title: Characterisation and comparison of the host response of 6 tissue-based surgical implants in a subcutaneous in vivo rat model.

text: BACKGROUND Hernia repair often involves fascial augmentation using biologic prostheses. Small processing changes during preparation modulate host tissue response, which influence material efficacy and longevity. In this pilot study, a rat model was used to determine the specific influence of tissue origin, decellularisation treatment and 1,6-hexamethylene diisocyanate (HMDI) cross-linking. METHODS Materials (1 cm2) were implanted subcutaneously into 6-week-old Wistar rats (4 materials per animal, n=6/material per time point) for 2, 5, 7, 14 and 28 days. Histologic processing was carried out after resin infiltration, observing classical histopathology and pathologic indexing. Materials comprised 6 tissue-based grafts covering both experimental and commercial porcine decellularised dermal and small intestinal submucosal materials. RESULTS Subcutaneous delivery of biologics demonstrated material-specific inflammatory/host responses. Controlled variations of the PermacolTM manufacturing process showed sodium dodecyl sulfate (SDS) was the most proinflammatory decellularisation reagent, and HMDI cross-linking had no effect on host response. All materials remained recoverable after 28 days, although SurgisisTM had partially resorbed. CONCLUSION Differences in host responses exist between biologic implants for hernia repair in this rat model. It is postulated that these modifications are induced during processing and may have an effect on the clinical outcome of hernia repair.


title: Risk Profile of Symptomatic Lacunar Stroke Versus Nonlobar Intracerebral Hemorrhage.

text: BACKGROUND AND PURPOSE Although lacunar stroke (LS) and deep intracerebral hemorrhage (dICH) represent acute manifestations of the same pathological process involving cerebral small vessels (small vessel disease), it remains unclear what factors predispose to one phenotype rather than the other at individual level. METHODS Consecutive patients with either acute symptomatic LS or dICH were prospectively enrolled as part of a multicenter Italian study. We compared the risk factor profile of the 2 subgroups using multivariable logistic regression. RESULTS During a time course of 9.5 years, 1931 subjects (1434 LS and 497 dICH; mean age, 71.3±13.3 years; males, 55.5%) qualified for the analysis. Current smoking was associated with LS (odds ratio [OR], 2.17; P<0.001). Conversely, dICH cases were more likely to be hypertensive (OR, 1.87; P<0.001), excessive alcohol consumers (OR, 1.70; P=0.001), and more frequently under treatment with warfarin (OR, 2.05; P=0.010) and statins (OR, 3.10; P<0.001). Hypercholesterolemia, diabetes mellitus, and antiplatelet treatment were not associated with a specific small vessel disease manifestation. CONCLUSIONS The risk factor profile of dICH differs from that associated with LS. This might be used for disease risk stratification at individual level.


title: Dressings for treating foot ulcers in people with diabetes: an overview of systematic reviews.

text: BACKGROUND Foot ulcers in people with diabetes mellitus are a common and serious global health issue. Dressings form a key part of ulcer treatment, with clinicians and patients having many different types to choose from. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. OBJECTIVES To summarize data from systematic reviews of randomised controlled trial evidence on the effectiveness of dressings for healing foot ulcers in people with diabetes mellitus (DM). METHODS We searched the following databases for relevant systematic reviews and associated analyses: the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2015, Issue 2); Database of Abstracts of Reviews of Effects (DARE; The Cochrane Library 2015, Issue 1); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, 14 April 2015); Ovid EMBASE (1980 to 14 April 2015). We also handsearched the Cochrane Wounds Group list of reviews. Two review authors independently performed study selection, risk of bias assessment and data extraction. Complete wound healing was the primary outcome assessed; secondary outcomes included health-related quality of life, adverse events, resource use and dressing performance. MAIN RESULTS We found 13 eligible systematic reviews relevant to this overview that contained a total of 17 relevant RCTs. One review reported the results of a network meta-analysis and so presented information on indirect, as well as direct, treatment effects. Collectively the reviews reported findings for 11 different comparisons supported by direct data and 26 comparisons supported by indirect data only. Only four comparisons informed by direct data found evidence of a difference in wound healing between dressing types, but the evidence was assessed as being of low or very low quality (in one case data could not be located and checked). There was also no robust evidence of a difference between dressing types for any secondary outcomes assessed. AUTHORS' CONCLUSIONS There is currently no robust evidence for differences between wound dressings for any outcome in foot ulcers in people with diabetes (treated in any setting). Practitioners may want to consider the unit cost of dressings, their management properties and patient preference when choosing dressings.


title: Recombinase polymerase amplification: Emergence as a critical molecular technology for rapid, low-resource diagnostics.

text: Isothermal molecular diagnostics are bridging the technology gap between traditional diagnostics and polymerase chain reaction-based methods. These new techniques enable timely and accurate testing, especially in settings where there is a lack of infrastructure to support polymerase chain reaction facilities. Despite this, there is a significant lack of uptake of these technologies in developing countries where they are highly needed. Among these novel isothermal technologies, recombinase polymerase amplification (RPA) holds particular potential for use in developing countries. This rapid nucleic acid amplification approach is fast, highly sensitive and specific, and amenable to countries with a high burden of infectious diseases. Implementation of RPA technology in developing countries is critically required to assess limitations and potentials of the diagnosis of infectious disease, and may help identify impediments that prevent adoption of new molecular technologies in low resource- and low skill settings. This review focuses on approaching diagnosis of infectious disease with RPA.


title: Handling of Missing Outcome Data in Traumatic Brain Injury Research: A Systematic Review.

text: Traumatic brain injury (TBI) research commonly measures long-term functional outcome, but studies often suffer from missing data as patients are lost to follow-up. This review assesses the extent and handling of missing outcome data in the TBI literature and provides a practical guide for future research. Relevant electronic databases were searched from January 1, 2012 to October 27, 2017 for TBI studies that used the Glasgow Outcome Scale or Glasgow Outcome Scale-Extended (GOS/GOSE) as an outcome measure. Studies were screened and data extracted in line with Cochrane guidance. A total of 195 studies, 21 interventional, 174 observational, with 104,688 patients were included. Using the reported follow-up rates in a mixed model, on average 91% of patients were predicted to return to follow-up at 6 months post-injury, 84% at 1 year, and 69% at 2 years. However, 36% of studies provided insufficient information to determine the number of subjects at each time-point. Of 139 studies that did report missing outcome data, only 50% attempted to identify why data were missing, with just 4 reporting their assumption on the "missingness mechanism." The handling of missing data was heterogeneous, with the most common method being its exclusion from analysis. These results confirm substantial variability in the standard of reporting and handling of missing outcome data in TBI research. We conclude that practical guidance is needed to facilitate meaningful and accurate study interpretation, and therefore propose a framework for the handling of missing outcome data in future TBI research.


title: Emergency cricothyroidotomy performed by inexperienced clinicians--surgical technique versus indicator-guided puncture technique.

text: BACKGROUND To improve the ease and safety of cricothyroidotomy especially in the hand of the inexperienced, new instruments have been developed. In this study, we compared a new indicator-guided puncture technique (PCK) with standard surgical technique (ST) regarding success rate, performance time and complications. METHODS Cricothyroidotomy in 30 human cadavers performed by 30 first year anaesthesia residents. The set chosen for use was randomised: PCK-technique (n=15) and ST (n=15). Success rates, insertion times and complications were compared. Traumatic lesions were anatomically confirmed after dissection. RESULTS The ST-group had a higher success rate (100% vs 67%; p=0.04). There was no difference in time taken to complete the procedure (PCK 82 s. vs ST 95 s.; p=0.89). There was a higher complication rate in the PCK-group (67% vs 13%; p=0.04). Most frequent complication in the PCK-group was injury to the posterior tracheal wall (n=8), penetration to the oesophageal lumen (n=4) and injury to the thyroid and/or cricoid cartilage (n=5). In the ST-group in only 2 cases minor complications were observed (small vessel injury). CONCLUSIONS In this human cadaver study the PCK technique produced more major complications and more failures than the ST. In the hand of the inexperienced operator the standard surgical approach seems to be a safe procedure, which can successfully be performed within an adequate time. The PCK technique cannot be recommended for inexperienced operators.


title: Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule.

text: Bats are a major reservoir of emerging and re-emerging infectious diseases, including severe acute respiratory syndrome-like coronaviruses, henipaviruses, and Ebola virus. Although highly pathogenic to their spillover hosts, bats harbor these viruses, and a large number of other viruses, with little or no clinical signs of disease. How bats asymptomatically coexist with these viruses is unknown. In particular, little is known about bat adaptive immunity, and the presence of functional MHC molecules is mostly inferred from recently described genomes. In this study, we used an affinity purification/mass spectrometry approach to demonstrate that a bat MHC class I molecule, Ptal-N*01:01, binds antigenic peptides and associates with peptide-loading complex components. We identified several bat MHC class I-binding partners, including calnexin, calreticulin, protein disulfide isomerase A3, tapasin, TAP1, and TAP2. Additionally, endogenous peptide ligands isolated from Ptal-N*01:01 displayed a relatively broad length distribution and an unusual preference for a C-terminal proline residue. Finally, we demonstrate that this preference for C-terminal proline residues was observed in Hendra virus-derived peptides presented by Ptal-N*01:01 on the surface of infected cells. To our knowledge, this is the first study to identify endogenous and viral MHC class I ligands for any bat species and, as such, provides an important avenue for monitoring and development of vaccines against major bat-borne viruses both in the reservoir and spillover hosts. Additionally, it will provide a foundation to understand the role of adaptive immunity in bat antiviral responses.


title: An Alternative Method for Airway Management With Combined Tracheal Intubation and Rigid Bronchoscope.

text: An innovative technique for airway management, using a small-diameter, short-cuffed orotracheal tube for assisting rigid bronchoscopy in critical airway obstruction is reported. The device, part of the translaryngeal tracheostomy kit, "Fantoni method" (DAR TLT, Covidien, Minneapolis, MN), was placed beyond the stenosis and used in combination with the rigid bronchoscope. This procedure improves safety during the management of critical tracheal stenoses because the airway is constantly under the anesthesiologist's control. Consequently, inhalation anesthesia is feasible, use of neuromuscular blockade is possible, end-tidal carbon dioxide monitoring is reliable, and the distal airway is protected from blood and debris soilage during tumor debulking. Surgery is faster because it is uninterrupted.


title: Treatment of aortic arch aneurysms with a modular transfemoral multibranched stent-graft: initial experience.

text: OBJECTIVE To present an initial experience with a new modular transfemoral multibranched stent-graft for treating aortic arch aneurysms. METHODS Six patients, considered high risk for open surgery, were treated with a custom-made branched stent-graft. Two patients had aortic arch aneurysms, three had descending thoracic aortic aneurysms involving the distal arch, and one had a saccular aneurysm of the arch adjacent to the origin of the innominate artery. All patients had undergone a staged left carotid subclavian bypass before the endovascular procedure. Each branched graft had a 12-mm side branch for the innominate artery and an 8-mm side branch for the left common carotid artery. The branches were extended into their respective target arteries with covered self-expanding stents. RESULTS Aneurysm exclusion without endoleak was successful in 5 of the 6 patients, and 11 of the 12 target vessels were successfully cannulated and preserved. Patient 1 developed a type I endoleak that was managed successfully with coiling and gluing of the aneurysm sac. Patients 2, 3, 5, and 6 had uneventful placement of the prostheses, with successful exclusion of the aneurysm sac. In patient 4, cannulation of the innominate branch was unsuccessful, and an extra-anatomic bypass was necessary to perfuse the right carotid and vertebral arteries. CONCLUSIONS We have demonstrated the technical feasibility of a modular transfemoral branched stent-graft for treatment of aortic arch aneurysms. Our initial experience has shown that the method is relatively safe. Long-term follow-up is necessary to evaluate the efficacy and safety of this new device.


title: Covid-19, Coronavirus, SARS-CoV-2 and the small bowel.

text: Although SARS-CoV-2 may primarily enter the cells of the lungs, the small bowel may also be an important entry or interaction site, as the enterocytes are rich in angiotensin converting enzyme (ACE)-2 receptors. The initial gastrointestinal symptoms that appear early during the course of Covid-19 support this hypothesis. Furthermore, SARS-CoV virions are preferentially released apically and not at the basement of the airway cells. Thus, in the setting of a productive infection of conducting airway epithelia, the apically released SARS-CoV may be removed by mucociliary clearance and gain access to the GI tract via a luminal exposure. In addition, post-mortem studies of mice infected by SARS-CoV have demonstrated diffuse damage to the GI tract, with the small bowel showing signs of enterocyte desquamation, edema, small vessel dilation and lymphocyte infiltration, as well as mesenteric nodes with severe hemorrhage and necrosis. Finally, the small bowel is rich in furin, a serine protease which can separate the S-spike of the coronavirus into two "pinchers" (S1 and 2). The separation of the S-spike into S1 and S2 is essential for the attachment of the virion to both the ACE receptor and the cell membrane. In this special review, we describe the interaction of SARS-CoV-2 with the cell and enterocyte and its potential clinical implications.


title: Single Incision Laparoscopic Cholecystectomy for Gallbladder Duplication.

text: Duplication of the gallbladder is a rare congenital anomaly of the gallbladder, with an estimated prevalence of 1-3 per 3800 individuals. Unless properly diagnosed preoperatively, it can lead to biliary tract injuries and postoperative complications which may require reoperative surgeries. While previously reported cases have been treated with conventional laparoscopic cholecystectomy (LC), treatment with single incision laparoscopic surgery (SILS) has not been reported yet. We herein present the case of a 58-year-old female with gallbladder duplication who was successfully treated with SILS cholecystectomy.


title: Single-incision laparoscopic surgery: outcomes from 224 colonic resections performed at a single center using SILS.

text: BACKGROUND Compared with single-incision laparoscopy, multiport laparoscopy is associated with greater risk of postoperative wound pain, infection, incisional hernias, and suboptimal cosmetic outcomes. The feasibility of minimally invasive single-incision laparoscopic surgery (SILS) for colorectal procedures is well-established, but outcome data remain limited. METHODS Patients with benign diverticular disease, Crohn's disease, or ulcerative colitis admitted to Klinikum Leverkusen, Germany, for colonic resection between July 2009 and March 2011 (n = 224) underwent single-incision laparoscopic surgery using the SILS port system. Surgeons had ≥7 years' experience in laparoscopic colon surgery but no SILS experience. Patient demographic and clinical data were collected prospectively. Pain was evaluated by using a visual analog scale (0-10). Data were analyzed by using the SPSS PASW Statistics 18 database. RESULTS The majority of patients underwent sigmoid colectomy with high anterior resection (AR) or left hemicolectomy (n = 150) for diverticulitis. Our conversion rate to open surgery was 6.3 %, half in patients undergoing sigmoid colectomy with high AR or left hemicolectomy, 95 % of whom had diverticulitis. Mean operating time was 166 ± 74 (range, 40-441) min in the overall population, with shorter times for single-port transanal tumor resection (SPTTR; 89 ± 51 min; range, 40-153 min) and longer times for proctocolectomy (325 min; range, 110-441 min). Mean hospital stay was approximately 10 days, longer after abdominoperineal rectal resection or proctocolectomy (12-16 days). Most complications occurred following sigmoid colectomy with high AR or left hemicolectomy [19/25 (76 %) of early and 4/5 (80 %) of late complications, respectively]. Pain was <4 on a scale of 0-10 in all cases on postoperative day 1, and typically decreased during the next 2 days. CONCLUSIONS Our findings support the feasibility and tolerability of colorectal surgery, conducted by experienced laparoscopic surgeons without specific training in use of the SILS port.


title: Detection of neurologic injury using vascular reactivity monitoring and glial fibrillary acidic protein.

text: New noninvasive methods for monitoring cerebrovascular pressure reactivity coupled with a blood-based assay for brain-specific injury in preterm infants could allow early diagnosis of brain injury and set the stage for improved timing and effectiveness of interventions. Using an adaptation of near-infrared spectroscopy, we report a case of a very low birth weight infant undergoing hemoglobin volume index monitoring as a measure of cerebrovascular pressure reactivity. During the monitoring period, this infant demonstrated significant disturbances in cerebrovascular pressure reactivity that coincided with elevation of serum glial fibrillary acidic protein and new findings of brain injury on head ultrasound. This case report demonstrates the potential of emerging noninvasive monitoring methods to assist in both detection and therapeutic management to improve neurologic outcomes of the very low birth weight neonate.


title: Effectiveness of surgical masks against influenza bioaerosols.

text: BACKGROUND Most surgical masks are not certified for use as respiratory protective devices (RPDs). In the event of an influenza pandemic, logistical and practical implications such as storage and fit testing will restrict the use of RPDs to certain high-risk procedures that are likely to generate large amounts of infectious bioaerosols. Studies have shown that in such circumstances increased numbers of surgical masks are worn, but the protection afforded to the wearer by a surgical mask against infectious aerosols is not well understood. AIM To develop and apply a method for assessing the protection afforded by surgical masks against a bioaerosol challenge. METHODS A dummy test head attached to a breathing simulator was used to test the performance of surgical masks against a viral challenge. Several designs of surgical masks commonly used in the UK healthcare sector were evaluated by measuring levels of inert particles and live aerosolised influenza virus in the air, from in front of and behind each mask. FINDINGS Live influenza virus was measurable from the air behind all surgical masks tested. The data indicate that a surgical mask will reduce exposure to aerosolised infectious influenza virus; reductions ranged from 1.1- to 55-fold (average 6-fold), depending on the design of the mask. CONCLUSION We describe a workable method to evaluate the protective efficacy of surgical masks and RPDs against a relevant aerosolised biological challenge. The results demonstrated limitations of surgical masks in this context, although they are to some extent protective.


title: Arthroscopic removal of osteochondral fragments in the dorsal pouch of the proximal intertarsal joint in 29 horses.

text: OBJECTIVE To describe the radiographic and surgical findings of horses with osteochondral fragments (OCF) in the proximal intertarsal joint (PIJ) and to detail the technique for arthroscopic fragment retrieval and report outcomes. STUDY DESIGN Retrospective case series. ANIMALS Twenty-nine horses (32 tarsi) with OCF in the PIJ. METHODS Medical records of horses with radiographic evidence of OCF in the PIJ were reviewed. Clinical features, number of fragments, location, arthroscopic appearance, and outcome were recorded. Technical modifications with visual aids specific to this arthroscopic technique are described. RESULTS Twenty-seven horses (93%) had radiographic evidence of osteochondritis dissecans lesions in the tarsocrural joint (TCJ). OCF were most commonly located distal to the medial trochlear ridge of the talus. In all cases, fragments were successfully retrieved with a technique based on exposing the fragments after resection of the proximal intertarsal joint capsule (PIJC). Fragments were visible from the TCJ prior resection of the PIJC in 4 of 32 tarsi. A third portal was created to access fragments located distal to the lateral trochlear ridge in 3 of 32 tarsi. Moderate intra-articular bleeding occurred when the PIJC was resected in 3 of 32 tarsi. One horse had postoperative swelling that resolved with conservative medical management. All horses with long-term follow-up available (16/29) started training or returned to their athletic career. CONCLUSION AND CLINICAL SIGNIFICANCE The arthroscopic technique based on resection of PIJC was effective in retrieving OCF in the PIJ and was associated with minor complications. The clinical relevance of these fragments in the PIJ remains unknown.


title: Health promotion interventions and policies addressing excessive alcohol use: a systematic review of national and global evidence as a guide to health-care reform in China.

text: AIMS Steady increases in alcohol consumption and related problems are likely to accompany China's rapid epidemiological transition and profit-based marketing activities. We reviewed research on health promotion interventions and policies to address excessive drinking and to guide health-care reform. METHODS We searched Chinese- and English-language databases and included 21 studies in China published between 1980 and 2013 that covered each policy area from the World Health Organization (WHO) Global Strategy to Reduce the Harmful Use of Alcohol. We evaluated and compared preventive interventions to the global alcohol literature for cross-national applicability. RESULTS In contrast with hundreds of studies in the global literature, 11 of 12 studies from mainland China were published in Chinese; six of 10 in English were on taxation from Taiwan or Hong Kong. Most studies demonstrated effectiveness in reducing excessive drinking, and some reported the reduction of health problems. Seven were randomized controlled trials. Studies targeted schools, drink-driving, work-places, the health sector and taxation. CONCLUSIONS China is the world's largest alcohol market, yet there has been little growth in alcohol policy research related to health promotion interventions over the past decade. Guided by a public health approach, the WHO Global Strategy and health reform experience in Russia, Australia, Mexico and the United States, China could improve its public health response through better coordination and implementation of surveillance and evidence-based research, and through programmatic and legal responses such as public health law research, screening and early intervention within health systems and the implementation of effective alcohol control strategies.


title: Reinforcement does not necessarily reduce the rate of staple line leaks after sleeve gastrectomy. A review of the literature and clinical experiences.

text: BACKGROUND Laparoscopic sleeve gastrectomy (SG) is an accepted bariatric procedure, with an advantaged by a low complication rate. A feared complication is stapler line leak. Buttressing materials have been suggested as a means of reducing staple line leak rates. We analyzed the leak rates from published series to help in demonstrating a potential cause. METHODS The study was institutional review board (IRB) approved retrospectively. A Medline search using the key words sleeve gastrectomy and bariatric surgery obtained 54 articles. Attention was restricted to 11 articles written in English that listed numbers of gastrectomy procedures and leaks. Poisson regression assessed the possibility that patients who received buttressing materials had a reduced rate of leaks. RESULTS Thirty-five patients were evaluated from Greece (15) and the United States (20); two patients developed staple line leaks that appeared to be related to problems associated with buttressing materials. Eleven prior studies and the present series yielded 1,589 procedures, 15 (0.94%) of which were complicated by leaks. The leak rate for patients who were known to have received reinforcement of some sort was 1.45 (95% confidence interval 0.41-3.43) times that for other patients. To detect a difference between 1% and 0.5% as statistically significant in 80% of cases, with a two tailed test and alpha set at 0.05, would require 9,346 procedures. CONCLUSIONS There is no reason to believe, at this point, that reduction in leak rates occur because reinforcement is used. Because the leak rate is small, the routine reinforcement of the staple line after sleeve gastrectomy is questionable at best, although a decrease in hemorrhage has been reported.


title: Assessment of gel-coated delayed self-gripping mesh.

text: BACKGROUND Mesh hernia repair is one of the most frequently performed procedures in general surgery. Recently, use of the self-gripping mesh demonstrated a beneficial effect on postoperative pain in inguinal hernia repairs. However, in intra-abdominal placement, the use of this novel mesh requires greater laparoscopic skill and dexterity because of the mesh's tendency to fold and adhere to itself and to any surrounding tissues. We hypothesized that gel-like coverage of a self-gripping mesh with a water-soluble film would allow delaying the immediate surface adhesion of the mesh to the tissue, which may allow greater freedom and ease in mesh placement for laparoscopic surgeons. METHODS In this ex vivo animal study, gel-coated self-gripping mesh (ProGrip) was compared with a control uncoated mesh in bovine and porcine tissue specimens and assessed for dislodgement shear forces before and after dissolving of the gel. RESULTS Gel coating of the mesh reduced preperitoneal dislodgement forces in a porcine abdominal wall specimen by 81% (8.05 ± 0.66 vs 1.53 ± 0.82 N, P < .01). Dissolving the gel markedly increased the anchoring forces (10.62 ± 3.70 vs 1.53 ± 0.82 N, P < .0001), and after dissolving the gel, the mesh shear dislodgement forces were similar and noninferior to the control mesh (8.05 ± 0.66 vs 10.62 ± 3.70 N, P = NS). CONCLUSIONS We believe that water-soluble gel coating does not impair the adhesive features of the self-gripping mesh and may simplify its use in open and laparoscopic procedures by allowing controlled activation of the self-gripping mechanism.


A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment.


title: Monitoring the Depth of Anesthesia Using a New Adaptive Neurofuzzy System.

text: Accurate and noninvasive monitoring of the depth of anesthesia (DoA) is highly desirable. Since the anesthetic drugs act mainly on the central nervous system, the analysis of brain activity using electroencephalogram (EEG) is very useful. This paper proposes a novel automated method for assessing the DoA using EEG. First, 11 features including spectral, fractal, and entropy are extracted from EEG signal and then, by applying an algorithm according to exhaustive search of all subsets of features, a combination of the best features (Beta-index, sample entropy, shannon permutation entropy, and detrended fluctuation analysis) is selected. Accordingly, we feed these extracted features to a new neurofuzzy classification algorithm, adaptive neurofuzzy inference system with linguistic hedges (ANFIS-LH). This structure can successfully model systems with nonlinear relationships between input and output, and also classify overlapped classes accurately. ANFIS-LH, which is based on modified classical fuzzy rules, reduces the effects of the insignificant features in input space, which causes overlapping and modifies the output layer structure. The presented method classifies EEG data into awake, light, general, and deep states during anesthesia with sevoflurane in 17 patients. Its accuracy is 92% compared to a commercial monitoring system (response entropy index) successfully. Moreover, this method reaches the classification accuracy of 93% to categorize EEG signal to awake and general anesthesia states by another database of propofol and volatile anesthesia in 50 patients. To sum up, this method is potentially applicable to a new real-time monitoring system to help the anesthesiologist with continuous assessment of DoA quickly and accurately.


title: Understanding Middle East respiratory syndrome.

text: Middle East respiratory syndrome is an infection caused by a novel coronavirus. The primary source of the virus is infected camels in several countries in the Arabian peninsula. The infection is acquired by coming into contact with infected animals, animal products, or with patients who have the syndrome. Mortality for this syndrome is 30% to 40%, and treatment is supportive because no antiviral therapy exists.


title: Long-term effect of the influenza A/H1N1 pandemic: attitudes and preventive behaviours one year after the pandemic.

text: This study aimed to describe changes in attitudes and behaviours regarding influenza A infection 1 year after the end of the pandemic. A cross-sectional study was performed based on two population-based telephone surveys including 1027 (February, 2010) and 1000 (February, 2011) participants in Spain. The percentages of the respondents who reported that they had adopted preventive measures to avoid Influenza infection declined 1 year after the pandemic. Influenza-related consultations decreased, whereas confidence in vaccination increased. Despite the decrease observed in adopting preventive measures, some behaviours were still being adopted long time after the pandemic in general population.


title: Nutritional Support in Coronavirus 2019 Disease.

text: The epidemic that broke out in Chinese Wuhan at the beginning of 2020 presented how important the rapid diagnosis of malnutrition (elevating during intensive care unit stay) and the immediate implementation of caloric and protein-balanced nutrition care are. According to specialists from the Chinese Medical Association for Parenteral and Enteral Nutrition (CSPEN), these activities are crucial for both the therapy success and reduction of mortality rates. The Chinese have published their recommendations including principles for the diagnosis of nutritional status along with the optimal method for nutrition supply including guidelines when to introduce education approach, oral nutritional supplement, tube feeding, and parenteral nutrition. They also calculated energy demand and gave their opinion on proper monitoring and supplementation of immuno-nutrients, fluids and macronutrients intake. The present review summarizes Chinese observations and compares these with the latest European Society for Clinical Nutrition and Metabolism guidelines. Nutritional approach should be an inseparable element of therapy in patients with COVID-19.


title: Microwave ablation of hepatic tumors abutting the diaphragm is safe and effective.

text: OBJECTIVE The purpose of this study was to evaluate the incidence of clinically significant diaphragmatic injuries and local tumor progression after microwave ablation of hepatic tumors abutting the diaphragm. MATERIALS AND METHODS This retrospective study included 55 peripheral hepatic tumors abutting the diaphragm treated by microwave ablation versus a control group of 15 centrally located tumors. Treated tumors were further subdivided according to the use of artificial ascites (fluid vs no fluid) and whether instilled fluid achieved displacement of the liver surface away from the diaphragm (displaced vs nondisplaced). Measurements of tumor size, distance to the diaphragm, ablation zone size, displacement distance, length of the ablation zone along the liver capsule, diaphragm thickness, diaphragmatic hernia, and local tumor progression were made on pre- and postablation CT and MRI. The electronic medical record was reviewed for patient self-reported pain scores and other symptoms. Data were analyzed by use of the Kruskal-Wallis and Fisher exact tests. RESULTS There were no cases of diaphragmatic hernia in peripheral or central tumors. Postablation diaphragm thickness was higher in peripheral hepatic tumors than in control tumors. Peripheral tumors had an overall higher incidence of postprocedure shoulder pain (18% vs 0%) and local tumor progression (5.5% vs 0%) compared with control tumors, but these differences did not achieve statistical significance (p = 0.2 and p = 1, respectively). CONCLUSION Our study shows that microwave ablation of peridiaphragmatic hepatic tumors is safe, without incidence of diaphragmatic hernia, and can be performed with a low rate of local tumor progression.


title: [CoViD-19 in Italy: homeless population needs protection.]

text: Italy is one of the most affected countries by the new coronavirus (CoViD-19) pandemic. In the country, there are an estimated 49,000-52,000 homeless people. People experiencing homelessness are among the potentially most vulnerable groups to the CoViD-19. Despite this, in Italy there is a worrying delay in implementation of a national coordinated strategy to protect homeless people from the potentially devastating effects caused by CoViD-19. In order to contain the epidemic among the most vulnerable people, we propose a short operational agenda based on the field experience of the medical-humanitarian organization Medici per i Diritti Umani (Doctors for Human Rights, Italy - MEDU) as well as on the example of initiatives taken by other countries.


title: CT imaging features of COVID-19 pneumonia: initial experience from Turkey.

text: PURPOSE We aimed to demonstrate the computed tomography (CT) findings observed at the initial presentation of coronavirus disease 2019 (COVID-19) pneumonia and reveal the most frequent infiltration and distribution patterns of the disease. METHODS One hundred and eighty-five patients (87 men, 98 women; mean age, 48.7 years), who underwent RT-PCR sampling and high-resolution CT examination in our hospital between March 15, 2020, and April 15, 2020, and got a definitive diagnosis of COVID-19 disease via initial or follow-up RT-PCR test, were included in the study. We comprehensively analyzed the most common and relatively rare CT imaging features (e.g., distribution pattern, density of the lesions, additional CT signs) in patients diagnosed with COVID-19 pneumonia. RESULTS Thirty-eight patients (20.6%) had no evidence of pneumonia on their initial high-resolution CT images. Among 147 patients (79.4%) who had parenchymal infiltration consistent with pneumonia, 10 (6.8%) had a negative baseline RT-PCR test, and positivity was detected as a result of repeated tests. Most of the patients had multifocal (89.1%) and bilateral (86.4%) lesions. The most common location, right lower lobe, was affected in 87.8% of the patients. Lesions were distributed predominantly at peripheral (87.1%) and posterior (46.3%) areas of lung parenchyma. Most of the patients had pure ground glass opacity (GGO) (82.3%) followed by GGO with consolidation (32.7%) and crazy paving pattern (21.8%). Pure consolidation, solid nodules, halo sign, reverse halo sign, vascular enlargement, subpleural line, air-bronchogram, and bronchiectasis were the other findings observed in at least 15% of the cases. Halo sign, acinar nodules, air-bubble sign, pleural thickening and effusion, mediastinal and/or hilar lymphadenopathy were seen rarely (2%-12.9%). Pericardial effusion, pneumothorax, cavitation, and tree-in-bud pattern were not detected in our study group. CONCLUSION Multifocal and bilateral GGO infiltration predominantly distributed in peripheral, posterior, and lower lung areas was the most common infiltration pattern.


title: We Need Compassionate Leadership Management Based on Evidence to Defeat COVID-19.

text: The current pandemic of coronavirus disease 2019 (COVID-19) has had unprecedented reach and shown the need for strong, compassionate and evidence-based decisions to effectively stop the spread of the disease and save lives. While aggressive in its response, Rwanda prioritized the lives of its people - a human right that some governments forget to focus on. The country took significant steps, before the first case and to limit the spread of the disease, rolled out a complete nationwide lockdown within one week of the first confirmed case, while also providing social support to vulnerable populations. This pandemic highlights the need for leaders to be educated on implementation science principles to be able to make evidence-based decisions through a multi-sectoral, integrated response, with consideration for contextual factors that affect implementation. This approach is critical in developing appropriate preparedness and response strategies and save lives during the current threat and those to come.


title: Roux-en-Y gastric bypass vs gastric banding for morbid obesity: a case-matched study of 442 patients.

text: HYPOTHESIS Gastric banding (GB) and Roux-en-Y gastric bypass (RYGBP) are used in the treatment of morbidly obese patients. We hypothesized that RYGBP provides superior results. DESIGN Matched-pair study in patients with a body mass index (BMI) less than 50. SETTING University hospital and regional community hospital with a common bariatric surgeon. PATIENTS Four hundred forty-two patients were matched according to sex, age, and BMI. INTERVENTIONS Laparoscopic GB or RYGBP. MAIN OUTCOME MEASURES Operative morbidity, weight loss, residual BMI, quality of life, food tolerance, lipid profile, and long-term morbidity. RESULTS Follow-up was 92.3% at the end of the study period (6 years postoperatively). Early morbidity was higher after RYGBP than after GB (17.2% vs 5.4%; P<.001), but major morbidity was similar. Weight loss was quicker, maximal weight loss was greater, and weight loss remained significantly better after RYGBP until the sixth postoperative year. At 6 years, there were more failures (BMI>35 or reversal of the procedure/conversion) after GB (48.3% vs 12.3%; P<.001). There were more long-term complications (41.6% vs 19%; P.001) and more reoperations (26.7% vs 12.7%; P<.001) after GB. Comorbidities improved more after RYGBP. CONCLUSIONS Roux-en-Y gastric bypass is associated with better weight loss, resulting in a better correction of some comorbidities than GB, at the price of a higher early complication rate. This difference, however, is largely compensated by the much higher long-term complication and reoperation rates seen after GB.


The Pope, condoms, and the evolution of HIV.


title: The effects of culture on guideline discordant gestational weight gain: a systematic review protocol.

text: BACKGROUND A significant proportion of women exceeds or does not meet the Institute of Medicine's gestational weight gain (GWG) guidelines. Inadequate, excessive GWG or weight loss during pregnancy is associated with an increased risk of negative maternal and fetal outcomes. Among the many determinants of GWG identified in the 2009 Institute of Medicine guidelines, culture was named as one of the few whose influence has not been fully explored. Some cultural beliefs may erroneously promote overeating as "eating for two" and discourage physical activity during pregnancy, but there is lack of empirical evidence on how culture affects GWG. The purpose of this systematic review is to examine the effects of culture on GWG. METHODS/DESIGN Ten electronic databases will be searched to identify studies reporting on the effects of culture on GWG. Grey literature, published conference abstracts, websites of relevant organizations and reference lists of included studies will also be searched. Studies that report on effects of culture, acculturation, ethnicity, race, nationality, ancestry and identity on GWG in adult women will be included. Quality of evidence will be evaluated using the grading of recommendations, assessment, development and evaluations (GRADE) approach to rating evidence. Study selection, data extraction and risk of bias assessment will be conducted by two independent reviewers, with disagreements being resolved by consensus or third party adjudication as needed. Formal meta-analyses will be conducted among included studies that are sufficiently statistically and clinically homogeneous. DISCUSSION This review will provide a comprehensive assessment and synthesis of current evidence and will draw attention to potential gaps where future research on the effects of culture on guideline discordant gestational weight gain remains to be conducted. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42015023399.


title: T cell engagement of cross-presenting microglia protects the brain from a nasal virus infection.

text: The neuroepithelium is a nasal barrier surface populated by olfactory sensory neurons that detect odorants in the airway and convey this information directly to the brain via axon fibers. This barrier surface is especially vulnerable to infection, yet respiratory infections rarely cause fatal encephalitis, suggesting a highly evolved immunological defense. Here, using a mouse model, we sought to understand the mechanism by which innate and adaptive immune cells thwart neuroinvasion by vesicular stomatitis virus (VSV), a potentially lethal virus that uses olfactory sensory neurons to enter the brain after nasal infection. Fate-mapping studies demonstrated that infected central nervous system (CNS) neurons were cleared noncytolytically, yet specific deletion of major histocompatibility complex class I (MHC I) from these neurons unexpectedly had no effect on viral control. Intravital imaging studies of calcium signaling in virus-specific CD8+ T cells revealed instead that brain-resident microglia were the relevant source of viral peptide-MHC I complexes. Microglia were not infected by the virus but were found to cross-present antigen after acquisition from adjacent neurons. Microglia depletion interfered with T cell calcium signaling and antiviral control in the brain after nasal infection. Collectively, these data demonstrate that microglia provide a front-line defense against a neuroinvasive nasal infection by cross-presenting antigen to antiviral T cells that noncytolytically cleanse neurons. Disruptions in this innate defense likely render the brain susceptible to neurotropic viruses like VSV that attempt to enter the CNS via the nose.


title: A Device to Predict Short-Term Healing Outcome of Chronic Wounds.

text: Objective: While myriads of studies have suggested that a survey of wound pH environment could indicate wound healing activities, it is not clear whether wound alkalinity can be used as a prognostic indicator of nonhealing wounds. Currently available systems cannot reliably assess the pH environment across wounds, which is the objective of this study. Approach: A disposable device, DETEC® pH, was developed and characterized on its ability to map wound alkalinity by pressing a freshly recovered wound dressing against its test surface. By comparing the wound's alkalinity and size reduction rates (∼7 days) following pH measurement, we assessed the capability of wound alkalinity to prognosticate subsequent short-term wound size reduction rates. Results: The device had high accuracy and specificity in determining the alkalinity of simulated wound fluids soaked onto wound dressing. The type of wound dressing type had an insignificant effect on its detection sensitivity. Upon testing discarded wound dressings from human patients, the device quickly determined alkaline and acidic wounds. Finally, statistical analyses of wound size reduction rates in wounds with various alkalinities confirmed that wound alkalinity has a strong influence on, at least, short-term wound healing activity. Innovation: Without directly contacting the patient, this device provides a quick assessment of wound alkalinity to prognosticate immediate and short-term wound healing activities. Conclusion: DETEC® pH may serve as a prognosis device for wound care specialists during routine wound assessment to predict wound healing progress. This information can assist the decision-making process in a clinical setting and augur well for chronic wound treatment. DETEC® pH can also be used as an aid for home health care nurses or health care providers to screen nonhealing wounds outside clinics.


title: Role of plants in the transmission of Asaia sp., which potentially inhibit the Plasmodium sporogenic cycle in Anopheles mosquitoes.

text: Biological control against malaria and its transmission is currently a considerable challenge. Plant-associated bacteria of the genus Asaia are frequently found in nectarivorous arthropods, they thought to have a natural indirect action on the development of plasmodium in mosquitoes. However, virtually nothing is known about its natural cycle. Here, we show the role of nectar-producing plants in the hosting and dissemination of Asaia. We isolated Asaia strains from wild mosquitoes and flowers in Senegal and demonstrated the transmission of the bacteria from infected mosquitoes to sterile flowers and then to 26.6% of noninfected mosquitoes through nectar feeding. Thus, nectar-producing plants may naturally acquire Asaia and then colonize Anopheles mosquitoes through food-borne contamination. Finally, Asaia may play an indirect role in the reduction in the vectorial capacity of Anopheles mosquitoes in a natural environment (due to Plasmodium-antagonistic capacities of Asaia) and be used in the development of tools for Asaia-based paratransgenetic malaria control.


title: Robotic resection of a middle mediastinal mass.

text: Aorto-pulmonary paraganglioma is an exceptionally rare condition, and its diagnosis and treatment are a challenge for the general thoracic surgeon. We describe the case of a 35 years old man who was incidentally diagnosed with a visceral mediastinal mass, deeply encased in the aorto-pulmonary window. To our knowledge this is the first case of its kind to be successfully treated with the adoption of a minimally invasive technique. We conclude that the dissection was made easier by the robotic instrumentation and by the camera system, and a minimally invasive approach would have been more difficult by traditional thoracoscopy.


title: [Logistic regression analysis of death risk factors of patients with severe and critical coronavirus disease 2019 and their predictive value].

text: OBJECTIVE To analyze the risk factors of death in patients with severe and critical coronavirus disease 2019 (COVID-19) and their predictive value. METHODS Using the clinical and epidemiological database of Yangtze River Shipping General Hospital in Wuhan, the clinical and epidemiological data of 105 patients with severe and critical COVID-19 from January to March in 2020 were collected. Multivariate unconditional Logistic regression method was used to analyze the death risk factors of patients during hospitalization. The receiver operating characteristic (ROC) curve was drawn according to the multivariate analysis results to construct a death prediction model; the prediction value of the model was analyzed. RESULTS The 105 patients with severe and critical COVID-19 were enrolled with 66 males (62.9%) and 39 females (37.1%). The age was (58.2±14.4) years old. Forty-two patients died in hospital and 63 survived. Among the dead patients, 69.0% (29/42) were male, and 78.6% (33/42) were over 60 years old. Compared with survival patients, the non-survival patients were older (years old: 59.2±12.5 vs. 51.2±11.4), and had more comorbidities, including coronary heart disease, hypertension, myocardial damage and thrombocytopenia (coronary heart disease: 33.3% vs. 11.1%, hypertension: 28.6% vs. 9.5%, myocardial damage: 73.8% vs. 11.1%, thrombocytopenia: 61.9% vs. 14.3%), and received more mechanical ventilation (92.9% vs. 44.4%), with significant differences (all P < 0.01). The variables of gender, age, basic diseases, mechanical ventilation and complications were included in the unconditional Logistic regression analysis, which showed that gender [odds ratio (OR) = 2.852, 95% confidence interval (95%CI) was 0.122-66.694], age (OR = 3.257, 95%CI was 0.466-18.584), coronary heart disease (OR = 7.337, 95%CI was 0.227-87.021), hypertension (OR = 5.517, 95%CI was 0.258-65.024) and concurrent myocardial damage (OR = 7.322, 95%CI was 0.278-95.020) and thrombocytopenia (OR = 3.968, 95%CI was 0.325-35.549) were independent risk factors for death in patients with severe and critical COVID-19 during hospitalization. According to the risk factors, the death prediction model was constructed and ROC curve was analyzed, which showed that the area under ROC curve (AUC) of death prediction model for predicting the mortality of patients with severe and critical COVID-19 during hospitalization was 0.804, the sensitivity was 83.8%, and the specificity was 82.3%. CONCLUSIONS Various risk factors are associated with the death of severe or critical COVID-19 patients, such as gender, age, basic diseases and complications. The death prediction model is constructed by gender, age, basic diseases with coronary heart disease and hypertension, concurrent myocardial damage and thrombocytopenia, which has certain predictive value for the death of patients with severe or critical COVID-19.


Hyperbaric oxygen treatment of novel coronavirus (COVID-19) respiratory failure.


COVID-19: collaboration will keep us ahead of the curve.


title: Possible Radio Interference Between Video Capsule Endoscopy and Second-Generation OmniPod Patch Pump.

text: Video capsule endoscopy (VCE) is a noninvasive diagnostic tool used to observe the small intestinal mucosa. We report a case of a 57-year-old woman with T2DM, treated with continuous subcutaneous insulin infusion using second-generation OmniPod patch pump, undergoing VCE (Given M2A; VCE Ltd, Yoqneam, Israel) for melena and anemia. During VCE, an abnormal interruption of communication between video capsule and its receiver occurred. Two hours after capsule ingestion, the patient activated the insulin pump infusion through the Personal Diabetes Manager (PDM) because she drank a sugary beverage for the first time after ingestion. Due to this, we decided to repeat VCE after the removal of the insulin pump and PDM: at this time, the capsule recorded for more than 10 h without any interruption. The video capsule and second-generation OmniPod patch pump use the same radio frequency and this may cause interference between these two devices. In patients using second-generation OmniPod patch pump undergoing VCE, we suggest to switch to intravenous insulin infusion or multiple daily injection or to use a different model of VCE, as MiRoCam (Intromedic, Seoul, Korea).


title: Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases

text: Artemisinins are sesquiterpene lactones with a peroxide moiety that are isolated from the herb Artemisia annua. It has been used for centuries for the treatment of fever and chills, and has been recently approved for the treatment of malaria due to its endoperoxidase properties. Progressively, research has found that artemisinins displayed multiple pharmacological actions against inflammation, viral infections, and cell and tumour proliferation, making them effective against diseases. Moreover, it has displayed a relatively safe toxicity profile. The use of artemisinins against different respiratory diseases has been investigated in lung cancer models and inflammatory-driven respiratory disorders. These studies revealed the ability of artemisinins in attenuating proliferation, inflammation, invasion, and metastasis, and in inducing apoptosis. Artemisinins can regulate the expression of pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), promote cell cycle arrest, drive reactive oxygen species (ROS) production and induce Bak or Bax-dependent or independent apoptosis. In this review, we aim to provide a comprehensive update of the current knowledge of the effects of artemisinins in relation to respiratory diseases to identify gaps that need to be filled in the course of repurposing artemisinins for the treatment of respiratory diseases. In addition, we postulate whether artemisinins can also be repurposed for the treatment of COVID-19 given its anti-viral and anti-inflammatory properties.


title: Seroma Formation in Rat Latissimus Dorsi Resection in the Presence of Biologics: The Role of Quilting.

text: BACKGROUND Seroma formation is a well-recognized complication associated with many operative procedures. Despite its ubiquity, a lack of definitive scientific understanding of the etiology, natural history, and biochemistry of seromas remains. We endeavored to create and examine seromas in a rat model in the setting of commonly used biologic implants and to examine the role of quilting sutures/mechanical fixation in mitigating seroma development. METHODS Female Sprague-Dawley rats were assigned to either Quilting or Nonquilting groups then subdivided into one of 3 porcine dermal implant groups (Permacol Surgical Implant, Strattice Reconstructive Tissue Matrix, or XCM Biologic Tissue Matrix) or control group. A 5-cm midline back incision was made, the skin reflected and the latissimus dorsi muscle resected bilaterally. Implants were sutured into the surgical bed using a running suture. The skin of nonquilted rats was closed with a running subcuticular suture. Quilted rats underwent placement of absorbable quilting sutures spaced 2 cm apart between the skin and underlying implant or muscle before skin closure. Postoperatively, rats were monitored for seroma formation with fluid aspirated as needed. At 28 or 90 days, rats were euthanized. Seroma and implants were examined grossly and under light microscopy. RESULTS Of nonquilted rats, 42/54 (78%) developed seromas compared with 19/46 (41%) of quilted rats (P < 0.05), defined by bursa cavity present at necropsy. When a biologic implant was present, 28/35 (80%) of nonquilted rats developed seromas compared with 12/33 (36%) of quilted rats (P < 0.05). In the control group, 14/19 (74%) of nonquilted rats developed seromas compared with 7/13 (54%) of quilted rats. This difference was not statistically significant. Bursa presence was confirmed histologically in all cases, with no difference in bursa character seen between groups. CONCLUSIONS This study confirms a reliable rat model of seroma formation, with most of the rats exhibiting at least subclinical seromas. There was no difference in seroma formation rate in the presence of biologic implants, and no differences in bursa character between implants. Mechanical fixation with quilting sutures decreased seroma rate significantly in all subgroups. All rats with seromas at necropsy had histological evidence of a bursa with no difference in appearance between groups.


An Expert Opinion From the European Society of Hypertension-European Union Geriatric Medicine Society Working Group on the Management of Hypertension in Very Old, Frail Subjects.


title: Trafficking of immune cells in the central nervous system.

text: The CNS is an immune-privileged environment, yet the local control of multiple pathogens is dependent on the ability of immune cells to access and operate within this site. However, inflammation of the distinct anatomical sites (i.e., meninges, cerebrospinal fluid, and parenchyma) associated with the CNS can also be deleterious. Therefore, control of lymphocyte entry and migration within the brain is vital to regulate protective and pathological responses. In this review, several recent advances are highlighted that provide new insights into the processes that regulate leukocyte access to, and movement within, the brain.


title: Health inequalities and infectious disease epidemics: a challenge for global health security.

text: In today's global society, infectious disease outbreaks can spread quickly across the world, fueled by the rapidity with which we travel across borders and continents. Historical accounts of influenza pandemics and contemporary reports on infectious diseases clearly demonstrate that poverty, inequality, and social determinants of health create conditions for the transmission of infectious diseases, and existing health disparities or inequalities can further contribute to unequal burdens of morbidity and mortality. Yet, to date, studies of influenza pandemic plans across multiple countries find little to no recognition of health inequalities or attempts to engage disadvantaged populations to explicitly address the differential impact of a pandemic on them. To meet the goals and objectives of the Global Health Security Agenda, we argue that international partners, from WHO to individual countries, must grapple with the social determinants of health and existing health inequalities and extend their vision to include these factors so that disease that may start among socially disadvantaged subpopulations does not go unnoticed and spread across borders. These efforts will require rethinking surveillance systems to include sociodemographic data; training local teams of researchers and community health workers who are able to not only analyze data to recognize risk factors for disease, but also use simulation methods to assess the impact of alternative policies on reducing disease; integrating social science disciplines to understand local context; and proactively anticipating shortfalls in availability of adequate healthcare resources, including vaccines. Without explicit attention to existing health inequalities and underlying social determinants of health, the Global Health Security Agenda is unlikely to succeed in its goals and objectives.


title: Comparative lower limb hemodynamics using neuromuscular electrical stimulation (NMES) versus intermittent pneumatic compression (IPC).

text: Deep Vein Thrombosis (DVT) is a life threatening condition and a serious concern among hospitalised patients, with death occurring in approximately 6% of cases. Intermittent pneumatic compression (IPC) is commonly used for DVT prevention, however suffers from low compliance and issues of usability and portability. Neuromuscular electrical stimulation (NMES) has been shown to improve lower limb hemodynamics but direct comparison with IPC in terms of hemodynamics is rare but very important to determine the potential effectiveness of NMES in DVT prevention.Lower limb IPC was compared to calf NMES, in 30 healthy volunteers (18-23 years). Each intervention was carried out on each leg, on the popliteal vein measured using Doppler ultrasound. All interventions produced significantly greater haemodynamic responses compared to baseline. Calf-IPC and NMES produced significant increases in venous blood velocity (cm/s) and volume of blood ejected per cycle (1 cycle of NMES expels 23.22 ml compared to the baseline ejected volume of 2.52 ml, measured over 1 s (p < 0.001 versues baseline).Improving lower limb hemodynamics is vital in preventing DVT. NMES resulted in larger ejected volumes compared to IPC (x3 greater than foot-IPC and x1.7 greater than calf-IPC) more effectively emptying the veins and soleal sinuses. This is an important finding as DVT occurs predominantly in the soleal sinuses. NMES is silent and portable and thus does not suffer many of the issues associated with IPC. This work supports the potential widespread application of NMES in hospital and home settings where the risk of DVT formation is high.


title: Accessibility of 'essential' alcohol in the time of COVID-19: Casting light on the blind spots of licensing?

text: Among the Australian and UK governments' responses to the COVID-19 pandemic has been the designation of outlets selling alcohol for off-premise consumption as 'essential' services, allowing them to remain open while pubs, hotels and restaurants have been forced to close. In a context of restrictions on movement outside the home in both countries, and where alcohol providers are trying to find new ways to reach their customers, this may lead to an intensification of the social and health harms associated with home drinking. By examining the current situation in both Australia and the UK, we argue that heightened risks from home drinking amid COVID-19 bring into sharp focus long-standing weaknesses within licensing systems in both countries: the regulation of off-premise outlets to minimise harms from drinking at home. We call for critical conversations on how licensing systems should be revised to take more responsibility for protecting people from the health and social harms associated with home drinking, both under COVID-19 and in the future.


No Rush to Judgment for Bariatric Surgery.


title: Assessing the role of cingulate cortex in bipolar disorder: neuropathological, structural and functional imaging data.

text: OBJECTIVES Most of the neuroanatomical models of bipolar disorder (BD) propose a key role for the anterior cingulate cortex (ACC). We provide here a review of currently available data regarding the CC neuroimaging and neuropathological alterations in BD. MATERIALS AND METHODS After an exploratory search of the MEDLINE, we first identified all English-written articles that provide separate data for BD patients and report original experimental data on cingulate gyrus. Subsequently, we selected those including neuroimaging or neuropathological data. Among the 161 articles updated through June 2007, 81 articles were retained using this procedure. RESULTS The review of in vivo volumetric imaging data, as well as ex vivo morphometric and histological studies indicates that BD patients show volume changes of the subgenual ACC (sgACC-BA 25 and part of 24) during the early stages of the disease. Whether this phenomenon is due to neuronal and glial depletion or damage of corticocortical connections is still a matter of debate. The resting state activity in the left BA 25 appears to be state dependent showing significant increase during mania and decrease during depressive phases. The presence of a deficient GABAergic activity in ACC is also documented. Pharmacological treatment partly restores BD-related functional imaging changes. CONCLUSION The present review reveals the striking discrepancies of the experimental results present both for functional and structural imaging studies but also for neuropathological analyses. Methodological and conceptual limitations are addressed with particular reference to the heterogeneity of BD clinical patterns. We also critically discuss the validity of CC changes as possible trait- or state-markers of the disease.


The End of Jacobson's Spread: Five Arguments Why An Anti-Intoxicant Vaccine Would Be Unconstitutional.


title: Long-Term Follow-Up of Retromuscular Incisional Hernia Repairs: Recurrence and Quality of Life.

text: PURPOSE Incisional hernia repair (IHR) with a mesh is necessary to achieve low recurrence rates and pain relief. In the short term, quality of life (QoL) is restored by IHR. Two centers pioneered the IHR in Sweden with the highly standardized Rives-Stoppa technique using a retromuscular mesh. We assessed long-term follow-up of recurrence rate and QoL. METHODS Medical records were searched for IHRs performed from 1998 to 2006 and included living patients with midline repairs. Questionnaires about physical status, complaints, and QoL (SF-36) were mailed, offering a clinical examination. Assessment of medical records of later surgery was performed in 2015. RESULTS Three hundred and one patients with midline incisional repairs were identified, and 217 accepted participation. Of these, 103 attended a clinical examination. Follow-up was 7 years until examination and 11 years to reassessment of medical records. In 26%, recurrent hernias were repaired. Postoperative complications were 26% Clavien-Dindo grade I-II and 1% grade III-IV. Mesh infections occurred in 1.4% without mesh removals, and 4% were reoperated because of complications. Overall recurrence rate was 8.1% and two-third of which were diagnosed at clinical examination. Recurrence after primary and recurrent hernia repair was 7.1 and 10.9%, respectively. Of all patients, 80% were satisfied; dissatisfaction was primarily caused by recurrence and chronic pain. SF-36 scores were 0.2 SD lower than the norm in all subscales, similar to those with 1-2 chronic conditions. CONCLUSIONS Midline retromuscular mesh IHR has a low long-term recurrence rate even after recurrent repair. Patient satisfaction was high although QoL was reduced.


title: Chloroplasts as expression platforms for plant-produced vaccines.

text: Production of recombinant subunit vaccines from genes incorporated in the plastid genome is advantageous because of the attainable expression level due to high transgene copy number and the absence of gene silencing; biocontainment as a consequence of maternal inheritance of plastids and no transgene presence in the pollen; and expression of multiple transgenes in prokaryotic-like operons. We discuss the core technology of plastid transformation in Chlamydomonas reinhardtii, a unicellular alga, and Nicotiana tabacum (tobacco), a flowering plant species, and demonstrate the utility of the technology for the production of recombinant vaccine antigens.


title: Comparison of a 3D head-mounted display (HMS-3000MT) and 3D passive polarizing display with 2D technique for first laparoscopic inguinal hernia repair by novice surgeons.

text: BACKGROUND Three-dimensional (3D) laparoscopy improves the surgical skills of novice surgeons and positively affects the learning curve in experimental settings. This study aimed to investigate the effect of a 3D passive polarizing display (3DPPD) and a novel 3D head-mounted display (3DHMD; HMS-3000MT) on the performance of the first laparoscopic inguinal hernia repair by novices and compare both systems with standard high-definition 2D (HD2D) laparoscopy. METHODS Patients with symptomatic inguinal hernia underwent transabdominal preperitoneal (TAPP) approach hernia repair using 3DHMD, 3DPPD, or a conventional HD2D laparoscopic system. All surgeries were performed for the first time by three laparoscopically novice surgeons. Operative performance was compared in terms of the time taken for mesh placement and peritoneal suturing under standardized conditions. Additionally, visual perception parameters and adverse effects were assessed. RESULTS The use of both 3D techniques shortened the time required for mesh placement and peritoneal suturing compared with the conventional HD2D approach. Generally, 3D laparoscopy was superior to HD2D laparoscopy in terms of visual perception parameters such as depth perception, sharpness, ghosting, and contrast. However, compared with the use of HD2D laparoscopy, the use of 3DHMD significantly impaired a surgeon's comfort, with the greatest impairment caused by ear discomfort, headaches, and facial and physical discomforts. CONCLUSIONS The 3DHMD and 3DPPD systems showed clear improvement in first hernia repair laparoscopy by novice surgeons in terms of surgical performance, as well as visual perception; however, the 3DHMD system was not superior to the 3DPPD system. The reduction in training time for new surgeons is obviously advantageous. In this respect, the 3D equipment may be a worthwhile investment.


title: Small changes in PDMMLA structure influence the adsorption behavior of ECM proteins and syndecan-4 on PDMMLA derivative surfaces: Experimental validation by tensiometric surface force measurements.

text: Cardiovascular diseases are the leading cause of death around the world according to the World Health Organization. In-stent restenosis is an inflammatory response of the immune system to endovascular stent implantation in atherosclerotic patients. Biocompatible and biodegradable polymers are of great interest in this field in order to limit the side effects of stent treatments. Poly([R,S]-3,3-dimethylmalic acid) (PDMMLA) is a new biodegradable statistical polyester which presents promising properties as a stent coating. In this work, we studied by dynamic tensiometry, the adhesion of extracellular matrix proteins (bovine serum albumin, fibronectin, fibrinogen, and vitronectin) and plasma membrane proteoglycan (syndecan-4) on three PDMMLA derivatives with different hydrophilicity levels. The results show that proteins have different adhesion profiles and affinity on these surfaces. They show similar behavior on the most hydrophilic surface, making hydrophilic, ionic and hydrogen type bonds. Then we compared each protein's individual profile to that of a mixture of all studied proteins. The comparison shows that vitronectin and syndecan-4 are the quantitatively dominating proteins adsorbed by specific interactions. Based on the results from previous studies, this work allowed us to identify the most important PDMMLA surface as a promising biomaterial for bioactive stent-coating.


title: 22G Acquire vs. 20G Procore needle for endoscopic ultrasound-guided biopsy of pancreatic masses: a randomized study comparing histologic sample quantity and diagnostic accuracy.

text: BACKGROUND : Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been suggested for obtaining high quality tissue samples from pancreatic tumors. We performed a multicenter randomized crossover trial comparing EUS-FNB with a 20G Procore needle vs. a 22G Acquire needle. The aims were to compare the quantity of targeted tissue (pancreas) and diagnostic accuracy for the two needles. METHODS : 60 patients admitted for EUS-FNB in three endoscopy units were included. One pass was performed consecutively with each needle, in a randomized order. Histologic material was studied in a blinded manner with respect to the needle. The primary end point was mean cumulative length of tissue core biopsies per needle pass. RESULTS : Final diagnosis was adenocarcinoma (n = 46; 77 %), neuroendocrine neoplasm (n = 11; 18 %), autoimmune pancreatitis (n = 2), and mass-forming chronic pancreatitis (n = 1). The mean cumulative length of tissue core biopsies per needle pass was significantly higher with the 22G Acquire needle at 11.4 mm (95 % confidence interval [CI] 9.0 - 13.8] vs. 5.4 mm (95 %CI 3.8 - 7.0) for the 20G Procore needle (P < 0.001), as was the mean surface area (3.5 mm2 [95 %CI 2.7 - 4.3] vs. 1.8 mm2 [95 %CI 1.2 - 2.3]; P < 0.001). Diagnostic adequacy and accuracy were 100 % and 87 % with the 22G Acquire needle, and 82 % and 67 % with the 20G Procore needle (P = 0.001 and P = 0.02, respectively). CONCLUSIONS : EUS-guided biopsy of pancreatic masses with the 22G Acquire needle provided more tissue for histologic evaluation and better diagnostic accuracy than the 20G Procore needle.


title: Immunosuppressive and immunomodulator therapy for rare or uncommon skin disorders in pandemic days.

text: Immunosuppressive and immunomodulatory therapies are important in dermatology, but indications are influenced by SARS-CoV-2. We will focus on are skin disorders such as autoimmune connective tissue disorders, neutrophilic dermatoses and vasculitis. Immunomodulators such as colchicine and antimalarials can easily be preferred taking their beneficial effects on Covid-19 into consideration and also given their wide spectrum of action. Among the conventional therapies, methotrexate, azathioprine and mycophenolate mofetil increase the risk of infection, and thus their use is recommended only when necessary and at low doses. On the other hand, use of cyclosporine is also not recommended as it increases the risk of hypertension, which is susceptible to Covid-19. Anti-TNF agents from among the biological therapies appear to be slightly risky in terms of susceptibility to infection. However, there are ongoing studies which suggest that some biological treatments may reduce cytokine storm impeding the Covid-19 progression as a result, in spite of their susceptibilities to Covid-19. Patients, who will be started on immunosuppressive therapy, should be tested for Covid-19 prior to the therapy, and in the event that Covid-19 is suspected, the therapy should be discontinued. This article is protected by copyright. All rights reserved.


In acute ischemic stroke, adding early endovascular treatment to usual care improved functional outcomes at 2 y.


title: Implementation of closed-loop-assisted intra-operative goal-directed fluid therapy during major abdominal surgery: A case-control study with propensity matching.

text: BACKGROUND Goal-directed fluid therapy (GDFT) has been associated with improved patient outcomes. However, implementation of GDFT protocols remains low despite growing published evidence and the recommendations of multiple regulatory bodies in Europe. We developed a closed-loop-assisted GDFT management system linked to a pulse contour monitor to assist anaesthesiologists in applying GDFT. OBJECTIVE To assess the impact of our closed-loop system in patients undergoing major abdominal surgery in an academic hospital without a GDFT programme. DESIGN A case-control study with propensity matching. SETTING Operating rooms, Erasme Hospital, Brussels. PATIENTS All patients who underwent elective open major abdominal surgery between January 2013 and December 2016. INTERVENTION Implementation of our closed-loop-assisted GDFT in April 2015. METHODS A total of 104 patients managed with closed-loop-assisted GDFT were paired with a historical cohort of 104 consecutive non-GDFT patients. The historical control group consisted of patients treated before the implementation of the closed-loop-system, and who did not receive GDFT. In the closed-loop group, the system delivered a baseline crystalloid infusion of 3 ml kg h and additional 100 ml fluid boluses of either a crystalloid or colloid for haemodynamic optimisation. MAIN OUTCOME MEASURES The primary outcome was intra-operative net fluid balance. Secondary outcomes were composite major postoperative complications, composite minor postoperative complications and hospital length of stay (LOS). RESULTS Baseline characteristics were similar in both groups. Patients in the closed-loop group had a lower net intra-operative fluid balance compared with the historical group (median interquartile range [IQR] 2.9 [1.6 to 4.4] vs. 6.2 [4.0 to 8.3] ml kg h; P < 0.001). Incidences of major and minor postoperative complications were lower (17 vs. 32%, P = 0.015 and 31 vs. 45%, P = 0.032, respectively) and hospital LOS shorter [median (IQR) 10 (6 to 15) vs. 12 (9 to 18) days, P = 0.022] in the closed-loop group. CONCLUSION Implementation of our closed-loop-assisted GDFT strategy resulted in a reduction in intra-operative net fluid balance, which was associated with reduced postoperative complications and shorter hospital LOS. TRIAL REGISTRATION NUMBER NCT02978430.


title: The importance of consistent advice during a pandemic: An analysis of Australian advice regarding personal protective equipment in healthcare settings during COVID-19.

text: BACKGROUND Lessons from previous pandemics emphasise the importance of consistent information and advice for healthcare workers (HCWs), particularly in relation to their use of personal protective equipment (PPE). OBJECTIVE The aim of this article is to review the consistency of advice regarding HCW use of PPE among Australian states and territories and 10 key Australian professional and advocacy organisations, against the Australian Government's national guidelines. DISCUSSION While some recommendations expand on the national guidelines, the Australian Government's efforts to work in concert with states, territories and peak professional and advocacy organisations are evident in the broadly consistent recommendations for the use of PPE by HCWs and other people working in healthcare settings across the country. The overall consistency of recommendations for the use of PPE shows a nationwide attempt to support and protect the healthcare workforce and the Australian community during the COVID-19 pandemic.


title: Single-Port Surgery in Inflammatory Bowel Disease: A Review of Current Evidence.

text: The majority of patients with Crohn's disease and up to 35 % of patients with ulcerative colitis will ultimately require surgery during the course of their disease. Over the past few years, surgical techniques and experience in minimal invasive surgery have evolved resulting in single-incision laparoscopic surgery. The aim of this approach is to diminish the surgical trauma by reducing the number of incision sites. This review discusses the benefits and disadvantages of single-port surgery in various procedures in patients with inflammatory bowel disease (IBD). Short-term postoperative results, functional outcome, and costs available in the literature will be discussed. Single-port surgery in IBD has several benefits when compared to multi-port laparoscopic surgery. By using fewer incisions, a potential reduction of postoperative pain with less morphine use can be accomplished. In addition, accelerated postoperative recovery can result in a shorter hospital stay. Furthermore, a superior cosmesis can be reached with placement of the port at the future ostomy site or at the umbilicus. Literature on single-port surgery in IBD consists mainly of case series and a few matched case series. These studies demonstrated that single-port surgery seems to be a safe and feasible approach for the surgical treatment of IBD patients.


title: [Prognostic value of myocardial injury in patients with COVID-19].

text: Objective: To analyze the prognostic value of myocardial injury in patients with COVID-19. Method: Confirmed cases of COVID-19 patients admitted from January 31st to February 5th at isolation ward of Renmin Hospital of Wuhan University were divided into non-survival group and survival group according to the clinical outcomes 5 weeks after admission. Data including demographics, comorbidities, vital signs, laboratory results were obtained. Cardiac injury was defined as serum concentration of high sensitivity cardiac troponin I (hs-cTnI) above 0.04 μg/L. Univariate and multivariate Cox regression were used to analyze the prognostic value of myocardial injury in patients with COVID-19. Kaplan-Meier analysis was used to plotted survival curve and analyze the impact of myocardial injury on the survival outcome of COVID-19 patients. Results: A total of 202 patients were included, the age was 63 (51, 70) years old, 88 (43.6%) of them were male, 85 (42.1%) of them had comorbidities, 125 (61.9%) of them were severely to critically ill. Till March 11, 33 patients died, all of them were critically ill patients. The age, proportion of males, comorbidities, respire rate, serum levels of hs-cTnI and incidence of heart failure in the non-survival group were significantly higher than those in the survival group (all P<0.05). The hospitalization time of non-survival group was significantly shorter than that of survival group (6(4, 9) vs. 32(23, 36), P<0.001). Myocardial injury was an important prognostic factor of COVID-19 (HR=5.382, 95%CI 2.404-12.05, P<0.001). Kaplan-Meier survival analysis showed that the presence of myocardial injury was significantly associated with the reduced survival rate among COVID-19 patients (P<0.001). Conclusion: Myocardial injury is an important prognostic factor of COVID-19, COVID-19 patients with myocardial injury face a significantly higher risk of death.


title: Nursing assistants: "he seems to be ill" - a reason for nurses to take action: validation of the Early Detection Scale of Infection (EDIS).

text: BACKGROUND Signs and symptoms of infection in frail elderly are atypical, causing delay in diagnosis and treatment. To improve communication between healthcare staff of signs and symptoms of infection we developed an instrument, using qualitative data from observations by nursing assistants when they suspected infection. The aim of this study was to assess the validity of nursing assistants observations by developing and testing the instrument for early detection of infection in elderly nursing home residents. METHODS The early detection of infection (EDIS) instrument was based on data from focus interviews with nursing assistants. Over one year the nursing assistants used EDIS to document episodes of suspected early signs and symptoms of infection in 204 nursing home residents. Two physicians classified documented episodes as "no infection", "possible infection", and "infection". The content validity of the 13 items of the EDIS was established to explore the relationships between the items. The construct validity was used to explore the relationship between the items and the presence or absence of infection. The predictive value of the developed model was evaluated by the percentage of correct classifications of the observed cases. Generalized linear model (ordinal multinomial distribution and logit link) was used. RESULTS Of the 388 events of suspected infection, 20 % were assessed as no infection, 31 % as possible infection and 49 % as infection. Content validity analysis showed that 12/13 of the items correlated significantly with at least one other statement. The range in number of significant inter-correlations was from 0 ("pain") to 8 ("general signs and symptoms of illness"). The construct validity showed that the items "temperature" , "respiratory symptoms" and "general signs and symptoms of illness" were significantly related to "infection", and these were also selected in the model-building. These items predicted correct alternative responses in 61 % of the cases. CONCLUSION The validation of EDIS suggests that the observation of "general signs and symptoms of illness", made by nursing assistants should be taken seriously in detecting early infection in frail elderly. Also, the statement "He/She is not as usual" should lead to follow-up.


title: Baloxavir for the treatment of Influenza in allogeneic hematopoietic stem cell transplant recipients previously treated with Oseltamivir.

text: BACKGROUND Seasonal influenza causes significant morbidity and mortality in allogeneic stem cell transplant (SCT) recipients. In this population, influenza virus can replicate for prolonged periods, despite neuraminidase inhibitor treatment, leading to resistance and treatment failure. Baloxavir targets the influenza polymerase and may be an effective treatment option in these patients. METHODS We used baloxavir to treat five allogeneic SCT recipients that were still symptomatic and shedding influenza virus after completing one or more treatment courses of oseltamivir and characterized the viral isolates before and during treatment. RESULTS Two patients were infected with influenza A/H1pdm09 carrying a neuraminidase variant (H275Y) linked to oseltamivir resistance. Both these two patients were successfully treated with baloxavir. Of the 3 patients infected with wild-type influenza virus, two cleared the virus after baloxavir treatment, while the third patient developed the polymerase I38T variant linked to baloxavir resistance. CONCLUSIONS Our data suggest that baloxavir treatment can be effective in treating neuraminidase inhibitor resistant influenza in profoundly immunocompromised patients. Randomized clinical trials are needed to define the role of baloxavir alone and combined with oseltamivir for treatment of influenza in SCT recipients and other immunocompromised populations.


title: Repeated Radiofrequency Ablation Combined With Ablated Lesion Elimination and Transarterial Chemoembolization Improves the Outcome of Solitary Huge Hepatocellular Carcinomas 10 m or Larger.

text: This study investigated the effectiveness of a new strategy, repeated radiofrequency (RF) ablation combined with ablated lesion elimination following transarterial chemoembolization (TACE)/transarterial embolization (TAE), for solitary huge hepatocellular carcinoma (SHHCC) 10 cm or larger. From July 2008 to October 2015, 39 consecutive patients with SHHCC were screened. Of these, 12 were treated with TACE/TAE and repeated RF ablation (TACE/TAE + RF ablation group) and the remaining 27 patients were treated with the aforementioned new strategy (new strategy group). Local tumor progression (LTP)-free survival, intrahepatic distant recurrence (IDR)-free survival, and overall survival (OS) rates were obtained using the Kaplan-Meier method. Univariate and multivariate analyses were performed on several clinicopathological variables to identify factors affecting long-term outcome and intrahepatic recurrence. Correlation analysis was also performed. The 1-, 2-, and 3-year LTP-free survival rates and OS rates were significantly higher in the new strategy group than in the TACE/TAE + RF ablation group (82.9% vs 58.3%, 73.9% vs 29.2%, 18.5% vs 9.7%, P = 0.002; 92.0% vs 75.0%, 84.0% vs 33.3%, 32.7% vs 16.7%, P = 0.025). However, there was no significant difference between the 2 groups in the 1-, 2-, and 3-year IDR-free survival rates (P = 0.108). Using univariate analysis, alpha-fetoprotein (AFP > 200 ng/mL), ablative margin (AM > 1.0 cm), and well-differentiated cells were found to be significant factors for predicting LTP, IDR, and OS. Surgical elimination was found to be a significant factor only for predicting OS. In multivariate analyses, AFP (>200 ng/mL), AM (>1.0 cm), and well-differentiated cells were found to be significant independent factors linked to LTP, IDR, and OS. Correlation analysis indicated that AM > 1.0 cm was strongly associated with surgical elimination (P < 0.001, correlation coefficient = 0.877). For patients with SHHCC who were initially excluded from surgery, the new strategy including repeated RF ablation combined with ablated lesion elimination following TACE/TAE should now be considered as an alternative treatment.


title: Integrative pharmacological mechanism of vitamin C combined with glycyrrhizic acid against COVID-19: findings of bioinformatics analyses.

text: OBJECTIVE Coronavirus disease 2019 (COVID-19) is a fatal and fast-spreading viral infection. To date, the number of COVID-19 patients worldwide has crossed over six million with over three hundred and seventy thousand deaths (according to the data from World Health Organization; updated on 2 June 2020). Although COVID-19 can be rapidly diagnosed, efficient clinical treatment of COVID-19 remains unavailable, resulting in high fatality. Some clinical trials have identified vitamin C (VC) as a potent compound pneumonia management. In addition, glycyrrhizic acid (GA) is clinically as an anti-inflammatory medicine against pneumonia-induced inflammatory stress. We hypothesized that the combination of VC and GA is a potential option for treating COVID-19. METHODS The aim of this study was to determine pharmacological targets and molecular mechanisms of VC + GA treatment for COVID-19, using bioinformational network pharmacology. RESULTS We uncovered optimal targets, biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of VC + GA against COVID-19. Our findings suggested that combinatorial VC and GA treatment for COVID-19 was associated with elevation of immunity and suppression of inflammatory stress, including activation of the T cell receptor signaling pathway, regulation of Fc gamma R-mediated phagocytosis, ErbB signaling pathway and vascular endothelial growth factor signaling pathway. We also identified 17 core targets of VC + GA, which suggest as antimicrobial function. CONCLUSIONS For the first time, our study uncovered the pharmacological mechanism underlying combined VC and GA treatment for COVID-19. These results should benefit efforts to address the most pressing problem currently facing the world.


title: Chickens host diverse picornaviruses originated from potential interspecies transmission with recombination.

text: While chickens are an important reservoir for emerging pathogens such as avian influenza viruses, little is known about the diversity of picornaviruses in poultry. We discovered a previously unknown diversity of picornaviruses in chickens in Hong Kong. Picornaviruses were detected in 87 cloacal and 7 tracheal samples from 93 of 900 chickens by reverse transcription-PCR, with their partial 3D(pol) gene sequences forming five distinct clades (I to V) among known picornaviruses. Analysis of eight genomes from different clades revealed seven different picornaviruses, including six novel picornavirus species (ChPV1 from clade I, ChPV2 and ChPV3 from clade II, ChPV4 and ChPV5 from clade III, ChGV1 from clade IV) and one existing species (Avian encephalomyelitis virus from clade V). The six novel chicken picornavirus genomes exhibited distinct phylogenetic positions and genome features different from related picornaviruses, supporting their classification as separate species. Moreover, ChPV1 may potentially belong to a novel genus, with low sequence homologies to related picornaviruses, especially in the P1 and P2 regions, including the predicted L and 2A proteins. Nevertheless, these novel picornaviruses were most closely related to picornaviruses of other avian species (ChPV1 related to Passerivirus A, ChPV2 and ChPV3 to Avisivirus A and Duck hepatitis A virus, ChPV4 and ChPV5 to Melegrivirus A, ChGV1 to Gallivirus A). Furthermore, ChPV5 represented a potential recombinant picornavirus, with its P2 and P3 regions possibly originating from Melegrivirus A. Chickens are an important reservoir for diverse picornaviruses that may cross avian species barriers through mutation or recombination.


title: Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2.

text: The distribution of the severe acute respiratory syndrome coronavirus (SARS-CoV) receptor, an angiotensin-converting enzyme 2 (ACE2), does not strictly correlate with SARS-CoV cell tropism in lungs; therefore, other cellular factors have been predicted to be required for activation of virus infection. In the present study, we identified transmembrane protease serine 2 (TMPRSS2), whose expression does correlate with SARS-CoV infection in the upper lobe of the lung. In Vero cells expressing TMPRSS2, large syncytia were induced by SARS-CoV infection. Further, the lysosome-tropic reagents failed to inhibit, whereas the heptad repeat peptide efficiently inhibited viral entry into cells, suggesting that TMPRSS2 affects the S protein at the cell surface and induces virus-plasma membrane fusion. On the other hand, production of virus in TMPRSS2-expressing cells did not result in S-protein cleavage or increased infectivity of the resulting virus. Thus, TMPRSS2 affects the entry of virus but not other phases of virus replication. We hypothesized that the spatial orientation of TMPRSS2 vis-a-vis S protein is a key mechanism underling this phenomenon. To test this, the TMPRSS2 and S proteins were expressed in cells labeled with fluorescent probes of different colors, and the cell-cell fusion between these cells was tested. Results indicate that TMPRSS2 needs to be expressed in the opposing (target) cell membrane to activate S protein rather than in the producer cell, as found for influenza A virus and metapneumoviruses. This is the first report of TMPRSS2 being required in the target cell for activation of a viral fusion protein but not for the S protein synthesized in and transported to the surface of cells. Our findings suggest that the TMPRSS2 expressed in lung tissues may be a determinant of viral tropism and pathogenicity at the initial site of SARS-CoV infection.


title: Characterizing the effect of Bortezomib on Rift Valley Fever Virus multiplication.

text: Rift Valley Fever Virus (RVFV) belongs to the family Bunyaviridae and is a known cause of epizootics and epidemics in Africa and the Middle East. With no FDA approved therapeutics available to treat RVFV infection, understanding the interactions between the virus and the infected host is crucial to developing novel therapeutic strategies. Here, we investigated the requirement of the ubiquitin-proteasome system (UPS) for the establishment of a productive RVFV infection. It was previously shown that the UPS plays a central role in RVFV multiplication involving degradation of PKR and p62 subunit of TFIIH. Using the FDA-approved proteasome inhibitor Bortezomib, we observed robust inhibition of intracellular and extracellular viral loads. Bortezomib treatment did not affect the nuclear/cytoplasmic distribution of the non-structural S-segment protein (NSs); however, the ability of NSs to form nuclear filaments was abolished as a result of Bortezomib treatment. In silico ubiquitination prediction analysis predicted that known NSs interactors (SAP30, YY1, and mSin3A) have multiple putative ubiquitination sites, while NSs itself was not predicted to be ubiquitinated. Immunoprecipitation studies indicated a decrease in interaction between SAP30 - NSs, and mSin3A - NSs in the context of Bortezomib treatment. This decrease in association between SAP30 - NSs also correlated with a decrease in the ubiquitination status of SAP30 with Bortezomib treatment. Bortezomib treatment, however, resulted in increased ubiquitination of mSin3A, suggesting that Bortezomib dynamically affects the ubiquitination status of host proteins that interact with NSs. Finally, we observed that expression of interferon beta (IFN-β) was increased in Bortezomib treated cells which indicated that the cellular antiviral mechanism was revived as a result of treatment and may contribute to control of viral multiplication.


title: Early 18F-FDG-PET/CT as a predictive marker for treatment response and survival in patients with metastatic colorectal cancer treated with irinotecan and cetuximab.

text: BACKGROUND To clarify if early reduction in standard uptake value (SUV) could predict metabolic response, radiologic response and overall survival (OS) in patients with metastatic colorectal cancer receiving third-line treatment. MATERIAL AND METHODS Patients were regardless of KRAS status, included in this phase II trial. They were treated with the monoclonal antibody, cetuximab, and the chemotherapeutic drug, irinotecan, every second week. A F18-fluorodeoxy glucose positron emission tomography/computed tomography (FDG-PET/CT) was scheduled before the first and second treatment, respectively, and then after every fourth treatment. Early metabolic response after one treatment and best overall metabolic response was calculated according to EORTC criteria (responders: ≥15% decrease in ∑SUVmax) and PERCIST (responders: ≥30% decrease in SULpeak). Best overall radiologic response was calculated according to RECIST 1.0. RESULTS By EORTC criteria, early metabolic response predicted partial metabolic response (PMR) with a high positive predictive value (PPV) of 0.875 and a high negative predictive value (NPV) of 0.714. Partial radiologic response was predicted with a low PPV of 0.368 but a high NPV of 1.0. By PERCIST, PMR was predicted with a high PPV of 0.826 and an intermediate NPV of 0.667 and partial radiologic response was predicted with a low PPV of 0.5 but a high NPV of 1.0. Median OS was nearly the same with the two criteria sets; 14.1 months for early metabolic responders and 9.9 months for non-responders using EORTC criteria and 13.5 and 10.1 months, respectively, using PERCIST. CONCLUSIONS With both EORTC criteria and PERCIST, early reduction in FDG uptake was predictive of a later partial metabolic and partial radiologic response to treatment. It was also predictive of significantly longer survival of early metabolic responders compared to non-responders. However, the sensitivities and specificities were not high enough to support clinical routine use.


title: Vaginal discharge caused by lymphatic malformation identified by lymphoscintigraphy combined with T2-weighted magnetic resonance imaging.

text: Prepubertal vaginal discharge is most commonly caused by vulvovaginitis and is rarely caused by lymphatic malformations, resulting in chylous vaginal discharge. The diagnosis of chylous vaginal discharge remains a challenge because of a knowledge gap. We describe a 12-year-old girl with intermittent vaginal discharge for 10 years. Although we found a high signal in the vagina on T2-weighted magnetic resonance imaging (MRI), the final diagnosis, vaginal lymphatic leakage, was established on lymphoscintigraphy. Lymphatic leakage in the vagina on lymphoscintigraphy was the key imaging feature of chylous vaginal discharge in this patient. Moreover, diffuse radioactivity was found in the abdomen and thorax on lymphoscintigraphy, which indicated the multiple cystic lymphatic malformations and intestinal lymphangiectasia combined with T2-weighted MRI. Thus, T2-weighted MRI could be used in combination with lymphoscintigraphy to simply identify chylous vaginal discharge.