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.


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.


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?


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.


title: Homemade proximal scalloped stent graft for thoracic endovascular aortic repair of zone 2 acute aortic syndrome.

text: OBJECTIVE The aim of this study was to evaluate the outcomes of homemade proximal scalloped stent grafts for thoracic endovascular aortic repair of zone 2 acute aortic syndrome. METHODS Between May 2015 and December 2015, 10 patients with unremitting symptoms or rupture secondary to an acute aortic syndrome involving zone 2 underwent urgent or emergency thoracic endovascular aortic repair. Among them, 8 were treated using homemade proximal scalloped stent grafts to preserve the patency of the left subclavian artery. Indications included traumatic transection (n = 3) and acute (n = 4) and subacute (n = 1) complicated type B aortic dissection. Follow-up computed tomography scans were performed at 1 week and 3 and 6 months. RESULTS The median duration for stent graft modification was 15 minutes (range, 14-17 minutes). The technical success rate was 100%; sealing was achieved in all cases with no type I endoleaks. All left subclavian arteries were patent, although 1 case was associated with a 50% stenosis. No deaths occurred as a consequence of the aortic repair, but 1 patient died of a traumatic renal hematoma on postoperative day 5. During a mean follow-up of 7.2 ± 2 months, there were no conversions to open surgical repair, aortic ruptures, paraplegia, retrograde dissection, or other aortic complications. CONCLUSIONS The use of the homemade proximal scalloped stent graft is both feasible and effective for left subclavian artery revascularization during thoracic endovascular aortic repair involving a spectrum of acute thoracic aortic pathology. This approach provides a rapid, reproducible method of scalloping the endograft. Durability concerns will need to be assessed in additional studies with long-term follow-up.


Cytokines and the still-baffling clinical biology of COVID-19.


Research During Unprecedented Times.


title: C-reactive protein level and microbial aetiology in patients hospitalised with acute exacerbation of COPD.

text: Both viruses and bacteria are thought to cause exacerbations of chronic obstructive pulmonary disease (COPD); however, the relative importance of each remains uncertain. C-reactive protein (CRP) levels increase during exacerbations but the relationship with aetiology is not established. We aimed to explore the relationship between serum CRP and the rate of detection of viruses and bacteria. This was a prospectively recruited, observational study of patients hospitalised with exacerbations of COPD. Nasopharyngeal swabs were tested for respiratory viruses by reverse transcriptase-PCR. Sputum and blood were collected for bacterial culture and urine tested for pneumococcal antigen. CRP levels were measured on sera. CRP and other factors associated with viral, bacterial or mixed detection were assessed using multiple logistic regression analysis. 264 patients with exacerbations of COPD were studied: 26% tested positive for respiratory viruses only, 13% had bacteria only, 12% had mixed viral/bacterial detection, and 49% had no pathogens detected. CRP level and temperature were strongly associated with viral detection rate (p<0.001 and p=0.004, respectively) and mixed viral/bacterial detection rate (p=0.02 and p=0.03, respectively) on multivariate analysis. Bacterial detection rate was not associated with CRP level or body temperature. This study supports the role of viruses as important aetiological agents causing exacerbations of COPD.


title: Chloroquine inhibits the release of inflammatory cytokines by human lung explants.

text: On human lung parenchymal explants, chloroquine concentration clinically achievable in the lung (100 μM) inhibited the lipopolysaccharide-induced release of TNF-α (by 76%), IL-6 (by 68%), CCL2 (by 72%) and CCL3 (by 67%). Beside its antiviral activity, chloroquine might also mitigate the cytokine storm associated with severe pneumonia caused by coronaviruses.


Capacity building during COVID-19: Utilising South Africa's underutilised international medical graduates.


title: Computed Tomography Perfusion, Magnetic Resonance Imaging, and Histopathological Findings After Laparoscopic Renal Cryoablation: An In Vivo Pig Model.

text: The present study investigates how computed tomography perfusion scans and magnetic resonance imaging correlates with the histopathological alterations in renal tissue after cryoablation. A total of 15 pigs were subjected to laparoscopic-assisted cryoablation on both kidneys. After intervention, each animal was randomized to a postoperative follow-up period of 1, 2, or 4 weeks, after which computed tomography perfusion and magnetic resonance imaging scans were performed. Immediately after imaging, open bilateral nephrectomy was performed allowing for histopathological examination of the cryolesions. On computed tomography perfusion and magnetic resonance imaging examinations, rim enhancement was observed in the transition zone of the cryolesion 1week after laparoscopic-assisted cryoablation. This rim enhancement was found to subside after 2 and 4 weeks of follow-up, which was consistent with the microscopic examinations revealing of fibrotic scar tissue formation in the peripheral zone of the cryolesion. On T2 magnetic resonance imaging sequences, a thin hypointense rim surrounded the cryolesion, separating it from the adjacent renal parenchyma. Microscopic examinations revealed hemorrhage and later hemosiderin located in the peripheral zone. No nodular or diffuse contrast enhancement was found in the central zone of the cryolesions at any follow-up stage on neither computed tomography perfusion nor magnetic resonance imaging. On microscopic examinations, the central zone was found to consist of coagulative necrosis 1 week after laparoscopic-assisted cryoablation, which was partially replaced by fibrotic scar tissue 4 weeks following laparoscopic-assisted cryoablation. Both computed tomography perfusion and magnetic resonance imaging found the renal collecting system to be involved at all 3 stages of follow-up, but on microscopic examination, the urothelium was found to be intact in all cases. In conclusion, cryoablation effectively destroyed renal parenchyma, leaving the urothelium intact. Both computed tomography perfusion and magnetic resonance imaging reflect the microscopic findings but with some differences, especially regarding the peripheral zone. Magnetic resonance imaging seems an attractive modality for early postoperative follow-up.


title: Gut microbiota and Covid-19- possible link and implications.

text: Covid-19 is a major pandemic facing the world today caused by SARS-CoV-2 which has implications on our understanding of infectious diseases. Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors. Role of the gut microbiota in influencing lung diseases has been well articulated. It is also known that respiratory virus infection causes perturbations in the gut microbiota. Diet, environmental factors and genetics play an important role in shaping gut microbiota which can influence immunity. Gut microbiota diversity is decreased in old age and Covid-19 has been mainly fatal in elderly patients which again points to the role the gut microbiota may play in this disease. Improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized in old people and immune-compromised patients. More trials may be initiated to see the effect of co-supplementation of personalized functional food including prebiotics/probiotics along with current therapies.


title: The Antidepressant Treatment Response Index as a Predictor of Reboxetine Treatment Outcome in Major Depressive Disorder.

text: Biomarkers to predict clinical outcomes early during the treatment of major depressive disorder (MDD) could reduce suffering and improve outcomes. A quantitative electroencephalogram (qEEG) biomarker, the Antidepressant Treatment Response (ATR) index, has been associated with outcomes of treatment with selective serotonin reuptake inhibitor antidepressants in patients with MDD. Here, we report the results of a post hoc analysis initiated to evaluate whether the ATR index may also be associated with reboxetine treatment outcome, given that its putative mechanism of action is via norepinephrine reuptake inhibition (NRI). Twenty-five adults with MDD underwent qEEG studies during open-label treatment with reboxetine at doses of 8 to 10 mg daily for 8 weeks. The ATR index calculated after 1 week of reboxetine treatment was significantly associated with overall Hamilton Depression Rating Scale (HAM-D) improvement at week 8 (r=0.605, P=.001), even after controlling for baseline depression severity (P=.002). The ATR index predicted response (≥50% reduction in HAM-D) with 70.6% sensitivity and 87.5% specificity, and remission (final HAM-D≤7) with 87.5% sensitivity and 64.7% specificity. These results suggest that the ATR index may be a useful biomarker of clinical response during NRI treatment of adults with MDD. Future studies are warranted to investigate further the potential utility of the ATR index as a predictor of noradrenergic antidepressant treatment response.


title: The analgesic efficacy of subcostal transversus abdominis plane block with Mercedes incision.

text: BACKGROUND Conventional perioperative analgesic modalities (e.g. opioids, epidural analgesia) have their own drawbacks, which limit their clinical application. This study investigated the opioid-sparing effectsof the oblique subcostal transversus abdominis plane (OSTAP) blockade with ropivacaine for the patients undergoing open liver resection with a Mercedes incision. METHODS 126 patients who were scheduled for open liver resection were enrolled in this study. Patients were randomly assigned to receive bilateral ultrasound-guided OSTAPblocks with either 0.375% ropivacaine (groupT) or 0.9% isotonic saline (group C). Both groups also received intravenous patient-controlled analgesia and intravenous 40 mg parecoxib every 12 h for a total of 3 days. Preoperative and intraoperative parameters, plus intraoperative and postoperative cumulative sufentanil consumption, were recorded. RESULTS 70 patients were enrolled in the study finally. There were no significant differences between the two groups with respect to preoperative parameters, and surgical and anesthetic characteristics. The intraoperative sufentanil use, cumulative sufentanil consumption at 5 min after extubation, 2 h, 4 h,12 h and 24 h after operation in group T was significantly less than that in group C (P = 0.001, 0.001, 0.000, 0.000, 0.001 and 0.044, respectively). Compared with group C, postoperative NRS pain scores at rest were significantly lower at 2 h and 4 h postoperatively in group T (P = 0.04and 0.02, respectively); NRS scores at the time of coughing were also significantly lower in group T than in group C at all time points except 5 min after extubation (all P < 0.001). Furthermore, compared with group C, the number of intraoperative vasodilator use, the extubation time and the incidence of nausea was reduced in group T. CONCLUSION Ultrasound-guided OSTAP block with ropivacaine can significantly decrease the perioperative cumulative dosage of analgesics and improve analgesic effect without obvious side effects for the patients who underwent an open liver resection with Mercedes incision when compared tothe ultrasound-guided OSTAP block with saline. TRIAL REGISTRATION The study protocol was registered at http://www.chictr.org.cn (ChiCTR-TRC- 14004827) on February 19, 2014.


title: Laparoscopic choledochal cyst excision: lessons learned in our experience.

text: BACKGROUND Choledochal cyst (CDC) is a rare biliary disorder. Surgical treatment consists of CDC excision and biliary-enteric reconstruction. Recently, some institutions have reported successful CDC excision by using minimally invasive techniques. In this study, we report our experience with the laparoscopic management of CDC, with a focus on key operative maneuvers that enhance the likelihood of successful excision. METHODS Following institutional review board approval, we performed a retrospective review of patients who underwent the laparoscopic excision of CDC and Roux-en-Y hepaticojejunostomy. Between October 2003 and November 2007, we performed laparoscopic CDC excision in 9 patients (8 female and 1 male). Median age was 4 years (range, 8 months to 16 years). There were 7 type I and 2 type IV cysts, according to Todani's classification. Average cyst size was 4.4 cm (range, 1.3-8.5). The procedures were performed by utilizing four or five trochars. RESULTS Six of 9 children presented with preoperative pancreatitis, 1 with abdominal pain, 1 with jaundice, and 1 was found incidentally. Three patients required the conversion to laparotomy due to dense adhesions, secondary to pancreatitis. Six patients underwent successful laparoscopic procedures, 5 had complete cyst excisions, and 1 underwent a proximal excision with distal mucosectomy. Of the 3 patients who required conversion, 2 underwent complete excisions; the other underwent a proximal excision, distal mucosectomy. There were no intraoperative complications. One patient had a postoperative bile leak that required an open hepaticojejunostomy revision. Eight patients had an uneventful recovery. Oral feedings were resumed within an average of 3.4 days (range, 2-9). Average time to discharge was 6.1 days (range, 5-12). Average follow-up time was 18 months (range, 4-48). No further laboratory abnormalities were detected in any of the patients. CONCLUSIONS Laparoscopic resection of CDC and Roux-en-Y hepaticojejunostomy in children is an excellent treatment option. Preoperative pancreatitis may cause increased technical difficulty, necessitating a conversion. Proximal excision with distal mucosectomy


Pediatric Traumatic Brain Injury: Is It Time to Consider Gender-Based Treatments?


title: [Clinical characteristics and influencing factors of patients with novel coronavirus pneumonia combined with liver injury in Shaanxi region].

text: Objective: To understand the clinical characteristics, change of liver function, influencing factors and prognosis in hospitalized patients with coronavirus disease-19 (COVID-19) combined with liver injury. Methods: The general conditions, biochemical indicators of liver, blood clotting mechanism, routine blood test, UGT1A1 * 28 gene polymorphism and other data of 40 cases with COVID-19 admitted to the isolation ward of Tangdu Hospital were retrospectively analyzed. The clinical characteristics, influencing factors and prognosis of liver injury in patients with liver injury group and those with normal liver function group were compared. The mean of two samples in univariate analysis was compared by t-test and analysis of variance. The counting data was measured by χ(2) tests. The non-normal distribution measurement data were described by the median, and the non-parametric test was used. Statistically significant influencing factors were used as the independent variables in univariate analysis. Multiple logistic regression analysis was used to analyze the main influencing factors of liver injury. Results: Of the 40 cases, 25 were male (62.5%) and 15 were female (37.5%), aged 22 to 83 (53.87 ± 15.84) years. Liver injury was occurred in 22 cases (55%) during the course of the disease. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level was initially increased (4.4 to 3.5 times of the normal value) along with decrease of albumin in the second week, and the difference was statistically significant (P < 0.001). Ten cases (43.5%) had highest abnormal total blood bilirubin (54.1 μmol/ L). There was no correlation between the increase in transaminase and the increase in total blood bilirubin (R = -0.006, P = 0.972). Three cases had prothrombin activity (PTA) of ≤ 50%, 10 cases had elevated FDP, and 13 cases had elevated D-dimer, all of whom were severe or critically ill. Liver function injury was more likely to occur in patients who used many types of drugs and large amounts of hormones (P = 0.002, P = 0.031), and there was no correlation with the TA6TA7 mutation in the UGT1A1 * 28 gene locus. Multiple regression analysis showed that the occurrence of liver injury was only related to critical illness. The liver function of all patients had recovered within one week after conventional liver protection treatment. Conclusion: COVID-19 combined with liver function injury may be due to the slight elevation of transaminase, mostly around the second week of the disease course. Severe patients have a higher proportion of liver injury, and critical type is an independent risk factor for liver injury.


title: An Experimental Study on the Relationship Among Airway Pressure, Pneumoperitoneum Pressure, and Central Venous Pressure in Pure Laparoscopic Hepatectomy.

text: OBJECTIVES To determine optimal settings for airway pressure (AWP), pneumoperitoneum pressure (PPP), and central venous pressure (CVP) in pure laparoscopic hepatectomy. BACKGROUND High PPP is often employed to control bleeding from the hepatic vein during pure laparoscopic hepatectomy; however, there is a risk of pulmonary gas embolism. We noted that decreases in AWP were often effective. METHODS After establishing carbon dioxide pneumoperitoneum in 6 male piglets and maintaining PPP at 25 mmHg, CVP was measured 3 times at each of 9 levels of airway pressure, which was increased in increments of 5 cmH2O from 0 to 40 cmH2O. CVP was measured in the same manner by maintaining PPP at 20, 15, 10, 5, and 0 mmHg, and in laparotomy. Correlation and regression analyses were performed among airway pressure, CVP, and pneumoperitoneum pressure. RESULTS Positive correlations were observed between AWP and CVP and between PPP and CVP (P < 0.001). Under high airway pressure, CVP was persistently higher than pneumoperitoneum pressure. Under low airway pressure, CVP did not increase or often decreased when PPP was higher than CVP. CONCLUSIONS By increasing pneumoperitoneum pressure, bleeding from the hepatic vein cannot be controlled under high airway pressure, but can be controlled under low airway pressure. However, under low airway pressure, the risk of pulmonary gas embolism increases when PPP is higher than CVP. We consider that reducing AWP is also effective for controlling bleeding from the hepatic vein and safer than increasing pneumoperitoneum pressure.


title: Backbone model of an aquareovirus virion by cryo-electron microscopy and bioinformatics.

text: Grass carp reovirus (GCRV) is a member of the aquareovirus genus in the Reoviridae family and has a capsid with two shells-a transcription-competent core surrounded by a coat. We report a near-atomic-resolution reconstruction of the GCRV virion by cryo-electron microscopy and single-particle reconstruction. A backbone model of the GCRV virion, including seven conformers of the five capsid proteins making up the 1500 molecules in both the core and the coat, was derived using cryo-electron microscopy density-map-constrained homology modeling and refinement. Our structure clearly showed that the amino-terminal segment of core protein VP3B forms an approximately 120-A-long alpha-helix-rich extension bridging across the icosahedral 2-fold-symmetry-related molecular interface. The presence of this unique structure across this interface and the lack of an external cementing molecule at this location in GCRV suggest a stabilizing role of this extended amino-terminal density. Moreover, part of this amino-terminal extension becomes invisible in the reconstruction of transcription-competent core particles, suggesting its involvement in endogenous viral RNA transcription. Our structure of the VP1 turret represents its open state, and comparison with its related structures at the closed state suggests hinge-like domain movements associated with the mRNA-capping machinery. Overall, this first backbone model of an aquareovirus virion provides a wealth of structural information for understanding the structural basis of GCRV assembly and transcription.


title: Self-Isolation Compliance In The COVID-19 Era Influenced By Compensation: Findings From A Recent Survey In Israel.

text: A new Coronavirus disease (COVID-19) outbreak is spreading since December 2019. In an attempt to contain the disease, health authorities call for self-quarantine of individuals suspected as exposures. Health officials assume the public will comply in high rates; however, studies suggest that a major obstacle to compliance for household quarantine is concern over loss of income. A cross sectional study of the adult population of Israel was conducted in the last week of February 2020 to assess public attitudes toward the COVID-19 outbreak. In particular, public compliance rates with self-quarantine were assessed depending on compensation for lost wages. The results suggest that when compensation was assumed, the compliance rate was 94%; yet, when compensation was removed, the compliance rate dropped to less than 57%. This study demonstrates that providing people with assurances for their livelihood during self-quarantine is an important component in compliance with public health regulations. [Editor's Note: This fast-track Ahead-of-Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].


title: The effect of pressure support on imposed work of breathing during paediatric extubation readiness testing.

text: BACKGROUND Paediatric critical care practitioners often make use of pressure support (PS) to overcome the perceived imposed work of breathing (WOBimp) during an extubation readiness test (ERT). However, no paediatric data are available that shows the necessity of adding of pressure support during such tests. We sought to measure the WOBimp during an ERT with and without added pressure support and to study its clinical correlate. This was a prospective study in spontaneously breathing ventilated children < 18 years undergoing ERT. Using tracheal manometry, WOBimp was calculated by integrating the difference between positive end-expiratory pressure (PEEP) and tracheal pressure (Ptrach) over the measured expiratory tidal volume (VTe) under two paired conditions: continuous positive airway pressure (CPAP) with and without PS. Patients with post-extubation upper airway obstruction were excluded. RESULTS A total of 112 patients were studied. Median PS during the ERT was 10 cmH2O. WOBimp was significantly higher without PS (median 0.27, IQR 0.20-0.50 J/L) than with added PS (median 0.00, IQR 0.00-0.11 J/L). Although there were statistically significant changes in spontaneous breath rate [32 (23-42) vs. 37 (27-46) breaths/min, p < 0.001] and higher ET-CO2 [5.90 (5.38-6.65) vs. 6.23 (5.55-6.94) kPa, p < 0.001] and expiratory Vt decreased [7.72 (6.66-8.97) vs. 7.08 (5.82-8.08) mL/kg, p < 0.001] in the absence of PS, these changes appeared clinically irrelevant since the Comfort B score remained unaffected [12 (10-13) vs. 12 (10-13), P = 0.987]. Multivariable analysis showed that changes in WOBimp occurred independent of endotracheal tube size. CONCLUSIONS Withholding PS during ERT does not lead to clinically relevant increases in WOBimp, irrespective of endotracheal tube size.


title: Are errors in otorhinolaryngology always a sign of medical malpractice? Review of the literature and new perspectives in the SARS-CoV-2 (COVID-19) era.

text: In medical practice, during certain procedures that usually are not regarded highly demanding, some skill-based errors, that might not be considered as medical malpractice, may occur. In fact, such errors can be caused by factors beyond the physician’s control.A review of Greek case law regarding medical malpractice in otorhinolaryngology was performed to identify cases of lawsuits that concerned medical errors during routine procedures. The analysis of the cases showed that some medical errors may cause serious complications, even if deviation from the standard of medical care is minimal. Thus, in some cases it may be difficult to make a distinction between preventable and unpreventable complications. Certain medical errors from routine medical procedures might be considered unpreventable and, therefore, classified as almost no-fault errors. A brief commentary regarding opportunities to further improve the medical liability system after the SARS-CoV-2 emergency is also given.


title: Early Vertebrate Evolution of the Host Restriction Factor Tetherin.

text: UNLABELLED Tetherin is an interferon-inducible restriction factor targeting a broad range of enveloped viruses. Its antiviral activity depends on an unusual topology comprising an N-terminal transmembrane domain (TMD) followed by an extracellular coiled-coil region and a C-terminal glycosylphosphatidylinositol (GPI) anchor. One of the two membrane anchors is inserted into assembling virions, while the other remains in the plasma membrane of the infected cell. Thus, tetherin entraps budding viruses by physically bridging viral and cellular membranes. Although tetherin restricts the release of a large variety of diverse human and animal viruses, only mammalian orthologs have been described to date. Here, we examined the evolutionary origin of this protein and demonstrate that tetherin orthologs are also found in fish, reptiles, and birds. Notably, alligator tetherin efficiently blocks the release of retroviral particles. Thus, tetherin emerged early during vertebrate evolution and acquired its antiviral activity before the mammal/reptile divergence. Although there is only limited sequence homology, all orthologs share the typical topology. Two unrelated proteins of the slime mold Dictyostelium discoideum also adopt a tetherin-like configuration with an N-terminal TMD and a C-terminal GPI anchor. However, these proteins showed no evidence for convergent evolution and failed to inhibit virion release. In summary, our findings demonstrate that tetherin emerged at least 450 million years ago and is more widespread than previously anticipated. The early evolution of antiviral activity together with the high topology conservation but low sequence homology suggests that restriction of virus release is the primary function of tetherin. IMPORTANCE The continuous arms race with viruses has driven the evolution of a variety of cell-intrinsic immunity factors that inhibit different steps of the viral replication cycle. One of these restriction factors, tetherin, inhibits the release of newly formed progeny virions from infected cells. Although tetherin targets a broad range of enveloped viruses, including retro-, filo-, herpes-, and arenaviruses, the evolutionary origin of this restriction factor and its antiviral activity remained obscure. Here, we examined diverse vertebrate genomes for genes encoding cellular proteins that share with tetherin the highly unusual combination of an N-terminal transmembrane domain and a C-terminal glycosylphosphatidylinositol anchor. We show that tetherin orthologs are found in fish, reptiles, and birds and demonstrate that alligator tetherin efficiently inhibits the release of retroviral particles. Our findings identify tetherin as an evolutionarily ancient restriction factor and provide new important insights into the continuous arms race between viruses and their hosts.


title: Newly Developed Laparoscopic Needle Holder That Facilitates Knot Tying Makes Vaginal Cuff Suturing Easy in Single-Port Laparoscopic Hysterectomy.

text: BACKGROUND To evaluate vaginal cuff closure times of a single-port laparoscopic hysterectomy using a newly developed Turkish-made laparoscopic needle holder (TMLNH) with a single-port laparoscopic hysterectomy using a laparoscopic needle holder with pistol handle (LNHPH). METHODS We retrospectively reviewed 68 patients who underwent single-port laparoscopic hysterectomy using a TMLNH (n = 38) or a LNHPH (n = 30). Patients' age, parity, body mass index, mean operating time, mean vaginal cuff suturing time, uterine weight, estimated blood loss, drop of hemoglobin level, return of bowel activity, hospital stay, conversion to multiport access, conversion to laparotomy, and postoperative and intraoperative outcomes were analyzed. RESULTS The TMLNH group had a shorter operative time ( P < .001) and a shorter vaginal cuff suturing time ( P < .001) compared with the LNHPH group during a single-port laparoscopic hysterectomy. There was no difference in intraoperative and postoperative complications. CONCLUSION The TMLNH facilitates vaginal cuff suturing and decreases operation time during a single-port laparoscopic hysterectomy. We proposed that the TMLNH is a promising technique for suturing and vaginal cuff closure in a single-port laparoscopic hysterectomy.


title: The Relationship Between Burnout, Depression, and Anxiety: A Systematic Review and Meta-Analysis.

text: Background: Burnout is a psychological syndrome characterized by emotional exhaustion, feelings of cynicism and reduced personal accomplishment. In the past years there has been disagreement on whether burnout and depression are the same or different constructs, as they appear to share some common features (e.g., loss of interest and impaired concentration). However, the results so far are inconclusive and researchers disagree with regard to the degree to which we should expect such overlap. The aim of this systematic review and meta-analysis is to examine the relationship between burnout and depression. Additionally, given that burnout is the result of chronic stress and that working environments can often trigger anxious reactions, we also investigated the relationship between burnout and anxiety. Method: We searched the online databases SCOPUS, Web of Science, MEDLINE (PubMed), and Google Scholar for studies examining the relationship between burnout and depression and burnout and anxiety, which were published between January 2007 and August 2018. Inclusion criteria were used for all studies and included both cross-sectional and longitudinal designs, published and unpublished research articles, full-text articles, articles written in the English language, studies that present the effects sizes of their findings and that used reliable research tools. Results: Our results showed a significant association between burnout and depression (r = 0.520, SE = 0.012, 95% CI = 0.492, 0.547) and burnout and anxiety (r = 0.460, SE = 0.014, 95% CI = 0.421, 0.497). However, moderation analysis for both burnout-depression and burnout-anxiety relationships revealed that the studies in which either the MBI test was used or were rated as having better quality showed lower effect sizes. Conclusions: Our research aims to clarify the relationship between burnout-depression and burnout-anxiety relationships. Our findings revealed no conclusive overlap between burnout and depression and burnout and anxiety, indicating that they are different and robust constructs. Future studies should focus on utilizing more longitudinal designs in order to assess the causal relationships between these variables.


title: Uvular injury during the perioperative period in patients undergoing general anesthesia.

text: OBJECTIVE The purpose of this study was to evaluate the incidence and causes of uvular injury in the patients that received general anesthesia in the perioperative period. STUDY DESIGN A 4-year retrospective review of cases of uvular injury and their resolution was conducted in adult patients who received general anesthesia at our institution. METHODS An extensive review was conducted of the quality assurance (QA) database maintained by the Department of Anesthesiology at our tertiary academic medical center. The database was searched for cases of uvular injury that occurred in adult patients undergoing general anesthesia that between January 2007 and December 2010. The medical records of identified patients were then obtained to evaluate the presentation, treatment and ultimate resolution of injury. RESULTS Ten cases of uvular injury were reported in the 28,788 general anesthetics conducted over a 3-year period in adult patients. This correlates to an incidence of 0.034%. Uvular injury occurred in mostly male patients (80%) during elective cases in the supine position. All cases were associated with endotracheal intubation. Additional objects, such as gastric tubes and esophageal temperature probes, were placed in the pharynx of 80% of these patients. Urologic procedures were associated with 50% of reported cases. Treatment ranged from observation to medical therapy. There were no permanent symptoms in any of the patients. CONCLUSION Uvular injury is a relatively rare complication that occurs in patients during the perioperative period who receive general anesthesia. While endotracheal intubation is closely associated with this type of injury, further study is required to elucidate the mechanism and other associated etiologic factors.


title: Comparison of SARS-CoV-2 spike protein binding to ACE2 receptors from human, pets, farm animals, and putative intermediate hosts.

text: The emergence of a novel coronavirus, SARS-CoV-2, resulted in a pandemic. Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. These variable amino acids are clustered at certain positions, mostly at the periphery of the binding site, while changes of the invariable residues prevent S-binding or infection of the respective animal. Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. Of note, Pigs and dogs, which are not or not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. Comparison of the RBD of S of SARS-CoV-2 with viruses from Bat-CoV-RaTG13 and Pangolin-CoV revealed that the latter contains only one substitution, whereas the Bat-CoV-RaTG13 exhibits five. However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. These analyses provide new insight into the receptor usage and animal source/origin of SARS-CoV-2.IMPORTANCE SARS-CoV-2 is threatening people worldwide and there are no drugs or vaccines available to mitigate its spread. The origin of the virus is still unclear and whether pets and livestock can be infected and transmit SARS-CoV-2 are important and unknown scientific questions. Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. Our analysis provides a framework for the prediction of potential hosts of SARS-CoV-2. We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. An exception are dogs and especially pigs, which, however, revealed relatively low ACE2 expression levels in the respiratory tract. Monitoring of animals is necessary to prevent the generation of a new coronavirus reservoir. Finally, our analysis also showed that SARS-CoV-2 may not be specifically adapted to any of its putative intermediate hosts.


Acute Pulmonary Embolism and COVID-19.


title: Sleep disorders in US military personnel: a high rate of comorbid insomnia and obstructive sleep apnea.

text: BACKGROUND Sleep disturbances are among the most common symptoms of military personnel who return from deployment. The objective of our study was to determine the presence of sleep disorders in US military personnel referred for evaluation of sleep disturbances after deployment and examine associations between sleep disorders and service-related diagnoses of depression, mild traumatic brain injury, pain, and posttraumatic stress disorder (PTSD). METHODS This was a cross-sectional study of military personnel with sleep disturbances who returned from combat within 18 months of deployment. Sleep disorders were assessed by clinical evaluation and polysomnogram with validated instruments to diagnose service-related illnesses. RESULTS Of 110 military personnel included in our analysis, 97.3% were men (mean age, 33.6 ± 8.0 years; mean BMI, 30.0 ± 4.3 kg/m2), and 70.9% returned from combat within 12 months. Nearly one-half (47.3%) met diagnostic criteria for two or more service-related diagnoses. Sleep disorders were diagnosed in 88.2% of subjects; 11.8% had a normal sleep evaluation and served as control subjects. Overall, 62.7% met diagnostic criteria for obstructive sleep apnea (OSA) and 63.6% for insomnia. The exclusive diagnoses of insomnia and OSA were present in 25.5% and 24.5% of subjects, respectively; 38.2% had comorbid insomnia and OSA. Military personnel with comorbid insomnia and OSA were significantly more likely to meet criteria for depression (P < .01) and PTSD (P < .01) compared with control subjects and those with OSA only. CONCLUSIONS Comorbid insomnia and OSA is a frequent diagnosis in military personnel referred for evaluation of sleep disturbances after deployment. This diagnosis, which is difficult to treat, may explain the refractory nature of many service-related diagnoses.


title: NREM sleep staging using WAV(CNS) index.

text: OBJECTIVE Visual scoring of 30-s epochs of sleep data is not always adequate to show the dynamic structure of sleep in sufficient details. It is also prone to considerable inter- and intra-rater variability. Moreover, it involves considerable training and experience, and is very tedious, time-consuming, labor-intensive and costly. Hence, automatic sleep staging is needed to overcome these limitations. Since naturally occurring NREM sleep and anesthesia have been reported to possess various underlying neurophysiological similarities, EEG-based depth-of-anesthesia monitors have started to penetrate into sleep research. This study investigates the ability of WAV(CNS) index (as implemented in NeuroSENSE depth-of-anesthesia monitor) to detect NREM sleep stages and wake state for full overnight PSG data. METHODS Full overnight PSG sleep data, obtained from 24 adolescents, was scored by a registered PSG technologist for different sleep stages. Retrospective analysis was performed on a single frontal channel using the WAV(CNS) algorithm. Non-parametric descriptive statistics were used to examine the relationship between WAV(CNS) index and sleep stages. RESULTS A strong correlation (ρ = 0.9458) was found between the WAV(CNS) index and NREM sleep stages, with WAV(CNS) index values decreasing with increasing sleep stages. Moreover, there was no significant overlap between different NREM sleep stages as classified by the WAV(CNS) index, which was able to significantly differentiate (P < 0.001) between all pairs of Awake and different NREM stages. CONCLUSIONS This study demonstrates that changes in the depth of natural NREM sleep are reflected sensitively by changes in the WAV(CNS) index. Hence, WAV(CNS) index may serve as an automatic real-time indicator of depth of natural sleep with high temporal resolution, and can possibly be of great use for automated sleep staging in routine/postoperative somnographic studies.


title: Does lateral lymph node dissection for low rectal cancer improve overall survival? Protocol for a systematic review and meta-analysis.

text: Introduction The best therapeutic strategy for treating lateral lymph nodes in patients with advanced mid to low rectal cancer remains unknown. Our objective is to determine which therapeutic strategy - lateral lymph node dissection versus radiochemotherapy - offers the best overall and recurrence-free survivals for these patients. Methods and analysis We will perform a systematic review and meta-analysis aiming at determining the overall and recurrence-free survivals of patients with total mesorectum excision with and without lateral lymph node dissection, in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. MEDLINE, Embase, Cochrane and Web of Science will be searched from inception to the 16th of January 2019 for original studies written in English or in French including patients who benefited from lateral lymph node dissection for low rectal cancer and reporting overall survival for patients with and without lateral lymph node dissection. Hazard ratios of overall and recurrence-free survivals extracted from included studies will be combined and compared between patients with and without lateral lymph node dissection. Risk of bias will be assessed by using the Newcastle-Ottawa scale.The systematic review and meta-analysis protocol is registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO) with number CRD42019123181. Ethics and dissemination No ethical clearance is required for this study. This review will be published in a peer- reviewed journal and will be presented at various national and international conferences.