title: Chlorhexidine gluconate or polyhexamethylene biguanide disc dressing to reduce the incidence of central-line-associated bloodstream infection: a feasibility randomized controlled trial (the CLABSI trial).

text: BACKGROUND A number of antimicrobial-impregnated discs to prevent central-line-associated bloodstream infection (CLABSI) are marketed but it is unclear which disc is most effective. AIM To investigate the feasibility and safety of comparing two antimicrobial-impregnated discs to prevent CLABSI. METHODS A single-centre, parallel group, randomized controlled trial was conducted in a 929-bed tertiary referral hospital. Hospital inpatients requiring a peripherally inserted central catheter were randomized to chlorhexidine gluconate (CHG) or polyhexamethylene biguanide (PHMB) disc dressing group. Dressings were replaced every seven days, or earlier, if clinically required. Participants were followed until device removal or hospital discharge. Feasibility outcomes included: proportion of potentially eligible participants who were enrolled; proportion of protocol violations; and proportion of patients lost to follow-up. Clinical outcomes were: CLABSI incidence, diagnosed by a blinded infection control practitioner; all-cause bloodstream infection (BSI); and product-related adverse events. FINDINGS Of 143 patients screened, 101 (71%) were eligible. Five (3.5%) declined participation. There was one post-randomization exclusion. Two (2%) protocol violations occurred in the CHG group. No patients were lost to follow-up. Three (3%) BSIs occurred; two (2%) were confirmed CLABSIs (one in each group) and one a mucosal barrier injury-related BSI. A total of 1217 device-days were studied, resulting in 1.64 CLABSIs per 1000 catheter-days. One (1%) disc-related adverse event occurred in the CHG group. CONCLUSION Disc dressings containing PHMB are safe to use for infection prevention at catheter insertion sites. An adequately powered trial to compare PHMB and CHG discs is feasible.


title: Prosthetic graft reconstruction after portal vein resection in pancreaticoduodenectomy: a multicenter analysis.

text: BACKGROUND Use of prosthetic grafts for reconstruction after portal vein (PV) resection during pancreaticoduodenectomy is controversial. We examined outcomes in patients who underwent vein reconstruction using polytetrafluoroethylene (PTFE). STUDY DESIGN Review of prospectively maintained databases at 3 centers identified all patients who underwent pancreaticoduodenectomy (PD) with vein resection and reconstruction using PTFE grafts between 1994 and 2009. Patient, operative, and outcomes variables were studied. Graft patency and survival were assessed using the Kaplan-Meier technique. RESULTS Thirty-three patients underwent segmental vein resection with interposition PTFE graft reconstruction. Median age was 67 years; median Eastern Cooperative Oncology Group score was 1. Most operations were performed for pancreatic adenocarcinoma (n = 28, 85%); 96% were T3 lesions or greater. Standard PD was performed in 12 (36%) patients, pylorus-preservation in 17 (52%), and total pancreatectomy in 4 (12%). Combined resection of portal and superior mesenteric veins (SMV) was required in 49%, with resection isolated to PV in 12% and SMV in 39%. Splenic vein ligation was necessary in 30%. Median graft diameter was 12 mm (range 8 to 20 mm), with the majority being ring-enforced (73%). Median operative and vascular clamp times were 463 and 41 minutes, respectively, with median blood loss of 1,500 mL. The negative margin rate was 64%. Overall morbidity rate was 46%, and 30-day mortality was 6%. No patients developed irreversible hepatic necrosis or graft infection. Pancreatic fistulas occurred in 3 (9.1%). With mean follow-up of 14 months, overall graft patency was 76%. Estimated median duration of graft patency was 21 months. Median survival was 12 months for pancreatic adenocarcinoma. CONCLUSIONS With careful patient selection, PTFE graft reconstruction of resected PV/SMV during pancreaticoduodenectomy is possible with minimal risk of hepatic necrosis or graft infection. Comparison studies to primary anastomosis and autologous vein reconstruction are necessary.


title: Off-label prescribing in the midst of a pandemic: The case of hydroxychloroquine.

text: There is currently no robust evidence to support prescribing hydroxychloroquine as a treatment or prophylaxis for COVID-19.


title: Recombinant protein-based viral disease diagnostics in veterinary medicine.

text: Identification of pathogens or antibody response to pathogens in human and animals modulates the treatment strategies for naive population and subsequent infections. Diseases can be controlled and even eradicated based on the epidemiology and effective prophylaxis, which often depends on development of efficient diagnostics. In addition, combating newly emerging diseases in human as well as animal healthcare is challenging and is dependent on developing safe and efficient diagnostics. Detection of antibodies directed against specific antigens has been the method of choice for documenting prior infection. Other than zoonosis, development of inexpensive vaccines and diagnostics is a unique problem in animal healthcare. The advent of recombinant DNA technology and its application in the biotechnology industry has revolutionized animal healthcare. The use of recombinant DNA technology in animal disease diagnosis has improved the rapidity, specificity and sensitivity of various diagnostic assays. This is because of the absence of host cellular proteins in the recombinant derived antigen preparations that dramatically decrease the rate of false-positive reactions. Various recombinant products are used for disease diagnosis in veterinary medicine and this article discusses recombinant-based viral disease diagnostics currently used for detection of pathogens in livestock and poultry.


title: Yemen field epidemiology training programme: a tool for strengthening the public health workforce.

text: Background The shortage of skilled public health workers, especially epidemiologists, remains an important challenge for building effective public health systems in many low-income countries, including Yemen. To address this need, in 2011 the Ministry of Public Health and Population established the Yemen Field Epidemiology Training Programme (Y-FETP). Aims To describe the Y-FETP and its strengths and challenges in addressing Yemen's National Health System (NHS) needs. Methods We describe the structure and functions of the Y-FETPs and analyse the achievements and challenges of the first 7 years of programme implementation as they relate to the NHS. Results The Y-FETP is a postgraduate competency-based training with the objective of strengthening capacity in field epidemiology so that events of public health importance can be detected and investigated in a timely and effective manner. Since its establishment, the Y-FETP has successfully trained 30 health professionals in advanced field epidemiology. Furthermore, trainees investigated over 100 outbreaks, analysed and evaluated 95 surveillance systems, conducted 30 planned studies and presented 70 oral and poster presentations at national and international conferences. The main challenges are low retention of graduates by the NHS and financial unsustainability. Conclusions The Y-FETP has strengthened the capacity of the Yemen health workforce and has been instrumental in supporting the NHS, especially during the war and the current crisis and health emergency as the security situation deteriorated and access to outside experts becomes limited. The programme provides a practical example of health systems strengthening through health workforce capacity development that can be replicated in countries with similar health workforce capacity challenges.


title: Protective Efficacy of Recombinant Modified Vaccinia Virus Ankara Delivering Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans. We tested a recombinant modified vaccinia virus Ankara (MVA) vaccine expressing full-length MERS-CoV spike (S) glycoprotein by immunizing BALB/c mice with either intramuscular or subcutaneous regimens. In all cases, MVA-MERS-S induced MERS-CoV-specific CD8(+) T cells and virus-neutralizing antibodies. Vaccinated mice were protected against MERS-CoV challenge infection after transduction with the human dipeptidyl peptidase 4 receptor. This MERS-CoV infection model demonstrates the safety and efficacy of the candidate vaccine.


title: Biodiversity, bioactive natural products and biotechnological potential of plant-associated endophytic actinobacteria.

text: Endophytic actinobacteria, which exist in the inner tissues of living plants, have attracted increasing attention among taxonomists, ecologists, agronomists, chemists and evolutionary biologists. Numerous studies have indicated that these prolific actinobacteria appear to have a capacity to produce an impressive array of secondary metabolites exhibiting a wide variety of biological activity, such as antibiotics, antitumor and anti-infection agents, plant growth promoters and enzymes, and may contribute to their host plants by promoting growth and enhancing their ability of withstanding the environmental stresses. These microorganisms may represent an underexplored reservoir of novel species of potential interest in the discovery of novel lead compounds and for exploitation in pharmaceutical, agriculture and industry. This review focuses on new findings in the isolation methods, bio- and chemical diversity of endophytic actinobacteria and reveals the potential biotechnological application. The facing problems and strategies for biodiversity research and bioactive natural products producing are also discussed.


title: Nanofibrillar cellulose-alginate hydrogel coated surgical sutures as cell-carrier systems.

text: Hydrogel nanomaterials, especially those that are of non-human and non-animal origins, have great potential in biomedical and pharmaceutical sciences due to their versatility and inherent soft-tissue like properties. With the ability to simulate native tissue function, hydrogels are potentially well suited for cellular therapy applications. In this study, we have fabricated nanofibrillar cellulose-alginate (NFCA) suture coatings as biomedical devices to help overcome some of the limitations related to cellular therapy, such as low cell survivability and distribution out of target tissue. The addition of sodium alginate 8% (w/v) increased the NFCA hydrogel viscosity, storage and loss moduli by slightly under one order of magnitude, thus contributing significantly to coating strength. Confocal microscopy showed nearly 100% cell viability throughout the 2-week incubation period within and on the surface of the coating. Additionally, typical morphologies in the dual cell culture of spheroid forming HepG2 and monolayer type SK-HEP-1 were observed. Twelve out of 14 NFCA coated surgical sutures remained intact during the suturing operation with various mice and rat tissue; however, partial peeling off was observed in 2 of the coated sutures. We conclude that NFCA suture coatings could perform as cell-carrier systems for cellular based therapy and post-surgical treatment.


title: Modified Robert Jones bandage can not reduce invisible blood loss after total knee arthroplasty: a randomized-controlled trial.

text: INTRODUCTION To compare the efficacy and safety of modified Robert Jones bandage (MRJB) and non-compressive dressing (NCD) on reducing invisible blood loss (IBL) after total knee arthroplasty (TKA). MATERIALS AND METHODS Eighty patients who underwent unilateral TKA were randomly assigned into two groups: MRJB and NCD groups. Pre- and post-operative hematocrit levels, amount of drained blood and transfused blood were measured and calculated into IBL. Pain score, amount of morphine usage, range of motion (ROM) at discharge, blood transfusion rate, and complications were also recorded and compared between both groups. RESULTS There was no significant difference in the mean IBL between MRJB (221.2 ± 233.3 ml) and NCD groups (158.5 ± 186.7 ml) (p = 0.219). Post-operative pain score at rest and during ambulation, amount of morphine usage, ROM at discharge, blood transfusion rate, and complications were also similar between two groups. CONCLUSIONS This study cannot determine the benefit of MRJB over NCD. The use of MRJB may not be necessary after primary TKA.


title: Cerebral oxygen saturation monitoring in preeclamptic pregnant women undergoing cesarean section with spinal anesthesia: a prospective, observational study.

text: It has been suggested that cerebral oximetry can detect acute and chronic changes in cerebral oxygen saturation due to pregnancy related complications. Furthermore, regional cerebral oxygenation saturation (rcSO2) decreases were obtained during spinal anesthesia for cesarean section. The aim of this prospective observational study is to compare the effects of spinal anesthesia on rcSO2 in preeclamptic and normotensive pregnant women. Preeclamptic (Group P, n = 24) and normotensive (Group N, n = 25) women with gestational week 32 and above, and scheduled for cesarean section under spinal anesthesia were included in this study. In addition to routine monitoring, rcSO2 values obtained with right and left frontal cerebral sensors (rcSO2right and rcSO2left) were recorded before (baseline) spinal injection and during the surgery. The baseline rcSO2 values were similar in both groups. In Group P, rcSO2left values were higher than Group N only 3 and 5 min after spinal injection. In Group N, rcSO2 values decreased from baseline 1, 3, 5, and 10 min after spinal injection. In Group P, rcSO2 values decreased from baseline 1, 3, 5, 10, 30 and 35 min after spinal injection and at the end of the operation. There was no difference between the number of declines and the patients with rScO2 below the cerebral hypoxic threshold. There was a positive correlation between rcSO2 and blood pressure only 5 min after spinal injection, but no correlation with peripheral oxygen saturation was detected during the operation. There is decrease in rcSO2 values after spinal anesthesia correlating with hypotension in preeclamptic women. However, the decrease is less than that of normotensive pregnant women, especially the first 5 min after spinal injection when the blood pressure is lowest. The clinical impact of these results and the relationship between cerebral desaturation and neurological complications remain to be determined.


Reassessing advance care planning in the light of covid-19.


title: ASSOCIATION OF INITIAL VIRAL LOAD IN SARS-CoV-2 PATIENTS WITH OUTCOME AND SYMPTOMS.

text: The dynamics of viral load (VL) of the 2019 novel coronavirus (SARS-CoV-2) and its association with different clinical parameters remain poorly characterized in the United States patient population. Herein we investigate associations between VL and parameters such as severity of symptoms, disposition (admission vs direct discharge), length of hospitalization, and admission to the intensive care unit, length of need for oxygen support and overall survival in a cohort of 205 patients from a tertiary care center in New York City. VL was determined using q-PCR and Log10 transformed for normalization. Univariate and multivariate regression models were used to test these associations. We found that diagnostic viral load is significantly lower in hospitalized patients than in patients not hospitalized (log10 VL = 3.3 vs.4.0; p=0.018) after adjusting for age, sex, race, BMI, and comorbidities. Higher VL was associated with shorter duration of the symptoms in all patients and hospitalized patients only and shorter hospital stay (coefficient =-2.02,-2.61, -2.18; p<0.001, p=0.002, p=0.013, respectively). No significant association was noted between VL, admission to ICU, length of oxygen support, and overall survival. Our findings suggest a higher shedding risk in less symptomatic patients; an important consideration for containment strategies in SARS-CoV-2. Furthermore, we identify a novel association between viral load and history of cancer. Larger studies are warranted to validate our findings.


title: The Chinese import ban and its impact on global plastic waste trade.

text: The rapid growth of the use and disposal of plastic materials has proved to be a challenge for solid waste management systems with impacts on our environment and ocean. While recycling and the circular economy have been touted as potential solutions, upward of half of the plastic waste intended for recycling has been exported to hundreds of countries around the world. China, which has imported a cumulative 45% of plastic waste since 1992, recently implemented a new policy banning the importation of most plastic waste, begging the question of where the plastic waste will go now. We use commodity trade data for mass and value, region, and income level to illustrate that higher-income countries in the Organization for Economic Cooperation have been exporting plastic waste (70% in 2016) to lower-income countries in the East Asia and Pacific for decades. An estimated 111 million metric tons of plastic waste will be displaced with the new Chinese policy by 2030. As 89% of historical exports consist of polymer groups often used in single-use plastic food packaging (polyethylene, polypropylene, and polyethylene terephthalate), bold global ideas and actions for reducing quantities of nonrecyclable materials, redesigning products, and funding domestic plastic waste management are needed.


Covid-19: medical students to be employed by NHS as part of epidemic response.


title: Health systems preparedness for COVID-19 pandemic.

text: Some nations in the world and some states in India have had more success in containing this pandemic. Recent efforts in strengthening the health sector have focused largely on reforms in modes of financing, but as the pandemic brings home to us, the main challenge in India remains the challenge of the organization of public services using a health systems understanding. A close to community comprehensive primary health care, quality assurance, and planned excess capacity in public health systems, a more robust disease surveillance systems that can integrate data on new outbreaks and the indigenous technological capacity to scale up innovation and manufacture of essential health commodities are some of our most important requirements for both epidemic preparedness and response.


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title: How Cyberpsychology and Virtual Reality Can Help Us to Overcome the Psychological Burden of Coronavirus.


title: The role of angiotensin-converting enzyme 2 in the pathogenesis of COVID-19: the villain or the hero?

text: Angiotensin-converting enzyme 2 (ACE 2) is the entry receptor for the novel coronavirus SARS-CoV-2, the aetiological agent of COVID-19. At the same time, ACE 2 expression decreases during COVID-19. Two seemingly contradictory relationships between the expression of ACE 2 and COVID-19 have been reported. Increased level of expression of ACE 2 may be a risk factor for the development of COVID-19 infection, while reduced ACE 2 expression during COVID-19 leads to acute respiratory distress syndrome. This article provides a comprehensive overview of available scientific knowledge about the role of ACE 2 in the pathogenesis of COVID-19, which is available up to current day. Also, it discusses unknown factors that we will have to reveal in order to understand the whole role of ACE 2 in the pathogenesis of COVID-19.


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title: Wildlife diseases in New Zealand: recent findings and future challenges.

text: Our knowledge of diseases in New Zealand wildlife has expanded rapidly in the last two decades. Much of this is due to a greater awareness of disease as a cause of mortality in some of our highly threatened species or as a limiting factor to the successful captive rearing of intensely managed species such as hihi (Notiomystis cincta), kiwi (Apteryx spp.) and kakapo (Strigops habroptilus). An important factor contributing to the increase of our knowledge has been the development of new diagnostic techniques in the fields of molecular biology and immunohistochemistry, particularly for the diagnosis and epidemiology of viral and protozoan diseases. Although New Zealand remains free of serious exotic viruses there has been much work on understanding the taxonomy and epidemiology of local strains of avipox virus and circoviruses. Bacterial diseases such as salmonellosis, erysipelas and tuberculosis have also been closely investigated in wildlife and opportunist mycotic infections such as aspergillosis remain a major problem in many species. Nutritional diseases such as hyperplastic goitre due to iodine deficiency and metabolic bone disease due to Ca:P imbalance have made significant impacts on some captive reared birds, while lead poisoning is a problem in some localities. The increasing use of wildlife translocations to avoid the extinction of threatened species has highlighted the need for improved methods to assess the disease risks inherent in these operations and other intensive conservation management strategies such as creching young animals. We have also become more aware of the likelihood of inbreeding suppression as populations of many species decrease or pass through a genetic bottleneck. Climate change and habitat loss, however, remain the greatest threats to biodiversity and wildlife health worldwide. Temperature changes will affect our wildlife habitats, alter the distribution of disease vectors and wildlife predators, or directly harm threatened species in vulnerable localities.


title: Umbilical hernias: the cost of waiting.

text: BACKGROUND Umbilical hernias are well described in the literature, but its impact on health care is less understood. The purpose of this study was to investigate the effect of non-operative management of umbilical hernias on cost, work absenteeism, and resource utilization. METHODS The Truven Health Database, consisting of 279 employers and over 3000 hospitals, was reviewed for all umbilical hernia patients, aged 18-64 who were enrolled in health plans for 12 months prior to surgery and 12 months after surgery. Patients were excluded if they had a recurrence or had been offered a "no surgery" approach within 1 year of the index date. The remaining patients were separated into surgery (open or laparoscopic repair) or no surgery (NS). Post-cost analysis at 90 and 365 days and estimated days off from work were reviewed for each group. RESULTS The non-surgery cohort had a higher proportion of females and comorbidity index. Adjusted analysis showed significantly higher 90 and 365 costs for the surgery group (p < 0.0001), though the cost difference did decrease over time. NS group had significantly higher estimated days of health-care utilization at both the 90 (1.99 vs. 3.58 p < 0.0001) and 365 (8.69 vs. 11.04 p < 0.0001) day post-index mark. A subgroup analysis demonstrated laparoscopic repair had higher costs compared to open primarily due to higher index procedure costs (p < 0.05). CONCLUSIONS Though the financial costs were found to be higher in the surgery group, the majority of these were due to the surgery itself. Significantly higher days of health-care utilization and estimated days off work were experienced in the NS group. It is our belief that early operative intervention will lead to decreased costs and resource utilization.


title: Prognostic Value of Novel Liquid Biomarkers in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide: A Prospective Observational Study.

text: BACKGROUND Several treatment options were recently added for metastatic castration-resistant prostate cancer (mCRPC). However, response to therapy is variable, and biomarkers that can guide treatment selection and response evaluation are lacking. Circulating RNAs are a promising source of biomarkers. We explored messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) as potential biomarkers in liquid biopsies of patients with mCRPC treated with enzalutamide. METHODS Forty patients were included in this prospective multicenter observational study. Whole blood was drawn at baseline and 1, 3, and 6 months after start of therapy. Four mRNAs, 6 miRNAs, and 5 lncRNAs were analyzed by quantitative PCR. RNA levels in 30 healthy individuals were used as controls. RNA expression data were analyzed by Kaplan-Meier and Cox regression analyses, and the primary end point was progression-free survival. Clinical factors were included in the multivariable Cox regression analysis. RESULTS Levels of 2 miRNAs, miR-375 and miR-3687, and 1 lncRNA, N-acetylated alpha-linked acidic dipeptidase like 2 antisense RNA 2 (NAALADL2-AS2), were more than 2-fold higher in patients with mCRPC compared with healthy volunteers. Patients with higher levels of miR-375 or miR-3687 showed a shorter time to progression. Patients with higher levels of NAALADL2-AS2 showed a longer time to progression. In the multivariable Cox regression analysis, higher miR-375, miR-3687 and serum prostate-specific antigen concentrations were shown to be independent predictors for shorter time to progression. CONCLUSIONS We identified miR-3687 as a novel prognostic marker for response in patients with CRPC treated with enzalutamide, and we confirmed the prognostic value of miR-375.


Neurologic complications of coronavirus infections.


title: Longitudinal Change of Medial and Lateral Patellar Stiffness After Reconstruction of the Medial Patellofemoral Ligament for Patients with Recurrent Patellar Dislocation.

text: BACKGROUND Longitudinal changes in patellar stiffness following reconstruction of the medial patellofemoral ligament for recurrent patellar dislocation at full extension are unknown. METHODS Fifteen consecutive patients (three men and twelve women, with a mean age of twenty-two years) with seventeen knees were matched by sex and age to thirty-two reference subjects in this prospective study. The follow-up period was a minimum of twenty-four months. The medial patellofemoral ligament reconstruction used an autograft semitendinosus tendon and an interference screw system with or without lateral release under 10 N of laterally directed force. The medial patellar stiffness and lateral patellar stiffness were measured in 0° of knee extension using the Patella Stability Tester preoperatively; postoperatively at three, six, twelve, and eighteen months; and at the time of the latest follow-up. Before and after the surgical procedure, patients were evaluated for apprehension and Kujala and Lysholm scores; radiographic examinations were performed to evaluate changes, including osteoarthritic changes. RESULTS The medial stiffness of the affected side before the surgical procedure was significantly lower than the lateral stiffness (p = 0.004) and the stiffness for healthy reference knees (p = 0.004). Medial stiffness three months after the surgical procedure was significantly elevated compared with lateral values (p = 0.027), preoperative values (p < 0.001), and reference group values (p = 0.002); reached the reference level by six months; and was maintained for up to two years. Furthermore, medial stiffness and lateral stiffness were well balanced after six months and this balance was sustained for up to two years postoperatively. No recurrent dislocation occurred during the follow-up period; one patient experienced apprehension. Postoperative radiographic findings and clinical scores were significantly improved at the time of the latest follow-up (p < 0.05). One knee progressed to patellofemoral osteoarthritis. CONCLUSIONS The value for medial stiffness was significantly improved three months after medial patellofemoral ligament reconstruction compared with the preoperative and lateral values and returned to the reference level by six months. Medial stiffness and lateral stiffness of the patella were well balanced by six months and retained that balance for up to two years, with good clinical results. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


RCVS council vote an opportunity for change.


title: Onyx versus nBCA and coils in the treatment of intracranial dural arteriovenous fistulas.

text: BACKGROUND AND PURPOSE Intracranial dural arteriovenous fistulas (DAVFs) with cortical venous drainage have significant morbidity and mortality. Complete closure of these lesions is necessary to reduce these risks. The purpose of our study was to compare the outcome of DAVFs treated with Onyx versus those treated with n-Butyl Cyanoacrylate (nBCA) and coil embolization in a case-control study. Compared with nBCA and coil embolization, we hypothesized that Onyx embolization for DAVF is safer and has a higher chance of complete obliteration, with no need for post-embolization surgery for the DAVF. MATERIALS AND METHODS From 1998 to 2015, 29 patients who had DAVFs were treated with endovascular embolization. Of these, 24 patients had imaging available for analysis. Successful closure rates, complications, and procedure time were compared between the embolization techniques. RESULTS The chance of not requiring post-embolization surgery with Onyx (81.8%) was significantly higher (p = 0.005) than with nBCA (22.22%). The complication rate with Onyx (9.1%) tended to be lower compared with that of nBCA (22.22%; p = 0.37). Procedural time was not significantly different between Onyx (mean 267 minutes) and nBCA (mean 288 minutes) (p = 0.59). The odds ratio of a DAVF being treated with Onyx and then requiring no follow-up surgery was 17.5 (95% CI 1.97-155.4). CONCLUSION Our case-control study suggests that Onyx embolization is superior to nBCA and coil embolization in completely obliterating DAVFs, with higher odds of no post-embolization surgery. We also found that Onyx is safe for embolization of DAVFs, with no associated neurological mortality and morbidity.


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title: Assessing the impact of budget controls on the prescribing behaviours of physicians treating dialysis-dependent patients.

text: OBJECTIVES This study examined whether outpatient haemodialysis providers changed their treatment practices with the establishment of an outpatient dialysis global budget (ODGB) through analysing the outpatient visits and medication received by those patients. METHODS A sample of 4668 observations (patient year) of 1350 haemodialysis with hypertension (HH) patients and 4668 observations of 1436 non-HH (NHH) patients were drawn from the National Health Insurance Research Database over the years from 1999 to 2005. The impact of ODGB on hypertension-related outpatient utilization of HH was estimated using the difference in difference (DID) method and examined in three stages: (1) the fee for service stage, the pre-ODGB (2000), (2) the phase-in stage (2001-2002) and (3) the post-ODGB stage (2003-2005). RESULTS ODGB implementation did not affect the number of dialysis visits for HH patients. However, it did lead to a reduction in fees for antihypertension drugs used by haemodialysis facilities. There was an increase of 4.06 visits per patient per year (P < 0.001) in the number of non-dialysis outpatient with antihypertensive drugs visits for HH patients compared with the control group. The total fees for antihypertensive drugs for HH patients increased by New Taiwan Dollars (NT$)13 008 (P < 0.001) per patient per year relative to the control group after the implementation of ODGB. CONCLUSIONS As ODGB was implemented, HH patients received fewer antihypertensive drugs during their dialysis visit. In addition, there was an increase in the number of non-dialysis outpatient visits by HH patients as well as increased payment in the drugs associated with their non-dialysis outpatient visits compared with the control group.


title: First-in-man use of a novel embolic protection device for patients undergoing transcatheter aortic valve implantation.

text: AIMS We describe the first-in-human experience with a novel cerebral embolic protection device used during transcatheter aortic valve implantation (TAVI). One current challenge of TAVI is the reduction of procedural stroke. Procedural mobilisation of debris is a known source of cerebral embolisation. Mechanical protection by transient filtration of cerebral blood flow might reduce the embolic burden during TAVI. We aimed to evaluate the feasibility and safety of the Claret CE Pro™ cerebral protection device in patients undergoing TAVI. METHODS AND RESULTS Patients scheduled for TAVI were prospectively enrolled at three centres. The Claret CE Pro™ (Claret Medical, Inc. Santa Rosa, CA, USA) cerebral protection device was placed via the right radial/brachial artery prior to TAVI and was removed after the procedure. The primary endpoint was technical success rate. Secondary endpoints encompassed procedural and 30-day stroke rates, as well as device-related complications. Deployment of the Claret CE Pro™ cerebral protection device was intended for use in 40 patients, 35 devices were implanted into the aortic arch. Technical success rate with delivery of the proximal and distal filter was 60% for the first generation device and 87% for the second-generation device. Delivery times for the first-generation device were 12.4±12.1 minutes and 4.4 ± 2.5 minutes for the second-generation device (p<0.05). The quantity of contrast used related to the Claret CE Pro System was 19.6 ± 3.8 ml. Captured debris was documented in at least 19 of 35 implanted devices (54.3%). No procedural transient ischaemic attacks, minor strokes or major strokes occurred. Thirty-day follow-up showed one minor stroke occurring 30 days after the procedure, and two major strokes both occurring well after the patient had completed TAVI. CONCLUSIONS The use of the Claret CE Pro™ system is feasible and safe. Capture of debris in more than half of the patients provides evidence for the potential to reduce the procedural cerebral embolic burden utilising this dedicated filter system during TAVI.


COVID-19 pandemic: what can pharmaceutical formulation and drug delivery experts offer?


title: Improving the trajectory of transpedicular transdiscal lumbar screw fixation with a computer-assisted 3D-printed custom drill guide.

text: Transpedicular transdiscal screw fixation is an alternative technique used in lumbar spine fixation; however, it requires an accurate screw trajectory. The aim of this study is to design a novel 3D-printed custom drill guide and investigate its accuracy to guide the trajectory of transpedicular transdiscal (TPTD) lumbar screw fixation. Dicom images of thirty lumbar functional segment units (FSU, two segments) of L1-L4 were acquired from the PACS system in our hospital (patients who underwent a CT scan for other abdomen diseases and had normal spine anatomy) and imported into reverse design software for three-dimensional reconstructions. Images were used to print the 3D lumbar models and were imported into CAD software to design an optimal TPTD screw trajectory and a matched custom drill guide. After both the 3D printed FSU models and 3D-printed custom drill guide were prepared, the TPTD screws will be guided with a 3D-printed custom drill guide and introduced into the 3D printed FSU models. No significant statistical difference in screw trajectory angles was observed between the digital model and the 3D-printed model (P > 0.05). Our present study found that, with the help of CAD software, it is feasible to design a TPTD screw custom drill guide that could guide the accurate TPTD screw trajectory on 3D-printed lumbar models.


title: Assessment of basic laparoscopic skills on virtual reality simulator or box trainer.

text: INTRODUCTION We investigated whether the peg transfer task is interchangeable between a VR simulator and a box trainer. Our research questions: (1) Are scores of the box trainer interchangeable with the virtual equivalent of the exercise; (2) does training on the box affect performance on the VR simulator and vice versa; and (3) which system is preferred? METHODS Experienced laparoscopists and medical interns were randomly assigned to one of two groups (V or B). They performed eight repetitions of the peg transfer task (4 on each simulator system) following a crossover study design. Group B started on the box trainer and group V started on the VR simulator. Opinion of participants was evaluated by a questionnaire. RESULTS A significant correlation was found between time to complete the task on the box and the VR simulator. The comparison of the performances per system showed that group B (N = 14) performed the peg transfer task on the VR simulator in significantly less time than group V (N = 14; p = 0.014). Overall, the box was preferred over the VR simulator. CONCLUSIONS Although performances on the box trainer and VR simulator were correlated, they were not interchangeable. The results also imply that assessment on the VR simulator after pretraining on the box is acceptable, whereas VR simulator training alone might not suffice to pass an assessment on a box trainer. More research is needed to validate the use of the VR simulator as a FLS and PLUS assessment instrument.


title: Mechanisms for Env glycoprotein acquisition by retroviruses.

text: A mandatory step in the formation of an infectious retroviral particle is the acquisition of its envelope glycoprotein (Env). This step invariably occurs by Env positioning itself in the host membrane at the location of viral budding and being incorporated along with the host membrane into the viral particle. In some ways, this step of the viral life cycle would appear to be imprecise. There is no specific sequence in Env or in the retroviral structural protein, Gag, that is inherently required for the production of an infectious Env-containing particle. Additionally, Env-defective proviruses can efficiently produce infectious particles with any of a number of foreign retroviral Env glycoproteins or even glycoproteins from unrelated viral families, a process termed pseudotyping. However, mounting evidence suggests that Env incorporation is neither passive nor random. Rather, several redundant mechanisms appear to contribute to the carefully controlled process of Env acquisition, many of which are apparently used by a wide variety of enveloped viruses. This review presents and discusses the evidence for these different mechanisms contributing to incorporation.


title: A Wrist-Worn Strap with an Array of Electrodes for Robust Physiological Sensing.

text: Robust sensing is one of the main challenges for wearable physiological monitoring because of the high dependency on the placement of electrodes on the body, retaining suitable contact between electrodes and skin, and the effect of motion artifacts. In this paper, we present a wrist-worn strap that includes a 2-D array of 48 miniature electrodes covering the bottom side of the wrist with good contact with the skin. Good skin contact directly impacts the sensing robustness. The array provides local measurements between adjacent electrodes that span the whole bottom side of the wrist with an area of 6.25×4.60 cm for robust sensing. The array allows for the automatic selection of the correct electrodes at the right location regardless of changes in the device placement on the wrist. In addition, using a large number of electrodes over a large area on the wrist ensures continuous contact of some electrodes with the skin during motion since all of the electrodes will not lose contact with the skin at the same time. We measured the electrode-skin impedance of the fabricated electrodes versus frequency and compared to other types of electrodes. We demonstrated good contact between all electrodes of the array and the skin by measuring electrode-skin impedance less than 10 k$\Omega$ at 16 kHz for all locations on the wrist strap. We also conducted measurements of impedance while the wearer was bending the wrist to validate the continuous contact of at least a subset of electrodes with the skin during such movements.


title: Absence of coronaviruses, paramyxoviruses, and influenza A viruses in seabirds in the southwestern Indian Ocean.

text: We investigated circulation of coronaviruses, paramyxoviruses, and influenza A viruses in eight seabird species of the southwestern Indian Ocean. Viruses were not detected by real-time polymerase chain reactions in the 338 tested cloacal swab samples, supporting that they did not circulate in the studied colonies at the time of sampling.


title: Lipomatosis of the trigeminal nerve causing trigeminal neuralgia: case report and literature review.

text: UNLABELLED Cerebellopontine angle lipomas are rare and attempts at surgical excision are associated with significant morbidity. Lipomatosis of nerve, the fatty infiltration of nerves, is a distinct entity. We present a case of intractible trigeminal neuralgia caused by lipomatosis of the trigeminal nerve. CLINICAL CASE A 25-year-old male presented with severe right-sided trigeminal neuralgia. Imaging showed a lesion involving the trigeminal nerve with signal characteristics of fat. At surgery the lesion was found to be a fatty infiltration of the nerve itself. Surgery was therefore limited to arachnoid adhesiolysis. The patient remains symptom-free and neurologically intact to date. Correctly identifying these lesions as lipomatosis of nerve rather than lipoma of the cerebellopontine angle make it clear that even partial surgical excision will inevitably result in neurological deficit and should not be attempted. However, in the case of intractable trigeminal neuralgia we demonstrate that surgery can still play a role.


title: [Clinical experience and critical issues.]

text: Bergamo is a rich and populous city of northern Italy and one of the epicentres of the worldwide pandemic CoViD-19. Despite the generosity of health workers, we are undergoing a severe humanitarian crisis that is stressing every aspect of daily life. From outside it is very hard to understand, because houses are closed for lockdown and are not destroyed as they would be in an earthquake. An outbreak is not "only" a sudden mass lethal incident, like a natural disaster, neither "only" a disease, to be treated by doctors, but a social phenomenon too. Historical and social elements are key factors for development (for example, intensive promiscuity between animals and humans) and spread of an epidemic (for example, health workers and ambulance rapidly become vector of the virus). Can medical responsibility change in times of pandemic? My answer, as anaesthetist and intensive care physician from Bergamo, is yes. When the global medical community is called on to face a pandemic of unprecedented scale, with little scientific evidence and "crazy numbers" describing the situation, honest and forthcoming advocacy is an ethical duty. Aim of this narrative report is to share a view point about the dilemma of moral responsibility.


title: Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial.

text: BACKGROUND The degree of antiplatelet response to clopidogrel has been associated with clinical outcomes. Studies have investigated whether adjustment of antiplatelet therapies based on a single platelet function test is beneficial. OBJECTIVES The aim of the study was to test the stability of platelet reactivity measurements over time among patients treated with standard and double doses of clopidogrel. METHODS The ELEVATE-TIMI 56 (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56) investigators genotyped 333 patients with coronary artery disease and randomized them to various clopidogrel regimens. Patients with at least 2 platelet function results on the same maintenance dose of clopidogrel (75 mg or 150 mg) were analyzed. Platelet aggregation was measured using P2Y12 reaction units (PRU). RESULTS In total, the mean platelet reactivity and the total number of nonresponders (PRU ≥230) with clopidogrel did not change between 2 periods for the 75-mg (22.4% vs. 21.9%; p = 0.86) and 150-mg doses of clopidogrel (11.5% vs. 11.5%; p = 1.00). In contrast, when evaluating each patient individually, 15.7% of patients taking clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their responder status when tested at 2 different time points (p < 0.001). Despite being treated with the same dose of clopidogrel, >40% of patients had a change in PRU >40 on serial sampling, which approximates the average PRU difference caused by increasing the clopidogrel dose from 75 mg to 150 mg. CONCLUSIONS Measurements of platelet reactivity vary over time in a significant proportion of patients. Thus, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy in clinical or research settings. (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56 [ELEVATE-TIMI 56]; NCT01235351).


title: The potential transmission of SARS-CoV-2 from patients with negative RT-PCR swab tests to others: two related clusters of COVID-19 outbreak.

text: In December 2019, a cluster of cases of acute respiratory illness, novel coronavirusinfected pneumonia, occurred in Wuhan, Hubei Province, China. The false-negative nasopharyngeal swabs of SARS-CoV-2 caused the delayed diagnosis of COVID-19 which hindered the prevention and control of the pandemic. The transmission risk of SARS-CoV-2 in negative nasopharyngeal swabs cases were little addressed previously. This study evaluated two clusters of COVID-19 in six patients. Four of six (66.7%) showed negative RNA of SARS-CoV-2 by nasopharyngeal swabs. All epidemiological, clinical and laboratory information was collected. The first cluster was a nosocomial infection of four health care providers at early January. One of them made sequential familial cluster of infection. All patients received either selfquarantined at home or were admitted to hospital for isolated treatment. All recovered and had anti-SARS-CoV-2 IgG and/or IgM positive (100%) for serological detection of SARS-CoV-2 at recovery stage. Our study provides a cautionary warning that negative results of nasopharyngeal swabs of suspected SARS-CoV-2 infection can increase the risk of nosocomial infection among health care providers. Serologic detection for anti-SARS-CoV-2 IgG and/or IgM is an important test in the assistant diagnosis of COVID-19.


title: Effect of chemical clarification of oral fluids on the detection of porcine reproductive and respiratory syndrome virus IgG.

text: Routine collection and testing of oral fluid (OF) samples facilitates porcine reproductive and respiratory syndrome virus (PRRSV) surveillance in commercial swine herds in a cost-effective, welfare-friendly fashion. However, OFs often contain environmental contaminants that may affect liquid handling and test performance. Traditional processing methods (e.g., filtration or centrifugation) are not compatible with high-throughput testing because of the burden of additional processing costs and time. OF "clarification" using chemical flocculants is an alternative approach not widely explored. Therefore, we evaluated the effect of chitosan-based clarification treatment on a commercial PRRSV OF ELISA. Serum and individual OFs were collected from vaccinated pigs ( n = 17) at -7 to 42 d post-vaccination and subdivided into 4 aliquots. Each aliquot was clarified (treatment A, B, C), with the 4th aliquot serving as untreated control. All samples were tested by PRRSV OF ELISA immediately after treatment and then were held at 4°C to be re-tested at 2, 4, 6, and 14 d post-treatment. Quantitative and qualitative treatment effects were evaluated. A Kruskal-Wallis test found no significant difference in ELISA S/P responses among treatments by days post-treatment. No difference was detected in the proportion of positive PRRSV antibody samples among treatments (Cochran Q, p > 0.05). Treatment of swine OFs using chitosan-based formulations did not affect the performance of a commercial PRRSV OF ELISA. Chitosan (or other flocculants) could improve OF characteristics and could be adapted for use in the field or in high-throughput laboratories.


Department of rehabilitation medicine in Shanghai response for coronavirus disease 2019: the impact and challenges.


title: Surface plasmon resonance for vaccine design and efficacy studies: recent applications and future trends.

text: The lack of a clear correlation between design and protection continues to present a barrier to progress in vaccine research. In this article, we outline how surface plasmon resonance (SPR) biosensors are emerging as tools to help resolve some of the key biophysical determinants of protection and, thereby, facilitate more rational vaccine design campaigns. SPR technology has contributed significantly to our understanding of the complex biophysical determinants of HIV neutralization and offers a platform for preclinical evaluation of vaccine candidates. In particular, the concept of reverse-engineering HIV vaccine targets based on known broadly neutralizing antibody modalities is explored and extended to include other infectious diseases, such as malaria and influenza, and other diseases such as cancer. The analytical capacity afforded by SPR includes serum screening to monitor immune responses and highly efficient quality-control surveillance measures. These are discussed alongside key technological advances, such as developments in sample throughput, and a perspective predicting continued growth and diversification of the role of SPR in vaccine development is proposed.


title: Driving improvements in emerging disease surveillance through locally relevant capacity strengthening.

text: Emerging infectious diseases (EIDs) threaten the health of people, animals, and crops globally, but our ability to predict their occurrence is limited. Current public health capacity and ability to detect and respond to EIDs is typically weakest in low- and middle-income countries (LMICs). Many known drivers of EID emergence also converge in LMICs. Strengthening capacity for surveillance of diseases of relevance to local populations can provide a mechanism for building the cross-cutting and flexible capacities needed to tackle both the burden of existing diseases and EID threats. A focus on locally relevant diseases in LMICs and the economic, social, and cultural contexts of surveillance can help address existing inequalities in health systems, improve the capacity to detect and contain EIDs, and contribute to broader global goals for development.


title: Will Coronavirus Disease 2019 Become Seasonal?

text: This manuscript explores the question of the seasonality of severe acute respiratory syndrome coronavirus 2 by reviewing 4 lines of evidence related to viral viability, transmission, ecological patterns, and observed epidemiology of coronavirus disease 2019 in the Southern Hemispheres' summer and early fall.


Therapeutic options for the 2019 novel coronavirus (2019-nCoV).


title: Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery.

text: The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a first step towards solution dosage form development. The parameters such as log P value were determined experimentally and compared with predicted values. The pH-dependent aqueous solubility and stability were investigated following standard protocols at 25°C and 37°C. Drug solubility enhancement was attempted utilizing both surfactants and cyclodextrins (CDs), and the drug/CD complexation was studied employing various techniques such as differential scanning calorimetry, Fourier transform infrared, nuclear magnetic resonance, and scanning electron microscopy. The experimental log P value suggested that the compound is fairly hydrophilic. Berberine chloride was found to be very stable up to 6 months at all pH and temperature conditions tested. Aqueous solubility of the drug was temperature dependent and exhibited highest solubility of 4.05 ± 0.09 mM in phosphate buffer (pH 7.0) at 25°C, demonstrating the effect of buffer salts on drug solubility. Decreased drug solubility was observed with increasing concentrations of ionic surfactants such as sodium lauryl sulfate and cetyl trimethyl ammonium bromide. Phase solubility studies demonstrated the formation of berberine chloride-HPβCD inclusion complex with 1:1 stoichiometry, and the aqueous solubility of the drug improved almost 4.5-fold in the presence of 20% HPβCD. The complexation efficiency values indicated that the drug has at least threefold greater affinity for hydroxypropyl-β-CD compared to randomly methylated-β-CD. The characterization techniques confirmed inclusion complex formation between berberine chloride and HPβCD and demonstrated the feasibility of developing an oral solution dosage form of the drug.


title: Antisperm antibodies and testicular blood flow after inguinal hernia mesh repair.

text: BACKGROUND Testicular flow studies after hernia mesh repair mostly showed different outcomes. The reason of infertility in some men after hernia repair is immunological factors. Aim of the study was to investigate the influence of mesh hernia repair on antisperm antibodies production and testicular blood flow and a connection among these parameters. MATERIALS AND METHODS A prospective interventional longitudinal cohort study was made on 82 male patients without exclusion criteria who had an inguinal hernia. Patients underwent laparoscopic TAPP or open tension-free hernia repair. Vascular ultrasound and antisperm antibodies were measured in the preoperative and postoperative periods. Main outcome measures were resistive index (RI), peak systolic velocity (PSV) cm/s, and end-diastolic velocity (EDV) cm/s in testicular blood flow measurement and the quantitative value of antisperm antibodies (ASA) in serum (IU/ml). RESULTS ASA significantly increased postoperatively only in patients who underwent open tension-free hernia repair (p < 0.001). ASA stayed in normal range in all patients except the one with postoperative complication. Friedman analysis showed significant change of the RI only on intratesticular (p < 0.001) and capsular artery level (0.02) in patients who underwent laparoscopic technique. PSV significantly changed on intratesticular (p < 0.001) and capsular artery level (p = 0.015) in the laparoscopic hernia repair. PSV showed significant change on intratesticular (p < 0.001) and testicular artery levels (p < 0.001) in the open tension-free hernia repair. EDV showed significant change only on testicular artery level (p = 0.032) in the patients who had open tension-free hernia repair. These blood flow parameters significantly increased in the early postoperative period and returned on basal value in the late postoperative period. Parameters of flow did not show any significant correlation with ASA. CONCLUSION Mesh hernia repairs without complication caused only a transitory change in testicular blood flow and no clinical significant autoimmune reaction.


title: Primary manual aspiration thrombectomy (MAT) for acute ischemic stroke: safety, feasibility and outcomes in 112 consecutive patients.

text: AIM To describe procedural aspects and clinical outcomes in a consecutive series of patients in whom manual aspiration thrombectomy (MAT) was performed as the first treatment modality with other techniques used only in case MAT did not yield recanalization. METHODS A retrospective review of a prospectively acquired acute stroke intervention database was performed. Primary MAT was carried out with a preference for the largest catheter considered to be trackable into the target occlusive lesion. The catheter was wedged into the thrombus followed by manual aspiration with a 20 ml syringe. RESULTS 112 consecutive patients were evaluated. The median age was 66 years and the median NIH Stroke Scale score was 17. Occlusion locations included the M1 (62%), M2 (8%), internal carotid artery terminus (19%) and the vertebrobasilar artery (11%). Patients with anterior occlusions had tandem extracranial/intracranial occlusive lesions in 18.7% Median time from symptom onset to groin puncture was 267 min, and from groin puncture to recanalization was 70 min. Successful recanalization (defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3) with primary MAT was 59% with a median of two passes. 41% of patients required the use of adjunctive therapy yielding an overall recanalization rate of TICI 2b/3 (86%) and TICI 3 (30.6%). Parenchymal hematoma of any type (PH1/PH2) was seen in 9.8% of patients, with symptomatic hemorrhage in 6%. Favorable outcomes (90-day modified Rankin Scale ≤2) were 46%. Mortality at 3 months was 31%. Primary MAT was associated with faster procedural times (mean 63 vs 97 min, p<0.0001) but not with higher rates of favorable outcomes. CONCLUSIONS Primary MAT is an alternative endovascular recanalization technique with reasonable first pass efficacy that will likely improve with technology and experience.


title: Comparison of four microwave ablation devices: an experimental study in ex vivo bovine liver.

text: PURPOSE To compare volume, sphericity, and short-axis diameter of the coagulation zone of four commercially available microwave ablation systems with three technical concepts in an ex vivo setting and to formulate mathematical models to predict these quantities. MATERIALS AND METHODS Two high-power systems (systems A and B), a system that enables simultaneous use of three antennas (system C), and a non-perfusion-cooled system that automatically adapts power and frequency (system D) were tested in ex vivo bovine livers (108 ablations). Coagulation volume, sphericity, and mean short-axis diameter were assessed, and mathematical functions were fitted for each system and assessed with the coefficient of determination (R(2)). Analysis of variance and Tukey post hoc tests were used for interdevice comparison after 5 and 10 minutes and after maximum recommended ablation time. RESULTS Volume and short-axis diameter were determined by using a mathematical model for every system, with coefficients of determination of 0.75-0.98 and 0.70-0.97, respectively. Correlation for determination of sphericity was lower (R(2) = 0.01-0.68). Mean results with ablation performed according to manufacturer recommendations were as follows: Volume, sphericity, and short-axis diameter were 57.5 cm(3), 0.75, and 43.4 mm, respectively, for system A; 72.3 cm(3), 0.68, and 45.5 mm, respectively, for system B; 17.1 cm(3), 0.58, and 26.8 mm, respectively, for system C (one antenna); 76.5 cm(3), 0.89, and 50.6 mm, respectively, for system C (three antennas); and 56.0 cm(3), 0.64, and 40.9 mm, respectively, for system D. Systems A (mean volume, 52.4 cm(3) ± 4.5 [standard deviation]) and B (39.4 cm(3) ± 1.7) reach large ablation zones with 5-minute ablation. CONCLUSION The largest ablation zone is obtained with systems B and C (three antennas) under maximum recommended ablation duration and with system A under short ablation time. The most spherical zone is obtained with system C (three antennas).


title: Louseborne Relapsing Fever among East African Refugees, Italy, 2015.

text: During June 9-September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.


title: Cancer and COVID-19: Unmasking their ties.

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and its clinical manifestation, the coronavirus disease 2019 (COVID19) have rapidly spread across the globe, leading to the declaration of a pandemic. While most present mild symptoms, it appears as though nearly 20% of confirmed patients develop significant complications. These include acute respiratory distress syndrome, septic shock and multi-organ failure, with a 3-6% mortality. A plethora of treatments has been or is being assessed, but to date, none has been proven effective. Management is mainly symptomatic, with organ support for the critically ill. Several reports, mainly case series, from across the world have concluded that patients with malignancy appear more susceptible to severe infection and mortality from COVID-19. This could be attributed to immunosuppression, co-existing medical conditions and underlying pulmonary compromise which is often the case in lung malignancy. Patients with haematological cancer and those who are receiving active chemotherapy treatment may be at greatest risk due to increased immunosuppression. This pandemic tested the resilience of worldwide health-care systems in an unprecedented manner. It has forced oncologists to rethink the entire diagnostic and therapeutic process, based on the local prevalence and impact of COVID-19. In this review we will discuss the impact of COVID-19 on patients affected by cancer, their diagnosis and management, as well as the pathophysiology of COVID-19 induced acute respiratory distress symptoms and currently investigated treatment approaches.


title: Continuous positive airway pressure and ventilation are more effective with a nasal mask than a full face mask in unconscious subjects: a randomized controlled trial.

text: INTRODUCTION Upper airway obstruction (UAO) is a major problem in unconscious subjects, making full face mask ventilation difficult. The mechanism of UAO in unconscious subjects shares many similarities with that of obstructive sleep apnea (OSA), especially the hypotonic upper airway seen during rapid eye movement sleep. Continuous positive airway pressure (CPAP) via nasal mask is more effective at maintaining airway patency than a full face mask in patients with OSA. We hypothesized that CPAP via nasal mask and ventilation (nCPAP) would be more effective than full face mask CPAP and ventilation (FmCPAP) for unconscious subjects, and we tested our hypothesis during induction of general anesthesia for elective surgery. METHODS In total, 73 adult subjects requiring general anesthesia were randomly assigned to one of four groups: nCPAP P0, nCPAP P5, FmCPAP P0, and FmCPAP P5, where P0 and P5 represent positive end-expiratory pressure (PEEP) 0 and 5 cm H2O applied prior to induction. After apnea, ventilation was initiated with pressure control ventilation at a peak inspiratory pressure over PEEP (PIP/PEEP) of 20/0, then 20/5, and finally 20/10 cm H2O, each applied for 1 min. At each pressure setting, expired tidal volume (Vte) was calculated by using a plethysmograph device. RESULTS The rate of effective tidal volume (Vte > estimated anatomical dead space) was higher (87.9% vs. 21.9%; P<0.01) and the median Vte was larger (6.9 vs. 0 mL/kg; P<0.01) with nCPAP than with FmCPAP. Application of CPAP prior to induction of general anesthesia did not affect Vte in either approach (nCPAP pre- vs. post-; 7.9 vs. 5.8 mL/kg, P = 0.07) (FmCPAP pre- vs. post-; 0 vs. 0 mL/kg, P = 0.11). CONCLUSIONS nCPAP produced more effective tidal volume than FmCPAP in unconscious subjects. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01524614.


title: Treatment options for symptomatic carotid stenosis: timing and approach.

text: Stroke is a major cause of morbidity and mortality and up to 15-20% of ischemic strokes can be attributed to atherosclerotic internal carotid artery disease. The treatment of carotid artery disease has been the subject of a wealth of literature in the past twenty years since the publication of the landmark randomized controlled trials, the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial, in the early 1990s. Although these landmark trials have helped establish the current guidelines for treatment of patients with symptomatic carotid artery disease, there have since been major advancements in the medical treatment of cardiovascular disease and there still remains a great deal of controversy regarding the timing and technical approach to carotid revascularization. In particular, there has been a wealth of literature to determine whether carotid endarterectomy or carotid stenting should be used for revascularization and when this revascularization should occur following onset of symptoms. This update offers an overview of the standards for diagnosis and medical treatment of patients with symptomatic carotid artery disease, the indications for surgical revascularization and a review of the most pertinent literature as it pertains to the more controversial issues of technical approach and timing of surgical revascularization following onset of symptoms in patients with carotid artery disease.


title: A novel liquid biopsy-based approach for highly specific cancer diagnostics: mitigating false responses in assaying patient plasma-derived circulating microRNAs through combined SERS and plasmon-enhanced fluorescence analyses.

text: Studies have shown that microRNAs, which are small noncoding RNAs, hold tremendous promise as next-generation circulating biomarkers for early cancer detection via liquid biopsies. A novel, solid-state nanoplasmonic sensor capable of assaying circulating microRNAs through a combined surface-enhanced Raman scattering (SERS) and plasmon-enhanced fluorescence (PEF) approach has been developed. Here, the unique localized surface plasmon resonance properties of chemically-synthesized gold triangular nanoprisms (Au TNPs) are utilized to create large SERS and PEF enhancements. With careful modification to the surface of Au TNPs, this sensing approach is capable of quantifying circulating microRNAs at femtogram/microliter concentrations. Uniquely, the multimodal analytical methods mitigate both false positive and false negative responses and demonstrate the high stability of our sensors within bodily fluids. As a proof of concept, microRNA-10b and microRNA-96 were directly assayed from the plasma of six bladder cancer patients. Results show potential for a highly specific liquid biopsy method that could be used in point-of-care clinical diagnostics to increase early cancer detection or any other diseases including SARS-CoV-2 in which RNAs can be used as biomarkers.


title: Daily Reportable Disease Spatiotemporal Cluster Detection, New York City, New York, USA, 2014-2015.

text: Each day, the New York City Department of Health and Mental Hygiene uses the free SaTScan software to apply prospective space-time permutation scan statistics to strengthen early outbreak detection for 35 reportable diseases. This method prompted early detection of outbreaks of community-acquired legionellosis and shigellosis.


title: Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies.

text: Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. 81mKr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99mTc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81mKr gas-ventilation and 99mTc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.


Erratum to: Porcine epidemic diarrhea virus: An emerging and re-emerging epizootic swine virus.


title: COVID-19: Notes From the Front Line, Singapore's Primary Health Care Perspective.

text: Coronavirus disease 2019 (COVID-19) is a rapidly progressing global pandemic against which nations are struggling for containment. Singapore is known to have promptly instituted aggressive public health and containment measures. A key pillar sustaining this is the response of its primary health care network. It is important for health care systems worldwide to recognize the value of a strong coordinated response to this crisis from a primary health perspective. There are best practices for early isolation and containment of suspect cases while protecting health care workers and limiting cross infections that are transferable across nations. We describe our framework for how our primary care clinics respond to this pandemic in the hope others may find solutions to their unique needs. Moving forward, there is a pressing need for more studies to enhance our understanding of the response of primary care during these public health crises.


title: Removal of emerging pollutants in aqueous phase by heterogeneous Fenton and photo-Fenton with Fe2O3-TiO2-clay heterostructures.

text: Fe2O3-TiO2-clay heterostructures have been prepared using an organo-bentonite as support, which organophilic character favored the fixation of TiO2. Furthermore, Fe2O3 was successfully anchored by wet impregnation. The resulting materials are characterized by a disordered layered structure and a mesoporous texture. The heterostructures were employed as catalysts for the removal of two pharmaceuticals, acetaminophen (ACE) and antipyrine (ANT), by heterogeneous Fenton and photo-Fenton processes. ACE removal under different operation conditions was studied in detail to establish structure-performance relationships, being the TiO2 formation and the developed texture the main factors controlling the activity. ANT showed a higher refractory behavior in oxidation by Fenton. Among the technologies studied, heterogeneous photo-Fenton achieved the best catalytic performance and higher kinetic rate and mineralization degree. Iron leaching was very low, lower than 5% of the initial iron load in all cases. This work demonstrates the potential application of these heterostructures for the removal of emerging pollutants of different nature.


title: Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination.

text: Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdown experiments further indicate that SMAD-mediated BMP signaling is largely required for differentiation-related processes rather than directly influencing self-renewal. Among the SMAD-associated genes, we further identified Dpysl2 (previously known as Crmp2) and the H3K27 demethylase Kdm6b (previously known as Jmjd3) as BMP4-modulated early neural differentiation regulators. Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators.


title: Serum cytokine responses in primary pneumonic plague patients.

text: The serum levels of interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10 of pneumonic plague patients were determined by enzyme-linked immunosorbent assay. IL-6 was the only elevated cytokine in the patients, and its level increased with a clear time course, indicating that IL-6 might be a prognostic marker for predicting the progression of plague.


title: Results of laparoscopic radiofrequency ablation for HCC. Could the location of the tumour influence a complete response to treatment? A single European centre experience.

text: INTRODUCTION In selected patients, radiofrequency ablation (RFA) is a well-established treatment for hepatocellular carcinoma (HCC). However, subcapsular or lesions close to adjacent viscera preclude a percutaneous approach. In this setting laparoscopic-RFA (LRFA) is a potential alternative. The aim of this study was to analyse the safety and feasibility of LRFA in patients with HCC. PATIENTS AND METHODS Retrospective study of patients with HCC meeting strict inclusion criteria who underwent LRFA at a single Institution from December 2000 to March 2013. RESULTS Forty-one patients underwent 42 LRFA of 51 nodules. The median size of the nodule was 2.5 (range 1.2-4.7) cm. Thirty-one tumours were subcapsular and 17 located near the gallbladder. Major complications occurred in 17 patients. The initial complete response (ICR) rate was 94% and was lower among tumours located adjacent to the gallbladder. At the end of the follow-up period, the sustained complete response (SCR) rate was 70% and was lower in tumours adjacent to the gallbladder while increased for subcapsular tumours. The 1-, 3- and 5-year overall survival rate was 92.6%, 64.5% and 43%, respectively. CONCLUSION LRFA of HCC is safe, feasible and achieves excellent results in selected patients. LRFA should be the first-line technique for subcapsular lesions as it minimizes the risk of tumoural seeding and improves ICR. Proximity to gallbladder interferes in treatment efficacy (lower rate of ICR and lower rate of SCR).


title: Mesenchymal stem cell-based angiotensin-converting enzyme 2 in treatment of acute lung injury rat induced by bleomycin.

text: BACKGROUND Acute lung injury (ALI) is a high incidence disease with no effective therapeutic method (mortality rate > 40%). The aim of this study was to find a new and effective therapeutic method for ALI. METHODS After the isolation of human umbilical cord mesenchymal stem cells (HUMSCs) from cesarean fetus, we transfected the HUMSCs with Lenti-ACE2 (angiotensin-converting enzyme 2) viral particles. Then we evaluated the therapeutic effect of HUMSCs harboring ACE2 on ALI, which induced by bleomycin (BLM) in rat model. RESULTS Our results showed that HUMSCs harboring ACE2 could attenuate ALI degree through reducing pulmonary inflammatory infiltration and degree of vascular permeability, repressing the mRNA level of pro-inflammatory cytokines, activating the mRNA level of anti-inflammatory cytokines and ACE2. Besides, results also demonstrated that HUMSCs harboring ACE2 gene had higher therapeutic effects to ALI than the single factor of HUMSCs or ACE2. CONCLUSIONS This research provided clues for the development of effective therapeutic methods to ALI using stem cell transplantation and gene therapy.


Psychological Distress and Loneliness Reported by US Adults in 2018 and April 2020.


title: Minimally invasive versus open surgery for acute Achilles tendon rupture: a systematic review.

text: INTRODUCTION This review provides a comprehensive description of clinical, functional outcomes, and complications after open and minimally invasive surgery for Achilles tendon ruptures. SOURCES OF DATA We systematically searched Medline (PubMED), EMBASE, CINHAL, Cochrane, Sports Discus and Google scholar databases using the combined keywords 'open repair', 'percutaneous surgery', 'minimally invasive surgery' 'Achilles tendon rupture', 'complications', 'infections', 'wound disorders' to identify articles published in English, Spanish, French and Italian. AREAS OF AGREEMENT Twelve studies fulfilled our inclusion criteria. Six studies were retrospective, five were randomized controlled trials and one was a prospective investigation. Of a total of 781 patients, 375 underwent open repair and 406 percutaneous surgery. Different procedures were performed for open and minimally invasive repair. AREAS OF CONTROVERSY The range of motion was significantly greater after percutaneous repair than open surgery. The number of complications that occurred after open surgery was higher than after minimally invasive surgery. GROWING POINTS Minimally invasive surgery is less expensive and less time demanding. AREAS TIMELY FOR DEVELOPING RESEARCH Minimally invasive and open surgery of the Achilles tendon are grossly equivalent. However, iatrogenic neurological complications are more frequent after percutaneous repair. Novel percutaneous repairs have been proposed to minimize the risk of sural nerve injury.


title: Fracture-induced changes in biomarkers CTX, PINP, OC, and BAP-a systematic review.

text: To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.


title: Does spinal excitability scale to the difficulty of the dual-task?

text: PURPOSE This study examined whether spinal excitability, as measured by the soleus Hoffmann reflex (H-reflex), is scaled to the difficulty level of the dual-task being performed. METHODS Twenty-two participants completed a combination of three balance task and three secondary cognitive (visuo-motor) task difficulty levels for a total of nine dual-task conditions. An additional eight participants were tested while performing the same three balance task difficulty levels on its own (i.e., single-tasking). The balance task required participants to maintain their balance on a fixed or rotating stabilometer while the visuo-motor task required participants to respond to moving targets presented on a monitor. Throughout each single- and dual-task trial, H-reflexes were elicited from the soleus. RESULTS Although dual-task performance, as quantified by visuo-motor task accuracy as well as the root mean square of the stabilometer position and velocity, decreased by 10-34% with increasing dual-task difficulty (p < 0.05), no changes in the soleus H-reflex amplitude were observed between dual-task conditions (p = 0.483-0.758). This contrasts to when participants performed the balance task as a single-task, where the H-reflex amplitude decreased by ~25% from the easy to the hard balance task difficulty level (p = 0.037). CONCLUSIONS In contrast to the commonly reported finding of a reduced soleus H-reflex amplitude when individuals perform a less posturally stable task by itself, the results indicate that spinal excitability is not modulated as a function of dual-task difficulty. It is possible that when an individual's attentional resource capacity is exceeded during dual-tasking, they become ineffective in regulating spinal excitability for balance control.


title: Vulnerable Children in a Dual Epidemic.

text: Two epidemics-Covid-19 and opioid use disorder (OUD) -are creating short- and long-term mental and physical health risks for vulnerable children and adolescents. Information about the risks to children from exposure to the coronavirus is still fragmentary, but even many healthy children are not getting appropriate health care, such as vaccinations or monitoring of developmental milestones during the Covid-19 pandemic. Children living in poverty are at heightened risk. Youngsters who are already dealing with OUD in their families-2.2 million as of 2017-face serious consequences stemming from trauma and stress. Although not officially designated by the Centers for Disease Control and Prevention as "adverse childhood experiences" ("ACEs"), these situations meet the CDC's criteria for inclusion, such as death or separation from a parent. It is important to recognize and meet the needs of all these children now and not just when the long-term consequences become apparent.


title: Impact of Pial Collaterals on Infarct Growth Rate in Experimental Acute Ischemic Stroke.

text: BACKGROUND AND PURPOSE Cerebral infarction evolves at different rates depending on available blood flow suggesting that treatment time windows vary depending on the degree of pial collateral recruitment. This work sought to mathematically model infarct growth and determine whether infarct volume growth can be predicted by angiographic assessment of pial collateral recruitment in an experimental MCA occlusion animal model. MATERIALS AND METHODS Pial collateral recruitment was quantified by using DSA, acquired 15 minutes following permanent MCA occlusion in 6 canines based on a scoring system (average pial collateral score) and arterial arrival time. MR imaging-based infarct volumes were measured 60, 90, 120, 180, 240 and 1440 minutes following MCA occlusion and were parameterized in terms of the growth rate index and final infarct volume (VFinal) as V(t) = VFinal [1 - e(-G × t)] (t = time). Correlations of the growth rate index and final infarct volume to the average pial collateral score and arterial arrival time were assessed by linear bivariate analysis. Correlations were used to generate asymptotic models of infarct growth for average pial collateral score or arterial arrival time values. Average pial collateral score- and arterial arrival time-based models were assessed by F tests and residual errors. RESULTS Evaluation of pial collateral recruitment at 15 minutes postocclusion was strongly correlated with 24-hour infarct volumes (average pial collateral score: r2 = 0.96, P < .003; arterial arrival time: r2 = 0.86, P < .008). Infarct growth and the growth rate index had strong and moderate linear relationships to the average pial collateral score (r2 = 0.89; P < .0033) and arterial arrival time (r2 = 0.69; P < .0419), respectively. Final infarct volume and the growth rate index were algebraically replaced by angiographically based collateral assessments to model infarct growth. The F test demonstrated no statistical advantage to using the average pial collateral score- over arterial arrival time-based predictive models, despite lower residual errors in the average pial collateral score-based model (P < .03). CONCLUSIONS In an experimental permanent MCA occlusion model, assessment of pial collaterals correlates with the infarct growth rate index and has the potential to predict asymptotic infarct volume growth.


title: A Patient with Eight Intracranial Aneurysms: Endovascular Treatment in Two Sessions.

text: The frequency of multiple intracranial aneurysms seen in patients with or without subarachnoid hemorrhage is high. The advancement of the endovascular technique and devices has ensured that endovascular treatment of intracranial aneurysms is the first choice in most cases, especially in unruptured ones. Different combinations of treatment modalities and techniques can be used in the management of multiple aneurysms. But in selected patients without subarachnoid hemorrhage, treatment of all aneurysms in one or more sessions with endovascular techniques is less traumatic than that with surgery. In the literature, the maximum number of aneurysms in one patient treated endovascularly and/or surgically is seven. In this case report, we present, with a review of the literature, a patient with eight intracranial aneurysms, all of which were treated in two sessions with various endovascular techniques. A 40-year-old female patient was admitted due to headache. Angiography showed eight aneurysms in the posterior circulation and, bilaterally, in the anterior circulation. All aneurysms were treated endovascularly in two sessions. In the treatment of the aneurysms, different endovascular techniques were used including flow diverters stents, stent-assisted coiling, Y-stent-assisted coiling, and coiling alone.


title: Angiotensin-converting enzyme 2: implications for blood pressure and kidney disease.

text: PURPOSE OF REVIEW Angiotensin-converting enzyme 2 (ACE 2), the main product of which is Ang 1-7, which binds to its receptor, Mas, is an important member of the renin-angiotensin system. RECENT FINDINGS A substantial body of research indicates that ACE2 is cardioprotective and renoprotective. ACE2 participates in a pathway that is counterregulatory to the effects of angiotensin II (Ang II). The mechanisms by which the protective effects of ACE2 occur are just beginning to be elucidated. SUMMARY As ACE2 appears to exert protective effects within the kidney and vasculature, recent data indicate that how it is expressed, what regulates it, and how it interacts with other biological systems may ultimately have clinical implications.


title: TRIM56 is an essential component of the TLR3 antiviral signaling pathway.

text: Members of the tripartite motif (TRIM) proteins are being recognized as important regulators of host innate immunity. However, specific TRIMs that contribute to TLR3-mediated antiviral defense have not been identified. We show here that TRIM56 is a positive regulator of TLR3 signaling. Overexpression of TRIM56 substantially potentiated extracellular dsRNA-induced expression of interferon (IFN)-β and interferon-stimulated genes (ISGs), while knockdown of TRIM56 greatly impaired activation of IRF3, induction of IFN-β and ISGs, and establishment of an antiviral state by TLR3 ligand and severely compromised TLR3-mediated chemokine induction following infection by hepatitis C virus. The ability to promote TLR3 signaling was independent of the E3 ubiquitin ligase activity of TRIM56. Rather, it correlated with a physical interaction between TRIM56 and TRIF. Deletion of the C-terminal portion of TRIM56 abrogated the TRIM56-TRIF interaction as well as the augmentation of TLR3-mediated IFN response. Together, our data demonstrate TRIM56 is an essential component of the TLR3 antiviral signaling pathway and reveal a novel role for TRIM56 in innate antiviral immunity.


title: Comparison of ED95 of Butorphanol and Sufentanil for gastrointestinal endoscopy sedation: a randomized controlled trial.

text: BACKGROUND Butorphanol, a synthetic opioid partial agonist analgesic, has been widely used to control perioperative pain. However, the ideal dose and availability of butorphanol for gastrointestinal (GI) endoscopy are not well known. The aim of this study was to evaluated the 95% effective dose (ED95) of butorphanol and sufentanil in GI endoscopy and compared their clinical efficacy, especially regarding the recovery time. METHODS The study was divided into two parts. For the first part, voluntary patients who needed GI endoscopy anesthesia were recruited to measure the ED95 of butorphanol and sufentanil needed to achieve successful sedation before GI endoscopy using the sequential method (the Dixon up-and-down method). The second part was a double-blind, randomized study. Two hundred cases of painless GI endoscopy patients were randomly divided into two groups (n = 100), including group B (butorphanol at the ED95 dose) and group S (sufentanil at the ED95 dose). Propofol was infused intravenously as the sedative in both groups. The recovery time, visual analogue scale (VAS) score, hand grip strength, fatigue severity scores, incidence of nausea and vomiting, and incidence of dizziness were recorded. RESULTS The ED95 of butorphanol for painless GI endoscopy was 9.07 μg/kg (95% confidence interval: 7.81-19.66 μg/kg). The ED95 of sufentanil was 0.1 μg/kg (95% CI, 0.079-0.422 μg/kg). Both butorphanol and sufentanil provided a good analgesic effect for GI endoscopy. However, the recovery time for butorphanol was significantly shorter than that for sufentanil (P < 0.05, group B vs. group S:21.26 ± 7.70 vs. 24.03 ± 7.80 min). CONCLUSIONS Butorphanol at 9.07 μg/kg was more effective than sufentanil for GI endoscopy sedation and notably reduced the recovery time. TRIAL REGISTRATION Chinese Clinical Trail Registry (Registration number # ChiCTR1900022780; Date of Registration on April 25rd, 2019).


title: A stochastic model for cancer stem cell origin in metastatic colon cancer.

text: Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.


title: Reversal agents: do we need to administer with neuromuscular monitoring - an observational study.

text: Background and Aims In clinical practice, in the majority of patients, recovery from the effect of muscle relaxants is assessed using subjective methods such as head lift, eye-opening, or by sustained hand grip after giving anticholinesterases (neostigmine) at the end of surgery. We planned a prospective observational cohort study to test the hypothesis that objective neuromuscular monitoring can help us in avoiding the use of anticholinesterases for reversal. Methods The patients posted for surgery of <2 h duration were included in the study. The cohort of patients was formed on the basis of those who were exposed to objective neuromuscular monitoring of recovery (train-of-four [TOF] ratio of 0.9 or more; exposed group) and the patients who were not exposed to objective neuromuscular monitoring (non-exposed group) acting as a control. Using objective neuromuscular monitoring, the time required for recovery from muscle relaxation when neostigmine was not given for reversal was noted and it was then compared with that of the control group. Results A total of 190 patients were enrolled over a period of 3 years. With the use of TOF ratio of 0.9 for extubation, patients safely recovered from neuromuscular blockade, without using neostigmine, with no difference in the mean recovery time (14.48 ± 1.138 min) as compared to the control group (12.14 ± 1.067 min, P = 0.139). There was no incidence of reintubation in post-operative period. Conclusion With objective neuromuscular monitoring, we can ensure complete recovery from the neuromuscular blockade while avoiding the use of anticholinesterases.


title: Real-time parameter estimation of Zika outbreaks using model averaging.

text: Early prediction of the final size of any epidemic and in particular for Zika disease outbreaks can be useful for health authorities in order to plan the response to the outbreak. The Richards model is often been used to estimate epidemiological parameters for arboviral diseases based on the reported cumulative cases in single- and multi-wave outbreaks. However, other non-linear models can also fit the data as well. Typically, one follows the so called post selection estimation procedure, i.e., selects the best fitting model out of the set of candidate models and ignores the model uncertainty in both estimation and inference since these procedures are based on a single model. In this paper we focus on the estimation of the final size and the turning point of the epidemic and conduct a real-time prediction for the final size of the outbreak using several non-linear models in which these parameters are estimated via model averaging. The proposed method is applied to Zika outbreak data in four cities from Colombia, during the outbreak ocurred in 2015-2016.


The Psychological Impact of COVID-19 Pandemic on Medical Staff in Guangdong, China: A Cross-Sectional Study.


title: Incidence of viral respiratory pathogens causing exacerbations in adult cystic fibrosis patients.

text: Respiratory infections caused by respiratory viruses are common in paediatric cystic fibrosis (CF) patients and are associated with increased morbidity. There is only little data on the incidence of viral respiratory pathogens causing exacerbations in the adult CF patient population. In this observational pilot study we show, by using molecular as well as conventional techniques for viral isolation, that during 1 y a viral pathogen could be isolated in 8/24 (33%) adult CF patients who presented with a pulmonary exacerbation. This result shows that there is a considerable incidence of viral pathogens in pulmonary exacerbations in adult CF patients. Newly identified viruses such as pandemic influenza A/H1N1, human metapneumovirus, human bocavirus, and human coronavirus NL63 were not detected in our population, except for 1 human coronavirus NL63.


WHO raises flu pandemic alert to level 5.


The challenging battle of mankind against COVID-19 outbreak: Is this global international biological catastrophe the beginning of a new era?


Efficacy of ventilation through a customized novel cuffed airway exchange catheter: a tracheal/lung model study.


title: Upregulation of endothelial cell adhesion molecules characterizes veins close to granulomatous infiltrates in the renal cortex of cats with feline infectious peritonitis and is indirectly triggered by feline infectious peritonitis virus-infected monocytes in vitro.

text: One of the most characteristic pathological changes in cats that have succumbed to feline infectious peritonitis (FIP) is a multifocal granulomatous phlebitis. Although it is now well established that leukocyte extravasation elicits the inflammation typically associated with FIP lesions, relatively few studies have aimed at elucidating this key pathogenic event. The upregulation of adhesion molecules on the endothelium is a prerequisite for stable leukocyte-endothelial cell (EC) adhesion that necessarily precedes leukocyte diapedesis. Therefore, the present work focused on the expression of the EC adhesion molecules and possible triggers of EC activation during the development of FIP. Immunofluorescence analysis revealed that the endothelial expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was elevated in veins close to granulomatous infiltrates in the renal cortex of FIP patients compared to non-infiltrated regions and specimens from healthy cats. Next, we showed that feline venous ECs become activated when exposed to supernatant from feline infectious peritonitis virus (FIPV)-infected monocytes, as indicated by increased adhesion molecule expression. Active viral replication seemed to be required to induce the EC-stimulating activity in monocytes. Finally, adhesion assays revealed an increased adhesion of naive monocytes to ECs treated with supernatant from FIPV-infected monocytes. Taken together, our results strongly indicate that FIPV activates ECs to increase monocyte adhesion by an indirect route, in which proinflammatory factors released from virus-infected monocytes act as key intermediates.


title: Quinoxaline Derivatives as Antiviral Agents: A Systematic Review.

text: BACKGROUND In recent decades, several viruses have jumped from animals to humans, triggering sizable outbreaks. The current unprecedent outbreak SARS-COV-2 is prompting a search for new cost-effective therapies to combat this deadly pathogen. Suitably functionalized polysubstituted quinoxalines show very interesting biological properties (antiviral, anticancer, and antileishmanial), ensuring them a bright future in medicinal chemistry. OBJECTIVES Focusing on the promising development of new quinoxaline derivatives as antiviral drugs, this review forms part of our program on the anti-infectious activity of quinoxaline derivatives. METHODS Study compiles and discusses recently published studies concerning the therapeutic potential of the antiviral activity of quinoxaline derivatives, covering the literature between 2010 and 2020. RESULTS A final total of 20 studies included in this review. CONCLUSIONS This review points to a growing interest in the development of compounds bearing a quinoxaline moiety for antiviral treatment. This promising moiety with different molecular targets warrants further investigation, which may well yield even more encouraging results regarding this scaffold.