title: Bioresorbable Electronic Stent Integrated with Therapeutic Nanoparticles for Endovascular Diseases.

text: Implantable endovascular devices such as bare metal, drug eluting, and bioresorbable stents have transformed interventional care by providing continuous structural and mechanical support to many peripheral, neural, and coronary arteries affected by blockage. Although effective in achieving immediate restoration of blood flow, the long-term re-endothelialization and inflammation induced by mechanical stents are difficult to diagnose or treat. Here we present nanomaterial designs and integration strategies for the bioresorbable electronic stent with drug-infused functionalized nanoparticles to enable flow sensing, temperature monitoring, data storage, wireless power/data transmission, inflammation suppression, localized drug delivery, and hyperthermia therapy. In vivo and ex vivo animal experiments as well as in vitro cell studies demonstrate the previously unrecognized potential for bioresorbable electronic implants coupled with bioinert therapeutic nanoparticles in the endovascular system.


title: Periprocedural and mid-term technical and clinical events after flow diversion for intracranial aneurysms.

text: OBJECT Flow diversion has emerged as a promising treatment alternative for cerebral aneurysms. As a new device, treatment-related events and complications are currently being characterized. METHODS Data on 100 consecutive procedures with the intention to use flow diversion were prospectively collected and analyzed retrospectively. RESULTS Ninety-five aneurysms were treated in 93 patients during 100 consecutive procedures in which the intention was to treat an intracranial aneurysm with flow diversion. Death occurred in 1% and permanent morbidity in 1%. However, periprocedural technical complications occurred in 35% of the procedures and included proximal device migration in 12%, incomplete device expansion in 9%, catheter-induced vasospasm in 6%, and artery perforation from the wire in 3%. Perioperative clinical events were seen in 28% (thromboembolism and access site complications were the most common, being observed in 6.5% of patients). Worsened extraocular motility was seen in 5.4% and resolved in 4/5 patients. Mean clinical follow-up was 17 months. There were no late clinical or technical issues resulting in permanent deficits, although one patient suffered worsening ataxia. Overall, using very strict angiographic criteria, complete angiographic obliteration was 50% at 6 months and 69% after 1 year. CONCLUSIONS Flow diversion for intracranial aneurysms is a safe and effective treatment. Technical and clinical events are common in the perioperative period. Careful perioperative care and proper management of technical and clinical events encountered is key to achieving low morbidity and mortality. Late clinical events can occur but are unlikely to result in permanent complications.


title: Solitary Cholinergic Stimulation Induces Airway Hyperreactivity and Transcription of Distinct Pro-inflammatory Pathways.

text: Airway hyperreactivity is a hallmark feature of asthma and can be precipitated by airway insults, such as ozone exposure or viral infection. A proposed mechanism linking airway insults to airway hyperreactivity is augmented cholinergic transmission. In the current study, we tested the hypothesis that acute potentiation of cholinergic transmission is sufficient to induce airway hyperreactivity. We atomized the cholinergic agonist bethanechol to neonatal piglets and forty-eight hours later measured airway resistance. Bethanechol-treated piglets displayed increased airway resistance in response to intravenous methacholine compared to saline-treated controls. In the absence of an airway insult, we expected to find no evidence of airway inflammation; however, transcripts for several asthma-associated cytokines, including IL17A, IL1A, and IL8, were elevated in the tracheas of bethanechol-treated piglets. In the lungs, prior bethanechol treatment increased transcripts for IFNγ and its downstream target CXCL10. These findings suggest that augmented cholinergic transmission is sufficient to induce airway hyperreactivity, and raise the possibility that cholinergic-mediated regulation of pro-inflammatory pathways might contribute.


title: Transciliary supraorbital approach (eyebrow approach) for resection of retrochiasmatic craniopharyngiomas: an alternative approach, case series, and literature review.

text: INTRODUCTION Craniopharyngiomas are known for an irregular growth pattern and extension into the retrochiasmatic space with adherence to adjacent structures. We describe the use of the transciliary supraorbital approach (eyebrow approach) for resection of craniopharyngiomas with retrochiasmatic extension. METHODS Our clinical database was reviewed to identify operative cases of craniopharyngiomas between July 1998 and January 2011. Only patients who had retrochiasmatic extension and underwent an eyebrow approach were included in this analysis. Endoscopy was used to aid surgical resection at the discretion of the surgeon. Six patients were identified (three from a retrospective review and three during the course of prospective follow-up evaluation). RESULTS The group included three men and three women (mean age: 41.2 years; range: 28-57 years). All patients had visual and hormonal deficits at presentation. Complete resection was achieved in four patients. Endoscopic assistance was used in three patients. Opening of the frontal sinus occurred in two cases during surgery; an additional surgical procedure was required for repair of a cerebrospinal fluid leak in one of these cases. The duration of clinical follow-up ranged from 18 to 97 months. All patients had excellent cosmetic results, visual improvement to a serviceable level, and a Karnofsky performance scale score ≥ 80. CONCLUSIONS The eyebrow approach is safe for resection of craniopharyngiomas with retrochiasmatic extension. This approach offers a reasonable surgical corridor for resection of the retrochiasmatic tumor component and can be enhanced using endoscopic assistance.


title: Az első két sikeres, convalescens friss fagyasztott plazmával történő terápia hazai alkalmazása intenzív osztályon kezelt, kritikus állapotú, COVID-19-fertőzésben szenvedő betegekben.

text: INTRODUCTION At present, neither specific curative treatment nor vaccines for novel coronavirus 2019 (COVID-19) are available. There is an urgent need to look for alternative strategies for COVID-19 treatment especially in the case of severe and/or critically ill patients with cytokine release syndrome (CRS). AIM Convalescent plasma proved to increase survival rates in other severe viral infections. Therefore, convalescent plasma could be a promising treatment option for severe COVID-19 patients. METHOD In our article, we present the first two critically ill Hungarian patients with COVID-19 infection treated with convalescent fresh frozen plasma. RESULTS At the time of plasma therapy both patients were on mechanical ventilation and received antiviral agents and a full scale of supportive care. Each patient received 3 × 200 mL of convalescent plasma of recently recovered donors with sufficient novel anti-coronavirus IgG titers. Subsequent to convalescent plasma infusion, oxygenization improved and inflammatory markers decreased in both individuals. As compared to pretransfusion, lymphocyte counts increased and interleukin-6 level lessened. Both patients were weaned from mechanical ventilation within 2 weeks of treatment. No severe adverse effects were observed. CONCLUSIONS Our experience indicates that convalescent plasma therapy is well tolerated and could potentially improve clinical outcomes. Optimal dose and timing as well as precise assessment of clinical benefit of convalescent plasma therapy will need further investigation in larger, well-controlled trials. This is the first report of the successful use of convalescent plasma in the treatment of critically ill patients with COVID-19 infection in Hungary. Orv Hetil. 2020; 161(27): 1111-1121.


title: Serosurvey for selected infectious agents in two sympatric species of cormorants (Phalacrocorax atriceps and Phalacrocorax magellanicus) from coastal Patagonia, Argentina.

text: We conducted a serologic survey for selected infectious agents on two sympatric cormorants, the Imperial Cormorant (Phalacrocorax atriceps) and the Rock Shag (Phalacrocorax magellanicus). Blood was collected from 267 Imperial Cormorants and 106 Rock Shags at 17 colonies along the Patagonia Atlantic shore during nine breeding seasons (1994, 1999-2001-2005-2008-2010). Antibodies to four pathogens were common to both species and frequently observed: avian paramyxovirus type 1 (56% of Imperial Cormorants and 56% of Rock Shags); avian adenovirus (67% of Imperial Cormorants and 40% of Rock Shags); infectious bronchitis virus serotypes IBV-41, IBV-46, IBV-99, and IBV-JMK (53% of Imperial Cormorants and 64% of Rock Shags); and Salmonella pullorum (18% of Imperial Cormorants and 7% of Rock Shags). Antibody prevalence for these pathogens varied significantly between species, except for avian paramyxovirus type 1. Exposure to avian paramyxovirus type 1 and all serotypes of infectious bronchitis virus varied significantly among seasons in both species. In contrast, the sporadic occurrence of positive titers suggest that cormorants had occasional exposure to Aspergillus spp. (3% of Rock Shags, only in 2000), avian paramyxovirus type 3 (5% of Rock Shags, only in 2008), Chlamydophila spp. (1% of Imperial Cormorants, only in 2010), and avian reovirus (1% of Rock Shags, only in 1999; 29% of Imperial Cormorants, in 2008 and 2010). Both species were antibody negative for avian encephalomyelitis virus, avian influenza virus, avian laryngotracheitis virus, avian paramyxovirus type 2, and infectious bursal disease virus. We provide the first information on pathogen exposure, indicated by detection of antibody in blood samples, for two sympatric species of South Atlantic cormorants. To determine major causes of morbidity and mortality in these birds future efforts should focus on necropsy surveys in cormorant colonies.


title: Early Outcomes of Outpatient Management of Kidney Transplant Recipients with Coronavirus Disease 2019.

text: BACKGROUND AND OBJECTIVES Outcomes of kidney transplant recipients diagnosed with coronavirus disease 2019 as outpatients have not been described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We obtained clinical data for 41 consecutive outpatient kidney transplant recipients with known or suspected coronavirus disease 2019. Chi-squared and Wilcoxon rank sum tests were used to compare characteristics of patients who required hospitalization versus those who did not. RESULTS Of 41 patients, 22 (54%) had confirmed coronavirus disease 2019, and 19 (46%) were suspected cases. Patients most commonly reported fever (80%), cough (56%), and dyspnea (39%). At the end of follow-up, 13 patients (32%) required hospitalization a median of 8 days (range, 1-16) after symptom onset, and 23 (56%) had outpatient symptom resolution a median of 12 days (4-23) after onset. Patients who required hospitalization were more likely to have reported dyspnea (77% versus 21%, P=0.003) and had higher baseline creatinine (median, 2.0 versus 1.3 mg/dl, P=0.02), but there were no other differences between groups. CONCLUSIONS In an early cohort of outpatient kidney transplant recipients with known or suspected coronavirus disease 2019, many had symptomatic resolution without requiring hospitalization.


title: Social amplification of risk in the Internet environment.

text: This article analyzes the dynamic process of risk amplification in the Internet environment with special emphasis on public concern for environmental risks from a high-speed railway tunnel construction project in South Korea. Environmental organizations and activists serving as social stations collected information about the project and its ecological impact, and communicated this with the general public, social groups, and institutions. The Internet provides social stations and the public with an efficient means for interactive communication and an open space for active information sharing and public participation. For example, while the website of an organization such as an environmental activist group can initially trigger local interest, the Internet allows this information to be disseminated to a much wider audience in a manner unavailable to the traditional media. Interaction among social stations demonstrates an amplifying process of public attention to the risk. Analyses of the volume of readers' comments to online newspaper articles and public opinions posted on message board of public and nonprofit organizations show the ripple effects of the amplification process as measured along temporal, geographical, and sectoral dimensions. Public attention is also influenced by the symbolic connotations of risk information. Interpretations of risk in religious, political, or legal terms intensify public concern for the environmental risk.


title: Automated DWI analysis can identify patients within the thrombolysis time window of 4.5 hours.

text: OBJECTIVE To develop an automated model based on diffusion-weighted imaging (DWI) to detect patients within 4.5 hours after stroke onset and compare this method to the visual DWI-FLAIR (fluid-attenuated inversion recovery) mismatch. METHODS We performed a subanalysis of the "DWI-FLAIR mismatch for the identification of patients with acute ischemic stroke within 4.5 hours of symptom onset" (PRE-FLAIR) and the "AX200 for ischemic stroke" (AXIS 2) trials. We developed a prediction model with data from the PRE-FLAIR study by backward logistic regression with the 4.5-hour time window as dependent variable and the following explanatory variables: age and median relative DWI (rDWI) signal intensity, interquartile range (IQR) rDWI signal intensity, and volume of the core. We obtained the accuracy of the model to predict the 4.5-hour time window and validated our findings in an independent cohort from the AXIS 2 trial. We compared the receiver operating characteristic curve to the visual DWI-FLAIR mismatch. RESULTS In the derivation cohort of 118 patients, we retained the IQR rDWI as explanatory variable. A threshold of 0.39 was most optimal in selecting patients within 4.5 hours after stroke onset resulting in a sensitivity of 76% and specificity of 63%. The accuracy was validated in an independent cohort of 200 patients. The predictive value of the area under the curve of 0.72 (95% confidence interval 0.64-0.80) was similar to the visual DWI-FLAIR mismatch (area under the curve = 0.65; 95% confidence interval 0.58-0.72; p for difference = 0.18). CONCLUSIONS An automated analysis of DWI performs at least as good as the visual DWI-FLAIR mismatch in selecting patients within the 4.5-hour time window.


title: Fully Automated Pulmonary Lobar Segmentation: Influence of Different Prototype Software Programs onto Quantitative Evaluation of Chronic Obstructive Lung Disease.

text: OBJECTIVES Surgical or bronchoscopic lung volume reduction (BLVR) techniques can be beneficial for heterogeneous emphysema. Post-processing software tools for lobar emphysema quantification are useful for patient and target lobe selection, treatment planning and post-interventional follow-up. We aimed to evaluate the inter-software variability of emphysema quantification using fully automated lobar segmentation prototypes. MATERIAL AND METHODS 66 patients with moderate to severe COPD who underwent CT for planning of BLVR were included. Emphysema quantification was performed using 2 modified versions of in-house software (without and with prototype advanced lung vessel segmentation; programs 1 [YACTA v.2.3.0.2] and 2 [YACTA v.2.4.3.1]), as well as 1 commercial program 3 [Pulmo3D VA30A_HF2] and 1 pre-commercial prototype 4 [CT COPD ISP ver7.0]). The following parameters were computed for each segmented anatomical lung lobe and the whole lung: lobar volume (LV), mean lobar density (MLD), 15th percentile of lobar density (15th), emphysema volume (EV) and emphysema index (EI). Bland-Altman analysis (limits of agreement, LoA) and linear random effects models were used for comparison between the software. RESULTS Segmentation using programs 1, 3 and 4 was unsuccessful in 1 (1%), 7 (10%) and 5 (7%) patients, respectively. Program 2 could analyze all datasets. The 53 patients with successful segmentation by all 4 programs were included for further analysis. For LV, program 1 and 4 showed the largest mean difference of 72 ml and the widest LoA of [-356, 499 ml] (p<0.05). Program 3 and 4 showed the largest mean difference of 4% and the widest LoA of [-7, 14%] for EI (p<0.001). CONCLUSIONS Only a single software program was able to successfully analyze all scheduled data-sets. Although mean bias of LV and EV were relatively low in lobar quantification, ranges of disagreement were substantial in both of them. For longitudinal emphysema monitoring, not only scanning protocol but also quantification software needs to be kept constant.


title: A plan template-based automation solution using a commercial treatment planning system.

text: PURPOSE The purpose of this study was to develop an auto-planning platform to be interfaced with a commercial treatment planning system (TPS). The main goal was to obtain robust and high-quality plans for different anatomic sites and various dosimetric requirements. METHODS Monaco (Elekta, St. Louis, US) was the TPS in this work. All input parameters for inverse planning could be defined in a plan template inside Monaco. A software tool called Robot Framework was used to launch auto-planning trials with updated plan templates. The template modifier external to Monaco was the major component of our auto-planning platform. For current implementation, it was a rule-based system that mimics the trial-and-error process of an experienced planner. A template was automatically updated by changing the optimization constraints based on dosimetric evaluation of the plan obtained in the previous trial, along with the data of the iterative optimization extracted from Monaco. Treatment plans generated by Monaco with all plan evaluation criteria satisfied were considered acceptable, and such plans would be saved for further evaluation by clinicians. The auto-planning platform was validated for 10 prostate and 10 head-and-neck cases in comparison with clinical plans generated by experienced planners. RESULTS The performance and robustness of our auto-planning platform was tested with clinical cases of prostate and head and neck treatment. For prostate cases, automatically generated plans had very similar plan quality with the clinical plans, and the bladder volume receiving 62.5 Gy, 50 Gy, and 40 Gy in auto-plans was reduced by 1%, 3%, and 5%, respectively. For head and neck cases, auto-plans had better conformity with reduced dose to the normal structures but slightly higher dose inhomogeneity in the target volume. Remarkably, the maximum dose in the spinal cord and brain stem was reduced by more than 3.5 Gy in auto-plans. Fluence map optimization only with less than 30 trials was adequate to generate acceptable plans, and subsequent optimization for final plans was completed by Monaco without further intervention. The plan quality was weakly dependent on the parameter selection in the initial template and the choices of the step sizes for changing the constraint values. CONCLUSION An automated planning platform to interface with Monaco was developed, and our reported tests showed preliminary results for prostate and head and neck cases.


title: Potential global pandemics: the role of the WHO and other public health bodies.

text: In light of the emergence of the new coronavirus in China, Emeritus Professor Alan Glasper, from the University of Southampton, discusses the response strategies adopted by international and national public health agencies.


Fourth step for ultrasound-guided central vein catheterization.


title: Ensuring safe practice during the pandemic.

text: Sam Foster, Chief Nurse, Oxford University Hospitals, considers the range of issues that needs to be considered to enable retired nurses and those redeployed from other areas to care for patients with COVID-19.


title: Microwave ablation of renal tumors: state of the art and development trends.

text: In the last decades an increased incidence of new renal tumor cases has been for clinically localized, small tumors <2.0 cm. This trend for small, low-stage tumors is the reflection of earlier diagnosis primarily as a result of the widespread and increasing use of non-invasive abdominal imaging modalities such as ultrasound, computerized tomography, and magnetic resonance imaging. Renal tumors are often diagnosed in elderly patients, with medical comorbidities whom the risk of surgical complications may pose a greater risk of death than that due to the tumor itself. In these patients, unsuitable for surgical approach, thermal ablation represents a valid alternative to traditional surgery. Thermal ablation is a less invasive, less morbid treatment option thanks to reduced blood loss, lower incidence of complications during the procedure and a less long convalescence. At present, the most widely used thermal ablative techniques are cryoablation, radiofrequency ablation and microwave ablation (MWA). MWA offers many benefits of other ablation techniques and offers several other advantages: higher intratumoral temperatures, larger tumor ablation volumes, faster ablation times, the ability to use multiple applicators simultaneously, optimal heating of cystic masses and tumors close to the vessels and less procedural pain. This review aims to provide the reader with an overview about the state of the art of microwave ablation for renal tumors and to cast a glance on the new development trends of this technique.


title: Factors supporting intrathecal humoral responses following viral encephalomyelitis.

text: Central nervous system (CNS) infections and autoimmune inflammatory disorders are often associated with retention of antibody-secreting cells (ASC). Although beneficial or detrimental contributions of ASC to CNS diseases remain to be defined, virus-specific ASC are crucial in controlling persistent CNS infection following coronavirus-induced encephalomyelitis. This report characterizes expression kinetics of factors associated with ASC homing, differentiation, and survival in the spinal cord, the prominent site of coronavirus persistence. Infection induced a vast, gamma interferon (IFN-γ)-dependent, prolonged increase in chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, and CXCL11 mRNA, supporting a role for chemokine (C-X-C motif) receptor 3 (CXCR3)-mediated ASC recruitment. Similarly, CD4 T cell-secreted interleukin-21, a critical regulator of both peripheral activated B cells and CD8 T cells, was sustained during viral persistence. The ASC survival factors B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferating-inducing ligand (APRIL) were also significantly elevated in the infected CNS, albeit delayed relative to the chemokines. Unlike IFN-γ-dependent BAFF upregulation, APRIL induction was IFN-γ independent. Moreover, both APRIL and BAFF were predominantly localized to astrocytes. Last, the expression kinetics of the APRIL and BAFF receptors coincided with CNS accumulation of ASC. Therefore, the factors associated with ASC migration, differentiation, and survival are all induced during acute viral encephalomyelitis, prior to ASC accumulation in the CNS. Importantly, the CNS expression kinetics implicate rapid establishment, and subsequent maintenance, of an environment capable of supporting differentiation and survival of protective antiviral ASC, recruited as plasmablasts from lymphoid organs.


title: Quantity of clot lysed after catheter-directed thrombolysis for iliofemoral deep venous thrombosis correlates with postthrombotic morbidity.

text: BACKGROUND International treatment guidelines now recognize the importance of thrombus removal to reduce postthrombotic morbidity when treating patients with extensive acute deep venous thrombosis (DVT). Studies have shown that thrombus resolution with catheter-directed thrombolysis in patients with iliofemoral DVT reduces postthrombotic morbidity, although patients unsuccessfully treated with catheter-directed thrombolysis (CDT) do not enjoy the same long-term benefit. The purpose of this study is to objectively assess whether the amount of clot reduction at the time of acute therapy correlates with long-term postthrombotic morbidity. METHODS Forty-two patients who underwent catheter-directed and/or pharmacomechanical lysis of iliofemoral DVT were quantitatively evaluated. Patients had their degree of clot lysis quantified and were divided into two main groups for comparison. Group I (n = 33) had >50% clot lysis (mean, 84%) and group II (n = 9) had < or =50% lysis (mean, 42%). At a mean follow-up interval of 14 months, the degree of chronic venous disease was assessed by evaluators blinded to the degree of clot lysis. Evaluation of postthrombotic morbidity was performed using the Villalta scale, and the clinical class of CEAP, and quality-of-life (QOL) was assessed using the Short Form Health Survey (SF-36). RESULTS Mean CEAP scores were 0.85 and 3.13 (P = .005), and Villalta scores were 2.38 and 6.25 (P = .009) in group I and group II, respectively. Patient QOL in group I was higher than group II in all parameters. Physical functioning (P = .035), role physical (P = .012), general health (P = .014), vitality (P < .001), and social functioning (P = .012) were all significantly better in group I. Bodily pain (P = .117), role emotional (P = .624), and mental health (P = .096) strongly favored group I patients but did not reach statistical significance. CONCLUSION Patients with extensive DVT treated with catheter-based interventions to eliminate thrombus suffer relatively little postthrombotic morbidity. The degree of clot lysis directly correlates with long-term outcome. Improved QOL, the Villalta scale, and clinical class of CEAP are linearly correlated with the amount of clot resolution.


title: Current concepts in negative pressure wound therapy.

text: Negative pressure wound therapy (NPWT) is becoming recognized in veterinary medicine as a viable option for the management of complex wounds. NPWT has many advantages over traditional wound care and results in quicker and improved wound healing in many instances. This article discusses the art and science of NPWT, as well as the many current indications, complications, advantages and disadvantages, and future directions of NPWT in small animal veterinary medicine. This therapy will likely have a growing role in veterinary medical practice for complicated wound management and other usages in coming years.


The Ethics of Creating a Resource Allocation Strategy During the COVID-19 Pandemic.


title: Refugee Policy Implications of U.S. Immigration Medical Screenings: A New Era of Inadmissibility on Health-Related Grounds.

text: Refugees frequently face extended delays in their efforts to enter the United States (U.S.) and those who are successful, in many cases, encounter overwhelming obstacles, inadequate resources, and a complex system of legal barriers. Travel restrictions based on equivocal health concerns and a drop in refugee admittance ceilings have complicated the situation. The authors retrieved and analyzed peer-reviewed journal articles, government agency press releases, media postings, epidemiologic factsheets, and relevant lay publications to critically assess U.S. policy regarding refugee resettlement based on health-related grounds. While refugees arguably exhibit an increased incidence of measles and tuberculosis compared with the U.S. population, the legitimacy of the medical examination will be undermined if other diseases that are endemic to refugee populations, yet currently deemed admissible, are used to restrict refugees from entering the U.S. This paper addressees the historic refugee policy of the U.S. and its consequent effect on the health of this vulnerable population. The needs of refugees should be carefully considered in the context of increased disease burden and the associated health care challenges of the country as a whole.


title: Molecular Imaging with Kupffer Cell-Targeting Nanobodies for Diagnosis and Prognosis in Mouse Models of Liver Pathogenesis.

text: PURPOSE Kupffer cells (KCs), the liver resident macrophages, are important mediators of tissue homeostasis and pathogen clearance. However, depending on the inflammatory stimuli, KCs have been involved in divergent hepato-protective or hepato-destructive immune responses. The versatility of KCs in response to environmental triggers, in combination with the specific biomarkers they express, make these macrophages attractive in vivo targets for non-invasive monitoring of liver inflammation or pathogenicity. This study aims to determine whether V-set and Ig domain-containing 4 (Vsig4) and C-type lectin domain family (Clec) 4, member F (Clec4F) can be used as imaging biomarkers for non-invasive monitoring of KCs during distinct liver inflammation models. PROCEDURE Flow cytometry (FACS), immuno-histochemistry (IHC), and single-photon emission computed tomography (SPECT) with Tc-99m labeled anti-Vsig4 or anti-Clec4F nanobodies (Nbs) was performed to evaluate in mice KC dynamics in concanavalin A (ConA)-induced hepatitis and in non-alcoholic steatohepatitis induced via methionine choline deficiency (MCD). RESULTS In homeostatic mice, Nbs targeting Clec4F were found to accumulate and co-localize with Vsig4-targeting Nbs only in the liver. Upon induction of acute hepatitis using ConA, down-regulation of the in vivo Nb imaging signal was observed, reflecting reduction in KC numbers as confirmed by FACS and IHC. On the other hand, induction of steatohepatitis resulted in higher signals in the liver corresponding to higher density of KCs. The Nb-imaging signals returned to normal levels after resolution of the investigated liver diseases. CONCLUSIONS Anti-Clec4F and anti-Vsig4 Nbs targeting KCs as molecular imaging biomarkers could allow non-invasive monitoring/staging of liver pathogenesis.


title: A recombinant, infectious human parainfluenza virus type 3 expressing the enhanced green fluorescent protein for use in high-throughput antiviral assays.

text: The ability to rescue an infectious, recombinant, negative-stranded, RNA virus from a complementary DNA (cDNA) clone, has led to new opportunities for measuring viral replication from a viral expressed reporter gene. In this study, the enhanced green fluorescent protein (EGFP) gene was inserted into the human parainfluenza virus type 3 (HPIV-3) antigenome and a recombinant, infectious virus was rescued. Maximum EGFP expression levels, measured by fluorescence, were seen at day 3. Comparison of a 3-day, viral expressed EGFP fluorescence assay to a 7-day, neutral red assay, based on complete cell destruction in virus infected MA-104 cells, yielded Z'-factor values of 0.83 and 0.70, respectively. A 3-day, endpoint EGFP-based antiviral assay and a 7-day, endpoint neutral red based antiviral assay were run in parallel to establish antiviral sensitivity profiles of 23 compounds based on selective index (SI) values. Using an SI threshold of 10, the EGFP-based antiviral assay had a sensitivity of 100% and a specificity of 54%. Thus, the use of an EGFP-based antiviral assay for testing potential antiviral compounds against HPIV-3 in a high-throughput format may be justified.


title: Systems pharmacology strategies for anticancer drug discovery based on natural products.

text: Cancer is a complex disease, known medically as malignant neoplasm. Natural products (NPs) play a very important role in anticancer drug discovery and a large number of NPs have been proven to have potential anticancer effects. Compared with newly synthesized chemical compounds, NPs show a favorable profile in terms of their absorption and metabolism in the body with low toxicity. Searching for multi-target natural drugs can be regarded as a solution to improve therapeutic efficacy and safety. In this work, we collected 104 cancer-associated target proteins from the Protein Data Bank. Based on the Universal Natural Products Database, all of the NPs were docked to 104 cancer-associated target proteins. Then we explored the potential of NPs and several herbs in anticancer drug discovery by using a network-based multi-target computational approach. The NPs with the most potential for anticancer drug discovery and their indications were predicted based on a docking score-weighted prediction model. We also explored the interactions between NPs and cancer target proteins to find the pathological networks, potential drug candidates and new indications.


title: The effect of adding active flexion to modified Kleinert regime on outcomes for zone 1 to 3 flexor tendon repairs. A prospective randomized trial.

text: In a prospective randomized study, we studied whether adding active flexion to a modified Kleinert regime changed outcomes of flexor tendon repairs in zone 1, 2 and 3 in 73 fingers (53 patients). Evaluation included active range of finger motion, grip and pinch strengths. Twelve months after surgery, the increase in range of active finger motion after adding active flexion was insignificant compared with that with the modified Kleinert regime. According to the Strickland criteria, 20 out of 29 fingers had excellent or good recovery after adding active flexion, as did 28 out of 34 fingers with the modified Kleinert regime; we could not detect significant improvement of the good and excellent rate. At 6 months, the pinch strength was significantly higher with the addition of active flexion. We failed to find that adding active finger flexion to the modified Kleinert regime improves the overall long-term results of repairs in zone 1 to 3, though recovery appeared faster, and the good and excellent recovery of zone 2 repairs was 17% greater with the active flexion protocol. LEVEL OF EVIDENCE I.


title: Topological analysis of SARS CoV-2 main protease.

text: There is an urgent necessity of effective medication against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which is producing the COVID-19 pandemic across the world. Its main protease (Mpro) represents an attractive pharmacological target due to its involvement in essential viral functions. The crystal structure of free Mpro shows a large structural resemblance with the main protease of SARS CoV (nowadays known as SARS CoV-1). Here, we report that average SARS CoV-2 Mpro is 1900% more sensitive than SARS CoV-1 Mpro in transmitting tiny structural changes across the whole protein through long-range interactions. The largest sensitivity of Mpro to structural perturbations is located exactly around the catalytic site Cys-145 and coincides with the binding site of strong inhibitors. These findings, based on a simplified representation of the protein as a residue network, may help in designing potent inhibitors of SARS CoV-2 Mpro.


Commentary: Digital histopathology in a private or commercial diagnostic veterinary laboratory.


title: The pediatric burden of human coronaviruses evaluated for twenty years.

text: BACKGROUND The epidemiology of human coronaviruses (HCoVs) has not been established using reverse transcription polymerase chain reaction techniques in a specimen collection that spans decades. METHODS We used real-time RT-PCR for 3 HCoVs, HCoV 229E, OC43, and NL63, to test nasal wash specimens that had been obtained from a cohort of children <5 years of age with upper or lower respiratory infection (URI, LRI) who were comprehensively followed during the period from 1977 to 2001. Prospectively collected clinical data and archival samples were analyzed. RESULTS HCoV was detected in 92/1854 (5.0%) of available samples with no known viral etiology of which 9% were 229E, 59% OC43, and 33% NL63. This represented 10/119 (8.4%) of LRI samples and 82/1735 (4.7%) of URI samples. HCoV was not detected every year, but occurred episodically. The recently described HCoV-NL63 was detected as early as 1981. HCoV was associated with 11.4 LRI episodes/1000 child-years <5 years of age (all in children <2 years of age) and 67.3 URI episodes/1000 child-years <5 years of age. CONCLUSIONS HCoV-NL63 and OC43 are associated with a significant proportion of LRI in children less than 2 years of age and a substantial number of medically attended URI episodes.


title: Coaxial Tubing Systems Increase Artificial Airway Resistance and Work of Breathing.

text: BACKGROUND Tubing systems are an essential component of the ventilation circuit, connecting the ventilator to the patient's airways. Coaxial tubing systems incorporate the inspiratory tube within the lumen of the expiratory one. We hypothesized that by design, these tubing systems increase resistance to air flow compared with conventional ones. METHODS We investigated the flow-dependent pressure gradient across coaxial, conventional disposable, and conventional reusable tubing systems from 3 different manufacturers. Additionally, the additional work of breathing and perception of resistance during breathing through the different devices were determined in 18 healthy volunteers. RESULTS The pressure gradient across coaxial tubing systems was up to 6 times higher compared with conventional ones (1.90 ± 0.03 cm H2O vs 0.34 ± 0.01 cm H2O, P < .001) and was higher during expiration compared with inspiration (P < .001). Additional work of breathing and perceived breathing resistance were highest in coaxial tubing systems, accordingly. CONCLUSIONS Our findings suggest that the use of coaxial tubing systems should be carefully considered with respect to their increased resistance.


title: Stent-Retriever Angioplasty for Recurrent Post-Subarachnoid Hemorrhagic Vasospasm - A Single Center Experience with Long-Term Follow-Up.

text: PURPOSE We report our experience of using stent-retrievers for recurrent cerebral vasospasm (CVS) secondary to aneurysmal subarachnoid hemorrhage (aSAH). METHODS We performed a retrospective review of our prospectively maintained institutional database to identify all patients with recurrent CVS and treated with stent-retrievers between April 2011 and May 2017. All patients were initially treated with intra-arterial (IA) vasodilators and were subsequently re-treated with stent-retrievers if they developed recurrent vasospasm. Patients were categorized into two groups, those in which IA vasodilators were given again prior to the stent-retriever deployment (VD-first) and those in which the stent-retriever was deployed first and IA vasodilators were given subsequently (SR-first). RESULTS We identified 12 patients (7 females, mean age 54.9 years), 5 in the VD-first and 7 in the SR-first cohorts. Stent-retriever lumen dilatation was attempted in 53 segments (VD-first 14, SR-first 39). Stent-retriever deployment was technically feasible in all cases. Vasodilation occurred in 71.4% (10/14 segments) in the VD-first group and 82.1% (32/39 segments) in SR-first group. Additional treatment was required in 5 segments. There was no recurrent vasospasm in the SR-first group; however, 3 patients (60%) in the VD-first group showed recurrent vasospasm. No angiographical abnormality was found at long-term follow-up (7 patients, mean 29.1 months). CONCLUSION The use of stent-retrievers to treat cerebral vasospasm is technically feasible and can cause long-term vasodilatation; however, this effect is maximized if stent-retrievers are used prior to infusion of IA vasodilators.


title: Obstetrical safety indicators for preventing hospital harms in low risk births: a scoping review protocol.

text: INTRODUCTION Optimising the safety of obstetric patient care is a primary concern for many hospitals. Performance indicators measuring aspects of patient care processes can lead to improvements in health systems and the prevention of harm to the patient. We present our protocol for a scoping review to identify indicators for obstetric safety in low risk births. We aim to identify indicators addressing preventable hospital harms, to summarise the data and synthesise results. METHODS AND ANALYSIS We will use methods described by Arksey and O'Malley and further expanded by Levac et al. We will search electronic databases such as Medline, Embase, CINAHL and the Cochrane Library, and websites from professional bodies and other organisations, using an iterative search strategy.Two reviewers will independently screen titles and abstracts of search results to determine eligibility for inclusion. If eligibility is not clear, the reviewers will screen the full text version. If reviewers' decisions regarding eligibility differ, a third reviewer will review the record. Two reviewers will independently extract data from records that meet our inclusion criteria using a standardised data collection form. We will narratively describe quantitative data, such as the frequency with which indicators are identified, and conduct a thematic analysis of the qualitative data. We will compile a comprehensive list of patient safety indicators and organise them according to concepts that best suit the data such as the Donabedian model or the Hospital Harm Framework. We will discuss the implications for future research, clinical practice and policy-making. We will report the conduct of the review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews checklist. ETHICS AND DISSEMINATION The sources of information included in this scoping review will be available to the public. Therefore, ethics approval is not warranted. We will disseminate results in a peer-reviewed publication, conference/event presentation(s) and stakeholder communications.


title: The effectiveness and characteristics of pregnancy yoga interventions: a systematic review protocol.

text: Background: The purpose of the proposed review is to systematically examine the clinical effectiveness of pregnancy yoga. The review will use the FITT (frequency, intensity, time/duration and type) principle of physical activity to characterise the different types of yoga interventions that have been evaluated in the included studies. Methods/design: The following electronic databases will be searched using a detailed search strategy: MEDLINE, PsycINFO, EMBASE, CINAHL, WHOLiS, AMED, ScieLo, ASSIA and Web of Science. Randomised control trials and quasi-experimental studies examining pregnancy yoga will be included. Titles, abstracts and full articles will be screened by two investigators independently to identify eligible studies. The Cochrane Collaboration's Risk of Bias Assessment tool will be used to assess study quality. Quality of the evidence will be evaluated using the GRADE criteria. A standardised data extraction form will be used to extract data. Effect sizes will be estimated using mean differences for continuous outcomes, and relative risks for dichotomous outcome. Where possible, pooling of effect estimates will be done using a random effect model. Discussion: This review will synthesise the best available evidence on the effectiveness of yoga during pregnancy and provide valuable high-quality information for clinicians and health policymakers. Findings will be disseminated through publication in a peer-reviewed journal and presentation at relevant conference proceedings. The review will make recommendations for the appropriate volume, intensity and type of pregnancy yoga for maximum effect and may have implications for policy and practice relating to pregnancy yoga as an intervention. Registration: PROSPERO, CRD42019119916. Registered on 11th January 2019.


title: Is sutureless thyroid surgery safe in the hands of surgical trainees. A single centre retrospective study.

text: BACKGROUND The safety and efficacy of sutureless thyroid surgery have been confirmed in many series. Equally, surgical expertise has been shown to influence postoperative outcome. This study aimed at investigating the safety of sutureless thyroid surgery in the hands of surgical trainees and to find out if this technique could be safely integrated into endocrine surgical training programs. METHODS A single center retrospective comparison of the outcome of surgeries performed by experienced surgical attendings and trainees was performed. The LigaSure Precise was used in all cases. RESULTS Two hundred and eight patients were included. The trainee group comprised of 61 cases managed by surgical trainees. Surgery was performed by surgical attendings in 147 cases (consultant group). The incidences of transient and permanent hypocalcaemia were 20.7 and 0.9% respectively, the corresponding values for recurrent nerve injury were 6.3 and 0.9%. Postoperative bleeding occurred in 3.4%. There was no difference amongst both groups with regard to postoperative outcome (p > 0.05). CONCLUSIONS While sutureless thyroid surgery was safely performed by surgical trainees without relevant increase in perioperative complications in our department, further larger scale studies would be needed to confirm this would be the case more widely.


title: A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles.

text: Viral infections still threaten human health all over the world, and many people die from viral diseases every year. However, there are no effective vaccines or drugs for preventing or managing most viral diseases. Thus, the discovery and development of broad-spectrum antiviral agents remain urgent. Here, we expressed and purified a venom peptide, Ev37, from the scorpion Euscorpiops validus in a prokaryotic system. We found that rEv37 can inhibit dengue virus type 2 (DENV-2), hepatitis C virus (HCV), Zika virus (ZIKV), and herpes simplex virus type 1 (HSV-1) infections in a dose-dependent manner at noncytotoxic concentrations, but that it has no effect on Sendai virus (SeV) and adenovirus (AdV) infections in vitro Furthermore, rEv37 alkalized acidic organelles to prevent low pH-dependent fusion of the viral membrane-endosomal membrane, which mainly blocks the release of the viral genome from the endosome to the cytoplasm and then restricts viral late entry. Taken together, our results indicate that the scorpion venom peptide Ev37 is a broad-spectrum antiviral agent with a specific molecular mechanism against viruses undergoing low pH-dependent fusion activation during entry into host cells. We conclude that Ev37 is a potential candidate for development as an antiviral drug.


title: Isolation and characterization of Salt Overly Sensitive family genes in spinach.

text: The Salt Overly Sensitive (SOS) pathway regulates intracellular sodium ion homeostasis as a salt-stress response in plants. This pathway involves three main genes designated as SOS1, SOS2, and SOS3, which are members of the Na+ /H+ exchanger (NHX), CBL-interacting protein kinase (CIPK), and Calcineurin B-like (CBL) gene families, respectively. To identify and characterize SOS genes in spinach (Spinacia oleracea), a species of the Amaranthaceae family, we conducted genome-wide identification and phylogenetic analyses of NHX, CIPK, and CBL genes from four Amaranthaceae species, Arabidopsis, and rice. Most Amaranthaceae genes exhibited orthologous relationships with Arabidopsis and/or rice, except a clade of Vac-type Amaranthaceae NHX genes. Phylogenetic analyses also revealed gene gain/loss events in Amaranthaceae species and the intron-less to intron-rich evolution of CIPK genes. A bacterial protein-rooted CIPK tree allowed naming most of the phylogenetic clades based on their evolutionary history. Single S. oleracea (So) SOS1, SOS2, and SOS3 proteins were identified. Direct protein-protein interaction was observed between SoSOS2 and SoSOS3 but not between SoSOS2 and SoSOS1 based on yeast two-hybrid assay. This may suggest distinct modes of action of spinach SOS proteins compared to Arabidopsis SOS proteins. Unlike SoSOS1 and SoSOS2, which were expressed at similar or higher levels in leaves than roots, SoSOS3 expression was significantly higher in roots than leaves, suggesting its greater importance in roots. The expression of SoSOS3 was upregulated in both roots and leaves under salinity compared to the control; however, SoSOS1 was only upregulated in roots. Thus, this study demonstrated the conservation of SOS pathway genes in spinach and also highlighted the complexity of SOS signaling in Amaranthaceae species. This article is protected by copyright. All rights reserved.


title: Complete Genome Sequence of a Novel Porcine Circovirus Type 3 Strain, CH/GX/1776D/2017, Isolated from Guangxi, China.

text: Porcine circovirus type 3 (PCV3) was first described in 2016 in U.S. swine herds as a pathogenic agent for pigs. To date, PCV3 has been reported to be widely circulating in the United States, China, South Korea, Brazil, Italy, and Poland. Here, we report the genome sequence of a PCV3 strain (CH/GX/1776D/2017) isolated from Guangxi Province in southern China. The sequence data presented in this study will help us better understand the molecular characteristics and genetic diversity of PCV3 in China.


Unexpected Benefits to Virtual Care During COVID-19.


title: Co-localization of constituents of the dengue virus translation and replication machinery with amphisomes.

text: Infections with dengue virus (DENV) are a significant public health concern in tropical and subtropical regions. However, little detail is known about how DENV interacts with the host-cell machinery to facilitate its translation and replication. In DENV-infected HepG2 cells, an increase in the level of LC3-II (microtubule-associated protein 1 light chain 3 form II), the autophagosomal membrane-bound form of LC3, was observed, and LC3 was found to co-localize with dsRNA and DENV NS1 protein, as well as ribosomal protein L28, indicating the presence of at least some of the DENV translation/replication machinery on autophagic vacuoles. Inhibition of fusion of autophagic vacuoles with lysosomes resulted in an increase in both intracellular and extracellular virus, and co-localization observed between mannose-6-phosphate receptor (MPR) and dsRNA and between MPR and LC3 identified the autophagic vacuoles as amphisomes. Amphisomes are formed as a result of fusion between endosomal and autophagic vacuoles, and as such provide a direct link between virus entry and subsequent replication and translation.


State of acute endovascular therapy: report from the 12th thrombolysis, thrombectomy, and acute stroke therapy conference.


title: A Prospective, Randomized Study between the Small Jaw® and the Harmonic Focus® in Open Thyroidectomy.

text: OBJECTIVES LigaSure Small Jaw(®) (LSJ) was recently developed and applied to thyroid surgery along with Harmonic Focus(®) (HF). We compared the 2 devices in open total thyroidectomy for papillary thyroid carcinoma (PTC). STUDY DESIGN A prospective, randomized study. SETTING Tertiary care center. METHODS This prospective, randomized study included 126 patients enrolled between December 2011 and June 2012. The numbers of patients in the LSJ group and the HF group were 64 and 62, respectively. Operative times, drain output, parathyroid status, complications, laboratory data, hospital stay, and analgesia requirements were analyzed. RESULTS Operation time, parathyroid status, postoperative complications including hypocalcemia, oral calcium supplement, calcium, parathyroid hormone, usage count of painkiller, and hospital stay were not different among the 2 groups. Ionized calcium on postoperative days 1, 2, and 10 was higher in the LSJ group (P = .04, P = .04, P = .01), and drain output was lower in the LSJ group (106.8 vs 123.6 mL, P = .01). CONCLUSIONS Open thyroidectomy for PTC using the HF or the LSJ was safe and effective and was not associated with any increase in complications. Surgical outcomes and operative morbidity were equivalent between the 2 groups.


title: Level of evidence and conflict of interest disclosure associated with higher citation rates in orthopedics.

text: OBJECTIVE To identify the scientific and nonscientific factors associated with rates of citation in the orthopedic literature. STUDY DESIGN AND SETTING All original clinical articles published in three general orthopedics journals between July 2002 and December 2003 were reviewed. Information was collected on variables plausibly related to rates of citation, including scientific and nonscientific factors. The number of citations at 5 years was ascertained and linear regression was used to identify factors associated with rates of citation. RESULTS In the multivariate analysis, factors associated with increased rates of citation at 5 years were high level of evidence (22.2 citations for level I or II vs. 10.8 citations for level III or IV; P=0.0001), large sample size (18.8 citations for sample size of 100 or more vs. 7.9 citations for sample size of 25 or fewer; P<0.0001), multiple institutions (15.2 citations for two or more centers vs. 11.1 citations for single center; P=0.023), self-reported conflict of interest disclosure involving a nonprofit organization (17.4 citations for nonprofit disclosure vs. 10.6 citations for no disclosure; P=0.027), and self-reported conflict of interest disclosure involving a for-profit company (26.1 citations for for-profit disclosure vs. 10.6 citations for no disclosure; P=0.011). CONCLUSION High level of evidence, large sample size, representation from multiple institutions, and conflict of interest disclosure are associated with higher rates of citation in orthopedics.


Prevention of skin damage caused by the protective equipment used to mitigate COVID-19.


title: Gastric Stenosis After Laparoscopic Sleeve Gastrectomy: Diagnosis and Management.

text: PURPOSE The use of laparoscopic sleeve gastrectomy (LSG) is increasing worldwide. Although post-LSG gastric stenosis (GS) is less frequent, it has not been well defined and lacks standardized management procedures. The objective of the present study was to describe a series of patients with GS symptoms after LSG and to develop a standardized management procedure for this complication. METHODS We performed a retrospective analysis of a prospective database of patients presenting with GS after LSG procedures performed between January 2008 and March 2014. The primary efficacy criterion was the frequency of post-LSG GS. GS was classified as functional (i.e. a gastric twist) or organic. The secondary efficacy criteria included the time interval between LSG and diagnosis of GS, the type of stenosis, the type of management, and the follow-up data. RESULTS During the study period, 1210 patients underwent primary or secondary LSG. Seventeen patients had post-operative symptoms of GS (1.4%); one patient had achalasia that had not been diagnosed preoperatively and thus was excluded from our analysis. The median time interval between LSG and diagnosis of GS was 47.2 days (1-114). Eleven patients had organic GS and six had functional GS. Seven patients required nutritional support. Endoscopic treatment was successful in 15 patients (88.2%) after balloon dilatation (n = 13) or insertion of a covered stent (n = 2). Two of the 15 patients required conversion to Roux-en-Y gastric bypass (11.8%). CONCLUSION GS after LSG is a rare complication but requires standardized management. Most cases can be treated successfully with endoscopic balloon dilatation.


title: Computed tomography scan based prediction of the vulnerable carotid plaque.

text: BACKGROUND Primary to validate a commercial semi-automated computed tomography angiography (CTA) -software for vulnerable plaque detection compared to histology of carotid endarterectomy (CEA) specimens and secondary validating calcifications scores by in vivo CTA with ex vivo non-contrast enhanced computed tomography (NCCT). METHODS From January 2014 to October 2016 53 patients were included retrospectively, using a cross-sectional design. All patients underwent both CTA and CEA. Sixteen patients had their CEA specimen NCCT scanned. The semi-automated CTA software analyzed carotid stenosis using different HU values defining plaque components. The predictive values of CTA based detection of vulnerable plaques were calculated. Quantification of calcifications on CTA using region of interest (ROI)-function and mathematical equations was done manually, and validated by NCCT of the CEA specimen. RESULTS The semi-automated CTA software had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 89.1% (95% CI, 73.6% - 96.4%), 31.3% (95% CI, 12.1% - 58.5%), 75% (95% CI, 59.3% - 86.2%) and 55.6% (95% CI, 22.6% - 84.6%). Strong correlation between in vivo CTA and ex vivo NCCT in quantification of calcification was observed, but CTA systematically underestimated calcificationsscore (CALS) with increasing calcification. CONCLUSION The CTA-software cannot be used in risk assessment of patients, due to poor specificity and NPV. The correlation between in vivo CTA and ex vivo NCCT was strong, proposing it to be used in both scientifically and clinical settings, but studies with larger sample sizes are needed.


Covid-19: all non-urgent elective surgery is suspended for at least three months in England.


title: Propranolol stops progressive multiple cerebral cavernoma in an adult patient.

text: OBJECTIVE To report a case of a patient with multiple cerebral cavernous malformations (CCM). OBSERVATION A 22year old man with mild von Willebrand disease presented with two occipital CCM, one of them with acute hemorrhage. Genetic testing for CCM1-3 did not reveal a mutation. Over a period of 54months, the patient suffered 26 new CCM hemorrhages despite multiple treatment attempts including thalidomide, simvastatin and hemostatic factors. Only after initiation of propranolol, which has already been successfully used in three children with giant cerebral cavernoma, the occurrence of new CCM with hemorrhages was completely stopped already at dose of 30mg daily - now for a period of 26months and without any other medications. CONCLUSION This case suggests a protective role for propranolol in preventing the occurrence of new cerebral cavernoma with hemorrhages in adults with multiple CCM.


Resuscitating Patient Rights during the Pandemic: COVID-19 and the Risk of Resurgent Paternalism.


title: World Workshop on Oral Medicine VII: Non-opioid pain management of head and neck chemo/radiation-induced mucositis: A systematic review.

text: OBJECTIVE To evaluate the current evidence regarding the effectiveness of non-opioid interventions for the therapeutic management of pain in head and neck cancer patients with oral mucositis resulting from radiotherapy only or chemoradiotherapy. MATERIALS AND METHODS A literature search was conducted which included randomised controlled trials that assessed patient-related outcome of pain in patients with oral mucositis associated with radiation therapy only or chemoradiotherapy. Literature searches were conducted in MEDLINE via Pubmed, Embase, Scopus and CINAHL. RESULTS The electronic searches identified 846 articles. Screening revealed that six articles met all eligibility inclusion criteria. Interventions showing statistically significant benefits to reduce oral mucositis associated pain compared to placebo included doxepin (p < 0.001, 95% CI -6.7 to -2.1), amitriptyline (p = 0.04), diclofenac (p < 0.01) and benzydamine (p = 0.014). CONCLUSIONS Non-opioid interventions, including topical doxepin, amitriptyline, diclofenac and benzydamine, were found to provide relief of pain due to mucositis, and when effective may allow for reduction in the use of opioids in pain management.


Latin America and Its Global Partners Toil to Procure Medical Supplies as COVID-19 Pushes the Region to Its Limit.


Ground-glass opacity on chest computed tomography in a young, athletic man with COVID-19-related pneumonia without hypoxemia.


title: Cholesterol conjugation potentiates the antiviral activity of an HIV immunoadhesin.

text: Immunoadhesins are engineered proteins combining the constant domain (Fc) of an antibody with a ligand-binding (adhesion) domain. They have significant potential as therapeutic agents, because they maintain the favourable pharmacokinetics of antibodies with an expanded repertoire of ligand-binding domains: proteins, peptides, or small molecules. We have recently reported that the addition of a cholesterol group to two HIV antibodies can dramatically improve their antiviral potency. Cholesterol, which can be conjugated at various positions in the antibody, including the constant (Fc) domain, endows the conjugate with affinity for the membrane lipid rafts, thus increasing its concentration at the site where viral entry occurs. Here, we extend this strategy to an HIV immunoadhesin, combining a cholesterol-conjugated Fc domain with the peptide fusion inhibitor C41. The immunoadhesin C41-Fc-chol displayed high affinity for Human Embryonic Kidney (HEK) 293 cells, and when tested on a panel of HIV-1 strains, it was considerably more potent than the unconjugated C41-Fc construct. Potentiation of antiviral activity was comparable to what was previously observed for the cholesterol-conjugated HIV antibodies. Given the key role of cholesterol in lipid raft formation and viral fusion, we expect that the same strategy should be broadly applicable to enveloped viruses, for many of which it is already known the sequence of a peptide fusion inhibitor similar to C41. Moreover, the sequence of heptad repeat-derived fusion inhibitors can often be predicted from genomic information alone, opening a path to immunoadhesins against emerging viruses.


title: Evaluation of national pandemic management policies-A hazard analysis of critical control points approach.

text: Analyses of pandemic preparedness policies revealed weaknesses in control systems of European nations. This reinforces the need to support countries in their endeavours to prevent and contain pandemics. A Hazard Analysis and Critical Control Points (HACCP) was applied to a generic plan to identify weaknesses in pandemic management policies, in order to develop recommendations for improving national pandemic management systems. Policy components considered in our analysis are command and control, early case detection and disease surveillance, and community containment management. The main critical areas identified in national pandemic control were: communication systems among all institutions and levels involved in pandemic management, guidelines and regulations describing how key personal and institutions should operate during a pandemic, training and dissemination of information to health care personnel involved in outbreak management. The HACCP analysis highlighted the need for agreed communication structures, clear division of responsibilities and harmonised policy guidelines at all levels of pandemic management. Being prepared is the key to successfully coordinate and implement response measures when a pandemic emerges.


Audio Interview: Preparing for the Spread of Covid-19.


title: Application of temporary inflow control of the Glissonean pedicle method provides a safe and easy technique for totally laparoscopic hemihepatectomy by Glissonean approach.

text: The Glissonian approach, due to its simplicity of procedure, is a technical procedure widely used in open hepatectomy. However, it is not easily applicable in the setting of the total laparoscopic approach because of movement restriction. We herein propose a new and simple method of performing hemihepatectomy by Glissonian approach called temporary inflow control of the Glissonian pedicle (TICGL) technique. Dissection of the Glisson pedicle from the liver parenchyma is done until the posterior margin of the pedicle is visualized, and is clamped with bulldog clamps. Encircling the pedicle is not necessary. Resection of the liver parenchyma is performed under inflow control of the resected side liver providing less bleeding. After sufficient resection is done so that the whole Glissonian pedicle structures are visualized, the pedicle is encircled, often very easily without the fear of bleeding from the posterior side of the pedicle, which is a common problem when encircling is done before parenchymal resection. The staplers may then be applied safely without injuring the major hepatic veins since they have been already exposed. Stapling is done while the tape is retracted toward the contralateral side. This retraction prevents injury or stricture of the contralateral Glissonian pedicle branch. The remnant liver parenchyma is resected and hepatectomy finalized. The TICGL technique provides a safe and easy way of performing major hemihepatectomies, not only by expert laparoscopic surgeons but by less experienced surgeons. It can therefore become a standard method of performing hemihepatectomy by Glissonian approach.


title: Retrieval study at 623 human mesh explants made of polypropylene--impact of mesh class and indication for mesh removal on tissue reaction.

text: Textile meshes frequently are implanted in the abdominal wall to reinforce a hernia repair. However, revisions for mesh associated complications confirm that these devices are not completely free of risk. Explanted devices offer an opportunity to define the impact of mesh structure on tissue response. This retrieval study analyses the tissue reaction to 623 polypropylene mesh samples (170 class 1 with large pores, and 453 class 2 with small pores) explanted for pain, infection, or recurrence. Histopathological assessment included morphometry of inflammatory infiltrate (IF) and connective tissue (CT), and of collagen 1/3 ratio. Half of the meshes were removed after more than 23 month. Despite large inter-individual differences removal for infection showed more IF than for pain or recurrence with significant correlation of IF with CT. Class 1 meshes with large pores showed less IF, CT, fistula formation, calcification, and bridging than class 2 meshes with small pores. Meshes removed for recurrence showed a lowered collagen 1/3 ratio in 70%. Large pore class 1 meshes showed an improved tissue response and may be considered as favorable to prevent inflammatory side effects. The presence of lowered collagen 1/3 ratio in most of the samples with recurrences stresses the relevance of an intact healing process. Late manifestation of complications demands long-lasting follow-up.


title: Effectiveness of the Middle East respiratory syndrome-coronavirus protocol in enhancing the function of an Emergency Department in Qatar.

text: OBJECTIVE This study aimed to investigate the effectiveness of a Middle East respiratory syndrome coronavirus (MERS-CoV) surveillance protocol in the Emergency Department (ED) at Hamad General Hospital. Effectiveness was measured by: (a) reduction in the number of patients admitted into the MERS-CoV tracking system; (b) identification of positive MERS-CoV cases; (c) containment of cross infectivity; and (d) increased efficiency in ED functioning. METHODS A retrospective chart review was carried out of all ED patients suspected of MERS-CoV during the height of the epidemic (August to October 2013). An algorithm was created on the basis of international guidelines to screen and triage suspected MERS-CoV patients. Once identified, patients were isolated, had a chest roentgenogram [chest radiography (CXR)] taken, and a nasopharyngeal swab for polymerase chain reaction (PCR) was sent with sputum samples for testing. Patients with normal CXR and mild respiratory symptoms were discharged with home isolation instructions until nasopharyngeal and sputum PCR results were available. Patients with fever and acute respiratory distress, with or without abnormal CXR, were treated in the hospital until tests proved negative for MERS-CoV. RESULTS The protocol successfully reduced the number of patients who needed to be tested for MERS-CoV from 12,563 to 514, identified seven positive cases, and did not lead to apparent cross infectivity that resulted in serious illness or death. The protocol also increased the efficiency of ED and cut the turnaround time for nasopharyngeal swab and sputum results from 3 days to 1 day. CONCLUSION A highly protocolized surveillance system limited the impact of MERS-CoV on ED functioning by identifying and prioritizing high-risk patients. The emergence of new infectious diseases requires constant monitoring of interventions to reduce the impact of epidemics on population health and health services.


title: Associations between use of prasugrel vs clopidogrel and outcomes by type of acute coronary syndrome: an analysis from the PROMETHEUS registry.

text: We sought to investigate the utilization of prasugrel and its association with outcomes relative to clopidogrel in three typical subgroups of ACS in a real-world setting. Prasugrel is superior to clopidogrel for reducing risk of ischemic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), but is associated with an increased risk of bleeding complications. PROMETHEUS was a retrospective multicenter observational study of 19,913 ACS patients undergoing PCI from 8 centers in the United States between 2010 and 2013. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause mortality, myocardial infarction, stroke or unplanned revascularization. The study cohort included 3285 (16.5%) patients with ST-segment elevation myocardial infarction (STEMI), 5412 (27.2%) patients with NSTEMI and 11,216 (56.3%) patients with unstable angina (UA). The frequency of prasugrel use at discharge was highest in STEMI and lowest in UA patients, 27.3% versus 22.2% versus 18.9% (p < 0.001). Use of prasugrel vs clopidogrel was associated with a lower rate of MACE in STEMI, NSTEMI, or UA at 1 year, but the differences were attenuated for all groups except for patients with UA (adjusted HR 0.81, 95% CI 0.69-0.94, p = 0.006) after propensity adjusted analysis. After adjustment, there was no difference in bleeding risk between prasugrel and clopidogrel for all groups at 1 year. STEMI patients were more likely to receive prasugrel compared to NSTEMI and UA patients. Prasugrel was associated with reduced adverse outcomes compared with clopidogrel in unadjusted analyses, findings that were largely attenuated upon adjustment and suggest preferential use of prasugrel in low vs high risk patients.


title: Robotic removal of eroded vaginal mesh into the bladder.

text: Vaginal mesh erosion into the bladder after midurethral sling procedure or cystocele repair is uncommon, with only a few cases having been reported in the literature. The ideal surgical management is still controversial. Current options for removal of eroded mesh include: endoscopic, transvaginal or abdominal (either open or laparoscopic) approaches. We, herein, present the first case of robotic removal of a large eroded vaginal mesh into the bladder and discuss potential benefits and limitations of the technique.


title: Comparison of Barbed Sutures in Porcine Flexor Tenorrhaphy.

text: Background: Barbed suture use has become more popular as technology and materials have advanced. Minimal data exist regarding performance of the 2 commercially available products, V-LocTM and StratafixTM in tendon repairs. The purpose of this study was to compare gap resistance and ultimate tensile strength of both suture materials and nonbarbed suture in a porcine ex vivo model. Methods: Porcine flexor tendons were harvested and divided into 3 groups of 10 of varying suture material (3-0 PDS™, 3-0 V- V-Loc 180™, or 3-0 Stratafix™). A modified 4-strand cruciate technique was used to repair each tendon. Knotless repair was performed using barbed suture, whereas a buried 6-throw square knot was done using conventional suture. A servohydrolic tester was used for biomechanical testing of linear 2-mm gap resistance and maximum tensile strength. Results: No difference was found in 2-mm gap resistance among the 3 groups. No difference was found in ultimate tensile strength between V-Loc™ (76.0 ± 9.4 N) and Stratafix™ (68.1 ± 8.4 N) repairs, but the ultimate strength of the PDS™ control group (83.4 ± 10.0 N) was significantly higher than that of Stratafix™. Conclusions: Barbed (knotless) and nonbarbed suture repairs demonstrate equivalent 2-mm gap resistance. Stratafix™ repairs show slightly inferior performance to nonbarbed repairs in ultimate tensile strength, although this occurred at gap distances far beyond the 2-mm threshold for normal tendon gliding. Both barbed and nonbarbed 4-strand cruciate flexor tendon repairs may require peripheral repair to withstand physiologic loads.


title: How to Produce Cheap and Easy Custom-Made Sterilizable Filtering Facepiece 2/3 Masks for Healthcare Providers During Pandemic COVID-19 Emergency.

text: On January 8, 2020, a novel coronavirus was officially announced as the causative pathogen of coronavirus disease (COVID-19) by the Chinese Center for Disease Control and Prevention.On February 26, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed patients and 2700 deaths.Protecting healthcare workers from infectious hazards is paramount to ensuring their safety in delivering health care.In addition, being able to protect healthcare workers, constituting the front-line response against high-threat respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2, is important for reducing secondary transmission in healthcare-associated outbreaks.Authors present a simple, reliable, and cheap protocol to produce a custom-made sterilizable filtering facepiece 2/3 masks for healthcare providers during pandemic COVID-19 emergency.


title: Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63.

text: The human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding with higher efficiency than NL63-S. Shedding most likely accounted for the previously observed ACE2 downregulation but was dispensable for viral replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2-positive Vero cells and reduced ACE2 expression, indicating robust receptor interference in the context of SARS-CoV but not NL63 infection.


Smartphone based ROP (S-ROP) screening-opportunities and challenges.


Cholestasis: current issues and plan for the future.


title: Increased level of protection of respiratory tract and kidney by combining different infectious bronchitis virus vaccines against challenge with nephropathogenic Brazilian genotype subcluster 4 strains.

text: Genotyping of seven infectious bronchitis virus (IBV) strains isolated in Brazil showed that all belonged to the common Brazilian genotype and that these strains were closest to the subcluster of strain IBV/Brazil/2007/USP-19. Pathotyping of four selected Brazilian strains showed that they all caused a considerable level of ciliostasis in the trachea but at a somewhat lower level than did M41 and Brazilian strains 50/96, 57/96, 62/96 and 64/96 representing four different serotypes that had been reported earlier. In contrast to the M41 challenge strain, all Brazilian isolates replicated in kidney tissue in a high percentage of non-vaccinated challenged birds, clearly showing that they are nephropathogenic. As for the tracheal protection, the results using Massachusetts (Mass) vaccination against the recent strains seemed to show protection higher on average than for the strains reported earlier. A single or twofold vaccination with a Mass vaccine resulted in a mean tracheal protection level against the four challenge strains of 92% and 90%, respectively, whereas a single and twofold vaccination with a Mass vaccine halved the percentage of infected kidneys (14% and 13%, respectively, P < .05) compared to that of the unvaccinated birds (27%). The combination of the Mass and the 793B vaccine provided on average a tracheal protection of 99% and a reduction of the percentage of infected kidneys to a mean of 2%. This was a significantly (P < .05) higher protection than that achieved by a single or twofold Mass vaccination, showing the added value of the 793B vaccination following priming with a vaccine of the Mass type.


title: Evaluation of cerebral circulation during retrograde perfusion by laser speckle flowgraphy.

text: Laser speckle flowgraphy (LSFG) is an ophthalmologic equipment that qualitatively detects the blood flow of the optic nerve head, which is known to be related with cerebral microcirculation. LSFG can also measure the mean blur rate, which quantitatively calculates the blood flow. We aimed to assess the utility of LSFG in the evaluation of cerebral perfusion during aortic surgery under hypothermic circulatory arrest with retrograde and antegrade cerebral perfusion. Two patients underwent total arch replacement for aneurysm. The blood flow of the optic nerve head was monitored with LSFG and the mean blur rate value was measured during the surgery. The LSFG could detect the blood flow quantitatively in the optic nerve head during both retrograde and antegrade cerebral perfusion; and the value was correlated with rSO2 value.


title: Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): an OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis.

text: INTRODUCTION Observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) to date investigating the efficacy of vitamin D supplementation in knee OA have reported conflicting results. Further research is needed to clarify the effects of vitamin D on patient-reported outcomes and determine whether there are patient subgroups who may benefit from the supplementation. The aim of this individual patient data (IPD) meta-analysis is to identify patient-level predictors of treatment response to vitamin D supplementation on pain and physical function. METHODS AND ANALYSIS A systematic literature search will be conducted for RCTs of vitamin D supplementation on knee OA. Authors of original RCTs will be contacted to obtain the IPD. The primary outcomes will include long-term (≥12 months) pain and physical function. Secondary outcomes will include medium-term (≥6 months and <12 months) and short-term (<6 months) pain and physical function, as well as patient global assessment, quality of life and adverse events. Potential treatment effect modifiers to be examined in the subgroup analyses include age, gender, body mass index, baseline knee pain severity and physical function, baseline vitamin D level, radiographic stage, presence of bone marrow lesions on MRI, presence of clinical signs of local inflammation and concomitant depressive symptoms. Both one-step and two-step modelling methods will be used to determine the possible modifiable effect of each subgroup of interest. ETHICS AND DISSEMINATION Research ethical or governance approval is exempt for this study as no new data are being collected. This study will be the first IPD meta-analysis to clarify the effect of vitamin D supplementation on clinical symptoms in different subgroups of patients with knee OA. The findings will be disseminated through peer-review publications and conference presentations. PROSPERO REGISTRATION NUMBER CRD42018107740.


title: Nonhuman Animals, Public Health, and Ethics: A First Step, But….

text: In December 2015, the Johns Hopkins Bloomberg School of Public Health held the first-ever summit on the intersection between nonhuman animal ethics and human health. The conference covered a variety of issues where animal health intersects with human health, including the wildlife trade, animal agriculture, and animal experimentation. This article provides a brief overview and critique of the summit.


title: Prone Positioning for Pregnant Women With Hypoxemia Due to Coronavirus Disease 2019 (COVID-19).

text: The coronavirus disease 2019 (COVID-19) pandemic has prompted expanded use of prone positioning for refractory hypoxemia. Clinical trials have demonstrated beneficial effects of early prone positioning for acute respiratory distress syndrome (ARDS), including decreased mortality. However, pregnant women were excluded from these trials. To address the need for low-cost, low-harm interventions in the face of a widespread viral syndrome wherein hypoxemia predominates, we developed an algorithm for prone positioning of both intubated and nonintubated pregnant women. This algorithm may be appropriate for a wide spectrum of hypoxemia severity among pregnant women. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is responsible for the clinical manifestations of COVID-19. This syndrome can manifest as severe pneumonia complicated by hypoxemia and ARDS. Given the current global COVID-19 pandemic, with a large number of ARDS cases, there is renewed interest in the use of prone positioning to improve oxygenation in moderate or severe hypoxemia. Among the populations who can benefit from prone positioning are pregnant women experiencing severe respiratory distress, as long as the physiologic changes and risks of pregnancy are taken into account.


title: Identifying and understanding the health and social care needs of Indigenous older adults with multiple chronic conditions and their caregivers: a scoping review.

text: BACKGROUND Indigenous people continue to experience high rates of multiple chronic conditions (MCC) at younger ages than other populations, resulting in an increase in health and social care needs. Those who provide services designed to address MCC for Indigenous communities require synthesized information to develop interventions that meet the needs of their older adult population. This review seeks to answer the research question: What are the health and social care needs, priorities and preferences of Indigenous older adults (living outside of long-term care settings) with MCC and their caregivers? METHODS A scoping review, guided by a refinement of the Arksey & O'Malley framework, was conducted. Articles were included if the authors reported on health and social care needs and priorities of older Indigenous adults. We also included articles that focused on Indigenous conceptions of wellness, resilience, well-being, and/or balance within the context of aging, and articles where authors drew from Indigenous specific worldviews, ways of knowing, cultural safety, cultural competence, cultural appropriateness, cultural relevance and community needs. RESULTS This scoping review included 9 articles that were examined using an Indigenous determinants of health (IDH) theoretical framework to analyze the needs of older adults and CGs. Five areas of needs were identified: accessible health services; building community capacity; improved social support networks; preservation of cultural values in health care; and wellness-based approaches. CONCLUSION The review highlights key determinants of health that influenced older adults' needs: education and literacy, ethnicity, and social support/network (proximal); health promotion and health care (intermediate); and a combination of historical and contemporary structures (distal). The findings highlight the importance of local Indigenous knowledge and perspectives to improve accessibility of culturally relevant health and social services.


title: African Swine Fever Epidemic, Poland, 2014-2015.

text: In Poland, African swine fever (ASF) emerged in February 2014; by August 2015, the virus had been detected in >130 wild boar and in pigs in 3 backyard holdings. We evaluated ASF spread in Poland during these 18 months. Phylogenetic analysis indicated repeated incursions of genetically distinct ASF viruses of genotype II; the number of cases positively correlated wild boar density; and disease spread was very slow. More cases were reported during summer than autumn. The 18-month prevalence of ASF in areas under various animal movement restrictions was 18.6% among wild boar found dead or killed by vehicles and only 0.2% in hunted wild boar. Repeated introductions of the virus into the country, the primary role of wild boar in virus maintenance, and the slow spread of the disease indicate a need for enhanced biosecurity at pig holdings and continuous and intensive surveillance for fast detection of ASF.


Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection.


Communicating Effectively With Hospitalized Patients and Families During the COVID-19 Pandemic.


title: Intravital pathophysiological comparison of acid- and alkali-burn injuries in a murine model.

text: BACKGROUND The breakdown of skin microcirculation plays a key role in the pathophysiology of chemical burns. Available data for alkali and acid injuries are rare. To determine the pathophysiological similarities and differences, two comparable in vivo acid and alkali burn models were developed. MATERIALS AND METHODS Deep partial-thickness acid burns (32% hydrochloric acid) or alkali burns (11% sodium hydroxide solution) were inflicted to the ears of hairless mice (n = 17). Intravital fluorescent microscopy was used to assess microcirculation, angiogenesis, and leukocyte-endothelium interaction over a 21-d period. RESULTS The angiogenesis occurred significantly faster after acid burns than after alkali burns in the first 3 days (nonperfused area day 3, 80% ± 9% [acid] versus 94% ± 17% [alkali]; P = 0.045) and then a significant acceleration occurs in the alkali group: nonperfused area day 14, 27% (alkali) versus 57% (acid), P = 0.004. The loss of functional vessel density was more pronounced after acid burns (directly after trauma, 87% [alkali] versus 79% [acid], P = 0.049). The other parameters such as rolling and sticking leukocytes, edema formation, and arteriolar and venular red blood cell velocities and diameters showed similar results. CONCLUSIONS The comparison of analogous intravital acid and alkali burns shows that despite many similarities in the microcirculatory parameters, there was a marked difference particularly in the course of the tissue regeneration by angiogenesis. The longer lasting destruction by alkali burns stands in contrast to the later onset but faster regeneration by angiogenesis compared with that by acid burns.


Mechanical Thrombectomy Trials with the Solitaire™ FR Device: A Global Perspective: Satellite Symposium - Wednesday, May 29, 2013.


title: Preclinical characterization of BMS-791325, an allosteric inhibitor of hepatitis C Virus NS5B polymerase.

text: BMS-791325 is an allosteric inhibitor that binds to thumb site 1 of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. BMS-791325 inhibits recombinant NS5B proteins from HCV genotypes 1, 3, 4, and 5 at 50% inhibitory concentrations (IC50) below 28 nM. In cell culture, BMS-791325 inhibited replication of HCV subgenomic replicons representing genotypes 1a and 1b at 50% effective concentrations (EC50s) of 3 nM and 6 nM, respectively, with similar (3 to 18 nM) values for genotypes 3a, 4a, and 5a. Potency against genotype 6a showed more variability (9 to 125 nM), and activity was weaker against genotype 2 (EC50, 87 to 925 nM). Specificity was demonstrated by the absence of activity (EC50s of >4 μM) against a panel of mammalian viruses, and cytotoxic concentrations (50%) were >3,000-fold above the HCV EC50. Resistance substitutions selected by BMS-791325 in genotype 1 replicons mostly mapped to a single site, NS5B amino acid 495 (P495A/S/L/T). Additive or synergistic activity was observed in combination studies using BMS-791325 with alfa interferon plus ribavirin, inhibitors of NS3 protease or NS5A, and other classes of NS5B inhibitor (palm site 2-binding or nucleoside analogs). Plasma and liver exposures in vivo in several animal species indicated that BMS-791325 has a hepatotropic disposition (liver-to-plasma ratios ranging from 1.6- to 60-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥ 10-fold above the inhibitor EC50s observed with HCV genotype 1 replicons. These findings support the evaluation of BMS-791325 in combination regimens for the treatment of HCV. Phase 3 studies are ongoing.


UK vets coping well with global pandemic.


Os direitos humanos das crianças com deficiência durante emergências de saúde: o desafio do COVID-19.


title: Production of isopropyl and butyl esters by Clostridium mono-culture and co-culture.

text: Production of esters from the acetone-butanol-ethanol (ABE) fermentation by Clostridium often focuses on butyl butyrate, leaving acetone as an undesired product. Addition of butyrate is also often needed because ABE fermentation does not produce enough butyrate. Here we addressed the problems using Clostridium beijerinckii BGS1 that preferred to produce isopropanol instead of acetone, and co-culturing it with Clostridium tyrobutyricum ATCC 25,755 that produced butyrate. Unlike acetone, isopropanol could be converted into ester using lipase and acids. C. tyrobutyricum ATCC 25,755 produced acids at pH 6, while C. beijerinckii BGS1 produced mainly solvents at the same pH. When the two strains were co-cultured, more butyrate was produced, leading to a higher titer of esters than the mono-culture of C. beijerinckii BGS1. As the first study reporting the production of isopropyl butyrate from the Clostridium fermentation, this study highlighted the potential use of lipase and co-culture strategy in ester production.


title: Practical considerations in the anaesthetic management of patients during a COVID-19 epidemic.

text: We read with interest the excellent Association guidelines [1] for the anaesthetic management of patients during a COVID-19 outbreak. We concur with these guidelines, which are not dissimilar to our hospital's protocols since Singapore reported its first case of COVID-19 on 23 January 2020. To date, there have been 226 confirmed cases in Singapore with no deaths reported [2]. We are preparing for many more when community transmission becomes widespread and every patient presenting for surgery becomes a potential asymptomatic infected case. We would like to highlight additional anaesthetic considerations in this COVID-19 pandemic. Our discussion is limited to patients not known to be COVID infected.


title: Successful vaccination strategies that protect aged mice from lethal challenge from influenza virus and heterologous severe acute respiratory syndrome coronavirus.

text: Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP(3014)) or wild-type VEE glycoproteins (VRP(3000)) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP(3000)-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP(3014)-based vaccines were not. The superior protection for the aged observed with VRP(3000)-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP(3000) vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP(3014) platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.


title: TRAF4 knockdown triggers synergistic lethality with simultaneous PARP1 inhibition in endometrial cancer.

text: Endometrial cancer (EC) is one of the most common cancers among females worldwide. Advanced stage patients of EC have poor prognosis. Inevitable side effects and treatment tolerance of chemotherapy for EC remain to be addressed. Our results in this study showed that EC cells with higher tumor necrosis factor receptor-associated factor 4 (TRAF4) expression have lower sensitivity to poly ADP-ribose polymerase 1 (PARP1) inhibitors. Upon TRAF4 knockdown, the colony numbers of EC cells were markedly down-regulated, and the markers of DNA double-strand breakage were significantly up-regulated after the treatment of olaparib, a PARP1 inhibitor. TRAF4 knockdown reduced the phosphorylation of protein kinase B (Akt), promoted DNA double-strand breakage, and decreased levels of DNA repair related proteins, including phosphorylated-DNA-dependent protein kinase (p-DNA-PK) and RAD51 recombinase (RAD51). In addition, TRAF4's effect on the sensitivity of EC cells to olaparib was further found to be mainly mediated by Akt phosphorylation. Moreover, in vivo results showed that TRAF4 knockdown enhanced the sensitivity of EC to PARP1 inhibitors using a mouse xenograft model. Collectively, our data suggest that combined application of TRAF4 knockdown and PARP1 inhibition can be used as a promising strategy for synthetic lethality in EC treatment.


title: What factors predict recurrence of a spontaneous pneumothorax?

text: BACKGROUND The purpose of this retrospective study was to identify the risk factors for postoperative recurrence for the patients with a spontaneous pneumothorax (SP). A total of 214 patients were studied over a period of five years. Of these patients, 189 (88.3%) and 25 (11.7%) underwent video assisted thoracoscopic surgery (VATS) and an open approach for treatment, respectively. There were 35 (16.4%) postoperative recurrences. METHODS The data on patient characteristics, surgical details, and perioperative outcomes were analyzed. We compared the clinicopathological characteristics between recurrent and non-recurrent cases, and used logistic regression models to predict the risk factors for postoperative recurrence. RESULTS The differences in the age, gender, lesion site, location, ipsilateral SP (ISP), and contralateral SP (CSP) did not reach statistical significance between the two groups. However, the incidence of recurrence was higher in the subjects without any smoking history, and who had comorbidities, and a history of surgery for ISP. Concerning intraoperative factors, there were no significant differences with regard to the approach, buttress stapling, covering, surgeon, or length of the operation. The postoperative recurrence rate was higher in the patients who had been hand-stitched compared to those who had undergone instrument-based repair for blebs. There were no significant differences in the perioperative outcomes. The logistic regression models indicated that non smokers, those with comorbidities, and those who had previously undergone surgery for ISP had a higher rate of postoperative recurrence. CONCLUSIONS We conclude that a history of no smoking, the existence of comorbidities, previous surgery for ISP, and hand stitching increase the risk of postoperative recurrence. Therefore, surgeons must be aware of these risk factors, and more carefully monitor such patients for recurrence.


title: Usefulness of repair using Hem-o-lok™ for peritoneal tear as a complication of totally extraperitoneal repair: Case series.

text: Introduction Peritoneal tear (PT) is a frequent intraoperative event during totally extraperitoneal repair (TEP). We aimed to introduce our surgical technique for PT during TEP to avoid the more difficult TEP procedure.MethodsOne surgeon with 10 years of experience performed our TEP method in 147 TEP cases from January 2012 to June 2019. We investigated the repair time of each repair technique using endoscopic suturing (suturing group, SG) and endoscopic Hem-o-lok stapling (CG). Results Twenty-three (15.6%) PT cases occurred as TEP complication. The mean repair times (with standard deviation) of the PT were 16.2 ± 13 and 7.6 ± 7.0 min in the SG and CG, respectively, indicating a significant difference (P = 0.043). The repair time of the PT using Hem-o-lok (Teleflex, Wayne, PA, USA) stapling was shorter than that using endoscopic suturing, which was significantly different despite the length of the PT. Conclusion Hem-o-lok stapling is feasible in case of PT during TEP.


title: Stop playing with data: there is no sound evidence that Bacille Calmette-Guérin may avoid SARS-CoV-2 infection (for now).

text: Since the beginning of the COVID-19 epidemic, a possible explanation for the high heterogeneity of infection/mortality rates across involved countries was hinted in the prevalence of tuberculosis vaccination with Bacille Calmette-Guérin (BCG). A systematic review was therefore performed on May 2, 2020. A total of 13 articles were ultimately retrieved, 12 of them as preprint papers. All articles were ecological studies of low quality. Most of them did not include main confounding factors (i.e. demographic of the assessed countries, share of peo- ple residing in urban settings, etc.), and simply assessed the differences among incidence/mortality of COVID-19 with vaccination rates or by having vs. having not any vaccination policy for BCG. Even though all studies shared the very same information sources (i.e. international registries for BCG vaccination rates and open source data for COVID-19 epidemics), results were conflicting, with later studies apparently denying any true correlation between COVID-19 occurrence and BCG vaccination rates and/or policies. As a consequence, there is no sound evidence to recommend BCG vaccination for the prevention of COVID-19.


Antiviral gets the jump on coronaviruses.