title: The predictive performance of propofol target-controlled infusion during robotic-assisted laparoscopic prostatectomy with CO2 pneumoperitoneum in the head-down position.

text: PURPOSE Propofol clearance can be reduced when cardiac output (CO) is decreased. This clearance reduction may alter the pharmacokinetics of propofol and worsen the predictive performance of target-controlled infusion (TCI) of propofol. The head-down position (HDP) and CO2 pneumoperitoneum, which are required for robotic-assisted laparoscopic prostatectomy (RALP), may cause changes in CO. We investigated the predictive performance of propofol TCI during CO2 pneumoperitoneum in patients who underwent RALP in the HDP. METHODS Fifteen male patients received propofol TCI using the Diprifusor model. Propofol concentrations were measured at seven time points: (T1) 15 min after anesthesia induction; (T2) before the insufflation; (T3, T4, and T5) 15, 60, and 90 min, respectively, after insufflation in the HDP; (T6) before the release of pneumoperitoneum in the HDP; and (T7) 15 min after the release of pneumoperitoneum in the supine position. Cardiac index (CI) was assessed using an arterial pulse contour CO monitor. The predictive performance of propofol TCI was evaluated by calculating the performance errors (PE) in propofol concentrations for each data point. The relationship between CI and PE was examined. Median PE (MDPE) and median absolute PE (MDAPE) were calculated as measures of bias and accuracy, respectively. RESULTS A total of 104 blood samples were analyzed. There was significantly negative correlation between CI and PE. The predictive performance of propofol TCI during pneumoperitoneum in the HDP was acceptable (MDPE = - 1.5% and MDAPE = 18.8%). CONCLUSION The predictive performance of propofol TCI during RALP with CO2 pneumoperitoneum in the HDP was acceptable.


title: Software tools to support title and abstract screening for systematic reviews in healthcare: an evaluation.

text: BACKGROUND Systematic reviews are vital to the pursuit of evidence-based medicine within healthcare. Screening titles and abstracts (T&Ab) for inclusion in a systematic review is an intensive, and often collaborative, step. The use of appropriate tools is therefore important. In this study, we identified and evaluated the usability of software tools that support T&Ab screening for systematic reviews within healthcare research. METHODS We identified software tools using three search methods: a web-based search; a search of the online "systematic review toolbox"; and screening of references in existing literature. We included tools that were accessible and available for testing at the time of the study (December 2018), do not require specific computing infrastructure and provide basic screening functionality for systematic reviews. Key properties of each software tool were identified using a feature analysis adapted for this purpose. This analysis included a weighting developed by a group of medical researchers, therefore prioritising the most relevant features. The highest scoring tools from the feature analysis were then included in a user survey, in which we further investigated the suitability of the tools for supporting T&Ab screening amongst systematic reviewers working in medical research. RESULTS Fifteen tools met our inclusion criteria. They vary significantly in relation to cost, scope and intended user community. Six of the identified tools (Abstrackr, Colandr, Covidence, DRAGON, EPPI-Reviewer and Rayyan) scored higher than 75% in the feature analysis and were included in the user survey. Of these, Covidence and Rayyan were the most popular with the survey respondents. Their usability scored highly across a range of metrics, with all surveyed researchers (n = 6) stating that they would be likely (or very likely) to use these tools in the future. CONCLUSIONS Based on this study, we would recommend Covidence and Rayyan to systematic reviewers looking for suitable and easy to use tools to support T&Ab screening within healthcare research. These two tools consistently demonstrated good alignment with user requirements. We acknowledge, however, the role of some of the other tools we considered in providing more specialist features that may be of great importance to many researchers.


title: Dual roles of DNA repair enzymes in RNA biology/post-transcriptional control.

text: Despite consistent research into the molecular principles of the DNA damage repair pathway for almost two decades, it has only recently been found that RNA metabolism is very tightly related to this pathway, and the two ancient biochemical mechanisms act in alliance to maintain cellular genomic integrity. The close links between these pathways are well exemplified by examining the base excision repair pathway, which is now well known for dual roles of many of its members in DNA repair and RNA surveillance, including APE1, SMUG1, and PARP1. With additional links between these pathways steadily emerging, this review aims to provide a summary of the emerging roles for DNA repair proteins in the post-transcriptional regulation of RNAs. WIREs RNA 2016, 7:604-619. doi: 10.1002/wrna.1353 For further resources related to this article, please visit the WIREs website.


title: Association between the employment status and the presence of depressive symptoms in men and women in Mexico.

text: This study aims to estimate the relationship between employment status and depressive symptoms among Mexican adults, as well as to explore its differential effect by gender. Cross-sectional study of 36,516 adults between 20 and 59 years of age taken from the 2012 Mexican National Health and Nutrition Survey. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale (CES-D), and the employment status was determined a week before the survey. Logistic regression models were stratified by gender and education level and adjusted by sociodemographic and health-related conditions to estimate the association between depressive symptoms and employment status. The prevalence of clinically depressive symptoms was 7.59% for men and 18.62% for women. In the case of men, those who were unemployed were more likely to present depressive symptoms (OR = 1.66; 95%CI: 1.08-2.55) than those who were working. For women, employment status is not associated with the presence of depressive symptoms, except in students (OR = 1.57; 95%CI: 1.02-2.43) compared with those who were working. In both genders, disability preventing one from working was associated with depressive symptoms. Although being employed has been reported to be associated with lower levels of psychiatric morbidity, the estimated effect is different for men and women. Occupational health policies should consider these conditions.


title: Laparoscopic ovariectomy in dogs: a comparison of the LigaSure™ and the SonoSurg™ systems.

text: OBJECTIVES The objective of this study was to evaluate the surgical times for removal of ovaries, and the frequency of intra-operative complications with two different instruments used for canine laparoscopic ovariectomy. METHODS A randomised prospective clinical study. Laparoscopic ovariectomy was performed under general anaesthesia on 10 healthy female dogs admitted for elective ovariectomy. Each ovary was randomly assigned to removal by use of either a SonoSurg™ ultrasonic surgical device (Olympus), or a LigaSure™ vessel-sealing system (Valleylab/Covidien). Surgical time for removal of each ovary was measured and the frequency of intra-operative complications was recorded. A follow-up was made by interview with the owners, 2·5 years after surgery. RESULTS The two techniques did not statistically differ with regard to surgical time, or frequency of complications. All owners were very satisfied with the procedure. CLINICAL RELEVANCE Both the SonoSurg™ and the LigaSure™ devices appear to be effective, safe and easy to use when performing laparoscopic ovariectomy in dogs.


title: Co-colonization by Streptococcus pneumoniae and Staphylococcus aureus in the throat during acute respiratory illnesses.

text: Pneumonia due to either Streptococcus pneumoniae (Sp) or Staphylococcus aureus (Sa) accounts for most mortality after influenza and acute respiratory illness (ARI). Because carriage precedes infection, we estimated Sp and Sa carriage to examine the co-colonization dynamics between Sp, Sa and respiratory viruses in the presence of ARI in the oropharynx. We tested oropharyngeal specimens of community subjects (aged ⩾2 years) with ARI for the presence of influenza A and B, 11 other common respiratory viruses, Sp and Sa, using real-time PCR. A total of 338 participants reported 519 ARI episodes of which 119 (35%) carried Sp, 52 (13%) carried Sa and 25 (7%) carried both. Thirty-five subjects tested positive for influenza, of which 14 (40%) carried Sp and six (17%) carried Sa, significantly more than in the influenza-negative group (P = 0·03 and P = 0·04, respectively). In subjects infected by any virus compared to those with no virus, Sp carriage (39·2% vs. 27·9%, P = 0·03) but not Sa carriage (11·6% vs. 14%, P = 0·6) was more frequent. For children, when Sa was present, Sp carriage tended to be less frequent than expected given the presence of viral infection, but not significantly [observed relative risk 1·14, 95% confidence interval (CI) 0·4-3·1; with a relative excess risk due to interaction of -0·11]. Independent of age, Sp carriers were more likely to return that season with subsequent ARI (odds ratio 2·14, 95% CI 1·1-4·3, P = 0·03). Both Sp and Sa carriage rates in the oropharynx increase during influenza infection in children. However, no negative interaction between Sp and Sa was observed. Sp carriers are more likely to suffer subsequent ARI episodes than non-carriers.


title: Comparison of multiple viral population characterization methods on a candidate cross-protection Citrus tristeza virus (CTV) source.

text: Citrus tristeza virus (CTV) is the most economically important virus found on citrus and influences production worldwide. The 3' half of the RNA genome is generally conserved amongst sources, whereas the 5' portion is more divergent, allowing for the classification of the virus into a number of genotypes based on sequence diversity. The acknowledged genotypes of CTV are continually being expanded, and thus far include T36, T30, T3, VT, B165, HA16-5, T68 and RB. The genotype composition of the CTV populations of a potential cross protection source in Mexican lime was studied whilst comparing different techniques of viral population characterization. Cloning and sequencing of an ORF 1a fragment, genotype specific RT-PCRs and Illumina sequencing of the p33 gene as well as RNA template enrichment through immuno-capture was done. Primers used in the cloning and sequencing proved to be biased towards detection of the VT genotype. RT-PCR and Illumina sequencing using the two different templates provided relatively comparable results, even though the immuno-captured enriched template provided less than expected CTV specific data, while the RT-PCRs and p33 sequencing cannot be used to make inferences about the rest of the genome; which may vary due to recombination. The source was found to contain multiple genotypes, including RB and VT. When choosing a characterization method, the features of the virus under study should be considered. It was found that Illumina sequencing offers an opportunity to gain a large amount of information regarding the entire viral genome, but challenges encountered are discussed.


title: Dynamic evaluation of near-infrared peripheral oximetry in healthy volunteers: a comparison between INVOS and EQUANOX.

text: PURPOSE The present study aimed to compare peripheral regional tissue oxygen saturation (rSO2) values and desaturation/resaturation rates given by INVOS and EQUANOX devices. MATERIALS AND METHODS Twenty healthy volunteers were investigated during 4 experimental steps: baseline, hyperoxia, ischemia, and reperfusion. For each volunteer, 2 sensors INVOS and 2 sensors EQUANOX were placed on both left and right calves. Blood pressure, heart rate, and peripheral pulse oximetry were monitored. RESULTS Peripheral rSO2 ranged from 40% to 95% (INVOS) and from 47% to 100% (EQUANOX): 81±12 vs 82±9 (P=.469). A significant relationship was found at baseline between absolute values of INVOS and EQUANOX (n=40; R2=0.159; P=.011). Bias was -0.4%, and limits of agreement were ±15.1%. The percent maximum differences vs baseline values during dynamic maneuvers were 33%±19% (95% confidence interval, 24-42) and 21%±14% (95% confidence interval, 15-28) for INVOS and EQUANOX, respectively. No significant relationship was observed between percent maximum differences in INVOS and EQUANOX (n=20; R2=0.128; P=.122). Rates of desaturation/resaturation during occlusive vascular tests were 3.65% per minute vs 2.36% per minute (P=.027) and 30.42% per minute vs 16.28% per minute (P=.004) for INVOS and EQUANOX, respectively. CONCLUSIONS INVOS and EQUANOX are not comparable in measuring both absolute values and dynamic changes of peripheral rSO2 and near-infrared spectroscopy-derived parameters during occlusion vascular tests.


title: Open mini-flank partial nephrectomy: an essential contemporary operation.

text: Secondary to the widespread use of the modern imaging techniques of computed tomography, magnetic resonance imaging, and ultrasound, 70% of renal tumors today are detected incidentally with a median tumor size of less than 4 cm. Twenty years ago, all renal tumors, regardless of size were treated with radical nephrectomy (RN). Elective partial nephrectomy (PN) has emerged as the treatment of choice for small renal tumors. The basis of this paradigm shift is three major factors: (1) cancer specific survival is equivalent for T1 tumors (7 cm or less) whether treated by PN or RN; (2) approximately 45% of renal tumors have indolent or benign pathology; and (3) PN prevents or delays the onset of chronic kidney disease, a condition associated with increased cardiovascular morbidity and mortality. Although PN can be technically demanding and associated with potential complications of bleeding, infection, and urinary fistula, the patient derived benefits of this operation far outweigh the risks. We have developed a "mini-flank" open surgical approach that is highly effective and, coupled with rapid recovery postoperative care pathways associated with a 2-day length of hospital stay.


title: Probing the metastable state of influenza hemagglutinin.

text: Viral entry into host cells is mediated by membrane proteins in a metastable state that transition to a more stable state upon a stimulus. For example, in the influenza envelope protein hemagglutinin (HA), the low pH in the endosome triggers a transition from the metastable prefusion conformation to the stable fusion conformation. To identify probes that interfere with HA function, here we screened a library of H7 HA peptides for inhibition of H7 HA-mediated entry. We discovered a peptide, PEP87 (WSYNAELLVAMENQHTI), that inhibited H7 and H5 HA-mediated entry. PEP87 corresponds to a highly conserved helical region of the HA2 subunit of HA that self-interacts in the neutral pH conformation. Mutagenesis experiments indicated that PEP87 binds to its native region in the HA trimer. We also found that PEP87 is unstructured in isolation but tends to form a helix as evidenced by CD and NMR studies. Fluorescence, chemical cross-linking, and saturation transfer difference NMR data suggested that PEP87 binds to the neutral pH conformation of HA and disrupts the HA structure without affecting its oligomerization state. Together, this work provides support for a model in which PEP87 disrupts HA function by displacing native interactions of the neutral pH conformation. Moreover, our observations indicate that the HA prefusion structure (and perhaps the metastable states of other viral entry proteins) is more dynamic with transient motions being larger than generally appreciated. These findings also suggest that the ensemble of prefusion structures presents many potential sites for targeting in therapeutic interventions.


title: Laparoscopic hand-assisted liver resection for tumours in the left lateral section.

text: Context The role of the laparoscopic left lateral sectionectomy (LLLS) is debatable, and Level-1 data are lacking. Aims The aim of the study is to evaluate the feasibility and safety of this approach. Settings and Design This was a retrospective study. Subjects and Methods From 2007 to 2014, patients undergoing LLLS were identified from two institutions. Statistical Analysis Used Continuous variables were compared between groups with Student's t-test or Mann-Whitney test, as appropriate by type of distribution. Categorical variables were compared with Chi-square or Fisher's exact test, depending on the number of observations. Results Thirty-eight patients were included in the study. The mean age was 63.5 + 13 years (range, 31-89), and the mean number of tumours was 1.7 + 1.5. Eleven (29%) patients underwent LLS combined with an additional liver resection (combined resections group). The mean duration of the operation and the mean estimated blood loss were significantly decreased in the LLS group compared to the combined resection group (101 + 71 min vs. 208 + 98 min and 216 + 217 ml vs. 450 + 223 ml; P < 0.05 for both, respectively). The major complications rate was 8% and no mortality occurred. Conclusions In a subset of carefully selected cases, LLLS may provide the benefits of laparoscopy. This does not appear to compromise perioperative morbidity rates. We believe that this approach may serve as a training platform for surgical trainees.


title: A Network Pharmacology Approach to Explore the Potential Mechanisms of Huangqin-Baishao Herb Pair in Treatment of Cancer.

text: BACKGROUND The aim of this study was to identify the bioactive ingredients of Huangqin-Baishao herb pair and to reveal its anti-cancer mechanisms through a pharmacology approach. MATERIAL AND METHODS Detailed information on compounds in the HQ-BS herb pair was obtained from the Traditional Chinese medicine systems pharmacology (TCMSP) and screened by the criteria of OB ≥30% and DL ≥0.18. A systematic drug targeting model (SysDT) was used for compound targets prediction, and then the targets were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The protein-protein interaction (PPI) network of HQ-BS targets was constructed, after identifying core networks through Cytoscape plugins. RESULTS We found 47 bioactive compounds of HQ-BS and 107 human-derived targets. A compound target network and a target signal pathway network were constructed and used for topological analysis. Kaempferol, beta-sitosterol, stigmasterol, wogonin, and oroxylin-a were identified as core compounds and pathways in cancer. The calcium signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, chemical carcinogenesis, estrogen signaling pathway, proteoglycans in cancer, HIF-1 signaling pathway, thyroid hormone signaling pathway, VEGF signaling pathway, small cell lung cancer, prostate cancer, colorectal cancer, NOD-like receptor signaling pathway, and T cell receptor signaling pathway were found to be potential signals of HQ-BS in treating cancer. Through PPI network analysis, TNF signaling pathway, tryptophan metabolism, proteoglycans in cancer, cell cycle, and chemical carcinogenesis sub-networks were obtained. CONCLUSIONS HQ-BS contains various bioactive compounds, including flavonoids, phytosterols, and other compounds, and these compounds can inhibit or activate multiple targets and pathways against cancer.


Challenges of pancreatic cancer chemotherapy in the COVID-19 era.


title: Viral mutation rates.

text: Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 10(-8) to 10(-6) s/n/c for DNA viruses and from 10(-6) to 10(-4) s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mutation rate and genome size among RNA viruses, but this result requires further experimental testing. Contrary to some suggestions, the mutation rate of retroviruses is not lower than that of other RNA viruses. We also show that nucleotide substitutions are on average four times more common than insertions/deletions (indels). Finally, we provide estimates of the mutation rate per nucleotide per strand copying, which tends to be lower than that per cell infection because some viruses undergo several rounds of copying per cell, particularly double-stranded DNA viruses. A regularly updated virus mutation rate data set will be available at www.uv.es/rsanjuan/virmut.


Helen Salisbury: Practising in the dark.


title: Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex.

text: Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.


title: Use of ferrets for electrophysiologic monitoring of ion transport.

text: Limited success achieved in translating basic science discoveries into clinical applications for chronic airway diseases is attributed to differences in respiratory anatomy and physiology, poor approximation of pathologic processes, and lack of correlative clinical endpoints between humans and laboratory animal models. Here, we discuss advantages of using ferrets (Mustela putorus furo) as a model for improved understanding of human airway physiology and demonstrate assays for quantifying airway epithelial ion transport in vivo and ex vivo, and establish air-liquid interface cultures of ferret airway epithelial cells as a complementary in vitro model for mechanistic studies. We present data here that establishes the feasibility of measuring these human disease endpoints in ferrets. Briefly, potential difference across the nasal and the lower airway epithelium in ferrets could be consistently assessed, were highly reproducible, and responsive to experimental interventions. Additionally, ferret airway epithelial cells were amenable to primary cell culture methods for in vitro experiments as was the use of ferret tracheal explants as an ex vivo system for assessing ion transport. The feasibility of conducting multiple assessments of disease outcomes supports the adoption of ferrets as a highly relevant model for research in obstructive airway diseases.


title: The era of genomic epidemiology.

text: The recent revolution in genomics is already having a profound impact on the practice of epidemiology. The purpose of this commentary is to demonstrate how genomics and epidemiology will continue to rely heavily on each other, now and in the future, by illustrating a number of interaction points between these 2 disciplines: (1) the use of genomics to estimate disease heritability; (2) the impact of genomics on analytical study design; (3) how genome-wide data can be employed to effectively overcome residual population stratification arising from selection bias; (4) the importance of genomics as a tool in epidemiological investigation; (5) the importance of epidemiology in the collection of adequately phenotyped samples for genomics studies, and (6) for unraveling the clinical and therapeutic relevance of genetic variants once they are discovered.


title: Measles-vectored vaccine approaches against viral infections: a focus on Chikungunya.

text: INTRODUCTION The large global burden of viral infections and especially the rapidly spreading vector-borne diseases and other emerging viral diseases show the need for new approaches in vaccine development. Several new vaccine technology platforms have been developed and are under evaluation. Areas covered: This article discusses the measles vector platform technology derived from the safe and highly efficacious measles virus vaccine. The pipeline of measles-vectored vaccine candidates against viral diseases is reviewed. Particular focus is given to the Chikungunya vaccine candidate as the first measles-vectored vaccine that demonstrated safety, immunogenicity, and functionality of the technology in humans even in the presence of pre-existing anti-measles immunity and thus achieved proof of concept for the technology. Expert commentary: Demonstrating no impact of pre-existing anti-measles immunity in humans on the response to the transgene was fundamental for the technology and indicates that the technology is suitable for large-scale immunization in measles pre-immune populations. The proof of concept in humans combined with a large preclinical track record of safety, immunogenicity, and efficacy for a variety of pathogens suggest the measles vector platform as promising plug-and-play vaccine platform technology for rapid development of effective preventive vaccines against viral and other infectious diseases.


title: Early results of endovascular treatment of patients with bilateral stenoses of the internal carotid arteries using proximal protection systems at 30-day follow-up.

text: BACKGROUND Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, carotid artery stenting (CAS) with use of proximal protection systems (PPS) plays an very important role as alternative treatment modality, especially in patients with critical, symptomatic lesions. This study was single-centre study to evaluate the technical and clinical success of proximal protection devices as the first choice for embolic protection in symptomatic and asymptomatic carotid stenosis in patients with bilateral, advanced lesions of carotid arteries (bilateral stenoses or stenosis and occlusion). METHODS This was a post hoc analysis, with 30-day follow up. We analyzed results of treatment of 38 patients who underwent 38 CAS with PPS, 17 such procedures in asymptomatic (group A), and 21 in symptomatic individuals (group B). The GORE® Flow Reversal System (W.L. Gore, Flagstaff, AZ, USA) was used in 2 patients, and the Mo.Ma Ultra device (Medtronic, Minneapolis, MN, USA) in 36 patients. Mean age was 68±7 years, 65% percent of patient were male. RESULTS There were no procedural and during 30-day follow-up neurologic events. Intolerance of occlusion system occurred in 4 patients (11%) in both groups with any later symptoms. Risk factors of this adverse event comprised: lesions of the left internal carotid lesion and coexisiting diabetes mellitus. CONCLUSIONS CAS in high risk patients with bilateral lesions of carotid arteries with the use of PPS seems to be a relatively very safe procedure.


title: Silk flow-diverter stent for the treatment of complex intracranial aneurysms: A one-year follow-up multicenter study.

text: Background Flow-diverter stents have been successfully used in the treatment of complex aneurysms with limited therapeutic alternatives. We report our experience using the Silk flow diverter (SFD; Balt Extrusion, Montmorency, France) for the treatment of complex aneurysms in four Argentine centers. Methods We conducted a retrospective review of 246 consecutive patients who were treated with the SFD at four Argentine centers between January 2009 and January 2017. The patient and aneurysm characteristics, as well as the details of the procedure, were analyzed. The angiographic and clinical findings were recorded during and immediately after the procedure and at 12-month follow-up. Results Angiography follow-up at 12 months was possible in 235 patients (95.5%) with 282 aneurysms. A total of 265 aneurysms (93.9%) presented with complete occlusion of the aneurysmal sac (class 1) and 17 aneurysms (6.1%) presented with partial occlusion (class 2). The 12-month clinical follow-up showed 11 patients with major events (seven, scale 2; five, scale 3; and two, scale 4). The morbidity and mortality rates were 4.2% (11/289) and 2.1% (5/289), respectively. Conclusions The treatment of aneurysms with the SFD was associated with a low rate of complications and a high percentage of aneurysmal occlusion. These findings suggest that SFD is an effective and safe alternative in the endovascular treatment of complex aneurysms.


title: Clinical characteristics of human bocavirus infections compared with other respiratory viruses in Spanish children.

text: BACKGROUND Human bocavirus (HBoV) can be found in a substantial proportion of children with respiratory tract diseases. The relative importance of HBoV in viral respiratory tract illnesses is not yet well known. OBJECTIVE In this study, we looked for HBoV in pediatric patients to determine the incidence of HBoV as single infection and compared it with other commonly found respiratory viruses to describe the clinical differences associated with HBoV infections in children. PATIENTS AND METHODS A prospective study was conducted on children less than 14 years old, admitted with respiratory infection from September 2005 to August 2007 to the Pediatrics Department of the Severo Ochoa Hospital, Madrid, Spain. We studied the frequency of HBoV and 15 other respiratory viruses in nasopharyngeal aspirates and compared the clinical course of the infections caused by HBoV with those caused by other common respiratory viruses. RESULTS Positive results were confirmed in 435 (61.2%) of the 710 children studied. A single virus was detected in 308 patients. HBoV was found in 99 (13.9%) samples, but it was recovered as a single virus in only 35. Most of patients with HBoV infection (75%) were aged < or =26 months. The most common clinical diagnosis was recurrent wheezing (53%), followed by bronchiolitis (32%). Clinical differences were observed between HBoV and respiratory syncytial virus (RSV) infections (children were older and bronchiolitis less frequent), adenovirus (fever less frequent in HBoV group), and rhinovirus-associated infections (less hypoxia in HBoV group). CONCLUSIONS HBoV was the fourth most frequent single virus after RSV, rhinovirus, and adenovirus in children hospitalized because of respiratory infection. It was associated with recurrent wheezing and bronchiolitis showing a different clinical course from other virus in terms of diagnosis, fever, and age.


title: The role of single-incision laparoscopic surgery in abdominal and pelvic surgery: a systematic review.

text: OBJECTIVE This review aimed to determine the role of single-incision laparoscopic surgery (SILS) in abdominal and pelvic operations. DATA SOURCES The Medline, EMBASE, and PsycINFO databases were systematically searched until October 2009 using "single-incision laparoscopic surgery" and related terms as keywords. References from retrieved articles were reviewed to broaden the search STUDY SELECTION The study included case reports, case series, and empirical studies that reported SILS in abdominal and pelvic operations. DATA EXTRACTION Number of patients, type of instruments, operative time, blood loss, conversion rate, length of hospital stay, length of follow-up evaluation, and complications were extracted from the reviewed items DATA SYNTHESIS The review included 102 studies classified as level 4 evidence. Most of these studies investigated SILS in cholecystectomy (n=34), appendectomy (n=24), and nephrectomy (n=17). For these procedures, operative time, hospital stay, and complications were comparable with those of conventional laparoscopy. Conversion to conventional laparoscopy was seldom performed in cholecystectomy (range, 0-24%) and more frequent in appendectomy (range, 0-41%) and nephrectomy (range, 0-33%). CONCLUSION The potential benefits of SILS include superior cosmesis and possibly shorter operative time, lower costs, and a shortened time to full physical recovery. Careful case selection and a low threshold of conversion to conventional laparoscopic surgery are essential. Multicenter, randomized, prospective studies are needed to compare short- and long-term outcome measures against those of conventional laparoscopic surgery.


title: Median infectious dose of human norovirus GII.4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age.

text: Human noroviruses (NoVs), a major cause of viral gastroenteritis, are difficult to study due to the lack of a cell-culture and a small-animal model. Pigs share with humans the types A and H histo-blood group antigens on the intestinal epithelium and have been suggested as a potential model for studies of NoV pathogenesis, immunity and vaccines. In this study, the effects of age and a cholesterol-lowering drug, simvastatin, on the susceptibility of pigs to NoV infection were evaluated. The median infectious dose (ID50) of a genogroup II, genotype 4 (GII.4) 2006b variant was determined. The ID50 in neonatal (4-5 days of age) pigs was ≤2.74×10(3) viral RNA copies. In older pigs (33-34 days of age), the ID50 was 6.43×10(4) but decreased to <2.74×10(3) in simvastatin-fed older pigs. Evidence of NoV infection was obtained by increased virus load in the intestinal contents, cytopathological changes in the small intestine, including irregular microvilli, necrosis and apoptosis, and detection of viral antigen in the tip of villi in duodenum. This GII.4 variant was isolated in 2008 from a patient from whom a large volume of stool was collected. GII.4 NoVs are continuously subjected to selective pressure by human immunity, and antigenically different GII.4 NoV variants emerge every 1-2 years. The determination of the ID50 of this challenge virus is valuable for evaluation of protection against different GII.4 variants conferred by NoV vaccines in concurrence with other GII.4 variants in the gnotobiotic pig model.


title: Development of a lateral flow immunoassay strip for rapid detection of IgG antibody against SARS-CoV-2 virus.

text: The ongoing worldwide SARS-CoV-2 epidemic clearly has a tremendous influence on public health. Molecular detection based on oral swabs was used for confirmation of SARS-CoV-2 infection. However, high false negative rates were reported. We describe here the development of a point-of-care (POC) serological assay for the detection of IgG antibody against SARS-CoV-2. The principle of a lateral flow immunoassay strip (LFIAs) consists of fixing SARS-CoV-2 nucleocapsid protein to the surface of the strip and coupling anti-human IgG with colloidal gold nanoparticles (Au NPs). A series of parameters of this method were optimized, including the concentration of coating antigen, BSA blocking concentration and pH value for conjugation. The entire detection process took 15-20 min with a volume of 80 μL of the analyte solution containing 10 μL of serum and 70 μL sample diluent. The performance of the established assay was evaluated using serum samples of the clinically diagnosed cases of Coronavirus Disease 2019 (COVID-19). Our results indicated that the LFIAs for SARS-CoV-2 had satisfactory stability and reproducibility. As a result, our fast and easy LFIAs could provide a preliminary test result for physicians to make the correct diagnosis of SARS-CoV-2 infections along with alternative testing methods and clinical findings, as well as seroprevalence determination, especially in low-resource countries.


MicroRNAs as Biomarkers in CS-resistant/Neutrophilic Asthma: Still a Long Way to Go!


title: Assessing the impact of a 2-day laparoscopic intestinal workshop.

text: BACKGROUND Surgical educators have responded to the demand for increased skills in minimally invasive surgery by offering short technique-focused workshops at academic centres. The purpose of this study was to determine the impact of a comprehensive laparoscopic intestinal workshop for the adoption of laparoscopic colonic surgery. METHODS A 2-day comprehensive laparoscopic intestinal surgery workshop included didactic teaching and supervised hands-on practice of numerous laparoscopic colon resections on a cadaveric model. Participants completed pre-, post- and 6-month postcourse questionnaires. RESULTS The participants (n = 39) had been in practice for a mean of 10 (interquartile range 3-18) years. Fifty-one percent (n = 20) were already performing laparoscopic colectomies as part of their practices prior to the course. Regardless of whether they were performing laparoscopic colectomies prior to the course or not, attending the 2-day workshop improved their self-assessed preparedness to perform laparoscopic colectomies. Six months after the intestinal workshop, 10 of 16 respondents who were not performing laparoscopic colectomies prior to the course had performed at least 1 since the course. Seven of these individuals had a preceptor for their first case. Reasons cited for not performing a laparoscopic colectomy since the workshop included perceived inadequate surgical skill set, a lack of preceptor and the lack of an appropriate patient. CONCLUSION A comprehensive laparoscopic intestinal workshop contributed to the perceived acquisition of advanced laparoscopic surgical skills. Local laparoscopic preceptorship was an important adjunct to the workshop for the incorporation of laparoscopic colorectal surgery into practice.


title: A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties.

text: This report describes the design, generation and testing of Ylanthia, a fully synthetic human Fab antibody library with 1.3E+11 clones. Ylanthia comprises 36 fixed immunoglobulin (Ig) variable heavy (VH)/variable light (VL) chain pairs, which cover a broad range of canonical complementarity-determining region (CDR) structures. The variable Ig heavy and Ig light (VH/VL) chain pairs were selected for biophysical characteristics favorable to manufacturing and development. The selection process included multiple parameters, e.g., assessment of protein expression yield, thermal stability and aggregation propensity in fragment antigen binding (Fab) and IgG1 formats, and relative Fab display rate on phage. The framework regions are fixed and the diversified CDRs were designed based on a systematic analysis of a large set of rearranged human antibody sequences. Care was taken to minimize the occurrence of potential posttranslational modification sites within the CDRs. Phage selection was performed against various antigens and unique antibodies with excellent biophysical properties were isolated. Our results confirm that quality can be built into an antibody library by prudent selection of unmodified, fully human VH/VL pairs as scaffolds.


Appearance of an electrocardiogram tracing on a bispectral index monitor with plausible BIS values.


title: Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement.

text: Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)-a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.


title: Child Development Outcomes of DIR/Floortime TM-based Programs: A Systematic Review.

text: BACKGROUND. Occupational therapy is often part of the multi-disciplinary approach within the Developmental, Individual-differences, Relationship-based (DIR) FloortimeTM Model. The model addresses the emotional development of children, which is considered to be critical for the other child developmental areas. PURPOSE. This review serves to inform practitioner decision-making about the use of this model, as no systematic reviews exist on child development outcomes. METHODS. The systematic search included Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Cochrane. For critical appraisal, the McMaster Critical Review was utilized. FINDINGS. Nine studies were identified with varying quality levels. Outcomes were mostly reported for increased socio-emotional development. IMPLICATIONS. The evidence base for this model is emerging from a published research perspective. It is recommended that the use of this model be supported by sound clinical reasoning processes, intervention fidelity, use of valid outcome measures, and regular monitoring. Higher quality research is urgently needed to progress the research base for this intervention.


title: Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis.

text: OBJECTIVE To investigate the efficacy and safety of prostate-specific antigen (PSA) testing to screen for prostate cancer. DESIGN Systematic review and meta-analysis. DATA SOURCES Electronic search of Cochrane Central Register of Controlled Trials, Web of Science, Embase, Scopus, OpenGrey, LILACS, and Medline, and search of scientific meeting abstracts and trial registers to April 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials comparing PSA screening with usual care in men without a diagnosis of prostate cancer. DATA EXTRACTION At least two reviewers screened studies, extracted data, and assessed the quality of eligible studies. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. We used a random effects model to obtain pooled incidence rate ratios (IRR) and, when feasible, conducted subgroup analyses (defined a priori) based on age, frequency of screening, family history, ethnicity, and socioeconomic level, as well as a sensitivity analysis based on the risk of bias. The quality of the evidence was assessed with the GRADE approach. RESULTS Five randomised controlled trials, enrolling 721 718 men, were included. Studies varied with respect to screening frequency and intervals, PSA thresholds for biopsy, and risk of bias. When considering the whole body of evidence, screening probably has no effect on all-cause mortality (IRR 0.99, 95% CI 0.98 to 1.01; moderate certainty) and may have no effect on prostate-specific mortality (IRR 0.96, 0.85 to 1.08; low certainty). Sensitivity analysis of studies at lower risk of bias (n=1) also demonstrates that screening seems to have no effect on all-cause mortality (IRR 1.0, 0.98 to 1.02; moderate certainty) but may have a small effect on prostate-specific mortality (IRR 0.79, 0.69 to 0.91; moderate certainty). This corresponds to one less death from prostate cancer per 1000 men screened over 10 years. Direct comparative data on biopsy and treatment related complications from the included trials were limited. Using modelling, we estimated that for every 1000 men screened, approximately 1, 3, and 25 more men would be hospitalised for sepsis, require pads for urinary incontinence, and report erectile dysfunction, respectively. CONCLUSIONS At best, screening for prostate cancer leads to a small reduction in disease-specific mortality over 10 years but has does not affect overall mortality. Clinicians and patients considering PSA based screening need to weigh these benefits against the potential short and long term harms of screening, including complications from biopsies and subsequent treatment, as well as the risk of overdiagnosis and overtreatment. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42016042347.


title: REPLY: Factors Other Than Climate Are Likely to Influence Alcohol Consumption.

text: We would like to thank Selck et al. for their letter. The issue they raise has both methodological and scientific interest. We clearly acknowledge in our discussion the limitations of our approach to estimate the causal impact of cold weather on alcoholic cirrhosis at a population level. In addition, as highlighted in the accompanying editorial, these associations at a population level might not hold at an individual level, and the causes of differences in alcohol intake between populations and individuals might not be the same.


title: Avian coronavirus isolated from a pigeon sample induced clinical disease, tracheal ciliostasis, and a high humoral response in day-old chicks.

text: The detection of avian coronaviruses (AvCoV) in wild birds and the emergence of new AvCoV have increased in the past few years. In the present study, the pathogenicity of three AvCoV isolates was investigated in day-old chicks. One AvCoV isolated from a pigeon, which clustered with the Massachusetts vaccine serotype, and two AvCoV isolated from chickens, which grouped with a Brazilian genotype lineage, were used. Clinical signs, gross lesions, histopathological changes, ciliary activity, viral RNA detection, and serology were evaluated during 42 days post infection. All AvCoV isolates induced clinical signs, gross lesions in the trachea, moderate histopathological changes in the respiratory tract, and mild changes in other tissues. AvCoV isolated from the pigeon sample caused complete tracheal ciliostasis over a longer time span. Specific viral RNA was detected in all tissues, but the highest RNA loads were detected in the digestive tract (cloacal swabs and ileum). The highest antibody levels were also detected in the group infected with an isolate from the pigeon. These results confirm the pathogenicity of Brazilian variants, which can cause disease and induce gross lesions and histopathological changes in chickens. Our results suggest that non-Galliformes birds can also play a role in the ecology of AvCoV.


title: Health problems and healthcare service utilisation amongst homeless adults in Africa- a scoping review.

text: BACKGROUND Homelessness is a growing concern as it affects a large number of people worldwide. Individuals and families experiencing homelessness are vulnerable in terms of health and underutilise health services. Despite being a global problem, not much is known about the range and breath of literature exploring health problems and health care service utilisation among homeless adults in Africa. OBJECTIVES To identify the nature and scope of existing evidence on physical and mental health, and health service utilisation among homeless adults in Africa. The review aimed to examine how research is conducted, identify gaps, guide future research, and make recommendations for development and implementation of policies and practices. METHODS A search of articles and reports involving six databases: Scopus, MEDLINE, CINAHL, PubMed, African Journal Online, and Google Scholar was conducted from June 2018 to February 2019. Studies published between 1980 and 2019 that examined the health problems and health service utilisation among homeless adults in Africa were considered. Manual search in reference lists and grey literature was also done to add reports. Data was extracted manually using a charting developed. A descriptive analysis and narrative synthesis were performed. RESULTS Of 761 records found, 14 satisfied the pre-determined inclusion and exclusion criteria. Three themes emerged from the studies: Physical health problems, mental health problems; and healthcare services utilisation. Of the 14 included studies, nine studied and reported physical health problems such as sexually transmitted infections, injuries and disabilities, respiratory and cardiac diseases. Five studies explored mental health problems such as psychotic disorders, mood disorders, self-harm and suicidal behaviour. Only five studies investigated utilisation of different types of health care services among homeless people. CONCLUSIONS Evidence shows that homeless adults suffered from a range of physical and mental health problems, and underutilisation of health care services. However, there is lack of information on the complex interrelationship between homelessness and health, as well as differences in prevalence of health problems among the various sub-groups of homeless. There is also lack of information regarding utilisation other important healthcare services such as mental health services, alcohol and drugs services, and accident and emergency service, and future researches should address that. Also, attention should be given to intervention models for complex and effective physical and psychiatric care as well as social support to address the homeless people's health vulnerabilities.


title: Evaluating use cases for human challenge trials in accelerating SARS-CoV-2 vaccine development.

text: Human challenge trials (HCTs) have been proposed as a means to accelerate SARS-CoV-2 vaccine development. We identify and discuss three potential use cases of HCTs in the current pandemic: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We outline the limitations of HCTs and find that HCTs are likely to be most useful for vaccine candidates currently in preclinical stages of development. We conclude that, while currently limited in their application, there are scenarios in which HCTs would be extremely beneficial. Therefore, the option of conducting HCTs to accelerate SARS-CoV-2 vaccine development should be preserved. As HCTs require many months of preparation, we recommend an immediate effort to (1) establish guidelines for HCTs for COVID-19; (2) take the first steps toward HCTs, including preparing challenge virus and making preliminary logistical arrangements; and (3) commit to periodically re-evaluating the utility of HCTs.


title: Unexpected interference of baby wash products with a cannabinoid (THC) immunoassay.

text: OBJECTIVES The results of newborn drug screening have far-reaching impact not only in healthcare, but also in the legal domain. Therefore, the accuracy of these results cannot be undervalued. When false positive cannabinoid (THC) screening results for this population were suspected at our institution, a multidisciplinary approach was initiated to evaluate the screening process for any pre-analytical or analytical sources of error or interference. DESIGN AND METHODS Mixtures of drug-free urine with various commercial products and materials that commonly contact newborns in our nursery were prepared and tested using the immunoassay screening methods in our laboratory. Additional commercial products were similarly tested; and when available, individual surfactants common to the interfering products were also evaluated. RESULTS Addition of Head-to-Toe Baby Wash to drug-free urine produced a dose dependent measureable response in the THC immunoassay. Addition of other commercially available baby soaps gave similar results, and subsequent testing identified specific chemical surfactants that reacted with the THC immunoassay. CONCLUSION We have identified commonly used soap and wash products used for newborn and infant care as potential causes of false positive THC screening results. Such results in this population can lead to involvement by social services or false child abuse allegations. Given these consequences, it is important for laboratories and providers to be aware of this potential source for false positive screening results and to consider confirmation before initiating interventions. Most importantly, we demonstrate the need for active involvement in the "total testing process," as sources of error are not confined to the laboratory walls.


title: Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 protein has unique biological functions that have not been described in the viral proteins of any RNA viruses; expressed SARS-CoV nsp1 protein has been found to suppress host gene expression by promoting host mRNA degradation and inhibiting translation. We generated an nsp1 mutant (nsp1-mt) that neither promoted host mRNA degradation nor suppressed host protein synthesis in expressing cells. Both a SARS-CoV mutant virus, encoding the nsp1-mt protein (SARS-CoV-mt), and a wild-type virus (SARS-CoV-WT) replicated efficiently and exhibited similar one-step growth kinetics in susceptible cells. Both viruses accumulated similar amounts of virus-specific mRNAs and nsp1 protein in infected cells, whereas the amounts of endogenous host mRNAs were clearly higher in SARS-CoV-mt-infected cells than in SARS-CoV-WT-infected cells, in both the presence and absence of actinomycin D. Further, SARS-CoV-WT replication strongly inhibited host protein synthesis, whereas host protein synthesis inhibition in SARS-CoV-mt-infected cells was not as efficient as in SARS-CoV-WT-infected cells. These data revealed that nsp1 indeed promoted host mRNA degradation and contributed to host protein translation inhibition in infected cells. Notably, SARS-CoV-mt infection, but not SARS-CoV-WT infection, induced high levels of beta interferon (IFN) mRNA accumulation and high titers of type I IFN production. These data demonstrated that SARS-CoV nsp1 suppressed host innate immune functions, including type I IFN expression, in infected cells and suggested that SARS-CoV nsp1 most probably plays a critical role in SARS-CoV virulence.


title: Committee opinion no. 555: hospital disaster preparedness for obstetricians and facilities providing maternity care.

text: Numerous occurrences in the past decade have brought the issue of disaster preparedness, and specifically hospital preparedness, to the national forefront. Much of the work in this area has focused on large hospital system preparedness for various disaster scenarios. Many unique features of the obstetric population warrant additional consideration in order to optimize the care received by expectant mothers and their fetuses or newborns in the face of future natural or biologic disasters.


title: Clinical Outcomes of Comparing Soft Tissue Alternatives to Free Gingival Graft: A Systematic Review and Meta-Analysis .

text: OBJECTIVES This systematic review and meta-analysis aimed to compare clinical outcomes and width of keratinized tissue (KT) around teeth, following the soft tissue alter- natives and free gingival graft (FGG) procedures. The specific graft materials that were explored were extracellular matrix membrane, bilayer collagen membrane, living cellular construct, and acellular dermal matrix. METHODS Four different databases were queried to identify human controlled clinical trials and randomized controlled clinical trials that fulfilled the eligibility criteria. Relevant studies were identified by 3 independent reviewers, compiling the results of the electronic and handsearches. Studies identified through electronic and handsearches were reviewed by title, abstract, and full text using Covidence Software. Primary outcome in the present study was change in the width of KT. Results of the included studies were pooled to estimate the effect size, expressed as weighted mean differences and 95% confidence interval. A random-effects model was used to perform the meta-analyses. RESULTS Six hundred thirty-eight articles were screened by title, 55 articles were screened by abstracts, and 34 full-text articles were reviewed. Data on quantitative changes in width of KT were provided in 7 studies. Quantitative analyses revealed a significant difference in changes in width of KT between patients treated with soft tissue alternatives and patients treated with FGGs (P < .001). The weighted mean difference of changes in the width of KT was 21.39 (95% confidence interval: 21.82 to 20.96; heterogeneity I 5 70.89%), indicating patients who were treated with soft tissue alternatives gained 1.39 mm less KT width compared with the patients who received free gingival graft. CONCLUSIONS Based on the clinical outcomes, the results of this systematic review and meta-analysis showed that soft tissue alternatives result in an increased width of KT. Patients in the soft tissue alternatives group obtained 1.39 mm less KT compared with those in the FGGs group.


title: An Ethnographic Manifestation of Religious Life of Gadaba Tribe in Its Changing Dimensions.

text: The captivating tribal communities living across the length and breadth of the state of Central India and mostly in Odisha have enriched the cultural heritage of the region by their cultural diversities. Gadaba's religious life reflected through their rich folk traditions of songs, dance, music, rituals and festivals celebrated round the year adds colourful dimensions to their very existence. The amazing conglomeration of traditions, beliefs, sorrows and philosophies that together constitute and vitalize the religion of tribes has descended from antiquity and has been preserved unimpaired to the present day. Every dimension of their life covering round the year activities is intimately connected with religion and the world view associated with it. It is these aspects of their culture that give meaning and depth to their lives and solidarity to their social structure. However, in recent days many changes have been taken place in traditional religious life of Gadaba tribe. Against this backdrop, this paper has tried to explore some of that core structure of Gadaba's religious life as well as the changing dimensions of their religious manifestation.


title: FiY101: A quick guide for newly qualified doctors.

text: Final-year medical students in the UK have been allowed to voluntarily apply for early provisional registration in response to the COVID-19 pandemic, allowing these foundation interim year-1 (FiY1) doctors to assist in service provision in hospitals where resources and staffing may be strained. The authors, as recently qualified foundation year-1 (FY1) doctors, use this article to draw on their own experiences, and those of their colleagues, to provide advice on key topics that may not have been covered, or not covered sufficiently, in medical education, such as prescribing, rotas, wellbeing, and useful apps and websites.


title: New suture materials for midline laparotomy closure: an experimental study.

text: BACKGROUND Midline laparotomy closure carries a significant risk of incisional hernia. This study examines the behavior of two new suture materials, an elastic material, polyurethane (PUe), and a barbed polydioxanone (PDXb) suture thread in a rabbit model of midline incision closure. METHODS Three 2-cm midline incisions were made in 68 New Zealand White rabbits. The incisions were closed by running suture using four 3/0 threads: polypropylene (PP) (Surgipro®, Covidien), PUe (Assuplus®, Assut Europe), PDX (Assufil®, Assut Europe) or PDXb (Filbloc®, Assut Europe). Animals in each suture group were euthanized 3 weeks and 6 months after surgery. Histological sections of the tissue-embedded sutures were subjected to morphological, collagen expression, macrophage response and uniaxial tensiometry studies. RESULTS No signs of wound dehiscence or complications were observed. At 3 weeks, all sutures were surrounded by connective tissue composed mainly of collagen III. PUe showed greater collagen I expression than the other sutures. All sutures elicited a macrophage response that diminished from 3 weeks to 6 months (p < 0.001). This response was similar for the non-reabsorbable sutures (PP and PUe) yet PDXb showed a significantly greater response than the other reabsorbable suture (PDX) at 3 weeks (p < 0.01). At this early time point, the tensile strength of PUe was similar to that of control intact tissue (p > 0.05). CONCLUSION Three weeks after surgery, PUe revealed more collagen I deposition than the remaining materials and this translated to a similar biomechanical behavior to linea alba, that could avoid the appearance of short term dehiscences and thus reduce the incidence of incisional hernia. PDXb provides no additional advantages in their behavior regarding PDX suture.


COVID-19 Research in Brief: 16 May to 22 May, 2020.


Wastewater monitoring and public health surveillance of SARS-CoV-2.


title: Percutaneous mechanical thrombectomy in the treatment of acute iliofemoral deep vein thrombosis: a systematic review.

text: BACKGROUND Conventional treatment of deep vein thrombosis (DVT) of the lower extremities by anticoagulation alone has been proven to be insufficient to prevent recurrence and post-thrombotic syndrome (PTS). Early restoration of venous patency and preservation of valvular function by endovascular surgery has been advocated. The aim of this study was to review the efficacy and safety of percutaneous mechanical thrombectomy (PMT) against catheter-directed thrombolysis (CDT) in the treatment of acute iliofemoral DVT. METHODS Three hundred sixty-nine articles were identified through screening of the PubMed, EMBASE, and Cochrane databases from January 2006 to December 2016. RESULTS Fifteen retrospective studies and one prospective registry, totalling 1170 patients, were recruited for qualitative synthesis. The venous patency rate ranged from 75% to 100% with mean follow-up of 12.3 months. The rates of PTS and recurrent DVT were less than 17% and 15%, respectively. The overall mortality rate was 0.26%. Compared with CDT, PMT was shown to reduce PTS at 1 year (Villalta score: 2.1 ± 3.0 in the PMT group and 5.1 ± 4.1 in the CDT group, P=0.03) and bleeding complications (packed cells transfused: 0.2 ± 0.3 units in the pharmacomechanical thrombectomy group and 1.2 ± 0.7 units in the CDT group, P<0.05). CONCLUSION Percutaneous mechanical thrombectomy is a safe and effective treatment for acute iliofemoral DVT in terms of restoration of venous patency, prevention of DVT recurrence, and PTS. Compared with CDT alone, PMT offers a lower risk of PTS and bleeding complications.


Sterile Technique.


Supporting children with autism spectrum disorder in the face of the COVID-19 pandemic.


title: Healthcare costs and outcomes for patients undergoing tracheostomy in an Australian tertiary level referral hospital.

text: Objective Patients undergoing tracheostomy represent a unique cohort, as often they have prolonged hospital stay, require multi-disciplinary, resource-intensive care, and may have poor outcomes. Currently, there is a lack of data around overall healthcare cost for these patients and their outcomes in terms of morbidity and mortality. The objective of the study was to estimate healthcare costs and outcomes associated in tracheostomy patients at a tertiary level hospital in South Australia. Design Retrospective review of prospectively collected data in patients who underwent tracheostomy between July 2009 and May 2015. Methods Overall healthcare-associated costs, length of mechanical ventilation, length of intensive care unit stay, and mortality rates were assessed. Results A total of 454 patients with tracheostomies were examined. Majority of the tracheostomies (n = 386 (85%)) were performed in intensive care unit patients, predominantly using bedside percutaneous approach (85%). The median length of hospital stay was 44 (29-63) days and the in-hospital mortality rate was 20%. Overall total cost of managing a patient with tracheostomy was median $192,184 (inter-quartile range $122560-$295553); mean 225,200 (range $5942-$1046675) Australian dollars. There were no statistically significant differences in any of the measured outcomes, including costs, between patients who underwent percutaneous versus surgical tracheostomy and patients who underwent early versus late tracheostomy in their intensive care unit stay. Factors that predicted (adjusted R 2 = 0.53) the cost per patient were intensive care unit length of stay and hospital length of stay. Conclusion Hospitalised patients undergoing tracheostomy experience high morbidity and mortality and typically experience highly resource-intensive and costly healthcare.


title: Inhibition of USP10 induces degradation of oncogenic FLT3.

text: Oncogenic forms of the kinase FLT3 are important therapeutic targets in acute myeloid leukemia (AML); however, clinical responses to small-molecule kinase inhibitors are short-lived as a result of the rapid emergence of resistance due to point mutations or compensatory increases in FLT3 expression. We sought to develop a complementary pharmacological approach whereby proteasome-mediated FLT3 degradation could be promoted by inhibitors of the deubiquitinating enzymes (DUBs) responsible for cleaving ubiquitin from FLT3. Because the relevant DUBs for FLT3 are not known, we assembled a focused library of most reported small-molecule DUB inhibitors and carried out a cellular phenotypic screen to identify compounds that could induce the degradation of oncogenic FLT3. Subsequent target deconvolution efforts allowed us to identify USP10 as the critical DUB required to stabilize FLT3. Targeting of USP10 showed efficacy in preclinical models of mutant-FLT3 AML, including cell lines, primary patient specimens and mouse models of oncogenic-FLT3-driven leukemia.


title: 3CL Hydrolase Based Multi Epitope Peptide Vaccine Against Sars-CoV-2 Using Immunoinformatics.

text: The present study provides the first multi-epitope vaccine construct using 3CL hydrolase protein of SARS-CoV-2. The coronavirus 3CL hydrolase (Mpro) enzyme is essential for proteolytic maturation of the virus. This research was based on immunoinformatics and structural vaccinology strategies. The design of the multi epitope vaccine was built using HTLs and CTLs epitopes from 3CL hydrolase protein along with adjuvant to enhance immune response; these are joined to each other by short peptide linkers. The vaccine also carries potential B-cell linear epitope regions, B-cell discontinuous epitopes, and Interferon-γ inducing epitopes. Epitopes of the constructed multi epitope vaccine was found to be antigenic, nonallergic, nontoxic, and cover large human population worldwide. The vaccine construct was modeled, validated and refined by different programs to achieve high-quality 3D structure. The resulting high-quality model was applied for conformational B cell epitope selection and docking analyses with toll-like receptor-3 for understanding the capability of vaccine to elicit an immune response. Insilico cloning and Codon adaptation were also performed into the pET-19b plasmid vector. The designed multi-epitope peptide vaccine may prompt the development of a vaccine to control SARS-CoV-2 infection. This article is protected by copyright. All rights reserved.


title: Laparoscopic umbilical hernia repair is the preferred approach in obese patients.

text: INTRODUCTION The optimal method of umbilical hernia repair (UHR) in the obese population, laparoscopic vs open, is not standardized. The purpose of this study was to determine the optimal surgical option for UHR in the obese population. METHODS A retrospective chart review was conducted on 123 obese patients (body mass index [BMI] >30) who underwent UHR from 2003 to 2009 at a single institution. Patients were grouped by surgical approach (open vs laparoscopic). Intraoperative and postoperative courses were compared. Follow-up in the postoperative period was obtained from patient records and telephone interviews. RESULTS Of the 123 patients undergoing UHR, 40 and 83 patients were operated on with the laparoscopic and open approach, respectively. Patients were well matched by demographics as well as comorbidities. No difference in the mean BMI was shown between the laparoscopic and open groups (37 vs 35, P = not significant, respectively). The operative time was significantly prolonged in the laparoscopic group (106 vs 71 minutes, P < .01). Intraoperatively, no complications occurred in either group. In the immediate postoperative period, 1 patient who underwent laparoscopic UHR was readmitted for small bowel obstruction, and 2 patients in the open group were readmitted, 1 for pain control and 1 for wound infection. Follow-up was achieved in 63% of the laparoscopic group and 58% of the open group with a mean follow-up of 15 months in the laparoscopic group and 20 months in the open group (P = not significant). A significant increase in wound infection was reported in the open group with mesh insertion when compared with the laparoscopic procedure (26% vs 4%, P < .05, respectively). No hernia recurrence was shown in the laparoscopic vs the open group with mesh insertion (0% vs 4%, P = not significant, respectively). CONCLUSIONS In obese patients, the laparoscopic approach was associated with a significantly lower rate of postoperative infection and no hernia recurrence. Laparoscopic hernia repair may be the preferred option in the obese patient.


title: Evaluation of 99mTc-Z IGF1R:4551-GGGC affibody molecule, a new probe for imaging of insulin-like growth factor type 1 receptor expression.

text: Overexpression of insulin-like growth factor-1 receptor (IGF-1R) in several cancers is associated with resistance to therapy. Radionuclide molecular imaging of IGF-1R expression in tumors may help in selecting the patients that will potentially respond to IGF-1R-targeted therapy. Affibody molecules are small (7 kDa) non-immunoglobulin-based scaffold proteins that are well-suited probes for radionuclide imaging. The aim of this study was the evaluation of an anti-IGF-1R affibody molecule labeled with technetium-99m using cysteine-containing peptide-based chelator GGGC at C-terminus. ZIGF1R:4551-GGGC was efficiently and stably labeled with technetium-99m (radiochemical yield 97 ± 3%). (99m)Tc-ZIGF1R:4551-GGGC demonstrated specific binding to IGF-1R-expressing DU-145 (prostate cancer) and MCF-7 (breast cancer) cell lines and slow internalization in vitro. The tumor-targeting properties were studied in BALB/c nu/nu mice bearing DU-145 and MCF-7 xenografts. [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551 was used for comparison. The biodistribution study demonstrated high tumor-to-blood ratios (6.2 ± 0.9 and 6.9 ± 1.0, for DU-145 and MCF-7, respectively, at 4 h after injection). Renal radioactivity concentration was 16-fold lower for (99m)Tc-ZIGF1R:4551-GGGC than for [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551 at 4 h after injection. However, the liver uptake of (99m)Tc-ZIGF1R:4551-GGGC was 1.2- to 2-fold higher in comparison with [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551. A possible reason for the elevated hepatic uptake of (99m)Tc-ZIGF1R:4551-GGGC is a high lipophilicity of amino acids in the binding site of ZIGF1R:4551, which is not compensated in (99m)Tc-ZIGF1R:4551-GGGC. In conclusion, (99m)Tc-ZIGF1R:4551-GGGC can visualize the IGF-1R expression in human tumor xenografts and provides low retention of radioactivity in kidneys. Further development of this imaging agent should include molecular design aimed at reducing the hepatic uptake.


Obstetric anesthesia and COVID 19 times.


title: Mapping evidence on access to healthcare information by women of reproductive age in low-and-middle-income countries: scoping review protocol.

text: BACKGROUND Research shows that there are inadequate interventions in resource-limited settings that could enable women of reproductive age to access and use health services in those settings. The main objective of this scoping review is to map the evidence on access to healthcare information by women of reproductive age in LMICs. METHOD AND ANALYSIS The primary search will include Google Scholar, Science Direct, PubMed, EBSCOhost (Academic search complete, CINAHL with full text, MEDLINE with full text, MEDLINE), Emerald, Embase, CDSR, PsycINFO, published and peer review journals, organisational projects, conference papers, reference list, grey literature sources, as well as reports related to this objective will be included in the study. Identified keywords will be used to search articles from the studies. The articles and abstracts will be screened by two independent reviewers (JS and TPMT). Inclusion and exclusion criteria will be considered to guide the screening. A thematic content analysis will be used to present the narrative account of the reviews, using NVivo computer software (version 11). DISCUSSIONS The scoping review will focus on women of reproductive age in LMICs. We anticipate finding relevant literature on the interventions aimed at accessing health care services in LMICs. The study findings will help reveal research gaps to guide future research. SCOPING REVIEW REGISTRATION Not registered with PROSPERO (not needed). PROTOCOL AND REGISTRATION This scoping review was not registered.


title: Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E.

text: The tocotrienol vitamin E has potent antioxidant property, however absorption is low due to high lipid solubility. A self emulsifying preparation of tocotrienol rich vitamin E (SF-TRE) had been reported to increase their bioavailability. This randomized, placebo controlled, blinded end point clinical study aimed to determine the effects of 50, 100 and 200 mg daily of SF-TRE and placebo for two months on arterial compliance and vitamin E blood levels. Assessment of arterial compliance by carotid femoral pulse wave velocity (PWV) and augmentation index (AI), plasma vitamin E, serum total cholesterol and low density lipoprotein cholesterol were taken before and after 2 months' treatment in 36 healthy males. Un-supplemented tocotrienol levels were low, after treatment, all SF-TRE treated groups had significantly higher plasma alpha, delta and delta tocotrienol concentrations compared to placebo. Augmentation index change from baseline to end of treatment for groups placebo, 50, 100, and 200 mg were 2.22+/-1.54, -6.59+/-2.84, -8.72+/-3.77, and -6.27+/-2.67% respectively (p=0.049, 0.049, and 0.047 respectively). Groups 100 and 200 mg showed significant improvement after treatment with pulse wave velocity reductions of 0.77 m/s and 0.65 m/s respectively (p=0.007 and p=0.002). There was no effect of SF-TRE on serum lipids. We conclude that there was a trend towards improvement in arterial compliance with 2 months' of SF-TRE.


title: Polyanalgesic Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel.

text: INTRODUCTION The use of intrathecal (IT) infusion of analgesic medications to treat patients with chronic refractory pain has increased since its inception in the 1980s, and the need for clinical research in IT therapy is ongoing. The Polyanalgesic Consensus Conference (PACC) panel of experts convened in 2000, 2003, and 2007 to make recommendations on the rational use of IT analgesics based on preclinical and clinical literature and clinical experiences. METHODS The PACC panel convened again in 2011 to update the standard of care for IT therapies to reflect current knowledge gleaned from literature and clinical experience. A thorough literature search was performed, and information from this search was provided to panel members. Analysis of published literature was coupled with the clinical experience of panel members to form recommendations regarding the use of IT analgesics to treat chronic pain. RESULTS After a review of literature published from 2007 to 2011 and discussions of clinical experience, the panel created updated algorithms for the rational use of IT medications for the treatment of neuropathic pain and nociceptive pain. CONCLUSIONS The advent of new algorithmic tracks for neuropathic and nociceptive pain is an important step in improving patient care. The panel encourages continued research and development, including the development of new drugs, devices, and safety recommendations to improve the care of patients with chronic pain.


title: A preliminary systematic review and meta-analysis of randomized-controlled trials of cognitive remediation therapy for anorexia nervosa.

text: Cognitive remediation therapy (CRT) for anorexia nervosa (AN) was developed as an adjuvant treatment to target set-shifting and central coherence inefficiencies important in AN and to ultimately improve clinical outcomes of those with AN. The primary aim of this preliminary systematic review and meta-analysis was to determine the effect of CRT for AN relative to control treatments in randomized-controlled trials (RCTs) on neuropsychological inefficiencies at end-of-treatment. Secondary aims were to assess the effect of CRT for AN on dropout, eating-disorder-related, and other psychological outcomes at end-of-treatment. Systematic review and meta-analytic procedures were conducted in accordance with PRISMA Guidelines. RCTs evaluating CRT for AN compared to a control treatment were identified via ProQuest, PsycINFO, PubMed, and SCOPUS. Seven RCTs and one quasi-RCT of CRT for AN were included. RCT quality ratings ranged from fair (n = 3) to good (n = 4). Random-effects meta-analysis was conducted using Hedge's g. Study heterogeneity was assessed using I2 and publication bias was assessed with Begg's adjusted-rank correlation and the trim-and-fill method. CRT was not associated with improvement in central coherence compared to control treatments at end-of-treatment (g = 0.25, 95% CI = -0.35, 0.85, k = 3). Set-shifting outcomes were mixed due to heterogeneity of set-shifting measures across studies. CRT may prevent dropout; yet, more studies are needed to draw conclusions. CRT did not confer advantage over control treatments for eating-disorder-related and other psychological outcomes at end-of-treatment. Future RCTs of CRT for AN should use precise measures to assess constructs (particularly for set shifting), increase sample size, and implement longitudinal follow-up. (Word Count: 247 words).


Covid-19: Risk of second wave is very real, say researchers.


title: COVID-19: a defining moment for clinical pharmacology?

text: COVID-19 is overshadowing society across the world and it will redefine many aspects of how we live and work in the future. In a crisis, people are rightly looking for solutions from their leaders and experts and their response and actions will define them for years to come. COVID-19 may also be such a defining moment for clinical pharmacology in terms of its role in drug development and therapy. Though most drug development takes years from discovery to approval, for the COVID-19 pandemic, drug development is on a fundamentally different timeline.


title: Phosphate and nitrate uptake dynamics in Palmaria palmata (Rhodophyceae): ecological and physiological aspects of nutrient availability.

text: Uptake dynamics of dissolved inorganic phosphate (DIP) and dissolved inorganic nitrate (DIN) in young Palmaria palmata (n=49), cultivated in a range of DIP concentrations (0.0-6.0 µmol · L-1 ) and non-limiting DIN concentration (50 µmol · L-1 ) under fully controlled laboratory conditions, were quantified in a 'pulse-and-chase' approach over 5 weeks. Two different uptake rates were specified: (1) surge uptake (VS ) after starvation and (2) maintenance uptake with filled nutrient pools (VM ). VS for DIP of 1.57±0.29 µmol · cm-2 · d-1 and DIN of 15.6±4.3 µmol · cm-2 · d-1 , as well as VM for DIP of 0.57±0.22 µmol · cm-2 · d-1 and DIN of 5.6±2.1 µmol · cm-2 · d-1 were calculated. In addition, an absolute size of the internal storage capacity (ISC) for DIP of 22 µmol · cm2 and DIN of 222 µmol · cm2 was determined. A DIP to DIN uptake ratio of 1:10 under VM showed a weekly rhythmic uptake pattern, highlighted by a high correlation between DIP and DIN uptake (R=0.943). VS for DIN did not occur under DIP depletion, but uptake rates increased with increasing DIP availability. Hence, DIP availability limited access to DIN, which was also reflected by total dissolvable protein concentrations in sporophytes, which ranged from 10.2±2.5% to 24.6±8.0% dry weight depending on DIP availability. Similarly, total dissolvable carbohydrate concentration ranged from 22.1±3.6% to 54.3±12.3% dry weight. The data presented in this study opens further insight into ecological and physiological aspects of nutrient availability in P. palmata and allows for an optimization in cultivation.


Stenting in acute stroke: counterpoint.


Impending Shortages of Kidney Replacement Therapy for COVID-19 Patients.


What COVID-19 outbreak in Iran teaches us about virtual medical education.


Bariatric surgery to treat severely obese patients with type 2 diabetes: A consensus statement.


Partha Kar: Covid-19 and ethnicity-why are all our angels white?


title: F-18-fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected infection.

text: PURPOSE To assess the value of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with CT in critically ill patients suspected of having an infection. METHODS FDG-PET CT scans requested for evaluation of a suspected infection or inflammatory process in critically ill, mechanically ventilated patients were analyzed (blinded for the final clinical diagnosis) and compared with clinical follow-up. RESULTS Thirty-five FDG-PET/CT scans performed in 33 ICU patients (28 adults and 5 children), median age 58 years (range 1 month-72 years), were analyzed. Twenty-one FDG-PET/CT scans were true positive. Three FDG-PET/CT scans were considered false positive, in one case leading to additional diagnostic procedures (specificity 79%). Additionally, 11 true negatives were found (sensitivity 100%), leading to an overall accuracy of 91%. CONCLUSIONS FDG-PET/CT scanning is of additional value in the evaluation of suspected infection in critically ill patients in whom conventional diagnostics did not lead to a diagnosis. Apart from the high accuracy, in this study it appeared that, in addition to conventional diagnostic techniques that were routinely performed, a normal FDG-PET/CT ruled out important infections requiring prolonged antibiotic therapy or drainage. Since sensitivity is lower in highly metabolic active tissues (e.g., endocarditis, meningitis), the FDG-PET/CT scan is not suited to detect infections in these tissues.


title: Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force.

text: The COVID-19 pandemic has raised a host of ethical challenges, but key among these has been the possibility that health care systems might need to ration scarce critical care resources. Rationing policies for pandemics differ by institution, health system, and applicable law. Most seem to agree that a patient's ability to benefit from treatment and to survive are first-order considerations. However, there is debate about what clinical measures should be used to make that determination and about other factors that might be ethically appropriate to consider. In this paper, we discuss resource allocation and several related ethical challenges to the healthcare system and society, including how to define benefit, how to handle informed consent, the special needs of pediatric patients, how to engage communities in these difficult decisions, and how to mitigate concerns of discrimination and the effects of structural inequities.


title: Impact of fixed implant supported prostheses in edentulous patients: protocol for a systematic review.

text: INTRODUCTION Edentulism is a debilitating and irreversible condition described as the 'final marker of disease burden for oral health'. Therapy with dental implants is being used on a large scale to replace missing teeth and to rehabilitate edentulous patients with overdentures and implant supported fixed dentures as a method of solving the problem of instability and lack of retention associated with conventional removable prostheses. Fixed implant supported prostheses are an alternative for implant rehabilitation treatment that allow patients to have new fixed teeth. They can be indicated in partial or total edentulous patients, and they can replace single teeth, or teeth and supporting tissues (hybrid prosthesis). They overcome the limitations of conventional dentures, increasing stability and retention, providing functional and psychological advantages for the patients. METHODS AND ANALYSIS We will electronically search for randomised controlled trials evaluating the effects of fixed implant supported prostheses in edentulous patients in the following databases: Pubmed/MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. We will also try to obtain literature screening references of included studies, searching for trial protocols in the WHO International Clinical Trials Registry Platform, reviewing International Team for Implantology conference proceedings and searching for non-published studies through Open Gray. Two researchers will independently undertake selection of studies, data extraction and assessment of the quality of the included studies. Data synthesis and subgroup analyses will be performed using special Review Manager software. Data will be combined in a meta-analysis using a random effects model. RESULTS The results will be presented as risk ratios for dichotomous data, and as mean difference or standardised mean difference for continuous data. ETHICS AND DISSEMINATION No ethics approval is considered necessary. The results of this study will be disseminated via peer reviewed publications and social networks. TRIAL REGISTRATION NUMBER CRD42015022086.


title: [Asymptomatic and pre-symptomatic cases of COVID-19 contribution to spreading the epidemic and need for targeted control strategies].

text: The asymptomatic carrier state of COVID-19 has become a topic of concern for preventing a possible epidemic rebound. This review describes and defines the COVID-19 asymptomatic carrier state and outlines methods for identifying counting and reporting these cases. The author elaborates that the asymptomatic carrier state can be further divided into asymptomatic infection and pre-symptomatic infection after extended follow-up based on the nature of disease progression. The author presents the limited available data about infectiousness of asymptomatic and pre-symptomatic cases and their possible contributions to the overall epidemic of COVID-19 observed so far in China. Challenges of a possible second epidemic wave of COVID-19 caused by asymptomatic and pre-symptomatic cases are discussed and suggestions for control strategies and scientific research are provided.


title: Impact of stroke mechanism in acute basilar occlusion with reperfusion therapy.

text: Objective We aimed to evaluate the impact of underlying mechanism of basilar artery (BA) occlusion on the outcomes after endovascular therapy (EVT) for reperfusion and the outcome factors associated with each mechanism, and to identify radiologic parameters enabling to distinguish the underlying mechanism. Methods From a registry database, 194 consecutive patients with acute BA occlusion who underwent EVT were analyzed. Stroke mechanism, classified into in situ atherosclerotic thrombosis (ISAT) and embolism, clot sign location profiles in pre-angiography magnetic resonance image (MRI), parameters of angiography and EVT, and reperfusion were assessed. Poor outcome was defined as a modified Rankin-Scale score at 90 days of 3-6. Results The mean age was 68.8±11.8 years (range 21-92 years) and seventy-eight (40.2%) were female patients. 102 (52.6%) patients were classified into an embolism mechanism and 92 (47.4%) into an ISAT mechanism. Overall, ISAT mechanism compared with embolism was significantly associated with poor outcomes (P = 0.002), along with the NIHSS scores, reperfusion status, and collateral status. In the embolism group, reperfusion (P = 0.001), NIHSS scores (P < 0.001), and onset-to-treatment time (P = 0.030) were significant outcome factors. However, in the ISAT group, baseline collateral status (P = 0.001) and NIHSS scores (P < 0.001) were significant outcome factors. A clot sign at the distal BA segment on pre-angiography MRI was strongly associated with embolism mechanism (P < 0.001). Interpretation Stroke mechanism has a major influence on outcomes, and outcome predictors differ according to the underlying mechanism in acute BA occlusion with EVT. Clot sign profile on pre-angiography MRI might be useful to determine the underlying mechanism.


title: Delayed prophylaxis with unfractionated heparin increases the risk of venous thromboembolic events in patients with moderate to severe traumatic brain injury: a retrospective analysis.

text: BACKGROUND Venous thromboembolism (VTE) is a recognized complication in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Currently, no standard exists for optimal timing or a pharmacological agent for VTE prophylaxis (pharmacological thromboprophylaxis - PTP) in patients with TBI. PTP is often delayed out of fear of causing extension of intracranial hemorrhage (ICH). The purpose of this study was to report the frequency of VTE and ICH progression after initiation of PTP with a continuous infusion of unfractionated heparin in patients with moderate to severe TBI, and to identify risk factors associated with development of VTE. METHODS In this single-center retrospective study, patients with moderate to severe TBI admitted to the ICU of a Swiss Level I Trauma Center over a three-year period were analyzed. RESULTS In 23 (13%) of the 177 patients included in the study a VTE episode occurred during the hospital stay. ICH progression after initiation of PTP occurred in 7 (4%) patients. In a multivariable logistic regression model, only the timing of initiation of PTP was identified as an independent predictor of VTE. CONCLUSIONS In this study population, the risk of developing VTE increased with the delay of initiation of a pharmacological VTE prophylaxis, while ICH progression after initiation of PTP was a rare event.


title: Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial.

text: BACKGROUND Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. METHODS For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. FINDINGS Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0·83, 95% CI 0·63-1·09; p=0·18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1·91, 1·06-3·44; p=0·0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0·82; appendix); these events included pulmonary embolism (two patients [<1%] vs four [1%] patients; p=0·41) and sepsis (seven [1%] vs six [1%]; p=0·79). INTERPRETATION In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. FUNDING National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians' Services Incorporated.


title: Middle East Respiratory Syndrome Coronavirus and Severe Acute Respiratory Syndrome Coronavirus.

text: Emerging infectious diseases continue to be of a significant importance worldwide with the potential to cause major outbreaks and global pandemics. In 2002, the world had witnessed the appearance of the severe acute respiratory syndrome coronavirus in China which disappeared abruptly within 6 months. About a decade later, a new and emerging novel coronavirus named the Middle East respiratory syndrome coronavirus (MERS-CoV) was described in a patient from Saudi Arabia. These two coronaviruses shared multiple similarities in the epidemiology, clinical presentations, and posed challenges in its prevention and management. Seven years since its discovery, MERS-CoV continues to be a lethal zoonotic pathogen capable of causing severe pneumonia with high case fatality rates and the ability to cause large health care-associated outbreaks.


title: Comparison of the Diagnostic Yield of EUS Needles for Liver Biopsy: Ex Vivo Study.

text: BACKGROUND AND AIMS EUS-guided liver biopsy is an emerging method of liver tissue acquisition which is safe and had been shown to produce excellent histological yield. There is limited data comparing the diagnostic yield of different FNA needles. We aimed to compare the diagnostic performance of four commercially available 19-gauge FNA needles. METHODS Four FNA needles and one percutaneous needle were used to perform liver biopsies on two human cadaveric livers: Cook Echotip Procore™, Olympus EZ Shot 2™, Boston Scientific Expect Slimline™, Covidien SharkCore™, and an 18-gauge percutaneous needle (TruCore™, Argon Medical Devices). Each needle obtained biopsies by three, six, and nine complete back-and-forth motions of the needle ("throw") with a fanning technique. The combined lengths of specimen fragments and the total number of complete portal tracts (CPT) were measured by a blinded pathologist. One-way analysis of variance (ANOVA) and Bonferroni correction were used for statistical analysis. RESULTS A total of 52 liver biopsies were performed. The Covidien SharkCore needle had significantly greater number of CPT compared to other FNA needles. The number of "throws" did not impact the number of CPT significantly. There was no statistically significant difference in mean total specimen length between each FNA needle type. CONCLUSION The Covidien SharkCore needle produced superior histological specimen by capturing more CPT, possibly due to its unique needle design.


title: Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a WHO priority pathogen for which vaccines are urgently needed. Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. Using a "plug-and-display" SpyTag/SpyCatcher system, we coupled RBD to lumazine synthase (LS) particles producing multimeric RBD-presenting particles (RBD-LS). RBD-LS vaccination induced antibody responses of high magnitude and quality (avidity, MERS-CoV neutralizing capacity, and mucosal immunity) with cross-clade neutralization. The antibody responses were associated with blocking viral replication and upper and lower respiratory tract protection against MERS-CoV infection in rabbits. This arrayed multivalent presentation of the viral RBD using the antigen-SpyTag/LS-SpyCatcher is a promising MERS-CoV vaccine candidate and this platform may be applied for the rapid development of vaccines against other emerging viruses such as SARS-CoV-2.