title: Protein refolding using chemical refolding additives.

text: In laboratories and manufacturing settings, a rapid and inexpensive method for the preparation of a target protein is crucial for promoting resesrach in protein science and engineering. Inclusion-body-based protein production is a promising method because high yields are achieved in the upstream process, although the refolding of solubilized, unfolded proteins in downstream processes often leads to significantly lower yields. The most challenging problem is that the effective condition for refolding is protein dependent and is therefore difficult to select in a rational manner. Accordingly, considerable time and expense using trial-and-error approaches are often needed to increase the final protein yield. Furthermore, for certain target proteins, finding suitable conditions to achieve an adequate yield cannot be obtained by existing methods. Therefore, to convert such a troublesome refolding process into a routine one, a wide array of methods based on novel technologies and materials have been developed. These methods select refolding conditions where productive refolding dominates over unproductive aggregation in competitive refolding reactions. This review focuses on synthetic refolding additives and describes the concepts underlying the development of reported chemical additives or chemical-additive-based methods that contribute to the emergence of a universal refolding method.


Potential mechanisms by which the oxygen-ozone (O2-O3) therapy could contribute to the treatment against the coronavirus COVID-19.


title: Comparison of Abbott ID Now, Diasorin Simplexa, and CDC FDA EUA methods for the detection of SARS-CoV-2 from nasopharyngeal and nasal swabs from individuals diagnosed with COVID-19.

text: Dozens of in vitro diagnostics (IVDs) have received emergency use authorization (EUA) from the U.S. Food & Drug Administration (FDA) for the detection of SARS-CoV-2, but little has been studied to determine how well these assays perform using clinical specimens.….


Silver Linings: An Opportunity to Improve Clinical Paradigms After the COVID-19 Pandemic.


title: Could interferon-gamma be a therapeutic target for treating heart failure?

text: The cytokine interferon-gamma (IFN-γ) is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. While a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will (1) discuss the source of IFN-γ in the diseased heart; (2) summarize the data from animal studies; (3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; (4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and (5) present the clinical evidence supporting a role for IFN-γ in heart failure.


title: Isolation of an infectious endogenous retrovirus in a proportion of live attenuated vaccines for pets.

text: The genomes of all animal species are colonized by endogenous retroviruses (ERVs). Although most ERVs have accumulated defects that render them incapable of replication, fully infectious ERVs have been identified in various mammals. In this study, we isolated a feline infectious ERV (RD-114) in a proportion of live attenuated vaccines for pets. Isolation of RD-114 was made in two independent laboratories using different detection strategies and using vaccines for both cats and dogs commercially available in Japan or the United Kingdom. This study shows that the methods currently employed to screen veterinary vaccines for retroviruses should be reevaluated.


title: Superior vena cava syndrome: role of the interventionalist.

text: Superior vena cava syndrome results from the obstruction of blood flow through the superior vena cava and is most often due to thoracic malignancy. However, benign etiologies are on the rise secondary to more frequent use of intravascular devices such as central venous catheters and pacemakers. Although rarely a medical emergency, the symptoms can be alarming, particularly to the patient. Traditionally, superior vena cava syndrome has been managed with radiotherapy and chemotherapy. But interventional endovascular techniques have made inroads that offer a safe, rapid, and durable response. In many cases, it may be the only reasonable treatment. Because of this, an approach to endovascular treatment of this condition must be in the armamentarium of the interventional radiologist. This review will provide the reader with an insight into the etiology, pathophysiology, and various management principles of superior vena cava syndrome. The focus will be on understanding the techniques used during various endovascular interventions, including angioplasty, stenting, and pharmacomechanical thrombolysis. Discussion will also be centred on possible complications and current evidence as well as controversies regarding these approaches.


title: Laparoscopic gastrectomy with D2 lymphadenectomy for gastric cancer: initial Egyptian experience at the National Cancer Institute.

text: BACKGROUND Laparoscopic gastrectomy has been used as a superior alternative to open gastrectomy for the treatment of early gastric cancer. However, the application of laparoscopic D2 lymphadenectomy remains controversial. This study aimed to evaluate the feasibility and outcomes of laparoscopic gastrectomy with D2 lymphadenectomy for gastric cancer. RESULTS Between May 2016 and May 2018, twenty-five consecutive patients with gastric cancer underwent laparoscopic D2 gastrectomy: eighteen patients (72%) underwent distal gastrectomy, four patients (16%) underwent total gastrectomy, and three patients (12%) underwent proximal gastrectomy. The median number of lymph nodes retrieved was 18 (5-35). A positive proximal margin was detected in 2 patients (8%). The median operative time and amount of blood loss were 240 min (200-330) and 250 ml (200-450), respectively. Conversion to an open procedure was performed in seven patients (28%). The median hospital stay period was 8 days (6-30), and the median time to start oral fluids was 4 days (3-30). Postoperative complications were detected in 4 patients (16%). There were two cases of mortality (8%) in the postoperative period, and two patients required reoperation (8%). CONCLUSIONS Laparoscopic gastrectomy with D2 lymphadenectomy can be carried out safely and in accordance with oncologic principles.


Guidelines for laparoscopic peritoneal dialysis access surgery.


title: Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial.

text: BACKGROUND The Solitaire Flow Restoration Device is a novel, self-expanding stent retriever designed to yield rapid flow restoration in acute cerebral ischaemia. We compared the efficacy and safety of Solitaire with the standard, predicate mechanical thrombectomy device, the Merci Retrieval System. METHODS In this randomised, parallel-group, non-inferiority trial, we enrolled patients from 18 sites (17 in the USA and one in France). Patients were eligible for inclusion if they had acute ischaemic stroke with moderate to severe neurological deficits and were treatable by thrombectomy within 8 h of stroke symptom onset. We used a computer-generated randomisation sequence to randomly allocate patients to receive thrombectomy treatment with either Solitaire or Merci (1:1; block sizes of four and stratified by centre and stroke severity). The primary endpoint was Thrombolysis In Myocardial Ischemia (TIMI) scale 2 or 3 flow in all treatable vessels without symptomatic intracranial haemorrhage, after up to three passes of the assigned device, as assessed by an independent core laboratory, which was masked to study assignment. Primary analysis was done by intention to treat. A prespecified efficacy stopping rule triggered an early halt to the trial. The study is registered with ClinicalTrials.gov, number NCT 01054560. RESULTS Between February, 2010, and February, 2011, we randomly allocated 58 patients to the Solitaire group and 55 patients to the Merci group. The primary efficacy outcome was achieved more often in the Solitaire group than it was in the Merci group (61%vs 24%; difference 37% [95% CI 19-53], odds ratio [OR] 4·87 [95% CI 2·14-11·10]; p(non-inferiority)<0·0001, p(superiority)=0·0001). More patients had good 3-month neurological outcome with Solitaire than with Merci (58%vs 33%; difference 25% [6-43], OR 2·78 [1·25-6·22]; p(non-inferiority)=0·0001, p(superiority)=0·02). 90-day mortality was lower in the Solitaire group than it was in the Merci group (17 vs 38; difference -21% [-39 to -3], OR 0·34 [0·14-0·81]; p(non-inferiority)=0·0001, p(superiority)=0·02). INTERPRETATION The Solitaire Flow Restoration Device achieved substantially better angiographic, safety, and clinical outcomes than did the Merci Retrieval System. The Solitaire device might be a future treatment of choice for endovascular recanalisation in acute ischaemic stroke. FUNDING Covidien/ev3.


title: Efficacy and safety of a vessel sealing system in oral cancer resection and reconstructive surgery.

text: OBJECTIVE Currently, many studies are being performed that focus on the efficacy and safety of the vessel sealing system (VSS) in various fields of surgery. However, in the field of oral cancer surgery, the efficacy and safety of VSS use have not been clarified. METHODS One hundred and fifty-one patients underwent oral cancer resection and reconstructive surgery. They were divided into two groups: Ligasure vessel sealing system (LVSS) group and conventional surgery (CS) as control. Intra-operative blood loss, operating time, and incidence of post-operative complications and recurrence were analyzed. RESULTS LVSS use significantly reduced intra-operative blood loss. The operating time was shortened only in mandibular gingiva cancer surgery. There were no differences between the two groups with regard to the incidence of post-operative complications and recurrence. CONCLUSIONS LVSS use was found to be effective and proved to be efficient and safe, and may be useful in oral cancer surgery.


title: Evaluating the Commercial Airliner Cabin Environment with Different Air Distribution Systems.

text: Ventilation systems for commercial airliner cabins are important in reducing contaminant transport and maintaining thermal comfort. To evaluate the performance of a personalized displacement ventilation system, a conventional displacement ventilation system, and a mixing ventilation system, this study first used the Wells-Riley equation integrated with CFD to obtain the SARS quanta value based on a specific SARS outbreak on a flight. This investigation then compared the three ventilation systems in a seven-row section of a fully occupied, economy-class cabin in Boeing 737 and Boeing 767 airplanes. The SARS quanta generation rate obtained for the index patient could be used in future studies. For all the assumed source locations, the passengers' infection risk by air in the two planes was the highest with the mixing ventilation system, while the conventional displacement ventilation system produced the lowest risk. The personalized ventilation system performed the best in maintaining cabin thermal comfort and can also reduce the infection risk. This system is recommended for airplane cabins. This article is protected by copyright. All rights reserved.


title: Perioperative Considerations During Emergency General Surgery in the Era of COVID-19: A U.S. Experience.

text: The novel coronavirus SARS-CoV-2 (COVID-19) strain has caused a pandemic that affects everyday clinical practice. Care of patients with acute surgical problems is adjusted to minimize exposing health care providers to this highly contagious virus. Our goal is to describe a specific and reproducible perioperative protocol aiming to keep health care providers safe and, simultaneously, not compromise standard of care for surgical patients.


title: Cure or curse? Ambivalent attitudes towards neuroleptic medication in schizophrenia and non-schizophrenia patients.

text: Neuroleptic non-compliance remains a serious challenge for the treatment of psychosis. Non-compliance is predominantly attributed to side effects, lack of illness insight, reduced well-being or poor therapeutic alliance. However, other still neglected factors may also play a role. Further, little is known about whether psychiatric patients without psychosis who are increasingly prescribed neuroleptics differ in terms of medication compliance or about reasons for non-compliance by psychosis patients. As direct questioning is notoriously prone to social desirability biases, we conducted an anonymous survey. After a strict selection process blind to results, 95 psychiatric patients were retained for the final analyses (69 participants with a presumed diagnosis of schizophrenia psychosis, 26 without psychosis). Self-reported neuroleptic non-compliance was more prevalent in psychosis patients than non-psychosis patients. Apart from side effects and illness insight, main reasons for non-compliance in both groups were forgetfulness, distrust in therapist, and no subjective need for treatment. Other notable reasons were stigma and advice of relatives/acquaintances against neuroleptic medication. Gain from illness was a reason for non-compliance in 11-18% of the psychosis patients. Only 9% of all patients reported no side effects and full compliance and at the same time acknowledged that neuroleptics worked well for them. While pills were preferred over depot injections by the majority of patients, depot was judged as an alternative by a substantial subgroup. Although many patients acknowledge the need and benefits of neuroleptic medication, non-compliance was the norm rather than the exception in our samples.


title: The Effects of Social Media Use on Preventive Behaviors during Infectious Disease Outbreaks: The Mediating Role of Self-relevant Emotions and Public Risk Perception.

text: While there has been increasing attention to the role of social media during infectious disease outbreaks, relatively little is known about the underlying mechanisms by which social media use affects risk perception and preventive behaviors during such outbreaks. Using data collected during the 2015 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea, this study explores the relationships among social media use, risk perception, and preventive behaviors by examining the mediating role of two self-relevant emotions: fear and anger. The findings demonstrate that social media use is positively related to both of these emotions, which are also positively related to the public's risk perception. The findings also indicate that social media use can significantly increase preventive behaviors via the two self-relevant emotions and the public's risk perception.


Benefits, Open questions and Challenges of the use of Ultrasound in the COVID-19 pandemic era. The views of a panel of worldwide international experts.


title: Screening strategies for hypertension.

text: BACKGROUND Hypertension is a major public health challenge affecting more than one billion people worldwide; it disproportionately affects populations in low- and middle-income countries (LMICs), where health systems are generally weak. The increasing prevalence of hypertension is associated with population growth, ageing, genetic factors, and behavioural risk factors, such as excessive salt and fat consumption, physical inactivity, being overweight and obese, harmful alcohol consumption, and poor management of stress. Over the long term, hypertension leads to risk for cardiovascular events, such as heart disease, stroke, kidney failure, disability, and premature mortality. Cardiovascular events can be preventable when high-risk populations are targeted, for example, through population-wide screening strategies. When available resources are limited, taking a total risk approach whereby several risk factors of hypertension are taken into consideration (e.g. age, gender, lifestyle factors, diabetes, blood cholesterol) can enable more accurate targeting of high-risk groups. Targeting of high-risk groups can help reduce costs in that resources are not spent on the entire population. Early detection in the form of screening for hypertension (and associated risk factors) can help identify high-risk groups, which can result in timely treatment and management of risk factors. Ultimately, early detection can help reduce morbidity and mortality linked to it and can help contain health-related costs, for example, those associated with hospitalisation due to severe illness and poorly managed risk factors and comorbidities. OBJECTIVES To assess the effectiveness of different screening strategies for hypertension (mass, targeted, or opportunistic) to reduce morbidity and mortality associated with hypertension. SEARCH METHODS An Information Specialist searched the Cochrane Register of Studies (CRS-Web), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS) Bireme, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) without language, publication year, or publication status restrictions. The searches were conducted from inception until 9 April 2020. SELECTION CRITERIA Randomised controlled trials (RCTs) and non-RCTs (NRCTs), that is, controlled before and after (CBA), interrupted time series (ITS), and prospective analytic cohort studies of healthy adolescents, adults, and elderly people participating in mass, targeted, or opportunistic screening of hypertension. DATA COLLECTION AND ANALYSIS Screening of all retrieved studies was done in Covidence. A team of reviewers, in pairs, independently assessed titles and abstracts of identified studies and acquired full texts for studies that were potentially eligible. Studies were deemed to be eligible for full-text screening if two review authors agreed, or if consensus was reached through discussion with a third review author. It was planned that at least two review authors would independently extract data from included studies, assess risk of bias using pre-specified Cochrane criteria, and conduct a meta-analysis of sufficiently similar studies or present a narrative synthesis of the results. MAIN RESULTS We screened 9335 titles and abstracts. We identified 54 potentially eligible studies for full-text screening. However, no studies met the eligibility criteria. AUTHORS' CONCLUSIONS There is an implicit assumption that early detection of hypertension through screening can reduce the burden of morbidity and mortality, but this assumption has not been tested in rigorous research studies. High-quality evidence from RCTs or programmatic evidence from NRCTs on the effectiveness and costs or harms of different screening strategies for hypertension (mass, targeted, or opportunistic) to reduce hypertension-related morbidity and mortality is lacking.


title: Call for a bigger vision.

text: Science in Canada cannot realize its full potential without clear direction from government.


title: Identification and management of cardiometabolic risk in Canada: a position paper by the cardiometabolic risk working group (executive summary).

text: With the objectives of clarifying the concepts related to "cardiometabolic risk," "metabolic syndrome" and "risk stratification" and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group presents an executive summary of a detailed analysis and position paper that offers a comprehensive and consolidated approach to the identification and management of cardiometabolic risk. The above concepts overlap and relate to the atherogenic process and development of type 2 diabetes. However, there is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider ethnicity-related risk factors in order to appropriately evaluate all individuals in their diverse patient populations.


title: Robotic-assisted laparoscopic myomectomy: the feasibility in single-site system.

text: Objective To evaluate the feasibility of robotic single-site myomectomy (RSSM). Methods Medical records of 355 consecutive women who underwent robotic-assisted laparoscopic myomectomy were retrospectively reviewed. Clinical characteristics were compared between multi-site and single-site systems. After 1:1 propensity score matching for the total myoma number, largest myoma size, and total tumor weight (105 women in each group), surgical outcomes were also compared between the 2 systems. Results A total of 105 (29.6%) and 250 (70.4%) women underwent RSSM and robotic multi-site myomectomy (RMSM), respectively. RSSM was more commonly performed in women with lower body mass index (21.6 vs. 22.5 kg/m2, P=0.014), without peritoneal adhesions (7.6% vs. 24.8%, P<0.001), and less (2.6 vs. 4.6, P<0.001) and smaller (6.3 vs. 7.7 cm, P<0.001) myomas compared to RMSM. After propensity score matching, the largest myoma size (P=0.143), total myoma number (P=0.671), and tumor weight (P=0.510) were not significantly different between the 2 groups. Although the docking time was significantly longer in the RSSM group (5.1 vs. 3.8 minutes, P=0.005), total operation time was similar between RSSM and RMSM groups (145.9 vs. 147.3 minutes, P=0.856). Additionally, hemoglobin decrement was lower in the RSSM group than in the RMSM group (1.4 vs. 1.8 g/dL, P=0.009). No surgical complication was observed after RSSM, while 1 ileus and 2 febrile complications occurred in women that underwent RMSM (0% vs. 2.9%, P=0.246). Conclusion Although RMSM is preferred for women with multiple large myomas in real clinical practice, RSSM seems to be a feasible surgical method for less complicated cases, and is associated with minimal surgical morbidity.


title: Improved arterial blood oxygenation following intravenous infusion of cold supersaturated dissolved oxygen solution.

text: BACKGROUND One of the primary goals of critical care medicine is to support adequate gas exchange without iatrogenic sequelae. An emerging method of delivering supplemental oxygen is intravenously rather than via the traditional inhalation route. The objective of this study was to evaluate the gas-exchange effects of infusing cold intravenous (IV) fluids containing very high partial pressures of dissolved oxygen (>760 mm Hg) in a porcine model. METHODS Juvenile swines were anesthetized and mechanically ventilated. Each animal received an infusion of cold (13 °C) Ringer's lactate solution (30 mL/kg/hour), which had been supersaturated with dissolved oxygen gas (39.7 mg/L dissolved oxygen, 992 mm Hg, 30.5 mL/L). Arterial blood gases and physiologic measurements were repeated at 15-minute intervals during a 60-minute IV infusion of the supersaturated dissolved oxygen solution. Each animal served as its own control. RESULTS Five swines (12.9 ± 0.9 kg) were studied. Following the 60-minute infusion, there were significant increases in PaO2 and SaO2 (P < 0.05) and a significant decrease in PaCO2 (P < 0.05), with a corresponding normalization in arterial blood pH. Additionally, there was a significant decrease in core body temperature (P < 0.05) when compared to the baseline preinfusion state. CONCLUSIONS A cold, supersaturated dissolved oxygen solution may be intravenously administered to improve arterial blood oxygenation and ventilation parameters and induce a mild therapeutic hypothermia in a porcine model.


title: Initial experience of single-port surgery assisted by percutaneous instruments for gastric bypass: a combination of safety and minimally invasive surgery.

text: BACKGROUND We present here the first reported cases of patients undergoing gastric bypass with a hybrid technique that involves a new concept of percutaneous instruments and provides the advantages of minimally invasive single-port surgery while maintaining the triangulation, safety, and timing of operative procedures. METHODS This was a prospective pilot study of eight patients selected for gastric bypass between December 2011 and January 2012 and treated by a technique that combined single SSL port and percutaneous surgical set PPS. We performed hand-sewn gastrojejunostomy in all cases. We analyzed preliminary results at 1 month and focused on the feasibility of the technique, duration of surgery, perioperative complications, and cosmetic results. The Ethics Committee of our institution approved this study and we obtained the informed consent of each patient. RESULTS We completed the procedure successfully in all patients. No conversions to laparotomy or classic laparoscopy were required. The average time of surgery was 112 min (85-155). Length of hospital stay was 4 days (3-5). One patient was re-admitted on the seventh postoperative day for gastrointestinal bleeding from the gastrojejunostomy suture and treated by endoscopic clipping. Residual scars were less than 2 cm for the single midline port and 2 mm for the percutaneous instruments. CONCLUSIONS This new technique combines the advantages of single-port surgery with the safety of conventional laparoscopy by using percutaneous instruments and leaves minimal scarring. It is likely that the use of percutaneous instrumentation will become widespread in all areas of laparoscopic surgery.


title: A novel technique to retrieve a maldeployed vascular closure device.

text: PURPOSE To report a novel technique for endovascular retrieval of a maldeployed vascular closure device, obviating the need for a femoral cutdown. TECHNIQUE To remove a 6-F Angio-Seal device that embolized to the superficial femoral artery, the contralateral common femoral artery was accessed, and an 8-F, 65-cm-long sheath was inserted just proximal to the embolus. A second semistiff 0.035-inch buddy wire was advanced past the lesion along the sheath. A 0.014-inch wire was advanced past the embolus, and a SpiderFX embolic protection device was deployed 1 cm past the embolized Angio-Seal device. The sheath was advanced so as to push the embolus into the filter. The sheath and the filter containing the Angio-Seal device were then removed. CONCLUSION Endovascular retrieval of an embolized Angio-Seal device can be done using an embolic filter device, restoring arterial flow to the limb.


Nepalese Medical Students in the COVID-19 Pandemic: Ways Forward.


title: Fate of Environmental Pollutants.

text: This annual review covers the literature published in 2017 on topics related to the occurrence and fate of emerging environmental pollutants in wastewater. Due to the vast amount of literature published on this topic, we have discussed only a portion of the quality research publications, due to the limitation of space. The abstract search was carried out using Web of Science, and the abstracts were selected based on their relevance. In few cases, full-text articles were referred to better understand new findings. This review is divided into the following sections: antibioticresistant bacteria (ARBs) and antibiotic-resistant genes (ARGs), disinfection by-products (DBPs), estrogens, pesticides, pharmaceuticals and personal care products (PPCPs), and microplastics, a new section added this year.


title: Guidance for management of cancer surgery during the COVID-19 pandemic.

text: Summary During the coronavirus disease 2019 (COVID-19) pandemic, delaying lifesaving cancer surgeries must be done with extreme caution and thoughtfulness. Modelling indicates that delays in high-risk cancer surgeries beyond 6 weeks could affect long-term outcomes for thousands of Canadians. Consequently, it is possible that postponing cancer surgery without consideration of its implications could cost more lives than can be saved by diverting all surgical resources to COVID-19. This article provides general guidance on supporting curative surgical treatment where appropriate and with available resources.


Industry shows increased appetite for macrophage biology.


title: Targeted benefits of prolonged-infusion piperacillin-tazobactam in an in vitro infection model of Pseudomonas aeruginosa.

text: Given the inconsistent clinical findings, our goal was to characterize the pharmacodynamics (PDs) of prolonged-infusion piperacillin-tazobactam (TZP) in an in vitro pharmacodynamic model of Pseudomonas aeruginosa. Specifically, the study was designed to investigate the influence of MIC on the activity of prolonged-infusion TZP using pharmacokinetics (PKs) consistent with a non-critically ill patient population. There was no benefit with prolonged- compared with standard-infusion TZP against isolates with susceptible MICs of 8 or 16 mg/L. However, prolonged-infusion TZP produced more than two times the final bacterial kill against less susceptible isolates with an intermediate MIC of 32 mg/L. The PDs of TZP were well described by a sigmoid Emax model (r(2) = 0.84) where %ƒT>MIC thresholds of 27 and 75% were associated with bacteriostatic and bactericidal effects, respectively. However, the well-established PD relationship with %ƒT>MIC was not observed with prolonged-infusion TZP. In conclusion, this study characterizes the targeted benefits of prolong-infusion TZP based on pathogen MIC, and supports the assertion that the benefits are selective and most likely observed in patients with less susceptible pathogens or altered PKs.


Guidelines for privileging, credentialing, and proctoring to perform GI endoscopy.


Proposed protocol to keep COVID-19 out of hospitals.


title: Antibiotic prophylaxis for prevention of urinary tract infections in the first year of life in children with vesicoureteral reflux diagnosed in the workup of antenatal hydronephrosis: a systematic review.

text: BACKGROUND Children with antenatal hydronephrosis (ANH) diagnosed with postnatal asymptomatic vesicoureteral reflux (VUR) are thought to be at higher risk of urinary tract infection (UTI). As such, continuous antibiotic prophylaxis (CAP) is empirically recommended until age of toilet training; however, there are limited data to support this. The objective of this systematic review was to summarize the existing data and compare UTI rates in infants with asymptomatic VUR on CAP during the first year of life, to those not on CAP. Secondary objectives were to determine associated risk factors with UTI development. METHODS A systematic search of all relevant studies and abstracts was conducted using 4 electronic databases by utilizing appropriate key words by an expert hospital librarian. Eligible studies included children with prenatal hydronephrosis, asymptomatic VUR with or without CAP, and reported on development of UTI in the first year. RESULTS Of 6903 citations screened, 18 were selected, giving a total population of 829 (69.4% male, median age 57 days) who met the inclusion criteria. Most studies were retrospective and of low-quality evidence. Overall, 15.4% of patients developed at least one breakthrough UTI and females had a higher risk of UTI (odds ratio (OR) 2.3, 95% CI 1.1-4.7). Comparison with children not taking CAP was not readily reported, and meta-analysis could not be completed. CONCLUSIONS Randomized controlled trials and standardized reporting of clinical variables are required to understand the protective effect of antibiotic prophylaxis in this cohort.


title: Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment.

text: OBJECTIVES Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality. DESIGN Prospective cohort study from December 4, 2011, to April 7, 2013. SETTING General and cardiac/cardiovascular PICUs at seven sites. PATIENTS Randomly selected PICU patients from their first PICU admission. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of ≥ 3 from preillness to hospital discharge) were 4.6% (site range, 2.6-7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3-5.0%). Morbidity and mortality were significantly (p < 0.001) associated with physiological instability (measured with the Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality III score. The three-level goodness-of-fit test indicated satisfactory performance for the derivation and validation sets (p > 0.20). Predictive ability assessed with the volume under the surface was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios. CONCLUSIONS New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality.


title: Increased diaphragmatic contribution to inspiratory effort during neurally adjusted ventilatory assistance versus pressure support: an electromyographic study.

text: BACKGROUND Neurally adjusted ventilatory assist (NAVA), regulated exclusively by the electromyographic activity (EA) of the diaphragm (EAdi), could affect the distribution of neural drive to the various inspiratory muscles. The objective of this study was to compare EAdi, EA of the scalene (EAscal), and EA of the alae nasi (EAan), according to the ventilatory mode and assist level in 12 mechanically ventilated patients. METHODS Seven assist levels of pressure support ventilation (PSV) and NAVA were sequentially applied. EAdi, EAscal, and EAan were quantified and expressed as a percentage of their maximum values. The relative contributions of extradiaphragmatic muscles to inspiratory efforts were assessed by calculating EAscal/EAdi and EAan/EAdi ratios. Three assist levels for each of the two ventilatory modes that resulted in EAdi values of 80 to 100%, 60 to 80%, and 40 to 60% were assigned to three groups (N1, N2, and N3). Results are expressed as median and interquartile range. RESULTS EA of inspiratory muscles decreased during PSV and NAVA (P < 0.0001). Although EAdi remained constant within groups (P = 0.9), EAscal was reduced during NAVA compared with PSV in N1 and N3 (65% [62 to 64] and 27% [18 to 34] in NAVA vs. 90% [81 to 100] and 49% [40 to 55] in PSV, P = 0.007). Altogether, EAscal/EAdi and EAan/EAdi ratios were lower in NAVA than PSV (0.7 [0.6 to 0.7] and 0.7 [0.6 to 0.8] in NAVA vs. 0.9 [0.8 to 1.1] and 0.9 [0.7 to 1.1] in PSV, P < 0.05). CONCLUSIONS NAVA and PSV both reduced extradiaphragmatic inspiratory muscle activity, in proportion to the level of assistance. Compared with PSV, NAVA resulted in a predominant contribution of the diaphragm to inspiratory effort.


Pectoralis block for breast surgery: A surgical concern?


Posterior Tracheal Laceration Treated with a Stent.


title: Post-consumer plastic packaging waste in England: Assessing the yield of multiple collection-recycling schemes.

text: The European Commission (EC) recently introduced a 'Circular Economy Package', setting ambitious recycling targets and identifying waste plastics as a priority sector where major improvements are necessary. Here, the authors explain how different collection modalities affect the quantity and quality of recycling, using recent empirical data on household (HH) post-consumer plastic packaging waste (PCPP) collected for recycling in the devolved administration of England over the quarterly period July-September 2014. Three main collection schemes, as currently implemented in England, were taken into account: (i) kerbside collection (KS), (ii) household waste recycling centres (HWRCs) (also known as 'civic amenity sites'), and (iii) bring sites/banks (BSs). The results indicated that: (a) the contribution of KS collection scheme in recovering packaging plastics is higher than HWRCs and BBs, with respective percentages by weight (wt%) 90%, 9% and 1%; (b) alternate weekly collection (AWC) of plastic recyclables in wheeled bins, when collected commingled, demonstrated higher yield in KS collection; (c) only a small percentage (16%) of the total amount of post-consumer plastics collected in the examined period (141 kt) was finally sent to reprocessors (22 kt); (c) nearly a third of Local Authorities (LAs) reported insufficient or poor data; and (d) the most abundant fractions of plastics that finally reached the reprocessors were mixed plastic bottles and mixed plastics.


Borrow crisis tactics to get COVID-19 supplies to where they are needed.


title: Comparative evaluation of three-dimensional Gd-EOB-DTPA-enhanced MR fusion imaging with CT fusion imaging in the assessment of treatment effect of radiofrequency ablation of hepatocellular carcinoma.

text: PURPOSE To assess the feasibility of fusion of pre- and post-ablation gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) to evaluate the effects of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), compared with similarly fused CT images PATIENTS AND METHODS This retrospective study included 67 patients with 92 HCCs treated with RFA. Fusion images of pre- and post-RFA dynamic CT, and pre- and post-RFA Gd-EOB-DTPA-MRI were created, using a rigid registration method. The minimal ablative margin measured on fusion imaging was categorized into three groups: (1) tumor protruding outside the ablation zone boundary, (2) ablative margin 0-<5.0 mm beyond the tumor boundary, and (3) ablative margin ≥5.0 mm beyond the tumor boundary. The categorization of minimal ablative margins was compared between CT and MR fusion images. RESULTS In 57 (62.0%) HCCs, treatment evaluation was possible both on CT and MR fusion images, and the overall agreement between them for the categorization of minimal ablative margin was good (κ coefficient = 0.676, P < 0.01). MR fusion imaging enabled treatment evaluation in a significantly larger number of HCCs than CT fusion imaging (86/92 [93.5%] vs. 62/92 [67.4%], P < 0.05). CONCLUSIONS Fusion of pre- and post-ablation Gd-EOB-DTPA-MRI is feasible for treatment evaluation after RFA. It may enable accurate treatment evaluation in cases where CT fusion imaging is not helpful.


title: Immunopathology of SARS-CoV-2 Infection: Immune Cells and Mediators, Prognostic Factors, and Immune-Therapeutic Implications.

text: The present is a comprehensive review of the immunopathology of Covid-19. The immune reaction to SARS-CoV-2 infection is characterized by differentiation and proliferation of a variety of immune cells with immune mediator production and release, and activation of other pathogen resistance mechanisms. We fully address the humoral and cellular immune changes induced by the virus, with particular emphasis on the role of the "cytokine storm" in the evolution of the disease. Moreover, we also propose some immune alterations (i.e., inflammatory parameters, cytokines, leukocytes and lymphocyte subpopulations) as prognostic markers of the disease. Furthermore, we discuss how immune modifying drugs, such as tocilizumab, chloroquine, glucocorticoids and immunoglobulins, and blood purification therapy, can constitute a fundamental moment in the therapy of the infection. Finally, we made a critical analysis of a number of substances, not yet utilized, but potentially useful in SARS-CoV-2 patients, such as IFN lambda, TNF blockers, ulinastatin, siponimod, tacrolimus, mesenchymal stem cells, inhibitors of mononuclear macrophage recruitment, IL-1 family antagonists, JAK-2 or STAT-3 inhibitors.


Underpromise, overdeliver.


title: Intraoperative cone beam computed tomography-guided endovascular recanalization of an interrupted aorta.

text: A 42-year-old man sustained a stroke secondary to malignant hypertension and was found to have complete aortic interruption. We report a case of real-time image-guided endovascular repair to highlight the value of preprocedural planning and intraprocedural cone beam computed tomography. Two-dimensional fluoroscopy enhanced with three-dimensional landmarks from cone beam computed tomography was used to direct a Nykanen radiofrequency wire (Baylis Medical, Montreal, Quebec, Canada) through the interruption, avoiding critical adjacent structures. A covered Cheatham-Platinum stent (NuMED, Inc, Hopkinton, NY) was deployed successfully, recanalizing the thoracic aorta. The pressure gradient normalized, and the patient was discharged on postoperative day 1. At 10-month follow-up, the patient was on an antihypertensive regimen of two minimum-dose drugs.


title: McGRATH MAC video laryngoscope for insertion of a transoesophageal echocardiography probe: A randomised controlled trial.

text: BACKGROUND Transoesophageal echocardiography (TOE) probe insertion in anaesthetised patients can cause pharyngeal and oesophageal injuries. Kim et al. have shown that insertion assisted by a Macintosh laryngoscope can reduce such complications but it may sometimes be difficult to observe the passage of a TOE probe. The McGRATH MAC (McGRATH) has been shown to provide a better view of the glottis, piriform fossa and oesophageal inlet during tracheal intubation than the Macintosh. OBJECTIVE We hypothesised that the McGRATH provided better visualisation of the oesophageal inlet and was useful as an aid to TOE probe placement, possibly reducing the incidence of pharyngeal injury related to insertion, compared with the Macintosh. DESIGN A randomised controlled trial. SETTING The study was conducted in a university hospital from February to December 2014. PATIENTS One hundred patients undergoing elective surgery under intraoperative TOE monitoring were randomised to either a Macintosh group or a McGRATH group. INTERVENTIONS Macintosh and McGRATH were used to visualise the passage of the TOE probe and guide its insertion. MAIN OUTCOME MEASURES Visibility of the oesophageal inlet, the number of TOE insertion attempts and incidence of pharyngeal mucosal injury after the TOE probe had been removed were assessed. RESULTS The percentage of patients in whom the oesophageal inlet was visible was higher in the McGRATH group (88%) than in the Macintosh group (41%) (P < 0.01). The number of TOE probe insertion attempts was significantly smaller in the McGRATH group than in the Macintosh group (P = 0.039). The incidence of pharyngeal mucosal injury was significantly smaller in the McGRATH group (4%) than in the Macintosh group (16%; P = 0.042). CONCLUSION The McGRATH provided a better view of the oesophageal inlet and was useful as an aid to TOE probe placement, possibly reducing the incidence of pharyngeal injury related to its insertion. TRIAL REGISTRATION University Hospital Medical Information Network in Japan (UMIN) 000012970.


title: Chronic kidney disease and valvular heart disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

text: Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research.


Do no harm: reaffirming the value of evidence and equipoise while minimizing cognitive bias in the COVID-19 era.


title: Molecular epidemiology of human coronavirus OC43 reveals evolution of different genotypes over time and recent emergence of a novel genotype due to natural recombination.

text: Although human coronavirus OC43-OC43 (HCoV-OC43) is the coronavirus most commonly associated with human infections, little is known about its molecular epidemiology and evolution. We conducted a molecular epidemiology study to investigate different genotypes and potential recombination in HCoV-OC43. Twenty-nine HCoV-OC43 strains from nasopharyngeal aspirates, collected from 2004 to 2011, were subjected to RNA-dependent RNA polymerase (RdRp), spike, and nucleocapsid gene analysis. Phylogenetic analysis showed at least three distinct clusters of HCoV-OC43, although 10 unusual strains displayed incongruent phylogenetic positions between RdRp and spike genes. This suggested the presence of four HCoV-OC43 genotypes (A to D), with genotype D most likely arising from recombination. The complete genome sequencing of two genotype C and D strains and bootscan analysis showed recombination events between genotypes B and C in the generation of genotype D. Of the 29 strains, none belonged to the more ancient genotype A, 5 from 2004 belonged to genotype B, 15 from 2004 to 2006 belonged to genotype C, and 1 from 2004 and all 8 from 2008 to 2011 belonged to the recombinant genotype D. Molecular clock analysis using spike and nucleocapsid genes dated the most recent common ancestor of all genotypes to the 1950s, genotype B and C to the 1980s, genotype B to the 1990s, and genotype C to the late 1990s to early 2000s, while the recombinant genotype D strains were detected as early as 2004. This represents the first study to describe natural recombination in HCoV-OC43 and the evolution of different genotypes over time, leading to the emergence of novel genotype D, which is associated with pneumonia in our elderly population.


title: Rational design of an ESIPT-based fluorescent probe for selectively monitoring glutathione in live cells and zebrafish.

text: Glutathione (GSH), an extremely important antioxidant, is a major participant in maintaining redox homeostasis and tightly associated with various clinical diseases. Thus, accurate and rapid detection of intracellular GSH is imperative to elucidate its role in physiological and pathological processes. Herein, by modifying 2-(2'-hydroxyphenyl) benzothiazole (HBT) scaffold, we developed an excited-state intramolecular proton transfer (ESIPT)-based fluorescent probe BTFMD for tracking GSH, which exhibited good selectivity, excellent water solubility, a large Stokes shift (181 nm) and fast response rate (within 10 min). Furthermore, the probe was successfully applied for imaging of endogenous GSH in live cells and zebrafish, and probing into the role of GSH in the development of cancer and Parkinson's disease.


docid: gbrjsjoh

title: Pandemic influenza and health system resource gaps in Bali: an analysis through a resource transmission dynamics model.

text: The failure to contain pandemic influenza A(H1N1) 2009 in Mexico has shifted global attention from containment to mitigation. Limited surveillance and reporting have, however, prevented detailed assessment of mitigation during the pandemic, particularly in low- and middle-income countries. To assess pandemic influenza case management capabilities in a resource-limited setting, the authors used a health system questionnaire and density-dependent, deterministic transmission model for Bali, Indonesia, determining resource gaps. The majority of health resources were focused in and around the provincial capital, Denpasar; however, gaps are found in every district for nursing staff, surgical masks, and N95 masks. A relatively low pathogenicity pandemic influenza virus would see an overall surplus for physicians, antivirals, and antimicrobials; however, a more pathogenic virus would lead to gaps in every resource except antimicrobials. Resources could be allocated more evenly across Bali. These, however, are in short supply universally and therefore redistribution would not fill resource gaps.


title: Bacteriophages as vehicles for gene delivery into mammalian cells: prospects and problems.

text: INTRODUCTION The identification of more efficient gene delivery vehicles (GDVs) is essential to fulfill the expectations of clinical gene therapy. Bacteriophages, due to their excellent safety profile, extreme stability under a variety of harsh environmental conditions and the capability for being genetically manipulated, have drawn a flurry of interest to be applied as a newly arisen category of gene delivery platforms. AREAS COVERED The incessant evolutionary interaction of bacteriophages with human cells has turned them into a part of our body's natural ecosystem. However, these carriers represent several barriers to gene transduction of mammalian cells. The lack of evolvement of specialized machinery for targeted cellular internalization, endosomal, lysosomal and proteasomal escape, cytoplasmic entry, nuclear localization and intranuclear transcription poses major challenges to the expression of the phage-carried gene. In this review, we describe pros and cons of bacteriophages as GDVs, provide an insight into numerous barriers that bacteriophages face for entry into and subsequent trafficking inside mammalian cells and elaborate on the strategies used to bypass these barriers. EXPERT OPINION Tremendous genetic flexibility of bacteriophages to undergo numerous surface modifications through phage display technology has proven to be a turning point in the uncompromising efforts to surmount the limitations of phage-mediated gene expression. The revelatory outcomes of the studies undertaken within the recent years have been promising for phage-mediated gene delivery to move from concept to reality.


Editorial: The Year in Review Amidst the COVID-19 Crisis.


title: Preventive behaviors and mental distress in response to H1N1 among university students in Guangzhou, China.

text: OBJECTIVE To investigate the level of and factors involved in influenza virus subtype H1N1 (H1N1)-related preventive behaviors and mental distress among university students in Guangzhou. PARTICIPANTS Self-administered questionnaires were used to collect data for 825 students from 2 universities. RESULTS A total of 49.7% of the participants held misconception(s) concerning H1N1 transmission. Less than 30% washed their hands >10 times/d; 72.3% did not reduce the frequency of touching their mouths, noses, and eyes; only 9.3% would wear face masks if they had influenza-like symptoms. However, 45% worried that one/one's family would contract H1N1, 10.7% were panicking/feeling depressed/feeling emotionally disturbed as a result of H1N1, and 14.9% were fearful about the WHO's H1N1 pandemic announcement. Almost all cognitive variables of this study were significantly associated with mental distress caused by fear of H1N1 (odds ratio [OR] = 0.29-3.81), but very few were associated with adoption of preventive measures (OR = 0.65-1.90). CONCLUSIONS Preventive measures are warranted to alleviate distress in the population studied via health education and promotion.


Reply to "Critical Review of the Literature on Chest CT and Coronavirus Disease (COVID-19): Data Adjustment".


COVID-19: review Indigenous peoples' data.


title: Sensitivity and specificity of on-farm scoring systems and nasal culture to detect bovine respiratory disease complex in preweaned dairy calves.

text: The California (CA) and Wisconsin (WI) clinical scoring systems have been proposed for bovine respiratory disease complex (BRDC) detection in preweaned dairy calves. The screening sensitivity (SSe), for estimating BRDC prevalence in a cohort of calves, diagnostic sensitivity (DSe), for confirming BRDC in ill calves, and specificity (Sp) were estimated for each of the scoring systems, as well as for nasal swab cultures for aerobic bacteria and mycoplasma species. Thoracic ultrasound and auscultation were used as the reference standard tests interpreted in parallel. A total of 536 calves (221 with BRDC and 315 healthy) were sampled from 5 premises in California. The SSe of 46.8%, DSe of 72.6%, and Sp of 87.4% was determined for the CA system. The SSe of 46.0%, DSe of 71.1%, and Sp of 91.2% was determined for the WI system. For aerobic culture, the SSe was 43.4%, DSe was 52.6%, and Sp was 71.3%; for Mycoplasma spp. culture, the SSe was 57.5%, DSe was 68.9%, and Sp was 59.7%. The screening and diagnostic sensitivities of the scoring systems were not significantly different but the Sp of the WI system was greater by 3.8%. Scoring systems can serve as rapid on-farm tools to determine the burden of BRDC in preweaned dairy calves. However, users may expect the SSe to be less than the DSe when confirming BRDC in an ill calf.


title: Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the "end of the road" for renal denervation?

text: Resistant hypertension is a common medical problem that is increasing with the advent of an increasingly older and heavier population. The etiology of resistant hypertension is almost always multifactorial, but the results of numerous studies indicate that renal sympathetic activation is a particularly common cause of resistance to antihypertensive treatment. Consistent with the belief in a pivotal role of renal sympathetic stimulation, there has been a growing interest in renal denervation (RDN) treatment strategies. The long-awaited results of SYMPLICITY HTN-3 study disclosed that the reduction in blood pressure by the SYMPLICITY device did not differ from that in the sham-procedure arm of the study. In the present article, we identify several factors that explain why the study failed to demonstrate any benefit from the intervention. The reasons are multifactorial and include inadequate screening at entry and frequent medication changes during the study. Additional problems include the lack of experience of many operators with the SYMPLICITY device and procedure variability, as attested to by a diminished number of ablation "quadrants." Also a factor was the inability of the first generation Medtronic device to allow four ablations to be performed simultaneously. We recommend that future RDN studies adhere to more rigorous screening procedures, and utilize newer multi-site denervation systems that facilitate four ablations simultaneously. Drug optimization should be achieved by monitoring adherence throughout the study. Nevertheless, we are optimistic about a future role of RDN. To optimize chances of success, increased efforts are necessary to identify the appropriate patients for RDN and investigators must use second and third generation denervation devices and techniques.


docid: oylksebk

title: Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity.

text: Staufen (STAU)1-mediated mRNA decay (SMD) is a posttranscriptional regulatory mechanism in mammals that degrades mRNAs harboring a STAU1-binding site (SBS) in their 3'-untranslated regions (3' UTRs). We show that SMD involves not only STAU1 but also its paralog STAU2. STAU2, like STAU1, is a double-stranded RNA-binding protein that interacts directly with the ATP-dependent RNA helicase up-frameshift 1 (UPF1) to reduce the half-life of SMD targets that form an SBS by either intramolecular or intermolecular base-pairing. Compared with STAU1, STAU2 binds ~10-fold more UPF1 and ~two- to fivefold more of those SBS-containing mRNAs that were tested, and it comparably promotes UPF1 helicase activity, which is critical for SMD. STAU1- or STAU2-mediated augmentation of UPF1 helicase activity is not accompanied by enhanced ATP hydrolysis but does depend on ATP binding and a basal level of UPF1 ATPase activity. Studies of STAU2 demonstrate it changes the conformation of RNA-bound UPF1. These findings, and evidence for STAU1-STAU1, STAU2-STAU2, and STAU1-STAU2 formation in vitro and in cells, are consistent with results from tethering assays: the decrease in mRNA abundance brought about by tethering siRNA-resistant STAU2 or STAU1 to an mRNA 3' UTR is inhibited by downregulating the abundance of cellular STAU2, STAU1, or UPF1. It follows that the efficiency of SMD in different cell types reflects the cumulative abundance of STAU1 and STAU2. We propose that STAU paralogs contribute to SMD by "greasing the wheels" of RNA-bound UPF1 so as to enhance its unwinding capacity per molecule of ATP hydrolyzed.


title: Engineering attenuated virus vaccines by controlling replication fidelity.

text: Long-lasting protection against viral infection is best achieved by vaccination with attenuated viruses. Obtaining stably attenuated vaccine strains has traditionally been an empirical process, which greatly restricts the number of effective vaccines for viral diseases. Here we describe a rational approach for engineering stably attenuated viruses that can serve as safe and effective vaccines. Our approach exploits the observation that restricting viral population diversity by increasing replication fidelity greatly reduces viral tissue tropism and pathogenicity. We show that poliovirus variants with reduced genetic diversity elicit a protective immune response in an animal model of infection. Indeed, these novel vaccine candidates are comparable in efficacy to the currently available Sabin type 1 vaccine strain, but have the added advantage of being more stable, as their increased replication fidelity prevents reversion to the pathogenic wild-type phenotype. We propose that restricting viral quasispecies diversity provides a general approach for the rational design of stable, attenuated vaccines for a wide variety of viruses.


title: Exploring the Feasibility of Pipeline Embolization Device Compared With Stent-Assisted Coiling to Treat Non-saccular, Unruptured, Intradural Vertebral Artery Aneurysms.

text: Object: The pipeline embolization device (PED) has been used to treat non-saccular, unruptured, intradural vertebral artery aneurysms at some institutions. However, there is an absence of large controlled studies validating the feasibility of this treatment. This study aimed to explore the therapeutic feasibility of PED by comparing PED treatment with controlled stent-assisted coiling (SAC). Materials and Methods: Thirty-two PED procedures were matched in a 1:2 manner with 64 SAC procedures based on patient age, sex, aneurysm size, and aneurysm location. Technical factors, procedural complications, angiographic results, and clinical outcomes were analyzed and compared. Results: There was no statistically significant difference in technical factors and procedural complications between the two groups (PED vs. SAC, 9.4 vs. 4.7%, P = 0.397). In multivariate analysis, smoking and therapeutic modality were identified as independent predictors of occlusion. Smoking was a risk factor for aneurysm obliteration [hazard ratio (HR) 0.53; 95% confidence interval (CI), 0.31-0.89; P = 0.018]. Aneurysms treated with PED were more likely to achieve obliteration over time compared with aneurysms treated with SAC (HR 2.97; 95% CI, 1.79-4.93; P < 0.001). The rate of favorable clinical outcomes (modified Rankin Scale (mRS), 0-2) was similar between the two groups (PED vs. SAC, 100 vs. 96.9%, P = 0.551). In the SAC group, one patient had neurological deficit with an mRS of four at the latest follow-up. There was no mortality in either group. Conclusions: The PED and SAC groups showed similar technical factors, procedural complications, angiographic results, and favorable clinical outcomes. Aneurysms treated with PED were more prone to obliteration over time than aneurysms treated with SAC. These outcomes suggest, based on short-term follow-up, PED is a safe and feasible strategy for the treatment of non-saccular, unruptured, intradural vertebral artery aneurysms.


title: One-stop outpatient management of accessory auricle in children with titanium clip.

text: Introduction. Literature on ideal management of accessory auricles is limited. Traditionally, accessory auricles are managed by paediatricians with suture ligation at the base of the accessory auricle to induce ischaemic necrosis (Mehmi et al, 2007). This method can be associated with complications and poor cosmesis thus leading to the vogue of surgical excision ( Frieden et al, 1995; Sebben, 1989). We present our experience in managing these lesions in children with the application of a titanium clip in a one-stop outpatient setting. Methods. Data was collected retrospectively through review of patient records and telephone questionnaire identifying outcomes from the parents' perspective. Results. Of 42 patients, 24 (57.1%) responded. Eleven (26.2%) underwent surgical excision, 6 (14.3%) had no intervention, and 1 (2.4%) was not contactable. All parents were happy with the outcome and would recommend this management to other parents. Twenty-three (96%) had no complications apart from a tiny residual nubbin, which was considered cosmetically acceptable. One child had a residual nubbin that grew in size requiring surgical excision at later stage. Conclusion. Management of accessory auricles by the application of a titanium clip in one-stop outpatient setting is safe, simple, quick, and well tolerated with no need for admission, anaesthesia, or followup due to the low complication rate.


title: COVID-19 Pandemic and Role of Human Saliva as a Testing Biofluid in Point-of-Care Technology.

text: Novel coronavirus disease 2019 (COVID-19) outbreak has termed as a controllable pandemic, and the entire world has come to a standstill trying to mitigate the disease with health systems. Health care providers, around the globe, are fighting day and night. Currently, rapid testing is taking place with the help of nasopharyngeal, oropharyngeal swab, bronchoalveolar lavage, sputum, urine, and blood. All these approaches are invasive or embarrassing to the infected person. It is observed that salivary glands are hosting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) because of angiotensin-converting enzyme 2 and the detection of high viral loads in the saliva and is playing a crucial role in virus transmission, especially from individuals showing absolutely no symptoms. Saliva is proving to be a promising noninvasive sample specimen for the diagnosis of COVID-19, thus helping to monitor the infection and prevent it from further spreading by prompt isolation.


title: Coronavirus Infections in Pediatric Outpatients with Febrile Respiratory Tract Infections in Hiroshima, Japan, over a 3-Year Period.

text: Previously, we conducted a 3-year prospective study to determine the viral causes of acute respiratory tract infections among 495 febrile pediatric outpatients. We collected 495 nasopharyngeal aspirate specimens, and used both real-time PCR assays and viral culture to test each for respiratory viruses other than coronavirus. Here, we used real-time PCR to test the 495 archival specimens for four human coronavirus strains. We identified 15 coronavirus-positive specimens: eight with OC43, 5 with NL63, 2 with HKU1, and none with 229E. Of the 15 children (5 boys) infected with human coronavirus, the mean age was 3.5 years, and the age range was 1.1 to 5.8 years; one child was diagnosed with lower respiratory infection; the other 14 were diagnosed with upper respiratory infection. Of these 15 patients, none were hospitalized, 5 were infected with coronavirus alone, 8 were co-infected with another virus, and 2 were co-infected with 2 other viruses. The multi-virus infections involved 6 adenoviruses, 3 respiratory syncytial viruses, 2 parainfluenza viruses, and 1 rhinovirus. In conclusion, the burden of human coronaviruses was relatively light among this cohort of 495 pediatric outpatients, and the incidence of these infections was low.


title: Surgical glove-port single-incision laparoscopic gastric wedge resection of gastrointestinal stromal tumors: initial experience with 2 cases.

text: Gastrointestinal stromal tumors are localized mainly in the stomach, and the therapeutic approach is surgical resection. Laparoscopy can be performed for tumors located in the greater curvature of the stomach. Among the treatment alternatives, a single-incision laparoscopic technique is used more frequently than standard laparoscopy due to the successful results of laparoscopic surgery. Here, we report the use of single-incision surgical glove-port laparoscopy for the resection of 2 gastrointestinal stromal tumors localized in the greater curvature of stomach.


title: Surgical outcomes of total thyroidectomy using the LigaSure™ Small Jaw versus LigaSure Precise™: A retrospective study of 2000 consecutive patients.

text: BACKGROUND We compared surgical outcomes of LigaSure™ Small Jaw, which is a multifunctional thermal device that incorporates a tissue divider versus LigaSure Precise™ in thyroid surgery. METHODS A retrospective, single-center study was carried out in an acute-care teaching hospital in Barcelona, Spain. Between January 2008 and June 2015, consecutive patients scheduled for total thyroidectomy were included in the study. Surgical outcomes were operative time, length of skin incision, use of a suction drain, intraoperative bleeding, postoperative complications and length of hospital stay. RESULTS A total of 2000 patients were included (LigaSure™ Small Jaw, n = 1000; LigaSure Precise™, n = 1000). Demographics and indication for surgery were similar in both groups. A significant and independent shorter operative time (median 40 vs. 65 min, P = 0.002), smaller length of the skin incision (mean [SD] 4 [2] vs. 7 [3] cm, P = 0.031), lower percentages of patients with suction drain (15% vs. 66%, P = 0.012) and intraoperative bleeding (4% vs. 9%, P = 0.045) and reduced length of stay (median 1 vs. 3 days, P = 0.039) were found in the LigaSure™ Small Jaw than in the LigaSure Precise™. Postoperative complications including haematoma, hypoparathyroidism and recurrent laryngeal nerve injury were similar. CONCLUSIONS The LigaSure™ Small Jaw in thyroid surgery results in significant less blood loss and operative time as well as shorter hospital stay compared to LigaSure Precise™. These findings could have direct application in daily practice.


title: Establishing the first mobile stroke unit in the United States.

text: BACKGROUND AND PURPOSE Recently, the Mobile Stroke Unit (MSU) concept was introduced in Germany demonstrating prehospital treatment of more patients within the first hour of symptom onset. However, the details and complexities of establishing such a program in the United States are unknown. We describe the steps involved in setting up the first MSU in the United States. METHODS Implementation included establishing leadership, fund-raising, purchase and build-out, knitting a collaborative consortium of community stakeholders, writing protocols to ensure accountability, radiation safety, purchasing supplies, licensing, insurance, establishing a base station, developing a communication plan with city Emergency Medical Services, Emergency Medical Service training, staffing, and designing a research protocol. RESULTS The MSU was introduced after ≈1 year of preparation. Major obstacles to establishing the MSU were primarily obtaining funding, licensure, documenting radiation safety protocols, and establishing a smooth communication system with Emergency Medical Services. During an 8 week run-in phase, ≈2 patients were treated with recombinant tissue-type plasminogen activator per week, one-third within 60 minutes of symptom onset, with no complications. A randomized study to determine clinical outcomes, telemedicine reliability and accuracy, and cost effectiveness was formulated and has begun. CONCLUSION The first MSU in the United States has been introduced in Houston, TX. The steps needed to accomplish this are described.


Transjugular Intrahepatic Portosystemic Shunt Creation in a 5.5-kg Infant with Refractory Variceal Hemorrhage: Case Report and Review of the Literature.


POINT: should academic physicians lecture as members of industry speaker bureaus? Yes.


title: Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer: a new treatment option for fecal incontinence.

text: PURPOSE NASHA Dx gel has been used extensively for treatments in the field of urology. This study was performed to evaluate NASHA Dx gel as an injectable anal canal implant for the treatment of fecal incontinence. METHODS Thirty-four patients (5 males, 29 females; median age, 61 years; range, 34 to 80) were injected with 4 x 1 ml of NASHA Dx gel, just above the dentate line in the submucosal layer. The primary end point was change in the number of incontinence episodes and a treatment response was defined as a 50 percent reduction compared with pretreatment. All patients were followed up at 3, 6, and 12 months. RESULTS The median number of incontinence episodes during four weeks was 22 (range, 2 to 77) before treatment, at 6 months it was 9 (range, 0 to 46), and at 12 months it was 10 (range, 0 to 70, P = 0.004). Fifteen patients (44 percent) were responders at 6 months, compared with 19 (56 percent) at 12 months. No long-term side effects or serious adverse events were reported. CONCLUSIONS Submucosal injection of NASHA Dx gel is an effective treatment for fecal incontinence. The effect is sustained for at least 12 months. The treatment is associated with low morbidity.


Prioritizing Access to Surgical Care During the Coronavirus Pandemic.


Remote psychophysical evaluation of olfactory and gustatory functions in early-stage coronavirus disease 2019 patients: the Bologna experience of 300 cases.


title: Passive continuous positive airway pressure ventilation during cardiopulmonary resuscitation: a randomized cross-over manikin simulation study.

text: While controlled ventilation is most frequently used during cardiopulmonary resuscitation (CPR), the application of continuous positive airway pressure (CPAP) and passive ventilation of the lung synchronously with chest compressions and decompressions might represent a promising alternative approach. One benefit of CPAP during CPR is the reduction of peak airway pressures and therefore a potential enhancement in haemodynamics. We therefore evaluated the tidal volumes and airway pressures achieved during CPAP-CPR. During CPR with the LUCAS™ 2 compression device, a manikin model was passively ventilated at CPAP levels of 5, 10, 20 and 30 hPa with the Boussignac tracheal tube and the ventilators Evita® V500, Medumat® Transport, Oxylator® EMX, Oxylog® 2000, Oxylog® 3000, Primus® and Servo®-i as well as the Wenoll® diver rescue system. Tidal volumes and airway pressures during CPAP-CPR were recorded and analyzed. Tidal volumes during CPAP-CPR were higher than during compression-only CPR without positive airway pressure. The passively generated tidal volumes increased with increasing CPAP levels and were significantly influenced by the ventilators used. During ventilation at 20 hPa CPAP via a tracheal tube, the mean tidal volumes ranged from 125 ml (Medumat®) to 309 ml (Wenoll®) and the peak airway pressures from 23 hPa (Primus®) to 49 hPa (Oxylog® 3000). Transport ventilators generated lower tidal volumes than intensive care ventilators or closed-circuit systems. Peak airway pressures during CPAP-CPR were lower than those during controlled ventilation CPR reported in literature. High peak airway pressures are known to limit the applicability of ventilation via facemask or via supraglottic airway devices and may adversely affect haemodynamics. Hence, the application of ventilators generating high tidal volumes with low peak airway pressures appears desirable during CPAP-CPR. The limited CPAP-CPR capabilities of transport ventilators in our study might be prerequisite for future developments of transport ventilators.


Shattuck Lecture. Chronic infectious disease and the future of health care delivery.


Science, policy, people, and public health: What Is COVID-19 teaching us?


docid: bnhggixf

title: Cancers mimicking fungal infections.

text: Primary and metastatic malignancies may occasionally mimic or coexist with cutaneous fungal infections. The authors report 3 cases of cancers that were initially presumed to be cutaneous fungal infections. Dermatologists should maintain a low threshold for skin biopsy in patients with persistent or refractory fungal infections.


title: Simple stapled division of aberrant artery during thoracoscopic resection of pulmonary sequestration.

text: Pulmonary sequestration is a rare developmental abnormality where pulmonary tissue lacks normal connections to the tracheobronchial tree, in addition to its having an anomalous systemic blood supply. Lobectomy via open thoracotomy has long been the procedure of choice for the resection of pulmonary sequestration. We present three cases of thoracoscopic lobectomies performed using video-assisted thoracic surgery (VATS). Transection of the associated aberrant artery was performed using only a single staple.


Editorial: Managing the march of COVID-19: lessons from the HIV and AIDS epidemic.


title: Intracellular membrane association of the N-terminal domain of classical swine fever virus NS4B determines viral genome replication and virulence.

text: Classical swine fever virus (CSFV) causes a highly contagious disease in pigs that can range from a severe haemorrhagic fever to a nearly unapparent disease, depending on the virulence of the virus strain. Little is known about the viral molecular determinants of CSFV virulence. The nonstructural protein NS4B is essential for viral replication. However, the roles of CSFV NS4B in viral genome replication and pathogenesis have not yet been elucidated. NS4B of the GPE- vaccine strain and of the highly virulent Eystrup strain differ by a total of seven amino acid residues, two of which are located in the predicted trans-membrane domains of NS4B and were described previously to relate to virulence, and five residues clustering in the N-terminal part. In the present study, we examined the potential role of these five amino acids in modulating genome replication and determining pathogenicity in pigs. A chimeric low virulent GPE- -derived virus carrying the complete Eystrup NS4B showed enhanced pathogenicity in pigs. The in vitro replication efficiency of the NS4B chimeric GPE- replicon was significantly higher than that of the replicon carrying only the two Eystrup-specific amino acids in NS4B. In silico and in vitro data suggest that the N-terminal part of NS4B forms an amphipathic α-helix structure. The N-terminal NS4B with these five amino acid residues is associated with the intracellular membranes. Taken together, this is the first gain-of-function study showing that the N-terminal domain of NS4B can determine CSFV genome replication in cell culture and viral pathogenicity in pigs.


title: The open reading frame 3a protein of severe acute respiratory syndrome-associated coronavirus promotes membrane rearrangement and cell death.

text: The genome of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains eight open reading frames (ORFs) that encode novel proteins. These accessory proteins are dispensable for in vitro and in vivo replication and thus may be important for other aspects of virus-host interactions. We investigated the functions of the largest of the accessory proteins, the ORF 3a protein, using a 3a-deficient strain of SARS-CoV. Cell death of Vero cells after infection with SARS-CoV was reduced upon deletion of ORF 3a. Electron microscopy of infected cells revealed a role for ORF 3a in SARS-CoV induced vesicle formation, a prominent feature of cells from SARS patients. In addition, we report that ORF 3a is both necessary and sufficient for SARS-CoV-induced Golgi fragmentation and that the 3a protein accumulates and localizes to vesicles containing markers for late endosomes. Finally, overexpression of ADP-ribosylation factor 1 (Arf1), a small GTPase essential for the maintenance of the Golgi apparatus, restored Golgi morphology during infection. These results establish an important role for ORF 3a in SARS-CoV-induced cell death, Golgi fragmentation, and the accumulation of intracellular vesicles.


title: Safety and curability of laparoscopic gastrectomy in elderly patients with gastric cancer.

text: BACKGROUND Elderly patients are often considered as a high-risk population for major abdominal surgery due to reduced functional reserve and increased comorbidities. The aim of this study was to assess the safety and curability of laparoscopic gastrectomy in elderly patients with gastric cancer compared with short- and long-term outcomes in non-elderly patients. METHODS We retrospectively investigated 386 patients who underwent laparoscopic gastrectomy for gastric cancer between January 2007 and December 2015 at the Digestive Disease Center, Showa University, Northern Yokohama Hospital. We categorized the patients into two groups by age: the elderly patients (≥ 75 years old) and the non-elderly patients (< 74 years old). Patient characteristics, clinicopathologic and operative findings, and short- and long-term outcomes were investigated and compared between the two groups. RESULTS The elderly group showed a significantly higher rate of comorbidities (73.1 vs. 49.2%, P < 0.001), and American Society of Anesthesiologists (ASA) scores ≥ 2 (76.3 vs. 43.7%, P < 0.001), and using anticoagulant agents (25.8 vs. 7.9%, P < 0.001) than the non-elderly group. The postoperative morbidity and mortality did not differ between the two groups (19.4 vs. 18.8%; P = 0.880, 2.2 vs. 0%; P = 0.058). In the multivariate analysis, male sex was the only risk factor for postoperative morbidity after laparoscopic gastrectomy. However, age was not found to be a risk factor. The 5-year overall survival ratio was significantly lower in the elderly group than in the non-elderly group (67.7 vs. 85.0%; P < 0.001). However, the 5-year disease-specific survival ratio was similar in the two groups (84.8 vs. 89.1%; P = 0.071). CONCLUSION Laparoscopic gastrectomy for gastric cancer could be safely performed in elderly patients with acceptable postoperative morbidity and curability.


title: Cerebral oxygenation and blood flow in normal term infants at rest measured by a hybrid near-infrared device (BabyLux).

text: BACKGROUND The BabyLux device is a prototype optical neuro-monitor of cerebral oxygenation and blood flow for neonatology integrating time-resolved reflectance spectroscopy and diffuse correlation spectroscopy. METHODS Here we report the variability of six consecutive 30 s measurements performed in 27 healthy term infants at rest. Poor data quality excluded four infants. RESULTS Mean cerebral oxygenation was 59.6 ± 8.0%, with intra-subject standard deviation of 3.4%, that is, coefficient of variation (CV) of 5.7%. The inter-subject CV was 13.5%. Mean blood flow index was 2.7 × 10-8 ± 1.56 × 10-8 (cm2/s), with intra-subject CV of 27% and inter-subject CV of 56%. The variability in blood flow index was not reduced by the use of individual measures of tissue scattering, nor accompanied by a parallel variability in cerebral oxygenation. CONCLUSION The intra-subject variability for cerebral oxygenation variability was improved compared to spatially resolved spectroscopy devices, while for the blood flow index it was comparable to that of other modalities for estimating cerebral blood flow in newborn infants. Most importantly, the simultaneous measurement of oxygenation and flow allows for interpretation of the high inter-subject variability of cerebral blood flow as being due to error of measurement rather than to physiological instability.


Doing the day's work well: my unlikely COVID-19 renaissance.


How accurate is our picture of the pandemic?


title: Outcomes of and risk factors for presumed canine H3N2 influenza virus infection in a metropolitan outbreak.

text: OBJECTIVE To determine clinical signs, case fatality rate, and factors associated with positive results of PCR testing for canine influenza virus (CIV) in dogs during an H3N2 CIV outbreak in the Atlanta area. DESIGN Cross-sectional study. ANIMALS 220 dogs with a nasal swab specimen submitted to an Atlanta-area diagnostic laboratory between May 1 and July 2, 2015, for PCR assay detection of CIV specifically or CIV and 5 other respiratory pathogens. PROCEDURES Veterinarians of tested dogs were surveyed by various means to collect information regarding clinical signs, survival status at the time of survey completion, vaccination history (≤ 12 months prior to testing), and travel history (≤ 2 months prior to testing). Data were compared between CIV-positive and CIV-negative dogs. RESULTS Surveys for 120 (55%) dogs were completed. Forty (33%) of these dogs had positive results of CIV testing. No significant differences were identified between CIV-positive and CIV-negative dogs regarding breed, sex, reproductive status, duration of clinical signs prior to testing, other dogs in the household, or travel history. When other factors were controlled for, CIV-positive dogs were more likely to be adult (> 1 year of age) than juvenile (≤ 1 year of age) and to be inappetent. Only 1 (3%) CIV-positive dog died during the study period (shortly after it was evaluated because of respiratory signs). CONCLUSIONS AND CLINICAL RELEVANCE From May 1 to July 2, 2015, the reported clinical signs of dogs tested during the Georgia H3N2 CIV outbreak were similar to those reported for dogs with H3N8 CIV infection, and the case fatality rate was low.


[Evaluation of different genes in the RT-PCR detection of SARS-CoV-2 in respiratory samples and its evolution in infection].


title: Limbic and paralimbic structures driving ictal central apnea.

text: OBJECTIVE To precisely identify cortical regions that modulate breathing, and delineate a network of cortical structures that underpin ictal central apnea (ICA) during epileptic seizures. METHODS We electrically stimulated multiple cortical structures in patients undergoing stereotactic EEG (SEEG) evaluation before epilepsy surgery. Structures investigated were orbitofrontal cortex, anterior and posterior cingulate and subcallosal gyri, insula, hippocampus, parahippocampal gyrus, amygdala, temporo-polar cortex, antero-mesial fusiform gyrus, and lateral and basal temporal cortices. Chest/abdominal excursions using thoracic/abdominal belts, peripheral capillary oxygen saturation, end tidal and transcutaneous carbon dioxide, and airflow were continuously monitored. RESULTS Nineteen consecutive adult patients (10 female) aged 18-69 years were investigated. Transient central apnea was elicited in 13/19 patients with amygdala, hippocampus head and body, anterior parahippocampal gyrus, and antero-mesial fusiform gyrus. Insula, cingulate, subcallosal, orbitofrontal, lateral, and basal temporal cortices stimulation did not induce apnea. Apnea duration was associated with stimulus duration (p < 0.001) and current intensity (p = 0.004). CONCLUSIONS These findings suggest a limbic/paralimbic mesial temporal breathing modulation network that includes amygdala, hippocampus, anterior parahippocampal, and antero-mesial fusiform gyri. These structures likely represent anatomical and functional substrates for ICA, a putative sudden unexpected death in epilepsy (SUDEP) breathing biomarker. Damage to such areas is known to occur in high SUDEP risk patients and SUDEP victims, and may underpin the prolonged ICA that is thought to be particularly dangerous. Furthermore, inclusive targeting of apnea-producing structures in SEEG implantations, peri-ictal breathing signal recordings, and stringent analysis of apneic sequences in seizure semiology may enhance accurate identification of symptomatogenic and seizure onset zones for epilepsy surgery.


title: Paravertebral block catheter breakage by electrocautery during thoracic surgery.

text: Advantages of thoracic paravertebral analgesia (TPA) include placement of the catheter closer to the surgical field; however, the catheter can become damaged during the operation. We experienced a case of intraoperative TPA catheter breakage that prompted us to perform an experiment to investigate possible causes. A 50-year-old male underwent a thoracoscopic lower lobectomy under general anesthesia with TPA via an intercostal approach. Following surgery, it was discovered that the catheter had become occluded, as well as cut and fused, so we reopened the incision and removed the residual catheter. From that experience, we performed an experiment to examine electrocautery-induced damage in normal (Portex™, Smith's Medical), radiopaque (Perifix SoftTip™, BBraun), and reinforced (Perifix FX™, BBraun) epidural catheters (n = 8 each). Chicken meat was penetrated by each catheter and then cut by electrocautery. In the normal group, breakage occurred in 8 and occlusion in 6 of the catheters, and in the radiopaque group breakage occurred in 8 and occlusion in 7. In contrast, breakage occurred in only 3 and occlusion in none in the reinforced group, with the 5 without breakage remaining connected only by the spring coil. Furthermore, in 7 of the reinforced catheters, electric arc-induced thermal damage was observed at the tip of the catheter. A TPA catheter for thoracic surgery should be inserted via the median approach, or it should be inserted after surgery to avoid catheter damage during surgery.


Theme 4: Invasive management of (recurrent) VTE and PTS.


title: Extended thymectomy, left pneumonectomy, pericardiectomy and partial pleurectomy for a large thymoma, using only a median sternotomy.

text: We present a case of a large thymoma with invasion to the hilum of the lung and pleural dissemination. A 58-year-old woman was diagnosed with a type B2 thymoma, with suspected pericardium, pulmonary artery and left lung invasion and pleural metastasis (Masaoka-Koga stage IVb). A radical resection was planned after systemic chemotherapy. Through a median sternotomy, we resected the tumour, and after confirmation of pericardium and left lung invasion, we also performed resection of the pericardium, of the lung and of the pleural metastasis. The median sternotomy allowed a safe dissection of pulmonary vessels and main bronchus.


title: A Case of Juxtaglomerular Cell Tumor, or Reninoma, of the Kidney Treated by Retroperitoneoscopy-Assisted Nephron-Sparing Partial Nephrectomy Through a Small Pararectal Incision.

text: A 15-year-old girl was found to be hypertensive (230-270/140-170 mm Hg) without any subjective symptoms. Magnetic resonance imaging confirmed the presence of a well-defined 22 mm hypodense lesion in the lower pole of the left kidney, located close to the renal hilum. Plasma rennin activity was elevated (75 ng/mL/h), and reninoma was diagnosed. Retroperitoneoscopy-assisted nephron-sparing surgery was planned. The retroperitoneum was accessed through a 4 cm left pararectal upper abdominal incision. Following blunt dissection, the abdominal wall was elevated with a lifting bar and lifting retractor, inserted below the 12th rib in the anterior axillary line to create sufficient working space in the retroperitoneal cavity without the need for pneumoperitoneum. Three 5 mm trocars were introduced above the superior iliac crest for the camera and the assistant. Gerota's fascia was opened and the kidney exposed. The surgeon dissected the left kidney through the minilaparotomy incision under both direct vision and using the magnified view on the monitor, which was particularly effective for the lateral and posterior sides of the kidney. The posterior peritoneum was incised intentionally next to the diaphragm to allow further mobilization of the kidney. Diathermy was used to remove the tumor and a layer of surrounding normal parenchymal tissue at least 0.5 cm thick. The histopathologic diagnosis was reninoma. Ischemia time was 14 minutes. Postoperatively, both plasma rennin activity and blood pressure were normal (1.9 ng/mL/h and 90-110/70-80 mm Hg, respectively). After follow-up of 12 months, there is no evidence of recurrence.


title: Spatio-temporal distribution of negative emotions on Twitter during floods in Chennai, India, in 2015: a post hoc analysis.

text: BACKGROUND Natural disasters are known to take their psychological toll immediately, and over the long term, on those living through them. Messages posted on Twitter provide an insight into the state of mind of citizens affected by such disasters and provide useful data on the emotional impact on groups of people. In 2015, Chennai, the capital city of Tamil Nadu state in southern India, experienced unprecedented flooding, which subsequently triggered economic losses and had considerable psychological impact on citizens. The objectives of this study are to (i) mine posts to Twitter to extract negative emotions of those posting tweets before, during and after the floods; (ii) examine the spatial and temporal variations of negative emotions across Chennai city via tweets; and (iii) analyse associations in the posts between the emotions observed before, during and after the disaster. METHODS Using Twitter's application programming interface, tweets posted at the time of floods were aggregated for detailed categorisation and analysis. The different emotions were extracted and classified by using the National Research Council emotion lexicon. Both an analysis of variance (ANOVA) and mixed-effect analysis were performed to assess the temporal variations in negative emotion rates. Global and local Moran's I statistic were used to understand the spatial distribution and clusters of negative emotions across the Chennai region. Spatial regression was used to analyse over time the association in negative emotion rates from the tweets. RESULTS In the 5696 tweets analysed around the time of the floods, negative emotions were in evidence 17.02% before, 29.45% during and 11.39% after the floods. The rates of negative emotions showed significant variation between tweets sent before, during and after the disaster. Negative emotions were highest at the time of disaster's peak and reduced considerably post disaster in all wards of Chennai. Spatial clusters of wards with high negative emotion rates were identified. CONCLUSIONS Spatial analysis of emotions expressed on Twitter during disasters helps to identify geographic areas with high negative emotions and areas needing immediate emotional support. Analysing emotions temporally provides insight into early identification of mental health issues, and their consequences, for those affected by disasters.


Coronavirus & Contracts: How the Coronavirus May Trigger Force Majeure.


title: Epilepsy care in the COVID-19 era.

text: The COVID-19 pandemic will impact on how care for chronic conditions is delivered. We use epilepsy to exemplify how care for patients will be affected, and suggest ways in which healthcare systems can respond to deliver the most effective care. Where face-to-face outpatient appointments have been cancelled, telemedicine can facilitate remote clinical consultations for new and follow-up epilepsy clinic patients while reducing the risk of infection to both patients and healthcare staff. First-seizure patients will need investigation pathways rationalised, while those with chronic epilepsy will need to have reliable alternative avenues to access clinical advice. At the same time, neurologists should support emergency departments and acute medical units, advising on appropriate management of seizures and other acute neurological presentations. Ultimately, the revolution in our clinical practice is unlikely to cease after this pandemic, with reconfiguration of services likely to bring improvements in efficiency and convenience, and a reduced environmental impact.


title: Knowing Your Team: Rapid Assessment of Residents and Fellows for Effective Horizontal Care Delivery in Emergency Events.

text: Background Horizontal care, in which clinicians assume roles outside of their usual responsibilities, is an important health care systems response to emergency situations. Allocating residents and fellows into skill-concordant clinical roles, however, is challenging. The most efficient method to accomplish graduate medical education (GME) assessment and deployment for horizontal care is not known. Objective We designed a categorization schema that can efficiently facilitate clinical and educational horizontal care delivery for trainees within a given institution. Methods In September 2019, as part of a general emergency response preparation, a 4-tiered system of trainee categorization was developed at one academic medical center. All residents and fellows were mapped to this system. This single institution model was disseminated to other institutions in 2020 as the COVID-19 pandemic began to affect hospitals nationally. In March 2020, a multi-institution collaborative launched the Trainee Pandemic Role Allocation Tool (TPRAT), which allows institutions to map institutional programs to COVID-19 roles within minutes. This was disseminated to other GME programs for use and refinement. Results The emergency response preparation plan was disseminated and selectively implemented with a positive response from the emergency preparedness team, program directors, and trainees. The TPRAT website was visited more than 100 times in the 2 weeks after its launch. Institutions suggested rapid refinements via webinars and e-mails, and we developed an online user's manual. Conclusions This tool to assess and deploy trainees horizontally during emergency situations appears feasible and scalable to other GME institutions.


title: Compartmentalization of endoplasmic reticulum quality control and ER-associated degradation factors.

text: Recent studies are delineating a detailed picture of the architecture and function of the endoplasmic reticulum (ER) and the early secretory pathway, showing the existence of dynamic compartmentalization of ER quality control and ER-associated degradation (ERAD) factors. The compartmentalization is regulated by ER protein load and in turn regulates protein processing and cell fate. This compartmentalization is intimately linked to the protein quality control processes, protein disposal through ERAD, the unfolded protein response, and the initiation of apoptosis. It includes novel compartments, the ER-derived quality control compartment (ERQC), vesicles implicated in "ERAD-tuning," and the mitochondria-associated membranes (MAMs).


title: Transanal minimally invasive surgery (TAMIS) using a new disposable device: our initial experience.

text: Disposable single-port surgery devices have been used for transanal minimally invasive surgery (TAMIS). Their advantage, compared to transanal endoscopic microsurgery, is that they do not require special equipment or training. The aim of this study was to assess our initial experience using the single-site laparoscopic (SSL™) access system (Ethicon Endo-Surgery, Cincinnati, OH, USA) for TAMIS. Five patients eligible for local excision of rectal tumors, four males and one female, mean age 58 years (range 50-78), underwent surgery using the SSL™ device. The average distance from anal verge was 4 cm (range 1-6). Four patients had an initial diagnosis of adenoma, and one had a previous endoscopic excision of a T1 adenocarcinoma with positive margins. In one patient, due to the lack of exposure, the procedure was converted to a low anterior resection. In the remaining four patients, average setup time was 7 minutes (range 4-15) and average operative time was 52 minutes (range 38-72). All resection margins were tumor free. There were no postoperative complications. Two of the presumed adenomas were intramucosal adenocarcinomas, while one patient had a T2 tumor and underwent radical surgery. Although at the present time the appropriate use of local excision is still under debate, TAMIS is a technique with great potential. Because of its simplicity and similarity with conventional laparoscopic surgery, it can be learned easily by surgeons not trained in transanal endoscopic microsurgery.


Decisive and strong leadership and intersectoral action from South Africa in response to the COVID-19 virus.