title: A low-power bio-potential acquisition system with flexible PDMS dry electrodes for portable ubiquitous healthcare applications.

text: This work describes a bio-potential acquisition system for portable ubiquitous healthcare applications using flexible polydimethylsiloxane dry electrodes (FPDEs) and a low-power recording circuit. This novel FPDE used Au as the skin contact layer, which was made using a CO2 laser and replica method technology. The FPDE was revised from a commercial bio-potential electrode with a conductive snap using dry electrodes rather than wet electrodes that proposed reliable and robust attachment for the purpose of measurement, and attaching velcro made it wearable on the forearm for bio-potential applications. Furthermore, this study proposes a recording device to store bio-potential signal data and provides portability and low-power consumption for the proposed acquisition system. To acquire differential bio-potentials, such as electrocardiogram (ECG) signals, the proposed recording device includes a low-power front-end acquisition chip fabricated using a complementary metal-oxide-semiconductor (CMOS) process, a commercial microcontroller (MSP430F149), and a secure digital (SD) card for portable healthcare applications. The proposed system can obtain ECG signals efficiently and are comfortable to the skin. The power consumption of the system is about 85 mW for continuous working over a 3 day period with two AA batteries. It can also be used as a compact Holter ECG system.


title: Combinations of physical activity, sedentary time, and sleep duration and their associations with depressive symptoms and other mental health problems in children and adolescents: a systematic review.

text: BACKGROUND For optimal health benefits, the Canadian 24-Hour Movement Guidelines for Children and Youth (aged 5-17 years) recommend an achievement of high levels of physical activity (≥60 min of moderate-to-vigorous physical activity), low levels of sedentary behaviour (≤2 h of recreational screen time), and sufficient sleep (9-11 h for children or 8-10 h for adolescents) each day. The objective of this systematic review was to examine how combinations of physical activity, sedentary time, and sleep duration relate to depressive symptoms and other mental health indicators among children and adolescents. METHODS Literature was obtained through searching Medline, EMBASE, PsycINFO, and SportDiscus up to September 30, 2019. Peer-reviewed studies published in English or French were included if they met the following criteria: population (apparently healthy children and adolescents with a mean age of 5-17 years), intervention/exposure (combinations of physical activity, sedentary time, and sleep duration), and outcomes (depressive symptoms and other mental health indicators). A risk of bias assessment was completed for all included studies using the methods described in the Cochrane Handbook. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the quality of evidence for each health indicator. Narrative syntheses were employed to describe the results due to high levels of heterogeneity across studies. RESULTS A total of 13 cross-sectional studies comprised in 10 papers met inclusion criteria. Data across studies involved 115,540 children and adolescents from 12 countries. Overall, the findings indicated favourable associations between meeting all 3 recommendations and better mental health indicators among children and adolescents when compared with meeting none of the recommendations. There was evidence of a dose-response gradient between an increasing number of recommendations met and better mental health indicators. Meeting the screen time and sleep duration recommendations appeared to be associated with more mental health benefits than meeting the physical activity recommendation. The quality of evidence reviewed was "very low" according to GRADE. CONCLUSIONS The findings indicate favourable associations between meeting all 3 movement behaviour recommendations in the 24-h guidelines and better mental health indicators among children and adolescents. There is a clear need for high-quality studies that use robust measures of all movement behaviours and validated measures of mental health to increase our understanding in this topic area.


title: Laparoscopic splenectomy for hereditary spherocytosis-preliminary report.

text: Splenectomy is considered standard surgical therapy in hereditary spherocytosis. The procedure is indicated in patients with severe anemia, recurrent hemolytic, and aplastic crises. The aim of the study was to assess treatment outcomes in patients with hereditary spherocytosis who underwent total or partial laparoscopic splenectomy. Fifteen patients aged 4-17 yr underwent laparoscopic splenectomy from 2009 to 2012. Partial and total splenectomies were performed (five and 10 children, respectively). Hematologic parameters, liver function tests, and splenic volume before and after the surgery were analyzed retrospectively. Total follow-up was 1-30 months. Hospitalization and operating time were similar in both groups. In partial splenectomy group, branches of splenic arteries gave better blood supply than short gastric vessels. In both groups, hematologic parameters were improved. Postoperative markedly elevated platelet count was maintained up to 6 months, and after that, platelet count gradually decreased to normal values. Bilirubin level was decreased in early postoperative period; however, it increased later to achieve levels lower than in preoperative period. No severe general infections were observed in both groups. Laboratory parameters (hemoglobin and bilirubin concentrations and RBC) after the surgery improved in all patients, and the effect was maintained during 12 months of follow-up. Platelet count increased significantly after the surgery and was maintained at high levels during the next 6 months. However, it returned to preoperative levels within a year after the surgery. Our study showed that partial splenectomy was not inferior to total splenectomy. However, full assessment requires longer follow-up and larger group of patients.


Nervous system: subclinical target of SARS-CoV-2 infection.


LAPAROSCOPIC SURGERY AND THE COVID-19 PANDEMIC: A WORD FROM A DIFFERENT HYMN SHEET.


title: Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS).

text: BACKGROUND Severe acute respiratory syndrome (SARS) is an acute respiratory disease caused by a novel coronavirus, which first appeared in Foshan City, China on 22 December 2002. Chinese herbs were used in its treatment. OBJECTIVES To evaluate the possible effectiveness and safety of Chinese herbs combined with Western medicines versus Western medicines alone for SARS patients. SEARCH METHODS We searched CENTRAL 2012, Issue 3, MEDLINE (1966 to February Week 4, 2012), EMBASE (1990 to March 2012) and the Chinese Biomedical Literature (Issue 3, 2012). SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs of Chinese herbs combined with Western medicines versus Western medicines alone for patients diagnosed with SARS. DATA COLLECTION AND ANALYSIS Two review authors (XL, MZ) independently extracted trial data. We extracted dichotomous and continuous data with 95% confidence intervals (CI). For dichotomous data, we used risk ratio (RR). For continuous data, we calculated mean differences (MD). We calculated overall results based on the random-effects model if heterogeneity existed between studies. If no heterogeneity was detected between the studies, we used the fixed-effect model. We used the Z score and the Chi(2) test with significance being set at P < 0.05 to test heterogeneity. No severe adverse events were reported. MAIN RESULTS We included 12 RCTs and one quasi-RCT. A total of 640 SARS patients and 12 Chinese herbs were identified. We did not find Chinese herbs combined with Western medicines decreased mortality versus Western medicines alone. Two herbs may improve symptoms. Five herbs may improve lung infiltrate absorption. Four herbs may decrease the dosage of corticosteroids. Three herbs may improve the quality of life of SARS patients. One herb may shorten the length of hospital stay. AUTHORS' CONCLUSIONS Chinese herbs combined with Western medicines made no difference in decreasing mortality versus Western medicines alone. It is possible that Chinese herbs combined with Western medicines may improve symptoms, quality of life and absorption of pulmonary infiltration, and decrease the corticosteroid dosage for SARS patients. The evidence is weak because of the poor quality of the included trials. Long-term follow-up of these included trials is needed.


title: Inhibitors of SARS-3CLpro: virtual screening, biological evaluation, and molecular dynamics simulation studies.

text: SARS-CoV from the coronaviridae family has been identified as the etiological agent of Severe Acute Respiratory Syndrome (SARS), a highly contagious upper respiratory disease that reached epidemic status in 2002. SARS-3CL(pro), a cysteine protease indispensible to the viral life cycle, has been identified as one of the key therapeutic targets against SARS. A combined ligand and structure-based virtual screening was carried out against the Asinex Platinum collection. Multiple low micromolar inhibitors of the enzyme were identified through this search, one of which also showed activity against SARS-CoV in a whole cell CPE assay. Furthermore, multinanosecond explicit solvent simulations were carried out using the docking poses of the identified hits to study the overall stability of the binding site interactions as well as identify important changes in the interaction profile that were not apparent from the docking study. Cumulative analysis of the evaluated compounds and the simulation studies led to the identification of certain protein-ligand interaction patterns which would be useful in further structure based design efforts.


The Role of Scientific Publishing in the SARS-CoV-2 Pandemic.


title: Revised sleeve gastrectomy: another option for weight loss failure after sleeve gastrectomy.

text: INTRODUCTION Laparoscopic sleeve gastrectomy (LSG) is becoming a very common bariatric procedure, based on several advantages it carries over more complex bariatric procedures such as gastric bypass or duodenal switch (DS), and a better quality of life over gastric banding. However, in the long-term follow-up, weight loss failure and intractable severe reflux after primary LSG can necessitate further surgical interventions, and revisional sleeve gastrectomy (ReSG) can represent an option to correct these. METHODS From October 2008 to June 2013, 36 patients underwent an ReSG for progressive weight regain, insufficient weight, or severe gastroesophageal reflux in 'La Casamance' Private Hospital. All patients with weight loss failure after primary LSG underwent radiological evaluation. If Gastrografin swallow showed a huge unresected fundus or an upper gastric pouch dilatation, or if the computed tomography (CT) scan volumetry revealed a gastric tube superior to 250 cc, ReSG was proposed. RESULTS Thirty-six patients (34 women, two men; mean age 41.3 years) with a body mass index (BMI) of 39.9 underwent ReSG. Thirteen patients (36.1 %) had their original LSG surgery performed at another hospital and were referred to us for weight loss failure. Twenty-four patients (66.6 %) out of 36 had a history of gastric banding with weight loss failure. Thirteen patients (36.1 %) were super-obese (BMI > 50) before primary LSG. The LSG was realized for patients with morbid obesity with a mean BMI of 47.1 (range 35.4-77.9). The mean interval time from the primary LSG to ReSG was 34.5 months (range 9-67 months). The indication for ReSG was insufficient weight loss for 19 patients (52.8 %), weight regain for 15 patients (41.7 %), and 2 patients underwent ReSG for invalidating gastroesophageal reflux disease. In 24 cases the Gastrografin swallow results were interpreted as primary dilatation, and in the remaining 12 cases results were interpreted as secondary dilatation. The CT scan volumetry was realized in 21 cases, and it has revealed a mean gastric volume of 387.8 cc (range 275-555 cc). All 36 cases were completed by laparoscopy with no intraoperative incidents. The mean operative time was 43 min (range 29-70 min), and the mean hospital stay was 3.9 days (range 3-16 days). One perigastric hematoma was recorded. The mean BMI decreased to 29.2 (range 20.24-37.5); the mean percentage of excess weight loss was 58.5 % (±25.3) (p < 0.0004) for a mean follow-up of 20 months (range 6-56 months). CONCLUSIONS The ReSG may be a valid option for failure of primary LSG for both primary or secondary dilatation. Long-term results of ReSG are awaited to prove efficiency. Further prospective clinical trials are required to compare the outcomes of ReSG with those of Roux en Y Gastric Bypass or DS for weight loss failure after LSG.


title: The pathophysiology of acute pain: animal models.

text: PURPOSE OF REVIEW Trauma, surgery, and burns are three common clinical scenarios that are associated with significant acute pain. This review describes the pathophysiology of acute pain utilizing three preclinical models: surgery, burn, and fracture. RECENT FINDINGS In general, there is greater interest directed toward peripheral mediators of acute pain. Studies indicate that treatment against nerve growth factor, interleukins, and ischemic-like mediators may provide valuable avenues for treatment of acute pain. By targeting the periphery, analgesic therapies may have reduced side-effects. SUMMARY Peripheral mediators of acute pain can vary depending upon the type of injury. Treatment aimed toward those mediators specific to the injury may improve acute pain management in the future. It will be important to translate these findings into clinical trials in the future.


title: Click-chemistry-derived triazole ligands of arginine-glycine-aspartate (RGD) integrins with a broad capacity to inhibit adhesion of melanoma cells and both in vitro and in vivo angiogenesis.

text: A click chemistry approach was applied for the discovery of triazole-based arginine-glycine-aspartate (RGD) mimetics by Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction, which showed binding affinity properties toward α(v)β(3)/α(v)β(5) integrins. Biological assays showed compound 18 capable of binding α(v)β(3) integrin with nanomolar affinity according to a two-sites model, and molecular modeling studies revealed a peculiar π-stacking interaction between the triazole ring and Tyr178 side chain. Accordingly, compound 18 inhibited the adhesion of integrin-expressing human melanoma cells to RGD-containing proteins of the extracellular matrix, such as vitronectin, fibronectin, and osteopontin, and also angiogenesis in in vitro and in vivo experimental models. The relevant biological effects exerted by compound 18 suggest its potential application as an antiangiogenic agent in the diagnosis and therapy of tumors where α(v)β(3) integrin expression is up-regulated.


title: Low concentration of heparin used for permanent catheters canal locking is effective and diminishes the risk of bleeding.

text: PURPOSE There is an increasing number of patients being dialyzed with permanent catheters (PC). In the majority of cases, heparin is used to maintain PC patency. This practice causes clotting disturbances due to heparin leakage and may predispose the patient to bleeding episodes. It has not been well studied whether lowering heparin concentration for canal locking decreases short-term bleeding complications after PC placement. METHODS This was a prospective single-center randomized open-label trial conducted in hemodialyzed patients undergoing PC insertion. Low concentration of heparin (LCH) 2,500 IU/ml versus high concentration of heparin (HCH) 5,000 IU/ml was randomly used for catheter lumens locking. The primary endpoint was the occurrence of bleeding within 24 h after catheter placement. The effects of clinical and laboratory data on bleeding events were analyzed as secondary endpoints. RESULTS Seventy-five patients (37 in LCH) were enrolled in the study. Only in the HCH group we found a significant prolongation of activated partial thromboplastin time (APTT) 2 h after PC placement (p < 0.001). There was a higher number of bleeding episodes in the HCH group (n = 16; 42.1%) than in the LCH group (n = 7; 18.9%) (χ(2) = 4.74; p = 0.029). In univariate analysis, assignment to HCH, baseline APTT, use of low molecular weight heparin, and femoral localization were associated with bleeding events. In multivariate analysis, the use of HCH (odds ratio [OR] 3.64; 95% confidence interval [95% CI] 1.10-12.05) and baseline APTT (OR 1.12; 95% CI 1.002-1.250) predicted bleeding after PC insertion. CONCLUSION LCH used for canals locking decreases bleeding events in the first 24 hours after permanent catheter placement, compared to HCH.


title: What factors explain the geographical range of mammalian parasites?

text: Free-living species vary substantially in the extent of their spatial distributions. However, distributions of parasitic species have not been comprehensively compared in this context. We investigated which factors most influence the geographical extent of mammal parasites. Using the Global Mammal Parasite Database we analysed 17 818 individual geospatial records on 1806 parasite species (encompassing viruses, bacteria, protozoa, arthropods and helminths) that infect 396 carnivore, ungulate and primate host species. As a measure of the geographical extent of each parasite species we quantified the number and area of world ecoregions occupied by each. To evaluate the importance of variables influencing the summed area of ecoregions occupied by a parasite species, we used Bayesian network analysis of a subset ( n = 866) of the parasites in our database that had at least two host species and complete information on parasite traits. We found that parasites that covered more geographical area had a greater number of host species, higher average phylogenetic relatedness between host species and more sampling effort. Host and parasite taxonomic groups had weak and indirect effects on parasite ecoregion area; parasite transmission mode had virtually no effect. Mechanistically, a greater number of host species probably increases both the collective abundance and habitat breadth of hosts, providing more opportunities for a parasite to have an expansive range. Furthermore, even though mammals are one of the best-studied animal classes, the ecoregion area occupied by their parasites is strongly sensitive to sampling effort, implying mammal parasites are undersampled. Overall, our results support that parasite geographical extent is largely controlled by host characteristics, many of which are subsumed within host taxonomic identity.


title: First outbreak with chimeric swine enteric coronavirus (SeCoV) on pig farms in Slovakia - lessons to learn.

text: This report describes the first disease outbreak caused by chimeric swine enteric coronavirus (SeCoV) on two pig farms in Slovakia in early 2015. The infection was introduced by import of two breeding boars which were placed in provisional quarantine in a unit not strictly separated from other healthy pigs in the same building. Subsequently, loss of appetite and diarrhoea were observed in both boars during the first three days in the isolation unit. The infection gradually spread to the farrowing area and throughout the farm in two weeks and later to another nearby farm. Yellow watery diarrhoea accompanied by dehydration and death was observed in piglets with a mortality ranging from 30 to 35%. In the absence of an available vaccine, the pregnant sows were dosed by mouth with a 10% suspension prepared from the intestine and faeces of infected piglets in warm water. Three weeks after dosing, new litters of piglets were born which remained healthy with no development of diarrhoea.


title: Long-term follow-up after robotic thymectomy for nonthymomatous myasthenia gravis.

text: BACKGROUND Thymectomy is recognized as a significant component in the treatment of myasthenia gravis. However, controversy exists as to the optimal surgical approach. This investigation summarizes our experience performing extended thymectomy using a robotic technique in a large group of patients with significant follow-up. METHODS Data collection for patients undergoing robotic thymectomy for nonthymomatous myasthenia gravis over a 6-year period was prospectively performed. Patients were assessed using the Myasthenia Gravis Foundation of America's quantitative disease severity score and the post intervention status classification. RESULTS During the study period, 75 patients underwent thymectomy by this method. Mean preoperative myasthenia gravis severity score was 2.7. Mean operative time was 113±46 minutes. Extubation in the operating room occurred in 73 (98%) patients. Mean intensive care stay and total hospital length of stay were 0.9 and 2.2 days respectively. Mean interval between surgery and return to work (or prethymectomy activities of daily living) was 15±6 days. Significant improvement of myasthenia gravis symptoms occurred in 65 (87%) patients with a mean follow-up of 45±14 months. CONCLUSIONS Robotic-assisted thymectomy is a safe and effective technique for patients with symptomatic myasthenia gravis. It allowed an extended thymectomy to be performed without the associated length of stay or recovery period of a transsternal approach while producing comparable rates of symptom improvement.


title: Defining human dendritic cell progenitors by multiparametric flow cytometry.

text: Human dendritic cells (DCs) develop from progressively restricted bone marrow (BM) progenitors: these progenitor cells include granulocyte, monocyte and DC progenitor (GMDP) cells; monocyte and DC progenitor (MDP) cells; and common DC progenitor (CDP) and DC precursor (pre-DC) cells. These four DC progenitors can be defined on the basis of the expression of surface markers such as CD34 and hematopoietin receptors. In this protocol, we describe five multiparametric flow cytometry panels that can be used as a tool (i) to simultaneously detect or phenotype the four DC progenitors, (ii) to isolate DC progenitors to enable in vitro differentiation or (iii) to assess the in vitro differentiation and proliferation of DC progenitors. The entire procedure from isolation of cells to flow cytometry can be completed in 3-7 h. This protocol provides optimized antibody panels, as well as gating strategies, for immunostaining of BM and cord blood specimens to study human DC hematopoiesis in health, disease and vaccine settings.


Don't rush to deploy COVID-19 vaccines and drugs without sufficient safety guarantees.


title: The effect of ambiguous data on phylogenetic estimates obtained by maximum likelihood and Bayesian inference.

text: Although an increasing number of phylogenetic data sets are incomplete, the effect of ambiguous data on phylogenetic accuracy is not well understood. We use 4-taxon simulations to study the effects of ambiguous data (i.e., missing characters or gaps) in maximum likelihood (ML) and Bayesian frameworks. By introducing ambiguous data in a way that removes confounding factors, we provide the first clear understanding of 1 mechanism by which ambiguous data can mislead phylogenetic analyses. We find that in both ML and Bayesian frameworks, among-site rate variation can interact with ambiguous data to produce misleading estimates of topology and branch lengths. Furthermore, within a Bayesian framework, priors on branch lengths and rate heterogeneity parameters can exacerbate the effects of ambiguous data, resulting in strongly misleading bipartition posterior probabilities. The magnitude and direction of the ambiguous data bias are a function of the number and taxonomic distribution of ambiguous characters, the strength of topological support, and whether or not the model is correctly specified. The results of this study have major implications for all analyses that rely on accurate estimates of topology or branch lengths, including divergence time estimation, ancestral state reconstruction, tree-dependent comparative methods, rate variation analysis, phylogenetic hypothesis testing, and phylogeographic analysis.


title: Hepatocyte spheroids as an alternative to single cells for transplantation after ex vivo gene therapy in mice and pig models.

text: BACKGROUND Autologous hepatocyte transplantation after ex vivo gene therapy is an alternative to liver transplantation for metabolic liver disease. Here we evaluate ex vivo gene therapy followed by transplantation of single-cell or spheroid hepatocytes. METHODS Pig and mouse hepatocytes were isolated, labeled with zirconium-89 and returned to the liver as single cells or spheroids. Biodistribution was evaluated through positron emission tomography-computed tomography. Fumarylacetoacetate hydrolase-deficient pig hepatocytes were isolated and transduced with a lentiviral vector containing the Fah gene. Animals received portal vein infusion of single-cell or spheroid autologous hepatocytes after ex vivo gene delivery. Portal pressures were measured and ultrasound was used to evaluate for thrombus. Differences in engraftment and expansion of ex vivo corrected single-cell or spheroid hepatocytes were followed through histologic analysis and animals' ability to thrive off 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione. RESULTS Positron emission tomography-computed tomography imaging showed spheroid hepatocytes with increased heterogeneity in biodistribution as compared with single cells, which spread more uniformly throughout the liver. Animals receiving spheroids experienced higher mean changes in portal pressure than animals receiving single cells (P < .01). Additionally, two animals from the spheroid group developed portal vein thrombi that required systemic anticoagulation. Immunohistochemical analysis of spheroid- and single-cell-transplanted animals showed similar engraftment and expansion rates of fumarylacetoacetate hydrolase-positive hepatocytes in the liver, correlating with similar weight stabilization curves. CONCLUSION Ex vivo gene correction of autologous hepatocytes in fumarylacetoacetate hydrolase-deficient pigs can be performed using hepatocyte spheroids or single-cell hepatocytes, with spheroids showing a more heterogeneous distribution within the liver and higher risks for portal vein thrombosis and increased portal pressures.


title: Epigenetic Dysregulation in Virus-Associated Neoplasms.

text: The oncoproteins of human tumor viruses regularly interact with the cellular epigenetic machinery. Such interactions alter the epigenome of the host cell and reprogram its gene expression pattern. Altered levels or redistribution of (cytosine-5)-DNA methyltransferases and changes in the cellular methylome were observed in Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), hepatitis D virus (HDV), hepatitis C virus (HCV), and human papillomavirus (HPV) associated neoplasms and cell lines. Methylation-mediated silencing of cellular promoters was also noted in Merkel cell polyomavirus (MCPyV) positive Merkel cell carcinomas, and, as discussed elsewhere, in EBV-associated malignancies and adenovirus-induced rodent tumors as well. Promoter activation also occurred, either associated with DNA hypomethylation or with the induction of euchromatic histone modifications by viral oncoproteins. It is worthy to notice that HCV infection induced large, hypomethylated blocks of cellular chromatin, although the exact molecular mechanism remains to be elucidated. In hepatoma cells expressing HBx, the oncoprotein encoded by the HBV genome, demethylation of the repetitive satellite 2 sequences was observed, due to downregulation of the de novo DNA methyltransferase DNMT3B. Tax and HBZ, the oncoproteins of human T-cell lymphotropic virus type I (HTLV-I), can both activate and silence distinct cellular promoters by interacting with cellular enzymes involved in histone modification.


title: The role of thrombolysis in the clinical management of deep vein thrombosis.

text: The cornerstones of current management of deep vein thrombosis (DVT) are the routine use of anticoagulant therapy, graduated elastic compression stockings, and early ambulation. Thrombolytic therapy was previously reserved only for patients with life-, limb-, or organ-threatening complications. However, the postthrombotic syndrome has been increasingly recognized as a frequent and serious long-term complication of DVT. In parallel, endovascular thrombolytic methods have evolved considerably in recent years, prompting discussion and controversy as to whether they should be more liberally used. In some centers, pharmacomechanical catheter-directed thrombolysis is now routinely used in the treatment of acute iliofemoral DVT. Randomized trials are currently under way to determine when the use of pharmacomechanical catheter-directed thrombolysis is appropriate in patients presenting with acute proximal DVT.


title: Anosmia in COVID-19 Associated with Injury to the Olfactory Bulbs Evident on MRI.

text: Patients with coronavirus disease 2019 (COVID-19) may have symptoms of anosmia or partial loss of the sense of smell, often accompanied by changes in taste. We report 5 cases (3 with anosmia) of adult patients with COVID-19 in whom injury to the olfactory bulbs was interpreted as microbleeding or abnormal enhancement on MR imaging. The patients had persistent headache (n = 4) or motor deficits (n = 1). This olfactory bulb injury may be the mechanism by which the Severe Acute Respiratory Syndrome coronavirus 2 causes olfactory dysfunction.


title: Expanding laparoscopic cholecystectomy to rural Mongolia.

text: BACKGROUND Although laparoscopic cholecystectomy was first introduced in Mongolia in 1994, the benefits of the laparoscopic approach have been largely unavailable to the majority of the population. The burden of gallbladder disease in Mongolia is significant. Despite the barriers to expanding laparoscopic surgery in Mongolia (lack of physical resources and adequate training opportunities, a difficult political situation, and an austere environment), the Health Sciences University of Mongolia (HSUM) began looking for ways to further the development of laparoscopy for the entire country, including the rural areas where half the population resides. METHODS Combined didactic and practical training courses lasting 2 weeks were developed collaboratively by a private nongovernmental organization and HSUM. The courses were taught at tertiary care centers in the capital city (Ulaanbaatar) and in a smaller, rural city (Erdenet), the regional northern referral center. Demographic data, preoperative diagnosis, ultrasound and operative findings, operative times, length of hospital stay, and intraoperative and postoperative complication rates were compared from 2007-2008 from hospitals in Ulaanbaatar and Erdenet. RESULTS A total of 36 surgeons participated in the training classes, and a total of 410 laparoscopic cholecystectomies were performed. Ultrasound was used as a diagnostic tool in all cases. There was no significant difference in intraoperative or postoperative complications between hospitals in the capital, where the procedures were performed by skilled laparoscopic surgeons, and in Erdenet, where the training courses first introduced laparoscopic cholecystectomy. Neither were there differences in complication rates between cases during the teaching and nonteaching periods. CONCLUSIONS Laparoscopic cholecystectomy can be expanded safely to the regional diagnostic referral centers in rural Mongolia through short-term training courses as a method to markedly improve access and outcomes for the 50% of the country previously denied the benefits of minimally invasive surgery.


title: SARS-COV-2 in Ophthalmology: Current Evidence and Standards for Clinical Practice.

text: INTRODUCTION COVID-19 is caused by the coronavirus SARS-CoV-2. Ocular manifestations have been reported including conjunctivitis and retinal changes. Therefore, it is of the utmost importance to clarify eye involvement in COVID-19 in order to help with its diagnosis and to further prevent its transmission. The purpose of this review is to describe the structure and transmission of SARS-CoV-2, reported ocular findings and protection strategies for ophthalmologists. MATERIAL AND METHODS Literature search on PubMed for relevant articles using the keywords 'COVID-19', 'coronavirus', and 'SARS-CoV-2' in conjunction with 'ophthalmology' and 'eye'. Moreover, official recommendations of ophthalmological societies were reviewed. RESULTS Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct, the eye is rarely involved in human SARS-CoV-2 infection and the SARS-CoV-2 RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with COVID-19 is also extremely low. DISCUSSION The eye can be affected by SARS-CoV-2, which is supported by some reports of conjunctivitis and retinal changes, but its role in the spread of the disease is still unknown. CONCLUSION Given the current scarce evidence, more research is needed to clarify the relationship between SARS-CoV-2 and the eye.


title: Hemodialysis tunneled central venous catheters: five-year outcome analysis.

text: BACKGROUND Tunneled central venous catheters (tCVCs) are considered inferior to arteriovenous fistulas (AVFs) and grafts in all nephrology guidelines. However, they are being increasingly used as hemodialysis vascular access. The purpose of this study was to document the natural history of tCVCs and determine the rate and type of catheter replacement. METHODS This was a prospective study of 141 patients who underwent hemodialysis with tCVCs between January 2008 and December 2012. The patients used 154 tCVCs. Standard protocols about management of tCVCs, according to European Renal Best Practice, were well established. All catheters were inserted in the internal jugular vein. Criteria for catheter removal were persistent bloodstream infection, detection of an outbreak of catheter-related bloodstream (CRBS) infections, or catheter dysfunction. Event rates were calculated per 1,000 catheter days; tCVC cumulative survival was estimated by Kaplan-Meier analysis. RESULTS Catheter replacement occurred in 15 patients (0.29 per 1,000 days); catheter dysfunction was the main cause of replacement (0.18 per 1,000 days), typically within 12 months of surgical insertion. A total of 53 CRBS events in 36 patients were identified (0.82 per 1,000 days); 17 organisms, most commonly Gram-positive pathogens, were isolated; 87% of CVC infections were treated by systemic antibiotics associated with lock therapy. tCVC cumulative survival was 91% at 1 year, 88% at 2 years and 85% at 4 years. CONCLUSIONS Our data show a high survival rate of tCVCs in hemodialysis patients, with low incidence of catheter dysfunction and CRBS events. These data justify tCVC use for hemodialysis vascular access, also as first choice, especially in patients with exhausted peripheral access and limited life expectancy.


title: The bumper technique for advancing a large profile microcatheter.

text: Operators commonly encounter difficulty maneuvering a microcatheter beyond the distal lip of wide neck aneurysms and aneurysms in challenging locations. Few techniques have been described to guide operators in these particular situations. In this case report of a 56-year-old woman with a 16 mm ophthalmic artery aneurysm, the microcatheter continually snagged the distal aneurysm lip, preventing delivery of a flow diverter into the distal parent vessel. In troubleshooting this obstacle, a second microguidewire was introduced alongside the microcatheter and was used to cover the distal lip of the aneurysm to prevent further snagging. The second guidewire successfully deflected the microcatheter into the distal vessel, a technique that we have aptly dubbed the 'bumper technique'.


title: Geriatric units at the beginning of the 2020 COVID-19 epidemic in France.

text: The COVID-19 epidemic that started in November in China became a national epidemic from March 16, 2020 with the declaration of population containment in order to reduce the spread of the virus in France. From March 17 to March 27, 2020, the monitoring unit of the French society of geriatrics and gerontology decided to conduct a survey to analyze the implementation of the mobilization of geriatric units, given that this epidemic had shown that it resulted in excess mortality mainly among the elderly. The survey was able to bring together the response of 34 services, nine of which were located in a high epidemic cluster zone. Dedicated acute geriatric units for patients infected with COVID-19 were present in eight facilities, only outside the cluster zones. Nine geriatric follow-up and rehabilitation services were dedicated, an additional telemedicine activity concerned 35% of the facilities, and family listening and tablet communication facilities concerned 36% of the facilities. This survey is a snapshot of an initial moment in the epidemic. It provides an opportunity to describe the context in which this epidemic occurred in terms of geriatric policy, and to assess the responsiveness and inventiveness of these services in meeting the needs of the elderly.


IST-3 stroke trial data available.


title: Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis.

text: Alphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053-16058, 2014, https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4+ T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10-/- mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain.IMPORTANCE Alphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. The Th1 pathogenic cell subtype that developed in IL-10-deficient mice infected with a less virulent virus was distinct from the Th17 subtype that developed in response to a more virulent virus, indicating a role for virus strain in determining the immune response. Slow production of antibody in the nervous system led to delayed virus clearance. Therefore, both the virus strain and the host response to infection are important determinants of outcome.


Covid-19: transforming healthcare will require collaboration and innovative policies.


title: Experience with thoracoscopic tracheal surgery in infants and children.

text: PURPOSE Complex thoracoscopic procedures in infants and children, such as tracheoesophageal fistula (TEF) repair and lung resection, have already been shown to be safe and efficacious in infants and children. This study evaluated the application of thoracoscopic techniques in more complex, unusual tracheal anomalies. METHODS From January 2002 to October 2008, 9 patients with more rare anatomic tracheal anomalies, between the thoracic inlet and the carina, were treated by thoracoscopy. Ages ranged from 5 months to 8 years and weights ranged from 5.4 to 8 years and from 5.9 to 42 kg. Pathology included 3 H-type TEFs, 2 recurrent TEFs following previous open repair of an esophageal atresia with fistula, resection of a giant tracheal pouch, and 3 tracheobronchi with associated abnormal lung parenchyma. RESULTS All procedures were successfully completed thoracoscopically. Operative times ranged from 60 to 130 minutes. Procedures included division and closure of the 3 H-type fistulas and 2 recurrent fistulas, resection of the tracheal pouch, 2 upper lobectomies, and resection of an aberrant upper lobe segment by segmentectomy. There were no operative or postoperative complications. Chest tubes were left in for an average of 1 day, and hospital stay averaged 2.2 days. CONCLUSIONS Thoracoscopy provides an excellent technique for approaching tracheal pathology from the level of the thoracic inlet to the carina. A thoracoscopic approach avoids the morbidity of a major thoracotomy and virigule or a major neck exploration while providing greater exposure, especially in the upper thorax.


title: Web Exclusive. Annals Graphic Medicine - Progress Notes: The Fog of COVID.

text: [Figure: see text].


title: Analysis of inter-system variability of systolic and diastolic intraventricular pressure gradients derived from color Doppler M-mode echocardiography.

text: Assessment of intraventricular pressure gradients (IVPG) using color Doppler M-mode echocardiography has gained increasing interest in the evaluation of cardiac function. However, standardized analysis tools for IVPG quantification are missing. We aimed to evaluate the feasibility, the test-retest observer reproducibility, and the inter-system variability of a semi-automated IVPG quantification algorithm. The study included forty healthy volunteers (50% were men). All volunteers were examined using two ultrasound systems, the Philips Epiq 7 and the General Electric Vivid 6. Left ventricular diastolic (DIVPG) and systolic (SIVPG) intraventricular pressure gradients were measured from the spatiotemporal distribution of intraventricular propagation flow velocities using color Doppler M-mode in standard apical views. There was good feasibility for both systolic and diastolic IVPG measurements (82.5% and 85%, respectively). Intra and inter-observer test-retest variability measured with the intraclass correlation coefficient were 0.98 and 0.93 for DIVPG respectively, and 0.95 and 0.89 for SIVPG respectively. The inter-system concordance was weak to moderate with Lin's concordance correlation coefficient of 0.59 for DIVPG and 0.25 for SIVPG. In conclusion, it is feasible and reproducible to assess systolic and diastolic IVPG using color Doppler M-mode in healthy volunteers. However, the inter-system variability in IVPG analysis needs to be taken into account, especially when using displayed data.


title: Concealment of Potential Exposure to COVID-19 and Its Impact on Outbreak Control: Lessons from the HIV Response.

text: Globally, more than 4 million people have been infected with COVID-19, and more than 300,000 deaths have been reported across 188 countries. Concealment of one's potential exposure to the virus has negative implications for the spread of COVID-19 across the socio-ecological spectrum, including the futility of contact-tracing efforts, exposure of frontline staff, and the spread of COVID-19 in the community. We draw lessons learned from HIV to discuss stigma and the attribution of blame surrounding the phenomenon of concealment of one's potential exposure to COVID-19 using a socio-ecological perspective. This article also illustrates the psychosocial aspect of the disease, and the negative repercussions of concealment of potential exposure on transmission in the community and to front-liners, healthcare resources, and outbreak containment.


The epic battle against coronavirus misinformation and conspiracy theories.


title: Evaluation of 177Lu-DOTA-sst2 antagonist versus 177Lu-DOTA-sst2 agonist binding in human cancers in vitro.

text: UNLABELLED Somatostatin receptor targeting of neuroendocrine tumors using radiolabeled somatostatin agonists is today an established method to image and treat cancer patients. However, in a study using an animal tumor model, somatostatin receptor antagonists were shown to label sst(2)- and sst(3)-expressing tumors in vivo better than agonists, with comparable affinity even though they are not internalized into the tumor cell. In the present study, we evaluated the in vitro binding of the antagonist (177)Lu-DOTA-pNO(2)-Phe-c (DCys-Tyr-DTrp-Lys-Thr-Cys) DTyrNH(2) ((177)Lu-DOTA-BASS) or the (177)Lu-DOTATATE agonist to sst(2)-expressing human tumor samples. METHODS Forty-eight sst(2)-positive human tumor tissue samples (9 ileal carcinoids, 10 pheochromocytomas, 7 breast carcinomas, 10 renal cell carcinomas, and 12 non-Hodgkin lymphomas) were analyzed by in vitro receptor autoradiography for the expression of sst(2), comparing the binding capacity of (177)Lu-DOTA-BASS and (177)Lu-DOTATATE in successive tissue sections. The autoradiograms were quantitated using an electronic autoradiography detection system. RESULTS In all cases, the radiolabeled antagonist bound to more receptor sites than did the agonist. The mean ratios of the antagonist (177)Lu-DOTA-BASS to the agonist (177)Lu-DOTATATE were 4.2 ± 0.5 in the 9 ileal carcinoids, 12 ± 3 in the 10 pheochromocytomas, 11 ± 4 in the 7 breast carcinomas, 5.1 ± 0.6 in the 10 renal cell carcinomas, and 4.8 ± 0.7 in the 12 non-Hodgkin lymphomas. CONCLUSION The present in vitro human data, together with previous in vivo animal tumor data, are strong arguments indicating that sst(2) antagonists may be worth testing in vivo in patients in a wide range of tumors including nonneuroendocrine tumors.


title: Results of laparoscopic repair of primary and recurrent incisional hernias at a single UK institution.

text: In this study incisional hernia repairs at a single UK institution between 1994 and 2008 were analyzed with respect to short-term and long-term results. Prospectively collected data were analyzed retrospectively to ascertain outcomes, complications, and recurrences. Two hundred and twenty-seven operations were performed with 35% of the operations being for recurrent hernias. A self-centering suture technique was used. Median operating time was 55 minutes. There were 8 conversions and median hospital stay was 1 night. There were 52 complications (23%) including 3 postoperative bleeds, 3 mesh infections, and 4 small bowel obstructions. Median postoperative follow-up was 53 months. There were 25 recurrences (11%) being detected, a median of 17 months after initial operation. In this large series, laparoscopic incisional hernia repair is safe and is associated with a short hospital stay. Recurrences after repair remain a concern prompting the development of strategies to try and minimize the likelihood of this occurring.


title: Retained Wireless Capsule Endoscope in a Girl with suspected Crohn's Disease.

text: Wireless capsule endoscopy (WCE) is one of the great milestones in the field of gastroenterology. It is versatile in image acquisition, painless and can reach parts of the small bowel not amenable to conventional endoscopy. The commonest complication with WCE is retention of the capsule. We report a case of retained capsule in a child who was being investigated for obscure gastrointestinal bleeding (OGIB). Operative intervention was required for its retrieval after two weeks of expectant management.


title: Suppression of somatosensory stimuli during motor planning may explain levels of balance and mobility after stroke.

text: The ability to actively suppress, or gate, irrelevant sensory information is required for safe and efficient walking in sensory-rich environments. Both motor attention and motor planning alter somatosensory evoked potentials (SEPs) in healthy adults. This study's aim was to examine the effect of motor attention on processing of irrelevant somatosensory information during plantar flexion motor planning after stroke. Thirteen healthy older adults and 11 individuals with stroke participated. Irrelevant tibial nerve stimulation was delivered while SEPs were recorded over Cz, overlaying the leg portion of the sensorimotor cortex at the vertex of the head. Three conditions were tested in both legs: (1) Rest, (2) Attend To, and (3) Attend Away from the stimulated limb. In conditions 2 and 3, relevant vibration cued voluntary plantar flexion movements of the stimulated (Attend To) or non-stimulated (Attend Away) leg. SEP amplitudes were averaged during motor planning per condition. Individuals with stroke did not show attention-mediated gating of the N40 component associated with irrelevant somatosensory information during motor planning. It may be that dysfunction in pathways connecting to area 3b explains the lack of attention-mediated gating of the N40. Also, attention-mediated gating during motor planning explained significant and unique variance in a measure of community balance and mobility combined with response time. Thus, the ability to gate irrelevant somatosensory information appears important for stepping in both older adults and after stroke. Our data suggest that therapies that direct motor attention could positively impact walking after stroke.


NO SIGNIFICANT EFFECT OF COVID-19 ON IMMUNOLOGICAL AND VIROLOGICAL PARAMETERS IN PATIENTS WITH HIV-1 INFECTION.


title: Assisted mechanical ventilation: the future is now!

text: Assisted ventilation is a highly complex process that requires an intimate interaction between the ventilator and the patient. The complexity of this form of ventilation is frequently underappreciated by the bedside clinician. In assisted mechanical ventilation, regardless of the specific mode, the ventilator's gas delivery pattern and the patient's breathing pattern must match near perfectly or asynchrony between the patient and the ventilator occurs. Asynchrony can be categorized into four general types: flow asynchrony; trigger asynchrony; cycle asynchrony; and mode asynchrony. In an article recently published in BMC Anesthesiology, Hodane et al. have demonstrated reduced asynchrony during assisted ventilation with Neurally Adjusted Ventilatory Assist (NAVA) as compared to pressure support ventilation (PSV). These findings add to the growing volume of data indicating that modes of ventilation that provide proportional assistance to ventilation - e.g., NAVA and Proportional Assist Ventilation (PAV) - markedly reduce asynchrony. As it becomes more accepted that the respiratory center of the patient in most circumstances is the most appropriate determinant of ventilatory pattern and as the negative outcome effects of patient-ventilator asynchrony become ever more recognized, we can expect NAVA and PAV to become the preferred modes of assisted ventilation!


title: Recombinant Chimpanzee Adenovirus Vaccine AdC7-M/E Protects against Zika Virus Infection and Testis Damage.

text: The recent outbreak of Zika virus (ZIKV) has emerged as a global health concern. ZIKV can persist in human semen and be transmitted by sexual contact, as well as by mosquitoes, as seen for classical arboviruses. We along with others have previously demonstrated that ZIKV infection leads to testis damage and infertility in mouse models. So far, no prophylactics or therapeutics are available; therefore, vaccine development is urgently demanded. Recombinant chimpanzee adenovirus has been explored as the preferred vaccine vector for many pathogens due to the low preexisting immunity against the vector among the human population. Here, we developed a ZIKV vaccine based on recombinant chimpanzee adenovirus type 7 (AdC7) expressing ZIKV M/E glycoproteins. A single vaccination of AdC7-M/E was sufficient to elicit potent neutralizing antibodies and protective immunity against ZIKV in both immunocompetent and immunodeficient mice. Moreover, vaccinated mice rapidly developed neutralizing antibody with high titers within 1 week postvaccination, and the elicited antiserum could cross-neutralize heterologous ZIKV strains. Additionally, ZIKV M- and E-specific T cell responses were robustly induced by AdC7-M/E. Moreover, one-dose inoculation of AdC7-M/E conferred mouse sterilizing immunity to eliminate viremia and viral burden in tissues against ZIKV challenge. Further investigations showed that vaccination with AdC7-M/E completely protected against ZIKV-induced testicular damage. These data demonstrate that AdC7-M/E is highly effective and represents a promising vaccine candidate for ZIKV control.IMPORTANCE Zika virus (ZIKV) is a pathogenic flavivirus that causes severe clinical consequences, including congenital malformations in fetuses and Guillain-Barré syndrome in adults. Vaccine development is a high priority for ZIKV control. In this study, to avoid preexisting anti-vector immunity in humans, a rare serotype chimpanzee adenovirus (AdC7) expressing the ZIKV M/E glycoproteins was used for ZIKV vaccine development. Impressively, AdC7-M/E exhibited exceptional performance as a ZIKV vaccine, as follows: (i) protective efficacy by a single vaccination, (ii) rapid development of a robust humoral response, (iii) durable immune responses, (iv) robust T cell responses, and (v) sterilizing immunity achieved by a single vaccination. These advantages of AdC7-M/E strongly support its potential application as a promising ZIKV vaccine in the clinic.


title: Inequalities and identity processes in crises: Recommendations for facilitating safe response to the COVID-19 pandemic.

text: Structural inequalities and identity processes are pivotal to understanding public response to COVID-19. We discuss how identity processes can be used to promote community-level support, safe normative behaviour, and increase compliance with guidance. However, we caution how government failure to account for structural inequalities can alienate vulnerable groups, inhibit groups from being able to follow guidance, and lead to the creation of new groups in response to illegitimate treatment. Moreover, we look ahead to the longitudinal impacts of inequalities during pandemics and advise government bodies should address identity-based inequalities to mitigate negative relations with the public and subsequent collective protest.


title: A prospective randomized comparison of traditional laparoendoscopic single-site surgery with needlescopic-assisted laparoscopic nephrectomy in the porcine model.

text: BACKGROUND AND PURPOSE Laparoendoscopic single-site (LESS) surgery produces virtually no scar but is technically challenging because of the loss of triangulation. The objective of this study is to compare classic transumbilical LESS nephrectomy with needlescopic-assisted laparoscopy (NAL) surgery. In doing so, we evaluated whether the addition of a single 2-mm subcostal port could restore triangulation while not jeopardizing recovery or cosmetic outcome in the porcine model. MATERIALS AND METHODS Ten female farm pigs were randomized to laparoscopic nephrectomy with either LESS or NAL. In LESS, a TriPort was placed through a single 2.5-cm umbilical incision. In NAL, 5- and 10-mm ports were placed in the umbilicus and a 2-mm port was placed in the midclavicular line. Preoperative, perioperative, and postoperative parameters were compared. Variables were analyzed with the Wilcoxon signed-rank test and two-tailed Fisher exact test. Cosmesis was evaluated objectively using the Vancouver Scar Scale and subjectively by a blinded dermatologist. A cost analysis was performed. RESULTS Estimated blood loss was minimal in both groups (28.8 mL in LESS and 9.4 mL in NAL). Operative time was significantly shorter in NAL (103 vs 150 min; P<0.001). There was no difference in complications (2 vs 1; P=0.500), objective cosmesis (3.9 vs 3.8; P>0.2), or subjective cosmesis (2 vs 3; P=0.500). The NAL protocol had significantly lower disposable equipment costs ($363 vs $1696). CONCLUSIONS The addition of a 2-mm subcostal port and the restoration of triangulation in the NAL protocol enable shorter operative times, increased surgeon comfort, improved technical ease, and lower costs while maintaining the scarless cosmesis of the traditional LESS protocol.


Recognition for contributions to feline infectious disease research.


title: Closed-loop fluid resuscitation: robustness against weight and cardiac contractility variations.

text: BACKGROUND Surgical patients present with a wide variety of body sizes and blood volumes, have large differences in baseline volume status, and may exhibit significant differences in cardiac function. Any closed-loop fluid administration system must be robust against these differences. In the current study, we tested the stability and robustness of the closed-loop fluid administration system against the confounders of body size, starting volume status, and cardiac contractility using control engineering methodology. METHODS Using an independently developed previously published hemodynamic simulation model that includes blood volumes and cardiac contractility, we ran a Monte-Carlo simulation series with variation in starting blood volume and body weight (phase 1, weight 35-100 kg), and starting blood volume and cardiac contractility (phase 2, contractility from 1500 [severe heart failure] to 6000 [hyperdynamic]). The performance of the controller in resuscitating to the target set point was evaluated in terms of milliliters of blood volume error from optimal, with <250 mL of error defined as "successful." RESULTS One thousand simulations were run for each of the 2 phases of the study. The phase 1 mean blood volume error ± SD from optimal was 25 ± 59 mL. The phase 2 mean blood volume error from optimal was -60 ± 89 mL. The lower 95% Clopper-Pearson binomial confidence interval for resuscitation to within 250 mL of optimal blood volume for phase 1 and 2 was 99.6% and 97.1%, respectively. CONCLUSION The results indicate that the controller is highly effective in targeting optimal blood and stroke volumes, regardless of weight, contractility or starting blood volume.


title: Relationship between brain computed tomography findings and bispectral index score in patients presenting with head trauma.

text: OBJECTIVE Head trauma is one of the most important emergency health problems both in the world and in our country. The objective in our study is to (i) state the correlation between the findings of bispectral index score (BIS) and computed tomography (CT), which are used to evaluate the level of consciousness of patients with isolated head trauma, and (ii) investigate objective results about the patient's level of consiousness/alertness according to the CT modality, which is used frequently. METHODS This prospective study was carried out between 03.01.2014 and 09.01.2014 in the emergency department of Fatih Sultan Mehmet Education and Research Hospital. The average BIS scores were correlated with the Glasgow Coma Scale (GCS) point, the Canadian CT Head Rule major and minor criteria, and the pathologic findings in CT imaging. The patients' demographic features, vital signs at admission, and arrival times at the hospital were investigated. RESULTS In our study, 64 (31.7%) patients were female, and 138 (68.3%) patients were male. The mean BIS scores were 84.99±11.20 (86.05) and 93.78±3.80 (95.05) in patients with and without CT pathologies, respectively. The correlation between CT pathology and BIS scores was statistically significant: BIS scores were lower in patients with CT pathologies (p=0.001; p<0.01). There was a statistically significant positive correlation between the BIS and GCS scores (45.6%) (p<0.05). CONCLUSION We showed that most head traumas occur after dangerous accidents, and according to the results, we can predict that males are more frequently affected than females. There was a statistically significant positive correlation between BIS scores and GCS points. In our study, the BIS scores were statistically significantly lower in patients with CT pathology than in patients without. We can predict that if the BIS score of the patient is low, then there will be the presence of pathology on CT imaging.


title: Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study.

text: BACKGROUND Acute respiratory infections (ARI) are a major cause of morbidity in infancy worldwide, with cough and wheeze being alarming symptoms to parents. We aimed to analyze in detail the viral aetiology of ARI with such symptoms in otherwise healthy infants, including rhinoviruses and recently discovered viruses such as human metapneumovirus (HMPV), coronavirus NL63 and HKU1, and human bocavirus (HBoV). METHODS We prospectively followed 197 unselected infants during their first year of life and assessed clinical symptoms by weekly standardized interviews. At the first ARI with cough or wheeze, we analyzed nasal swabs by sensitive individual real time polymerase chain reaction assays targeting 16 different respiratory viruses. RESULTS All 112 infants who had an ARI had cough, and 39 (35%) had wheeze. One or more respiratory viruses were found in 88 of 112 (79%) cases. Fifteen (17%) dual and 3 (3%) triple infections were recorded. Rhino- (23% of all viruses) and coronaviruses (18%) were most common, followed by parainfluenza viruses (17%), respiratory syncytial virus (RSV) (16%), HMPV (13%), and HBoV (5%). Together rhinoviruses, coronaviruses, HMPV, and HBoV accounted for 60% (65 of 109) of viruses. Although symptom scores and need for general practitioner (GP) consultations were highest in infants infected with RSV, they were similar in infants infected with other viruses. Viral shedding at 3 weeks occurred in 20% of cases. CONCLUSIONS Rhinoviruses, coronaviruses, HMPV, and HBoV are common pathogens associated with respiratory symptoms in otherwise healthy infants. They should be considered in the differential diagnosis of the aetiology of ARI in this age group.


title: Comparison of suturing techniques in the formation of collagen scaffold tubes for composite tubular organ tissue engineering.

text: In order to construct tubes for tissue engineering of composite tubular organs in the gastrointestinal tract, suturing techniques were investigated with regards to (a) type of suture material, (b) state of scaffold, (c) technical variations and (d) changes in scaffold morphology. Collagen scaffolds of 13 mm diameter and 3 mm thickness, in both dry and wet states, were sutured using braided and monofilament sutures. Four suture techniques were employed (a) continuous loop, (b) interrupted loops, (c) interrupted edge sutures and (d) continuous running edge suture. Scanning electron microscopic imaging was performed on the 4 tubes sutured. Monofilament sutures were used for tube formation as braided sutures were unsuitable. Dry scaffolds demonstrated tears during knot tying and fractures when bent around a stent. The interrupted and continuous running edge suture were the most suitable suturing techniques in wet scaffolds; further confirmed by scanning electron microscopy imaging. Our approach to tissue engineer segments of the gastrointestinal tract involves cell-seeding on scaffolds to permit attachment in vitro and later wrapping of scaffold layers of heterogeneous cells to create composite tissue. Scaffolds in wet state can be better sutured with monofilament materials using either the interrupted or running continuous edge suture technique.


title: [Transanal resection using a single port trocar: a new approach to NOTES].

text: INTRODUCTION The morbidity and mortality, along with the functional changes that arise from radical surgery of rectal cancer, has led to an increasing interest in local treatment in the early stages of cancer of the rectum. Conventional transanal surgery has a high recurrence rate, for this reason transanal endoscopic microsurgery (TEM) is considered the treatment of choice in the last few years in large rectal adenomas and in early rectal cancer (low risk T1). PATIENTS AND METHOD We have intervened five patients, four with a diagnosis of villous adenoma of the rectum, and one in situ rectal carcinoma, using this new transanal approach, with a single port device. RESULTS The locations of the lesions were in the mid-rectum, at a mean distance of 9 cm (range 6-10) from the anal margin. All of them were situated in the posterior side. The resection margins were negative in all cases. The mean size of the adenomas was 4 cm, three being sessile shaped, and one with a short, thick pedicle (>1cm); the size of the carcinoma was 3 cm. The mean surgical time was 55 minutes. All the patients were discharged 48 hours after the surgical procedure. CONCLUSION We believe that the transanal endoscopic approach with a single port device is a simple, easily reproducible and cost-effective procedure when compared to TEM.


title: Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein.

text: Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes on the basis of their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of advanced antibody discovery platforms.


title: Paclitaxel-Coated Balloon in Infrapopliteal Arteries: 12-Month Results From the BIOLUX P-II Randomized Trial (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapoplit

text: OBJECTIVES The aim of BIOLUX P-II (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries) trial was to compare the safety and efficacy of a novel paclitaxel-coated drug-eluting balloon (DEB) versus an uncoated balloon (percutaneous transluminal angioplasty [PTA]) in de novo or native restenotic lesions of the infrapopliteal arteries in patients with claudication and critical limb ischemia. BACKGROUND DEB have shown promising results in femoropopliteal lesions, but data for infrapopliteal lesions are scarce. METHODS In this prospective, multicenter, randomized first-in-man study, 72 patients were randomized 1:1 to either a Passeo-18 Lux DEB (Biotronik AG, Buelach, Switzerland) (n = 36) or Passeo-18 PTA (n = 36). Follow-up assessments were scheduled at 1, 6, and 12 months, with angiographic assessment at 6 months. Adverse events were adjudicated by an independent clinical events committee, and angiographic parameters were assessed by an independent core laboratory. RESULTS The primary safety endpoint (a composite of all-cause mortality, target extremity major amputation, target lesion thrombosis, and target vessel revascularization at 30 days) was 0% in the DEB group versus 8.3% in the PTA group (p = 0.239). The primary performance endpoint (patency loss at 6 months) was 17.1% in the DEB group versus 26.1% in the PTA group (p = 0.298), and major amputations of the target extremity occurred in 3.3% versus 5.6% of the patients at 12 months, respectively. CONCLUSIONS The Passeo-18 Lux DEB has been proven to be safe and effective in infrapopliteal lesions with comparable outcomes to PTA.


title: Severe Stroke Patients With Left-Sided Occlusion of the Proximal Anterior Circulation Benefit More From Thrombectomy.

text: Background and Purpose: Endovascular thrombectomy improves the functional independence of patients with proximal anterior circulation occlusion. However, a subset of patients fail to benefit from thrombectomy procedures, the reasons for which remain poorly defined. In this study, we investigated whether the effectiveness of thrombectomy was affected by left- or right-sided occlusion among patients with similar stroke severities. Methods: Patients with proximal anterior circulation occlusion (internal carotid or M1 of middle cerebral artery) treated with the Solitaire stent retriever within 8 h of the onset of acute ischemic stroke were enrolled from the Yijishan Hospital of Wannan Medical College. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS) on admission. The functional outcomes were assessed using the modified Rankin scale (mRS) at 90 days. Results: We enrolled 174 patients including 90 left-sided occlusion and 84 right-sided occlusion. The NIHSS scores on admission were higher in the left-sided (median, 19; interquartile range, 16 to 20) compared to the right-sided occlusion group (median, 15, interquartile range, 13 to 18) (P < 0.001). Following adjustment for potential risk factors, patients with left-sided occlusion had higher rates of functional independence (mRS ≤ 2) and lower rates of mortality (mRS = 6) compared to the right-sided occlusion patients (39.5 vs. 19.6% and 28.9 vs. 47.8%, respectively) in the severe stroke group (NIHSS ≥ 15). Conclusions: In severe stroke patients with proximal anterior circulation occlusion, stent retriever thrombectomy within 8 h of the onset of symptoms provides more benefits to left-sided occlusion.


title: Prevalence, Comorbidity and Predictor of Separation Anxiety Disorder in Children and Adolescents.

text: Separation Anxiety Disorder(SAD) is one of the earliest anxiety disorders. The effect of this disorder on the performance of children and adolescents reveals the need for awareness of the prevalence and comorbidity of this disorder in each region. This study is a cross-sectional analytical study implemented in all provinces of Iran. The instrument used in this study is the Persian version of the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version(K-SADA-PL) questionnaire. The total number of participants was 29,699. The overall prevalence of SAD was 5.3%. The comorbidity rate of 65.3% was found between SAD and other psychiatric disorders. Specific phobia and oppositional defiant disorder had the highest comorbidity with this disorder in the studied population. The more prevalence of separation anxiety disorder in the age range of 6-9 years old highlights the need for early detection of this disorder and targeting screening programs in childhood and adolescence.


title: Steroid-induced osteonecrosis: the number of lesions is related to the dosage.

text: Severe acute respiratory syndrome (SARS) is a newly described infectious disease caused by the SARS coronavirus which attacks the immune system and pulmonary epithelium. It is treated with regular high doses of corticosteroids. Our aim was to determine the relationship between the dosage of steroids and the number and distribution of osteonecrotic lesions in patients treated with steroids during the SARS epidemic in Beijing, China in 2003. We identified 114 patients for inclusion in the study. Of these, 43 with osteonecrosis received a significantly higher cumulative and peak methylprednisolone-equivalent dose than 71 patients with no osteonecrosis identified by MRI. We confirmed that the number of osteonecrotic lesions was directly related to the dosage of steroids and that a very high dose, a peak dose of more than 200 mg or a cumulative methylprednisolone-equivalent dose of more than 4000 mg, is a significant risk factor for multifocal osteonecrosis with both epiphyseal and diaphyseal lesions. Patients with diaphyseal osteonecrosis received a significantly higher cumulative methylprednisolone-equivalent dose than those with epiphyseal osteonecrosis. Multifocal osteonecrosis should be suspected if a patient is diagnosed with osteonecrosis in the shaft of a long bone.


title: Facemasks for the prevention of infection in healthcare and community settings.

text: Facemasks are recommended for diseases transmitted through droplets and respirators for respiratory aerosols, yet recommendations and terminology vary between guidelines. The concepts of droplet and airborne transmission that are entrenched in clinical practice have recently been shown to be more complex than previously thought. Several randomised clinical trials of facemasks have been conducted in community and healthcare settings, using widely varying interventions, including mixed interventions (such as masks and handwashing), and diverse outcomes. Of the nine trials of facemasks identified in community settings, in all but one, facemasks were used for respiratory protection of well people. They found that facemasks and facemasks plus hand hygiene may prevent infection in community settings, subject to early use and compliance. Two trials in healthcare workers favoured respirators for clinical respiratory illness. The use of reusable cloth masks is widespread globally, particularly in Asia, which is an important region for emerging infections, but there is no clinical research to inform their use and most policies offer no guidance on them. Health economic analyses of facemasks are scarce and the few published cost effectiveness models do not use clinical efficacy data. The lack of research on facemasks and respirators is reflected in varied and sometimes conflicting policies and guidelines. Further research should focus on examining the efficacy of facemasks against specific infectious threats such as influenza and tuberculosis, assessing the efficacy of cloth masks, investigating common practices such as reuse of masks, assessing compliance, filling in policy gaps, and obtaining cost effectiveness data using clinical efficacy estimates.


title: SARS-CoV-2 detection in patients with influenza-like illness.

text: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei Province, China in late December 2019. We re-analysed 640 throat swabs collected from patients in Wuhan with influenza-like-illness from 6 October 2019 to 21 January 2020 and found that 9 of the 640 throat swabs were positive for SARS-CoV-2 RNA by quantitative PCR, suggesting community transmission of SARS-CoV2 in Wuhan in early January 2020.


title: COVID-19 and dengue: a deadly duo.

text: While COVID-19 wreaks havoc across the world, countries in South and South-East Asia and Latin America are faced with the prospect of a second epidemic: dengue. Further complicating the picture is that the early signs and symptoms of dengue and COVID-19 could be similar, making it a risk that patients may be wrongly diagnosed early in the course of disease. This is confounded further by a report from Singapore of false-positive dengue antibody testing in two COVID-19 patients, and the presence of co-infection of dengue and COVID-19 in Thailand. Unless urgent measures are taken, there is a risk that dengue and COVID-19 could overwhelm healthcare systems across multiple countries.


title: Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura.

text: Recovery from acute episodes of thrombotic thrombocytopenic purpura (TTP) appears complete except for minor cognitive abnormalities and risk for relapse. The Oklahoma TTP-HUS (hemolytic uremic syndrome) Registry enrolled 70 consecutive patients from 1995 to 2011 with ADAMTS13 activity <10% at their initial episode; 57 survived, with follow-up through 2012. The prevalence of body mass index (BMI), glomerular filtration rate (GFR), urine albumin/creatinine ratio (ACR), hypertension, major depression, systemic lupus erythematosus (SLE), and risk of death were compared with expected values based on the US reference population. At initial diagnosis, 57 survivors had a median age of 39 years; 45 (79%) were women; 21 (37%) were black; BMI and prevalence of SLE (7%) were greater (P < .001) than expected; prevalence of hypertension (19%; P = .463) was not different. GFR (P = .397) and ACR (P = .793) were not different from expected values. In 2011-2012, prevalence of hypertension (40% vs 23%; P = .013) and major depression (19% vs 6%; P = .005) was greater than expected values. Eleven patients (19%) have died, a proportion greater than expected compared with US and Oklahoma reference populations (P < .05). TTP survivors may have greater risk for poor health and premature death.


Why Use Anything But a Standard Spontaneous Breathing Trial to Determine Readiness for Ventilator Discontinuation?


title: Outside-in? Acute fetal systemic inflammation in very preterm chronically catheterized sheep fetuses is not driven by cells in the fetal blood.

text: BACKGROUND The preterm birth syndrome (delivery before 37 weeks gestation) is a major contributor to the global burden of perinatal morbidity and death. The cause of preterm birth is complex, multifactorial, and likely dependent, at least in part, on the gestational age of the fetus. Intrauterine infection is frequent in preterm deliveries that occur at <32 weeks gestation; understanding how the fetus responds to proinflammatory insult will be an important step towards early preterm birth prevention. However, animal studies of infection and inflammation in prematurity commonly use older fetuses that possess comparatively mature immune systems. OBJECTIVE Aiming to characterize acute fetal responses to microbial agonist at a clinically relevant gestation, we used 92-day-old fetuses (62% of term) to develop a chronically catheterized sheep model of very preterm pregnancy. We hypothesized that any acute fetal systemic inflammatory responses would be driven by signaling from the tissues exposed to Escherichia coli lipopolysaccharide that is introduced into the amniotic fluid. STUDY DESIGN Eighteen ewes that were carrying a single fetus at 92 days of gestation had recovery surgery to place fetal tracheal, jugular, and intraamniotic catheters. Animals were recovered for 24 hours before being administered either intraamniotic E coli lipopolysaccharide (n = 9) or sterile saline solution (n = 9). Samples were collected for 48 hours before euthanasia and necroscopy. Fetal inflammatory responses were characterized by microarray analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS Intraamniotic lipopolysaccharide reached the distal trachea within 2 hours. Lipopolysaccharide increased tracheal fluid interleukin-8 within 2 hours and generated a robust inflammatory response that was characterized by interleukin-6 signaling pathway activation and up-regulation of cell proliferation but no increases in inflammatory mediator expression in cord blood RNA. CONCLUSIONS In very preterm sheep fetuses, lipopolysaccharide stimulates inflammation in the fetal lung and fetal skin and stimulates a systemic inflammatory response that is not generated by fetal blood cells. These data argue for amniotic fluid-exposed tissues that play a key role in driving acute fetal and intrauterine inflammatory responses.


title: Demonstration and mitigation of aerosol and particle dispersion during mastoidectomy relevant to the COVID-19 era.

text: BACKGROUND COVID-19 has become a global pandemic with a dramatic impact on healthcare systems. Concern for viral transmission necessitates the investigation of otologic procedures that use high-speed drilling instruments, including mastoidectomy, which we hypothesized to be an aerosol generating procedure. METHODS Mastoidectomy with a high-speed drill was simulated using fresh-frozen cadaveric heads with fluorescein solution injected into the mastoid air cells. Specimens were drilled for one-minute durations in test conditions with and without a microscope. A barrier drape was fashioned from a commercially available drape (the OtoTent). Dispersed particulate matter was quantified in segments of an octagonal test grid measuring 60 cm in radius. RESULTS Drilling without a microscope dispersed fluorescent particles 360 degrees, with the areas of highest density in quadrants near the surgeon and close to the surgical site. Using a microscope or varying irrigation rates did not significantly reduce particle density or percent surface area with particulate. Using the OtoTent significantly reduced particle density and percent surface area with particulate across the segments of the test grid beyond 30 cm (which marked the boundary of the OtoTent) compared with the microscope only and no microscope test conditions (Kruskall-Wallis test, p = 0.0066). CONCLUSIONS Mastoidectomy with a high-speed drill is an aerosol generating procedure, a designation that connotes the potential high risk of viral transmission and need for higher levels of personal protective equipment. A simple barrier drape significantly reduced particulate dispersion in this study and could be an effective mitigation strategy in addition to appropriate personal protective equipment.


title: Collateral status and tissue outcome after intra-arterial therapy for patients with acute ischemic stroke.

text: Intra-arterial therapy (IAT) for ischemic stroke aims to save brain tissue. Collaterals are thought to contribute to prolonged penumbra sustenance. In this study, we investigate the effect of collateral status on brain tissue salvage with IAT. In 500 patients randomized between IAT and standard care, collateral status was graded from 0 (absent) to 3 (good). Final infarct volumes (FIV) were calculated on post-treatment CT. FIVs were compared between treatment groups per collateral grade. Multivariable linear regression with interaction terms was performed to study whether collaterals modified IAT effect on FIV. Four-hundred-forty-nine patients were included in the analysis. Median FIV for the IAT group was significantly lower with 54.5 mL (95% IQR: 21.8-145.0) than for the controls with 81.8 mL (95% IQR: 40.0-154.0) ( p = 0.020). Treatment effect differed across collateral grades, although there was no significant interaction (unadjusted p = 0.054; adjusted p = 0.105). For grade 3, IAT resulted in a FIV reduction of 30.1 mL ( p = 0.024). For grade 2 and 1, this difference was, respectively, 28.4 mL ( p = 0.028) and 28.4 mL ( p = 0.29). For grade 0, this was 88.6 mL ( p = 0.28) in favour of controls. IAT saves substantially more brain tissue as compared to standard care. We observed a trend of increasing effect of IAT with higher collateral grades.


title: Increased interleukin-17 producing effector memory T cells in the end-stage renal disease patients.

text: Patients with end-stage renal disease (ESRD) exhibit immune dysregulation, but the precise immunological profile and the effect of hemodialysis (HD) on it has not been investigated fully. Thirty-eight ESRD patients (22 on HD and 16 in pre-dialysis) and 24 healthy volunteers were included. We compared the T cell immune profiles as in these patients. Among the effector T cell subset, the percentages of Th17 and Th2 cells were significantly higher in the ESRD group than in the healthy controls (P<0.05). The percentage of Th1 cells did not differ significantly between these groups. The percentages of Th1, Th2 and Th17 cells did not differ significantly (P>0.05) between the two subgroups within the ESRD group. The CCR4(-)CCR6(+)/CD4(+) T cell percentage was also significantly higher in the ESRD group. The naïve T cell (T(naïve)) percentage was significantly lower in the ESRD group, and the difference between patients and controls was greater in the pre-dialysis patients than in the HD patients (P<0.05, for each comparison). By contrast, the percentages of central memory T cells (T(CM)) and effector memory T (T(EM)) cells were significantly higher in the ESRD group. Interleukin-17 production by T(EM) cells was significantly higher in the ESRD group. The severity of uremia was related negatively to the T(naïve) cell percentage but positively to the T(CM) and T(EM) cell percentages. The percentages of T(EM) and CD45RA(+) T effector memory subsets of CD8(+) T cells were significantly higher in the ESRD group (P<0.05). The result of this study showed significantly altered T cell-associated immunity and that it could not be corrected with hemodialysis.


title: CD9 induces cellular senescence and aggravates atherosclerotic plaque formation.

text: CD9, a 24 kDa tetraspanin membrane protein, is known to regulate cell adhesion and migration, cancer progression and metastasis, immune and allergic responses, and viral infection. CD9 is upregulated in senescent endothelial cells, neointima hyperplasia, and atherosclerotic plaques. However, its role in cellular senescence and atherosclerosis remains undefined. We investigated the potential mechanism for CD9-mediated cellular senescence and its role in atherosclerotic plaque formation. CD9 knockdown in senescent human umbilical vein endothelial cells significantly rescued senescence phenotypes, while CD9 upregulation in young cells accelerated senescence. CD9 regulated cellular senescence through a phosphatidylinositide 3 kinase-AKT-mTOR-p53 signal pathway. CD9 expression increased in arterial tissues from humans and rats with age, and in atherosclerotic plaques in humans and mice. Anti-mouse CD9 antibody noticeably prevented the formation of atherosclerotic lesions in ApoE-/- mice and Ldlr-/- mice. Furthermore, CD9 ablation in ApoE-/- mice decreased atherosclerotic lesions in aorta and aortic sinus. These results suggest that CD9 plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that CD9 is a novel target for prevention and treatment of vascular aging and atherosclerosis.


title: Synthesis and biological evaluation of a novel 99mTc(CO)3 complex of ciprofloxacin dithiocarbamate as a potential agent to target infection.

text: The ciprofloxacin dithiocarbamate (CPFXDTC) was radiolabeled with [(99m)Tc(CO)(3)(H(2)O)(3)](+) intermediate to form the (99m)Tc(CO)(3)-CPFXDTC complex in high yield. The (99m)Tc(CO)(3)-CPFXDTC complex was characterized by HPLC and its stability in serum was studied. Its partition coefficient indicated that it was a lipophilic complex. The bacterial binding efficiency of (99m)Tc(CO)(3)-CPFXDTC was almost the same as that of (99m)TcN-CPFXDTC, and was higher than that of (99m)Tc-ciprofloxacin. Biodistribution results in induced infection mice showed (99m)Tc(CO)(3)-CPFXDTC had higher uptake at the sites of infection and better abscess/blood and abscess/muscle ratios than those of (99m)Tc-ciprofloxacin and (99m)TcN-CPFXDTC. Single photon emission computed tomography (SPECT) static imaging study in infected rabbits demonstrated the uptake in the left thigh infection lesion was observable, while no accumulation in the right thigh muscle was found. These results suggested (99m)Tc(CO)(3)-CPFXDTC would be a promising candidate for further evaluation as infection imaging agent.


title: Raccoon rabies virus variant transmission through solid organ transplantation.

text: IMPORTANCE The rabies virus causes a fatal encephalitis and can be transmitted through tissue or organ transplantation. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation. OBJECTIVES To investigate whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients from the same donor. DESIGN Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients. Viral ribonucleic acid was extracted from tissues and amplified for nucleoprotein gene sequencing for phylogenetic comparisons. MAIN OUTCOMES AND MEASURES Determination of whether the donor died from undiagnosed rabies and whether other organ recipients developed rabies. RESULTS In retrospect, the donor's clinical presentation (which began with vomiting and upper extremity paresthesias and progressed to fever, seizures, dysphagia, autonomic dysfunction, and brain death) was consistent with rabies. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9% identical across the entire N gene (1349/1350 nucleotides), thus confirming organ transplantation as the route of transmission. The 3 other organ recipients remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis (range, 0.3-40.8 IU/mL). CONCLUSIONS AND RELEVANCE Unlike the 2 previous clusters of rabies virus transmission through solid organ transplantation, there was a long incubation period in the recipient who developed rabies, and survival of 3 other recipients without pretransplant rabies vaccination. Rabies should be considered in patients with acute progressive encephalitis of unexplained etiology, especially for potential organ donors. A standard evaluation of potential donors who meet screening criteria for infectious encephalitis should be considered, and risks and benefits for recipients of organs from these donors should be evaluated.


title: Perioperative Presentation of COVID-19 Disease in a Liver Transplant Recipient.

text: Coronavirus disease 2019 (COVID-19) is highly contagious. It may rapidly progress to acute respiratory distress syndrome (ARDS) and result in multiorgan dysfunction or death in some cases.(1,2) Here, we report the case of a patient with hepatocellular carcinoma (HCC) who underwent liver transplantation and experienced COVID-19 infection during the perioperative period. This case may help clinicians by alerting them to potential COVID-19 infection in transplant recipients during the outbreak.


COVID-19 in paediatric rheumatology patients treated with b/tsDMARDs: a cross-sectional patient survey study.


title: Gaps remain in China's ability to detect emerging infectious diseases despite advances since the onset of SARS and avian flu.

text: Early detection of emerging infections in China is critical to the health of the 1.3 billion Chinese people and to the world. China's surveillance system for endemic infectious diseases has improved greatly since 2003, but the country's ability to conduct surveillance for laboratory-confirmed infections remains underdeveloped. This is dangerous for China, the world's most populous country, which has been the focus of global attention since outbreaks of severe acute respiratory syndrome (SARS) and avian influenza. We describe China's public health advances since the 2003 SARS outbreak and conclude that China must now invest far more in pathogen-based surveillance. An enhanced disease-detection system in China will help prevent and contain outbreaks before they cause substantial illness and death in China and other countries.


title: Identification by next-generation sequencing of Aichivirus B in a calf with enterocolitis and neurologic signs.

text: An 11-d-old Holstein bull calf was presented to the Veterinary Medical Teaching Hospital at the University of Wisconsin-Madison because of a 4-d history of diarrhea and persistent low-grade fever. Initial diagnosis was enteritis caused by Cryptosporidium and rotavirus. During hospitalization, the calf became stuporous and was only responsive to noxious stimuli, with hypotonia of all 4 limbs, tail, head, and neck. A cerebrospinal fluid analysis revealed xanthochromia, with marked lymphocytic pleocytosis, which was suggestive of viral meningitis and/or encephalitis. Aichivirus B, which belongs to the Kobuvirus genus, was tentatively identified in spinal fluid by next-generation DNA sequencing. This virus can affect a multitude of species, including humans and cattle, and has been isolated from both healthy and diarrheic individuals. However, to date, a possible connection with neurologic disease has not been described, to our knowledge.


title: Comparing responses to natural, accidental and deliberate biological events.

text: Disease outbreaks - whether naturally occurring, or resulting from the unintentional or deliberate release of pathogens and/or toxins - can have significant consequences in terms of human, economic, environmental and material costs and put a serious strain on the state's capacity to adequately respond to threats to public, animal or plant health. This paper aims to compare responses to natural, accidental and deliberate biological events. The author examines the characteristics of each type of biological event and reviews relevant international mechanisms for addressing disease outbreaks. The paper further examines the prerequisites for an effective disease response, regardless of whether the biological event has occurred naturally, is the result of an accident or has been caused deliberately.


title: Racial and health insurance disparities of inpatient spine augmentation for osteoporotic vertebral fractures from 2005 to 2010.

text: BACKGROUND AND PURPOSE Vertebroplasty and kyphoplasty are frequently utilized in the treatment of symptomatic vertebral body fractures. While prior studies have demonstrated disparities in the treatment of back pain and care for osteoporotic patients, disparities in spine augmentation have not been investigated. We investigated racial and health insurance status differences in the use of spine augmentation for the treatment of osteoporotic vertebral fractures in the United States. MATERIALS AND METHODS Using the Nationwide Inpatient Sample from 2005 to 2010, we selected all discharges with a primary diagnosis of vertebral fracture (International Classification of Diseases-9 code 733.13). Patients who received spine augmentation were identified by using International Classification of Diseases-9 procedure code 81.65 for vertebroplasty and 81.66 for kyphoplasty. Patients with a diagnosis of cancer were excluded. We compared usage rates of spine augmentation by race/ethnicity (white, black, Hispanic, and Asian/Pacific Islander) and insurance status (Medicare, Medicaid, self-pay, and private). Comparisons among groups were made by using χ(2) tests. A multivariate logistic regression analysis was fit to determine variables associated with spine augmentation use. RESULTS A total of 228,329 patients were included in this analysis, of whom 129,206 (56.6%) received spine augmentation. Among patients with spine augmentation, 97,022 (75%) received kyphoplasty and 32,184 (25%) received vertebroplasty; 57.5% (92,779/161,281) of white patients received spine augmentation compared with 38.7% (1405/3631) of black patients (P < .001). Hispanic patients had significantly lower spine augmentation rates compared with white patients (52.3%, 3777/7222, P < .001) as did Asian/Pacific Islander patients (53.1%, 1784/3361, P < .001). The spine augmentation usage rate was 57.2% (114,768/200,662) among patients with Medicare, significantly higher than that of those with Medicaid (43.9%, 1907/4341, P < .001) and those who self-pay (40.2%, 488/1214, P < .001). CONCLUSIONS Our findings demonstrate substantial racial and health insurance-based disparities in the inpatient use of spinal augmentation for the treatment of osteoporotic vertebral fracture.


title: Transcranial Photobiomodulation for the Treatment of Major Depressive Disorder. The ELATED-2 Pilot Trial.

text: OBJECTIVE Our objective was to test the antidepressant effect of transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light in subjects suffering from major depressive disorder (MDD). BACKGROUND t-PBM with NIR light is a new treatment for MDD. NIR light is absorbed by mitochondria; it boosts cerebral metabolism, promotes neuroplasticity, and modulates endogenous opioids, while decreasing inflammation and oxidative stress. MATERIALS AND METHODS We conducted a double-blind, sham-controlled study on the safety and efficacy (change in Hamilton Depression Rating Scale [HAM-D17] total score at end-point) of adjunct t-PBM NIR [823 nm; continuous wave (CW); 28.7 × 2 cm2; 36.2 mW/cm2; up to 65.2 J/cm2; 20-30 min/session], delivered to dorsolateral prefrontal cortex, bilaterally and simultaneously, twice a week, for 8 weeks, in subjects with MDD. Baseline observation carried forward (BOCF), last observation carried forward (LOCF), and completers analyses were performed. RESULTS The effect size for the antidepressant effect of t-PBM, based on change in HAM-D17 total score at end-point, was 0.90, 0.75, and 1.5 (Cohen's d), respectively for BOCF (n = 21), LOCF (n = 19), and completers (n = 13). Further, t-PBM was fairly well tolerated, with no serious adverse events. CONCLUSIONS t-PBM with NIR light demonstrated antidepressant properties with a medium to large effect size in patients with MDD. Replication is warranted, especially in consideration of the small sample size.


Diagnostics and the coronavirus: don't let the standards slip.