title: A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication.

text: We report the discovery and optimization of a potent inhibitor against the papain-like protease (PLpro) from the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). This unique protease is not only responsible for processing the viral polyprotein into its functional units but is also capable of cleaving ubiquitin and ISG15 conjugates and plays a significant role in helping SARS-CoV evade the human immune system. We screened a structurally diverse library of 50,080 compounds for inhibitors of PLpro and discovered a noncovalent lead inhibitor with an IC(50) value of 20 microM, which was improved to 600 nM via synthetic optimization. The resulting compound, GRL0617, inhibited SARS-CoV viral replication in Vero E6 cells with an EC(50) of 15 microM and had no associated cytotoxicity. The X-ray structure of PLpro in complex with GRL0617 indicates that the compound has a unique mode of inhibition whereby it binds within the S4-S3 subsites of the enzyme and induces a loop closure that shuts down catalysis at the active site. These findings provide proof-of-principle that PLpro is a viable target for development of antivirals directed against SARS-CoV, and that potent noncovalent cysteine protease inhibitors can be developed with specificity directed toward pathogenic deubiquitinating enzymes without inhibiting host DUBs.


Rapid Implementation of Telehealth in Hospital Psychiatry in Response to COVID-19.


title: Unexpected Biliopancreatic Limb Obstruction after Gastric Bypass Revision.

text: INTRODUCTION Biliopancreatic limb obstruction is a surgical emergency in patients who have undergone gastric bypass surgery. This case report presents an unexpected cause of biliopancreatic limb obstruction and the importance of prompt intervention. MATERIAL AND METHODS A 37-year-old woman presented with complaints of weight regain (BMI increased from 27 to 33.3 kg/m2) and bile reflux and was found to have marginal ulcers on endoscopy. She had undergone loop gastric bypass with Braun anastomosis in 2009 at another center for morbid obesity (BMI = 43 kg/m2). Roux-en-Y gastric bypass (RYGB) was created after the separation of gastro-jejunostomy (GJ) and jejuno-jejunostomy (JJ). On the fifth postoperative day, the patient was readmitted with signs of peritonitis. Urgent relaparoscopy showed Biliopancreatic limb (BP) obstruction. It was then and that we understood intraoperatively the uncut Roux-en-Y caused stricture between the previous GJ and JJ staple lines. Side-to-side jejuno-jejunostomy between the proximal dilated and the distal collapsed biliopancreatic limb was performed. RESULT The patient recovered uneventfully and was discharged after drain removal. CONCLUSION Biliopancreatic limb obstruction requires prompt decision for relaparoscopy. Timely intervention is necessary to prevent postoperative morbidity. Reviewing the operative video or notes of the primary surgery can minimize the chance of mismanagement during revision surgery.


title: Laparoscopic extralevator abdominal perineal excision of the rectum: the best of both worlds.

text: We report a combined laparoscopic and open technique for extralevator abdominal perineal excision of the rectum. The key steps are a laparoscopic rectal dissection limited distally by the coccyx. The open, prone, perineal dissection affords excellent views and allows a cylindrical specimen to be obtained. The resulting perineal defect is closed by a biological mesh. Extralevator abdominal perineal excision of the rectum offers a superior oncological specimen with reduced circumferential resection margin involvement compared to traditional techniques. Combined with a laparoscopic approach, this also has the potential to improve postoperative recovery and reduce morbidity.


title: Diphtheria in Mayotte, 2007-2015.

text: Epidemiology of diphtheria in the southwestern Indian Ocean is poorly documented. We analyzed 14 cases of infection with toxigenic Corynebacterium diphtheriae reported during 2007-2015 in Mayotte, a French department located in this region. Local control of diphtheria is needed to minimize the risk for importation of the bacterium into disease-free areas.


title: Pelargonium sidoides preparation EPs 7630 in COPD: health-related quality-of-life and other patient-reported outcomes in adults receiving add-on therapy.

text: OBJECTIVE Patient-reported outcomes (PRO) such as health-related quality-of-life (HRQoL) belong to the most important criteria for the evaluation of medical therapies in clinical trials or practice-based benefit assessments. This study, therefore, revisited results of an earlier published clinical trial investigating the effects of the herbal drug preparation from the roots of Pelargonium sidoides EPs 7630, administered as add-on therapy in patients suffering from chronic obstructive pulmonary disease (COPD), with respect to HRQoL and other PRO. METHODS A total of 199 adults diagnosed with COPD stages II/III and receiving standard treatment according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) were randomly assigned to add-on therapy with EPs 7630 or placebo for 24 weeks. HRQoL (disease-specific St. George's Respiratory Questionnaire, SGRQ; current HRQoL state according to the EuroQuol visual analog scale, EQ VAS) and PRO (Integrative Medicine Outcomes Scale, IMOS; Integrative Medicine Patient Satisfaction Scale, IMPSS; symptom severity score of cough, sputum production and sternal pain while coughing; duration of inability to work) were assessed at each study visit or documented daily by the patient in a patient diary, respectively. RESULTS At week 24, all HRQoL and PRO measures showed a more pronounced improvement under EPs 7630 than under placebo (EQ VAS, p < .001; SGRQ total score, p < .001; symptom severity score of cough, sputum production, and sternal pain while coughing, p = .021; duration of inability to work, p = .004; two-sided t-test each; IMOS, p < .001, IMPSS, p < .001, two-sided Mantel-Haenszel test each). Moreover, the difference seen for the SGRQ exceeded the SGRQ minimal clinically important difference (MCID) threshold of 4 points. CONCLUSIONS Add-on therapy with EPs 7630 led to an improvement in HRQoL and other PRO in adult patients with COPD compared to placebo while showing a good long-term tolerability.


title: Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial.

text: OBJECTIVE Specific genetic or biological markers may predict inadequate response to therapy for major depressive disorder (MDD). The objective of the current post hoc analysis was to evaluate the effect of specific biological and genetic markers on the antidepressant efficacy of adjunctive L-methylfolate 15 mg versus placebo from a trial of inadequate responders to selective serotonin reuptake inhibitors (SSRIs). METHOD The double-blind, randomized, placebo-controlled trial used the sequential parallel comparison design. Outpatients with SSRI-resistant MDD (DSM-IV criteria) received L-methylfolate 15 mg/d for 60 days, placebo for 30 days followed by L-methylfolate 15 mg/d for 30 days, or placebo for 60 days. The effects of baseline levels of select biological and genetic markers individually and combined on treatment response to L-methylfolate versus placebo were evaluated; the primary response measure was the 28-Item Hamilton Depression Rating Scale (HDRS-28). The first patient was enrolled July 14, 2009, and the last patient completed April 28, 2011. RESULTS Seventy-five patients were enrolled. Patients with specific biological (body mass index ≥ 30 kg/m², elevated plasma levels of high-sensitivity C-reactive protein or 4-hydroxy-2-nonenal, low S-adenosylmethionine/S-adenosylhomocysteine ratio) and genetic markers at baseline had significantly (P ≤ .05) greater pooled mean change from baseline on the HDRS-28 with L-methylfolate versus placebo. Pooled mean change from baseline on the Clinical Global Impressions-Severity of Illness scale was significantly (P < .05) greater with L-methylfolate versus placebo for most genetic markers. Most combinations of baseline biological and genetic markers predicted significantly (P ≤ .05) greater reductions in pooled mean change from baseline in HDRS-28 scores with L-methylfolate versus placebo. CONCLUSIONS Biomarkers associated with inflammation or metabolism and genomic markers associated with L-methylfolate synthesis and metabolism may identify patients with SSRI-resistant depression who are responsive to adjunctive therapy with L-methylfolate 15 mg. Confirmatory studies are needed. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00955955.


title: Role of Ceacam1 in VEGF induced vasculogenesis of murine embryonic stem cell-derived embryoid bodies in 3D culture.

text: CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a type I transmembrane glycoprotein involved in cell-cell adhesion has been shown to act as an angiogenic factor for mouse and human endothelial cells. Based on the ability of CEACAM1 to initiate lumen formation in human mammary epithelial cells grown in 3D culture (Matrigel), we hypothesized that murine CEACAM1 may play a similar role in vasculogenesis. In order to test this hypothesis, murine embryonic stem (ES) cells stimulated with VEGF were differentiated into embryoid bodies (EB) for 8 days (-8-0 d) and transferred to Matrigel in the presence or absence of anti-CEACAM1 antibody for an additional 12 days (0-12 d). In the absence of anti-CEACAM1 antibody or in the presence of an isotype control antibody, the EB in Matrigel underwent extensive sprouting, generating lengthy vascular structures with well-defined lumina as demonstrated by confocal microscopy, electron microscopy, and immunohistochemical analysis. Both the length and architecture of the vascular tubes were inhibited by anti-CEACAM1 mAb CC1, a mAb that blocks the cell-cell adhesion functions of CEACAM1, thus demonstrating a critical role for this cell-cell adhesion molecule in generating and maintaining vasculogenesis. QRT-PCR analysis of the VEGF treated ES cells grown under conditions that convert them to EB revealed expression of Ceacam1 as early as -5 to -3 d reaching a maximum at day 0 at which time EBs were transferred to Matrigel, thereafter levels at first declined and then increased over time. Other markers of vasculogenesis including Pecam1, VE-Cad, and Tie-1 were not detected until day 0 when EBs were transferred to Matrigel followed by a steady increase in levels, indicating later roles in vasculogenesis. In contrast, Tie-2 and Flk-1 (VEGFR2) were detected on day five of EB formation reaching a maximum at day 0 on transfer to Matrigel, similar to Ceacam1, but after which Tie-2 declined over time, while Flk-1 increased over time. QRT-PCR analysis of the anti-CEACAM1 treated ES cells revealed a significant decrease in the expression of Ceacam1, Pecam1, Tie-1, and Flk-1, while VE-Cad and Tie-2 expression were unaffected. These results suggest that the expression and signaling of CEACAM1 may affect the expression of other factors known to play critical roles in vasculogenesis. Furthermore this 3D model of vasculogenesis in an environment of extracellular matrix may be a useful model for comparison to existing models of angiogenesis.


title: Parents' Experience When Present During a Child's Resuscitation: An Integrative Review.

text: Understanding perceptions of parents is necessary to meet parents' needs during a child's resuscitation. Parent presence at pediatric resuscitations has been slow to become consistent practice in all hospital settings and remains controversial. The purpose of this integrative review was to synthesize research on parents' experience while present during a child's resuscitation to improve understanding for health care providers and to facilitate application in practice. Nine studies met inclusion criteria, identifying four major themes. Parents experienced conflicting emotions, articulated a need for communication and support, reported that being physically present was comforting, and described their reactions to the experience. The available research on parents' experience during presence at their child's resuscitation offers a foundation for further detailed study. Further study is needed about parents' perspective of support needed while present during a child's resuscitation, as well as about any long-term effects of presence on parent stress and coping.


title: Incidence of sharps injuries in surgical units, a meta-analysis and meta-regression.

text: BACKGROUND Sharps injuries occur often among surgical staff, but they vary considerably. METHODS We searched PubMed and Embase for studies assessing the incidence of sharps injuries. We combined the incidence rates of similar studies in a random effects meta-analysis and explored heterogeneity with meta-regression. RESULTS We located 45 studies of which 11 were randomized control trials, 15 were follow-up studies, and 19 were cross-sectional studies. We categorized injuries as self-reported, glove perforations, or administrative injuries. We calculated the population at risk as person-years and as person-operations (po). Meta-analysis of the incidence rate based on the best outcome measure resulted in 13.2 injuries per 100 time-units (95% confidence interval [CI], 4.7-37.1; I2 = 100%). Per 100 person-years, the injury rate was 88.2 (95% CI, 61.3-126.9; 21 studies) for self-reported injuries, 40.0 for perforations (95% CI, 19.2-83.5; 15 studies), and 5.8 for administrative injuries (95% CI, 2.7-12.2; 5 studies). Per 100 po, the respective figures were 2.1 (95% CI, 0.8-5.0; 4 studies), 11.1 (95% CI, 6.6-18.9, 15 studies), and 0.1 (95% CI, 0.05-0.21). I2 values were all above 90%. Meta-regression indicated lower incidence rates in studies that used perforations per po. CONCLUSIONS A surgeon will have a sharps injury in about 1 in 10 operations . Reporting of sharps injuries in surgical staff should be standardized per 100 po and be assessed in prospective follow-up studies.


title: MS2 virus inactivation by atmospheric-pressure cold plasma using different gas carriers and power levels.

text: In this study, airborne MS2 bacteriophages were exposed for subsecond time intervals to atmospheric-pressure cold plasma (APCP) produced using different power levels (20, 24, and 28 W) and gas carriers (ambient air, Ar-O2 [2%, vol/vol], and He-O2 [2%, vol/vol]). In addition, waterborne MS2 viruses were directly subjected to the APCP treatment for up to 3 min. MS2 viruses with and without the APCP exposure were examined by scanning electron microscopy (SEM), reverse transcription-PCR (RT-PCR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Viral inactivation was shown to exhibit linear relationships with the APCP generation power and exposure time (R(2) > 0.95 for all energy levels tested) up to 95% inactivation (1.3-log reduction) after a subsecond airborne exposure at 28 W; about the same inactivation level was achieved for waterborne viruses with an exposure time of less than 1 min. A larger amount of reactive oxygen species (ROS), such as atomic oxygen, in APCP was detected for a higher generation power with Ar-O2 and He-O2 gas carriers. SEM images, SDS-PAGE, and agarose gel analysis of exposed waterborne viruses showed various levels of damage to both surface proteins and their related RNA genes after the APCP exposure, thus leading to the loss of their viability and infectivity.


title: Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE cerebral oximeter: a prospective observational crossover study in volunteers.

text: PURPOSE Previous studies have found that most cerebral oximeters are subject to inaccuracies secondary to extracranial contamination of the cerebral oximetric signals. We hypothesized that the more advanced second-generation FORE-SIGHT ELITE cerebral oximeter would be significantly less affected by extracranial tissue hypoxemia than the more widely used first-generation INVOS™ 5100C monitor. METHODS Twenty healthy volunteers aged 18-45 yr had the INVOS and FORE-SIGHT probes placed on their forehead in a random sequence while in the supine position. A pneumatic head cuff was then placed around each volunteer's head just below both the oximeter and a concomitantly placed scalp forehead pulse oximeter probe. The subjects' scalp cerebral oxygen saturation (SctO2) values were measured and compared using the two different devices in sequence, both before and after scalp tissue ischemia was induced by the pneumatic cuff. RESULTS Extracranial ischemia resulted in a significant reduction in SctO2 values from baseline in both devices. The INVOS 5100C recorded a median [interquartile range] decrease in SctO2 from baseline at five minutes of 15.1% [12.6 - 17.6], while that recorded by the FORESIGHT ELITE device was 8.6% [4.0 -12.3] at five minutes (median difference, 7.9%; 99% confidence interval, 1.9 to 16.5; P = 0.002). CONCLUSION Updated technological algorithms employed in the FORE-SIGHT ELITE cerebral oximeter may be responsible for less extracranial contamination than was observed in the previous-generation INVOS 5100C device. The impact that this extracranial contamination may have on the clinical use of these devices remains to be determined.


title: Progress in the tissue engineering and stem cell industry "are we there yet?".

text: This report presents a detailed update to our 2008 publication on the tissue engineering (TE) and stem cell industry. Data are reported through mid 2011 showing an almost three-fold growth in commercial sales over the past 4 years. In addition, the number of companies selling products or offering services has increased over two-fold to 106, and they are generating a remarkable $3.5 billion in sales. Overall, the TE and stem cell sector is spending $3.6 billion and employing almost 14,000 employees. These data suggest the TE and stem cell industry has stabilized and is on a path pointing toward continued success.


title: Canadian federal support for climate change and health research compared with the risks posed.

text: For emerging public health risks such as climate change, the Canadian federal government has a mandate to provide information and resources to protect citizens' health. Research is a key component of this mandate and is essential if Canada is to moderate the health effects of a changing climate. We assessed whether federal support for climate change and health research is consistent with the risks posed. We audited projects receiving federal support between 1999 and 2009, representing an investment of Can$16 million in 105 projects. Although funding has increased in recent years, it remains inadequate, with negligible focus on vulnerable populations, limited research on adaptation, and volatility in funding allocations. A federal strategy to guide research support is overdue.


title: Deposition pattern of aerosolized Legionella using an ex vivo human-porcine respiratory model.

text: Legionella are bacteria responsible for severe lung pathologies. However how they enter and are deposited within the respiratory tract remains poorly documented. Data using animal testing led to the establishment of mathematical models allowing the estimation of aerosol dispersion risks. But direct extrapolation to humans is questionable and experimental models more physiologically representative of the inhalation route are welcome. The aim of this study was to develop a model as close as possible to the human anatomy and physiology allowing determining the deposition pattern of aerosolized Legionella while limiting in vivo experiments. To that purpose, we adapted the chimeric respiratory tract model we previously developed. This original model consisted of a replica of the human upper respiratory airways made by additive manufacturing connected to ex vivo porcine lungs ventilated by passive expansion, as for humans in physiological conditions. These experiments didn't imply specific animal sacrifices as pigs were bred for human consumption and lungs were considered as wastes by the slaughterhouse. Fluorescent Legionella were aerosolized and visualized using Cellvizio® Lab (probe-based confocal fluorescence microscope). Legionella were found in the whole respiratory tract. Broncho-alveolar lavages were also performed and the amount of Legionella reaching the thoracic region was quantified by culture and qPCR. Legionella were found preferentially in the left upper lobe compared to the right lower lobe. To our knowledge, it is the first time that experiments mimicking so closely human exposure by inhalation are performed while limiting animal experiments and providing a model for further Legionella infectious risk assessment.


title: The burden of lung disease in Hong Kong: a report from the Hong Kong Thoracic Society.

text: BACKGROUND AND OBJECTIVE The burden of lung disease in Hong Kong is not known. This study determined the mortality and hospitalization rates of respiratory diseases in Hong Kong in 2005, their trend in the past decade and their incidence/prevalence. METHODS Mortality data were obtained from the Department of Health and hospitalization data from the Hospital Authority, Hong Kong. Incidence/prevalence data were obtained from local registries or local studies. Trends of mortality and hospitalization rates of various respiratory diseases from 1997 and 2005 were calculated after age standardization and were tested for significance using negative binomial regression analysis. Age standardized mortality rates in Hong Kong were compared with those of the UK and globally. RESULTS Respiratory disease was the most common cause of mortality and hospitalization in Hong Kong in 2005. Globally and in the UK, cardiovascular disease ranked first in mortality. Respiratory infections ranked first in respiratory mortality, followed by respiratory tract cancer and chronic obstructive lung disease. Respiratory infections also ranked first followed by chronic obstructive lung disease in the utilization of respiratory inpatient bed-days. While mortality rates from all respiratory diseases decreased in the past decade, hospitalization rates remained unchanged. Unlike other respiratory diseases, mortality from respiratory infections have increased since 2001. Smoking is the most important risk factor in non-communicable respiratory diseases. CONCLUSIONS Respiratory disease is responsible for the highest health-care burden locally. Increased efforts in improving management and prevention of these diseases, including tobacco control, improving air quality and vaccination against influenza and pneumococci, are necessary.


title: Modified delta-shaped gastroduodenostomy consisting of linear stapling and single-layer suturing with the operator positioned between the patient's legs: A technique preventing intraoperative duodenal injury and postoperative anastomotic stenosis.

text: BACKGROUND The drawback of the delta-shaped gastroduodenostomy (DSG) in totally laparoscopic distal gastrectomy (TLDG) is the presence of intraoperative duodenal injury and postoperative anastomotic stenosis, which can occur due to a relatively short duodenal bulb diameter. MATERIALS AND METHODS From June 2013 to June 2019, 35 patients with gastric cancer underwent TLDG with a modified DSG consisting of linear stapling and single-layer hand suturing in our institution. All anastomotic procedures were performed by the right hand of the operator positioned between the patient's legs. Linear stapling of the posterior walls of the remnant stomach and duodenum without creating a gap was performed using a 45-mm linear stapler, considering the prevention of intraoperative duodenal injury. The stapler entry hole was closed using a single-layer full-thickness hand suturing technique with knotted sutures and a knotless barbed suture. We described the clinical data and outcomes in the present retrospective patient series. RESULTS No intraoperative duodenal injury occurred in any of the 35 patients. The median staple length at linear stapling of the posterior walls of the remnant stomach and duodenum was 41.7 ± 4.2 (30-45) mm, and 2 patients (5.7%) had a staple length of 30 mm. There were no incidences of postoperative anastomotic stenosis. CONCLUSIONS We suggest that a modified DSG consisting of linear stapling and single-layer hand suturing performed by an operator positioned between the patient's legs can be one option for B-Ⅰ reconstruction following TLDG because it can aid in preventing both intraoperative duodenal injury and postoperative anastomotic stenosis.


title: Design, synthesis, antiviral, and cytotoxic evaluation of novel phosphonylated 1,2,3-triazoles as acyclic nucleotide analogues.

text: The 1,3-dipolar cycloaddition of diethyl 2-azidoethyl-, 3-azidopropyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropylphosphonates with selected N-propargyl nucleobases gave a series of the phosphonylated 1,2,3-triazole acyclonucleosides in which the phosphonate residue and nucleobases were linked by three- and four-carbon chains. Under standard conditions (TMSBr, ethanol), all synthesized O,O-diethylphosphonates were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses. Unfortunately, no antiviral activity was observed at 100 μM.


title: Onyx extravasation during embolization of a brain arteriovenous malformation.

text: During Onyx embolization to treat brain arteriovenous malformation (AVM), carefully observing the penetration of Onyx to the nidus is important in order to avoid complications such as hemorrhage, ischemia, and difficulty with microcatheter removal. We encountered a case of Onyx extravasation during embolization of a cerebellar AVM confirmed by surgical resection and pathological analysis. The patient was a 44-year-old man with Spetzler-Martin grade I cerebellar AVM who underwent Onyx embolization prior to resection of the brain AVM. While injecting Onyx into the nidus using the "plug-and-push" technique, Onyx extravasation was observed. Onyx injection was paused and subsequently restarted, thereby allowing continuation of embolization. An oblate Onyx cast that was entirely covered in cerebellar tissue was removed during total resection of the AVM, performed the same day. The surgically removed oblate Onyx cast did not contain brain tissue or vessel wall, and immunohistochemical staining against glial fibrillary acidic protein (GFAP) showed Onyx penetration into GFAP-positive cerebellar tissue. Onyx extravasation was confirmed based on intraoperative findings during resection as well as pathological findings. The patient has been followed for four years postoperatively, and adverse events caused by Onyx extravasation have not been observed. Unexpected cast of Onyx, remote from the vascular architecture of the AVM, may represent an intra-parenchymal extravasation.


title: Diaphragm function and weaning from mechanical ventilation: an ultrasound and phrenic nerve stimulation clinical study.

text: BACKGROUND Diaphragm dysfunction is defined by a value of twitch tracheal pressure in response to magnetic phrenic stimulation (twitch pressure) amounting to less than 11 cmH2O. This study assessed whether this threshold or a lower one would predict accurately weaning failure from mechanical ventilation. Twitch pressure was compared to ultrasound measurement of diaphragm function. METHODS In patients undergoing a first spontaneous breathing trial, diaphragm function was evaluated by twitch pressure and by diaphragm ultrasound (thickening fraction). Receiver operating characteristics curves were computed to determine the best thresholds predicting failure of spontaneous breathing trial. RESULTS Seventy-six patients were evaluated, 48 (63%) succeeded and 28 (37%) failed the spontaneous breathing trial. The optimal thresholds of twitch pressure and thickening fraction to predict failure of the spontaneous breathing trial were, respectively, 7.2 cmH2O and 25.8%, respectively. The receiver operating characteristics curves were 0.80 (95% CI 0.70-0.89) for twitch pressure and 0.82 (95% CI 0.73-0.93) for thickening fraction. Both receiver operating characteristics curves were similar (p = 0.83). A twitch pressure value lower than 11 cmH2O (the traditional cutoff for diaphragm dysfunction) predicted failure of the spontaneous breathing trial with a sensitivity of 89% (95% CI 72-98%) and a specificity of 45% (95% CI 30-60%). CONCLUSIONS Failure of spontaneous breathing trial can be predicted with a lower value of twitch pressure than the value defining diaphragm dysfunction. Twitch pressure and thickening fraction had similar strong performance in the prediction of failure of the spontaneous breathing trial.


title: Impact of extracranial contamination on regional cerebral oxygen saturation: a comparison of three cerebral oximetry technologies.

text: BACKGROUND Cerebral oximetry is a noninvasive technology using near-infrared spectroscopy (NIRS) to estimate regional cerebral oxygen saturation. Although NIRS cerebral oximetry is being increasingly used in many clinical settings, interdevice technologic differences suggest potential variation in the ability to accurately acquire brain oxygenation signals. The primary objective of this study was to determine if NIRS-derived regional cerebral oxygen saturation measurements accurately account for oxygen saturation contamination from extracranial tissue. METHODS Twelve healthy volunteers had each of three NIRS devices (FORE-SIGHT [CAS Medical Systems Inc; Brandford, CT], INVOS 5100C-PB [Covidien; Boulder, CO], and EQUANOX Classic 7600 [Nonin Medical Inc; Plymouth, MN]) randomly applied to the forehead. After this, a circumferential pneumatic head cuff was positioned such that when inflated, hypoxia-ischemia would be produced in the extracranial scalp tissue beneath the NIRS cerebral oximeters. Comparisons among the three devices were made of the NIRS measurements before and following hypoxia-ischemia produced in the scalp tissue with inflation of the head cuff. RESULTS The induction of extracranial hypoxia-ischemia resulted in a significant reduction in regional cerebral oxygen saturation measurements in all three NIRS devices studied. At 5 min postinflation of the pneumatic head cuff, the INVOS demonstrated a 16.6 ± 9.6% (mean ± SD) decrease from its baseline (P = 0.0001), the FORE-SIGHT an 11.8 ± 5.3% decrease from its baseline (P < 0.0001), and the EQUANOX a 6.8 ± 6.0% reduction from baseline (P = 0.0025). CONCLUSIONS Extracranial contamination appears to significantly affect NIRS measurements of cerebral oxygen saturation. Although the clinical implications of these apparent inaccuracies require further study, they suggest that the oxygen saturation measurements provided by cerebral oximetry do not solely reflect that of the brain alone.


title: Nontraditional modes of mechanical ventilation: progress or distraction?

text: As technology continues to develop, a wide range of novel and nontraditional modes of mechanical ventilation have become available for the management of critically ill patients. Proportional assist ventilation, neurally adjusted ventilatory assist and adaptive support ventilation are three novel modes of ventilation, which attempt to optimize patient-ventilator synchrony. Improved interactions between patient and ventilator may be important in improving clinical outcomes. Another important priority for mechanically ventilated patients is lung protection, and nontraditional modes of ventilation that may be implemented to minimize ventilator-associated lung injury include airway pressure release ventilation and high-frequency ventilation. Novel and nontraditional modes of ventilation may represent important tools in the critical care environment; however, continued investigation is needed to determine the overall impact of these various approaches on outcomes for mechanically ventilated patients.


A 55-Year-Old Man with a Trachea Undressed.


title: Crystal structure of the mouse hepatitis virus ns2 phosphodiesterase domain that antagonizes RNase L activation.

text: Prior studies have demonstrated that the mouse hepatitis virus (MHV) A59 strain ns2 protein is a member of the 2H phosphoesterase family and exhibits 2',5'-phosphodiesterase (PDE) activity. During the IFN antiviral response, ns2 cleaves 2',5'-oligoadenylate (2-5A), a key mediator of RNase L activation, thereby subverting the activation of RNase L and evading host innate immunity. However, the mechanism of 2-5A cleavage by ns2 remains unclear. Here, we present the crystal structure of the MHV ns2 PDE domain and demonstrate a PDE fold similar to that of the cellular protein, a kinase anchoring protein 7 central domain (AKAP7(CD)) and rotavirus VP3 carboxy-terminal domain. The structure displays a pair of strictly conserved HxT/Sx motifs and forms a deep, positively charged catalytic groove with β-sheets and an arginine-containing loop. These findings provide insight into the structural basis for 2-5A binding of MHV ns2.


title: Randomized clinical trial of stapler hepatectomy versus LigaSure™ transection in elective hepatic resection.

text: BACKGROUND Previous studies have demonstrated stapler hepatectomy and use of various energy devices to be safe alternatives to the clamp-crushing technique in elective hepatic resection. In this randomized trial, the effectiveness and safety of stapler hepatectomy were compared with those of parenchymal transection with the LigaSure™ vessel sealing system. METHOD Patients scheduled for elective liver resection at two tertiary-care centres were randomized during surgery to stapler hepatectomy or transection with the LigaSure™ device. Total intraoperative blood loss was the primary efficacy endpoint. Transection time, duration of operation, perioperative complications and length of hospital stay were recorded as secondary endpoints. RESULTS A total of 138 patients were analysed, 69 in the LigaSure™ and 69 in the stapler hepatectomy group. Baseline characteristics were well balanced between the groups. Mean intraoperative blood loss was significantly higher in the LigaSure™ group than the stapler hepatectomy group: 1101 (95 per cent c.i. 915 to 1287) versus 961 (752 to 1170) ml (P = 0·028). The parenchymal transection time was significantly shorter in the stapler group (P = 0·005), as was the total duration of operation (P = 0·027). Surgical morbidity did not differ between the groups, nor did the grade of complications. CONCLUSION Stapler hepatectomy was associated with reduced blood loss and a shorter duration of operation than the LigaSure™ device for parenchymal transection in elective partial hepatectomy. Registration number: NCT01858987 (http://www.clinicaltrials.gov).


title: Energy vessel sealing systems versus mechanical ligature of the inferior mesenteric artery in laparoscopic sigmoidectomy.

text: PURPOSE With the development of new devices, our ligation technique of the inferior mesenteric artery changed from mechanical ligature (ML) to energized vessel sealing systems (EVSS) ligature. The aim of this study was to determine if EVSS could be considered as safe and effective as the more convention ML of the inferior mesenteric vessels division during elective laparoscopic left colectomy. METHODS Between 2001 and 2014, 200 consecutive patients (111 males) of mean age 54.1 years were operated laparoscopically for a symptomatic sigmoid diverticulitis. Vascular interruptions were performed using mechanical ligatures including double clipping, staples or surgical thread (100 patients) or, starting from 2006, with EVSS thereafter (100 patients). Section of the inferior mesenteric artery is performed systematically at its origin in our institution for teaching purposes. Technical results were prospectively collected perioperatively and postoperatively. RESULTS There was no mortality. Mean operating time was 253.7 and 200.7 min in the ML and EVSS groups, respectively (p < 0.001). Mean hospital stay was 10.4 and 8.1 days (p < 0.001). Thirty-day complications occurred in 31 versus 25 % of patients (p = 0.26). Leakage with peritonitis occurred in 3 patients in the ML group. Hemorrhagic events occurred in both groups (2 in ML group versus 1 in EVSS group). Limitations of the study are its retrospective design and the bias due to the comparison of two historical cohorts. CONCLUSIONS EVSS for the inferior mesenteric artery are as safe and effective as ML in elective sigmoidectomy for diverticular disease with lower operative time and hospital stay.


title: Method of preparing a decellularized porcine tendon using tributyl phosphate.

text: Extracellular matrix (ECM) materials are currently utilized for soft tissue repair applications such as vascular grafts, tendon reconstruction, and hernia repair. These materials are derived from tissues such as human dermis and porcine small intestine submucosa, which must be rendered acellular to prevent disease transmission and decrease the risk of an immune response. The ideal decellularization technique removes cells and cellular remnants, but leaves the original collagen architecture intact. The tissue utilized in this study was the central tendon of the porcine diaphragm, which had not been previously investigated for soft tissue repair. Several treatments were investigated during this study including peracetic acid, TritonX-100, sodium dodecyl sulfate, and tri(n-butyl) phosphate (TnBP). Of the decellularization treatments investigated, only 1% TnBP was effective in removing cell nuclei while leaving the structure and composition of the tissue intact. Overall, the resulting acellular tissue scaffold retained the ECM composition, strength, resistance to enzymatic degradation, and biocompatibility of the original tissue, making 1% TnBP an acceptable decellularization treatment for porcine diaphragm tendon.


title: Pathology-based validation of FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer.

text: PURPOSE FDG PET is increasingly incorporated into radiation treatment planning of head and neck cancer. However, there are only limited data on the accuracy of radiotherapy target volume delineation by FDG PET. The purpose of this study was to validate FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer against the pathological method as the standard. METHODS Twelve patients with head and neck cancer and 28 metastatic lymph nodes eligible for therapeutic neck dissection underwent preoperative FDG PET/CT. The metastatic lymph nodes were delineated on CT (NodeCT) and ten PET segmentation tools were used to assess FDG PET-based nodal volumes: interpreting FDG PET visually (PETVIS), applying an isocontour at a standardized uptake value (SUV) of 2.5 (PETSUV), two segmentation tools with a fixed threshold of 40% and 50%, and two adaptive threshold based methods. The latter four tools were applied with the primary tumour as reference and also with the lymph node itself as reference. Nodal volumes were compared with the true volume as determined by pathological examination. RESULTS Both NodeCT and PETVIS showed good correlations with the pathological volume. PET segmentation tools using the metastatic node as reference all performed well but not better than PETVIS. The tools using the primary tumour as reference correlated poorly with pathology. PETSUV was unsatisfactory in 35% of the patients due to merging of the contours of adjacent nodes. CONCLUSION FDG PET accurately estimates metastatic lymph node volume, but beyond the detection of lymph node metastases (staging), it has no added value over CT alone for the delineation of routine radiotherapy target volumes. If FDG PET is used in radiotherapy planning, treatment adaptation or response assessment, we recommend an automated segmentation method for purposes of reproducibility and interinstitutional comparison.


Myocarditis detected after COVID-19 recovery.


title: Two-year analysis of the Japanese cohort from the Zilver PTX randomized controlled trial supports the validity of multinational clinical trials.

text: PURPOSE To report a subgroup analysis comparing safety and effectiveness outcomes in Japanese and non-Japanese patients as part of a prospective, multinational, randomized controlled trial (ClinicalTrials.gov identifier NCT00120406) evaluating a paclitaxel-coated drug-eluting stent (DES) compared to percutaneous transluminal angioplasty (PTA) for treating peripheral artery disease. METHODS Patients were randomly assigned to primary DES or PTA. In the Japanese cohort, 27 patients (21 men; mean age 71.2±9.6 years) were randomized to PTA and 25 patients (19 men; mean age 69.8±10.2 years) to primary DES. In the non-Japanese cohort, 211 patients (131 men; mean age 67.3±10.6 years) were randomized to PTA and 211 patients (136 men; mean age 67.6±9.5 years) to primary DES. Outcome measures included event-free survival (EFS), freedom from target lesion revascularization (TLR), patency, stent fracture, and sustained clinical benefit through 2 years. RESULTS Safety and effectiveness outcomes were similar in the Japanese and non-Japanese cohorts, although the outcomes in the Japanese cohort treated with primary DES were numerically better. In the DES group, the 2-year EFS was 92.0% vs. 85.0% (p=0.61), freedom from TLR was 96.0% vs. 85.5% (p=0.55), primary patency was 80.0% vs. 74.3% (p=0.61), and clinical benefit was sustained in 88.5% vs. 80.5% of patients (p=0.31) in the Japanese and non-Japanese cohorts, respectively. Stent fractures were seen in 4 of 457 stents at 12 months: 3 in the Japanese cohort and 1 in the non-Japanese cohort. CONCLUSION The subgroup analysis comparing Japanese and non-Japanese patients supports the safety and effectiveness of the paclitaxel-coated DES in Japanese patients with stenotic lesions in the femoropopliteal arteries. The lack of major differences associated with ethnicity in these 2-year outcomes supports the validity and value of multinational clinical trials.


Required COVID Mandatories.


title: Evaluation and Comparison of Contemporary Energy-Based Surgical Vessel Sealing Devices.

text: INTRODUCTION We evaluated and compared five currently available energy-based vessel sealing devices to assess typical surgical metrics. METHODS We tested Caiman 5 (C5), Harmonic Scalpel Ace Plus (HA), Harmonic Ace +7 (HA7), LigaSure (LS), and Enseal G2 (ES) on small (2-5 mm), medium (5.1-7 mm), and large (7.1-9 mm) vessels obtained from 15 Yorkshire pigs. Vessels were randomly sealed and transected. We recorded sealing and transection time, charring and carbonization, thermal spread, and bursting pressure (BP). Specimens were sent for histopathologic evaluation of seal quality and thermal spread. RESULTS A total of 246 vessels were evaluated: 125 were arteries and 121 were veins. There was no difference in BPs for small size arteries. For medium arteries, C5 provided the highest BP (proximal and distal jaw), followed by HA7, ES, LS, and HA [1740, 1600, 1165, 1165, 981, and 571 mm Hg, respectively, HA<C5-D(<0.001); HA<C5-P(<0.001); HA<ES(0.002); HA<HA7(0.002); HA7<C5-P(0.026); ES<C5-P(0.026); LS<C5-P(0.001); LS<C5-D(0.014)]. For large arteries, C5 and LS provided highest BP followed by HA7, ES, and HA [1676, 530, 467, 467, and 254 mm Hg, respectively, C5<HA(<0.001); C5<HA7(0.006); C5<ES(0.006); C5<LS(0.012)]. There were no bursting pressure failures for C5, HA7, and LS up to 9 mm vessels. For medium and large size arteries, HA had bursting failure of 20% and 40%, respectively. The ES was significantly less efficient with small, medium, and large arteries with bursting failure rates of 10%, 40%, and 80%, respectively. CONCLUSIONS In this study, C5 outperformed all other devices. However, all of the devices provide a seal that was superphysiologic in that all burst pressures were >250 mm Hg.


title: Anemia tolerance during normo-, hypo-, and hypervolemia.

text: BACKGROUND Restrictive intraoperative fluid management has been demonstrated to improve outcome of visceral and lung surgery in several studies. However, subsequent hypovolemia (HOV) may be accompanied by a decrease of anemia tolerance, resulting in increased transfusion needs. We therefore investigated the effect of volume status on anemia tolerance. STUDY DESIGN AND METHODS Eighteen domestic pigs of either sex (mean weight, 23.5 ± 4.8 kg) were anesthetized, ventilated, and randomized into three experimental groups: normovolemia (no intervention), HOV (blood loss of 40% of blood volume), and hypervolemia (HEV; volume infusion of 40% of blood volume). The animals were then hemodiluted until their individual critical hemoglobin concentrations (Hbcrit ) were reached by the exchange of whole blood for hydroxyethyl starch (HES; 130:0.4). Subsequently, organ-specific hypoxia was assessed using pimonidazole tissue staining in relevant organs. Hemodynamic and metabolic variables were also investigated. RESULTS Despite significant differences in exchangeable blood volume, Hbcrit was the same in all groups (2.3 g/dL, NS). During HOV, tissue hypoxia was aggravated in the myocardium, brain, and kidneys, whereas tissue oxygenation of the liver and intestine was not influenced by volume status. HEV increased tissue hypoxia in the lungs, but did not impact tissue oxygenation of other organs. CONCLUSIONS The combination of hemorrhagic HOV with subsequent anemia leads to accentuated tissue hypoxia, revealed by a significant increase in pimonidazole binding at Hbcrit , in heart, lungs, brain, and kidney. The lungs were the only organ that showed increased tissue hypoxia after pretreatment of HES infusion and subsequent anemia by normovolemic hemodilution.


title: Comparison between trans-obturator trans-vaginal mesh and traditional anterior colporrhaphy in the treatment of anterior vaginal wall prolapse: results of a French RCT.

text: INTRODUCTION AND HYPOTHESIS To compare the efficacy of a collagen-coated polypropylene mesh and anterior colporrhaphy in the treatment of stage 2 or more anterior vaginal wall prolapse. METHODS Prospective, randomized, multicenter study conducted between April 2005 and December 2009. The principal endpoint was the recurrence rate of stage 2 or more anterior vaginal wall prolapse 12 months after surgery. Secondary endpoints consisted of functional results and mesh-related morbidity. RESULTS One hundred and forty-seven patients were included, randomized and analyzed: 72 in the anterior colporrhaphy group and 75 in the mesh group. The anatomical success rate was significantly higher in the mesh group (89%) than in the colporrhaphy group (64%) (p = 0.0006). Anatomical and functional recurrence was also less frequent in the mesh group (31.3% vs 52.2%, p = 0.007). Two patients (2.8%) were reoperated on in the colporrhaphy group for anterior vaginal wall prolapse recurrence. No significant difference was noted regarding minor complications. An erosion rate of 9.5% was noted. De novo dyspareunia occurred in 1/14 patients in the colporrhaphy group and in 3/13 patients in the mesh group. An analysis of the quality of life questionnaires showed an overall improvement in both groups, with no statistical difference between them. Satisfaction rates were high in both groups (92% in the colporrhaphy group and 96% in the mesh group). CONCLUSION Trans-obturator Ugytex mesh used to treat anterior vaginal wall prolapse gives better 1-year anatomical results than traditional anterior colporrhaphy, but with small a increase in morbidity in the mesh group.


Ethical, green and sustainable nuclear medicine.


title: Learning from our immunological history: What can SARS-CoV teach us about SARS-CoV-2?

text: Many strategies are being deployed to rapidly uncover targetable mechanisms of infection for SARS-CoV-2, and Hoffman et al exploit our understanding and immunological experience with SARS-CoV in our global race to understand, mitigate, and eventually prevent COVID-19.


title: Utilization of municipal solid and liquid wastes for bioenergy and bioproducts production.

text: Municipal wastes, be it solid or liquid, are rising due to the global population growth and rapid urbanization and industrialization. Conventional management practice involving recycling, combustion, and treatment/disposal is deemed unsustainable. Solutions must be sought to not only increase the capacity but also improve the sustainability of waste management. Research has demonstrated that the non-recyclable waste materials and bio-solids can be converted into useable heat, electricity, or fuel and chemical through a variety of processes, including gasification, pyrolysis, anaerobic digestion, and landfill gas in addition to combustion, and wastewater streams have the potential to support algae growth and provide other energy recovery options. The present review is intended to assess and analyze the current state of knowledge in the municipal solid wastes and wastewater treatment and utilization technologies and recommend practical solution options and future research and development needs.


title: Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn's disease: report of the OPERA study.

text: OBJECTIVE This phase II, randomised, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PF-00547659, a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule (MAdCAM) to selectively reduce lymphocyte homing to the intestinal tract, in patients with moderate-to-severe Crohn's disease (CD). DESIGN Eligible adults were aged 18-75 years, with active moderate-to-severe CD (Crohn's Disease Activity Index (CDAI) 220-450), a history of failure or intolerance to antitumour necrosis factor and/or immunosuppressive agents, high-sensitivity C reactive protein >3.0 mg/L and ulcers on colonoscopy. Patients were randomised to PF-00547659 22.5 mg, 75 mg or 225 mg or placebo. The primary endpoint was CDAI 70-point decrease from baseline (CDAI-70) at week 8 or 12. RESULTS In all, 265 patients were eligible for study entry. Although CDAI-70 response was not significantly different with placebo versus PF-00547659 treatment at weeks 8 or 12, remission rate was greater in patients with higher baseline C reactive protein (>5 mg/L vs >18.8 mg/L, respectively). Soluble MAdCAM decreased significantly from baseline to week 2 in a dose-related manner and remained low during the study in PF-00547659-treated patients. Circulating β7+ CD4+ central memory T-lymphocytes increased at weeks 8 and 12 with PF-00547659 treatment. No safety signal was seen. CONCLUSIONS Clinical endpoint differences between PF-00547659 and placebo did not reach statistical significance in patients with moderate-to-severe CD. PF-00547659 was pharmacologically active, as shown by a sustained dose-related decrease in soluble MAdCAM and a dose-related increase in circulating β7+ central memory T cells. TRIAL REGISTRATION NUMBER NCT01276509; Results.


title: Role of Telehealth in the Management of COVID-19: Lessons Learned from Previous SARS, MERS, and Ebola Outbreaks.

text: Concerns about the prevention and management of COVID-19 are on the rise, as it is crucial in contagious epidemics that travel and transfer of the patients be minimal for diagnosis, treatment, and follow-ups. Telemedicine or telehealth can play an important role, especially with previous successful experiences in the management of acute infectious respiratory epidemics such as SARS and MERS. In order to better control the rapid spread of coronavirus and manage the COVID-19 crisis, both developed and developing countries can improve the efficiency of their health system by replacing a proportion of face-to-face clinical encounters with telehealth. Recent technological advancement facilitates this reform, but there is a need for national or state-wide rules and regulations to be adapted accordingly.


title: Review article: closed-loop systems in anesthesia: is there a potential for closed-loop fluid management and hemodynamic optimization?

text: Closed-loop (automated) controllers are encountered in all aspects of modern life in applications ranging from air-conditioning to spaceflight. Although these systems are virtually ubiquitous, they are infrequently used in anesthesiology because of the complexity of physiologic systems and the difficulty in obtaining reliable and valid feedback data from the patient. Despite these challenges, closed-loop systems are being increasingly studied and improved for medical use. Two recent developments have made fluid administration a candidate for closed-loop control. First, the further description and development of dynamic predictors of fluid responsiveness provides a strong parameter for use as a control variable to guide fluid administration. Second, rapid advances in noninvasive monitoring of cardiac output and other hemodynamic variables make goal-directed therapy applicable for a wide range of patients in a variety of clinical care settings. In this article, we review the history of closed-loop controllers in clinical care, discuss the current understanding and limitations of the dynamic predictors of fluid responsiveness, and examine how these variables might be incorporated into a closed-loop fluid administration system.


title: Stonehenge technique is associated with faster aortic clamp time in group of minimally invasive aortic valve replacement via right infra-axillary thoracotomy.

text: BACKGROUND Trans-right axillary aortic valve replacement (TAX-AVR) remains uncommon. We developed a special method to pull the heart closer to the right chest wall to make the surgery as easy and safe as aortic valve replacement via median sternotomy. Because the retraction sutures lifting the ascending aorta and aortic root are arranged circularly around the wound, we named this technique "Stonehenge technique". METHODS We examined 47 patients who underwent aortic valve replacement through a small right infra-axillary thoracotomy as the initial surgical therapy. These patients were divided into two groups: the conventional TAX-AVR group that underwent AVR via the conventional small right axillary incision approach (n = 20) and the TAX-AVR with SH group that underwent AVR with the Stonehenge technique (n = 27). RESULTS The aortic cross-clamp and the extracorporeal circulation time were significantly shorter in the TAX-AVR with SH group than in the conventional TAX-AVR group (conventional TAX-AVR group: 125.5 ± 47.9; TAX-AVR with SH group: 96.0 ± 14.0, p = 0.004, and conventional TAX-AVR group: 163.8 ± 55.9; TAX-AVR with SH group: 140.0 ± 16.8, p = 0.04). CONCLUSION The outcomes of this technique depend on the site of the retraction sutures in the opened pericardium, direction of pull, amount of force applied, and precautions taken. If performed correctly, the ascending aorta and the root can be pulled from the wound to within the surgeon's fingers' reach, thereby reducing aortic cross-clamp and extracorporeal circulation times in group of minimally invasive aortic valve replacement via right infra-axillary thoracotomy.


title: Impact of a custom-made 3D printed ergonomic grip for direct laryngoscopy on novice intubation performance in a simulated easy and difficult airway scenario-A manikin study.

text: Direct laryngoscopy using a Macintosh laryngoscope is the most widely used approach; however, this skill is not easy for novices and trainees. We evaluated the performance of novices using a laryngoscope with a three-dimensional (3D)-printed ergonomic grip on an airway manikin. Forty second-year medical students were enrolled. Endotracheal intubation was attempted using a conventional Macintosh laryngoscope with or without a 3D-printed ergonomic support grip. Primary outcomes were intubation time and overall success rate. Secondary outcomes were number of unsuccessful attempts, first-attempt success rate, airway Cormack-Lehane (CL) grade, and difficulty score. In the easy airway scenario, intubation time, and the overall success rate were similar between two group. CL grade and ease-of-use scores were significantly better for those using the ergonomic support grip (P < 0.05). In the difficult airway scenario, intubation time (49.7±37.5 vs. 35.5±29.2, P = 0.013), the first-attempt success rate (67.5% vs. 90%, P = 0.029), number of attempts (1.4±0.6 vs. 1.1±0.4, P = 0.006), CL grade (2 [2, 2] vs. 2 [1, 1], P = 0.012), and ease-of-use scores (3.5 [2, 4] vs. 4 [3, 5], P = 0.008) were significantly better for those using the ergonomic support grip. Linear mixed model analysis showed that the ergonomic support grip had a favorable effect on CL grade (P<0.001), ease-of-use scores (P<0.001), intubation time (P = 0.015), and number of intubation attempts (P = 0.029). Our custom 3D-printed ergonomic laryngoscope support grip improved several indicators related to the successful endotracheal intubation in the easy and difficult scenario simulated on an airway manikin. This grip may be useful for intubation training and practice.


title: Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells.

text: Protein ubiquitination regulates important innate immune responses. The discovery of viruses encoding deubiquitinating enzymes (DUBs) suggests they remove ubiquitin to evade ubiquitin-dependent antiviral responses; however, this has never been conclusively demonstrated in virus-infected cells. Arteriviruses are economically important positive-stranded RNA viruses that encode an ovarian tumor (OTU) domain DUB known as papain-like protease 2 (PLP2). This enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cellular proteins. To dissect this dual specificity, which relies on a single catalytic site, we determined the crystal structure of equine arteritis virus PLP2 in complex with ubiquitin (1.45 Å). PLP2 binds ubiquitin using a zinc finger that is uniquely integrated into an exceptionally compact OTU-domain fold that represents a new subclass of zinc-dependent OTU DUBs. Notably, the ubiquitin-binding surface is distant from the catalytic site, which allowed us to mutate this surface to significantly reduce DUB activity without affecting polyprotein cleavage. Viruses harboring such mutations exhibited WT replication kinetics, confirming that PLP2-mediated polyprotein cleavage was intact, but the loss of DUB activity strikingly enhanced innate immune signaling. Compared with WT virus infection, IFN-β mRNA levels in equine cells infected with PLP2 mutants were increased by nearly an order of magnitude. Our findings not only establish PLP2 DUB activity as a critical factor in arteriviral innate immune evasion, but the selective inactivation of DUB activity also opens unique possibilities for developing improved live attenuated vaccines against arteriviruses and other viruses encoding similar dual-specificity proteases.


Rare CT manifestions of an asymptomatic girl with COVID-19.


title: Impact of the COVID-19 epidemic on census, organization and activity of a large urban Emergency Department.

text: BACKGROUND The spread of coronavirus disease 2019 (COVID-19) is overwhelming the response of many regional health services across Italy. This article aims to report and discuss the data of the first 8 weeks of COVID-19 epidemic in the emergency department (ED) of the University Hospital of Parma. METHODS The ED visits were analyzed as follows: total ED visits, divided in COVID-19/ non-COVID-19 cases, and in trauma-related/non-trauma-related cases; outcome (i.e., discharged, admitted, dead in the ED) of patients, altogether or stratified according to triage class; age classes of the entire ED population. RESULTS Total ED visits decreased starting from the first days of the outbreak, then exhibiting progressive growth afterwards. COVID suspected cases rapidly increased, whereas non-COVID suspected dropped and remained well below the standard. Trauma-related cases declined, both as ED visits and as hospital admissions. The percentage and absolute number of patients admitted to hospital wards progressively increased, rapidly overwhelming the number of cases that could be discharged. The admission rate in the lowest priority classes also displayed a marked increase. The youngest age classes dramatically declined, whilst the oldest progressively increased, remaining considerably over the standard rate of the local ED. CONCLUSIONS The COVID-19 pandemic has obliged the health care systems to undergo a paradigm shift. Even triage criteria have partially lost their meaning, as shown by the dramatic increase of hospital admissions, even in the lowest priority classes. A deep re-organizational process of the ED was undertaken. Hospitals must be constantly resilient and prepared to these new emergencies in terms of equipment, medical and nurses staff, larger bed capacity in short time, availability of intensive and sub-intensive beds, and flexibility.


title: Optimizing working-space in laparoscopy: measuring the effect of mechanical bowel preparation in a porcine model.

text: BACKGROUND Adequate working space is a prerequisite for safe and efficient minimal access surgery. No objective data exist in literature about the effect of mechanical bowel preparation (MBP) on working space in laparoscopic surgery. We objectively measured this effect with computed tomography in a porcine laparoscopy model. METHODS Using standardized anesthesia, twelve 20-kg pigs without MBP and eight 20-kg pigs with MBP were studied with computed tomography at intra-abdominal pressure (IAP) levels of 0, 5, 10, and 15 mmHg. Volumes and dimensions of the pneumoperitoneum were measured on reconstructed CT images and compared between the pigs with and those without MBP. RESULTS A reproducible and statistically significant increase of approximately 500 ml in pneumoperitoneum volume was found in the MBP group at all levels of IAP. This represents a 43 % relative increase at a pneumoperitoneum pressure of 5 mmHg, 21 % at IAP 10 mmHg, and 18 % at IAP 15 mmHg. Peak inspiratory pressure was lower at IAP 0 and 5 mmHg in the MBP group. Anteroposterior diameter in the group with MBP was lower at 0 mmHg, but abdominal dimensions were similar in both groups at all other IAPs. This shows that the gain in working space is due to a diminished volume of the intra-abdominal content and not to compression or displacement of the bowel. CONCLUSIONS MBP increases working space by reducing bowel content. Especially at low intra-abdominal working pressures, the increase in working space associated with MBP could represent an important benefit in challenging laparoscopic surgery.


title: Occult Pulsatile Tinnitus in Association with a Prominent Vein of Hypoglossal Canal: Two Case Reports.

text: The pathway of the vein of hypoglossal canal has not been mentioned in venous origin pulsatile tinnitus. We wished to clarify the possible complications related to this venous variant. We described 2 rare cases of troublesome pulsatile tinnitus associated with prominent vein of hypoglossal canal, which communicates with the jugular bulb and the marginal sinus. Both cases were successfully treated by positioning a stent across the vein of hypoglossal canal and jugular bulb. The 2 present clinical cases represent the first report of such a condition. The therapeutic decision-making is discussed in relation to the persistent pulsatile tinnitus and the etiopathologic hypothesis put forward.


title: Pulmonary infections in the athlete.

text: Despite their general high level of health, athletes are not free from the threat of developing pulmonary infection. Prompt diagnosis and proper treatment are important given the effects of pulmonary infection upon athletic performance and time away from training. This article reviews common etiologies of community-acquired pneumonia and a more in-depth discussion of mycoplasma pneumonie and influenza. Current treatment guidelines, acute bronchitis, fungal pulmonary infection, and return to play principles also are discussed.


Memento Mori.


title: Domestic violence and COVID-19: Our hidden epidemic.

text: In times of disaster, domestic violence rates tend to increase. This is a concern in the context of COVID-19, which is a more prolonged crisis than most of those studied.


title: The kidney in COVID-19: protagonist or figurant?

text: The etiology of injury in COVID-19 patients is diverse and multifactorial. Autopsy and biopsy studies reveal, alongside podocyte and tubular cell anomalies, the presence of virion within the cells. Evidence suggests that, in addition to the direct cytopathic effect of SARS- CoV2 on the glomeruli and renal tubules, there is also the indirect effect of cell-mediated immunity, the cytokines storm and the cross-talk between organs with possible systemic effects of the disease. These mechanisms are interconnected and have profound therapeutic implications involving extracorporeal removal of inflammatory cytokines. Dialysis patients, and children, in particular, should be classified as "at high risk" of contracting the disease. Infections are one of the most frequent causes of death in children with chronic renal failure who undergo dialysis. The reasons for this particular susceptibility are to be found in the compromised immune system, secondary to chronic malnutrition, immunosuppressive therapy, and uremia, frequent contact with healthcare personnel and other patients attending the dialysis unit and in need of the presence of other family members during treatment.


title: INFECTIOUS COMPLICATIONS AS A PREDICTOR OF MORTALITY IN PATIENTS WITH NON-HODGKIN LYMPHOMA RECEIVING RITUXIMAB-CONTAINING CHEMOTHERAPY.

text: Background Rituximab is a monoclonal antibody that increases the disease-free and overall survival of patients with non-Hodgkin lymphoma (NHL) CD20+. The objective of this study is to describe the prevalence and spectrum of infections in patients with NHL receiving rituximab-containing chemotherapy and the impact on survival. Materials and Methods From January 2011 to December 2012, all patients diagnosed with NHL who received at least one dose of rituximab were included. Results During the study period, 265 patients received rituximab; 108 (40.8%) males; the mean age was 60 ± 15 years. There were 177 infections in 85 patients, being the most common febrile neutropenia (n = 38; 21.5%) and mucosal barrier injury-related infections (n = 28; 15.8%). In 88 events (49%), there was a microbiologic diagnosis, being bacterial infection the most frequent (39.6%), but tuberculosis (TB) was developed in 4 cases (1.5%; incidence rate 721/100,000 person-year). During follow-up, 71 patients died (27%); in 35 cases, it was related to infection. There were no differences in follow-up between those who died due to infection versus those who died from another cause (p = 0.188). Multivariate analysis for mortality showed that age >60 years, failure to achieve a complete response, and development of an infectious complication increased the risk of death. Conclusions It is important to perform a screening test for TB in all patients who will receive rituximab and maintain a constant monitoring to detect an infectious process and begin treatment as soon as possible.


Mobilization and Preparation of a Large Urban Academic Center During the COVID-19 Pandemic.


Active machine learning helps drug hunters tackle biology.


title: Evolution in health and medicine Sackler colloquium: Evolution and public health.

text: Evolution and its elements of natural selection, population migration, genetic drift, and founder effects have shaped the world in which we practice public health. Human cultures and technologies have modified life on this planet and have coevolved with myriad other species, including microorganisms; plant and animal sources of food; invertebrate vectors of disease; and intermediate hosts among birds, mammals, and nonhuman primates. Molecular mechanisms of differential resistance or susceptibility to infectious agents or diets have evolved and are being discovered with modern methods. Some of these evolutionary relations require a perspective of tens of thousands of years, whereas other changes are observable in real time. The implications and applications of evolutionary understanding are important to our current programs and policies for infectious disease surveillance, gene-environment interactions, and health disparities globally.


title: The baric probe: a novel long-term implantable intracranial pressure monitor with ultrasound-based interrogation.

text: OBJECT Prompt diagnosis of shunt malfunction is critical in preventing neurological morbidity and death in individuals with hydrocephalus; however, diagnostic methods for this condition remain limited. For several decades, investigators have sought a long-term, implantable intracranial pressure (ICP) monitor to assist in the diagnosis of shunt malfunction, but efforts have been impeded by device complexity, marked measurement drift, and limited instrumentation lifespan. In the current report, the authors introduce an entirely novel, simple, compressible gas design that addresses each of these problems. METHODS The device described herein, termed the "baric probe," consists of a subdural fluid bladder and multichannel indicator that monitors the position of an air-fluid interface (AFI). A handheld ultrasound probe is used to interrogate the baric probe in vivo, permitting noninvasive ICP determination. To assess the function of device prototypes, ex vivo experiments were conducted using a water column, and short- and long-term in vivo experiments were performed using a porcine model with concurrent measurements of ICP via a fiberoptic monitor. RESULTS Following a toe region of approximately 2 cm H(2)O, the baric probe's AFI demonstrated a predictable linear relationship to ICP in both ex vivo and in vivo models. After a 2-week implantation of the device, this linear relationship remained robust and reproducible. Further, changes in ICP were observed with the baric probe, on average, 3 seconds in advance of the fiberoptic ICP monitor reading. CONCLUSIONS The authors demonstrate "proof-of-concept" and feasibility for the baric probe, a long-term implantable ICP monitor designed to facilitate the prompt and accurate diagnosis of shunt malfunction. The baric probe showed a consistent linear relationship between ICP and the device's AFI in ex vivo and short- and long-term in vivo models. With a low per-unit cost, a reduced need for radiography or CT, and an indicator that can be read with a handheld ultrasound probe that interfaces with any smart phone, the baric probe promises to simplify the care of patients with shunt-treated hydrocephalus throughout both the developed and the developing world.


title: Vitamin C promotes wound healing through novel pleiotropic mechanisms.

text: Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC administration suppresses pro-inflammatory responses while promoting anti-inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by altering the inflammatory, proliferative and remodelling phases of wound healing. Mice unable to synthesise VitC (Gulo(-/-) ) were used in this study. VitC was provided in the water (sufficient), withheld from another group (deficient) and supplemented by daily intra-peritoneal infusion (200 mg/kg, deficient + AscA) in a third group. Full thickness excisional wounds (6 mm) were created and tissue collected on days 7 and 14 for histology, quantitative polymerase chain reaction (qPCR) and Western blotting. Human neonatal dermal fibroblasts (HnDFs) were used to assess effects of In conclusion, VitC favorably on proliferation. Histological analysis showed improved wound matrix deposition and organisation in sufficient and deficient +AscA mice. Wounds from VitC sufficient and deficient + AscA mice had reduced expression of pro-inflammatory mediators and higher expression of wound healing mediators. Supplementation of HnDF with AscA induced the expression of self-renewal genes and promoted fibroblast proliferation. VitC favourably impacts the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodelling.


title: Mitophagy in viral infections.

text: Antiviral innate immune responses and apoptosis are the two major factors limiting viral infections. Successful viral infection requires the virus to take advantage of the cellular machinery to bypass cellular defenses. Accumulated evidences show that autophagy plays a crucial role in cell-to-virus interaction. Here, we focus on how viruses subvert mitophagy to favor viral replication by mitigating innate immune responses and apoptotic signaling.


title: Assessing Eating Behaviour Using Upper Limb Mounted Motion Sensors: A Systematic Review.

text: Wearable motion tracking sensors are now widely used to monitor physical activity, and have recently gained more attention in dietary monitoring research. The aim of this review is to synthesise research to date that utilises upper limb motion tracking sensors, either individually or in combination with other technologies (e.g., cameras, microphones), to objectively assess eating behaviour. Eleven electronic databases were searched in January 2019, and 653 distinct records were obtained. Including 10 studies found in backward and forward searches, a total of 69 studies met the inclusion criteria, with 28 published since 2017. Fifty studies were conducted exclusively in laboratory settings, 13 exclusively in free-living settings, and three in both settings. The most commonly used motion sensor was an accelerometer (64) worn on the wrist (60) or lower arm (5), while in most studies (45), accelerometers were used in combination with gyroscopes. Twenty-six studies used commercial-grade smartwatches or fitness bands, 11 used professional grade devices, and 32 used standalone sensor chipsets. The most used machine learning approaches were Support Vector Machine (SVM, n = 21), Random Forest (n = 19), Decision Tree (n = 16), Hidden Markov Model (HMM, n = 10) algorithms, and from 2017 Deep Learning (n = 5). While comparisons of the detection models are not valid due to the use of different datasets, the models that consider the sequential context of data across time, such as HMM and Deep Learning, show promising results for eating activity detection. We discuss opportunities for future research and emerging applications in the context of dietary assessment and monitoring.


title: Restoring heat stress-associated reduction in middle cerebral artery velocity does not reduce fatigue in the heat.

text: Heat-induced hyperventilation may reduce PaCO2 and thereby cerebral perfusion and oxygenation and in turn exercise performance. To test this hypothesis, eight volunteers completed three incremental exercise tests to exhaustion: (a) 18 °C ambient temperature (CON); (b) 38 °C (HEAT); and (c) 38 °C with addition of CO2 to inspiration to prevent the hyperventilation-induced reduction in PaCO2 (HEAT + CO2 ). In HEAT and HEAT + CO2 , rectal temperature was elevated prior to the exercise tests by means of hot water submersion and was higher (P < 0.05) than in CON. Compared with CON, ventilation was elevated (P < 0.01), and hence, PaCO2 reduced in HEAT. This caused a reduction (P < 0.05) in mean cerebral artery velocity (MCAvmean ) from 68.6 ± 15.5 to 53.9 ± 10.0 cm/s, which was completely restored in HEAT + CO2 (68.8 ± 5.8 cm/s). Cerebral oxygenation followed a similar pattern. V ˙ O 2 m a x was 4.6 ± 0.1 L/min in CON and decreased (P < 0.05) to 4.1 ± 0.2 L/min in HEAT and remained reduced in HEAT + CO2 (4.1 ± 0.2 L/min). Despite normalization of MCAvmean and cerebral oxygenation in HEAT + CO2 , this did not improve exercise performance, and thus, the reduced MCAvmean in HEAT does not seem to limit exercise performance.


title: Older adults' perspectives on the process of becoming users of assistive technology: a qualitative systematic review and meta-synthesis.

text: PURPOSE To identify, synthesize, and evaluate existing literature concerning the process of becoming a user of assistive technology (AT). METHOD A systematic review and meta-synthesis were carried out. Five bibliographic databases (MEDLINE via PubMed, CINAHL, Web of Science, PsycINFO and SocINDEX) were systematically searched up to 13th of March 2017, using two sets of search terms: (i) elderly and synonyms and (ii) assistive technology and similar words, and combined with a qualitative research filter. Articles were screened, read and critically assessed. The meta-synthesis was guided by Ricoeur's theory of interpretation. RESULTS Seventeen out of 4645 articles were included. Five phases emerged relating to the process of becoming a user of AT: phase A: Evaluating need, phase B: Acknowledging need, phase C: Incorporating the AT into daily life, phase D: Using the AT, and phase E: Future use. Three transitions, describing factors essential to moving from one phase to the next, were identified; from phase A-B: Valued activities are threatened, from phase B-C: Obtaining the AT and from phase C-D: Trust in the AT. No transition was identified from phase D-E. CONCLUSION The meta-synthesis led to a deeper understanding of the process of older adults becoming users of AT, by exploring findings across the included articles. The identified phases and transitions in the systematic review serve as an analytical framework for understanding the process from the older adult's perspective. This review advocates for using a client-centred approach throughout the entire delivery process. Implications for rehabilitation The process of the older adult becoming a user of AT involves an individualized time factor, and this supports the practice of individualized follow-up. The process of becoming a user of AT is closely related to self-image; healthcare professionals should support not only the use of AT but also the older adult's emotional adjustment to a new self-image. The process is highly influenced by the older adult's social context; healthcare professionals should consider involving the client's social network in the AT delivery process.


Üzüm Ö, Çağlar A, Küme T, Sayıner A, Er A, Akgül F, Ulusoy E, Yılmaz D, Duman M. Are cytokines and cortisol important predictors for the severity of pediatric croup: A case control study. Turk J Pediatr 2017; 59: 281-287. The aim of this study is to investigate the role of cytokines (TNF-α, IL-6, IL-10, and PAF), cortisol, and IgE in the pathogenesis of croup and the factors determining its clinical severity. Patients diagnosed with croup at the Pediatric Emergency Department were included and thirty healthy children were included as a control group. Patients` demographic characteristics, clinical findings, recurrent croup history, and patient-family atopy history were recorded. Patients were grouped according to the Westley croup scoring system. Blood samples were taken from the control group and the patients for cytokines and cortisol. Respiratory pathogens were studied with PCR. Sixty-nine pediatric cases who were diagnosed as croup were included in the study (34 mild, 31 moderate, 4 severe). Group comparisons were made in terms of mild and moderate/severe groups. In the moderate/severe group, IL-10 and cortisol levels were higher than the mild group. The moderate/severe cortisol levels between 12:00 am-6:00 pm were found to be higher. PAF and TNF-alpha levels were detected to be higher in patients with a history of atopy. Viral agents were isolated in 45 patients; rhinovirus PCR tests were positive in 22 patients. In this study, rhinovirus was the most common etiology for croup. Increased levels of IL-10 and cortisol in the moderate/severe group indicate that different systemic and local mechanisms may play a role in the pathogenesis of croup.


title: Penicillium subrubescens adapts its enzyme production to the composition of plant biomass.

text: Penicillium subrubescens is able to degrade a broad range of plant biomass and it has an expanded set of Carbohydrate Active enzyme (CAZyme)-encoding genes in comparison to other Penicillium species. Here we used exoproteome and transcriptome analysis to demonstrate the versatile plant biomass degradation mechanism by P. subrubescens during growth on wheat bran and sugar beet pulp. On wheat bran P. subrubescens degraded xylan main chain and side residues from Day 2 of cultivation, whereas it started to degrade side chains of pectin in sugar beet pulp prior to attacking the main chain on Day 3. In addition, on Day 3 the cellulolytic enzymes were highly increased. Our results confirm that P. subrubescens adapts its enzyme production to the available plant biomass and is a promising new fungal cell factory for the production of CAZymes.


title: Stent-assisted coiling treatment of pediatric traumatic pseudoaneurysm resulting from tumor surgery.

text: BACKGROUND Traumatic intracranial pseudoaneurysms in children are typically the result of blunt or penetrating head injury. There are isolated reports of pseudoaneurysm as the result of intracranial aneurysm surgery in both adults and children. Treatment of these lesions, both surgically and endovascularly, can be complicated due to the known variability of arterial wall thickness in traumatic pseudoaneurysms. CASE REPORT We describe a child who underwent successful craniopharyngioma resection following staged surgical procedures. Follow-up imaging 8 months after the operation demonstrated an enlarging pseudoaneurysm of the left supraclinoid carotid artery. The lesion was successfully treated with stenting of the vessel and coil placement between the stent and the aneurysmal segment of the artery. Follow-up angiographic imaging 6 months later revealed complete obliteration of the aneurysm and normalization of the carotid artery lumen. CONCLUSION To our knowledge, this is the first report of a pseudoaneurysm secondary to a surgical intervention in childhood that was treated with stent-assisted coiling. This strategy of vascular reconstruction is increasingly used in adults and appears safe to implement in the pediatric population. However, the long-term outcomes and the value of using an antiplatelet regimen in this young population are still to be determined.


title: Heavy-resistance exercise-induced increases in jump performance are not explained by changes in neuromuscular function.

text: Post-activation potentiation (PAP) is the increased involuntary muscle twitch response to stimulation following strong contraction. The enhancement to whole-body explosive muscular performance (PE) after heavy-resistance exercise is often attributed to modulations in neuromuscular function that are proposed to reflect PAP, but the evidence to support this is equivocal. We assessed the neuromuscular basis of PE using transcranial magnetic stimulation (TMS) of the primary motor cortex, and electrical stimulation of the femoral nerve. Eleven male athletes performed heavy-resistance exercise with measures of countermovement jump (CMJ) pre- and 8 min post-exercise. Pre-exercise and after the final CMJ, single- and paired-pulse TMS were delivered during submaximal isometric knee-extensor contractions to measure corticospinal excitability, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF), with motor evoked potentials recorded from rectus femoris. Twitch responses to motor nerve stimulation during and post maximum-knee-extensor contractions were studied to quantify voluntary activation (VA) and potentiated twitch (Qtw,pot ). The experimental protocol successfully induced PE (+4 ± 1% change in CMJ, P = 0.01), but no changes were observed for maximum voluntary force, VA, corticospinal excitability, SICI or ICF (all P > 0.05), and Qtw,pot declined (P < 0.001). An enhancement of muscular performance after heavy-resistance exercise was not accompanied by PAP, or changes in measures of neuromuscular function.


title: Pressurized Metered-Dose Inhalers Versus Nebulizers in the Treatment of Mechanically Ventilated Subjects With Artificial Airways: An In Vitro Study.

text: BACKGROUND The primary focus of previous aerosol research during mechanical ventilation was the endotracheal tube (ETT). Consequently, there are limited data in the literature on the delivery of inhaled medications administered with different aerosol devices in mechanically ventilated patients with a tracheostomy tube (TT). The purpose of this study was to quantify and compare the efficiency of aerosol devices in a lung model of an intubated and mechanically ventilated adult with a TT. METHODS An in vitro lung model was constructed to simulate a ventilator-dependent adult with a Portex TT and a Mallinckrodt ETT (8-mm inner diameter). Aerosol was collected distal to the bronchi of an adult mannikin on a filter attached to a passive test lung. A ventilator delivered adult breathing parameters (tidal volume 450 mL, breathing frequency 20 breaths/min, peak expiratory flow 40 L/min, and inspiratory-expiratory ratio 1:3) to the airway. A jet nebulizer and pressurized metered-dose inhaler (pMDI) were placed in the inspiratory limb of the circuit 15 cm from the Y-adapter. The jet nebulizer was operated at 8 L/min to deliver albuterol sulfate (2.5 mg/3 mL), whereas an albuterol pMDI was actuated 4 times with a spacer. Drug was eluted from the filter and analyzed by spectrophotometry. RESULTS Drug delivered via a TT was marginally greater compared with an ETT using the jet nebulizer and pMDI (P = .10 and .046, respectively). Although delivery efficiency with the pMDI was 3-fold greater than with the jet nebulizer with both a TT and an ETT (P = .001 and .002, respectively), the jet nebulizer delivered greater drug mass compared with the pMDI with either a TT (P = .01) or an ETT (P = .005). CONCLUSIONS Aerosol drug delivery via a TT was greater than with an ETT, whereas the delivery efficiency of a pMDI via either airway was greater than that of a jet nebulizer.


title: Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

text: BACKGROUND Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING Bill & Melinda Gates Foundation.


title: Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle.

text: The SARS-CoV-2 pandemic that originated from Wuhan, China, in December 2019 has impacted public health, society and economy and the daily lives of billions of people in an unprecedented manner. There are currently no specific registered antiviral drugs to treat or prevent SARS-CoV-2 infections. Therefore, drug repurposing would be the fastest route to provide at least a temporary solution while better, more specific drugs are being developed. Here we demonstrate that the antiparasitic drug suramin inhibits SARS-CoV-2 replication, protecting Vero E6 cells with an EC50 of ∼20 μM, which is well below the maximum attainable level in human serum. Suramin also decreased the viral load by 2-3 logs when Vero E6 cells or cells of a human lung epithelial cell line (Calu-3) were treated. Time of addition and plaque reduction assays performed on Vero E6 cells showed that suramin acts on early steps of the replication cycle, possibly preventing binding or entry of the virus. In a primary human airway epithelial cell culture model, suramin also inhibited the progression of infection. The results of our preclinical study warrant further investigation and suggest it is worth evaluating whether suramin provides any benefit for COVID-19 patients, which obviously requires safety studies and well-designed, properly controlled randomized clinical trials.


title: The comparative politics of COVID-19: The need to understand government responses.

text: COVID-19 has created a ramifying public health, economic, and political crisis throughout many countries in the world. While globally the pandemic is at different stages and far from under control in some countries, now is the time for public health researchers and political scientists to start understanding how and why governments responded the way they have, explore how effective these responses appear to be, and what lessons we can draw about effective public health policymaking in preparation of the next wave of COVID-19 or the next infectious disease pandemic. We argue that there will be no way to understand the different responses to COVID-19 and their effects without understanding policy and politics. We propose four key focuses to understand the reasons for COVID-19 responses: social policies to crisis management as well as recovery, regime type (democracy or autocracy), formal political institutions (federalism, presidentialism), and state capacity (control over health care systems and public administration). A research agenda to address the COVID-19 pandemic that takes politics as a serious focus can enable the development of more realistic, sustainable interventions in policies and shape our broader understanding of the politics of public health.


title: Peer mentoring for professional and personal growth in academic medicine.

text: Mentorship is a critical component of career development, particularly in academic medicine. Peer mentorship, which does not adhere to traditional hierarchies, is perhaps more accessible for underrepresented groups, including women and minorities. In this article, we review various models of peer mentorship, highlighting their respective advantages and disadvantages. Structured peer mentorship groups exist in different settings, such as those created under the auspices of formal career development programs, part of training grant programs, or through professional societies. Social media has further enabled the establishment of informal peer mentorship through participatory online groups, blogs, and forums that provide platforms for peer-to-peer advice and support. Such groups can evolve rapidly to address changing conditions, as demonstrated by physician listserv and Facebook groups related to the COVID-19 pandemic. Peer mentorship can also be found among colleagues brought together through a common location, interest, or goal, and typically these relationships are informal and fluid. Finally, we highlight here our experience with intentional formation of a small peer mentoring group that provides structure and a safe space for professional and social-emotional growth and support. In order to maximize impact and functionality, this model of peer mentorship requires commitment among peers and a more formalized process than many other peer mentoring models, accounting for group dynamics and the unique needs of members. When done successfully, the depth of these mentoring relationships can produce myriad benefits for individuals with careers in academic medicine including, but not limited to, those from underrepresented backgrounds.


title: Evaluating Real-World Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology.

text: BACKGROUND Left atrial appendage occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials. Evaluating real-life clinical outcomes in atrial fibrillation patients receiving the WATCHMAN left atrial appendage closure technology was designed to collect prospective multicenter outcomes of thromboembolic events, bleeding, and mortality for patients implanted with a WATCHMAN in routine daily practice. METHODS One thousand twenty patients with a WATCHMAN implant procedure were prospectively followed in 47 centers. Left atrial appendage occlusion indication was based on the European Society of Cardiology guidelines. Follow-up and imaging were performed per local practice up to a median follow-up of 2 years. RESULTS Included population was old (age 73.4±8.9 years), at high risk for stroke (311 prior ischemic stroke/transient ischemic attack and 153 prior hemorrhagic stroke) and bleeding (318 prior major bleeding), with CHA2DS2-VASc score ≥5 in 49%, hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, Labile international normalized ratio, elderly, drugs/alcohol concomitantly ≥3 in 40% and oral anticoagulation contraindication in 72%. During follow-up, 161 patients (16.4%) died, 22 strokes were observed (1.3/100 patient-years, 83% reduction versus historic data), and 47 major nonprocedural bleeding events (2.7/100 patient-years, 46% reduction versus historic data). Stroke and bleeding rates were consistently lower than historic data in those with prior ischemic (-76% and -41%) or hemorrhagic (-81% and 67%) stroke and prior bleeding (-85% and -30%). Lowest bleeding rates were seen in patients with early discontinuation of dual antiplatelet therapy. Patients with early discontinuation of antithrombotic therapy showed lower bleeding rates, while they were highest for those with prior bleeding. Device thrombus was observed in 34 patients (4.1%) and was not correlated to drug regimen during follow-up ( P=0.28). CONCLUSIONS During the complete 2-year follow-up of Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology, patients with a WATCHMAN left atrial appendage occlusion device had consistently low rates of stroke and nonprocedural bleeding, although most were contraindicated to oral anticoagulation and used only single antiplatelet therapy or nothing. CLINICAL TRIAL REGISTRATION URL: https://clinicaltrials.gov . Unique identifier: NCT01972282.