title: Predicting Protein-Protein Interactions Using BiGGER: Case Studies.

text: The importance of understanding interactomes makes preeminent the study of protein interactions and protein complexes. Traditionally, protein interactions have been elucidated by experimental methods or, with lower impact, by simulation with protein docking algorithms. This article describes features and applications of the BiGGER docking algorithm, which stands at the interface of these two approaches. BiGGER is a user-friendly docking algorithm that was specifically designed to incorporate experimental data at different stages of the simulation, to either guide the search for correct structures or help evaluate the results, in order to combine the reliability of hard data with the convenience of simulations. Herein, the applications of BiGGER are described by illustrative applications divided in three Case Studies: (Case Study A) in which no specific contact data is available; (Case Study B) when different experimental data (e.g., site-directed mutagenesis, properties of the complex, NMR chemical shift perturbation mapping, electron tunneling) on one of the partners is available; and (Case Study C) when experimental data are available for both interacting surfaces, which are used during the search and/or evaluation stage of the docking. This algorithm has been extensively used, evidencing its usefulness in a wide range of different biological research fields.


title: Predicting Human Microbe-Drug Associations via Graph Convolutional Network with Conditional Random Field.

text: MOTIVATION Human microbes play critical roles in drug development and precision medicine. How to systematically understand the complex interaction mechanism between human microbes and drugs remains a challenge nowadays. Identifying microbe-drug associations can not only provide great insights into understanding the mechanism, but also boost the development of drug discovery and repurposing. Considering the high cost and risk of biological experiments, the computational approach is an alternative choice. However, at present, few computational approaches have been developed to tackle this task. RESULTS In this work, we leveraged rich biological information to construct a heterogeneous network for drugs and microbes, including a microbe similarity network, a drug similarity network, and a microbe-drug interaction network. We then proposed a novel Graph Convolutional Network (GCN) based framework for predicting human Microbe-Drug Associations, named GCNMDA. In the hidden layer of GCN, we further exploited the Conditional Random Field (CRF), which can ensure that similar nodes (i.e., microbes or drugs) have similar representations. To more accurately aggregate representations of neighborhoods, an attention mechanism was designed in the CRF layer. Moreover, we performed a random walk with restart (RWR) based scheme on both drug and microbe similarity networks to learn valuable features for drugs and microbes respectively. Experimental results on three different datasets showed that our GCNMDA model consistently achieved better performance than seven state-of-the-art methods. Case studies for three microbes including SARS-CoV-2 and two antimicrobial drugs (i.e., Ciprofloxacin and Moxifloxacin) further confirmed the effectiveness of GCNMDA in identifying potential microbe-drug associations. AVAILABILITY Python codes and dataset are available at: https://github.com/longyahui/GCNMDA. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.


title: On-demand endoscopic CO2 insufflation with feedback pressure regulation during natural orifice transluminal endoscopic surgery (NOTES) peritoneoscopy induces minimal hemodynamic and respiratory changes.

text: BACKGROUND Endoscopic insufflation has been associated with marked increase in intra-abdominal pressure (IAP) and hemodynamic and respiratory changes during transgastric surgery. OBJECTIVE To investigate the hemodynamic and respiratory effects during intraperitoneal cavity exploration through 3 different natural orifice transluminal endoscopic surgery (NOTES) access locations compared with laparoscopy. DESIGN AND SETTING Survival experiments using 40 female pigs randomized to transgastric, transcolonic, transvaginal, and laparoscopic peritoneoscopy. INTERVENTIONS On-demand endoscopic insufflation of CO(2) with feedback pressure regulation was used in NOTES with a maximum pressure of 14 mm Hg. In the laparoscopy group, the IAP was maintained at 14 mm Hg. NOTES procedures were performed by an endoscopist (with the assistance of a gynecologist in the transvaginal group and a second endoscopist in the transgastric and transrectal groups) and laparoscopy by 2 surgeons. MAIN OUTCOME MEASUREMENTS Invasive hemodynamic and respiratory data. Blood samples were drawn for gas analyses. RESULTS All experiments except one in the transrectal group were completed. The IAP was significantly lower in all NOTES groups compared with the laparoscopy group. A significant increase in mean systemic arterial blood pressure was observed in the laparoscopy group at 15 and 30 minutes of intraperitoneal cavity exploration, but it remained unchanged during all NOTES procedures. An increase in airway pressures was observed at 15 and 30 minutes of peritoneoscopy in the animals undergoing laparoscopy, whereas those parameters remained unchanged in the NOTES groups. The laparoscopy group showed a significant impairment in pulmonary gas exchange (decrease in Pao(2), increase in Paco(2), and decrease in arterial pH) after 30 minutes of peritoneoscopy, whereas only a slight increase in Paco(2) was observed in the transrectal and transvaginal groups. LIMITATIONS Healthy animal model. CONCLUSION On-demand endoscopic insufflation of CO(2) with feedback pressure regulation can minimize the risk of hemodynamic and respiratory compromise caused by acute changes in IAP.


title: Influenza virus h5 DNA vaccination is immunogenic by intramuscular and intradermal routes in humans.

text: Avian influenza virus causes outbreaks in domestic and wild birds around the world, and sporadic human infections have been reported. A DNA vaccine encoding hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially tested in two randomized phase I clinical studies. Vaccine Research Center study 304 (VRC 304) was a double-blinded study with 45 subjects randomized to placebo, 1 mg of vaccine, or 4 mg of vaccine treatment groups (n = 15/group) by intramuscular (i.m.) Biojector injection. VRC 305 was an open-label study to evaluate route, with 44 subjects randomized to intradermal (i.d.) injections of 0.5 mg by needle/syringe or by Biojector or 1 mg delivered as two 0.5-mg Biojector injections in the same deltoid or as 0.5 mg in each deltoid (n = 11/group). Injections were administered at weeks 0, 4, and 8 in both studies. Antibody responses to H5 were assessed by hemagglutination inhibition (HAI) assay, enzyme-linked immunosorbent assay (ELISA), and neutralization assay, and the H5 T cell responses were assessed by enzyme-linked immunospot and intracellular cytokine staining assays. There were no vaccine-related serious adverse events, and the vaccine was well tolerated in all groups. At 1 mg, i.d. vaccination compared to i.m. vaccination induced a greater frequency and magnitude of response by ELISA, but there were no significant differences in the frequency or magnitude of response between the i.d. and i.m. routes in the HAI or neutralization assays. T cell responses were more common in subjects who received the 1- or 4-mg dose i.m. These studies demonstrated that the DNA vaccine encoding H5 is safe and immunogenic and served to define the proper dose and route for further studies. The i.d. injection route did not offer a significant advantage over the i.m. route, and no difference was detected by delivery to one site versus splitting the dose between two sites for i.d. vaccine administration. The 4-mg dose (i.m) was further investigated in prime-boost regimens.


title: Early use of glucocorticoids was a risk factor for critical disease and death from pH1N1 infection.

text: BACKGROUND Glucocorticoids increase the risk of developing critical disease from viral infections. However, primary care practitioners in China use them as antipyretics, potentially exposing hundreds of millions to this risk. METHODS We enrolled all patients with confirmed pandemic influenza A (pH1N1) virus infection aged ≥3 years with available medical records at 4 Shenyang City hospitals from 20 October to 30 November 2009. A critical patient was any confirmed, hospitalized pH1N1 patient who developed ≥1 of the following: death, respiratory failure, septic shock, failure or insufficiency of ≥2 nonpulmonary organs, mechanical ventilation, or ICU admission. In a retrospective cohort study, we evaluated the risk of developing critical illness in relation to early (≤72 hours of influenza-like illness [ILI] onset) glucocorticoids treatment. RESULTS Of the 83 hospitalized case-patients, 46% developed critical illness, 17% died, and 37% recovered and were discharged. Critically ill and other patients did not differ by underlying conditions and severity, median temperature at first clinic visit, and other measured risk factors. Of 17 patients who received early glucocorticoid treatment, 71% subsequently developed critical disease compared with 39% of 66 patients who received late (>72 hours) or no glucocorticoid treatment (RR(M-H) = 1.8, 95% CI = 1.2-2.8, after adjusting for 2 summary variables; ie, presence of underlying diseases and presence of underlying risk factors). Proportional hazards modeling showed that use of glucocorticoids tripled the hazard of developing critical disease (hazard ratio [HR] = 2.9, 95% CI = 1.3-6.2, after adjusting for the same summary variables). CONCLUSIONS Early use of parenteral glucocorticoids therapy for fever reduction and pneumonia prevention increases the risk for critical disease or death from pH1N1 infection. We recommend that guidelines on glucocorticoid use be established and enforced.


title: [Intubation with a tube exchanger on an intubation trainer. Influence of tube tip position on successful intubation].

text: BACKGROUND Securing the airway using a tube exchanger catheter is an important and useful technique in anesthesia. Its success is mainly hampered by tube tip impingement of laryngeal structures. Advancing the tracheal tube along its normal curvature via a tube exchanger catheter has a high risk of tube tip impingement mainly of right laryngeal structures. The authors achieved successful clinical experience by rotating the tracheal tube 90° anticlockwise (ventral tube tip position) before railroading the tube via a tube exchanger catheter or a fiber optic bronchoscope through the larynx. AIM The aim of the study was to investigate the influence of the tracheal tube tip position while intubating an airway trainer over a tube exchange catheter. MATERIAL AND METHODS Volunteer anesthetists with varying years of professional experience were asked to intubate an intubation mannequin (Laerdal Airway Management Trainer) using the orotracheal route with an established tube exchange catheter (Cook Airway Exchange Catheter, 11F). Two different brands of tracheal tubes (Rüsch and Covidien, ID 7.0 mm) were used in a randomized order, each with the tracheal tube tip at first positioned right (90°), then ventrally (0°), left (270°) and finally dorsally (180°), resulting in eight intubation attempts for each participant. To ensure the correct tube tip position the tube was withdrawn before every intubation attempt until the tube tip position was visualized. The oropharnyx, larynx, trachea and tube were sufficiently lubricated with silicon spray (Rüsch Silikospray). The tube and airway exchange catheter size selection were made according to the clinical trial of Loudermilk et al. Successful endotracheal intubation without resistance was recorded for each tube tip position and tracheal tube brand. RESULTS In total 20 anesthetists (13 consultants and 7 residents) with a median of 9.5 years (range 3-37 years) of professional experience participated in the study. Overall 160 intubation attempts were performed, 2 participants showed no successful intubation attempts at all and 38 out of 160 intubation attempts (23.8 %) were successful. Intubation success with the tracheal tube tip placed ventrally (0°) was 60 % followed by the left (270°) and right (90°) tracheal tube tip positions with 27.5 % and 7.5 % intubation success, respectively. With the tube tip placed dorsally (180°) none of the 40 intubation attempts were successful. Intubation attempts with the Rüsch tube were more successful (28.8 %) than those with the Covidien tube (18.8 %). Placing the tracheal tube tip ventrally, the Rüsch tube was twice as successful as the Covidien tube with 16 (80 %) versus 8 attempts (40 %, p = 0.011). There was no correlation between professional experience and intubation success (p = 0.362). CONCLUSION Tube insertion via an airway exchange catheter or a fiberoptic bronchoscope is a basic technique in anesthesia. Knowledge about the difficulties and their prevention are essential for every anesthetist. The gap between the airway exchange catheter, the fiber bronchoscope and the tube diameters is one of the major reasons for tube tip impingement. This investigation showed that intubation success via a tube exchange catheter, as investigated in an intubation mannequin, is considerably influenced by the tracheal tube tip position. A 90° anticlockwise rotation, placing the tracheal tube tip ventrally, considerably increased intubation success. This is of particular importance if an anesthesia department has no appropriately sized tube exchange catheters or fiber bronchoscope for every age group of patients.


Survival After Laparoscopic vs Abdominal Hysterectomy.


title: Robotic single-site supracervical hysterectomy with manual morcellation: Preliminary experience.

text: AIM To evaluate the feasibility, safety and peri- and postoperative outcomes of robotic single-site supracervical hysterectomy (RSSSH) for benign gynecologic disease. METHODS We report 3 patients who received RSSSH for adenomyosis of the uterus from November 2015 to April 2016. We evaluated the feasibility, safety and outcomes among these patients. RESULTS The mean surgical time was 244 min and the estimated blood loss was 216 mL, with no blood transfusion necessitated. The docking time was shortened gradually from 30 to 10 min. We spent 148 min on console operation. Manual morcellation time was also short, ranging from 5 to 10 min. The mean hospital stay was 5 d. Lower VAS pain score was also noted. There is no complication during or after surgery. CONCLUSION RSSSH is feasible and safe, incurs less postoperative pain and gives good cosmetic appearance. The technique of in-bag, manual morcellation can avoid tumor dissemination.


title: Plasmodium falciparum Plasmepsin V (PfPMV): Insights into recombinant expression, substrate specificity and active site structure.

text: Plasmepsin V from Plasmodium falciparum (PfPMV) is responsible for the cleavage of the Plasmodium export element (PEXEL) motif at the N-terminus of several hundreds of the exported proteins. PfPMV is necessary for parasite viability and has become a novel promising target for antimalarial therapy. The first recombinant expression of soluble, active PfPMV as thioredoxin fusion proteins is reported herein. Two truncated forms of PfPMV were fused to thioredoxin (Trx) to generate Trx-PfPMVp37 and Trx-PfPMVm84. The fusion proteins were successfully purified using Ni(2+) affinity chromatography in combination with ATP treatment to eliminate Escherichia coli HSP60 contaminant. Trx-PfPMVm84 could hydrolyze the PEXEL-containing peptides more efficiently than Trx-PfPMVp37. Interestingly, both Trx-PfPMVs preferred to cleave PfEMP2 peptide over HRPII peptide. The replacement of Ser with Val or Glu at P1' position created a substrate with 75% reduction in the enzyme activity, whereas the substitution of Ile with Lys or Glu at P2 position reduced the cleavage efficiency by 30%. The activity of Trx-PfPMVm84 was inhibited by PMSF and nelfinavir but not by pepstatin A. After the removal of Trx domain, activities of both enzymes toward PfEMP2 and HRPII peptides were fitted to the Michaelis-Menten model to determine kinetic parameters. The Km values toward both peptides were apparently much lower than the previously reported data although with similar kcat values. Along with an improved PfPMV preparation protocol, these findings have provided insights into its substrate specificity at P2 and P1' positions as well as interactions among the enzyme, substrates, and inhibitors.


COVID-ARDS Clarified: A Vascular Endotype?


title: Mechanical Conflict System: A Novel Operant Method for the Assessment of Nociceptive Behavior.

text: A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine (2.5 and 5 mg/kg), and the tachykinin NK1 receptor antagonist, RP 67580 (1 and 10 mg/kg). Results indicate that escape latency increased as a function of probe height in both naive and CCI rats. Pregabalin (10 and 30 mg/kg) and morphine (5 mg/kg), but not RP 67580, decreased latency to escape in CCI rats suggesting an antinociceptive effect. In contrast, morphine (10 mg/kg) but not pregabalin (30 mg/kg) increased escape latency in naive rats suggesting a possible anxiolytic action of morphine in response to light-induced fear. No order effects following multiple test sessions were observed. We conclude that the MCS is a valid method to assess behavioral signs of affective pain in rodents.


title: Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion.

text: BACKGROUND AND PURPOSE The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement. METHODS A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy. RESULTS Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001). CONCLUSIONS A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy.


title: Multiple-electrode radiofrequency ablations using Octopus® electrodes in an in vivo porcine liver model.

text: OBJECTIVES The objective of this study was to determine the in vivo efficacy of radiofrequency ablation (RFA) in porcine liver using Octopus® electrodes for creating a large coagulation compared with RFA using clustered electrodes. METHODS A total of 39 coagulations were created using a 200-W generator and clustered electrodes or Octopus electrodes during laparotomy in 19 pigs. Radiofrequency was applied to the livers using four protocols: (1) Group A-1, monopolar mode using a clustered electrode (n=11); (2) Group A-2, monopolar mode using an Octopus electrode (n=11); (3) Group B-1, consecutive monopolar mode using three, clustered electrodes (n=8); and (4) Group B-2, switching monopolar mode using two Octopus electrodes (n=9). The energy efficiency, shape, diameters (D) and volume (V) of the coagulation volume were compared in each of the two groups. RESULTS The mean maximum D and V of the coagulations in Group A-2 (4.7 cm and 33.1 cm(3), respectively) were significantly larger than those in Group A-1 (4.1 cm and 20.3 cm(3), respectively) (p<0.05). Furthermore, the mean minimum D, maximum D and V of the coagulations in Group B-2 were significantly larger than those in Group B-1, i.e. 5.3 vs 4.0 cm, 6.6 vs 4.9 cm and 66.9 vs 30.2 cm(3), respectively (p<0.05). The energy efficiencies were also significantly higher in Groups A-2 and B-2 than in Groups A-1 and B-1 (p<0.05). CONCLUSION The Octopus electrodes were more efficient for creating a large ablation zone than clustered electrodes, and the efficacy of RFA with Octopus electrodes can be amplified in the switching monopolar mode.


title: Clinical experience with single-port access laparoscopic cystectomy and myomectomy.

text: OBJECTIVE This study was performed to assess our clinical experience with single-port access (SPA) laparoscopic cystectomy and myomectomy and the surgical outcomes of those procedures at our institution. METHODS The authors evaluated the surgical outcomes of SPA laparoscopic cystectomy in 293 patients and SPA laparoscopic myomectomy in 246 patients. The surgical outcomes comprised operation time, the amount of blood loss during the operation, the change in hemoglobin (before and after the operation), the change in hematocrit (before and after the operation), switching to the multi-port access method, complications, transfusions, and the duration of the postoperative hospital stay. RESULTS The Pearson correlation coefficient and the Spearman correlation coefficient between the operation time and the amount of blood loss were 0.312 and 0.321 for SPA laparoscopic cystectomy, respectively, and 0.706 and 0.674 for SPA laparoscopic myomectomy, respectively. The drops in hemoglobin and hematocrit were 1.33±0.78 g/dL and 4.14%±2.45%, respectively, in SPA laparoscopic cystectomy, while the corresponding figures were 1.34±1.13 g/dL and 4.17%±3.24% in SPA laparoscopic myomectomy, respectively. CONCLUSION This study reported the surgical outcomes of SPA laparoscopic cystectomy and myomectomy and compared them to previously published findings on traditional laparoscopic cystectomy and myomectomy. No significant differences were found in the surgical outcomes between SPA and traditional laparoscopic cystectomy and myomectomy.


title: A role of apolipoprotein D in triglyceride metabolism.

text: Apolipoproteins (apo) are constituents of lipoproteins crucial for lipid homeostasis. Aberrant expression of apolipoproteins is associated with metabolic abnormalities. Here we characterized apolipoprotein D (apoD) in triglyceride metabolism. Unlike canonical apolipoproteins that are mainly produced in the liver, apoD is an atypical apolipoprotein with broad tissue distribution. We show that circulating apoD is present mainly in HDL and, to a lesser extent, in LDL and VLDL and that its plasma levels were reduced in db/db mice with visceral obesity and altered lipid metabolism. Elevated apoD production, derived from adenovirus-mediated gene transfer, resulted in significant reduction in plasma triglyceride levels in mice. This effect was attributable to en-hanced LPL activity and improved catabolism of triglyceride-rich particles. In contrast, VLDL triglyceride production remained unchanged in response to elevated apoD production. These findings were recapitulated in high-fat-induced obese mice. Obese mice with elevated apoD production exhibited significantly improved triglyceride profiles, correlating with increased plasma LPL activity and enhanced postprandial fat tolerance. ApoD was shown to promote LPL-mediated hydrolysis of VLDL in vitro, correlating with its TG-lowering action in vivo. Apolipoprotein D plays a significant role in lipid metabolism. These data provide important clues to clinical observations that genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of metabolic syndrome.


title: Endoscopic stenting of gastric staple line leak following sleeve gastrectomy.

text: Laparoscopic sleeve gastrectomy is known to be associated with a risk of gastric staple line leak. We report on our experience with endoscopic stenting of the anomalous leaking tract. Three cases of post sleeve gastric leak confirmed by computed tomography scan were treated by endoscopic stenting of their leak with a plastic endoprosthesis under fluoroscopic and endoscopic guidance. Endoscopic stenting by means of biliary or pancreatic endoprosthesis was successful in the three patients. The median number of endoscopy procedures per patient was 1.3. Stents were extracted 6 to 10 weeks after their placement. Neither morbidity nor recurrence was noticed on follow-up. Endoscopic stenting of gastric staple line leak following sleeve gastrectomy proved to be an efficacious technique for leak healing.


title: Laparoendoscopic single-site surgery adrenalectomy - own experience and matched case-control study with standard laparoscopic adrenalectomy.

text: INTRODUCTION At our institution, laparoendoscopic single-site surgery (LESS) has been established as a technique for laparoscopic nephrectomy since 2011, and since 2012 in selected cases for adrenalectomy (AE) as well. AIM To compare LESS AE with standard laparoscopic AE (SLAE). MATERIAL AND METHODS Between 3/2012 and 7/2014, 35 adrenalectomies were performed. In 18 (51.4%), a LESS approach was chosen. Indications were strictly non-complicated cases (body mass index (BMI) < 34 kg/m(2), tumour ≤ 7 cm, non-malignant aetiology, no previous surgery). All LESS procedures were done by one surgeon. Standard equipment was a 10 mm rigid 0° camera, Triport+, one pre-bent grasper, and a sealing instrument. The approach was pararectal in all cases except one (transumbilical in a slim man). Three patients with LESS were excluded (2 partial AEs only, one adrenal cancer converted to SLAE and then to open surgery). These 15 LESS AE procedures were compared to 15 SLAEs with similar characteristics chosen among 54 SLAEs performed in the period 1/2008-2/2012. RESULTS In 8 cases (53.3%) of LESS AE, a 3 mm port was added to elevate the liver/spleen. Mean parameters of LESS AE vs. SLAE (Wilcoxon test): maximal tumour diameter 43.7 mm vs. 36.1 mm (p = 0.28), time of surgery 63.3 min vs. 55.3 min (p = 0.22), blood loss 38.0 ml vs. 38.0 ml (p = 0.38), BMI 26.9 kg/m(2) vs. 28.5 kg/m(2) (p = 0.13), discharge from hospital 5.4 days vs. 3.9 days (p = 0.038). There were no complications in either group. CONCLUSIONS The LESS AE is feasible in selected cases, especially small left-sided tumours in thin patients with no history of previous abdominal operations, but requires an additional port in half of the cases.


title: Perioperative outcomes and costs of laparoscopic versus open inguinal hernia repair.

text: PURPOSE Studies comparing laparoscopic (LIHR) vs. open inguinal hernia repair (OIHR) have shown similar recurrence rates but have disagreed on perioperative outcomes and costs. The aim of this study is to compare laparoscopic vs. open outcomes and costs. METHODS The National Surgical Quality Improvement Program (NSQIP) was used to compare durations of surgery, anesthesia time, and length of stay (LOS). The University HealthSystem Consortium (UHC) was used to review the cost and complications between approaches. Patients were matched on demographics, year of procedure and surgical approach between datasets for statistical analysis. RESULTS A sample of 5468 patients undergoing OIHR (N = 4,693) or LIHR (N = 775) was selected from UHC from 2008-2011. An identical number of patients from NSQIP were matched to those from UHC resulting in a total of 10,936 records. LIHR patients had shorter duration of wait from admission to operation (p < 0.05). Conversely, LIHR patients had longer operating time (p < 0.05), duration of anesthesia (p < 0.05), and time in the operating room (p < 0.05).Overall complication rate was higher in open (3.1 vs. 1.8 %, p < 0.05). Cost favored open over LIHR ($4360 vs $5105). The cost discrepancy mainly stemmed from LIHR supplies ($1448 vs. $340; p < 0.05) and OR services ($1380 vs. $1080; p < 0.05). CONCLUSION This study demonstrates the LOS and perioperative outcomes were superior in the LIHR group; however, the overall cost was higher due to the supplies. Advancement in technology, surgeons' skill level and preference of supplies are all factors in decreasing the overall cost of LIHR.


Editorial Comment to Practical ex-vivo evaluation of application of surgical clips to sutures during re-approximation of renal tissue in partial nephrectomy.


title: Home monitoring of daytime mouthpiece ventilation effectiveness in patients with neuromuscular disease.

text: Mouthpiece ventilation (MPV) allows patients with neuromuscular disease to receive daytime support from a portable ventilator, which they can disconnect at will, for example, for speaking, eating, swallowing, and coughing. However, MPV carries a risk of underventilation. Our purpose here was to evaluate the effectiveness of daytime MPV under real-life conditions. Eight wheelchair-bound patients who used MPV underwent daytime polygraphy at home with recordings of airflow, mouthpiece pressure, thoracic and abdominal movements, peripheral capillary oxygen saturation (SpO2), and transcutaneous partial pressure of carbon dioxide (PtcCO2). Times and durations of tasks and activities were recorded. The Apnea-Hypopnea Index (AHI) was computed. Patient-ventilator disconnections ≥3 minutes and episodes of hypoventilation defined as PtcCO2>45 mmHg were counted. Patient-ventilator asynchrony events were analyzed. The AHI was >5 hour(-1) in two patients. Another patient experienced unexplained 3% drops in arterial oxygen saturations at a frequency of 70 hour(-1). Patient-ventilator disconnections ≥3 minutes occurred in seven of eight patients and were consistently associated with decreases in SpO2 and ≥5-mmHg increases in PtcCO2; PtcCO2 rose above 45 mmHg in two patients during these disconnections. The most common type of patient-ventilator asynchrony was ineffective effort. This study confirms that MPV can be effective as long as the patient remains connected to the mouthpiece. However, transient arterial oxygen desaturation and hypercapnia due to disconnection from the ventilator may occur, without inducing unpleasant sensations in the patients. Therefore, an external warning system based on a minimal acceptable value of minute ventilation would probably be useful.


title: The role of host genetics in the immune response to SARS-CoV-2 and COVID-19 susceptibility and severity.

text: This article provides a review of studies evaluating the role of host (and viral) genetics (including variation in HLA genes) in the immune response to coronaviruses, as well as the clinical outcome of coronavirus-mediated disease. The initial sections focus on seasonal coronaviruses, SARS-CoV, and MERS-CoV. We then examine the state of the knowledge regarding genetic polymorphisms and SARS-CoV-2 and COVID-19. The article concludes by discussing research areas with current knowledge gaps and proposes several avenues for future scientific exploration in order to develop new insights into the immunology of SARS-CoV-2.


title: Virus-host coevolution in a persistently coxsackievirus B3-infected cardiomyocyte cell line.

text: Coevolution of virus and host is a process that emerges in persistent virus infections. Here we studied the coevolutionary development of coxsackievirus B3 (CVB3) and cardiac myocytes representing the major target cells of CVB3 in the heart in a newly established persistently CVB3-infected murine cardiac myocyte cell line, HL-1(CVB3). CVB3 persistence in HL-1(CVB3) cells represented a typical carrier-state infection with high levels (10(6) to 10(8) PFU/ml) of infectious virus produced from only a small proportion (approximately 10%) of infected cells. CVB3 persistence was characterized by the evolution of a CVB3 variant (CVB3-HL1) that displayed strongly increased cytotoxicity in the naive HL-1 cell line and showed increased replication rates in cultured primary cardiac myocytes of mouse, rat, and naive HL-1 cells in vitro, whereas it was unable to establish murine cardiac infection in vivo. Resistance of HL-1(CVB3) cells to CVB3-HL1 was associated with reduction of coxsackievirus and adenovirus receptor (CAR) expression. Decreasing host cell CAR expression was partially overcome by the CVB3-HL1 variant through CAR-independent entry into resistant cells. Moreover, CVB3-HL1 conserved the ability to infect cells via CAR. The employment of a soluble CAR variant resulted in the complete cure of HL-1(CVB3) cells with respect to the adapted virus. In conclusion, this is the first report of a CVB3 carrier-state infection in a cardiomyocyte cell line, revealing natural coevolution of CAR downregulation with CAR-independent viral entry in resistant host cells as an important mechanism of induction of CVB3 persistence.


Twentieth-Century Lessons for a Modern Coronavirus Pandemic.


title: Resectional One Anastomosis Gastric Bypass/Mini Gastric Bypass as a Novel Option for Revision of Restrictive Procedures: Preliminary Results.

text: Background Revisional surgery is becoming a common and challenging practice in bariatric centers. The aim of this study was to evaluate resectional one anastomosis gastric bypass/mini gastric bypass (R-OAGB/MGB) as a revisional procedure. Methods From January 2016 to February 2017, data on 21 consecutive patients undergoing R-OAGB/MGB for weight loss failure after primary restrictive procedures were prospectively collected and analysed. Results Mean age was 39 ± 12 years (18-65), and 11 (52.3%) were women. The mean operative time was 96.4 ± 20.9 min (range, 122-80), and the mean postoperative stay was 47.8 ± 7.4 hours (range, 36-73). There were no deaths and no procedure-related complications. The mean body mass index (BMI) decreased from 42.9 ± 6.5 at the time of R-OAGB/MGB to 28.5 ± 4 at the 12-month follow-up. At that time point, the mean percentage of BMI loss (%EBL) and the mean percentage of total body weight loss (%TWL) reached 81.6 ± 0.17% and 35 ± 0.01%, respectively. Conclusion R-OAGB/MGB was technically straightforward, effective, and safe in this at-surgical risk population. R-OAGB/MGB should be added to the armamentarium of revisional bariatric procedures considering its technical aspects and the potential advantage on weight loss.


Instructions for Obtaining ANESTHESIOLOGY Continuing Medical Education (CME) Credit.


title: Systematic Review of Community- and Home-Based Interventions to Support Parenting and Reduce Risk of Child Maltreatment Among Families With Substance-Exposed Newborns.

text: Substance-exposed newborns (SENs) are at increased risk of child maltreatment, out-of-home placement, and poor health and developmental outcomes. The purpose of this systematic review is to synthesize existing research on community- and home-based interventions designed to improve parenting and reduce risk of maltreatment for families with SENs, applying a program logic framework. The review includes studies that used preexperimental, quasi-experimental, and experimental designs. Twelve interventions were identified. Of the nine studies that used more rigorous experimental or quasi-experimental designs, five showed positive effects on at least one parenting or child maltreatment outcome, although some studies showed high risk of bias. Full coherence among the intended participants, theory of change, and program components was observed for only two interventions. The findings suggest a need for more rigorous research to develop and test interventions that are grounded in theory and prior research and that address the unique needs of families with SENs.


Digital health and care in pandemic times: impact of COVID-19.


title: Clostridium sordellii as a Cause of Fatal Septic Shock in a Child with Hemolytic Uremic Syndrome.

text: Clostridium sordellii is a toxin producing ubiquitous gram-positive anaerobe, mainly associated with trauma, soft tissue skin infections, and gynecologic infection. We report a unique case of a new strain of Clostridium sordellii (not present in the Center for Disease Control (CDC) database) infection induced toxic shock syndrome in a previously healthy two-year-old male with colitis-related hemolytic uremic syndrome (HUS). The patient presented with dehydration, vomiting, and bloody diarrhea. He was transferred to the pediatric critical care unit (PICU) for initiation of peritoneal dialysis (PD). Due to increased edema and intolerance of PD, he was transitioned to hemodialysis through a femoral vascular catheter. He subsequently developed severe septic shock with persistent leukocytosis and hypotension, resulting in subsequent death. Stool culture confirmed Shiga toxin producing Escherichia coli 0157:H7. A blood culture was positively identified for Clostridium sordellii. Clostridium sordelli is rarely reported in children; to our knowledge this is the first case described in a pediatric patient with HUS.


title: Internet+ and COVID-19 - A short report.

text: OBJECTIVE COVID-19 broke out in China at the end of 2019 and spread rapidly around the world. The World Health Organization designated COVID-19 as a global pandemic on March 11, 2020. China has adopted its own country-specific comprehensive prevention and control measures, and, as a result, the domestic COVID-19 epidemic became effectively controlled in China in mid-March 2020. During the COVID-19 epidemic, remarkable changes have taken place in China's domestic learning, living, and working methods, primarily in terms of the synergy between the Internet Plus (Internet+) strategy and the leadership of the Chinese government.


title: A provisional strategy for treating true bifurcation lesions employing a scoring balloon for the side branch: final results of the AGILITY trial.

text: BACKGROUND The provisional approach for bifurcation stenting with side-branch balloon angioplasty is associated with dissections and suboptimal results requiring kissing balloon techniques or bailout stenting. We hypothesized that using a scoring balloon for the side branch and a drug-eluting stent for the main vessel might improve outcomes of true bifurcation lesions. METHODS AND RESULTS A total of 93 patients with complex bifurcations were enrolled in a multicenter, single-arm, prospective clinical trial. A drug-eluting stent was deployed in the main vessel following dilatation of the side-branch stenosis with a scoring balloon. The overall angiographic success rate was 93.5%, and procedural success rate was 91.4%. The final diameter stenosis was 13.9% ± 7.2% for the main vessel and 33.3% ± 22.9% for the side branch. Crossover to stent deployment in the side branch was required in 10.8%. The postscoring balloon dissection rate was 8.2% and 6% (all ≤ class C) for the main vessel and side branch respectively, which was reduced to 1.1 and 2.1% poststenting. At 9-month follow-up, the composite MACE rate [cardiac death, myocardial infarction, or target lesion revascularization (TLR)] was 5.4%, including a TLR rate of 3.3% (1.1% from hospital discharge to 9 months). CONCLUSION The 9-month results of the AGILITY trial support a simple provisional strategy for treating complex true bifurcation lesions with deployment of a drug-eluting stent in the main vessel after dilatation of the side-branch vessel with a scoring balloon. This strategy was associated with excellent and safe procedural results, a low rate of crossover to side-branch stenting, and favorable outcomes.


title: Developing a new, national approach to surveillance for ventilator-associated events*.

text: OBJECTIVE To develop and implement an objective, reliable approach to surveillance for ventilator-associated events in adult patients. DESIGN The Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group in September 2011. Working Group members included representatives of stakeholder societies and organizations and federal partners. MAIN RESULTS The Working Group finalized a three-tier, adult surveillance definition algorithm for ventilator-associated events. The algorithm uses objective, readily available data elements and can identify a broad range of conditions and complications occurring in mechanically ventilated adult patients, including but not limited to VAP. The first tier definition, ventilator-associated condition (VAC), identifies patients with a period of sustained respiratory deterioration following a sustained period of stability or improvement on the ventilator, defined by changes in the daily minimum fraction of inspired oxygen or positive end-expiratory pressure. The second tier definition, infection-related ventilator-associated complication (IVAC), requires that patients with VAC also have an abnormal temperature or white blood cell count, and be started on a new antimicrobial agent. The third tier definitions, possible and probable VAP, require that patients with IVAC also have laboratory and/or microbiological evidence of respiratory infection. CONCLUSIONS Ventilator-associated events surveillance was implemented in January 2013 in the CDC's National Healthcare Safety Network. Modifications to improve surveillance may be made as additional data become available and users gain experience with the new definitions.


title: [Public health in the first wave: a research agenda for cooperation under Covid-19].

text: Covid-19 represents one of the largest challenges in the recent history of public health. It is fundamental that we strengthen scientific cooperation under a common goal: to protect the health of the population. In this article, we present ideas that need urgent and collaborative efforts. We discuss the estimation of the magnitude of the epidemic through a nationwide seroprevalence panel, as well as new strategies to monitor the epidemic in real time. We also analyze the negative externalities associated to the pandemic. Finally, we present a general framework to develop ideas to come out of the lockdown, highlighting the importance of implementing sustainable and equitable structural interventions. We call for solidarity and cooperation, focusing our efforts and creativity in the resolution of the problems that currently affect Mexico and the world.


title: Smoking cessation care among patients with head and neck cancer: a systematic review.

text: OBJECTIVE To examine the effectiveness of smoking cessation interventions in improving cessation rates and smoking related behaviour in patients with head and neck cancer (HNC). DESIGN A systematic review of randomised and non-randomised controlled trials. METHODS We searched the following data sources: CENTRAL in the Cochrane Library, MEDLINE, EMBASE, PsycINFO and CINAHL up to February 2016. A search of reference lists of included studies and Google Scholar (first 200 citations published online between 2000 and February 2016) was also undertaken. The methodological quality of included studies was assessed using the Effective Public Health Practice Project Quality Assessment Tool (EPHPP). 2 study authors independently screened and extracted data with disagreements resolved via consensus. RESULTS Of the 5167 studies identified, 3 were eligible and included in the review. Trial designs of included studies were 2 randomised controlled trials and 1 non-randomised controlled trial. 2 studies received a weak methodological rating and 1 received a moderate methodological rating. The trials examine the impact of the following interventions: (1) nurse delivered cognitive-behaviour therapy (CBT) via telephone and accompanied by a workbook, combined with pharmacotherapy; (2) nurse and physician brief advice to quit and information booklets combined with pharmacotherapy; and (3) surgeon delivered enhanced advice to quit smoking augmented by booster sessions. Only the trial of the nurse delivered CBT and pharmacotherapy reported significant increases in smoking cessation rates. 1 study measured quit attempts and the other assessed consumption of cigarettes per day and readiness to change. There was no significant improvement in quit attempts or cigarettes smoked per day among patients in the intervention groups, relative to control. CONCLUSIONS There are very few studies evaluating the effectiveness of smoking cessation interventions that report results specific to the HNC population. The 3 trials identified reported equivocal findings. Extended CBT counselling coupled with pharmacotherapy may be effective. TRIAL REGISTRATION NUMBER CRD42016016421.


title: Endovascular Management of Abdominal Aortic Aneurysms: the Year in Review.

text: OPINION STATEMENT Endovascular aneurysm repair (EVAR) has become the predominant method of treatment for abdominal aortic aneurysms (AAA). The use of conscious sedation with local anesthesia and percutaneous femoral access has further decreased the morbidity of the procedure. Current devices can more effectively manage increasingly "hostile" aneurysm necks, while chimney grafts or dedicated fenestrated stent-grafts can be used for juxta-renal disease with favorable results. However, endovascular repair does present a new set of challenges, and endoleaks remain an area of concern. While there is general consensus that type I and type III endoleaks require treatment, type II endoleaks are the topic of ongoing research and debate. Development of devices and techniques to prevent and treat endoleak continues to progress. Advances in contrast-enhanced ultrasound are reducing reliance on computed tomography for post-operative monitoring. This is an important step in this population at high risk for the development of kidney failure. Despite these many innovations, further research is needed to optimize the care of patients with AAA.


title: Definition of periprosthetic joint infection: is there a consensus?

text: BACKGROUND The diagnosis of periprosthetic joint infection (PJI) continues to pose a challenge. While many diagnostic criteria have been proposed, a gold standard for diagnosis is lacking. Use of multiple diagnostic criteria within the joint arthroplasty community raises concerns in patient treatment and comparison of research pertaining to PJI. QUESTIONS/PURPOSES We (1) determined the variation in existing diagnostic criteria, (2) compared the existing criteria to a proposed new set of criteria that incorporates aspirate cell count analysis, and (3) investigated the variations between the existing criteria and the proposed criteria. PATIENTS AND METHODS We retrospectively identified 182 patients undergoing 192 revision knee arthroplasties who had a preoperative joint aspiration analysis at our institution between April 2002 and November 2009. We excluded 20 cases due to insufficient laboratory parameters, leaving 172 cases for analysis. We applied six previously published sets of diagnostic criteria for PJI to determine the variation in its incidence using each set of criteria. We then compared these diagnostic criteria to our proposed new criteria and investigated cases where disagreement occurred. RESULTS We identified 41 cases (24%) in which at least one established criteria set classified the case as infected while at least one other criteria set classified the case as uninfected. With our proposed criteria, the infected/uninfected ratio was 92/80. The proposed criteria had a large variance in sensitivity (54%-100%), specificity (39%-100%), and accuracy (53%-100%) when using each of the established criteria sets as the reference standard. CONCLUSIONS The discrepancy between definitions of infection complicates interpretation of the literature and the treatment of failed TKAs owing to PJI. Based on our findings, we suggest establishing a common set of diagnostic criteria utilizing aspirate analysis to improve the treatment of PJI and facilitate interpretation of the literature. LEVEL OF EVIDENCE Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.


title: The griffithsin dimer is required for high-potency inhibition of HIV-1: evidence for manipulation of the structure of gp120 as part of the griffithsin dimer mechanism.

text: Griffithsin (Grft) is a protein lectin derived from red algae that tightly binds the HIV envelope protein gp120 and effectively inhibits virus infection. This inhibition is due to the binding by Grft of high-mannose saccharides on the surface of gp120. Grft has been shown to be a tight dimer, but the role of the dimer in Grft's anti-HIV function has not been fully explored. To investigate the role of the Grft dimer in anti-HIV function, an obligate dimer of Grft was designed by expressing the protein with a peptide linker between the two subunits. This "Grft-linker-Grft" is a folded protein dimer, apparently nearly identical in structural properties to the wild-type protein. A "one-armed" obligate dimer was also designed (Grft-linker-Grft OneArm), with each of the three carbohydrate binding sites of one subunit mutated while the other subunit remained intact. While both constructed dimers retained the ability to bind gp120 and the viral surface, Grft-linker-Grft OneArm was 84- to 1,010-fold less able to inhibit HIV than wild-type Grft, while Grft-linker-Grft had near-wild-type antiviral potency. Furthermore, while the wild-type protein demonstrated the ability to alter the structure of gp120 by exposing the CD4 binding site, Grft-linker-Grft OneArm largely lost this ability. In experiments to investigate gp120 shedding, it was found that Grft has different effects on gp120 shedding for strains from subtype B and subtype C, and this might correlate with Grft function. Evidence is provided that the dimer form of Grft is critical to the function of this protein in HIV inhibition.


title: Postprocedural, midterm, and long-term results of cerebral aneurysms treated with flow-diverter devices: 7-year experience at a single center.

text: OBJECTIVE Flow diversion has emerged as a viable treatment option for selected intracranial aneurysms and recently has been gaining traction. The aim of this study was to evaluate the safety and effectiveness of flow-diverter devices (FDDs) over a long-term follow-up period. METHODS The authors retrospectively reviewed all cerebral aneurysm cases that had been admitted to the Division of Neurosurgery of the Università degli Studi di Napoli between November 2008 and November 2015 and treated with an FDD. The records of 60 patients (48 females and 12 males) harboring 69 cerebral aneurysms were analyzed. The study end points were angiographic evidence of complete aneurysm occlusion, recanalization rate, occlusion of the parent artery, and clinical and radiological evidence of brain ischemia. The occlusion rate was evaluated according to the O'Kelly-Marotta (OKM) Scale for flow diversion, based on the degree of filling (A, total filling; B, subtotal filling; C, entry remnant; D, no filling). Postprocedural, midterm, and long-term results were strictly analyzed. RESULTS Complete occlusion (OKM D) was achieved in 63 (91%) of 69 aneurysms, partial occlusion (OKM C) in 4 (6%), occlusion of the parent artery in 2 (3%). Intraprocedural technical complications occurred in 3 patients (5%). Postprocedural complications occurred in 6 patients (10%), without neurological deficits. At the 12-month follow-up, 3 patients (5%) experienced asymptomatic cerebral infarction. No further complications were observed at later follow-up evaluations (> 24 months). There were no reports of any delayed aneurysm rupture, subarachnoid or intraparenchymal hemorrhage, ischemic complications, or procedure- or device-related deaths. CONCLUSIONS Endovascular treatment with an FDD is a safe treatment for unruptured cerebral aneurysms, resulting in a high rate of occlusion. In the present study, the authors observed effective and stable aneurysm occlusion, even at the long-term follow-up. Data in this study also suggest that ischemic complications can occur at a later stage, particularly at 12-18 months. On the other hand, no other ischemic or hemorrhagic complications occurred beyond 24 months.


title: An advanced RFID-based system to localize gastric and colon cancers during laparoscopic surgery.

text: BACKGROUND We aimed to improve the tumor localization system using radiofrequency identification (RFID) technology used during laparoscopic surgery for gastric and colorectal cancer. To this end, we developed a detection algorithm and designed improvement for the RFID clip. METHODS To evaluate the proposed system, a swine-based animal study was conducted, followed by experiments on porcine stomachs and colons using the EASIE-R simulator. The success rates of endoscopic clipping, detection time, and detection accuracy, which is the distance between the detection point and RFID tag, were measured. RESULTS Results of the in vivo swine animal study showed success in all three clippings and detections of the RFID clips. Results of the 60 RFID endoclip attempts using the EASIE-R simulator showed a total clipping success rate of 85.0% (n = 51/60; stomach, 83.3%, n = 25/30; colon, 86.7%, n = 26/30). The median detection times were 29.2 s for the stomach and 25.5 s for the colon. The median detection accuracy was 4.0 mm for the stomach and 4.5 mm for the colon. CONCLUSIONS We confirmed that the proposed RFID-based system showed improvements over the system of a previous study. This RFID-based system is effective at localizing gastric and colorectal tumors.


title: Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia.

text: Critical limb ischemia (CLI) is a serious condition that entails a high risk of lower limb amputation. Despite revascularization being the gold-standard therapy, a considerable number of CLI patients are not suited for either surgical or endovascular revascularization. Angiogenic therapies are emerging as an option for these patients but are currently still under investigation. Before application in humans, those therapies must be tested in animal models and its mechanisms must be clearly understood. An animal model of hindlimb ischemia (HLI) has been developed by the ligation and excision of the distal external iliac and femoral arteries and veins in mice. A comprehensive panel of tests was assembled to assess the effects of ischemia and putative angiogenic therapies at functional, histologic and molecular levels. Laser Doppler was used for the flow measurement and functional assessment of perfusion. Tissue response was evaluated by the analysis of capillary density after staining with the anti-CD31 antibody on histological sections of gastrocnemius muscle and by measurement of collateral vessel density after diaphonization. Expression of angiogenic genes was quantified by RT-PCR targeting selected angiogenic factors exclusively in endothelial cells (ECs) after laser capture microdissection from mice gastrocnemius muscles. These methods were sensitive in identifying differences between ischemic and non-ischemic limbs and between treated and non-treated limbs. This protocol provides a reproducible model of CLI and a framework for testing angiogenic therapies.


title: [Pandemic and mental adjustment disorders. Therapy options].

text: The article considers the main triggers of adjustment and anxiety disorders in the time of pandemic that brings significant changes in all life dimensions with the high uncertainty level. The article highlights a role of coronavirus infodemic in the development of anxiety disorders. The main targets for cognitive, emotional and behavioral interventions are suggested. Recommendations for anxiety adjustment disorders psychopharmacotherapy with the use of tranquillizers as treatment of choice are given. Prevention measures for medical doctors working in conditions of pandemic are proposed.


title: Rebooting Bioresilience: A Multi-OMICS Approach to Tackle Global Catastrophic Biological Risks and Next-Generation Biothreats.

text: Global Catastrophic Biological Risks (GCBRs) refer to biological events-natural, deliberate, and accidental-of a global and lasting impact. This challenges the life scientists to raise their game on two hitherto neglected innovation frontiers: a veritable "futures" thinking to "think the unthinkable," and "systems thinking" so as to see both the trees and the forest when it comes to GCBRs. This innovation analysis article outlines the promise of Omics systems science biotechnologies, for example, to deploy rapid fire diagnostics for health security crises at GCBR level, possibly involving neopathogens and/or incurring epidemics (e.g., severe acute respiratory syndrome [SARS] and Ebola) that collectively threaten the lives of global society and interdependent biological ecosystems. Moreover, Omics encourages thinking beyond immediacy and in long-term strategies for biopreparedness and response innovation when the timelines are aggressive and compressed in response to crises such as GCBRs, but also to non-global but surging, multiple threats occurring as successive, overlapping, or distinct events, rather than as distinct entities-a prospect enforcing a reboot in Bioresilience. We define Next-Generation Bioresilience as "a systems approach against natural, accidental and perpetrated GCBRs using Omics technologies, and a shift in mentality, whereby the systems approach is expanded to include multiple plausible futures and expose unchecked assumptions attendant to risks, beyond technological determinism." In sum, it is time to think about the realistic potential of Omics biotechnologies beyond clinical practice and precision medicine so as to harness the opportunities and address the uncertainties associated not only with GCBRs but also with other emerging Omics applications in health and society.


title: How well do vaccines for Bordetella bronchiseptica work in dogs? A critical review of the literature 1977-2014.

text: Bordetella bronchiseptica (Bb) has long been causally associated with respiratory disease in dogs. Parenteral and intranasal vaccines for this pathogen have been in common use since their development in the late 1970s and early 1980s and recently a commercial oral Bb vaccine has become available. Overall, the literature (comprising experimental infection models and field studies) documents the efficacy of these vaccines in stimulating disease-sparing mucosal and systemic immune responses that can be associated with reduced growth of Bb in vivo. However, many of the published studies are limited by flaws in experimental design, most notably a failure to consider the biological and statistical implications of the 'pen effect'. Many questions related to the longevity of vaccine induced immunity against Bb and the impact of natural exposure on herd immunity remain unanswered.


title: Primary Symptoms, Comorbidities, and Outcomes of 431 Hospitalized Patients with Confirmative RT-PCR Results for COVID-19.

text: This study aimed to evaluate the primary symptoms, comorbidities, and outcomes of inpatients with confirmed reverse transcription-PCR (RT-PCR) for SARS-CoV-2 infection among 2077 suspected/diagnosed cases of COVID-19. Based on the results of Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression, age, and suggestive chest X-ray (CXR) findings for SARS-CoV-2 infection, cardiovascular diseases, diabetes mellitus, chronic lung diseases, and intensive care units admission had significant associations with positive RT-PCR results for COVID-19 infection. Also, the highest area under the curve (AUC) was related to cough (AUC = 0.53, 95% CI: 0.51-0.56), dyspnea (AUC = 0.52, 95% CI: 0.50-0.54), and abnormal CXR (AUC = 0.52, 95% CI: 0.50-0.54), as significant predictors. This study showed that some symptoms including cough and dyspnea, as well as abnormal CXR, could be proper predictors of positive RT-PCR result for SARS-CoV-2 infection. It seems that patients with underlying disease(s), such as cardiovascular diseases, diabetes mellitus, and chronic lung diseases, had a higher probability to have positive RT-PCR for SARS-CoV-2 infection than those with no underlying disease(s).


title: One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities.

text: In addition to members causing milder human infections, the Coronaviridae family includes potentially lethal zoonotic agents causing severe acute respiratory syndrome (SARS) and the recently emerged Middle East respiratory syndrome. The ∼30-kb positive-stranded RNA genome of coronaviruses encodes a replication/transcription machinery that is unusually complex and composed of 16 nonstructural proteins (nsps). SARS-CoV nsp12, the canonical RNA-dependent RNA polymerase (RdRp), exhibits poorly processive RNA synthesis in vitro, at odds with the efficient replication of a very large RNA genome in vivo. Here, we report that SARS-CoV nsp7 and nsp8 activate and confer processivity to the RNA-synthesizing activity of nsp12. Using biochemical assays and reverse genetics, the importance of conserved nsp7 and nsp8 residues was probed. Whereas several nsp7 mutations affected virus replication to a limited extent, the replacement of two nsp8 residues (P183 and R190) essential for interaction with nsp12 and a third (K58) critical for the interaction of the polymerase complex with RNA were all lethal to the virus. Without a loss of processivity, the nsp7/nsp8/nsp12 complex can associate with nsp14, a bifunctional enzyme bearing 3'-5' exoribonuclease and RNA cap N7-guanine methyltransferase activities involved in replication fidelity and 5'-RNA capping, respectively. The identification of this tripartite polymerase complex that in turn associates with the nsp14 proofreading enzyme sheds light on how coronaviruses assemble an RNA-synthesizing machinery to replicate the largest known RNA genomes. This protein complex is a fascinating example of the functional integration of RNA polymerase, capping, and proofreading activities.


title: Two sides of the same coin? On the history and phenomenology of chronic fatigue and burnout.

text: BACKGROUND Burnout and chronic fatigue syndrome (CFS) are two fatigue syndromes which have developed largely independently from each other, yet whose similarities in symptoms can be a source of confusion. We aim to explore the phenomenology of burnout and CFS in a historical context as this may provide some insight into the links and relationship between these conditions. METHOD A narrative review based on literature in the fields of history, social science and medicine. RESULTS The origins of CFS lie within medicine, whereas burnout developed in a psychological setting. As well as symptoms, burnout and CFS also share similar themes such as an overload process triggering illness onset, the need for restoration of depleted energy, external causal attributions and the characteristics of people suffering from these illnesses. However, these themes are expressed in either psychological or medical terms according to the historical background. CONCLUSION Despite their similarities, there have been few direct comparisons of the two concepts. Culture, illness perceptions and accountability are important issues in both conditions and could contribute to their differences. Comparing burnout and CFS within one sample frame, thus looking beyond the psychology/medicine divide, could be a useful first step towards understanding their relationship.


title: The optimal strategy for proximal mesh fixation during laparoscopic ventral rectopexy for rectal prolapse: an ex vivo study.

text: BACKGROUND Laparoscopic ventral rectopexy (LVR) is an established technique for the treatment of rectal prolapse. Several techniques and devices can be used for proximal mesh fixation on the sacral promontory during this procedure. The aim of this study was to compare the fixation strength of a recently introduced screw for mesh fixation on the promontory during LVR with two other frequently used techniques. METHODS An ex vivo experimental model using a porcine spinal column was designed to measure the strength of proximal mesh fixation. In a laparoscopic box trainer, a polypropylene mesh was anchored on the spinal column using three different fixation methods, i.e., the Protack 5-mm tacker device, Ethibond Excel 2-0 stitches, and the Karl Storz screw. Subsequently, increasing traction was applied to the mesh. This traction was applied at a standardized angle as determined by measuring the mean angle between the site of distal mesh fixation on the rectum and a line straight through the sacral promontory on 12 random dynamic MR scans of the pelvic floor after the LVR procedure. The applied force was measured at the moment that the fixation broke, using a calibrated electronic Newton meter. All fixation methods were tested ten times. RESULTS The mean angle, as measured on the MR scans, was 100°. The mean disruption force, which led to a break of the proximal mesh fixation, was 58 N for the three Protack tacks, 55 N for the two stitches, and 70 N for the new screw. The use of a screw therefore led to a significantly stronger fixation compared to the use of stitches (p ≤ 0.05). No significant difference was determined between the tacks and the screw fixation and between the tacks and the stitches fixation. CONCLUSION The new screw for proximal mesh fixation during LVR procedures offers similar fixation strength when compared to tacks. The use of one screw for proximal mesh fixation is therefore a reasonable alternative to the use of several tacks or sutures.


Heterogeneity of Acute Respiratory Distress Syndrome in COVID-19: "Typical" or Not?


title: Glottic Stenosis: An Anatomic Analysis and New Treatment With a Self-Retaining Interarytenoid Spring.

text: INTRODUCTION: Endotracheal (ET) intubation is a common cause of acquired glottic stenosis. Severe cases often require an irreversible arytenoidectomy/cordectomy, which typically results in poor voice quality. Adult human cadaver larynges were studied to gain insights about ET tube-induced posterior glottic injuries, hoping to create a less invasive remedy. STUDY DESIGN: Human cadaver investigation and case reports. METHODS: Microlaryngeal assessments were done on 10 human cadaver larynges (5 men, 5 women) with and without ET tubes. After supracricoid soft tissue resection, measurements were obtained, including the distance between the outer diameter of the ET tube and the medial aspect of the cricoarytenoid joint facet. Additionally, measurements of the circumferential arc of differently sized ET tubes were made alongside both cricoarytenoid joint capsules. This information was used to design a silastic stent that would function as a self-retaining interarytenoid spring to treat posterior glottic stenosis in 5 patients. Four of 5 patients included in the clinical study were tracheotomy dependent, primarily because of glottic stenosis. The human surgical technique is described in detail. RESULTS: The shortest distance between the outer diameter of the ET tube to the medial cricoid facet averaged 5.02 mm in men and 3.62 mm in women. On the basis of the diameter of the intralaryngeal component of the initially round stent, and the position of the cricoarytenoid joint facets, the interarytenoid spring would have a subtended arc between 110° and 175°. These data helped fashion parameters for modifying a conventional T-tube to form a new self-retaining silastic interarytenoid spring. The first 5 human cases have been successful, allowing effective tracheotomy tube decannulation and excellent voice quality. CONCLUSIONS: The anatomic investigation herein provided key insights into ET tube-induced glottic stenosis and facilitated a new straightforward procedure to surgically improve the airway yet preserve excellent vocal function in patients with acquired glottic stenosis. Level of Evidence: NA.


title: [Prevention and control program on 2019 novel coronavirus infection in children's digestive endoscopy center].

text: 2019年12月以来，湖北省武汉市陆续出现新型冠状病毒（2019-nCoV）感染病例，疫情蔓延至我国各地及境外。人群对2019-nCoV普遍易感，已陆续发现儿童病例。发热不再是早期的主要表现，感染者也可表现为乏力、干咳和恶心、呕吐等症状，少数以消化道症状为首发表现而就诊。在鼻咽拭子、痰、下呼吸道分泌物、血液、粪便等标本中可检测出2019-nCoV核酸。疫情流行期间，原则上如非必须，应推迟消化内镜诊疗。但病情需要或需急诊消化内镜诊疗时，应认真评估，掌握诊疗指征，做好个人防护，严格执行消毒隔离规范。现结合儿童消化内镜诊疗特点，制定疫情流行期间儿童消化内镜中心应对2019-nCoV感染的防控方案，防止医院内感染发生。以期能对一线儿童消化内镜诊疗医护人员在2019-nCoV流行期间的工作及疫情防控起到建议与指导作用。.


title: Delivery room interventions to prevent bronchopulmonary dysplasia in preterm infants: a protocol for a systematic review and network meta-analysis.

text: INTRODUCTION As gestational age decreases, incidence of bronchopulmonary dysplasia (BPD) and chronic lung disease increases. There are many interventions used in the delivery room to prevent acute lung injury and consequently BPD in these patients. The availability of different treatment options often poses a practical challenge to the practicing neonatologist when it comes to making an evidence-based choice as the multitude of pairwise systematic reviews including Cochrane reviews that are currently available only provide a narrow perspective through head-to-head comparisons. METHODS AND ANALYSIS We will conduct a systematic review of all randomised controlled trials evaluating delivery room interventions within the first golden hour after birth for prevention of BPD. The primary outcome includes BPD. Secondary outcomes include death at 36 weeks of postmenstrual age or before discharge; severe intraventricular haemorrhage (grade 3 or 4 based on the Papile criteria); any air leak syndromes (including pneumothorax or pulmonary interstitial emphysema); retinopathy of prematurity (any stage) and neurodevelopmental impairment at 18-24 months. We will search from their inception to August 2018, the following databases: Medline, EMBASE and Cochrane Central Register of Controlled Trials as well as grey literature resources. Two reviewers will independently screen titles and abstracts, review full texts, extract information and assess the risk of bias and the confidence in the estimate (with Grading of Recommendations Assessment, Development and Evaluation approach). This review will use Bayesian network meta-analysis approach which allows the comparison of the multiple delivery room interventions for prevention of BPD. We will perform a Bayesian network meta-analysis to combine the pooled direct and indirect treatment effect estimates for each outcome, effectiveness and safety of delivery room interventions for prevention of BPD. ETHICS AND DISSEMINATION The proposed protocol is a network meta-analysis, which has been registered on PROSPERO International prospective register of systematic reviews (CRD42018078648). The results will provide an evidence-based guide to choosing the right sequence of early postnatal interventions that will be associated with the least likelihood of inducing lung injury and BPD in preterm infants. Furthermore, we will identify knowledge gaps and will encourage further research for other therapeutic options. Therefore, its results will be disseminated through peer-reviewed publications and conference presentations. Due to the nature of the design, no ethics approval is necessary.


title: The world haunted by Covid-19.

text: In this time of confinement due to COVID-19 pandemic some reflections have been made e it has never been as clear as people can benefit from science. From the simple gesture of washing your hands like many others used during the quarantine, they have been identified by previous studies. In this way, we reinforce the need to maintain investments in the science.


title: Technique of Roux-en-Y reconstruction using overlap method after laparoscopic total gastrectomy for gastric cancer: 100 consecutively successful cases.

text: BACKGROUND We have established a standard procedure for Roux-en-Y (RY) reconstruction in laparoscopic total gastrectomy (LTG) using esophagojejunostomy by the overlap method (OL). We report on our RY reconstruction technique and special approaches, and evaluate the usefulness of our reconstruction method based on the surgical results of 100 patients we have experienced to date. METHODS We performed LTG in 100 patients with gastric cancer. After total gastrectomy using five ports, the resected stomach was extracted through a small laparotomy. Through that, we performed sacrifice of the jejunum, Y limb anastomosis, creation of the lifted jejunum. As the OL, a side-to-side anastomosis of the lifted jejunum to the esophageal stump was laparoscopically performed using a linear stapler in an isoperistaltic direction, and the entry hole was closed with full-thickness suturing. The lifted jejunum was fixed with suture to the duodenal stump at a location where the esophagojejunostomy site was made linear, and the duodenal stump was buried. The mesenteric gap was laparoscopically closed with suture. RESULTS The median operative time in 100 patients undergoing LTG was 385 min, the median blood loss was 65 mL, and the median time required for the OL was 32 min. The mean hospitalization period was 10 days, and postoperative complications included bleeding requiring reoperation in one patient; other complications such as pancreatic fistula in five patients (5 %) were treated conservatively. No complication associated with anastomosis occurred. CONCLUSION In RY reconstruction using the OL, there were no complications associated with the anastomosis site in 100 consecutive patients, such as anastomotic leak or stenosis, indicating that it is a very useful and safe reconstruction method.


title: Implications of small-bowel transit time in the detection rate of capsule endoscopy: A multivariable multicenter study of patients with obscure gastrointestinal bleeding.

text: AIM To define the role of small-bowel transit time in the detection rate of significant small-bowel lesions. METHODS Small-bowel capsule endoscopy records, prospectively collected from 30 participating centers in the Lombardy Registry from October 2011 to December 2013, were included in the study if the clinical indication was obscure gastrointestinal bleeding and the capsule reached the cecum. Based on capsule findings, we created two groups: P2 (significant findings) and P0-1 (normal/negligible findings). Groups were compared for age, gender, small-bowel transit time, type of instrument, modality of capsule performance (outpatients vs inpatients), bowel cleanliness, and center volume. RESULTS We retrieved and scrutinized 1,433 out of 2,295 capsule endoscopy records (62.4%) fulfilling the inclusion criteria. Patients were 67 ± 15 years old, and 815 (57%) were males. In comparison with patients in the P0-1 group, those in the P2 group (n = 776, 54%) were older (P < 0.0001), had a longer small-bowel transit time (P = 0.0015), and were more frequently examined in low-volume centers (P < 0.001). Age and small-bowel transit time were correlated (P < 0.001), with age as the sole independent predictor on multivariable analysis. Findings of the P2 group were artero-venous malformations (54.5%), inflammatory (23.6%) and protruding (10.4%) lesions, and luminal blood (11.5%). CONCLUSION In this selected, prospectively collected cohort of small-bowel capsule endoscopy performed for obscure gastrointestinal bleeding, a longer small-bowel transit time was associated with a higher detection rate of significant lesions, along with age and a low center volume, with age serving as an independent predictor.


title: Development of a Model of Porcine Epidemic Diarrhea in Microminipigs.

text: Porcine epidemic diarrhea virus (PEDV) induces an often fatal gastrointestinal disease in piglets. In this study, we performed a PEDV infection experiment with the Microminipig, the smallest of experimental minipigs, as a novel small animal model. We orally inoculated a neonatal Microminipig with an intestinal homogenate of a PEDV-infected pig and housed it in a small cage originally designed for rats in an animal biosafety level 2 facility. The infected Microminipig showed the typical signs of porcine epidemic diarrhea (PED), such as watery diarrhea, loss of appetite and weight loss. We also recognized a high amount of excreted PEDV in its rectal swabs and villus atrophy of the small intestine. These results suggest that the Microminipig is a good small animal model for PED, which may contribute to a better understanding of the pathogenesis of PEDV.


title: Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application on the healthy equine eye.

text: OBJECTIVE To determine if corneal epithelial cell integrity is detrimentally affected by short-term administration of 1.0% morphine sulfate. Additionally, we sought to determine if topical 1.0% morphine applied to the equine cornea would result in ocular or systemic absorption. ANIMAL STUDIED Six healthy horses. PROCEDURE Morphine sulfate (1.0%) was applied topically to one eye every four hours for 72 h before horses were euthanized. Serum samples were collected at varying time points during the study and aqueous and vitreous humor were collected immediately after euthanasia. Morphine quantification in serum, aqueous, and vitreous humor was performed by ELISA. Treated and control corneas were submitted for histopathology. Horses were monitored for adverse ocular and systemic effects throughout the study period. RESULTS All horses developed mild mucoid ocular discharge in the treated eye. One horse developed a fever during treatment. Morphine was detected in the aqueous humor of the treated eye for all horses with mean ± standard deviation of 165.18 ng/mL ± 87.69 ng/mL. Morphine was detected in vitreous humor of the treated eye of 5 of 6 horses with mean ± standard deviation of 4.87 ± 4.46 ng/mL. Morphine was detected in the serum of 5 of 6 horses at varying time points. Maximum systemic concentration reached in a single horse was 6.98 ng/mL. Corneal histopathology revealed no difference in microscopic appearance between morphine-treated and control corneas. CONCLUSIONS Topical administration of 1.0% morphine sulfate did not appear to cause any significant ocular or systemic adverse effects. Topical ophthalmic morphine application resulted in both ocular and systemic absorption.


title: Human-leukocyte antigen class I Cw 1502 and class II DR 0301 genotypes are associated with resistance to severe acute respiratory syndrome (SARS) infection.

text: One-hundred and thirty confirmed cases of severe acute respiratory syndrome (SARS) were recruited to evaluate their anti-SARS-coronavirus (CoV) antibody status and human leukocyte antigen (HLA) types in September 2006, 3 y after the SARS outbreaks in Taiwan. Western blot assay showed that 6.9% of participants still had anti-spike and anti-nucleocapside antibodies. A case-control study of the association of HLA with SARS revealed that the HLA-Cw1502 and DR0301 alleles conferred resistance against SARS infection (p<0.05).


Hypoalbuminemia, Coagulopathy and Vascular Disease in Covid-19.


title: A randomized, controlled trial of Panax quinquefolius extract (CVT-E002) to reduce respiratory infection in patients with chronic lymphocytic leukemia.

text: BACKGROUND Chronic lymphocytic leukemia (CLL) patients are at high risk for acute respiratory illness (ARI). OBJECTIVE We evaluated the safety and efficacy of a proprietary extract of Panax quinquefolius, CVT-E002, in reducing ARI. METHODS This was a double-blind, placebo-controlled, randomized trial of 293 subjects with early-stage, untreated CLL conducted January-March 2009. RESULTS ARI was common, occurring on about 10% of days during the study period. There were no significant differences of the 2 a priori primary end points: ARI days (8.5 ± 17.2 for CVT-E002 vs 6.8 ± 13.3 for placebo) and severe ARI days (2.9 ± 9.5 for CVT-E002 vs 2.6 ± 9.8 for placebo). However, 51% of CVT-E002 vs 56% of placebo recipients experienced at least 1 ARI (difference, -5%; 95% confidence interval [CI], -16% to 7%); more intense ARI occurred in 32% of CVT-E002 vs 39% of placebo recipients (difference, -7%; 95% CI, -18% to 4%), and symptom-specific evaluation showed reduced moderate to severe sore throat (P = .004) and a lower rate of grade ≥3 toxicities (P = .02) in CVT-E002 recipients. Greater seroconversion (4-fold increases in antibody titer) vs 9 common viral pathogens was documented in CVT-E002 recipients (16% vs 7%, P = .04). LIMITATIONS Serologic evaluation of antibody titers was not tied to a specific illness, but covered the entire study period. CONCLUSION CVT-E002 was well tolerated. It did not reduce the number of ARI days or antibiotic use; however, there was a trend toward reduced rates of moderate to severe ARI and significantly less sore throat, suggesting that the increased rate of seroconversion most likely reflects CVT-E002-enhanced antibody responses.


title: Autophagy of pathogens alarms the immune system and participates in its effector functions.

text: Macroautophagy is a main catabolic pathway of eukaryotic cells, delivering cytoplasmic constituents for lysosomal degradation. Originally described as a starvation response, it has now been realised that macroautophagy supports many aspects of innate and adaptive immunity by facilitating innate pathogen detection and antigen presentation, as well as pathogen clearance and lymphocyte expansion. In the first half of this review, we summarise new insights into substrate selection and macroautophagic support of vesicular transport pathways, which underlie macroautophagic regulation of afferent and efferent immunity to pathogens, as outlined in the second half of the review. Applying this increased mechanistic understanding to infectious disease settings should allow us to identify further pathways for pathogen restriction, which can be explored for therapeutic manipulations of macro-autophagy.


title: Preoperative factors and 3-year weight change in the Longitudinal Assessment of Bariatric Surgery (LABS) consortium.

text: BACKGROUND Limited data guide the prediction of weight loss success or failure after bariatric surgery according to presurgery factors. There is significant variation in weight change after bariatric surgery and much interest in identifying preoperative factors that may contribute to these differences. This report evaluates the associations of a comprehensive set of baseline factors and 3-year weight change. SETTING Ten hospitals in 6 geographically diverse clinical centers in the United States. METHODS Adults undergoing a first bariatric surgical procedure as part of clinical care by participating surgeons were recruited between 2006 and 2009. Participants completed research assessments utilizing standardized and detailed data collection on over 100 preoperative and operative parameters for individuals undergoing Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB). Weight was measured 3 years after surgery. Percent weight change for RYGB or LAGB from baseline to 3 years was analyzed as both a continuous and dichotomous outcome with cut points at 25% for RYGB and 10% for LAGB. Multivariable linear and logistic regression models were used to identify independent baseline predictors of the continuous and categorical outcomes, respectively. RESULTS The median weight loss 3 years after surgery for RYGB (n = 1513) participants was 31.5% (IQR: 24.6%-38.4%; range, 59.2% loss to .9% gain) of baseline weight and 16.0% (IQR: 8.1%-23.1%; range, 56.1% loss to 12.5% gain) for LAGB (n = 509) participants. The median age was 46 years for RYGB and 48 years for LAGB; 80% of RYGB participants and 75% of LAGB participants were female; and the median baseline body mass index (BMI) was 46 kg/m(2) for RYGB and 44 kg/m(2) for LAGB. For RYGB, black participants lost 2.7% less weight compared with whites and participants with diabetes at baseline had 3.7% less weight loss at year 3 than those without diabetes at baseline. There were small but statistically significant differences in weight change for RYGB in those with abnormal kidney function and current or recent smoking. For LAGB participants, those with a large band circumference had 75% greater odds of experiencing less than 10% weight loss after adjusting for BMI and sex. CONCLUSIONS Few baseline variables were associated with 3-year weight change and the effects were small. These results indicate that baseline variables have limited predictive value for an individual's chance of a successful weight loss outcome after bariatric surgery. TRIAL REGISTRATION NCT00465829, ClinicalTrials.gov.


title: Quality of Life and Surgical Outcome 1 Year After Open and Laparoscopic Incisional Hernia Repair: PROLOVE: A Randomized Controlled Trial.

text: OBJECTIVE Patients suffering from an incisional hernia after abdominal surgery have an impaired quality of life (QoL). Surgery aims to improve QoL with a minimum risk of further complications. The aim was to analyze QoL, predictors for outcome, including recurrence and reoperation rates during the first postoperative year. METHODS In a randomized controlled trial comparing laparoscopic and open mesh repair, 133 patients were assessed preoperatively and after 1 year with regard to QoL using the Short Form-36 (SF-36), visual analog scale (pain, movement limitation, and fatigue), and questions addressing abdominal wall complaints. Factors concerning recurrence, reoperations, satisfaction, and improved QoL were analyzed. RESULTS A total of 124 patients remained for analysis. All SF-36 scores except mental composite score increased, reaching and maintaining levels of the Swedish norm already after 8 weeks with no difference between groups. Event-free recovery was seen in 85% in the laparoscopic group and in 65% of the open cases (P < 0.010). Five recurrences occurred after laparoscopic surgery and 1 in the open group (P < 0.112). Overall, abdominal wall complaints decreased from 82% to 13% of the patients; and 92% were satisfied with the result after 1 year.In univariable logistic regression analyses laparoscopic surgery and male sex predicted an event-free recovery. Obesity (BMI > 30) predicted better outcome with regard to QoL. No predictors for recurrence or satisfaction were identified. CONCLUSIONS Patients with incisional hernia benefit substantially from surgery concerning QoL, independent of surgical technique. An event-free recovery occurred frequently after laparoscopic surgery. SF-36 seems well suited for assessing surgical outcome in patients after incisional hernia repair.


title: Porcine rotavirus C in pigs with gastroenteritis on Thai swine farms, 2011-2016.

text: Swine are economically important food animals, but highly contagious porcine epidemic diarrhea virus (PEDV) and rotavirus can afflict pig herds and contribute significantly to piglet morbidity and mortality. While there have been studies on rotavirus group A (RVA) in Thailand, reports of rotavirus group C (RVC) are limited. Here, we aimed to identify the prevalence of RVC circulating on Thai commercial swine farms. We analyzed 769 feces and intestine mucosal contents of pigs affected with diarrhea between 2011 and 2016 using RT-PCR specific for the PEDV spike (S), rotavirus glycoprotein (G) VP7, and protease-sensitive protein (P) VP4 genes. We found that 6.6% (51/769) of samples tested positive for RVC, of which 11 samples were co-infected with RVA and four samples were co-infected with PEDV. Three samples tested positive for all three viruses. Phylogenetic analysis of the VP7 gene showed that the most frequent RVC genotype was G1, which grouped with the prototypic RVC Cowden strain. While G6 and G9 were also common, G3 was relatively rare. Analysis of the VP4 gene revealed that the most common P type was P[5], followed by P[4], P[7], and P[1]. In all, there were six G/P combinations (G6P[5], G1P[1], G1P[4], G1P[5], G9P[4], and G9P[7]), of which G6P[5] was the most predominant.


title: Endothelial pyroptosis underlies systemic inflammatory response following radiofrequency ablation of hepatic hemangiomas.

text: This study investigated the relationship between endothelial pyroptosis and the occurrence of systemic inflammatory response (SIR) after radiofrequency (RF) ablation of hepatic hemangiomas. Thirty-two patients with hepatic hemangiomas were treated with RF ablation and blood samples of the patients were collected at different time points. Immunohistochemistry staining was performed to evaluate the expression of caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 in hepatic hemangioma and subablated hemangioma tissue. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were treated with sub-ablative hyperthermia with or without the addition of caspase-1 inhibitor, Ac-YVAD-CMK in the medium. Lactate dehydrogenase (LDH), IL-18, IL-1β, caspase-1 and GSDMD were measured by enzyme-linked immunosorbent assay, real-time PCR and Western blot methods. An elevation of general SIR parameters (CRP and WBC), pyroptosis-related inflammatory cytokines (IL-1β and IL-18) and LDH were observed 1-day post-RF ablation and their peak values were significantly correlated with ablated volume (p < .001) and ablation time (p < .001). Moreover, levels of pyroptosis-related inflammatory cytokines correlated well with general SIR parameters, respectively (p < .001). Immunohistochemical analysis showed the increased expression of caspase-1, GSDMD, IL-18 and IL-1β in the endothelial cells of subablated hemangioma. In vitro experiments showed that subablative hyperthermia induced the caspase-1-associated endothelial pyroptosis and Ac-YVAD-CMK attenuated pyroptosis. In conclusion, SIR in patients treated by RF ablation for hepatic hemangiomas was significantly associated with the ablated volume and ablation time and endothelial pyroptosis may involve in the occurrence of SIR following RF ablation of hepatic hemangiomas.


title: Role of intraoperative frozen section for assessing distal resection margin after anterior resection.

text: BACKGROUND AND AIMS The use of neoadjuvant long-course chemoradiotherapy (LCRT), shorter distal safety margins (DSMs) and stapled or intersphincteric resections has increased sphincter preservation rates. While intraoperative frozen section (IOFS) is not mandatory, it helps achieve negative distal resection margins (DRMs). Our aim was to audit the role of IOFS for DRM assessment while performing sphincter-saving rectal surgery and to identify those subgroups that would benefit the most from IOFS analysis. METHODS Patients who underwent rectal cancer surgery between 2009 and 2013 were identified from a prospectively maintained database. Patients who intraoperatively underwent an IOFS for DRM assessment were included in the study. Factors associated with a positive margin on IOFS were analysed. The sensitivity and specificity of IOFS were also assessed. RESULTS Of 250 patients, who had an anterior resection with an IOFS, 12 had an involved DRM. Of these patients, eight were involved by adenocarcinoma, two by acellular mucin, one by moderate dysplasia and one by adenoma confirmed on paraffin section. Positive margins had a 100 % intervention rate. There were two false negative on IOFS. IOFS had a sensitivity of 85.17 % with a specificity of 100 % and a negative predictive value of 99.16 %. Specimens with a positive IOFS were lower rectal (P < 0.05), poorly differentiated and post LCRT locally advanced tumours. CONCLUSIONS IOFS to confirm negative DRM is recommended in lower rectal tumours irrespective of DSM. It can be considered for locally advanced post LCRT poorly differentiated mid rectal tumours and avoided for upper rectal tumours.


title: Cytokine Storm in COVID19: A Neural Hypothesis.

text: Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.


SARS-CoV-2 Transmission and the Risk of Aerosol Generating Procedures.


title: An investigation into the diagnostic accuracy, reliability, acceptability and safety of a novel device for Continuous Ambulatory Vestibular Assessment (CAVA).

text: Dizziness is a common condition that is responsible for a significant degree of material morbidity and burden on health services. It is usually episodic and short-lived, so when a patient presents to their clinician, examination is normal. The CAVA (Continuous Ambulatory Vestibular Assessment) device has been developed to provide continuous monitoring of eye-movements, allowing insight into the physiological parameters present during a dizziness attack. This article describes the first clinical investigation into the medical and technical aspects of this new diagnostic system. Seventeen healthy subjects wore the device near continuously for up to thirty days, artificially inducing nystagmus on eight occasions. 405 days' worth of data was captured, comprising around four billion data points. A computer algorithm developed to detect nystagmus demonstrated a sensitivity of 99.1% (95% CI: 95.13% to 99.98%) and a specificity of 98.6% (95% CI: 96.54% to 99.63%). Eighty-two percent of participants wore the device for a minimum of eighty percent of each day. Adverse events were self-limiting and mostly the consequence of skin stripping from the daily replacement of the electrodes. The device was shown to operate effectively as an ambulatory monitor, allowing the reliable detection of artificially induced nystagmus.


title: Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1.

text: UNLABELLED Coronavirus spike (S) glycoproteins mediate receptor binding, membrane fusion, and virus entry and determine host range. Murine betacoronavirus (β-CoV) in group A uses the N-terminal domain (NTD) of S protein to bind to its receptor, whereas the β-CoVs severe acute respiratory syndrome CoV in group B and Middle East respiratory syndrome CoV in group C and several α-CoVs use the downstream C domain in their S proteins to recognize their receptor proteins. To identify the receptor-binding domain in the spike of human β-CoV HKU1 in group A, we generated and mapped a panel of monoclonal antibodies (MAbs) to the ectodomain of HKU1 spike protein. They did not cross-react with S proteins of any other CoV tested. Most of the HKU1 spike MAbs recognized epitopes in the C domain between amino acids 535 and 673, indicating that this region is immunodominant. Two of the MAbs blocked HKU1 virus infection of primary human tracheal-bronchial epithelial (HTBE) cells. Preincubation of HTBE cells with a truncated HKU1 S protein that includes the C domain blocked infection with HKU1 virus, but preincubation of cells with truncated S protein containing only the NTD did not block infection. These data suggest that the receptor-binding domain (RBD) of HKU1 spike protein is located in the C domain, where the spike proteins of α-CoVs and β-CoVs in groups B and C bind to their specific receptor proteins. Thus, two β-CoVs in group A, HKU1 and murine CoV, have evolved to use different regions of their spike glycoproteins to recognize their respective receptor proteins. IMPORTANCE Mouse hepatitis virus, a β-CoV in group A, uses the galectin-like NTD in its spike protein to bind its receptor protein, while HCoV-OC43, another β-CoV in group A, uses the NTD to bind to its sialic-acid containing receptor. In marked contrast, the NTD of the spike glycoprotein of human respiratory β-CoV HKU1, which is also in group A, does not bind sugar. In this study, we showed that for the spike protein of HKU1, the purified C domain, downstream of the NTD, could block HKU1 virus infection of human respiratory epithelial cells, and that several monoclonal antibodies that mapped to the C domain neutralized virus infectivity. Thus, the receptor-binding domain of HKU1 spike glycoprotein is located in the C domain. Surprisingly, two β-CoVs in group A, mouse hepatitis virus and HKU1, have evolved to use different regions of their spike glycoproteins to recognize their respective receptors.


title: Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for Coronavirus Exit from Endosomes.

text: UNLABELLED Coronaviruses are RNA viruses with a large zoonotic reservoir and propensity for host switching, representing a real threat for public health, as evidenced by severe acute respiratory syndrome (SARS) and the emerging Middle East respiratory syndrome (MERS). Cellular factors required for their replication are poorly understood. Using genome-wide small interfering RNA (siRNA) screening, we identified 83 novel genes supporting infectious bronchitis virus (IBV) replication in human cells. Thirty of these hits can be placed in a network of interactions with viral proteins and are involved in RNA splicing, membrane trafficking, and ubiquitin conjugation. In addition, our screen reveals an unexpected role for valosin-containing protein (VCP/p97) in early steps of infection. Loss of VCP inhibits a previously uncharacterized degradation of the nucleocapsid N protein. This inhibition derives from virus accumulation in early endosomes, suggesting a role for VCP in the maturation of virus-loaded endosomes. The several host factors identified in this study may provide avenues for targeted therapeutics. IMPORTANCE Coronaviruses are RNA viruses representing a real threat for public health, as evidenced by SARS and the emerging MERS. However, cellular factors required for their replication are poorly understood. Using genome-wide siRNA screening, we identified novel genes supporting infectious bronchitis virus (IBV) replication in human cells. The several host factors identified in this study may provide directions for future research on targeted therapeutics.