title: The epidemiology of sleep and obesity.

text: Sleep is a state of consciousness that is preserved across animal species whose exact function is not yet clear but which has a vital impact on health and well-being. Epidemiological evidence suggests sleep duration in both children and adults has been decreasing over the past half-century, while at the same time rates of overweight and obesity have been increasing. Short sleep duration along with other dimensions of poor sleep has been associated with obesity both cross-sectionally and longitudinally. These data suggest a potential causal relationship between poor sleep and greater rates of weight gain that may be related to effects of sleep on dietary intake or physical activity. However, there is also potential for reverse causation as obesity leads to many co-morbidities including sleep apnea that can disrupt sleep. Medium and long term interventional studies are needed to evaluate the potential for healthy sleep interventions to help combat the epidemic of obesity.


From Ebola to Zika: international emergencies and the securitization of global health.


title: Systematic review with meta-analysis: sirolimus- or everolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma.

text: BACKGROUND Calcineurin-inhibitor immunosuppressants (tacrolimus and ciclosporin) have been associated with an exposure-related increase in tumour recurrence following liver transplantation for hepatocellular carcinoma (HCC). Conversely, mechanistic target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been suggested to reduce recurrence rates and improve survival in this patient group. AIM To clarify the potential benefit of mTOR-inhibitors in HCC transplant patients by comparing recurrence and survival outcomes with calcineurin-inhibitor-based immunosuppression. METHODS A systematic review and meta-analysis was performed. The inclusion criteria were observational or interventional studies reporting the effect of early-initiated (<6 months post-transplant) mTOR-inhibitor-based immunosuppression on survival or tumour recurrence in patients transplanted with HCC, compared to a control of calcineurin-inhibitor-based therapy. RESULTS Meta-analysis demonstrated that compared with calcineurin-inhibitor controls, recurrence-free-survival was significantly increased with mTOR-inhibitor-based therapy at 1-year (Risk-Ratio (RR): 1.09, 95% CI: 1.01-1.18) and 3-years (RR: 1.1, 95% CI: 1.01-1.21) post-transplant, with a nonsignificant increase at 5-years (RR: 1.15, 95% CI: 0.99-1.35). Overall survival was improved at 1-year (RR: 1.07, 95% CI: 1.02-1.12), 3-years (RR: 1.1, 95% CI: 1.02-1.19), and 5-years (RR: 1.18, 95% CI: 1.08-1.29). Recurrence-rate was lower in the mTOR-inhibitor arm (RR: 0.67, 95% CI: 0.56-0.82), with no significant increase in acute rejection (RR: 1.1, 95% CI: 0.94-1.28). CONCLUSIONS mTOR-inhibitor-based immunosuppression may be a preferable option in patients transplanted with HCC. It improves recurrence-free-survival over at least three years and reduces the recurrence rate compared with standard calcineurin-inhibitor-based therapy, with no significant increase in the rate of acute rejection. Future research should clarify the effect in higher vs lower risk cohorts.


title: Prediction of bilateral cerebral oxygen desaturations from a single sensor in adult cardiac surgery: A prospective observational study.

text: BACKGROUND Monitoring regional cerebral oxygen saturation (rcSO2) with near-infrared spectroscopy is increasingly being performed in patients scheduled for cardiac surgery. It is sometimes difficult to monitor both frontal lobes due to anatomical or space compromises. However, it remains unclear whether the use of only one lateral or medial probe can provide adequate bilateral monitoring. OBJECTIVE To evaluate the efficacy of using a single lateral or medial probe to detect substantial desaturations on both sides. DESIGN A prospective observational study. SETTING Tertiary university teaching hospital. PATIENTS Seventeen adult patients undergoing elective cardiac surgery monitored with three near-infrared spectroscopy probes (two lateral and one medial) using an INVOS 5100C monitor. INTERVENTIONS The value of rcSO2 was recorded up to 19 times during each procedure. Substantial desaturation was defined as an absolute rcSO2 value of 50% or less or a decrease of more than 20% compared with baseline values on spontaneous ventilation with 21% oxygen. MAIN OUTCOME MEASURES The level of agreement between the three pairs of probes using the Bland-Altman method for repeated measures, and the grade of concordant and discordant results between the three pairs of probes by means of contingency tables and the κ coefficient. RESULTS We obtained 244 records per probe. Greater agreement was observed between the two lateral probes (mean ± SD of the differences between recordings was -0.9 ± 5.5); mean difference between left and medial, and right and medial probes was 2.4 ± 7.3 and 3.3 ± 6.7, respectively. The rate of discordant results between the two lateral probes was 5.7%, κ coefficient of 0.6 with 95% confidence interval (95% CI 0.4 to 0.8), and between the left and medial, and right and medial of 8.2 and 7.4%, with κ coefficients of 0.57 (95% CI 0.38 to 0.76) and 0.5 (95% CI 0.29 to 0.71), respectively. CONCLUSION In cardiac surgery patients in whom there is difficulty in accommodating two rcSO2 probes, a single lateral probe can effectively measure bilateral rcSO2 in specific scenarios.


title: Vertical transmission risk of SARS-CoV-2 infection in the third trimester: a systematic scoping review.

text: Background: Studies on COVID-19 infection in pregnancy thus far have largely focused on characterizing maternal and neonatal clinical characteristics. However, another evolving focus is assessing and mitigating the risk of vertical transmission amongst COVID-19-positive mothers. The objective of this review was to summarize the current evidence on the vertical transmission potential of COVID-19 infection in the third trimester and its effects on the neonate.Methods: OVID MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial (CENTRAL) were searched from January 2020 to May 2020, with continuous surveillance.Results: 18 studies met the inclusion criteria, consisting of 157 mothers and 160 neonates. The mean age of the pregnant patients was 30.8 years and the mean gestational period was 37 weeks and 1 d. Currently, there is currently no conclusive evidence to suggest that vertical transmission of SARS-CoV-2 occurs. Amongst 81 (69%) neonates who were tested for SARS-CoV-2, 5 (6%) had a positive result. However, amongst these 5 neonates, the earliest test was performed at 16 h after birth, and only 1 neonate was positive when they were later re-tested. However, this neonate initially tested negative at birth, suggesting that the SARS-CoV-2 infection was likely hospital-acquired rather than vertically transmitted. 13 (8%) neonates had complications or symptoms.Conclusions: The findings of this rapid descriptive review based on early clinical evidence suggest that vertical transmission of SARS-CoV-2 from mother to neonate/newborn did not occur. Future studies are needed to determine the optimal management of neonates born to COVID-19-positive mothers.


title: Recombinant Ov-ASP-1, a Th1-biased protein adjuvant derived from the helminth Onchocerca volvulus, can directly bind and activate antigen-presenting cells.

text: We previously reported that rOv-ASP-1, a recombinant Onchocerca volvulus activation associated protein-1, was a potent adjuvant for recombinant protein or synthetic peptide-based Ags. In this study, we further evaluated the adjuvanticity of rOv-ASP-1 and explored its mechanism of action. Consistently, recombinant full-length spike protein of SARS-CoV or its receptor-binding domain in the presence of rOv-ASP-1 could effectively induce a mixed but Th1-skewed immune response in immunized mice. It appears that rOv-ASP-1 primarily bound to the APCs among human PBMCs and triggered Th1-biased proinflammatory cytokine production probably via the activation of monocyte-derived dendritic cells and the TLR, TLR2, and TLR4, thus suggesting that rOv-ASP-1 is a novel potent innate adjuvant.


title: Relative Energy Expenditure Decreases during the First Year after Bariatric Surgery: A Systematic Review and Meta-Analysis.

text: The effect of bariatric surgery on resting energy expenditure (REE) remains unclear, particularly in terms of the REE/fat-free mass (FFM) ratio. We performed a systematic review with a meta-analysis on Roux-en-Y gastric bypass (RYGB) studies to investigate the effect of bariatric surgery on the REE/FFM ratio 6 and 12 months postoperatively. Five of the 13 records of 6-month data (n = 406) showed a reduction in the REE/FFM ratio without significant summary effects. As regards 12-month data (10 records, n = 713), there was a significant relative REE mean reduction of 1.95 kcal/kg in FFM (CI: -2.82 to -1.09; I2 = 28%; p < 0.00001). These findings suggest that bariatric surgery, specifically RYGB, leads to a decrease in the REE/FFM ratio during the first postoperative year, which may compromise long-term treatment outcomes.


title: Update on Exhaled Nitric Oxide in Clinical Practice.

text: Asthma is characterized by chronic airway inflammation. Fractional exhaled nitric oxide (Feno) has emerged as a marker of T-helper cell type 2-mediated allergic airway inflammation. Recent studies suggest a role for Feno testing as a point-of-care tool in the management of patients with asthma. This Topics in Practice Management article reviews current coverage and reimbursement issues related to Feno testing and provides an overview of pertinent recent studies.


Extracranial carotid disease revascularization.


title: Hantaviruses as zoonotic pathogens in Germany.

text: BACKGROUND Hantavirus disease is a zoonosis of increasing clinical importance. A new incidence peak was reached in Germany in 2012, with more than 2800 reported cases. These viruses are transmitted from small mammals to human beings. The disease begins with high fever and non-pathognomonic manifestations that can end in shock and organ failure. METHODS This article is based on a selective literature search, on the authors' experiences at the National Referral Laboratory for Hantavirus Infections (Nationales Konsiliarlaboratorium für Hantaviren), and on published recommendations from Germany and abroad. RESULTS Two hantavirus species cause clinically relevant infections in Germany. Puumala virus, which is transmitted by bank voles, causes large outbreaks of disease every 2 to 3 years in the southwestern and western regions of Germany and in the Bavarian Forest. Dobrava-Belgrad virus, transmitted by striped field mice, causes infections in the north and east of the country. Serological tests are available for primary and confirmatory diagnosis; moreover, viral nucleic acids can be amplified in the early phase of illness and compared with the viral nucleic acids from the reservoir hosts of the corresponding type of infection. Infections with American types of hantavirus have ca. 35% case fatality, and hantaviruses from southeastern Europe and Asia are also highly pathogenic; in contrast, the febrile illnesses caused by hantaviruses in Germany are usually relatively mild. CONCLUSION When persons living in high-risk areas present with fever of unknown origin or with renal dysfunction of unknown origin, physicians should consider the possibility of a hantavirus infection and should initiate the appropriate diagnostic evaluation.


title: Persistent aneurysm growth following pipeline embolization device assisted coiling of a fusiform vertebral artery aneurysm: a word of caution!

text: The complex morphology of vertebrobasilar fusiform aneurysms makes them one of the most challenging lesions treated by neurointerventionists. Different management strategies in the past included parent vessel occlusion with or without extra-intracranial bypass surgery and endovascular reconstruction by conventional stents. Use of flow diversion has emerged as a promising alternative option with various studies documenting its efficacy and safety. However, there are various caveats associated with use of flow diversion in patients with fusiform vertibrobasilar aneurysms especially in patients presenting with acute subarachnoid hemorrhage (SAH). We report a rare case of persistent aneurysmal growth after coiling and placement of the Pipeline Embolization Device (PED; ev3, Irvine, California, USA) for SAH from a fusiform vertebral artery aneurysm. As consequences of aneurysm rupture can be devastating especially in patients with a prior SAH, the clinical relevance of recognizing and understanding such patterns of failure cannot be overemphasized as highlighted in the present case.


How can I cope with redeployment?


How to organize an emergency department during the COVID-19 pandemic.


title: Systemic and Local Administration of Antimicrobial and Cell Therapies to Prevent Methicillin-Resistant Staphylococcus epidermidis-Induced Femoral Nonunions in a Rat Model.

text: S. epidermidis is responsible for biofilm-related nonunions. This study compares the response to S. epidermidis-infected fractures in rats systemically or locally injected with vancomycin or bone marrow mesenchymal stem cells (BMSCs) in preventing the nonunion establishment. The 50% of rats receiving BMSCs intravenously (s-rBMSCs) died after treatment. A higher cytokine trend was measured in BMSCs locally injected rats (l-rBMSCs) at day 3 and in vancomycin systemically injected rats (l-VANC) at day 7 compared to the other groups. At day 14, the highest cytokine values were measured in l-VANC and in l-rBMSCs for IL-10. µCT showed a good bony bridging in s-VANC and excellent both in l-VANC and in l-rBMSCs. The bacterial growth was lower in s-VANC and l-VANC than in l-rBMSCs. Histology demonstrated the presence of new woven bone in s-VANC and a more mature bony bridging was found in l-VANC. The l-rBMSCs showed a poor bony bridging of fibrovascular tissue. Our results could suggest the synergic use of systemic and local injection of vancomycin as an effective treatment to prevent septic nonunions. This study cannot sustain the systemic injection of BMSCs due to high risks, while a deeper insight into local BMSCs immunomodulatory effects is mandatory before developing cell therapies in clinics.


Frequent detection of respiratory viruses by real-time PCR in adenoid samples from asymptomatic children.


A personal approach for Parkinson's disease.


title: Immunization of mice with Lactobacillus casei expressing a beta-intimin fragment reduces intestinal colonization by Citrobacter rodentium.

text: Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in children from developing countries. Intimate adhesion of the bacteria to intestinal cells occurs via binding of the adhesin intimin to the TIR receptor exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of β-intimin (L. casei-Int(cv)) was tested as mucosal vaccines in mice against intestinal colonization with the murine pathogen Citrobacter rodentium. Oral or sublingual immunization of C57BL/6 mice with L. casei-Int(cv) induced anti-Int(cv) IgA in feces but no IgG in sera. Conversely, anti-Int(cv) IgG was induced in the sera of mice after sublingual immunization with purified Int(cv). All vaccines were able to decrease C. rodentium recovery from feces. However, this reduction was more evident and sustained over time in mice immunized with L. casei-Int(cv) by the sublingual route. These mice also displayed an increase in interleukin 6 (IL-6) and gamma interferon (IFN-γ) secretion by spleen cells 10 days after infection. Additionally, oral or sublingual immunization of C3H/HePas mice, which are highly susceptible to C. rodentium infection, with L. casei-Int(cv) induced anti-Int(cv) antibodies and significantly increased survival after challenge. Immunohistological analysis of colon sections revealed that C. rodentium was located in deep fractions of the tissue from C3H/HePas mice immunized with L. casei whereas superficial staining was observed in colon sections from mice immunized with L. casei-Int(cv.) The results indicate that vaccines composed of L. casei expressing intimin may represent a promising approach and that the C3H/HePas infection model with C. rodentium can be used to evaluate potential vaccines against EPEC.


title: Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas.

text: OBJECT Greater extent of resection (EOR) for patients with low-grade glioma (LGG) corresponds with improved clinical outcome, yet remains a central challenge to the neurosurgical oncologist. Although 5-aminolevulinic acid (5-ALA)-induced tumor fluorescence is a strategy that can improve EOR in gliomas, only glioblastomas routinely fluoresce following 5-ALA administration. Intraoperative confocal microscopy adapts conventional confocal technology to a handheld probe that provides real-time fluorescent imaging at up to 1000× magnification. The authors report a combined approach in which intraoperative confocal microscopy is used to visualize 5-ALA tumor fluorescence in LGGs during the course of microsurgical resection. METHODS Following 5-ALA administration, patients with newly diagnosed LGG underwent microsurgical resection. Intraoperative confocal microscopy was conducted at the following points: 1) initial encounter with the tumor; 2) the midpoint of tumor resection; and 3) the presumed brain-tumor interface. Histopathological analysis of these sites correlated tumor infiltration with intraoperative cellular tumor fluorescence. RESULTS Ten consecutive patients with WHO Grades I and II gliomas underwent microsurgical resection with 5-ALA and intraoperative confocal microscopy. Macroscopic tumor fluorescence was not evident in any patient. However, in each case, intraoperative confocal microscopy identified tumor fluorescence at a cellular level, a finding that corresponded to tumor infiltration on matched histological analyses. CONCLUSIONS Intraoperative confocal microscopy can visualize cellular 5-ALA-induced tumor fluorescence within LGGs and at the brain-tumor interface. To assess the clinical value of 5-ALA for high-grade gliomas in conjunction with neuronavigation, and for LGGs in combination with intraoperative confocal microscopy and neuronavigation, a Phase IIIa randomized placebo-controlled trial (BALANCE) is underway at the authors' institution.


title: Growth restriction and gender influence cerebral oxygenation in preterm neonates.

text: OBJECTIVE To investigate the effect of fetal growth restriction and gender on cerebral oxygenation in preterm neonates during the first 3 days of life. DESIGN Case-control study. SETTING Neonatal Intensive Care Unit of the Wilhelmina Children's Hospital, The Netherlands. PATIENTS 68 (41 males) small for gestational age (SGA) (birth weight <10th percentile) and 136 (82 males) appropriate for gestational age (AGA) (birth weight 20th-80th percentile) neonates, matched for gender, gestational age, ventilatory and blood pressure support. METHODS Regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE) as measured by near-infrared spectroscopy throughout the first 72 h of life were compared between SGA and AGA neonates. The effect of gender was also explored within these comparisons. RESULTS SGA neonates demonstrated higher rScO2 (71% SEM 0.2 vs 68% SEM 0.2) and lower cFTOE (0.25 SEM 0.002 vs 0.29 SEM 0.002) than AGA neonates. There was an independent effect of gender on rScO2 and cFTOE, resulting in the finding that SGA males displayed highest rScO2 and lowest cFTOE (73% SEM 0.3 respectively 0.24 SEM 0.003). AGA males and SGA females showed comparable rScO2 (69% SEM 0.2 vs 69% SEM 0.4) and cFTOE (0.28 SEM 0.002 vs 0.28 SEM 0.004). AGA females showed lowest rScO2 and highest cFTOE (66% SEM 0.2 respectively 0.30 SEM 0.002). CONCLUSIONS Growth restriction and gender influence cerebral oxygenation and oxygen extraction in preterm neonates throughout the first 3 days of life.


title: Adoption of a novel surgical innovation into clinical practice: protocol for a qualitative systematic review examining surgeon views.

text: INTRODUCTION Efficient adoption of clinically effective novel surgical innovations has great potential benefits for patients. Factors affecting the adoption of surgical innovation are not well understood and proposed models of adoption do not accurately correlate with historical evidence. This protocol is for a systematic review that aims to identify the qualitative evidence relating to surgeon views regarding the adoption of novel surgical innovation into clinical practice. METHODS AND ANALYSIS A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance will be performed. Two independent reviewers will search the following databases: MEDLINE, Embase, Science Direct, Scopus, Web of Science and the Cochrane Library of Systematic Reviews. Inclusion criteria are studies which report on the views of surgeons who adopt a novel surgical innovation into clinical practice. Each article will be screened for inclusion and assessed according to a Critical Appraisal Skills Programme tool. Data will be synthesised and analysed according to thematic analysis. Given the anticipated yield of a small heterogeneous body of evidence meeting the eligibility criteria for the review, a narrative-based summary is planned. ETHICS AND DISSEMINATION This review does not require formal ethical approval as it does not involve direct patient contact or patient-identifiable data. The results of this review will be published in a peer-reviewed journal and presented at relevant conferences. The results will also inform an empirical qualitative study exploring surgeon and other stakeholder views regarding the introduction of novel surgical technology and procedures into clinical practice. PROSPERO REGISTRATION NUMBER CRD42017076715.


title: Impact of hygiene of housing conditions on performance and health of two pig genetic lines divergent for residual feed intake.

text: Pigs selected for high performance may be more at risk of developing diseases. This study aimed to assess the health and performance of two pig lines divergently selected for residual feed intake (RFI) (low RFI (LRFI) v. high RFI (HRFI)) and housed in two contrasted hygiene conditions (poor v. good) using a 2×2 factorial design (n=40/group). The challenge period (Period 1), started on week zero (W0) when 12-week-old pigs were transferred to good or poor housing conditions. At week 6 (W6), half of the pigs in each group were slaughtered. During a recovery period (Period 2) from W6 to W13 to W14, the remaining pigs (n=20/group) were transferred in good hygiene conditions before being slaughtered. Blood was collected every three (Period 1) or 2 weeks (Period 2) to assess blood indicators of immune and inflammatory responses. Pulmonary lesions at slaughter and performance traits were evaluated. At W6, pneumonia prevalence was greater for pigs housed in poor than in good conditions (51% v. 8%, respectively, P<0.001). Irrespective of hygiene conditions, lung lesion scores were lower for LRFI pigs than for HRFI pigs (P=0.03). At W3, LRFI in poor conditions had the highest number of blood granulocytes (hygiene×line, P=0.03) and at W6, HRFI pigs in poor conditions had the greatest plasma haptoglobin concentrations (hygiene×line, P=0.02). During Period 1, growth rate and growth-to-feed ratio were less affected by poor hygiene in LRFI pigs than in HRFI pigs (hygiene×line, P=0.001 and P=0.02, respectively). Low residual feed intake pigs in poor conditions ate more than the other groups (hygiene×line, P=0.002). Irrespective of the line, fasting plasma glucose concentrations were higher in poor conditions, whereas fasting free fatty acids concentrations were lower than in good conditions. At the end of Period 2, pneumonia prevalence was similar for both housing conditions (39% v. 38%, respectively). During Period 2, plasma protein concentrations were greater for pigs previously housed in poor than in good conditions during Period 1. Immune traits, gain-to-feed ratio, BW gain and feed consumption did not differ during Period 2. Nevertheless, at W12, BW of HRFI previously housed in poor conditions was 13.4 kg lower than BW of HRFI pigs (P<0.001) previously housed in good conditions. In conclusion, health of the most feed efficient LRFI pigs was less impaired by poor hygiene conditions. This line was able to preserve its health, growth performance and its feed ingestion to a greater extent than the less efficient HRFI line.


title: Feline immunodeficiency virus and feline leukemia virus infection in free-ranging guignas (Leopardus guigna) and sympatric domestic cats in human perturbed landscapes on Chiloé Island, Chile.

text: Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are two of the most common viruses affecting domestic cats (Felis catus). During the last two decades, reports show that both viruses also infect or affect other species of the family Felidae. Human landscape perturbation is one of the main causes of emerging diseases in wild animals, facilitating contact and transmission of pathogens between domestic and wild animals. We investigated FIV and FeLV infection in free-ranging guignas (Leopardus guigna) and sympatric domestic cats in human perturbed landscapes on Chiloé Island, Chile. Samples from 78 domestic cats and 15 guignas were collected from 2008 to 2010 and analyzed by PCR amplification and sequencing. Two guignas and two domestic cats were positive for FIV; three guignas and 26 domestic cats were positive for FeLV. The high percentage of nucleotide identity of FIV and FeLV sequences from both species suggests possible interspecies transmission of viruses, facilitated by increased contact probability through human invasion into natural habitats, fragmentation of guigna habitat, and poultry attacks by guignas. This study enhances our knowledge on the transmission of pathogens from domestic to wild animals in the global scenario of human landscape perturbation and emerging diseases.


Using Time Wisely During COVID-19.


title: Successful medical treatment of an orbital osteoma in a dog.

text: A 6-year-old neutered male German Shepherd-mixed breed with a 2-month history of bilateral conjunctival hyperemia, epiphora, and a firm, slowly progressive swelling of the medial canthal region of the left eye (OS) was examined. Ophthalmic examination OS revealed a firm and smooth mass, extending from the medial canthus toward the medial orbital wall. Indirect ophthalmoscopy revealed indentation of the nasal part OS, which corresponded to the position of the orbital mass. Orbital neoplastic diseases were the main differential considerations. Computerized tomography revealed a bony smooth orbital mass without bone destructive features. Biopsy was performed, and histologic features were suggestive of osteoma. Systemic nonsteroidal anti-inflammatory (NSAID) drugs resulted in complete mass regression and absence of clinical signs for 5 years following initial diagnosis. This report describes the first case of canine orbital osteoma, which was responsive to NSAIDs.


Emergency departments must not return to pre-covid days of overcrowding and lack of safety, says college.


title: High-throughput sequencing and vaccine design.

text: Next-generation sequencing (NGS) technologies have reshaped genome research. The resulting increase in sequencing depth and resolution has led to an unprecedented level of genomic detail and thus an increasing awareness of the complexity of animal, human and pathogen genomes. This has resulted in new approaches to vaccine research. On the one hand, the increase in genome complexity challenges our ability to study and understand pathogen biology and pathogen-host interactions. On the other hand, the increase in genomic data also provides key information for developing and designing improved vaccines against pathogens that were previously extremely difficult to deal with, such as rapidly mutating RNA viruses or bacteria that have complex interactions with the host immune system. This review describes how the broad application of NGS technologies to genome research is affecting vaccine research. It focuses on implications for the field of viral genomics, and includes recent animal and human studies.


title: Restriction of in vivo infection by antifouling coating on urinary catheter with controllable and sustained silver release: a proof of concept study.

text: BACKGROUND Catheter Associated Urinary Tract Infections are among the most common urological infections world-wide. Bacterial biofilms and encrustation cause significant complications in patients with urinary catheters. The objective of the study is to demonstrate the efficacy and safety of an anti-microbial and anti-encrustation silver nanoparticle (AgNP) coating on silicone urinary catheter in two different animal models. METHODS Antifouling coating (P3) was prepared with alternate layers of polydopamine and AgNP and an outermost antifouling layer. Sixteen C57BL/6 female mice and two female PWG Micropigs® were used to perform the experiments. In mice, a 5 mm long silicone catheter with or without P3 was transurethrally placed into the urinary bladder. Micropigs were transurethrally implanted - one with P3 silicone catheter and the other with commercially available silver coated silicone catheter. Both models were challenged with E. coli. Bacteriuria was evaluated routinely and upon end of study (2 weeks for mice, 3 weeks for micropigs), blood, catheters and bladders were harvested and analysed for bacterial colonization and encrustation as well as for toxicity. RESULTS Lower bacterial colonization was seen on P3 catheters as well as in bladders of animals with P3 catheter. Bacteriuria was consistently less in mice with P3 catheter than with uncoated catheters. Encrustation was lower on P3 catheter and in bladder of micropig with P3 catheter. No significant toxicity of P3 was observed in mice or in micropig as compared to controls. The numbers were small in this proof of concept study and technical issues were noted especially with the porcine model. CONCLUSIONS Antifouling P3 coating reduces bacterial colonization on catheter and in animal bladders without causing any considerable toxicity for 2 to 3 weeks. This novel coating could potentially reduce the complications of indwelling urethral catheters.


title: A comparison of Diamond Forrester and coronary calcium scores as gatekeepers for investigations of stable chest pain.

text: To determine if calcium scores (CS) could act as a more effective gatekeeper than Diamond Forrester (DF) in the assessment of patients with suspected coronary artery disease (CAD). A sub-study of the Cardiac CT for the Assessment of Chest Pain and Plaque (CAPP) study, a randomised control trial evaluating the cost-effectiveness of cardiac CT in symptomatic patients with stable chest pain. Stable pain was defined as troponin negative pain without symptoms of unstable angina. 250 patients undergoing cardiac CT had both DF scores and CS calculated, with the accuracy of both evaluated against CT coronary angiogram. Criteria given in UK national guidelines were compared. Of the 250 patients, 4 withdrew. 140 (57 %) patients were male. The mean DF was 47.8 and mean CS 172.5. Of the 144 patients with non-anginal pain 19.4 % had significant disease (>50 % stenosis). In general the DF over estimated the presence of CAD whereas the CS reclassified patients to lower risk groups, with 91 in the high risk DF category compared to 26 in the CS. Both receiver operating curve and McNemar Bowker test analysis suggested the DF was less accurate in the prediction of CAD compared to CS [Formula: see text] Projected downstream investigations were also calculated, with the cost per number of significant stenoses identified cheaper with the CS criteria. Patients with suspected stable CAD are more accurately risk stratified by CS compared to the traditional DF. CS was more successful in the prediction of significant stenosis and appears to be more effective at targeting clinical resources to those patients that are in need of them.


title: The Surgical Outcomes of Totally Laparoscopic Stomach-partitioning Gastrojejunostomy for Gastric Outlet Obstruction: A Retrospective, Cohort Study.

text: BACKGROUND We have reported the effectiveness of laparoscopy-assisted stomach-partitioning gastrojejunostomy Roux-en-Y reconstruction (LASPGJ-RY) for gastric outlet obstruction (GOO). The aim of this study was to evaluate the surgical outcomes of totally laparoscopic stomach-partitioning gastrojejunostomy Roux-en-Y reconstruction (TLSPGJ-RY) for GOO. MATERIALS AND METHODS This retrospective study enrolled 19 consecutive patients with GOO. Surgical outcomes of LASPGJ-RY (LA group; n=8) and TLSPGJ-RY (TL group; n=11) between January 2004 and 2015 were compared. The patients' background characteristics, operative findings, postoperative complications, and period to starting postoperative chemotherapy were examined. RESULTS Eligible cases included 6 patients with gastric cancer, 4 with pancreatic cancer, 4 with duodenal cancer, 4 with urologic malignancies, and 1 with benign duodenal stenosis. The patients' background characteristics were not significantly different. In surgical outcomes, there were no significant differences in operating time, bleeding, complications (≥Clavien-Dindo grade IIIA), and postoperative hospital stay between the groups. The time to resume diet was significantly shorter in the TL group (median, 3 d; range, 3 to 6 d) than in the LA group (median, 5 d; range, 3 to 7 d; P=0.0093), and the number of patients who could receive chemotherapy after surgery was significantly higher in the TL group (P=0.039). CONCLUSIONS TLSPGJ-RY was a safe and feasible gastrojejunostomy procedure for GOO. TLSPGJ-RY might be useful for early resumption of oral intake after surgery.


title: Endovascular management of intracranial blister aneurysms: spectrum and limitations of contemporary techniques.

text: BACKGROUND Intracranial blister aneurysms are rare lesions that are notoriously more difficult to treat than typical saccular aneurysms. High complication rates associated with surgery have sparked considerable interest in endovascular techniques, though not well-studied, to treat blister aneurysms. OBJECTIVE To evaluate our experience using various endovascular approaches to treat blister aneurysms. METHODS All consecutive blister aneurysms treated using an endovascular approach by the study authors over a 3-year period were retrospectively analyzed. A literature review was also performed. RESULTS Nine patients with blister aneurysms underwent 11 endovascular interventions. In various combinations, stents were used in 8/11, coils in 5/11, and Onyx in 3/11 procedures. At mean angiographic follow-up of 200 days, 8/9 aneurysms were completely occluded by endovascular means alone requiring no further treatment and 1/9 aneurysms required surgical bypass/trapping after one failed surgical and two failed endovascular treatments. At mean clinical follow-up of 416 days, modified Rankin Scale scores were improved in six patients, stable in two, and worsened in one patient. One complication occurred in 11 procedures (9%), resulting in a permanent neurologic deficit. No unintended endovascular parent vessel sacrifice, intraprocedural aneurysmal ruptures, antiplatelet-related complications, post-treatment aneurysmal re-ruptures, or deaths occurred. CONCLUSION This series highlights both the spectrum and limitations of endovascular techniques currently used to treat blister aneurysms, including a novel application of stent-assisted Onyx embolization. Long-term follow-up and experience in larger studies are required to better define the role of endovascular therapy in the management of these difficult lesions.


title: Response to dopamine in prematurity: a biomarker for brain injury?

text: OBJECTIVE To identify factors associated with responsiveness to dopamine therapy for hypotension and the relationship to brain injury in a cohort of preterm infants. STUDY DESIGN The pharmacy database at St Louis Children's Hospital was retrospectively queried to identify infants who (a) were born <28 weeks gestation between 2012 and 2014, (b) received dopamine and (c) had blood pressure measurements from an umbilical arterial catheter. A control group was constructed from contemporaneous infants who did not receive dopamine. Mean arterial blood pressure (MABP) at baseline, 1 h and 3 h after initiating dopamine were obtained for each dopamine-exposed infant. MABP measurements at matched time points were obtained in the control group. RESULT Sixty-nine dopamine-treated and 45 control infants were included. Mean ΔMABP at 3 h was 4.5±6.3 mm of Hg for treated infants vs 1±2.9 for the control. Median dopamine starting dose was 2.5 μg kg(-1) min(-1). Dopamine-treated infants were less mature and of lower birth weight while also more likely to be intubated at 72 h, diagnosed with intraventricular hemorrhage (IVH) and to die. Failure to respond to dopamine was associated with greater likelihood of developing IVH (odds ratio (OR) 5.8, 95% confidence interval (CI) 1.1-42.3), while a strong response (ΔMABP>10 mm Hg) was associated with a reduction in risk of IVH (OR 0.1, 95% CI 0.01-0.8). CONCLUSION Low-moderate dose dopamine administration results in modest blood pressure improvements. A lack of response to dopamine is associated with a greater risk of IVH, whereas a strong response is associated with a decreased risk. Further research into underlying mechanisms and management strategies is needed.


title: Construction and immunogenic studies of a mFc fusion receptor binding domain (RBD) of spike protein as a subunit vaccine against SARS-CoV-2 infection.

text: Herein, we report that a recombinant fusion protein, containing a 457 amino acid SARS-CoV-2 receptor binding domain (RBD, residues 319-541) and a mouse IgG1 Fc domain, could induce highly potent neutralizing antibodies and stimulate humoral and cellular immunity in mice. The antibodies also effectively suppressed SARS-CoV-2 RBD binding to soluble ACE2, indicating that RBD-mFc may be further developed as a safe and effective SARS-CoV-2 vaccine.


title: Organising a COVID-19 Triage Unit: a Swiss Perspective.

text: BACKGROUND With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. METHODS Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. OBSERVATIONS A total of 1,265 patients were screened between March 10th 2020 and April 12th 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p<0.001). CONCLUSION Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems.


title: A proposal for the addressing the needs of the pediatric pulmonary work force.

text: Unprecedented opportunities and daunting difficulties are anticipated in the future of pediatric pulmonary medicine. To address these issues and optimize pediatric pulmonary training, a group of faculty from various institutions met in 2019 and proposed specific, long-term solutions to the emerging problems in the field. Input on these ideas was then solicited more broadly from faculty with relevant expertise and from recent trainees. This proposal is a synthesis of these ideas. Pediatric pulmonology was among the first pediatric specialties to be grounded deliberately in science, requiring its fellows to demonstrate expertise in scientific inquiry (1). In the future, we will need more training in science, not less. Specifically, the scope of scientific inquiry will need to be broader. The proposal outlined below is designed to help optimize the practices of current providers and to prepare the next generation to be leaders in pediatric care in the future. We are optimistic that this can be accomplished. Our broad objectives are (a) to meet the pediatric subspecialty workforce demand by increasing interest and participation in pediatric pulmonary training; (b) to modernize training to ensure that future pediatric pulmonologists will be prepared clinically and scientifically for the future of the field; (c) to train pediatric pulmonologists who will add value in the future of pediatric healthcare, complemented by advanced practice providers and artificial intelligence systems that are well-informed to optimize quality healthcare delivery; and (d) to decrease the cost and improve the quality of care provided to children with respiratory diseases.


title: Adjunctive Treatment with Rhodiola Crenulata in Patients with Chronic Obstructive Pulmonary Disease--A Randomized Placebo Controlled Double Blind Clinical Trial.

text: UNLABELLED Chronic obstructive pulmonary disease (COPD) is a low grade systemic inflammatory disease characterized by dyspnea and exercise intolerance even under standard therapy. Rhodiola crenulata (RC) has been shown to exert anti-inflammatory effects and to enhance exercise endurance, thereby having the potential to treat COPD. In this 12-week, randomized, double-blind, placebo-controlled clinical trial, 57 patients with stable moderate-to-severe COPD aged 70±8.8 years were given RC (250 mg twice/day) (n=38) or a placebo (250 mg twice/day) (n=19) in addition to their standard regimen. There were no significant differences in anthropometrics, quality of life, lung function, six-minute walk and incremental exercise tests between the two groups at enrollment. Over the 12 weeks, RC was well tolerated, significantly reduced triceps skin thickness (Δ=-1 mm, p=.04), change of FEV1 (4.5%, p=.03), and improved workload (Δ=10%, p=.01); although there were no significant differences in these factors between the two groups. However, there were significant between-group differences in tidal volume and ventilation-CO2-output ratio at peak exercise (both p=.05), which were significantly related to peak work rate (both p<.0001). RC tended to protect against acute exacerbation of COPD (p=.1) but not other measurements. RC did not improve the six-minute walk test distance but significantly improved tidal breathing and ventilation efficiency, most likely through improvements in work rate. Further studies with a larger patient population are needed in order to confirm these findings. TRIAL REGISTRATION ClinicalTrials.gov number NCT02242461.


title: Laparoendoscopic single-site surgery in kidney surgery: clinical experience and future perspectives.

text: Laparoscopic surgery of the upper urinary tract has reduced the morbidity related to large abdominal incisions and has resulted in significant advantages over open surgery. Nevertheless, the pursuit for even more minimally invasive alternatives to laparoscopy has led to the concept of scarless surgery and the approach of laparoendoscopic single-site surgery (LESS). LESS is currently a feasible approach for the majority of kidney surgical procedures, and there is intense debate regarding its efficiency and advantages. In the present review of the literature, the current status of upper urinary LESS and its advantages and disadvantages, as well the technological and technical evolution, are presented.


title: Prophylactic Negative Pressure Wound Therapy for Obese Women After Cesarean Delivery: A Systematic Review and Meta-analysis.

text: OBJECTIVE To summarize available studies on wound complication outcomes after prophylactic negative pressure wound therapy for obese women (body mass index 30 or greater). DATA SOURCES We conducted a systematic review and meta-analysis using electronic database search (PubMed, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Google scholar, and Web of Science), Cochrane, and trial registries including ClinicalTrials.gov. METHODS OF STUDY SELECTION We conducted an electronic search of research articles from 1966 to January 2017 for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies of negative pressure wound therapy compared with standard dressing after cesarean delivery among obese women. Our primary outcome was defined as a composite of wound complication, including wound or surgical site infection, cellulitis, seroma, hematoma, wound disruption, or dehiscence. For cohort studies and RCTs, we performed a descriptive systematic review. For available RCTs, we performed a meta-analysis and pooled risk ratios using a random-effects model. We assessed for heterogeneity using χ test for heterogeneity and I test. We assessed for publication bias using a funnel plot. TABULATION, INTEGRATION, AND RESULTS Of 10 studies meeting eligibility criteria, five were RCTs and five were cohort studies. Results of cohort studies were varied; however, all had a high potential for selection bias. In the meta-analysis, there was no difference in primary composite outcome among those women with negative pressure wound therapy (16.8%) compared with those who had standard dressing (17.8%) (risk ratio 0.97, 95% CI 0.63-1.49). There was no statistically significant heterogeneity (χ test 4.80, P=.31, I=17%). CONCLUSION Currently available evidence does not support negative pressure wound therapy use among obese women for cesarean wound complication prevention. SYSTEMATIC REVIEW REGISTRATION PROSPERO: International prospective register of systematic reviews, 42016033948.


title: Endovascular Therapy and Ethnic Disparities in Stroke Outcomes.

text: Background and Purpose Ethnic disparities in stroke are well described, with a higher incidence of disability and increased mortality in Blacks versus Whites. We sought to compare the clinical outcomes between those ethnic groups after stroke endovascular therapy (ET). Methods We performed a retrospective review of the prospectively acquired Grady Endovascular Stroke Outcomes Registry between September 1, 2010 and September 30, 2015. Patients were dichotomized into two groups - Caucasians and African-Americans - and matched for age, pretreatment glucose level, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Baseline characteristics as well as procedural and outcome parameters were compared. Results Out of the 830 patients treated with ET, 308 pairs of patients (n = 616) underwent primary analysis. African-Americans were younger (p < 0.01), had a higher prevalence of hypertension (p < 0.01) and diabetes (p = 0.04), and had higher Alberta Stroke Program Early CT Score values (p = 0.03) and shorter times to treatment (p = 0.01). Blacks more frequently had Medicaid coverage and less private insurance (29.6 vs. 11.4% and 41.5 vs. 60.3%, respectively, p < 0.01). The remaining baseline characteristics, including baseline NIHSS score and CT perfusion-derived ischemic core volumes, were well balanced. There were no differences in the overall distribution of 90-day modified Rankin scale scores (p = 0.28), rates of successful reperfusion (84.7 vs. 85.7%, p = 0.91), good outcomes (49.1 vs. 44%, p = 0.24), or parenchymal hematomas (6.5 vs. 6.8%, p = 1.00). Blacks had lower 90-day mortality rates (18 vs. 24.6%, p = 0.04) in univariate analysis, which persisted as a nonsignificant trend after adjustment for potential confounders (OR 0.52, 95% CI 0.26-1.03, p = 0.06). Conclusions Despite unique baseline characteristics, African-Americans treated with ET for large vessel occlusion strokes have similar outcomes as Caucasians. Greater availability of ET may diminish the ethnic/racial disparities in stroke outcomes.


Patient-Centered, Gynecology-Specific Prioritization of Non-urgent Surgeries During the COVID-19 Pandemic: Proposal of a Novel Scoring System.


title: Therapeutic application of CCK2R-targeting PP-F11: influence of particle range, activity and peptide amount.

text: BACKGROUND Targeted radionuclide therapy with high-energy beta-emitters is generally considered suboptimal to cure small tumours (<300 mg). Tumour targeting of the CCK2 receptor-binding minigastrin analogue PP-F11 was determined in a tumour-bearing mouse model at increasing peptide amounts. The optimal therapy was analysed for PP-F11 labelled with (90)Y, (177)Lu or (213)Bi, accounting for the radionuclide specific activities (SAs), the tumour absorbed doses and tumour (radio) biology. METHODS Tumour uptake of (111)In-PP-F11 was determined in nude mice bearing CCK2 receptor-transfected A431 xenografts at 1 and 4 h post-injection for escalating peptide masses of 0.03 to 15 nmol/mouse. The absorbed tumour dose was estimated, assuming comparable biodistributions of the (90)Y, (177)Lu or (213)Bi radiolabelled peptides. The linear-quadratic (LQ) model was used to calculate the tumour control probabilities (TCP) as a function of tumour mass and growth. RESULTS Practically achievable maximum SAs for PP-F11 labelled with (90)Y and (177)Lu were 400 MBq (90)Y/nmol and 120 MBq(177)Lu/nmol. Both the large elution volume from the 220 MBq (225)Ac generator used and reaction kinetics diminished the maximum achieved (213)Bi SA in practice: 40 MBq (213)Bi/nmol. Tumour uptakes decreased rapidly with increasing peptide amounts, following a logarithmic curve with ED50 = 0.5 nmol. At 0.03 nmol peptide, the (300 mg) tumour dose was 9 Gy after 12 MBq (90)Y-PP-F11, and for (111)In and (177)Lu, this was 1 Gy. A curative dose of 60 Gy could be achieved with a single administration of 111 MBq (90)Y labelled to 0.28 nmol PP-F11 or with 4 × 17 MBq (213)Bi (0.41 nmol) when its α-radiation relative biological effectiveness (RBE) was assumed to be 3.4. Repeated dosing is preferable to avoid complete tumour receptor saturation. Tumours larger than 200 mg are curable with (90)Y-PP-F11; the other radionuclides perform better in smaller tumours. Furthermore, (177)Lu is not optimal for curing fast-growing tumours. CONCLUSIONS Receptor saturation, specific radiopharmaceutical activities and absorbed doses in the tumour together favour therapy with the CCK2 receptor-binding peptide PP-F11 labelled with (90)Y, despite its longer β-particle range in tissue, certainly for tumours larger than 300 mg. The predicted TCPs are of theoretical nature and need to be compared with the outcome of targeted radionuclide experiments.


title: Health-related quality of life scores of typically developing children and adolescents around the world: a meta-analysis with meta-regression.

text: PURPOSE In the context of identifying consequences and evaluating interventions for rare diseases, health-related quality of life (HRQL) measures are often used. Conclusions about HRQL are difficult to make as the participants are likely drawn from different countries. A global estimate of HRQL with estimates of variation would permit pooling of data from diverse sources. The aim was to estimate a global HRQL score of typically developing children and adolescents on the Pediatric Quality of Life Inventory (PedsQL™) and to identify sources of variation across studies. METHODS A systematic search was conducted in December 2018 on four databases: MEDLINE, EMBASE, CINAHL and PsycINFO. Inclusion criteria were all population health studies or validation studies using the self-report version of the PedsQL™ for typically developing children aged 5 to 18 years. Quality appraisal was conducted using the Appraisal Tool for Cross-Sectional Studies. Meta-analysis and meta-regression were conducted. RESULTS A total of 66 studies with a sample size of 67,805 participants were included in this analysis. The average QOL score across all studies was 80.9 (CI 78.6-83.2). Univariate analyses showed that region, minimum age of sample and income of country, was associated with the total HRQL score. Subgroup analysis showed that there was an effect of age and region on HRQL scores. CONCLUSION Results of this review provide ranges of pediatric HRQL across personal factors and regions that can be used for normative comparisons of HRQL. Interpretation of scores on generic measures should always take into consideration the contextual influences in the child's life. REGISTRATION PROSPERO, CRD42019128313 https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019128313.


title: Vascular wall components in thrombi obtained by acute stroke thrombectomy: clinical significance and related factors.

text: BACKGROUND AND PURPOSE Vascular wall components (VWCs) are sometimes identified as collagen fibers in specimens retrieved by thrombectomy from acute stroke patients. However, their clinical significance and associated factors remain unclear. The purpose of this study was to clarify the factors associated with VWCs in retrieved thrombi. METHODS Consecutive acute stroke patients treated endovascularly using the Penumbra aspiration catheter or stent retrievers (SRs) at our institute from November 2013 to April 2016 were retrospectively reviewed, and the retrieved thrombi were evaluated histopathologically. VWCs were defined as banded collagen fibers with a distinct boundary observed at the rim or outside of the retrieved thrombi. Factors associated with the presence of VWCs were studied. RESULTS A total of 150 specimens (76 specimens retrieved by the Penumbra, 74 by SRs) from 101 patients (47 women, age 74.9±11.1 years) were investigated. Applied thrombectomy devices were aspiration catheters in 42 patients, SRs in 21 patients, and both in 38 patients. VWCs were observed in 24 specimens (16%) from 22 patients. A low proportion of erythrocyte components (41.7±24.8% vs 55.0±26.3%, P=0.01), a high frequency of the devices reaching the M2/P2 (75% vs 50%, P=0.02), and a high number of device passages (P for trend=0.02) were associated with VWC positive thrombi. Successful recanalization (Treatment in Cerebral Ischemia ≥2b) tended to be less frequent in patients with VWC positive thrombi than in those without (73% vs 89%, P=0.06). CONCLUSIONS The histopathology of occlusive thrombi, arterial sites where devices reached, and number of device passages, might affect the presence of VWCs in retrieved thrombi.


title: Procurement of lungs for transplantation following donation after circulatory death: the Alfred technique.

text: INTRODUCTION Donation after circulatory death (DCD) is an evolving method for lung transplantation (LTx) with results comparable to donation after brain death (DBD). MATERIALS AND METHODS DCD lung transplant program requires a systematic approach for an efficient utilization of hospital resources. The surgical techniques have been developed to minimize the ischemic time during lung procurement. We have presented our management protocol and the surgical techniques as used at the Alfred Hospital in Melbourne, Australia. RESULTS We have transplanted 92 recipients with lungs procured from 91 donors over an 8 year period from May 2006 to July 2014. This accounted for an extra 19% lung transplant operations performed during this time period. Operative mortality was 1% and 8 year survival was 71% in DCD lung recipients. CONCLUSIONS DCD lung transplantation provides an additional significant pool of lung donors with satisfactory short and long term outcomes.


title: Isolation and antimicrobial activities of actinobacteria closely associated with liquorice plants Glycyrrhiza glabra L. and Glycyrrhiza inflate BAT. in Xinjiang, China.

text: A total of 218 actinobacteria strains were isolated from wild perennial liquorice plants Glycyrrhiza glabra L. and Glycyrrhiza. inflate BAT. Based on morphological characteristics, 45 and 32 strains from G. inflate and G. glabra, respectively, were selected for further analyses. According to 16S rRNA sequence analysis, most of the strains belonged to genus Streptomyces and a few strains represented the rare actinobacteria Micromonospora, Rhodococcus and Tsukamurella. A total of 39 strains from G. inflate and 27 strains from G. glabra showed antimicrobial activity against at least one indicator organism. The range of the antimicrobial activity of the strains isolated from G. glabra and G. inflate was similar. A total of 34 strains from G. inflate and 29 strains from G. glabra carried at least one of the genes encoding polyketide synthases, non-ribosomal peptide synthetase and FADH2-dependent halogenase. In the type II polyketide synthase KSα gene phylogenetic analysis, the strains were divided into two major clades: one included known spore pigment production-linked KSα sequences and other sequences were linked to the production of different types of aromatic polyketide antibiotics. Based on the antimicrobial range, the isolates that carried different KSα types were not separated from each other or from the isolates that did not carry KSα. The incongruent phylogenies of 16S rRNA and KSα genes indicated that the KSα genes were possibly horizontally transferred. In all, the liquorice plants were a rich source of biocontrol agents that may produce novel bioactive compounds.


Modification of existing occupational therapeutic protocols in response to new normal life after COVID 19: Letter to the Editor.


title: A randomized, double-blind comparison of licorice versus sugar-water gargle for prevention of postoperative sore throat and postextubation coughing.

text: BACKGROUND One small study suggests that gargling with licorice before induction of anesthesia reduces the risk of postoperative sore throat. Double-lumen tubes are large and thus especially likely to provoke sore throats. We therefore tested the hypothesis that preoperative gargling with licorice solution prevents postoperative sore throat and postextubation coughing in patients intubated with double-lumen tubes. METHODS We enrolled 236 patients having elective thoracic surgery who required intubation with a double-lumen endotracheal tube. Patients were randomly assigned to gargle 5 minutes before induction of anesthesia for 1 minute with: (1) Extractum Liquiritiae Fluidum (licorice 0.5 g); or (2) Sirupus Simplex (sugar 5 g); each diluted in 30 mL water. Sore throat and postextubation coughing were evaluated 30 minutes, 90 minutes, and 4 hours after arrival in the postanesthesia care unit, and the first postoperative morning using an 11-point Likert scale by an investigator blinded to treatment. RESULTS The incidence of postoperative sore throat was significantly reduced in patients who gargled with licorice rather than sugar-water: 19% and 36% at 30 minutes, 10% and 35% at 1.5 hours, and 21% and 45% at 4 hours, respectively. The corresponding estimated treatment effects (relative risks) were 0.54 (95% CI, 0.30-0.99, licorice versus sugar-water; P = 0.005), 0.31 (0.14-0.68) (P < 0.001), and 0.48 (0.28-0.83) (P < 0.001). CONCLUSION Licorice gargling halved the incidence of sore throat. Preinduction gargling with licorice appears to be a simple way to prevent a common and bothersome complication.


title: Hemodynamic outcomes of the Ross procedure versus other aortic valve replacement: a systematic review and meta-analysis.

text: INTRODUCTION Life expectancy in young adults undergoing mechanical or bioprosthetic aortic valve replacement (AVR) may be reduced by up to 20 years compared to age matched controls. The Ross procedure is a durable, anticoagulation-sparing alternative. We performed a systematic review and meta-analysis to compare the valve hemodynamics of the Ross procedure versus other AVR. EVIDENCE ACQUISITION We searched Cochrane CENTRAL, MEDLINE and EMBASE from inception to February 2017 for randomized controlled trials (RCTs) and observational studies (n≥10 Ross). Independently and in duplicate, we performed title and abstract screening, full-text eligibility assessment, and data collection. We evaluated the risk of bias with the Cochrane and CLARITY tools, and the quality of evidence with the GRADE framework. EVIDENCE SYNTHESIS We identified 2 RCTs and 13 observational studies that met eligibility criteria (N.=1412). In observational studies, the Ross procedure was associated with a lower mean aortic gradient at discharge (MD -9 mmHg, 95% CI: -13 to -5, P<0.0001, I2=97%) and latest follow-up (MD -5 mmHg, 95% CI: -7 to -3, P<0.0001, I2=92%). There was no significant difference in the incidence of severe aortic regurgitation at latest follow-up (RR 1.3, 95% CI: 0.3 to 5.8, P=0.70, I2=30%). In RCTs, the Ross procedure was associated with a lower mean gradient at latest follow-up (MD -15 mmHg, 95% CI: -32 to 2, P=0.08, I2=99%). The mean pulmonic gradient for the Ross procedure was 18.0 mmHg (95% CI: 16 to 20, P<0.0001) at latest follow-up. The evidence for all outcomes from observational studies was deemed to be of very low quality, while the evidence from RCTs was downgraded for imprecision and moderately serious risk of bias. CONCLUSIONS Compared to conventional AVR, the Ross procedure was associated with better aortic valve hemodynamics. Future studies should evaluate the impact of the Ross procedure on exercise capacity and quality of life.


title: Viroporin activity of the JC polyomavirus is regulated by interactions with the adaptor protein complex 3.

text: Viroporins, which are encoded by a wide range of animal viruses, oligomerize in host cell membranes and form hydrophilic pores that can disrupt a number of physiological properties of the cell. Little is known about the relationship between host cell proteins and viroporin activity. The human JC polyomavirus (JCV) is the causative agent of progressive multifocal leukoencephalopathy. The JCV-encoded agnoprotein, which is essential for viral replication, has been shown to act as a viroporin. Here we demonstrate that the JCV agnoprotein specifically interacts with adaptor protein complex 3 through its δ subunit. This interaction interrupts adaptor protein complex 3-mediated vesicular trafficking with suppression of the targeting of the protein to the lysosomal degradation pathway and instead permits the transport of agnoprotein to the cell surface with resulting membrane permeabilization. The findings demonstrate a previously undescribed paradigm in virus-host interactions allowing the host to regulate viroporin activity and suggest that the viroporins of other viruses may also be highly regulated by specific interactions with host cell proteins.


Medically Vulnerable Clinicians and Unnecessary Risk During the COVID-19 Pandemic.


title: Spontaneous resolution of postoperative chylothorax following surgery for persistent right aortic arch in two dogs.

text: Two young dogs underwent surgical management of a persistent right aortic arch (PRAA) and developed chylothorax postoperatively. In both cases, the surgical procedure and anesthetic recovery were uncomplicated and routine. Following surgery, both patients appeared bright, alert, responsive, and previous signs of regurgitation had resolved. Dyspnea and tachypnea developed 1-2 days postoperatively in each patient, and chylous effusion was detected on thoracocentesis. For each case, a diagnosis of chylothorax was based on cytology and triglyceride concentrations of the aspirated pleural fluid. Similar protocols for monitoring were used in the treatment of each patient's chylothorax. The duration and volume of chylous effusion production were closely monitored via routine thoracostomy tube aspiration. Both dogs rapidly progressed to recovery with no additional complications. With diligent monitoring, chylothorax secondary to surgical trauma can resolve in a rapid, uncomplicated manner.


title: Bladder neck plication stitch: a novel technique during robot-assisted radical prostatectomy to improve recovery of urinary continence.

text: BACKGROUND AND PURPOSE Efforts to improve postprostatectomy incontinence have led to many modifications in surgical technique. We present our experience with a novel technique to improve continence outcomes in patients who are undergoing robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS A consecutive series of 159 patients after initiation of a bladder neck plication stitch was compared with the most recent group before the change. After completion of the vesicourethral anastomosis, a single suture was used to plicate the distal bladder neck. A structured questionnaire was used for follow-up. Continence criteria used were 1 pad per day for social continence and 0 pad per day for total continence. RESULTS A total of 334 patients were included in the study: 159 in the plication stitch group vs 175 in the control group. Average age was 59.1 vs 59.6 years, average body mass index was 27.9 vs 28.3 kg/m(2), and average prostate volume was 58.1 vs 60.9 cc, respectively. The mean time to reach social continence was 3.63±3.01 vs 5.33±4.89 weeks (P=0.004), and total continence was 5.10±3.80 vs 8.49±6.32 weeks (P=0.002), respectively. Chance of total continence improved with the bladder plication stitch: Odds ratio of 1.95±0.72 (P<0.001) at 1 month, 1.25±0.56 (P=0.113) at 3 months, and 2.07±0.66 (P=0.005) at 12 months. There were no bladder neck contractures or other urinary complications noted in either group. CONCLUSIONS The bladder plication stitch is a simple and effective technical modification for shortening the period of recovery of urinary continence in RARP patients. Randomized controlled trials are under way to further evaluate this technique.


Applying Harm Reduction Principles to Address Screen Time in Young Children Amidst the COVID-19 Pandemic.


title: Effect of aspirin continuation on blood loss and postoperative morbidity in patients undergoing laparoscopic cholecystectomy or colorectal cancer resection.

text: No consensus exists whether to continue or withdraw aspirin therapy perioperatively in patients undergoing major laparoscopic abdominal surgery. To investigate whether preoperative continuation of aspirin therapy increases blood loss and associated morbidity during laparoscopic cholecystectomy and colorectal cancer resection, we compared duration of surgical procedures, amount of intraoperative blood loss, rate of blood transfusion, length of postoperative stay, rate of conversion to open surgery, and reoperation within 48 hours between patients with and without aspirin therapy preoperatively. Twenty-nine of 270 patients who underwent laparoscopic cholecystectomy and 23 of 218 patients who underwent laparoscopic colorectal cancer resection, respectively, were on aspirin therapy. We found no significant difference in the investigated outcome between groups with the exception of longer surgical duration of laparoscopic cholecystectomy in aspirin-treated patients. Although underpowered, above findings may suggest that aspirin continuation is unlikely to increase blood loss or postoperative morbidity in patients undergoing laparoscopic cholecystectomy or colorectal cancer resection.


title: Atypical antipsychotic medications are independently associated with severe obstructive sleep apnea.

text: BACKGROUND Atypical antipsychotic (AA) medications are widely prescribed for their Food and Drug Administration-approved uses (acute mania, bipolar mania, psychotic agitation, bipolar maintenance, etc) and off-label indications. Although AA medications are associated with substantial weight gain, their tranquilizing effects may independently contribute to risk of obstructive sleep apnea (OSA) perhaps, by a reduction in activity of hypoglossal or recurrent activity of laryngeal nerve on the upper motor airway musculature. METHODS We hypothesized that AA medications are associated with more severe OSA independent of weight and neck circumference. Medical intake data and polysomnographic studies of patients referred to community hospital sleep disorders center were analyzed retrospectively. RESULTS Mean age of patients was 49.1 years, 55.1% were male, and mean body mass index (BMI) was 33.8 kg/m. Sixty-eight patients (8.1%) were taking AA at the time of polysomnography. There were no differences in age, sex, neck circumference and BMI of AA versus non-AA patients. The mean (SE) apnea-hypopnea index values were 29.2 (3.5)/h in AA patients and 21.3 (0.8)/h in non-AA patients (P = 0.03). Thirty-four percent of AA patients had severe OSA (apnea-hypopnea index > 30/h) compared with 23% of non-AA patients (P = 0.04). When adjusted for BMI, sex, and use of benzodiazepines and sleeping aids, the odds ratios of severe OSA in AA patients were 1.9 times in non-AA patients (95% confidence interval, 1.1-3.3). CONCLUSIONS Atypical antipsychotic medication use may increase the risk of more severe OSA independent of weight and neck circumference.


title: Ulnar collateral ligament strain of the thumb metacarpophalangeal joint: biomechanical comparison of two postoperative immobilization techniques.

text: BACKGROUND The aim of this study was to compare postoperative immobilization techniques of the thumb metacarpophalangeal (MP) ulnar collateral ligament (UCL) in a cadaver model of a noncompliant patient. METHODS A cadaveric model with fresh-frozen forearms was used to simulate pinch under two immobilization conditions: (1) forearm-based thumb spica splint alone and (2) forearm-based thumb spica splint with supplemental transarticular MP Kirschner wire fixation. Pinch was simulated by thumb valgus loading and flexor pollicis longus (FPL) loading. Ulnar collateral ligament displacements were measured and strain values calculated. Statistical analysis was performed using a repeated measures analysis of variance model. RESULTS With valgus thumb loading, we noted a significantly lower UCL strain in the splint and pin group compared to splint immobilization alone. Increased load was associated with a statistically significant increase in UCL strain within each immobilization condition. FPL loading resulted in negative displacement, or paradoxical shortening, of the UCL in both immobilization groups. CONCLUSIONS While immobilized, valgus thumb force, as opposed to MP flexion, is a likely contributor to UCL strain during simulated pinch representing noncompliance during the postoperative period. Supplemental thumb MP pin fixation more effectively protects the UCL from valgus strain. UCL shortening with FPL loading likely represents paradoxical MP extension due to flexion of the distal phalanx against the distal splint, suggesting attempted thumb flexion with splint immobilization alone does not jeopardize UCL repair. CLINICAL RELEVANCE This study provides a foundation to aid clinical decision-making after UCL repair. It reinforces the practice of surgeons who routinely pin their MP joints, but also brings to attention that the use of temporary MP pin fixation may be considered in difficult cases, such as those with potential noncompliance or tenuous repair.


title: Biochemical characterization of plasmepsin V from Plasmodium vivax Thailand isolates: Substrate specificity and enzyme inhibition.

text: Plasmepsin V (PMV) is a Plasmodium aspartic protease responsible for the cleavage of the Plasmodium export element (PEXEL) motif, which is an essential step for export of PEXEL containing proteins and crucial for parasite viability. Here we describe the genetic polymorphism of Plasmodium vivax PMV (PvPMV) Thailand isolates, followed by cloning, expression, purification and characterization of PvPMV-Thai, presenting the pro- and mature-form of PvPMV-Thai. With our refolding and purification method, approximately 1mg of PvPMV-Thai was obtained from 1g of washed inclusion bodies. Unlike PvPMV-Ind and PvPMV-Sal-1, PvPMV-Thai contains a four-amino acid insertion (SVSE) at residues 246-249. We have confirmed that this insertion did not interfere with the catalytic activity as it is located in the long loop (R241-E272) pointing away from the substrate-binding pocket. PvPMV-Thai exhibited similar activity to PfPMV counterparts in which PfEMP2 could be hydrolyzed more efficiently than HRPII. Substrate specificity studies at P1' showed that replacing Ser by Val or Glu of the PfEMP2 peptide markedly reduced the enzyme activity of PvPMV similar to that of PfPMV whereas replacing His by Val or Ser of the HRPII peptide increased the cleavage activity. However, the substitution of amino acids at the P2 position with Glu dramatically reduced the cleavage efficiency by 80% in PvPMV in contrast to 30% in PfPMV, indicating subtle differences around the S2 binding pocket of both PfPMV and PvPMV. Four inhibitors were also evaluated for PvPMV-Thai activity including PMSF, pepstatin A, nelfinavir, and menisporopsin A-a macrocyclic polylactone. We are the first to show that menisporopsin A partially inhibits the PvPMV-Thai activity at high concentration. Taken together, these findings provide insights into recombinant production, substrate specificity and inhibition of PvPMV-Thai.


title: Cidofovir gel as treatment of follicular spicules in multiple myeloma.

text: IMPORTANCE The cause of follicular spicules in multiple myeloma (MM) is not known. OBSERVATIONS We present a case of follicular spicules in a patient with MM, which is very reminiscent of trichodysplasia spinulosa caused by a polyomavirus. No trichodysplasia spinulosa-associated polyomavirus could be isolated from the skin lesions; however, the spicules were positive for Merkel cell carcinoma virus, which is also a polyomavirus. CONCLUSIONS AND RELEVANCE Follicular spicules in MM are probably not caused by the trichodysplasia spinulosa-associated virus. Merkel cell polyomavirus could contribute to the origin of this dermatosis.


title: Thirty-day readmission and reoperation after surgery for spinal tumors: a National Surgical Quality Improvement Program analysis.

text: OBJECTIVE The goal of this study was to use a large national registry to evaluate the 30-day cumulative incidence and predictors of adverse events, readmissions, and reoperations after surgery for primary and secondary spinal tumors. METHODS Data from adult patients who underwent surgery for spinal tumors (2011-2014) were extracted from the prospective National Surgical Quality Improvement Program (NSQIP) registry. Multivariable logistic regression was used to evaluate predictors of reoperation, readmission, and major complications (death, neurological, cardiopulmonary, venous thromboembolism [VTE], surgical site infection [SSI], and sepsis). Variables screened included patient age, sex, tumor location, American Society of Anesthesiologists (ASA) physical classification, preoperative functional status, comorbidities, preoperative laboratory values, case urgency, and operative time. Additional variables that were evaluated when analyzing readmission included complications during the surgical hospitalization, hospital length of stay (LOS), and discharge disposition. RESULTS Among the 2207 patients evaluated, 51.4% had extradural tumors, 36.4% had intradural extramedullary tumors, and 12.3% had intramedullary tumors. By spinal level, 20.7% were cervical lesions, 47.4% were thoracic lesions, 29.1% were lumbar lesions, and 2.8% were sacral lesions. Readmission occurred in 10.2% of patients at a median of 18 days (interquartile range [IQR] 12-23 days); the most common reasons for readmission were SSIs (23.7%), systemic infections (17.8%), VTE (12.7%), and CNS complications (11.9%). Predictors of readmission were comorbidities (dyspnea, hypertension, and anemia), disseminated cancer, preoperative steroid use, and an extended hospitalization. Reoperation occurred in 5.3% of patients at a median of 13 days (IQR 8-20 days) postoperatively and was associated with preoperative steroid use and ASA Class 4-5 designation. Major complications occurred in 14.4% of patients: the most common complications and their median time to occurrence were VTE (4.5%) at 9 days (IQR 4-19 days) postoperatively, SSIs (3.6%) at 18 days (IQR 14-25 days), and sepsis (2.9%) at 13 days (IQR 7-21 days). Predictors of major complications included dependent functional status, emergency case status, male sex, comorbidities (dyspnea, bleeding disorders, preoperative systemic inflammatory response syndrome, preoperative leukocytosis), and ASA Class 3-5 designation (p < 0.05). The median hospital LOS was 5 days (IQR 3-9 days), the 30-day mortality rate was 3.3%, and the median time to death was 20 days (IQR 12.5-26 days). CONCLUSIONS In this NSQIP analysis, 10.2% of patients undergoing surgery for spinal tumors were readmitted within 30 days, 5.3% underwent a reoperation, and 14.4% experienced a major complication. The most common complications were SSIs, systemic infections, and VTE, which often occurred late (after discharge from the surgical hospitalization). Patients were primarily readmitted for new complications that developed following discharge rather than exacerbation of complications from the surgical hospital stay. The strongest predictors of adverse events were comorbidities, preoperative steroid use, and higher ASA classification. These models can be used by surgeons to risk-stratify patients preoperatively and identify those who may benefit from increased surveillance following hospital discharge.


title: Reinforced staplers for distal pancreatectomy.

text: PURPOSE The safety and efficacy of reinforced staplers during distal pancreatectomy (DP) remain controversial because of the small sample size. This multicenter single-arm prospective study aims to evaluate the safety and efficacy of reinforced staplers with bioabsorbable material during DP. METHODS Between October 2014 and August 2015, 121 patients scheduled for DP were enrolled in this study at 11 institutions in Japan. The primary endpoint was the incidence of clinically relevant pancreatic fistula. Protocol treatment was defined as "distal pancreatectomy using reinforced staplers." RESULTS Per-protocol analysis of 105 patients was performed; 16 of the patients were excluded based on discontinuation of protocol treatment criteria. Clinically relevant pancreatic fistula occurred in 13 (12.4%) of 105 patients. The overall morbidity rate was 29.5% (31 of 105 patients) and severe complication (Clavien classification IIIa or more) was 10.5% (11/105). Mortality rate was 0%, although reoperations were performed on two patients (1.9%). Multivariate logistic regression analysis of independent risk factors for clinically relevant pancreatic fistula after DP using reinforced stapler closure was operative time more than 240 min (P = 0.047, odds ratio 5.79), registration numbers less than 10 (P = 0.046, odds ratio 13.01), and staple line hemorrhage (P = 0.003, odds ratio 16.34). CONCLUSION This study confirms the safety of reinforced staplers for pancreatic stump closure during DP. However, the efficacy of reinforced staplers for decreasing clinically relevant pancreatic fistula could not be drawn from this study. TRIAL REGISTRATION This prospective study was registered with ClinicalTrials.gov (NCT02270554) and UMIN Clinical Trial Registry (UMIN000015384).


title: Blood perfusion in Hewes tarsoconjunctival flaps in pigs measured by laser speckle contrast imaging.

text: Background Hewes flap is a tarsoconjunctival eyelid flap, based at the lateral canthal tendon, and rotated and stretched to repair lateral defects in the lower eyelid commonly following tumor surgery. The aim of the present study was to monitor perfusion in a Hewes flap during reconstruction, which to the best of our knowledge, has not previously been done. Methods A Hewes tarsoconjunctival eyelid flap was raised and the effects on blood perfusion of rotating the flaps by 90° and 180°, stretching the flaps with a force of 5 or 10 N, and repeated diathermic coagulation was monitored with laser speckle contrast imaging. Results Rotating the flaps by 90° did not significantly affect perfusion, while further rotation to 180° reduced blood perfusion to 75% of the baseline value. When the tarsoconjunctival flaps were both rotated 90° and stretched with 5 N, the perfusion was reduced even further, to 63%. A further reduction in perfusion, to 36%, was seen when the higher force of 10 N was applied. Diathermy decreased blood perfusion to 56% after being applied once. Successive applications led to further decreases: 43%, 31%, and 15%, after the second, third and fourth applications. Conclusions Perfusion in Hewes tarsoconjunctival flaps is affected by both rotation and stretching, but some perfusion is maintained despite these manipulations. Diathermy, however, has detrimental effects and should be avoided.


title: Toileting Behaviors Related to Urination in Women: A Scoping Review.

text: This scoping review explores the state of science regarding women's toileting behaviors, gaps in knowledge, and areas for future research. Online databases were searched to identify papers published in English between January 2010 through July 2019; the search identified 25 articles. The Toileting Behaviors-Women's Elimination Behaviors scale has been published in four validated language versions and used in 17 of the 25 studies. The most frequent behaviors include concern about public toilet cleanliness, delaying urination when busy or away from home, and using different toileting postures at and away from home. Determinants of toileting behaviors include environmental factors, chronic health conditions, and cognitive/psychological factors. Associations were found between toileting behaviors and lower urinary tract symptoms and between toileting postures and uroflowmetric parameters and post-void residual volume. Strategies that address modifiable determinants of toileting behaviors should be developed and tested in future research. Furthermore, little is known about the toileting behaviors and bladder health in older women and women from developing countries. Rigorous studies are needed to better understand the underlying mechanisms of toileting behaviors, the nature of associations between toileting behaviors and lower urinary tract symptoms, and effects of the environment on women's toileting behaviors.


title: Luminescent silicon nanostructures and COVID-19.

text: This Faraday Discussion volume is unique in the hundred plus year history of the Faraday Discussion series, being produced at a time of unprecedented circumstances worldwide and without the preceding Faraday Discussion conference having taken place.


title: Disease severity is associated with differential gene expression at the early and late phases of infection in nonhuman primates infected with different H5N1 highly pathogenic avian influenza viruses.

text: UNLABELLED Occasional transmission of highly pathogenic avian H5N1 influenza viruses to humans causes severe pneumonia with high mortality. To better understand the mechanisms via which H5N1 viruses induce severe disease in humans, we infected cynomolgus macaques with six different H5N1 strains isolated from human patients and compared their pathogenicity and the global host responses to the virus infection. Although all H5N1 viruses replicated in the respiratory tract, there was substantial heterogeneity in their replicative ability and in the disease severity induced, which ranged from asymptomatic to fatal. A comparison of global gene expression between severe and mild disease cases indicated that interferon-induced upregulation of genes related to innate immunity, apoptosis, and antigen processing/presentation in the early phase of infection was limited in severe disease cases, although interferon expression was upregulated in both severe and mild cases. Furthermore, coexpression analysis of microarray data, which reveals the dynamics of host responses during the infection, demonstrated that the limited expression of these genes early in infection led to a failure to suppress virus replication and to the hyperinduction of genes related to immunity, inflammation, coagulation, and homeostasis in the late phase of infection, resulting in a more severe disease. Our data suggest that the attenuated interferon-induced activation of innate immunity, apoptosis, and antigen presentation in the early phase of H5N1 virus infection leads to subsequent severe disease outcome. IMPORTANCE Highly pathogenic avian H5N1 influenza viruses sometimes transmit to humans and cause severe pneumonia with ca. 60% lethality. The continued circulation of these viruses poses a pandemic threat; however, their pathogenesis in mammals is not fully understood. We, therefore, investigated the pathogenicity of six H5N1 viruses and compared the host responses of cynomolgus macaques to the virus infection. We identified differences in the viral replicative ability of and in disease severity caused by these H5N1 viruses. A comparison of global host responses between severe and mild disease cases identified the limited upregulation of interferon-stimulated genes early in infection in severe cases. The dynamics of the host responses indicated that the limited response early in infection failed to suppress virus replication and led to hyperinduction of pathological condition-related genes late in infection. These findings provide insight into the pathogenesis of H5N1 viruses in mammals.


title: Is Bridging Necessary? A Pilot Study of Bridging versus Primary Stentriever-Based Endovascular Reperfusion in Large Anterior Circulation Strokes.

text: BACKGROUND We aimed to determine whether bridging provides additional benefits over primary stentriever-based endovascular reperfusion (SER) in patients with proximal middle cerebral artery (pMCA) strokes. METHODS Clinical and radiologic data from consecutive stroke patients with large anterior circulation infarcts involving the pMCA were analyzed. Stroke subtypes were categorized according to Trial of ORG 10172 in Acute Stroke Treatment criteria. Neurologic deficits were assessed with the National Institutes of Health Stroke Scale (NIHSS), and vessel recanalization was determined using the Thrombolysis in Cerebral Infarction scale at the end of SER. Good outcome was defined as a modified Rankin Scale (mRS) score of 2 or lesser. RESULTS Fifty-seven patients with a median age of 66 years were included. Of those, 24 received prior systemic tissue plasminogen activator and 33 received primary SER. Atrial fibrillation was more common in patients who underwent SER but there were no other between-group differences in baseline variables, procedure-related variables, or outcome parameters. Six patients died and 27 patients achieved an mRS of 2 or less at 90 days. Patients who were treated with tPA before SER needed less stentriever passes to recanalize the occluded vessel, but bridging did not impact the chances for either survival or favorable outcome. Age (odds ratio [OR], .92; 95% confidence interval [CI], .85-.98) and NIHSS score (OR, .12; 95% CI, .02-.78) were the only variables associated with outcome on multivariate analysis. CONCLUSIONS Primary SER and bridging resulted in equally high survival and good outcome rates. Our results suggest that the benefits of primary SER in such critically ill patients may bypass the need for bridging therapy and merit further study.


title: Using SELDI-TOF MS to identify serum biomarkers of rheumatoid arthritis.

text: OBJECTIVES No satisfactory biomarkers are currently available to screen for rheumatoid arthritis (RA). We have developed and evaluated surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) for detection and analysis of multiple proteins for distinguishing individuals with RA from control individuals. METHODS A total of 156 serum samples from 90 RA patients, 30 patients with ankylosing spondylitis (AS), and 36 healthy individuals were examined by SELDI technology. Spectral data were analysed by the support vector machine (SVM) approach and potential biomarkers were chosen for system training and were used to construct a diagnostic model. RESULTS Pattern 1, consisting of four protein peaks with m/z values of 3899, 4594, 7566, and 13,842, distinguished RA from the healthy samples with sensitivity of 90.0% and a specificity of 91.7%. Pattern 2, consisting of m/z peaks 4287 and 6471, distinguished RA from AS with a sensitivity of 86.7% and a specificity of 85.0%. CONCLUSION The combination of SELDI-TOF MS and SVM could facilitate the discovery of better biomarkers for RA and also provide a useful tool for molecular diagnosis in the future.


title: [Epidemiological characteristics of COVID-19 in Gansu province].

text: Objective: To understand the epidemiological characteristics of COVID-19 cases in different epidemic stages in Gansu province. Methods: Epidemiological investigation was conducted to collect the information of confirmed COVID-19 cases, including demographic, epidemiological and clinical information. Results: As of 25 February 2020, a total of 91 confirmed COVID-19 cases had been reported in Gansu. The epidemic of COVID-19 in Gansu can be divided as three different stages, i.e. imported case stage, imported-case plus indigenous case stage, and indigenous case stage. A total of 63 cases were clustered cases (69.23%), 3 cases were medical staff infected with non-occupational exposure. The initial symptoms included fever (54.95%, 50/91), cough (52.75%, 48/91), or fatigue (28.57%, 26/91), the proportion of each symptom showed a decreasing trend along with the three epidemic stages, but only the differences in proportions of fever (trend χ2=2.20, P<0.05) and fatigue (trend χ2=3.18, P<0.05) among the three epidemic stages were statistically significant. The cases with critical severe symptoms accounted for 42.85% (6/14), 23.73% (14/59) and 16.67% (3/18), respectively, in three epidemic stages, showed a decreasing trend (H=6.45, P<0.05). Also, the incubation period prolonged along with the epidemic stage (F=51.65, P<0.01), but the intervals between disease onset and hospital visit (F=5.32, P<0.01), disease onset and diagnosis (F=5.25, P<0.01) became shorter along with the epidemic stage. Additionally, the basic reproduction number (R0) had decreased from 2.61 in imported case stage to 0.66 in indigenous case stage. Conclusions: The COVID-19 epidemic in Gansu was caused by the imported cases, and about 2/3 cases were clustered ones. No medical worker was observed to be infected by occupational exposure. With the progression of COVID-19 epidemic in Gansu, the change in initial symptom and incubation period suggests, the early screening cannot only depend on body temperature monitoring.


title: Cerebral Venous Thrombosis Associated with COVID-19.

text: Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.


title: Feasibility of laparoscopic major hepatectomy for hepatic paragonimiasis: two case reports.

text: BACKGROUND Though accumulated evidence proved that laparoscopic major hepatectomy was technically feasible, it remains a challenging procedure and is limited to highly specialized centers. Paragonimiasis is one of the most important food-borne parasitic zoonoses caused by the trematode of the genus Paragonimus. Although hepatic paragonimiasis is rare, the previous studies had investigated hepatic paragonimiasis from different perspectives. However, the safety and feasibility of laparoscopic major hepatectomy for hepatic paragonimiasis have not yet been reported in the literature. METHODS We here present 2 cases of hepatic paragonimiasis at the deep parts of the liver with treatment by laparoscopic major hepatectomy. One case is a 32-year-old male patient who was admitted to the hospital due to upper abdominal discomfort without fever for 1 month. The clinical imaging revealed that there was a lesion about 5.9 × 3.7 cm in the boundary of right anterior lobe and right posterior lobe of the liver with rim enhancement and tract-like nonenhanced areas. The other one is a 62-year-old female patient who was referred to the hospital for 1 month of right upper abdominal pain and fever. The ultrasonography showed that there was a huge hypoechoic mass (about 10.8 × 6.3 cm) in middle lobe of the liver with tract-like nonenhanced areas. Both patients were from an endemic area of paragonimiasis and the proportion of eosinophil in the second case was increased. RESULTS The preoperative diagnosis of the first case was ambiguous and the hepatic paragonimiasis was considered for the second case. The first case underwent laparoscopic extended right posterior lobe hepatectomy and the other case underwent laparoscopic extended left hemihepatectomy. Both operations went very well and the operation times for the 2 cases were 275 minutes and 310 minutes, respectively. The 2 patients' postoperative recovery was smooth without major postoperative complications (such as, bleeding, bile leakage, and liver failure). Moreover, the 2 patients were discharged on the 6th day and 7th day after surgery, respectively. The postoperative histopathological examination manifested hepatic paragonimiasis in both patients. CONCLUSION This study suggests that the laparoscopic approach may be safe and technically feasible for hepatic paragonimiasis.


title: Helicobacter p ylori eradication treatment for gastric carcinoma prevention in asymptomatic or dyspeptic adults: systematic review and Bayesian meta-analysis of randomised controlled trials.

text: OBJECTIVES Recent meta-analyses of eradication therapy in Helicobacter pylori-infected adults reported significant reductions in gastric carcinoma risk. However, concerns about supporting unfocused screening and eradication programme in healthy, asymptomatic populations have arisen. We performed a systematic review and Bayesian meta-analysis to provide an accurate interpretation of randomised evidence on the preventive effectiveness of eradication therapy on gastric carcinoma risk. METHODS We searched databases including PubMed, Cochrane Central and Embase for reference and citation tracking without language restrictions, from inception through 31 July 2018. Paired investigators independently selected randomised controlled trials (RCTs) comparing eradication therapy with placebo or no treatment for asymptomatic or dyspeptic H. pylori-infected adults with no previous gastric carcinoma. The main outcome was gastric carcinoma incidence; secondary outcomes included gastric carcinoma-specific, non-gastric carcinoma and all-cause mortality. RESULTS A total of 5 population-based and 2 outpatient care-based RCTs involving 7303 adults were eligible. Eradication algorithms were heterogeneous, and unsuccessful eradication and reinfection were frequently observed. A Bayesian meta-analysis with competing risk outcomes found low-certainty evidence that eradication therapy might be more likely than control to reduce gastric carcinoma risk (HR=0.65; 95% credible interval (CrI) 0.41 to 1.0; I2 =11%). The CrIs included the null effects across the subgroup and sensitivity analyses, apart from those based on particular models that excluded two RCTs that enrolled subjects with specific histological findings only (HR=0.55; CrI 0.30 to 0.89; I2 =14%). The uncertainty of the average 41% risk reduction in gastric carcinoma-specific mortality included a clinically important mortality risk increase (HR=0.59 favouring eradication therapy; CrI 0.25 to 1.20; I2 =13%; low certainty). CONCLUSIONS There is insufficient evidence to support or refute the effectiveness of eradication therapy in preventing gastric carcinoma in H. pylori-infected, high-risk populations. Rigorously conducted large RCTs of healthy infected adults only would provide evidence of the true efficacy of successful eradication. PROSPERO registration number: CRD42014009245.


title: SUMO fusion technology for enhanced protein expression and purification in prokaryotes and eukaryotes.

text: The preparation of sufficient amounts of high-quality protein samples is the major bottleneck for structural proteomics. The use of recombinant proteins has increased significantly during the past decades. The most commonly used host, Escherichia coli, presents many challenges including protein misfolding, protein degradation, and low solubility. A novel SUMO fusion technology appears to enhance protein expression and solubility ( http://www.lifesensors.com ). Efficient removal of the SUMO tag by SUMO protease in vitro facilitates the generation of target protein with a native N-terminus. In addition to its physiological relevance in eukaryotes, SUMO can be used as a powerful biotechnology tool for enhanced functional protein expression in prokaryotes and eukaryotes.