title: Parenteral vaccination of mammalian livestock with Newcastle disease virus-based vector vaccines offers optimal efficacy and safety.

text: Newcastle disease virus (NDV) is an avian virus that is being evaluated as a vaccine vector for the delivery of foreign genes in mammals. The use of NDV as a vaccine vector in these species offers two major advantages. First, NDV is highly attenuated in mammals, rendering its use inherently safe. Second, mammals lack pre-existing NDV immunity, which minimizes the risk of vaccination failure. NDV-vector vaccines are generally administered to mammals via the respiratory route. We recently showed that intramuscular vaccination with NDV-based Rift Valley fever virus (RVFV) vaccines provides complete protection in mice and induces neutralizing antibodies in sheep and cattle, the main target species of RVFV. Here, we discuss the use of NDV as a vaccine vector for applications in mammalian livestock with an emphasis on the vaccination route. We also report the results of novel experiments that underscore our notion that vaccination via a parenteral route is more effective than immunization via the respiratory route.


title: Prevalence and genomic characteristics of a novel reassortment mammalian orthoreovirus type 2 in diarrhea piglets in Sichuan, China.

text: Mammalian orthoreovirus (MRV), which can infect almost all mammals, is a zoonotic virus. In this study, six strains of type 2 MRV (MRV2) were isolated from 7 diarrhea piglets from a farm that had an outbreak of diarrhea in piglets in 2018, which tested negative for porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and porcine group A rotavirus (RAV). The MRV2 isolate infected neonatal piglets, in which it induced severe diarrhea, while the virus was detected in multiple organs of piglets. Moreover, the complete genome of an MRV2 isolate was obtained, which was a novel reassortant MRV strain of human MRV, porcine MRV, chamois MRV, bat MRV, and mink MRV based on the nucleotide identity and phylogenetic tree. The S1 gene of isolate had eight unique amino acid mutations compared with available MRV2 S1 in the GenBank. To investigate the prevalence of this MRV2, 78 samples of diarrhea feces were collected from 10 pig farms in seven regions of Sichuan province. The obtained results showed that the positive rate of samples was 14% (11/78), and positive rate of farms was 60% (6/10), while the amplified fragments shared the identical amino acid mutations with the isolated strain, thus suggesting that this MRV2 strain was already prevalent in Sichuan province. The present study was first to isolate a pig-derived type 2 MRV strain in China, obtaining the complete genome of this strain, which furthers our understanding of the MRV2 epidemic and evolution.


title: Endovascular thrombectomy in the setting of aortic dissection.

text: BACKGROUND Recent studies have validated the use of endovascular thrombectomy in large vessel ischemic stroke provided patients are selected appropriately. However, to our knowledge, there have been no previously reported cases of endovascular thrombectomy in patients with aortic dissection. We report three such cases, two with chronic aortic dissections (including one with a history of Marfan syndrome) and another with an acute type B dissection. METHODS Case studies and review of relevant literature. RESULTS Three patients with a history of aortic dissection presented with acute onset right middle cerebral artery syndromes, two of whom had chronic aortic dissections that were status-post graft repair, while a third had an acute type B aortic dissection that had been managed with a femoral-to-femoral bypass. None of the three were candidates for intravenous tissue plasminogen activator. All three were found to have proximal right M1 occlusions on non-invasive imaging and were taken for endovascular thrombectomy via transfemoral, transradial, and transbrachial approaches, respectively. All three had successful recanalization (with Thrombolysis In Cerebral Infarction (TICI) 2b, TICI 3, and TICI 2b flow, respectively) along with clinical improvement, and none had procedure-related complications. CONCLUSIONS These three cases suggest that endovascular thrombectomy is feasible and can be done safely and efficaciously in patients with aortic dissections and those with Marfan syndrome, although the risks and benefits should be considered as part of any decision-making process. Given that endovascular therapy for acute stroke is now in many situations part of standard care, further studies will be necessary to delineate more precise inclusion and exclusion criteria.


title: Sleep spindle activity and cognitive performance in healthy children.

text: STUDY OBJECTIVES To investigate the association between indices of sleep spindle activity and cognitive performance in a sample of healthy children. DESIGN Correlational. Intelligence (Stanford-Binet) and neurocognitive functioning (NEPSY) were assessed, with sleep variables being measured during overnight polysomnography. SETTING Hospital sleep laboratory. PARTICIPANTS Twenty-seven healthy children (mean age 8.19 y; 14 female, 13 male). INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Participants underwent a single night of overnight polysomnography after completing measures of intelligence and neurocognitive functioning. Sleep spindles were visually identified by an experienced sleep scoring technician and separated algorithmically into fast (> 13 Hz) and slow spindle (< 13 Hz) categories. The number of fast spindles was significantly correlated with narrative memory (r(s) = 0.38) and sensorimotor functioning (-0.43). Mean central frequency of spindles was also significantly correlated with sensorimotor functioning (-0.41), planning ability (-0.41), and working memory (-0.54). CONCLUSIONS Basal sleep spindle activity is associated with different aspects of cognitive performance in children. To the extent that these associations in a pediatric population are different from what is known in adult sleep may play an important role in development.


docid: brcysneo

title: Randomized clinical trial of fibrin glue versus tacked fixation in laparoscopic groin hernia repair.

text: BACKGROUND Preliminary studies have indicated clinical advantages of mesh fixation using fibrin glue in transabdominal preperitoneal groin hernia repair (TAPP) compared with tack fixation. The aim of this randomized double-blinded, controlled, clinical trial is to compare fibrin glue with tacks fixation of mesh during TAPP. METHODS One hundred and twelve men with unilateral inguinal hernia were enrolled. Primary outcome was pain during coughing on postoperative day 1. Secondary outcomes were postoperative scores of pain at rest, discomfort, and fatigue (day 1 and cumulated day 0-3), incidence of moderate/severe nausea and/or vomiting, foreign-body sensation, and recurrence after 6 months. Outcome measures were assessed by visual analogue scale (VAS, 0-100 mm), verbal rating scale (no, light, moderate or severe) and numerical rating scales (NRS, 1-10). RESULTS One hundred patients were available for analysis. The fibrin group (n = 50) had significantly less pain during coughing on day 1 compared with the tacks group (n = 50) [median 23 (range 0-80) vs 35 (2-100) mm] (p = 0.020). Moreover, day 1 scores and all cumulated scores of pain during rest, discomfort, and fatigue were significantly lower in the fibrin group compared with the tacks group (all p-values ≤ 0.02). There was no significant difference in the incidence of nausea and/or vomiting (p > 0.05) or recurrence (fibrin glue n = 2, tacks n = 0, p = 0.241). Incidence of foreign-body sensation was significantly lower in the fibrin group at 1 month (p = 0.006). CONCLUSIONS Fibrin glue compared with tacks fixation improved the early postoperative outcome after TAPP. The trial was registered at clinicaltrials.gov NCT01000116.


title: Acute respiratory distress syndrome and pneumothorax.

text: Acute respiratory distress syndrome (ARDS) can occur during the treatment of several diseases and in several interventional procedures as a complication. It is a difficult situation to handle and special care should be applied to the patients. Mechanical ventilation is used for these patients and several parameters are changed constantly until compliance is achieved. However, a complication that is observed during the application of positive airway pressure is pneumothorax. In our current work we will present definition and causes of pneumothorax in the setting of intensive care unit (ICU). We will identify differences and similarities of this situation and present treatment options.


title: Duodenal stump fistula after gastrectomy for gastric cancer: risk factors, prevention, and management.

text: PURPOSE A duodenal stump fistula is one of the most severe complications after gastrectomy for gastric cancer. We aimed to analyze the risk factors for this problem, and to identify the methods used for its prevention and management. METHODS We retrospectively reviewed the clinical data of 716 consecutive patients who underwent curative gastrectomy with a duodenal stump for gastric cancer between 2008 and 2013. RESULTS A duodenal stump fistula occurred in 16 patients (2.2%) and there were 2 deaths in this group. Univariate analysis revealed age >60 years (odds ratio [OR], 3.09; 95% confidence interval [CI], 0.99-9.66), multiple comorbidities (OR, 4.23; 95% CI, 1.50-11.92), clinical T stage (OR, 2.91; 95% CI, 1.045-8.10), and gastric outlet obstruction (OR, 8.64; 95% CI, 2.61-28.61) to be significant factors for developing a duodenal stump fistula. Multivariate analysis identified multiple comorbidities (OR, 3.92; 95% CI, 1.30-11.80) and gastric outlet obstruction (OR, 5.62; 95% CI, 1.45-21.71) as predictors of this complication. CONCLUSION Multiple comorbidities and gastric outlet obstruction were the main risk factors for a duodenal stump fistula. Therefore, preventive methods and aggressive management should be applied for patients at high risk.


title: Acute and critical limb ischemia: when time is limb.

text: Acute and critical limb ischemia post significant rates of morbidity and death, and need to be promptly recognized and treated to avoid amputation. Perfusion should be thoroughly assessed using multiple methods, and patients should be considered for revascularization (angioplasty or bypass surgery) to restore blood perfusion. Underlying conditions that need to be assessed and treated include cardiovascular disease, diabetes, and infection.


title: Triterpenoid gene expression and phytochemical content in Iranian licorice under salinity stress.

text: Licorice is a well-known medicinal plant, containing various secondary metabolites of triterpenoid and phenolic families. The aim of this study is to evaluate the effect of salinity stress on the expression of key genes involved in the biosynthetic pathway of triterpenoids such as glycyrrhizin, betulinic acid, soyasaponins, and phytosterols in licorice root, as well as providing a phonemic platform to characterize antioxidant properties, glycyrrhizin, and total phenolic content. This study also includes measuring the gene expression level and glycyrrhizin content in leaves and roots of control plants. The studied genes included squalene synthase (SQS1 and SQS2), β-amyrin synthase (bAS), lupeol synthase (LUS), cycloartenol synthase (CAS), β-amyrin 11-oxidase (CYP88D6), and β-amyrin 24-hydroxylase (CYP93E6). Our results revealed that all of the mentioned genes were upregulated following the stress condition with different transcription rates. The highest increase (12-fold) was observed for the expression of the LUS gene, which is related to the betulinic acid pathway. Also, the highest content of glycyrrhizin was observed at 72 h post-treatment, which was consistent with the upregulated transcription levels of the glycyrrhizin pathway genes especially SQS1 and CYP88D6 at the same time. Correlation and stepwise regression analysis proved the key role of SQS1 gene in the biosynthetic pathway of glycyrrhizin. Antioxidant activity and phenolic content also were increased following stress condition. A comparison between the expression levels of SQS1 and other genes involved in the production of glycyrrhizin, phytosterols, and soyasaponins revealed a similar transcription trend, which shows the gene expression in the roots was significantly higher than the leaves. In contrast, SQS2 and LUS genes displayed a higher expression in leaf tissues. The genes related to betulinic acid biosynthetic pathway exhibited an expression rate different from other triterpenoid pathway genes, which could be observed in the leaves and roots of control plants and the roots of salt-treated plants. Furthermore, results showed that these two SQS genes have different expression rates due to different plant tissues (roots and leaves) and stress conditions. Importantly, in contrast to previous reports, we detected the glycyrrhizin in leaf tissues. This result may indicate the presence of a different genetic background in native Iranian licorice germplasm.


title: Transient expression systems for plant-derived biopharmaceuticals.

text: In the molecular farming area, transient expression approaches for pharmaceutical proteins production, mainly recombinant monoclonal antibodies and vaccines, were developed almost two decades ago and, to date, these systems basically depend on Agrobacterium-mediated delivery and virus expression machinery. We survey here the current state-of-the-art of this research field. Several vectors have been designed on the basis of DNA- and RNA-based plant virus genomes and viral vectors are used both as single- and multicomponent expression systems in different combinations depending on the protein of interest. The obvious advantages of these systems are ease of manipulation, speed, low cost and high yield of proteins. In addition, Agrobacterium-mediated expression also allows the production in plants of complex proteins assembled from subunits. Currently, the transient expression methods are preferential over any other transgenic system for the exploitation of large and unrestricted numbers of plants in a contained environment. By designing optimal constructs and related means of delivery into plant cells, the overall technology plan considers scenarios that envisage high yield of bioproducts and ease in monitoring the whole spectrum of upstream production, before entering good manufacturing practice facilities. In this way, plant-derived bioproducts show promise of high competitiveness towards classical eukaryotic cell factory systems.


title: Magnetic Resonance Mediated Radiofrequency Ablation.

text: To introduce magnetic resonance mediated radiofrequency ablation (MR-RFA), in which the MRI scanner uniquely serves both diagnostic and therapeutic roles. In MR-RFA scanner-induced RF heating is channeled to the ablation site via a Larmor frequency RF pickup device and needle system, and controlled via the pulse sequence. MR-RFA was evaluated with simulation of electric and magnetic fields to predict the increase in local specific-absorption-rate (SAR). Temperature-time profiles were measured for different configurations of the device in agar phantoms and ex vivo bovine liver in a 1.5 T scanner. Temperature rise in MR-RFA was imaged using the proton resonance frequency method validated with fiber-optic thermometry. MR-RFA was performed on the livers of two healthy live pigs. Simulations indicated a near tenfold increase in SAR at the RFA needle tip. Temperature-time profiles depended significantly on the physical parameters of the device although both configurations tested yielded temperature increases sufficient for ablation. Resected livers from live ablations exhibited clear thermal lesions. MR-RFA holds potential for integrating RF ablation tumor therapy with MRI scanning. MR-RFA may add value to MRI with the addition of a potentially disposable ablation device, while retaining MRI's ability to provide real time procedure guidance and measurement of tissue temperature, perfusion, and coagulation.


title: Tract length predicts successful closure with anal fistula plug in cryptoglandular fistulas.

text: PURPOSE Collagen anal fistula plug treatment of transsphincteric fistulas produces variable results. The purpose of our study was to determine whether long-tract fistulas (>4 cm) correlated with successful closure. METHODS All patients undergoing transsphincteric cryptoglandular fistula repair with anal fistula plugs were enrolled in a prospective database. Patients with Crohn's disease were excluded. Fistula tract length was measured intraoperatively by subtracting the remaining plug length from the original plug size. All procedures used standardized techniques and postoperative care pathways. The primary outcome was complete fistula closure assessed through both postoperative outpatient visits and a follow-up telephone questionnaire. RESULTS Forty-one patients with 42 fistula tracks were enrolled over a 39-month period. Complete closure was achieved in 18 of 42 (43%) fistulas at a mean follow-up of 25 months. Closure was not associated with gender, age, tract location, duration of seton, or length of follow-up. Successful closure was significantly associated with increased tract length, because fistulas longer than 4 cm were nearly 3 times more likely to heal compared with shorter fistulas ((14/23, 61%) vs (4/19, 21%), P = .004; relative risk = 2.8; 95% CI 1.14-7.03). CONCLUSIONS Anal fistula plug repair of cryptoglandular anorectal fistulas is more successful for long-tract fistulas. Although the overall success is modest, limiting surgical indications to fistulas exceeding 4 cm may maximize benefits of the plug technique.


docid: grdxesgp

title: Triamcinolone acetonide activates an anti-inflammatory and folate receptor-positive macrophage that prevents osteophytosis in vivo.

text: INTRODUCTION Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently reduce osteophytosis. Although widely applied in clinical care, the mechanism through which TA exerts this effect remains unknown. In this animal study, we investigated the in vivo effects of TA injections on macrophage activation, osteophyte development and joint degeneration. Furthermore, in vitro macrophage differentiation experiments were conducted to further explain working mechanisms of TA effects found in vivo. METHODS Osteoarthritis was induced in rat knees using papain injections and a running protocol. Untreated and TA-treated animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes. Synovial macrophage activation was measured in vivo using folate receptor β (FRβ)-targeted single-photon emission computed tomography/computed tomography. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology. To further explain the outcomes of our in vivo study, TA on macrophages was also studied in vitro. These cultured macrophages were either M1- or M2-activated, and they were analyzed using fluorescence-activated cell sorting for CD163 and FRβ expression as well as for messenger RNA (mRNA) expression of interleukin (IL)-10. RESULTS Our in vivo study showed that intra-articular injections with TA strongly enhanced FRβ(+) macrophage activation. Despite stimulated macrophage activation, osteophyte formation was fully prevented. There was no beneficial effect of TA against cartilage degradation or subchondral bone sclerosis. In vitro macrophage cultures showed that TA strongly induced monocyte differentiation towards CD163(+) and FRβ(+) macrophages. Furthermore, TA-stimulated M2 macrophages showed enhanced IL-10 expression at the mRNA level. CONCLUSIONS TA injections potently induce a CD163(+)- and FRβ(+)-activated macrophage with anti-inflammatory characteristics such as reduced IL-10 production in vitro and lack of osteophytosis in vivo.


title: The diagnosis and prevalence of persistent infection with bovine viral diarrhoea virus in South African feedlot cattle.

text: Bovine viral diarrhoea virus (BVDV) infection is an important viral infection affecting the cattle industry today. The prevalence of this infection in South African feedlots is unknown. Ear notch biopsies were collected from chronic poor doers and animals that appeared unthrifty upon entering feedlots, as well as animals entering the hospital pen with respiratory disease for the first time. A total of 1690 samples were collected: 1074 from the former category and 616 from the latter. A routine immunohistochemistry staining protocol showed that 49 animals tested positive, of which 43 (4%) came from the feedlot entry group and six (1%) from the hospitalised group. The prevalence of persistently infected cattle from this selected, nonrandom sample entering six large South African feedlots was found to be 2.9%, which is higher than the international rule of thumb that 0.5% of all cattle entering feedlots are persistently infected. There was no clear correlation between persistent infection and respiratory disease. Serum samples were also collected when possible and 10 positive cases were found. Results from enzyme-linked immunosorbent assays for antigen and antibody performed on these sera correlated well with those from the immunohistochemistry staining method in six cases, but in four cases the animals tested falsely positive owing to nonspecific staining. Immunohistochemistry staining on ear notch biopsies is thus a reliable diagnostic method to identify persistently infected animals with BVDV, but the pathologist should be aware of nonspecific positive staining.


title: The Metastatic Spine Disease Multidisciplinary Working Group Algorithms.

text: The Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied.


title: Laparoscopic resection of a residual retroperitoneal tumor mass of nonseminomatous testicular germ cell tumors.

text: BACKGROUND Resection of a residual retroperitoneal tumor mass (RRRTM) is standard procedure after combination chemotherapy for metastatic nonseminomatous testicular germ cell tumors (NSTGCT). METHODS At the University Medical Center Groningen, 79 consecutive patients with disseminated NSTGCT were treated with cisplatin combination chemotherapy between 2005 and 2007. Laparoscopic RRRTM was performed for patients with RRTM located less than 5 cm ventrally or laterally from the aorta or the vena cava. The 29 patients who fulfilled the criteria had a median age of 25 years (range, 16-59 years). The stages of disease before chemotherapy treatment according to the Royal Marsden classification were 2A (n = 6, 21%), 2B (n = 14, 48%), 2C (n = 3, 10%), and 4 with a lymph node status of N2 (n = 6, 21%). RESULTS The median duration of laparoscopy was 198 min (range, 122-325 min). The median diameter of the RRTM was 21 mm (range, 11-47 mm). Laparoscopic resection was successful for 25 patients (86%). Conversion was necessary for three patients (10%): two due to bleeding and one because of obesity. One nonplanned hand-assisted procedure (3%) also had to be performed. Histologic examination of the specimens showed fibrosis or necrosis in 12 patients (41%), mature teratoma in 16 patients (55%), and viable tumor in 1 patient (3%). The median hospital stay was 1 day (range, 1-6 days). During a median follow-up period of 47 months (29-70 months), one patient experienced an early relapse (1 month after the end of treatment) (4%). CONCLUSION For properly selected patients, laparoscopic resection of RRTM is an improvement in the combined treatment of disseminated NSTGCT and associated with a short hospital stay, minimal morbidity, rapid recovery, and a neat cosmetic result. Long-term data to prove oncologic efficacy are awaited.


title: A systematic review exploring the content and outcomes of interventions to improve psychological safety, speaking up and voice behaviour.

text: BACKGROUND Having psychologically safe teams can improve learning, creativity and performance within organisations. Within a healthcare context, psychological safety supports patient safety by enabling engagement in quality improvement and encouraging staff to speak up about errors. Despite the low levels of psychological safety in healthcare teams and the important role it plays in supporting patient safety, there is a dearth of research on interventions that can be used to improve psychological safety or its related constructs. This review synthesises the content, theoretical underpinnings and outcomes of interventions which have targeted psychological safety, speaking up, and voice behaviour within a healthcare setting. It aims to identify successful interventions and inform the development of more effective interventions. METHODS A key word search strategy was developed and used to search electronic databases (PsycINFO, ABI/Inform, Academic search complete and PubMed) and grey literature databases (OpenGrey, OCLC WorldCat, Espace). Covidence, an online specialised systematic review website, was used to screen records. Data extraction, quality appraisal and narrative synthesis were conducted on identified papers. RESULTS Fourteen interventions were reviewed. These interventions fell into five categories. Educational interventions used simulation, video presentations, case studies and workshops while interventions which did not include an educational component used holistic facilitation, forum play and action research meetings. Mixed results were found for the efficacy or effectiveness of these interventions. While some interventions showed improvement in outcomes related to psychological safety, speaking up and voice, this was not consistently demonstrated across interventions. Included interventions' ability to demonstrate improvements in these outcomes were limited by a lack of objective outcome measures and the ability of educational interventions alone to change deeply rooted speaking up behaviours. CONCLUSION To improve our understanding of the efficacy or effectiveness of interventions targeting psychological safety, speaking up and voice behaviour, longitudinal and multifaceted interventions are needed. In order to understand whether these interventions are successful, more objective measures should be developed. It is recommended that future research involves end users in the design phase of interventions, target both group and organisational levels, ensure visible leader support and work across and within interdisciplinary teams. PROSPERO REGISTRATION NUMBER CRD42018100659.


title: The SAVE Technique : Large-Scale Experience for Treatment of Intracranial Large Vessel Occlusions.

text: BACKGROUND The stent retriever assisted vacuum-locked extraction (SAVE) technique was introduced as an effective thrombectomy method in stroke patients suffering from intracranial large vessel occlusion (LVO). This article presents our multicenter, large-scale experience with SAVE. METHODS The study involved a retrospective core team analysis of 200 patients undergoing mechanical thrombectomy using the SAVE technique due to intracranial LVO at 4 German centers. Primary endpoints were first-pass and overall complete/near complete reperfusion, defined as a modified thrombolysis in cerebral infarction (mTICI) score of 2c and 3. Secondary endpoints were the number of passes, time from groin puncture to reperfusion, embolization to new territories (ENT), postinterventional symptomatic intracranial hemorrhage (sICH), and favorable outcome at discharge, defined as a modified Rankin Scale (mRS) score ≤ 2. RESULTS The median age was 78 years (interquartile range IQR 68-85). Median National Institutes of Health stroke scale (NIHSS) at admission was 16 (IQR 12-20). Occlusions sites were: internal carotid artery (ICA-T) in 39/200 (19.5%), M1 in 126/200 (63%), M2 in 30/200 (15%), and others in 5/200 (2.5%) cases. The primary endpoints were documented in 114/200 (57% first pass mTICI 2c or 3) and 154/200 (77% overall mTICI 2c or 3) patients, respectively. The overall median time from groin puncture to reperfusion was 34 min (IQR 25-52) with a median of 1 (IQR 1-2) attempts. An ENT was observed in 3 patients (1.5%) and the rate of sICH was 2.6%. The rate of successful reperfusion (mTICI ≥ 2b) on final angiograms was 95%. At discharge, 73/200 (36.5%) patients revealed a favorable outcome. CONCLUSION Mechanical thrombectomy using the SAVE technique seems to be effective, fast and safe. First-line use of SAVE leads to high rates of complete and near complete reperfusion.


title: N-Myc-induced metabolic rewiring creates novel therapeutic vulnerabilities in neuroblastoma.

text: N-Myc is a transcription factor that is aberrantly expressed in many tumor types and is often correlated with poor patient prognosis. Recently, several lines of evidence pointed to the fact that oncogenic activation of Myc family proteins is concomitant with reprogramming of tumor cells to cope with an enhanced need for metabolites during cell growth. These adaptions are driven by the ability of Myc proteins to act as transcriptional amplifiers in a tissue-of-origin specific manner. Here, we describe the effects of N-Myc overexpression on metabolic reprogramming in neuroblastoma cells. Ectopic expression of N-Myc induced a glycolytic switch that was concomitant with enhanced sensitivity towards 2-deoxyglucose, an inhibitor of glycolysis. Moreover, global metabolic profiling revealed extensive alterations in the cellular metabolome resulting from overexpression of N-Myc. Limited supply with either of the two main carbon sources, glucose or glutamine, resulted in distinct shifts in steady-state metabolite levels and significant changes in glutathione metabolism. Interestingly, interference with glutamine-glutamate conversion preferentially blocked proliferation of N-Myc overexpressing cells, when glutamine levels were reduced. Thus, our study uncovered N-Myc induction and nutrient levels as important metabolic master switches in neuroblastoma cells and identified critical nodes that restrict tumor cell proliferation.


title: Neurocognitive Correlates of Internet Search Skills for eHealth Fact and Symptom Information in a Young Adult Sample.

text: As the Covid 19 crisis has revealed, the internet is a first-line tool for learning critical health-related information. However, internet searches are a complex and dynamic process that can be fraught with subtleties and potential error. The mechanics of searching for and using electronic health (eHealth) information is ostensibly cognitively demanding; yet we know little about the role of neurocognitive abilities in this regard. Fifty-six young adults completed two naturalistic eHealth search tasks: fact-finding (eHealth Fact) and symptom-diagnosis (eHealth Search). Participants also completed neurocognitive tests of attention, psychomotor speed, learning/memory, and executive functions. Shorter eHealth symptom-diagnosis search time was related to better executive functions, while better eHealth symptom-diagnosis search accuracy was related to better episodic and prospective memory. In contrast, neither eHealth Fact search time nor its accuracy were related to any of the neurocognitive measures. Our findings suggest a differential relationship between neurocognitive abilities and eHealth search behaviors among young adults such that higher-order abilities may be implicated in eHealth searches requiring greater synthesis of information. Future work should examine the cognitive architecture of eHealth search in persons with neurocognitive disorders, as well as that of other aspects of eHealth search behaviors (e.g., search term generation, website reliability, and decision-making).


title: Laparoscopic resection of adrenal neuroblastoma without image-defined risk factors: a prospective study on 21 consecutive pediatric patients.

text: BACKGROUND Over the last 20 years MIS has progressively gained popularity in children with cancer. We therefore aimed at evaluating the safety of Minimally Invasive Surgery (MIS) resection in a series of children affected by adrenal neuroblastoma (NB) presenting without Image-Defined Risk Factors (IDRFs). METHODS An Institutional protocol for MIS resection of adrenal NB in pediatric patients without IDRFs has been applied since 2008. Absence of IDRFs represented the main indication for MIS in NB, regardless of tumor size. All pediatric patients who underwent MIS for NB between January 2008 and May 2013 were included. Specific technical considerations, demographic data, and outcome have been recorded. RESULTS Twenty-one patients underwent MIS resection for IDRFs-negative adrenal NB. Nine of these patients experienced preoperative downgrading of IDRFs after chemotherapy. Radiological median diameter of the mass was 30 mm (range 10-83 mm). Median operative time was 90 min. Median hospital stay was 4 days. All patients were treated successfully, without serious intraoperative complications. One mild intraoperative hemorrhage occurred and was treated without the need for conversion to open surgery nor blood transfusion was required. No postoperative complications, including port-site or peritoneal metastases were experienced. CONCLUSIONS This study demonstrated the safety and effectiveness of MIS for the resection of adrenal NB without IDRFs in children. Pediatric surgeons dedicated to oncology should be aware of this alternative approach to open resection.


title: Azacitidine-associated pleuropericardial effusion in myelodysplastic syndrome: A case report.

text: Azacitidine, a deoxyribonucleic acid hypomethylating agent, is used in the treatment of myelodysplastic syndrome. Common adverse effects of azacitidine include bone marrow suppression, injection site reactions, nausea, vomiting, diarrhea, and fatigue. This report focuses on pleuropericardial effusions, an infrequently reported and potentially reversible adverse effect of azacitidine. In this case report, pleuropericardial effusion manifested as the sole radiographic finding in the evaluation of cough occurring during the eighth cycle of treatment with azacitidine. Symptoms and radiographic abnormalities resolved with corticosteroids and diuretics, and the patient could continue with therapy.


title: VATS Plication of the Diaphragm: A Descriptive Observational 10-Year Southampton Experience.

text: OBJECTIVE The aim of the study was to report the safety and efficacy of video-assisted thoracoscopic (VATS) plication of the diaphragm at our institution between 2006 and 2016. METHODS Adult patients selected on etiology and combination of investigations including plain chest x-ray, computed tomography of chest and abdomen, lung functions in supine and sitting positions, radiological/ultrasonic screening for diaphragmatic movement, and phrenic nerve conduction studies. We incorporated a triportal VATS and Endostitch device for plication, using CO2 insufflation to maximum 12 mm Hg. Bilateral simultaneous plication and high-risk patients were electively admitted to intensive therapy unit postoperatively. RESULTS Thirty-five patients (24 males) had their diaphragm plicated. The mean age was 56.6 years (range = 23-76 years). The mean body mass index was 32.1 (range = 22.2-45.4). Twenty one were right, 13 left, 2 patients had VATS simultaneous bilateral plication, and 1 had sequential VATS bilateral plication. Paralysis was idiopathic in 17, posttraumatic in 5, postremoval of mediastinal tumor in 4, and postcardiac surgery in 3. All patients presented with lifestyle-limiting dyspnea and orthopnea, three were on nocturnal noninvasive ventilation. Five were diabetic and 16 were smokers. The mean supine forced expiratory volume in the first second was 62.5% of predicted. Twenty two were performed by VATS (63%), three converted to thoracotomy, and 13 were open limited thoracotomy (historic). The mean hospital stay was 4.5 days (range = 1-18, mode 2 days). Intensive therapy unit admission was required in six patients for mechanical ventilation 0 to 3 days. Five patients (14%) had no improvement in symptoms. There were no deaths, no 30-day readmissions, and no long-term neuralgia in this series. CONCLUSIONS We found minimal access VATS plication of the diaphragm to be feasible and safe, but no firm conclusions should be drawn from our limited resources. We report the feasibility of concomitant bilateral VATS plication of the diaphragm in two adults, and this was not previously reported in the adult population. There is a need for further good quality, prospective studies, and randomized controlled studies evaluating efficacy of VATS diaphragmatic plication.


COVID-19 and the Financial Health of US Hospitals.


title: Single incision thoracoscopic sympathectomy for hyperhidrosis.

text: Thoracal sympatectomy for hyperhidrosis and vasospastic vascular diseases is a rare method of surgical treatment. Three patients (1 male, 2 female; mean age 27.6; between 25 and 30) with palmar hyperhidrosis and/or axillary and dorsal hyperhidrosis who underwent single port thoracoscopic sympatectomy were analysed for age, sex, time of operation room, intraoperative and postoperative complications and length of hospital stay. Mean operating room time was 70 min (between 30 and 120 min). Mean length of hospital stay was 1 day. No postoperative complications were noted. Single incision laparoscopic surgery for hyperhidrosis is a safe method of treatment and an alternative to laparoscopy.


title: Combined radiofrequency ablation and high-dose rate brachytherapy for early-stage non-small-cell lung cancer.

text: PURPOSE This retrospective analysis reports the results of patients with early-stage inoperable non-small-cell lung cancer treated with radiofrequency ablation (RFA) followed by adjuvant high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS Seventeen medically inoperable patients with biopsy-proven Stage I non-small-cell lung cancer were treated with RFA followed by single fraction HDR brachytherapy. Brachytherapy catheters were inserted immediately after RFA, and one fraction of HDR brachytherapy was delivered on the same day. Doses of brachytherapy ranged from 14.4 to 20 Gy (median, 18 Gy). Patients were followed clinically and radiographically to determine tumor control and toxicity profile. RESULTS Median followup time was 22 months. Of the 17 patients, 3 patients have recurred locally. Each of the patients with local recurrences was originally treated for T2 disease. In total, three of seven cases with T2N0 disease experienced local recurrences, whereas all 9 patients with T1 disease were controlled locally. Five of the 17 patients required a chest tube posttreatment, and 1 patient developed an empyema. There were no deaths within 1 month of treatment. CONCLUSIONS RFA followed by HDR brachytherapy yields excellent local control with an acceptable toxicity profile for patients with otherwise inoperable early-stage lung cancer.


title: Uncovering the hidden villain within the human respiratory microbiome.

text: Respiratory tract infection increases the risk of secondary bacterial infection and causes mortality. Despite advances in the field of targeted molecular diagnostics, there are still failed attempts in identifying a valid causative etiological agent in a large proportion of respiratory tract infections. To date, a comprehensive list of human respiratory infection-associated eukaryotic viruses has been identified. However, there has been little progress towards the characterisation of the viruses that infect bacteria (phages), which are capable of mediating the transfer of virulence genes into non-pathogenic bacterial species to cause respiratory tract infections. With the advent of next-generation-sequencing, the application of an unbiased comparative metagenomic survey on the viral communities within the human respiratory tract may reveal to us how the phage virome changes between healthy individuals and respiratory tract infection patients. With this useful information, it will be feasible to develop an alternative phage-based diagnostic panel for respiratory tract infections. The review herein presents the current status of human airway microbiome research and highlights potential gaps which can be translated into research possibilities for future work on respiratory tract infection diagnosis.


title: Limb and back muscle activity adaptations to tripedal locomotion in dogs.

text: Alterations in muscle recruitment are key to the functional plasticity of the mammalian locomotor system. One particularly challenging situation quadrupeds may face is when the functionality of a limb is reduced or lost. To better understand how mammals manage in such situations and which muscular adaptations they exhibit when locomoting on three legs, we recorded the activity patterns of two limb and one back extensor muscle in nine dogs using surface electromyography. We compared the timing and the level of recruitment before and after the loss of a hindlimb was simulated. Both the intensity and the timing of the activity changed significantly in the m. vastus lateralis of the remaining hindlimb, consistent with this limb bearing a greater proportion of the body weight as well as with previously reported kinematic changes. In accordance with the greater body weight supported by the forelimbs, the m. triceps brachii showed first and foremost an increased level of excitation. The very asymmetrical changes in the timing and the level of activity in the m. longissimus dorsi reflects the highly asymmetrical functional requirements imposed on the trunk and the pelvis when one hindlimb is no longer involved in the production of locomotor work while the other hindlimb partially compensates the loss. Integration of our electromyographical findings with kinetic and kinematic results illustrates that dogs exhibited a well-coordinated response to the functional requirements of tripedalism and underlines the importance of moment-to-moment modulation in muscular recruitment for the functional plasticity of the mammalian locomotor system.


Laparoscopic gastric band slippage diagnosed with esophagogastroduodenoscopy in a 12-week gestation nulliparous patient.


title: Autophagy/virophagy: a "disposal strategy" to combat COVID-19.

text: Given the devastating consequences of the current COVID-19 pandemic and its impact on all of us, the question arises as to whether manipulating the cellular degradation (recycling, waste disposal) mechanism known as macroautophagy/autophagy (in particular, the selective degradation of virus particles, termed virophagy) might be a beneficial approach to fight the novel coronavirus, SARS-CoV-2. Knowing that "autophagy can reprocess everything", it seems almost inevitable that, sooner rather than later, a further hypothesis-driven work will detail the role of virophagy as a fundamental "disposal strategy" against COVID-19, yielding most needed therapeutic interventions. ABBREVIATIONS ATG, autophagy-related; CoV/CoVs coronavirus/coronaviruses; COVID-19, coronavirus disease 2019; MERS-CoV, Middle East respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.


US ventilator crisis brings patients and doctors face-to-face with life-or-death choices.


title: Utilization of sialylated glycans as coreceptors enhances the neurovirulence of serotype 3 reovirus.

text: Mammalian reoviruses display serotype-specific patterns of tropism and disease in the murine central nervous system (CNS) attributable to polymorphisms in viral attachment protein σ1. While all reovirus serotypes use junctional adhesion molecule-A as a cellular receptor, they differ in their utilization of carbohydrate coreceptors. This observation raises the possibility that carbohydrate binding by σ1 influences reovirus pathology in the CNS. In this study, we sought to define the function of carbohydrate binding in reovirus neuropathogenesis. Newborn mice were inoculated intramuscularly with wild-type strain type 3 Dearing (T3D) and T3D-σ1R202W, a point mutant T3D derivative that does not bind sialic acid (SA). Infected mice were monitored for survival, and viral loads at the sites of primary and secondary replication were quantified. Fewer mice inoculated with the wild-type virus survived in comparison to those inoculated with the mutant virus. The wild-type virus also produced higher titers in the spinal cord and brain at late times postinoculation but lower titers in the liver in comparison to those produced by the mutant virus. In addition, the wild-type virus was more virulent and produced higher titers in the brain than the mutant following intracranial inoculation. These animal infectivity studies suggest that T3D-σ1R202W harbors a defect in neural growth. Concordantly, compared with the wild-type virus, the mutant virus displayed a decreased capacity to infect and replicate in primary cultures of cortical neurons, a property dependent on cell surface SA. These results suggest that SA binding enhances the kinetics of reovirus replication in neural tissues and highlight a functional role for sialylated glycans as reovirus coreceptors in the CNS.


title: Esophageal tissue engineering.

text: Esophageal tissue engineering is still in an early state, and ideal methods have not been developed. Since the beginning of the 20th century, advances have been made in the materials that can be used to produce an esophageal substitute. Three approaches to scaffold-based tissue engineering have yielded good results. The first development concerned non-absorbable constructs based on silicone and collagen. The need to remove the silicone tube is the main disadvantage of this material. Polymeric absorbable scaffolds have been used since the 1990s. The main polymeric material used is poly (glycolic) acid combined with collagen. The problem of stenosis remains prevalent in most studies using an absorbable construct. Finally, decellularized scaffolds have been used since 2000. The promises of this new approach are unfulfilled. Indeed, stenosis occurs when the esophageal defect is circumferential regardless of the scaffold materials. Cell supplementation can decrease the rate of stenosis, but the type(s) of cells and their roles have not been defined. Finally, esophageal tissue engineering cannot provide a functional esophageal substitute, and further development is necessary prior to conducting human clinical studies.


From the Editor: At the heart of the mission of general practice.


COVID-19 infections are also affected by human ACE1 D/I polymorphism.


title: The temporoparietal fascia flap: a versatile tool for the dermatologic surgeon.

text: BACKGROUND Dermatologic surgeons may encounter challenging defects of the head and neck that are not amenable to repair with local flaps or grafts. OBJECTIVE We offer a comprehensive review of the temporoparietal fascia flap (TPFF) and provide a step-by-step illustration of its application performed under local anesthesia for a challenging reconstructive scenario. MATERIALS AND METHODS A 66-year-old male initially underwent Mohs micrographic surgery resulting in a large full-thickness defect at the postauricular scalp contiguous with a through-and-through defect of the upper right ear. A TPFF was performed under local anesthesia to reconstruct the surgical defect. RESULTS Complete healing in our patient was noted at 10 weeks after completion of the TPFF. However, granulation caused adherence of the ear to the postauricular scalp, which was corrected by a dividing incision to release the ear. At 4 weeks after the division, lateral projection of the ears was symmetric and readherence of the ear did not recur. CONCLUSION The TPFF is a highly versatile pedicled flap that can be performed under local anesthesia to reconstruct a variety of complex defects on the head and neck. This case reveals that the TPFF adds a powerful tool to the armamentarium of dermatologic surgeons.


title: Evaluation of three unchannelled videolaryngoscopes and the Macintosh laryngoscope in patients with a simulated difficult airway: a randomised, controlled trial.

text: This prospective randomised, controlled trial compares the performance of three unchannelled videolaryngoscopes (KingVision™ , Airtraq™ , A.P. Advance™ MAC) and the standard Macintosh laryngoscope. With ethics committee approval and written informed consent, 480 patients were included. A difficult airway was created with a cervical collar, limiting mouth opening and neck movement. Primary outcome was first-attempt orotracheal intubation success. Overall success, laryngeal view, intubation difficulty scale, handling, intubation times and side-effects were secondary outcomes. First-attempt success rates were: KingVision 90% (95% CI 83-94%), Airtraq 82% (74-88%), A.P. Advance MAC 49% (40-58%), Macintosh 44% (35-53%; p < 0.001). The 95% confidence interval of first-attempt success rate was thus below 90% for all devices, but the KingVision and the Airtraq performed better than the A.P. Advance MAC and the Macintosh laryngoscope. Also, performance was better with the KingVision and the Airtraq in terms of overall success, laryngeal view, intubation difficulty scale and quality of view. Problems with tube advancement were a frequent cause of intubation failure. In summary, the KingVision and the Airtraq performed better than the A.P. Advance MAC and the Macintosh laryngoscope. Success rates of the unchannelled KingVision and Airtraq were similar to those of their channelled versions reported previously, indicating that performance largely depends on blade design rather than the presence of a channel for tube advancement.


Quality improvement guidelines for percutaneous management of acute lower-extremity ischemia.


title: Structural architecture of an RNA that competitively inhibits RNase L.

text: Activation of RNase L endonuclease activity is part of the mammalian innate immune response to viral infection. The poliovirus RNA genome contains a sequence in its protein-coding region that can act as a competitive inhibitor of RNase L. Mutation, sequence, and functional analysis of this competitive inhibitor RNA (ciRNA) revealed that its activity depends on specific sequences, showed that a loop-loop hairpin interaction forms in the ciRNA, and suggested the presence of a loop E motif. These features lead to the hypothesis that the ciRNA's function is conferred in part by a specific three-dimensional folded RNA architecture. By using a combination of biophysical, mutational, and functional studies, we have mapped features of the three-dimensional architecture of the ciRNA in its unbound form. We show that the loop-loop interaction forms in the free ciRNA and affects the overall structure, perhaps forming long-range tertiary interactions with the loop E motif. Local tight RNA-RNA backbone packing occurs in parts of the structure, but the fold appears to be less stable than many other tightly packed RNAs. This feature may allow the ciRNA to accommodate the translocation of ribosomes and polymerase across this multifunctional region of the viral RNA but also to function as an RNase L inhibitor.


title: Poly-4-hydroxybutyrate (Phasix™) mesh onlay in complex abdominal wall repair.

text: BACKGROUND Poly-4-hydroxybutyric acid (P4HB, Phasix™) is a biosynthetic polymer that degrades by hydrolysis that can be woven into a mesh for use in soft tissue reinforcement. Herein, we describe our initial experience performing complex abdominal wall repair (CAWR) utilizing component separation and P4HB mesh as onlay reinforcement. METHODS All patients undergoing CAWR between June 2014 and May 2017 were followed prospectively for postoperative outcomes. Only those patients who underwent components separation with primary repair of the fascial edges followed by onlay of P4HB mesh were included in this study. RESULTS 105 patients (52 male, 53 female; mean age 59.2 years, range 22-84) met inclusion criteria. Mean BMI was 29.1 (range 16-48); 52% patients had prior attempted hernia repair, most with multiple medical comorbidities (71% of patients with ASA 3 or greater). 30% of cases were not clean at the time of repair (CDC class 2 or greater). Median follow-up was 36 months (range 9-63). Eighteen patients (17%) developed a hernia recurrence ranging from 2 to 36 months postoperatively. Five (5%) patients developed a localized superficial infection treated with antibiotics, three (2.8%) required re-operation for non-healing wounds, and six (6%) patients developed seroma. CONCLUSIONS These data demonstrate a relatively low rate of hernia recurrence, seroma, and other common complications of CAWR in a highly morbid patient population. Importantly, the rate of mesh infection was low and no patients required complete mesh removal, even when placed into a contaminated or infected surgical field.


title: Pan-intestinal capsule endoscopy in patients with postoperative Crohn's disease: a pilot study.

text: BACKGROUND Patients are at increased risk of disease recurrence after surgical treatment of Crohn's disease. Endoscopic detection of postoperative, ileo-colonic inflammation is well established, but the potential of pan-intestinal endoscopy is yet unknown. METHODS This prospective multicenter pilot study assessed the value of pan-intestinal capsule endoscopy using a colon capsule endoscope for the detection of inflammatory recurrence of Crohn´s disease. Patients who had been operatively treated for Crohn´s disease were included. Colon capsule endoscopy was performed 4-8 weeks (d1) and 4-8 months (d2) postoperatively together with ileo-colonoscopy at d2 using a modified Ruttgeerts index for evaluating disease activity. RESULTS Twenty-two patients were included into this study. At d1, significant disease activity (Ruttgeerts index ≥2) was detected in 3/16 (19%) of the patients. At d2, half of the patients (6/12) showed active disease, whereas ileo-colonoscopy revealed significant inflammation in 5/15 (33%). All patients rated as having active disease by ileo-colonoscopy had been revealed by PICE as well. These findings influenced the medical treatment in every case. CONCLUSION Pan-intestinal capsule endoscopy seems to be feasible in the postoperative surveillance of Crohn's disease. Disease activity is reliably detected. Especially, the findings in the small bowl might be a significant advantage in comparison to ileo-colonoscopy, as they can have significant impact on clinical management. Further studies with a larger number of patients are needed to confirm these findings and might lead to a replacement of the flexible ileo-colonoscopy with pan-intestinal capsule endoscopy in this indication in the future.


title: Surgical training in robotic surgery: surgical experience of robotic-assisted transabdominal preperitoneal inguinal herniorrhaphy with and without resident participation.

text: Robotic-assisted surgery is becoming more popular in general surgery. Implementation of a robotic curriculum is necessary and will influence surgical training. The aim of this study is to compare surgical experience and outcomes with and without resident participation in robotic inguinal herniorrhaphy. A retrospective review of patients who underwent either unilateral or bilateral robotic-assisted transabdominal preperitoneal (TAPP) inguinal herniorrhaphy, with and without resident participation as console surgeons from January through December 2015, was performed. Patient demographics, procedure-related data, postoperative variables, and follow-up data were analyzed. A total of 104 patients were included. Patients were significantly older in the Resident group (57.5 ± 14.1 vs 50.6 ± 13.5 years, p = 0.01). Gender, BMI, and ASA classification were similar between groups. There were similar mean operative times for unilateral (89.9 ± 19.5 vs 84.8 ± 22.2 min, p = 0.42) and bilateral (128.4 ± 21.9 vs 129.8 ± 50.9 min, p = 0.90) inguinal herniorrhaphy as well as mean robot console times for unilateral (73.2 ± 18.4 vs 67.3 ± 29.9 min, p = 0.44) and bilateral (115.5 ± 24.6 vs 109.3 ± 55.4 min, p = 0.67) inguinal herniorrhaphy with and without resident participation, respectively. Postoperative complications included urinary retention (11.1 vs 2.0%, p = 0.11), conversion to open repair (0 vs 2%, p = 0.48), and delayed reoperation (0 vs 4%, p = 0.22) with and without resident participation, respectively. Patients' symptoms/signs at follow-up were similar among groups. Robotic-assisted TAPP inguinal herniorrhaphy with resident participation as console surgeons did not affect the hospital operative experience or patient outcomes. This procedure can be implemented as part of the resident robotic curriculum with rates of morbidity equivalent to those of published studies.Level of evidence 2b.


title: Complete protection against severe acute respiratory syndrome coronavirus-mediated lethal respiratory disease in aged mice by immunization with a mouse-adapted virus lacking E protein.

text: Zoonotic coronaviruses, including the one that caused severe acute respiratory syndrome (SARS), cause significant morbidity and mortality in humans. No specific therapy for any human coronavirus is available, making vaccine development critical for protection against these viruses. We previously showed that recombinant SARS coronavirus (SARS-CoV) (Urbani strain based) lacking envelope (E) protein expression (rU-ΔE) provided good but not perfect protection in young mice against challenge with virulent mouse-adapted SARS-CoV (MA15). To improve vaccine efficacy, we developed a second set of E-deleted vaccine candidates on an MA15 background (rMA15-ΔE). rMA15-ΔE is safe, causing no disease in 6-week-, 12-month-, or 18-month-old BALB/c mice. Immunization with this virus completely protected mice of three ages from lethal disease and effected more-rapid virus clearance. Compared to rU-ΔE, rMA15-ΔE immunization resulted in significantly greater neutralizing antibody and SARS-CoV-specific CD4 and CD8 T cell responses. After challenge, inflammatory cell infiltration, edema, and lung destruction were decreased in the lungs of rMA15-ΔE-immunized mice compared to those in rU-ΔE-immunized 12-month-old mice. Collectively, these results show that immunization with a species-adapted attenuated coronavirus lacking E protein expression is safe and provides optimal immunogenicity and long-term protection against challenge with lethal virus. This approach will be generally useful for development of vaccines protective against human coronaviruses as well as against coronaviruses that cause disease in domestic and companion animals.


title: Frailty in patients undergoing transcatheter aortic valve implantation: a protocol for a systematic review.

text: INTRODUCTION Aortic stenosis is a significant cause of morbidity and mortality in older patients. The advent of transcatheter aortic valve implantation (TAVI) offers an alternative to surgical aortic valve replacement for patients with severe symptomatic aortic stenosis who are at high or intermediate risk of adverse events. Existing evidence highlights the importance of frailty as a predictor of poor outcomes post-TAVI. The objective of this study is to review the operationalisation of frailty instruments for TAVI recipients and determine clinical outcomes and the change in quality of life in frail patients undergoing TAVI. METHODS AND ANALYSIS Methods are reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. We will search relevant databases to identify published, completed but unpublished and ongoing studies. We will include studies of patients with aortic stenosis, diagnosed as frail and who underwent a TAVI procedure that report mortality, clinical outcomes or health-related quality of life. Retrospective or prospective cohort studies, randomised controlled trials and non-randomised controlled trials will be eligible for inclusion. Two researchers will independently screen articles for inclusion, with disagreements resolved by a third reviewer. One researcher will extract data with audit by a second researcher. The risk of bias in studies will be evaluated using the Quality in Prognosis Studies tool. Meta-analysis of mortality, survival curve and the change in quality of life will be performed if appropriate. Subgroup analysis, sensitivity analysis and meta-regression will be performed if necessary. ETHICS AND DISSEMINATION Due to the nature of this study, no ethical issues are foreseen. We will disseminate the results of our systematic review through a peer-reviewed journal. TRIAL REGISTRATION NUMBER CRD42018090597.


title: Oseltamivir compared with the Chinese traditional therapy maxingshigan-yinqiaosan in the treatment of H1N1 influenza: a randomized trial.

text: BACKGROUND Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING Eleven hospitals from 4 provinces in China. PATIENTS 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE Beijing Science and Technology Project and Beijing Nova Program.


title: Chronic peritoneal dialysis in children.

text: The incidence of end-stage renal disease in children is increasing. Peritoneal dialysis (PD) is the modality of choice in many European countries and is increasingly applied worldwide. PD enables children of all ages to be successfully treated while awaiting the ultimate goal of renal transplantation. The advantages of PD over other forms of renal replacement therapy are numerous, in particular the potential for the child to lead a relatively normal life. Indications for commencing PD, the rationale, preparation of family, technical aspects, and management of complications are discussed.


title: Association of Presence of Band Cells and Toxic Neutrophils with Systemic Inflammatory Response Syndrome and Outcome in Horses with Acute Disease.

text: BACKGROUND Band cells and toxic neutrophils are thought to indicate acute and severe systemic illness but no studies have investigated their importance in adult equine emergency admissions. OBJECTIVES The objective of this study was to evaluate the association of band cells and toxic neutrophils with systemic inflammatory response syndrome (SIRS) and outcome in horses. ANIMALS One hundred and five adult horses admitted on emergency basis to a private primary referral practice. METHODS Prospective observational study with sample collection. All horses admitted on emergency basis over the study period were included in the study if they had a CBC and a blood smear collected on admission. RESULTS The detection of band neutrophils on admission was associated with the SIRS status of the horse (RR = 2.80; 95% CI = 1.57-4.99; P < .001) and with poor outcome (RR = 1.88; 95% CI: 1.05-3.37; P = .038). Similarly, the presence of a neutrophil toxic grade higher than 3 was associated with SIRS (RR = 1.71; 95% CI: 1.03-2.82; P = .034) and death (RR = 2.34; 95% CI: 1.22-4.50, P = .007). The information gained from the blood smear review could not be captured by looking at only the WBC or neutrophil count. CONCLUSIONS AND CLINICAL IMPORTANCE The microscopic review of blood smears from critically ill horses to detect band cells or neutrophil toxic change is valuable and could help in assessing disease severity and prognosis in adult equine emergency admissions.


title: COVID-19 and Brazilian Indigenous Populations.

text: The newly discovered SARS-CoV-2 is the cause of COVID-19, including severe respiratory symptoms with an important lethality rate and high dissemination capacity. Considering the indigenous people of Brazil, it is feared that COVID-19 will spread to these communities, causing another stage of decimation. Despite advances in indigenous health care in the country, there are still many challenges due to the social vulnerability of this population, whose lands continue to be illegally exploited. Based on these considerations, this article discusses challenges in caring for the indigenous population in the context of the COVID-19 pandemic in Brazil.


title: Cerebral autoregulation in pregnancies complicated by diabetes and overweight.

text: AIM The aim of this study was to estimate the impact of diabetes and obesity on cerebral autoregulation in pregnancy. METHODS Cerebral autoregulation was evaluated in women with gestational diabetes, type 2 diabetes mellitus and/or overweight (body mass index ⩾ 25 kg m(-2)) and compared to a cohort of euglycaemic pregnant women. The autoregulation index was calculated using simultaneously recorded cerebral blood flow velocity in the middle cerebral artery and blood pressure. Autoregulation index values of 0 and 9 indicate absent and perfect autoregulation, respectively. RESULTS Autoregulation index in women with either diabetes (n = 33, 6.6 ± 1.1) or overweight (n = 21, 6.7 ± 0.6) was not significantly different to that in control patients (n = 23, 6.6 ± 0.8, p = 0.96). CONCLUSION Cerebral autoregulation is not impaired in pregnant women who have non-vasculopathic diabetes or overweight. This suggests that the increased risk of pre-eclampsia in diabetic and overweight women is not associated with early impaired cerebral autoregulation.


Response to: 'Incidence of severe COVID-19 in a Spanish cohort of 1037 patients with rheumatic diseases treated with biologics and JAK-inhibitors' by Jovani et al.


Covid-19: NHS outlines services to be prioritised to restart in next six weeks.


title: The Interference Phenomenon of Microcatheters in the Jailing Treatment for Internal Carotid Artery Side Wall Aneurysms with an Open Cell Stent System.

text: OBJECTIVE Excelsior XT-27 (Stryker Neurovascular, Fremont, CA, USA) or Rebar 27 (eV3 Covidien, Irvine, CA, USA) microcatheters have recently been used to overcome the limitations of the Renegade Hi-Flo microcatheter such as interference between two microcatheters (one for stent delivery and the other for cerebral aneurysm coiling) during the jailing technique. We evaluated differences and influential factors related to the interference phenomenon according to these two microcatheters group. MATERIALS AND METHODS Between June 2011 and September 2013, the jailing technique was applied to 94 internal cerebral artery (ICA) aneurysms. The jailing technique with the Neuroform EZ stent system was performed using Renegade (n = 22), Rebar (n = 35), and XT-27 microcatheters (n = 37). In the Renegade Hi-Flo microcatheter group, the jailing technique was successful in 19/22 patients (86.4%) and interference between the two microcatheters occurred in 6/21 patients (28.6%). In the Rebar and XT-27 microcatheter group, the jailing technique was successful in 71/72 patients (98.6%) and interference between the two microcatheters occurred in 1/72 patients (1.4%). RESULTS There was a significant difference in the interference between the two delivered microcatheters group (p-value < 0.000) and the carotid siphon angle (p-value: 0.004) in the univariate analysis. In the multiple logistic regression analysis, the Rebar and XT-27 microcatheter group (odds ratio [OD] [95% confidence interval (CI)]; 31.277 [3.138-311.729], p-value: 0.003) and the carotid siphon angle (OD [95%CI]; 0.959 [0.922-0.997], p-value: 0.035) were found to be influential factors in the interference phenomenon. CONCLUSION The Rebar 27 and XT-27 microcatheters were more successful and exhibited less interference between the two microcatheters than the Renegade Hi-Flo microcatheter.


title: The effect of mini-PEG-based spacer length on binding and pharmacokinetic properties of a 68Ga-labeled NOTA-conjugated antagonistic analog of bombesin.

text: The overexpression of gastrin-releasing peptide receptor (GRPR) in cancer can be used for peptide-receptor mediated radionuclide imaging and therapy. We have previously shown that an antagonist analog of bombesin RM26 conjugated to 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) via a diethyleneglycol (PEG2) spacer (NOTA-PEG2-RM26) and labeled with 68Ga can be used for imaging of GRPR-expressing tumors. In this study, we evaluated if a variation of mini-PEG spacer length can be used for optimization of targeting properties of the NOTA-conjugated RM26. A series of analogs with different PEG-length (n = 2, 3, 4, 6) was synthesized, radiolabeled and evaluated in vitro and in vivo. The IC50 values of natGa-NOTA-PEGn-RM26 (n = 2, 3, 4, 6) were 3.1 ± 0.2, 3.9 ± 0.3, 5.4 ± 0.4 and 5.8 ± 0.3 nM, respectively. In normal mice all conjugates demonstrated similar biodistribution pattern, however 68Ga-NOTA-PEG3-RM26 showed lower liver uptake. Biodistribution of 68Ga-NOTA-PEG3-RM26 was evaluated in nude mice bearing PC-3 (prostate cancer) and BT-474 (breast cancer) xenografts. High uptake in tumors (4.6 ± 0.6%ID/g and 2.8 ± 0.4%ID/g for PC-3 and BT-474 xenografts, respectively) and high tumor-to-background ratios (tumor/blood of 44 ± 12 and 42 ± 5 for PC-3 and BT-474 xenografts, respectively) were found already at 2 h p.i. of 68Ga-NOTA-PEG3-RM26. Results of this study suggest that variation in the length of the PEG spacer can be used for optimization of targeting properties of peptide-chelator conjugates. However, the influence of the mini-PEG length on biodistribution is minor when di-, tri-, tetra- and hexaethylene glycol are compared.


title: Single-incision laparoscopic trans-abdominal pre-peritoneal mesh hernia repair: a feasible approach.

text: BACKGROUND Single-incision laparoscopic surgery (SILS) is aimed at improving the cosmetic outcome following surgery. If the incision is made through the umbilicus, the surgery is almost 'scarless.' This is increasingly being used for laparoscopic cholecystectomy with good cosmetic results without compromising the safety of the operation. The challenge of this surgery lies in manipulating instruments within the limitations of the closely inserted ports. METHODS We describe the first case of SILS hernia repair via the trans-abdominal pre-peritoneal approach (TAPP) in a 39-year-old male as a day-case procedure. RESULTS The patient was discharged without any complications. CONCLUSIONS This novel surgical technique is feasible and improves cosmetic outcome without additional risk. The advantage of such an approach above and beyond cosmesis remains to be evaluated.


COVID-19 cumulative mortality rates for frontline healthcare staff in England.


title: Magnetic resonance imaging with gadoxetic acid for local tumour progression after radiofrequency ablation in patients with hepatocellular carcinoma.

text: OBJECTIVES To develop and validate a prediction model using magnetic resonance imaging (MRI) for local tumour progression (LTP) after radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients. METHODS Two hundred and eleven patients who had received RFA as first-line treatment for HCC were retrospectively analyzed. They had undergone gadoxetic acid-enhanced MRI before treatment, and parameters including tumour size; margins; signal intensities on T1-, T2-, and diffusion-weighted images, and hepatobiliary phase images (HBPI); intratumoral fat or tumoral capsules; and peritumoural hypointensity in the HBPI were used to develop a prediction model for LTP after treatment. This model to discriminate low-risk from high-risk LTP groups was constructed based on Cox regression analysis. RESULTS Our analyses produced the following model: 'risk score = 0.617 × tumour size + 0.965 × tumour margin + 0.867 × peritumoural hypointensity on HBPI'. This was able to predict which patients were at high risk for LTP after RFA (p < 0.001). Patients in the low-risk group had a significantly better 5-year LTP-free survival rate compared to the high-risk group (89.6 % vs. 65.1 %; hazard ratio, 3.60; p < 0.001). CONCLUSION A predictive model based on MRI before RFA could robustly identify HCC patients at high risk for LTP after treatment. KEY POINTS • Tumour size, margin, and peritumoural hypointensity on HBPI were risk factors for LTP. • The risk score model can predict which patients are at high risk for LTP. • This prediction model could be helpful for risk stratification of HCC patients.


title: Inhibition of sphingosine-1-phosphate-induced Th17 cells ameliorates alcoholic steatohepatitis in mice.

text: Chronic alcohol consumption is accompanied by intestinal inflammation. However, little is known about how alterations to the intestinal immune system and sphingolipids contribute to pathogenesis of alcoholic liver disease (ALD). We used WT mice, RORγt-deficient mice, sphingosine kinase-deficient mice and local gut anti-inflammatory, 5-aminosalicyclic acid (5-ASA)-treated mice in a chronic-binge ethanol feeding model. Targeted lipidomics assessed the sphingolipids in gut and liver samples. Gut immune cell populations, the amounts of sphingolipids, and the level of liver injury were examined. Results: Alcohol intake induces a pro-inflammatory shift in immune cell populations in the gut, including an increase in Th17 cells. Using RORγt-deficient mice, we found that Th17 cells are required for alcohol-associated gut inflammation and the development of ALD. Treatment with 5-ASA decreases alcohol-induced liver injury and reverses gut inflammation by the suppression of CD4+ /RORγt+ /IL-17A+ cells. Increased Th17 cells were due to upregulation of SK1 activity and RORγt activation. We found that S1P/S1PR1 signaling are required for the development of Th17 cell-mediated ALD. Importantly, in vivo intervention blocking of S1P/S1PR1 signaling markedly attenuated alcohol-induced liver inflammation, steatosis, and damage. Conclusion: Gut inflammation is a functional alteration of immune cells in ALD. Reducing gut Th17 cells leads to reduced liver damage. S1P signaling was crucial in the pathogenesis of ALD in a Th17 cell dependent manner. Furthermore, our findings suggest that compounds that reduce gut inflammation locally may represent a unique targeted approach in the treatment of ALD.


title: Transarterial chemoembolization using drug eluting beads and subsequent percutaneous MR-guided radiofrequency ablation in the therapy of intermediate sized hepatocellular carcinoma.

text: OBJECTIVE To evaluate safety, efficacy, survival and recurrence-free survival of transarterial chemoembolization (TACE) with drug eluting (DC) beads combined with MR-guided radiofrequency (RF) ablation for the treatment of hepatocellular carcinomas (HCC) larger than 3 cm. MATERIALS AND METHODS This retrospective study was approved by the institutional review board. 20 patients (69.6 years ± SD 8.8) with HCC underwent DC Bead TACE and subsequent MR-guided RF ablation. Treatment interval varied between 5 and 15 days. Mean HCC diameter was 39 mm ± SD 7 mm (range 31-50mm). Rates of recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS Technical success rate, primary and secondary technical effectiveness rate were 100%, 90% and 95%, respectively. Local tumour progression developed in one patient. Cumulative survival rates at 1, 3 and 5 years were 90% (Confidence Interval [CI]: 67%-97%), 50% (CI: 29%-70%), 27% (CI: 11%-51%) respectively. Median survival time was 37.4 months. During follow up (mean: 39.1 months ± SD 22.4; range 5-84 months), tumour progression in untreated liver developed in 14 cases. Cumulative recurrence-free survival rates at 1, 3 and 5 years were 48% (CI: 27-69%), 16% (5-39%), 16% (5-39%) respectively. Median recurrence-free survival time was 10.7 months. One major complication occurred due to misdiagnosed local recurrence. CONCLUSION In conclusion, we demonstrated that MR-guided RF ablation with subsequent DC Bead TACE is safe and effective in local tumour control in patients with intermediate sized HCC.


title: Ultrasound-guided transversus abdominis plane injection with computed tomography correlation: a cadaveric study.

text: BACKGROUND Ultrasound-guided transversus abdominis plane (TAP) injections are increasingly being used as an alternative to traditional perioperative analgesia in the abdominal region. With the use of a "blind" TAP block technique, these procedures have had variable success in cadaver and in vivo studies. For more accurate injection with the intended medication, ultrasound guidance allows visualization of the correct layer of the abdominal wall planes in which the thoracolumbar nerves reside. OBJECTIVE To assess the spread of various volumes of contrast placed under live ultrasound guidance into the TAP using computed tomography (CT). METHODS Four TAP blocks were performed on 2 fresh frozen cadaver torsos with predetermined contrast volumes of 5, 10, 15, or 20 mL. A CT scan of the cadaver was then performed and interpreted by a musculoskeletal radiologist. This cadaver study was carried out at a tertiary care academic medical center. RESULTS Cranial-caudal spread of injected contrast correlated with increasing injectate volume and was roughly 1 vertebral level (end plate to end plate) for the 5 mL injection and 2 vertebral levels for the 10, 15, and 20 mL injections. However, the degree of injectate spread may be different for live patients than for cadavers. CONCLUSION This study helps further the understanding of injectate spread following ultrasound-guided TAP injections. Specifically, it suggests that 15 mL provides additional cranial-caudal spread and may be an optimal volume of anesthesia.


title: Quarantined.

text: As an emergency medicine physician, I am used to working when most people are not working. At the end of February, the first patient in the U.S. to be diagnosed with COVID-19 without a travel history occurred in Sacramento, CA. Over 120 healthcare professionals who had contact with the patient were quarantined. Beginning of March, I worked in the emergency department and treated a patient with viral symptoms without a travel history who was admitted to the hospital.


title: Mechanical circulatory support for right ventricular failure.

text: OBJECTIVES The aim of this study was to explore the clinical utility of a commercially available centrifugal flow pump as a centrifugal flow-right ventricular support device (CF-RVSD) in patients with right ventricular failure (RVF). BACKGROUND RVF is associated with high in-hospital mortality. Limited data regarding efficacy of the CF-RVSD for RVF exist. METHODS We retrospectively reviewed data from 46 patients receiving a CF-RVSD for RVF from a registry comprising data from 8 tertiary-care hospitals in the United States. CF-RVSD use was recorded in the setting of acute myocardial infarction; myocarditis; chronic left heart failure; after valve surgery, orthotopic heart transplantation, left ventricular assist device surgery, coronary bypass grafting. Devices were implanted via the percutaneous (n = 22) or surgical (n = 24) route. RESULTS No intraprocedural mortality was observed. Mean time from admission to CF-RVSD implantation was 5.7 ± 8.5 days, with a mean of 6,769 ± 789 rotations/min, providing 4.2 ± 1.3 l/min of flow. Mean duration of support was 5.4 ± 5.1 days. Mean arterial pressure (65 ± 12 mm Hg vs. 73 ± 14 mm Hg; p < 0.05), right atrial pressure (21 ± 8 mm Hg vs. 16 ± 7 mm Hg; p = 0.05), pulmonary artery systolic pressure (43 ± 15 mm Hg vs. 33 ± 15 mm Hg; p = 0.01), and cardiac index (1.7 ± 0.7 vs. 2.2 ± 0.6; p = 0.01) were improved within 48 h of CF-RVSD implantation. Total in-hospital mortality was 57% and was lowest in the setting of left ventricular assist device implantation, chronic left heart failure, and acute myocardial infarction. Increased age, biventricular failure, and Thrombolysis In Myocardial Infarction-defined major bleeding were associated with increased in-hospital mortality. CONCLUSIONS Use of the CF-RVSD for RVF is clinically feasible and associated with improved hemodynamic status. Observations from the registry of patients who have received this device may support the development of prospective studies that will examine the role of percutaneous circulatory support for RVF.


title: Population pharmacokinetics of lamotrigine in Indian epileptic patients.

text: PURPOSE The aim of this analysis was to describe the pharmacokinetics of oral lamotrigine (LTG) in Indian epileptic patients using a population pharmacokinetic (PPK) modeling approach to confirm that the PK is similar to that of the Caucasian population, and to evaluate and confirm the impact of covariates predictive of inter-individual variability using a simulation platform. METHODS Blood samples were obtained from 95 patients, and LTG plasma concentrations were determined. Population PK modeling was performed using NONMEM. A one-compartment PK model with first-order absorption and elimination was used to describe the LTG PK. Log-likelihood profiling and normalized prediction distribution errors (NPDE) were used for model evaluation. A simulation study was performed to investigate dose regimens. RESULTS Clearance (CL) was estimated to be 2.27 L/h with inter-individual variability (IIV) of 29 CV%. Volume of distribution (V) was estimated to be 53.6 L (31 CV% IIV). Body weight and concurrent use of carbamazepine and valproate were identified as significant covariates on clearance. Log-likelihood profiling indicated that parameters could be estimated with adequate precision, and NPDE indicated that the model adequately described the data observed. The simulation study illustrated the impact of carbamazepine and valproate on LTG PK, and negligible differences in PK between Indian and Caucasian patients. CONCLUSIONS This is the first PK analysis of LTG in Indian patients. The population PK model developed adequately described the data observed. Comparison of identified PK parameters with previous PK analyses in Caucasian patients indicates that CL of LTG is similar, while V is somewhat lower compared with Caucasian patients, but this is not expected to lead to relevant differences in PK profiles during steady state.


Beyond the Respiratory System: A Case Report Highlighting the Impact of COVID-19 in Mental Illness and Its Physical Consequences.


title: The Effect of Carotid Chemoreceptor Inhibition on Exercise Tolerance in Chronic Heart Failure.

text: Purpose Chronic heart failure (CHF) is characterized by heightened sympathetic nervous activity, carotid chemoreceptor (CC) sensitivity, marked exercise intolerance and an exaggerated ventilatory response to exercise. The purpose of this study was to determine the effect of CC inhibition on exercise cardiovascular and ventilatory function, and exercise tolerance in health and CHF. Methods Twelve clinically stable, optimally treated patients with CHF (mean ejection fraction: 43 ± 2.5%) and 12 age- and sex-matched healthy controls were recruited. Participants completed two time-to-symptom-limitation (TLIM) constant load cycling exercise tests at 75% peak power output with either intravenous saline or low-dose dopamine (2 μg⋅kg-1⋅min-1; order randomized). Ventilation was measured using expired gas data and operating lung volume data were determined during exercise by inspiratory capacity maneuvers. Cardiac output was estimated using impedance cardiography, and vascular conductance was calculated as cardiac output/mean arterial pressure. Results There was no change in TLIM in either group with dopamine (CHF: saline 13.1 ± 2.4 vs. dopamine 13.5 ± 1.6 min, p = 0.78; Control: saline 10.3 ± 1.2 vs. dopamine 11.5 ± 1.3 min, p = 0.16). In CHF patients, dopamine increased cardiac output (p = 0.03), vascular conductance (p = 0.01) and oxygen delivery (p = 0.04) at TLIM, while ventilatory parameters were unaffected (p = 0.76). In controls, dopamine improved vascular conductance at TLIM (p = 0.03), but no other effects were observed. Conclusion Our findings suggest that the CC contributes to cardiovascular regulation during full-body exercise in patients with CHF, however, CC inhibition does not improve exercise tolerance.


title: Short-term outcomes of typical versus atypical lung segmentectomy by minimally invasive surgeries.

text: BACKGROUND Segmentectomy is increasingly used to resect lung nodules. Robotic-assisted thoracic surgery (RATS) is considered a safe and practical method for segmentectomy. Few studies have compared robotic surgery and video-assisted thoracic surgery (VATS) for lung segmentectomy. METHOD We retrospectively examined 215 consecutive patients who underwent typical (88 patients) or atypical (128 patients) segmentectomy by either robotic surgery or VATS. The postoperative characteristics including operation time, blood loss, pneumonia, tumor size, lymph nodes harvested, chest tube duration, prolonged air leak, atrial fibrillation, and postoperative hospital stay were recorded. RESULTS A total of 88 patients underwent typical segmentectomy, while 127 patients underwent atypical segmentectomy. A greater number of lymph nodes were resected via RATS than by VATS (13.24 ± 4.84 vs. 11.71 ± 3.89; P = 0.018). The operation time for typical segmentectomy was shorter than that for atypical segmentectomy (115.69 ± 22.32 vs. 131.68 ± 22.52; P = 0). No significant differences were found between RATS and VATS in terms of chest drainage duration and postoperative hospital stay. The incidence of postoperative complications including prolonged air leak and atrial fibrillation was not significantly different between typical segmentectomy and atypical segmentectomy. CONCLUSION Atypical segmentectomy is more complicated than typical segmentectomy, which may lead to increases in complications and operation time. Robotic surgery was safe and practical for segmentectomy compared to VATS and more lymph nodes could be dissected by RATS without increasing the risk of postoperative complications.


title: Endovascular treatment of cerebral mycotic aneurysm: a review of the literature and single center experience.

text: The management of mycotic aneurysm has always been subject to controversy. The aim of this paper is to review the literature on the intracranial infected aneurysm from pathogenesis till management while focusing mainly on the endovascular interventions. This novel solution seems to provide additional benefits and long-term favorable outcomes.


title: Hunting coronavirus severe acute respiratory syndrome coronavirus 2 (2019 novel coronavirus): From laboratory testing back to basic research

text: The rapid spread of coronavirus disease 2019 (COVID-19) in many countries causes citizens of daily inconvenience and even life-threat for elderly population. The invasion of the main pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; 2019 novel coronavirus [2019-nCoV]), into human body causes different levels of impact to various patients. One of the most important issues for COVID-19 is how to defend this virus with the ability to foresee the infected targets. Thus, we maintain the quarantined essentially as for as others saved from COVID-19. So far, the routine laboratory test to confirm whether infected by SARS-CoV-2/2019-nCoV or not is through real-time reverse transcription polymerase chain reaction (rRT-PCR; quantitative polymerase chain reaction [qPCR]) with certain sequence regions that recognize SARS-CoV-2/2019-nCoV RNA genome. The heavy loading of rRT-PCR (qPCR) machine and handling labor have tight-packed the instruments as well as the manpower almost in every country. Therefore, the alternative approaches are eagerly waiting to be developed. In this review article, we sort out some state-of-the-art novel approaches that might be applied for a fast, sensitive, and precise detection of SARS-CoV-2/2019-nCoV not only to help the routine laboratory testing but also to improve effective quarantine.


title: Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors: in silico analysis.

text: The sharp spurt in positive cases of novel coronavirus-19 (SARS-CoV-2) worldwide has created a big threat to human. In view to expedite new drug leads for COVID-19, Main Proteases (Mpro) of novel Coronavirus (SARS-CoV-2) has emerged as a crucial target for this virus. Nitric oxide (NO) inhibits the replication cycle of SARS-CoV. Inhalation of nitric oxide is used in the treatment of severe acute respiratory syndrome. Herein, we evaluated the phenyl furoxan, a well-known exogenous NO donor to identify the possible potent inhibitors through in silico studies such as molecular docking as per target analysis for candidates bound to substrate binding pocket of SARS-COV-2 Mpro. Molecular dynamics (MD) simulations of most stable docked complexes (Mpro-22 and Mpro-26) helped to confirm the notable conformational stability of these docked complexes under dynamic state. Furthermore, Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations revealed energetic contributions of key residues of Mpro in binding with potent furoxan derivatives 22, 26. In the present study to validate the molecular docking, MD simulation and MM-PBSA results, crystal structure of Mpro bound to experimentally known inhibitor X77 was used as control and the obtained results are presented herein. We envisaged that spiro-isoquinolino-piperidine-furoxan moieties can be used as effective ligand for SARS-CoV-2 Mpro inhibition due to the presence of key isoquinolino-piperidine skeleton with additional NO effect. Communicated by Ramaswamy H. Sarma.


title: Importance of controlling nanotube density for highly sensitive and reliable biosensors functional in physiological conditions.

text: Biosensors utilizing carbon nanotube field-effect transistors have a tremendous potential to serve as the basis for the next generation of diagnostic systems. While nanotubes have been employed in the fabrication of multiple sensors, little attention has previously been paid to how the nanotube density affects the biosensor performance. We conducted a systematic study of the effect of density on the performance of nanotube biosensors and discovered that this parameter is crucial to achieving consistently high performance. We found that devices with lower density offer higher sensitivity in terms of both detection limit and magnitude of response. The low density nanotube devices resulted in a detection limit of 1 pM in an electrolyte buffer containing high levels of electrolytes (ionic concentration ∼140 mM, matching the ionic strength of serum and plasma). Further investigation suggested that the enhanced sensitivity arises from the semiconductor-like behavior-strong gate dependence and lower capacitance-of the nanotube network at low density. Finally, we used the density-optimized nanotube biosensors to detect the nucleocapsid (N) protein of the SARS virus and demonstrated improved detection limits under physiological conditions. Our results show that it is critical to carefully tune the nanotube density in order to fabricate sensitive and reliable devices.


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title: David Oliver: Let's not forget care homes when covid-19 is over.


title: Hemodynamic monitoring and management of patients undergoing high-risk surgery: a survey among Chinese anesthesiologists.

text: Hemodynamic monitoring and optimization improve postoperative outcome during high-risk surgery. However, hemodynamic management practices among Chinese anesthesiologists are largely unknown. This study sought to evaluate the current intraoperative hemodynamic management practices for high-risk surgery patients in China. From September 2010 to November 2011, we surveyed anesthesiologists working in the operating rooms of 265 hospitals representing 28 Chinese provinces. All questionnaires were distributed to department chairs of anesthesiology or practicing anesthesiologists. Once completed, the 29-item questionnaires were collected and analyzed. Two hundred and 10 questionnaires from 265 hospitals in China were collected. We found that 91.4% of anesthesiologists monitored invasive arterial pressure, 82.9% monitored central venous pressure (CVP), 13.3% monitored cardiac output (CO), 10.5% monitored mixed venous saturation, and less than 2% monitored pulse pressure variation (PPV) or systolic pressure variation (SPV) during high-risk surgery. The majority (88%) of anesthesiologists relied on clinical experience as an indicator for volume expansion and more than 80% relied on blood pressure, CVP and urine output. Anesthesiologists in China do not own enough attention on hemodynamic parameters such as PPV, SPV and CO during fluid management in high-risk surgical patients. The lack of CO monitoring may be attributed largely to the limited access to technologies, the cost of the devices and the lack of education on how to use them. There is a need for improving access to these technologies as well as an opportunity to create guidelines and education for hemodynamic optimization in China.


title: Histopathological Response and Adhesion Formation After Omentectomy with Ultrasonic Energy, Bipolar Sealing, and Suture Ligation.

text: This study was designed to evaluate the histopathological response and intra-abdominal adhesion formation after an omentectomy in rats using the bipolar vessel-sealing device, ultrasonic coagulator, and suture ligation techniques. Forty Wistar albino rats were used, divided into four random groups. The rats underwent a midline laparotomy, and a partial omentectomy was performed using a 3-0 silk suture with suture ligation in group 1, bipolar device in group 2, and ultrasonic coagulator in group 3; only a laparotomy was performed on the control group. Lateral thermal damage was examined the same day, and a piece of the omentum was left in the animals to be examined on postoperative day 15. A relaparotomy was performed to assess adhesion formation and histopathological response. In pairwise comparisons, there was no statistically significant difference among the ultrasonic device, bipolar device, and suture ligation groups in terms of microscopic adhesion scoring; however, the scores of the bipolar device and suture ligation groups were significantly higher compared with those of the control group (p < 0.01). Furthermore, the macroscopic adhesion scores were significantly lower for the ultrasonic device group when compared with those of the bipolar device and suture ligation groups (p < 0.05 and p < 0.01). The ultrasonic device seems to be superior to the bipolar device and suture ligation in terms of macroscopic adhesion formation, but no significant difference was found in terms of the histopathological response in rats following an omentectomy. Further research may be required.


title: Colonic Foreign Body Retrieval Using a Modified TAMIS Technique with Standard Instruments and Trocars.

text: Background. Reports of retained colorectal foreign bodies (CFBs) are no longer considered uncommon. We present a case where a retained CFB was retrieved using a modified TAMIS technique using standard instruments and trocars. Case Report. A 52-year-old man presented with a CFB. We report our technique of extraction with standard laparoscopic instruments without specialized access platforms. Conclusions. This modified TAMIS technique is well suited for resource poor environments because it requires no specialized equipment, platforms, or additional skill sets compared to conventional laparoscopy.


title: A combinatorial library of lipid-like materials for delivery of RNAi therapeutics.

text: The safe and effective delivery of RNA interference (RNAi) therapeutics remains an important challenge for clinical development. The diversity of current delivery materials remains limited, in part because of their slow, multi-step syntheses. Here we describe a new class of lipid-like delivery molecules, termed lipidoids, as delivery agents for RNAi therapeutics. Chemical methods were developed to allow the rapid synthesis of a large library of over 1,200 structurally diverse lipidoids. From this library, we identified lipidoids that facilitate high levels of specific silencing of endogenous gene transcripts when formulated with either double-stranded small interfering RNA (siRNA) or single-stranded antisense 2'-O-methyl (2'-OMe) oligoribonucleotides targeting microRNA (miRNA). The safety and efficacy of lipidoids were evaluated in three animal models: mice, rats and nonhuman primates. The studies reported here suggest that these materials may have broad utility for both local and systemic delivery of RNA therapeutics.