACE2 as a cell receptor and its spike (S) protein mediates high membrane fusion activity. Comparing to that of SARS-CoV, the heptad repeat 1 (HR1) sequence in the S2 fusion protein of SARS-CoV-2 possesses markedly increased α-helicity and thermostability, as well as a higher binding affinity with its corresponding heptad repeat 2 (HR2) site. Then, we designed a HR2 sequence-based lipopeptide fusion inhibitor, termed IPB02, which showed highly potent activities in inhibiting the SARS-CoV-2 S protein-mediated cell-cell fusion and pseudovirus transduction. IPB02 also inhibited the SARS-CoV pseudovirus efficiently. Moreover, the structure and activity relationship (SAR) of IPB02 was characterized with a panel of truncated lipopeptides, revealing the amino acid motifs critical for its binding and antiviral capacities. Therefore, the presented results have provided important information for understanding the entry pathway of SARS-CoV-2 and the design of antivirals that target the membrane fusion step.IMPORTANCE The COVID-19 pandemic caused by SARS-CoV-2 presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. The S protein of coronaviruses mediates viral receptor-binding and membrane fusion thus being considered a critical target for antivirals. Herein, we report that the SARS-CoV-2 S protein evolves a high activity to mediate cell-cell fusion, significantly differing from the S protein of the previously emerged SARS-CoV. In comparison, the HR1 sequence in the fusion protein of SARS-CoV-2 adopts a much higher helical stability and can interact with the HR2 site to form a six-helical bundle structure more efficiently, underlying the mechanism of the enhanced fusion capacity. Also importantly, the design of membrane fusion inhibitors with high potencies against both SARS-CoV-2 and SARS-CoV has provided potential arsenals to combat the pandemic and tools to exploit the fusion mechanism.


Covid-19: Rules on sharing confidential patient information are relaxed in England.


Commentary: Long-term solutions to revive eye banking in India in COVID-19 era - Needs more than long-term corneal preservation.


title: Therapeutic Drug Monitoring of Dalbavancin Treatment in Severe Necrotizing Fasciitis in 3 Critically Ill Patients: A Grand Round.

text: BACKGROUND Dalbavancin, albeit indicated for the treatment of skin structure infections, is used for a much wider range of infections. This drug is characterized by a long half-life (more than 200 hours), a favorable safety profile, and an activity against a wide array of gram-positive organisms, including several strains of Staphylococci and Enterococci. METHODS In this study, we presented 3 cases of critically ill patients treated with dalbavancin. All patients were therapeutically monitored for plasma dalbavancin concentrations; ultrafiltrate dalbavancin concentrations were assessed in a patient undergoing continuous renal-replacement therapy. Dalbavancin concentrations were measured using a validated liquid chromatographic method coupled with mass spectrometry. RESULTS All 3 severely ill patients experiencing necrotizing fasciitis were successfully treated during the acute phase with dalbavancin. Dalbavancin clearance in patient 3 (0.334 L/h) was considerably increased compared with values measured in the other 2 patients (0.054 and 0.075 L/h) and with data reported in the literature (0.04-0.06 L/h). CONCLUSIONS Our case reports presented preliminary evidence that dalbavancin can be considered a therapeutic option for necrotizing fasciitis in intensive care unit patients. The role of hypoalbuminemia during dalbavancin exposure merits further investigation.


title: Our experience with laparoscopic partial gastrectomy by the 'lift-and-cut method' for gastric gastrointestinal stromal tumor with maximal preservation of the remnant stomach.

text: BACKGROUND Wedge resection is the most commonly used method in laparoscopic partial gastrectomy for gastric gastrointestinal stromal tumor (GIST). However, this method can involve inadvertent resection of additional gastric tissue and cause gastric deformation. To minimize the volume of resected gastric tissue, we have developed a laparoscopic partial gastrectomy with seromyotomy which we call the 'lift-and-cut method' for gastric GIST. Here, we report a case series of this surgery. METHOD First, the seromuscular layer around the tumor is cut. Because the mucosa and submucosa are extensible, the tumor is lifted toward the abdominal cavity. After sufficient lifting, the gastric tissue under the tumor is cut at the submucosal layer with a linear stapler (thus 'lift-and-cut method'). Finally, the defect in the seromuscular layer is closed with a hand-sewn suture. RESULTS From April 2011 to December 2015, 28 patients underwent laparoscopic partial gastrectomy by this method at Osaka Red Cross Hospital. Average operation time was 126 min (range 65-302 min) and average blood loss was 10 ml (range 0-200 ml). No intraoperative complications including tumor rupture or postoperative complications regarded as Clavien-Dindo Grade II or higher occurred. All patients took sufficient solid diet at discharge. Median postoperative hospital stay was 7 days (range 5-21 days). On median follow-up of 26.6 months (range 6-54 months), no recurrence was reported. CONCLUSION Laparoscopic partial gastrectomy by the lift-and-cut method is safe and simple, and widely applicable for gastric GIST.


title: Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection.

text: BACKGROUND Differentiation between septic and aseptic loosening of joint replacements is essential for successful revision surgery, but reliable markers for the diagnosis of low-grade infection are lacking. The present study was performed to assess intra-articular and systemic levels of antimicrobial peptides and proinflammatory cytokines as diagnostic markers for periprosthetic joint infection. METHODS Fifteen consecutive patients with staphylococcal periprosthetic joint infections and twenty control patients with aseptic loosening of total hip and knee replacements were included in this prospective, single-center, controlled clinical trial. Expression of the antimicrobial peptides human β-defensin-2 (HBD-2), human β-defensin-3 (HBD-3), and cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in serum and joint aspirates with use of cytometric bead arrays. C-reactive protein in serum, microbiology, and histopathology of periprosthetic tissue served as the "gold standard" for the diagnosis of infection. RESULTS The antimicrobial peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from patients with periprosthetic joint infection compared with patients with aseptic loosening, and the area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 0.745 and 0.875, respectively. Additionally, significant local increases in the proinflammatory cytokines interleukin (IL)-1β, IL-4, IL-6, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were observed to be associated with infection. Logistic regression analysis indicated that the combination of an antimicrobial peptide with another synovial fluid biomarker improved diagnostic accuracy; the AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3 and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial peptides and cytokines in serum that showed a significant systemic increase in association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC value of <0.75). CONCLUSIONS The present study showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection, and analysis of the levels in synovial fluid was more accurate than analysis of serum.


title: Clinical nursing and midwifery research in Latin American and Caribbean countries: A scoping review.

text: AIM To identify and describe published, nursing-led and midwifery-led, clinical research that has been conducted in Latin America and the Caribbean. BACKGROUND Peer-reviewed published research may correspond to and elucidate country's realities, priorities, and needs. DESIGN A 6-stage scoping review methodology was used to search scientific databases using an applied search strategy. DATA SOURCES Five databases were searched for articles published in English, Spanish, or Portuguese conducted in a Latin American or Caribbean country between January 1, 2006 and June 14, 2016. REVIEW METHODS Articles were independently considered for inclusion by 2 researchers, data extracted, and study characteristics described. RESULTS Of 6922 articles identified, 404 were included. The majority were conducted in Brazil (90.6%) followed by Chile (2.5%). Most were nurse-led (95.8%) and were implemented in hospitals (48.6%). Studies frequently explored patient knowledge or characterized patient populations (61.3%) and commonly assessed chronic disease (19.3%) or maternity/child health outcomes (15.9%). CONCLUSION Findings revealed a large number of publications but an uneven geographical distribution of nurse-led clinical research and an evident gap of midwifery-related research in Latin America and the Caribbean. Results may be used to build research agendas to promote nursing and midwifery research capacity and further establish evidence-based practice.


title: Renal denervation: effects on atrial electrophysiology and arrhythmias.

text: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Currently, atrial endocardial catheter ablation, mainly targeting focal discharges in the pulmonary veins, is the most widely used interventional treatment of drug-refractory AF. Despite technical improvements, results are not yet optimal. There is ongoing search for alternative and/or complementary interventional targets. Conditions associated with increased sympathetic activation such as hypertension, heart failure and sleep apnea lead to structural, neural and electrophysiological changes in the atrium thereby contributing to the progression from paroxysmal to persistent AF and increasing recurrence rate of AF after PVI. Until now, interventional modulation of autonomic nervous system was limited by highly invasive techniques. Catheter-based renal denervation (RDN) was introduced as a minimally invasive approach to reduce renal and whole body sympathetic activation with accompanying blood pressure control and left-ventricular morphological and functional changes in resistant hypertension. This review focuses on the potential atrial antiarrhythmic and antiremodeling effects of RDN in AF patients with hypertension, heart failure, and sleep apnea and discusses the possible role of RDN in the treatment of AF.


title: Chapter of Gastroenterologists professional guidance on risk mitigation for gastrointestinal endoscopy during COVID-19 pandemic in Singapore.

text: In this paper, we aimed to provide professional guidance to practising gastrointestinal (GI) endoscopists for the safe conduct of GI endoscopy procedures during the current coronavirus disease 2019 (COVID-19) pandemic and future outbreaks of similar severe respiratory tract infections in Singapore. It draws on the lessons learnt during the severe acute respiratory syndrome (SARS) epidemic and available published data concerning the COVID-19 pandemic. It addresses measures before, during and after endoscopy that must be considered for both non- infected and infected patients, and provides recommendations for practical implementation.


title: Community-acquired respiratory viral infections in lung transplant recipients.

text: PURPOSE OF REVIEW Community-acquired respiratory virus (CARV) infections are a significant cause of morbidity and sometimes mortality in lung transplant recipients (LTRs); this review will focus on the most recent advances in this field. RECENT FINDINGS Recent advancements in molecular diagnostics have resulted in the detection of higher rates of CARVs in LTRs. Persistence of rhinovirus has been implicated in the development of acute and chronic rejection, whereas the role of bocavirus remains uncertain. The data on the association of CARV infections with acute or chronic rejection remain less. A recent systematic review failed to show an association between CARV infections and acute or chronic rejection. Different routes of administration of antiviral medications, vaccines and newer promising antiviral medications are being evaluated to assess efficacy and safety. Similarly, newer strategies of vaccination may potentiate the immune response in these patients. SUMMARY With current advanced investigating tools, the full impact of CARV infections in LTR is increasingly coming to realization. Research for novel effective treatments and improved responses to current and new vaccines is ongoing; they would provide great benefit in solving this complex and ever-evolving problem.


title: Respiratory Symptoms and Complications of Zenker Diverticulum: Effect of Trans-Oral Septum Stapling.

text: BACKGROUND Zenker diverticulum is a rare condition commonly associated with dysphagia and respiratory symptoms/complications, which are alarming especially in the elderly population. Aim of this study was to investigate the prevalence of respiratory symptoms/complications and the effects of minimally invasive trans-oral surgery in these patients. METHODS Consecutive adult patients who underwent trans-oral septum stapling for Zenker diverticulum were included in a retrospective, observational cohort study. Pre- and postoperative symptoms, including chronic cough and aspiration pneumonia, were evaluated using a dedicated foregut questionnaire and were recorded on a prospectively maintained database. The operation was performed under general anesthesia. A barium swallow study and an upper gastrointestinal endoscopy were performed 6 months after the operation, and the foregut questionnaire was administered yearly. RESULTS A total of 139 patients were finally included in the study. The median age was 72 years. In 62 (44.6%, CI 36.2-53.3) patients, there was a history of chronic cough and/or aspiration pneumonia. Chronic cough was associated with pneumonia (p < 0.001), while pneumonia was associated with severe regurgitation (p < 0.042) and weight loss (p = 0.001). The overall postoperative morbidity rate was 2.2% and there was no mortality. The median postoperative hospital stay was 2 days (range 0-22). The median follow-up was 38 months (range 2-105). At 3 years, a statistically significant reduction in the rate of chronic cough (36.8 vs. 7.9%, p < 0.001), recurrent episodes of pneumonia (6.6 vs. 0.0%, p = 0.031), dysphagia (78.9 vs. 6.6%, p < 0.001), and regurgitation (67.1 vs. 6.6%, p < 0.001) was recorded. The probability of remaining symptom-free at 90 months of follow-up was 0.818 (CI: 0.745-0.899). CONCLUSIONS Trans-oral septum stapling is safe and can effectively reduce the burden of respiratory symptoms and complications associated with Zenker diverticulum.


title: Effects of daily vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients: a pilot trial.

text: BACKGROUND Although vitamin D is well known for its function in calcium homeostasis and bone mineralization, several studies have shown positive effects on muscle strength and physical function. In addition, vitamin D has been associated with pulmonary function and the incidence of airway infections. As vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients, supplementation might have a beneficial effect in these patients. OBJECTIVE To assess the effect of vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients. Secondary outcomes are pulmonary function, handgrip strength, exacerbation rate, and quality of life. METHODS We performed a randomized, double-blind, placebo-controlled pilot trial. Participants were randomly allocated to receive 1,200 IU vitamin D3 per day (n=24) or placebo (n=26) during 6 months. Study visits were conducted at baseline, and at 3 and 6 months after randomization. During the visits, blood was collected, respiratory muscle strength was measured (maximum inspiratory and expiratory pressure), physical performance and 6-minute walking tests were performed, and handgrip strength and pulmonary function were assessed. In addition, participants kept a diary card in which they registered respiratory symptoms. RESULTS At baseline, the mean (standard deviation [SD]) serum 25-hydroxyvitamin D (25(OH)D) concentration (nmol/L) was 42.3 (15.2) in the vitamin D group and 40.6 (17.0) in the placebo group. Participants with vitamin D supplementation had a larger increase in serum 25(OH)D compared to the placebo group after 6 months (mean difference (SD): +52.8 (29.8) vs +12.3 (25.1), P<0.001). Primary outcomes, respiratory muscle strength and physical performance, did not differ between the groups after 6 months. In addition, no differences were found in the 6-minute walking test results, handgrip strength, pulmonary function, exacerbation rate, or quality of life. CONCLUSION Vitamin D supplementation did not affect (respiratory) muscle strength or physical performance in this pilot trial in vitamin D-deficient COPD patients.


title: Perioperative and follow-up results in carotid artery stenting with contralateral carotid occlusion.

text: PURPOSE Contralateral carotid occlusion (CCO) increases the risk of carotid endarterectomy (CEA). We determined the outcome of carotid angioplasty and stenting (CAS), an alternative to CEA, in the setting of CCO through an independent analysis of imaging and clinical outcome. MATERIALS AND METHODS Medical records of 26 consecutive patients with CCO who underwent CAS by a single operator using the same procedural protocol (with distal protection and closed-cell stents) were retrospectively evaluated. National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores before and after CAS, periprocedural complications, and the restenosis rate were analyzed by independent stroke neurologists who were not involved in the care of the patients. RESULTS The median mRS score for the 26 patients was 1 (range 0-5) before and after CAS. All of the patients underwent clinical and imaging follow-up (mean 19.5 ± 14.3 and 11.6 ± 11.2 months, respectively). Thirty-day mortality/permanent morbidity rates were 0 %. One patient had hyperperfusion syndrome and was managed medically without sequelae; however, he had stent occlusion after 30 days, resulting in a decline in his mRS from 4 (preprocedure) to 5. Otherwise, there was no decline in mRS during the post-discharge follow-up. CONCLUSION According to an independent analysis of this single-operator series, CAS is safe and effective for the treatment of patients with CCO.


title: Vaccines against Ebola virus and Marburg virus: recent advances and promising candidates.

text: The filoviruses Ebola virus and Marburg virus are among the most dangerous pathogens in the world. Both viruses cause viral hemorrhagic fever, with case fatality rates of up to 90%. Historically, filovirus outbreaks had been relatively small, with only a few hundred cases reported. However, the recent West African Ebola virus outbreak underscored the threat that filoviruses pose. The three year-long outbreak resulted in 28,646 Ebola virus infections and 11,323 deaths. The lack of Food and Drug Administration (FDA) licensed vaccines and antiviral drugs hindered early efforts to contain the outbreak. In response, the global scientific community has spurred the advanced development of many filovirus vaccine candidates. Novel vaccine platforms, such as viral vectors and DNA vaccines, have emerged, leading to the investigation of candidate vaccines that have demonstrated protective efficacy in small animal and nonhuman primate studies. Here, we will discuss several of these vaccine platforms with a particular focus on approaches that have advanced into clinical development.


title: Recurrent arteriovenous malformation on palate after embolization combined surgical resection: preoperative magnetic resonance features and intraoperative angiographic findings.

text: Angiography is the gold standard for the diagnosis and complete resection of arteriovenous malformations (AVMs). The absence of residual AVM after surgery is commonly believed to reduce the risk of future hemorrhage. However, AVMs can recur after proven complete angiographic resection can occur, albeit rarely, especially in the pediatric population. We report a rare case of a recurrent AVM two years after complete resection in an adult patient. This case report shows that AVMs in adults can recur despite their rarity and despite postoperative angiography confirming complete removal. Moreover, in this case, the recurrent AVM involved a new feeding vessel that was not involved with the initial lesion.


title: Minimal sufficient balance randomization for sequential randomized controlled trial designs: results from the ESCAPE trial.

text: BACKGROUND We describe the implementation of minimal sufficient balance randomization, a covariate-adaptive randomization technique, used for the "Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times" (ESCAPE) trial. METHODS The ESCAPE trial is a prospective, multicenter, randomized clinical trial that enrolled subjects with the following main inclusion criteria: less than 12 h from symptom onset, age 18 years or older, baseline NIHSS score > 5, ASPECTS score > 5 and computed tomography angiography (CTA) evidence of carotid T/L or M1-segment middle cerebral artery (MCA) occlusion, and at least moderate collaterals by CTA. Patients were randomized using a real-time, dynamic, Internet-based, minimal sufficient balance randomization method that balanced the study arms with respect to baseline covariates including age, sex, baseline NIHSS score, site of arterial occlusion, baseline ASPECTS score and treatment with intravenously administered alteplase. RESULTS Permutation-based tests of group differences confirmed group balance across several baseline covariates including sex (p = 1.00), baseline NIHSS score (p = 0.95), site of arterial occlusion (p = 1.00), baseline ASPECTS score (p = 0.28), treatment with intravenously administered alteplase (p = 0.31), and age (p = 0.67). CONCLUSION Results from the ESCAPE trial demonstrate the feasibility and the benefit of this covariate adaptive randomization scheme in small-sample trials and for data monitoring endeavors. TRIAL REGISTRATION ESCAPE trial - NCT01778335 - at www.clinicaltrials.gov . Registered on 29 January 2013.


title: A hypothesis for pathobiology and treatment of COVID-19: the centrality of ACE1/ACE2 imbalance.

text: Angiotensin converting enzyme-2 (ACE2) is the receptor for the coronavirus SARS-CoV-2, which causes COVID-19. We propose the following hypothesis: Imbalance in the action of ACE1- and ACE2-derived peptides, thereby enhancing Angiotensin-II (ANG II) signaling, a primary driver of COVID-19 pathobiology. ACE1/ACE2 imbalance occurs due to the binding of SARS-CoV-2 to ACE2, reducing ACE2-mediated conversion of ANG II to ANG peptides that counteract pathophysiological effects of ACE1-generated ANGII. This hypothesis suggests several approaches to treat COVID-19 by restoring ACE1/ACE2 balance: 1) ANG II receptor blockers (ARBs); 2) ACE1 inhibitors (ACEIs); 3) Agonists of receptors activated by ACE2-derived peptides [e.g., ANG (1-7), which activates MAS1]; 4) Recombinant human ACE2 or ACE2 peptides as decoys for the virus. Reducing ACE1/ACE2 imbalance is predicted to blunt COVID-19-associated morbidity and mortality, especially in vulnerable patients. Importantly, approved ARBs and ACEIs can be rapidly repurposed to test their efficacy in treating COVID-19.


title: [Conventional respiratory support therapy for Severe Acute Respiratory Infections (SARI): Clinical indications and nosocomial infection prevention and control].

text: Severe acute respiratory infection (SARI) diseases (such as SARS, MERS, pH1N1) can rapidly progress to acute respiratory failure with high lethality. The outbreak of a novel coronavirus infection can lead to 15%~ 30% patients developing into acute respiratory distress syndrome (ARDS). Respiratory support is the most important therapy for SARI patients with respiratory failure. However, respiratory support is a high skilled technology, which means inappropriate application may bring related complications and cross infection of SARI pathogens among medical staff and non-medical personnel in hospital. Therefore, it is meaningful to established a standardized indication of respiratory support and to prevent related nosocomial transmission in SARI patients.


title: Fluid tagging for CT colonography: effectiveness of a 2-hour iodinated oral preparation after incomplete optical colonoscopy.

text: OBJECTIVE To evaluate the distal extent and attenuation of bowel opacification achieved after administration of a single low volume dose of oral contrast 2 hours before computed tomographic colonography (CTC) after incomplete optical colonoscopy. METHODS This retrospective study included 144 patients undergoing CTC after incomplete colonoscopy from April 2006 to July 2008 at 2 separate medical centers. Each patient received 20 to 30 mL of diatrizoate meglumine and diatrizoate sodium solution 2 hours before being scanned. RESULTS The distalmost extent of opacification was: stomach/small bowel, n = 13; cecum, n = 2; ascending colon, n = 7; transverse colon, n = 19; descending colon, n = 14; sigmoid colon, n = 24; rectum, n = 65. The mean attenuation of each opacified segment was: cecum, 449 Hounsfield units (HU); ascending colon, 474 HU; transverse colon, 468 HU; descending colon, 421 HU; sigmoid colon, 391 HU; and rectum, 382 HU. In 103 (71.5%) patients, oral contrast reached the distal colon (descending colon, sigmoid colon, or rectum). The oral contrast did not reach the colon in only 13 (9.0%) patients. CONCLUSIONS Oral administration of a small volume hyperosmolar oral contrast agent 2 hours before CTC results in satisfactory colonic opacification in the majority of patients. Adding same-day fluid tagging in incomplete colonoscopy patients presenting for completion CTC should result in adequate fluid opacification for most of the colon, especially proximal segments not visualized at the time of incomplete colonoscopy.


Science & SciLifeLab Prize. From persistence to cross-species emergence of a viral zoonosis.


title: A Single Center Experience with Coil Embolization for Cerebral Aneurysms Greater than 10 mm in the Internal Carotid Artery.

text: We investigated endovascular treatment for 10 mm or larger aneurysms in the internal carotid artery (IC), including the cavernous portion, the paraclinoid portion, and the posterior communication artery (PC). Between 2011 and 2014 at our hospital, there were 35 cases of aneurysms that were 10 mm or larger in the carotid artery. We analyzed these 35 cases retrospectively based on the size and location of the aneurysms, method of treatment, number of coils implanted, use of a stent, complications, rupture after treatment, ophthalmologic symptoms, and need for re-treatment. There was no bleeding after treatment. Of the 35 cases, four cases (11%) had permanent complications. Re-treatment was indicated in 11 cases (31%), including eight cases localized in the paraclinoid portion, two cases in the IC-PC, and one case in the cavernous portion. Among these re-treatment cases, two cases required a third treatment. Of the 16 cases with paraclinoid aneurysms, half required re-treatment. Of the 12 cases with ophthalmologic symptoms prior to treatment, 9 (75%) improved or had no change and 3 (25%) became worse. There were no complications in the 13 re-treatment procedures. Re-treatment is not uncommon, and a scheduled follow-up is needed. Coil embolization has been one of the main options for aneurysms that are 10 mm or larger in the IC. In the future, these large aneurysms will be treated with a flow diverter stent (FD).


Accelerated versus standard care in hip fracture patients: does speed save lives?


Remote controller.


Keep or release: experience on management of COVID-19 during maximum emergency in Bergamo and impact on patient outcomes.


title: Telemedicine in Germany during the COVID-19 Pandemic: Multiprofessional National Survey.

text: BACKGROUND In an effort to contain the effects of the COVID-19 pandemic, healthcare systems globally implemented telemedical solutions in order to overcome staffing, technical and infrastructural limitations. In Germany, a multitude of telemedical systems are already in function, while new approaches are rapidly developed in response to the crisis. However, the extent of current implementation within different healthcare settings, the user acceptance and perception as well as the hindering technical and regulatory obstacles remain unclear. OBJECTIVE To assess the current status quo of availability as well as routine use of telemedical solutions, the user acceptance and the subjectively perceived burdens on telemedical approaches. Furthermore to assess the perception of the quality of public information amongst professional groups and their preferred communication channels. METHODS A national online survey conducted on 14 consecutive days in March-April 2020, distributed to doctors, nurses and other medical professionals in German language. RESULTS A total of 2827 medical professionals participated in the study. 65.6% (n=1855) identified as doctors, 29.5% (n=833) as nursing staff and 4.9% (n=139) as others, e.g. therapeutic staff. A majority of participants rated the significance of telemedicine within the crisis as high (39%, n=1065) or neutral (26.4%, n=720), however there were significant differences between doctors and nurses (p=.01) as well as between the stationary sector compared to the ambulatory sector (p <.001). Telemedicine already is in routine use in 19.6% and in partial use in 40.2% of German healthcare providers. Participants working in private practices (40.2%, n=239) or private clinics (39.0%, n=23) experience less regulatory or technical obstacles, compared to university hospitals (49.2%, n=586). A majority of doctors rated the public information quality on COVID as good (50.8%, n= 942) or very good (11.5%, n=213), nurses rated the quality of public information significantly lower (p <.01). Participant's age negatively correlated with the perception of significance of the telemedicine (Spearmans's rho = -0.23; p <.001). CONCLUSIONS Telemedicine has a broad acceptance within German medical professionals. However, in order to establish telemedical structures within routine care, technical and regulatory burdens have to be overcome. CLINICALTRIAL


Prevent loss of life by providing all NHS staff with WHO standard personal protective equipment.


title: Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo.

text: mRNA has broad potential for treating diseases requiring protein expression. However, mRNA can also induce an immune response with associated toxicity. Replacement of uridine bases with pseudouridine has been postulated to modulate both mRNA immunogenicity and potency. Here, we explore the immune response and activity of lipid nanoparticle-formulated unmodified and pseudouridine-modified mRNAs administered systemically in vivo. Pseudouridine modification to mRNA had no significant effect on lipid nanoparticle physical properties, protein expression in vivo, or mRNA immunogenicity compared to unmodified mRNA when delivered systemically with liver-targeting lipid nanoparticles, but reduced in vitro transfection levels. Indicators of a transient, extracellular innate immune response to mRNA were observed, including neutrophilia, myeloid cell activation, and up-regulation of four serum cytokines. This study provides insight into the immune responses to mRNA lipid nanoparticles, and suggests that pseudouridine modifications may be unnecessary for therapeutic application of mRNA in the liver.


title: Usability evaluation methods employed to assess information visualisations of electronically stored patient data for clinical use: a protocol for a systematic review.

text: BACKGROUND The use of electronic records in healthcare is increasing. To avoid errors, it is essential that the data displays used by these systems are usable: efficient, effective and satisfying. A wide variety of display techniques are used to present clinical data, but the best methods to assess the usability of these techniques have not been determined. This systematic review will answer the question: What methods are employed to assess the usability of electronic visualisations of patient data for clinical use? The results of this systematic review will then be used to inform best assessment and design practice. METHODS MEDLINE, EMBASE, CINAHL, OpenGrey, and the Cochrane Database of Systematic Reviews will be searched for original studies related to the usability of electronic information visualisations of patient data for clinical use. Reference lists of eligible studies and relevant reviews will be explored to identify further eligible studies. DISCUSSION This systematic review will identify methods used to assess the usability of electronic information visualisations of patient data for clinical use. We will summarise the similarities and differences between the methods found. Our results will inform best practice when developing new user interfaces to display electronic patient data for clinical use. TRIAL REGISTRATION PROSPERO CRD42016041604.


title: Closed-loop gastric electrical stimulation versus laparoscopic adjustable gastric band for the treatment of obesity: a randomized 12-month multicenter study.

text: OBJECTIVE To compare the weight loss, change in quality of life (QOL) and safety of closed-loop gastric electrical stimulation (CLGES) versus adjustable gastric band (LAGB) in the treatment of obesity. METHODS This multicenter, randomized, non-inferiority trial randomly assigned the patients in a 2:1 ratio to laparoscopic CLGES versus LAGB and followed them for 1 year. We enrolled 210 patients, of whom 50 were withdrawn preoperatively. Among 160 remaining patients (mean age=39±11 years; 75% women; mean body mass index=43±6 kg m-2) 106 received CLGES and 54 received LAGB. The first primary end point was non-inferiority of CLGES versus LAGB, ascertained by the proportion of patients who, at 1 year, fulfilled: (a) a ⩾20% excess weight loss (EWL); (b) no major device- or procedure-related adverse event (AE); and (c) no major, adverse change in QOL. Furthermore, ⩾50% of patients had to reach ⩾25% EWL. The incidence and seriousness of all AE were analyzed and compared using Mann-Whitney's U-test. RESULTS At 1 year, the proportions of patients who reached all components of the primary study end point were 66.7 and 73.0% for the LAGB and CLGES group, respectively, with a difference of -6.3% and an upper 95% CI of 7.2%, less than the predetermined 10% margin for confirming the non-inferiority of CLGES. The second primary end point was also met, as 61.3% of patients in the CLGES group reached ⩾25% EWL (lower 95% CI=52.0%; P<0.01). QOL improved significantly and similarly in both groups. AE were significantly fewer and less severe in the CLGES than in the LAGB group (P<0.001). CONCLUSIONS AND RELEVANCE This randomized study confirmed the non-inferiority of CLGES compared with LAGB based on the predetermined composite end point. CLGES was associated with significantly fewer major AE.


title: Gene N proximal and distal RNA motifs regulate coronavirus nucleocapsid mRNA transcription.

text: Coronavirus subgenomic mRNA (sgmRNA) transcription requires a discontinuous RNA synthesis mechanism driven by the transcription-regulating sequences (TRSs), located at the 3' end of the genomic leader (TRS-L) and also preceding each gene (TRS-B). In transmissible gastroenteritis virus (TGEV), the free energy of TRS-L and cTRS-B (complement of TRS-B) duplex formation is one of the factors regulating the transcription of sgmRNAs. In addition, N gene sgmRNA transcription is controlled by a transcription-regulating motif, including a long-distance RNA-RNA interaction between complementary proximal and distal elements. The extension of complementarity between these two sequences increased N gene transcription. An active domain, a novel essential component of the transcription-regulating motif, has been identified. The active domain primary sequence was necessary for its activity. Relocation of the active domain upstream of the N gene TRS core sequence in the absence of the proximal and distal elements also enhanced sgmRNA N transcription. According to the proposed working model for N gene transcriptional activation, the long-distance RNA-RNA interaction relocates the distant active domain in close proximity with the N gene TRS, which probably increases the frequency of template switching during the synthesis of negative RNA. The transcription-regulating motif has been optimized to a minimal sequence showing a 4-fold activity increase in relation to the native RNA motif. Full-length TGEV infectious viruses were generated with the optimized transcription-regulating motif, which enhanced by 5-fold the transcription of the 3a gene and can be used in expression vectors based in coronavirus genomes.


title: Effects of temperature and organic loading rate on the performance and microbial community of anaerobic co-digestion of waste activated sludge and food waste.

text: Anaerobic co-digestion of waste activated sludge and food waste was investigated semi-continuously using continuously stirred tank reactors. Results showed that the performance of co-digestion system was distinctly influenced by temperature and organic loading rate (OLR) in terms of gas production rate (GPR), methane yield, volatile solids (VS) removal efficiency and the system stability. The highest GPR at 55 °C was 1.6 and 1.3 times higher than that at 35 and 45 °C with the OLR of 1 g VSL(-1)d(-1), and the corresponding average CH₄ yields were 0.40, 0.26 and 0.30 L CH₄ g(-1)VSadded, respectively. The thermophilic system exhibited the best load bearing capacity at extremely high OLR of 7 g VSL(-1)d(-1), while the mesophilic system showed the best process stability at low OLRs (< 5 g VSL(-1)d(-1)). Temperature had a more remarkable effect on the richness and diversity of microbial populations than the OLR.


title: A Case of Renal Pelvic Cancer Complicated by Horseshoe Kidney Treated with RoboSurgeon Gasless Single-Port Retroperitoneoscopic Nephroureterectomy.

text: A 78-year-old man who had a horseshoe kidney (HSK) visited us because of gross hematuria and suspicious urine cytology. CT and MRI revealed a right renal pelvic tumor of 28 mm in diameter. He underwent gasless single-port retroperitoneoscopic nephroureterectomy with division of the isthmus via the right pararectal small incision using the RoboSurgeon system. Pathological diagnosis was invasive urothelial carcinoma, grade 3, pT3, pN0, LVI0, RM0. He was discharged from hospital on the 6th postoperative day without any perioperative complication. He has no evidence of disease clinically and radiologically 19 months after the operation. Only a few cases of upper tract urothelial carcinoma complicated by HSK treated with minimally invasive surgery have been reported in English literature. This is the first case successfully managed with RoboSurgeon gasless single-port retroperitoneoscopic nephroureterectomy.


Coronavirus: three things all governments and their science advisers must do now.