title: A newly developed tracheal tube offering 'pressurised sealing' outperforms currently available tubes in preventing cuff leakage: A benchtop study.

text: BACKGROUND No currently used tracheal tube offers full protection against aspiration of oropharyngeal secretions into the lower airways. OBJECTIVE We developed a tracheal tube equipped with two polyvinylchloride (PVC) cuffs with a supplementary port opening between the cuffs through which a continuous positive pressure of 5 cmH2O is provided [double-cuffed PVC (PVCdc)]. We compared this PVCdc with four different cuff types (cylindrical PVC, conical PVC, cylindrical polyurethane and conical polyurethane). DESIGN A comparison study using an in-vitro benchtop model of an artificial rigid trachea. INTERVENTIONS Tracheal tubes were placed in the artificial trachea. Both cuffs were kept inflated at 25 cmH2O. Total 3 ml dyed water was placed above the cuff and leakage recorded under static and dynamic [5 cmH2O positive end-expiratory pressure (PEEP) alone or positive pressure ventilation plus 5 cmH2O PEEP] conditions. At the end of the dynamic experiments, PEEP was zeroed (PEEP alone) or the tracheal tubes were disconnected from the ventilator (positive pressure ventilation plus PEEP). RESULTS In the static model, leakage flows [medians (range)] were 9.8 (6.2 to 20) for the cylindrical PVC, 1.3 (0.2 to 3.8) for the conical PVC, 0.03 (0.007 to 0.1) for the cylindrical polyurethane, 0.04 (0.003 to 0.2) for the conical polyurethane and 0.0 (0.0 to 0.0) ml min for the PVCdc cuff (P < 0.001, PVCdc vs. all other cuffs). In the dynamic setting, no leakage was detected for up to 60 min with any of the cuffs studied. Loss of PEEP or tracheal tube disconnection resulted in dye inflow alongside all cuffs except for the PVCdc (P < 0.001, PVCdc vs. all other cuffs). CONCLUSION A 'pressure seal' incorporated in a double-cuffed tracheal tube prevented fluid passage into the lower airways. Clinically, this may translate into absence of inflow of bacteriologically contaminated secretions into the lungs and thus a lower incidence of ventilator-associated infection.


title: Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease.

text: Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and that has now been declared a global pandemic by the World Health Organization. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In this context, this study aimed to evaluate in silico the molecular interactions of drugs with therapeutic indications for treatment of COVID-19 (Azithromycin, Baricitinib and Hydroxychloroquine) and drugs with similar structures (Chloroquine, Quinacrine and Ruxolitinib) in docking models from the SARS-CoV-2 main protease (M-pro) protein. The results showed that all inhibitors bound to the same enzyme site, more specifically in domain III of the SARS-CoV-2 main protease. Therefore, this study allows proposing the use of baricitinib and quinacrine, in combination with azithromycin; however, these computer simulations are just an initial step for conceiving new projects for the development of antiviral molecules.


Covid-19: Patients who are improving could have treatment withdrawn if others could benefit more.


title: Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

text: OBJECTIVES The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.


title: Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods.

text: BACKGROUND Hypothermia is being used with increasing frequency to prevent or mitigate various types of neurologic injury. In addition, symptomatic fever control is becoming an increasingly accepted goal of therapy in patients with neurocritical illness. However, effectively controlling fever and inducing hypothermia poses special challenges to the intensive care unit team and others involved in the care of critically ill patients. OBJECTIVE To discuss practical aspects and pitfalls of therapeutic temperature management in critically ill patients, and to review the currently available cooling methods. DESIGN Review article. INTERVENTIONS None. MAIN RESULTS Cooling can be divided into three distinct phases: induction, maintenance, and rewarming. Each has its own risks and management problems. A number of cooling devices that have reached the market in recent years enable reliable maintenance and slow and controlled rewarming. In the induction phase, rapid cooling rates can be achieved by combining cold fluid infusion (1500-3000 mL 4 degrees C saline or Ringer's lactate) with an invasive or surface cooling device. Rapid induction decreases the risks and consequences of short-term side effects, such as shivering and metabolic disorders. Cardiovascular effects include bradycardia and a rise in blood pressure. Hypothermia's effect on myocardial contractility is variable (depending on heart rate and filling pressure); in most patients myocardial contractility will increase, although mild diastolic dysfunction can develop in some patients. A risk of clinically significant arrhythmias occurs only if core temperature decreases below 30 degrees C. The most important long-term side effects of hypothermia are infections (usually of the respiratory tract or wounds) and bedsores. CONCLUSIONS Temperature management and hypothermia induction are gaining importance in critical care medicine. Intensive care unit physicians, critical care nurses, and others (emergency physicians, neurologists, and cardiologists) should be familiar with the physiologic effects, current indications, techniques, complications and practical issues of temperature management, and induced hypothermia. In experienced hands the technique is safe and highly effective.


title: Identification and differentiation of human schistosomes by polymerase chain reaction.

text: Recent increasing number of travelers, immigrants and foreign workers from schistosomiasis endemic area has thus resulted in the importation of schistosomiasis to non-endemic countries. To avoid ova-induced pathogenicity, sensitive and specific diagnostic means at an early stage of infection are therefore crucial. In this study, we developed polymerase chain reaction (PCR) primers specific for human schistosome species. The PCR products were obtained in a species-specific manner (479 bp, Schistosoma mansoni; 365 bp, S. haematobium; 614 bp, S. japonicum; 303 bp, S. mekongi) and were detectable from 0.01 pg of total worm DNA (S. haematobium, S. japonicum, S. mekongi). The primer sets were also available for multiplex use. Although some difficulties were experienced in amplifying the parasite DNA from the infected animals, schistosome DNA could be detected from one day post infection. The PCR method described herein will therefore be beneficial to detect human schistosomiasis, after some improvements in this method.


Redefining physicians' role in assisted dying.


title: Hiatal hernia repair with the use of biologic meshes: a literature review.

text: During the past few years, biologic meshes, primarily evolved for routine and complex cases of abdominal wall reconstruction, have been evaluated in clinical cases and experimental models. Although there is published experience on the use of small intestine submucosa and human cadaveric dermis in hiatal hernia repair with encouraging results, porcine dermal collagen (PDC) matrix has not been subject of study to date in this patient population. A systematic review of the literature was conducted, aiming at evaluating the biomechanical characteristics of cross-linked PDC in comparison to synthetic and biologic meshes. Evidence shows that cross-linked PDC is superior to synthetic meshes in terms of incorporation, adhesion formation, and mesh fibrosis; their biodynamic and biotechnical characteristics do not seem to be superior to other bioprosthetic materials according to current data. The clinical and experimental results of cross-linked PDC implants justify their pilot clinical evaluation in hiatal hernia patients.


title: Temporal relationship between environmental influenza A and Epstein-Barr viral infections and high multiple sclerosis relapse occurrence.

text: BACKGROUND Multiple sclerosis (MS) relapses have been associated with viral and bacterial infection epidemics in MS patients who have not used interferon. OBJECTIVES We studied whether environmental viral infections in the general population can be associated with increased MS relapse occurrence using retrospective data from 1986 to 1995 when interferons were not yet available. METHODS Logistic regression modelling was used to compare retrospectively the monthly relapse occurrence from 407 MS patients in Turku University hospital archives and data on ten different specifically diagnosed viral infection epidemics in the general population of Southwestern Finland from 1986 to 1995. The outcome was the odds ratio (OR) of very high relapse occurrence versus low relapse occurrence, or moderate versus low relapse occurrence. RESULTS After a peak in diagnosed influenza A cases in the general population, the MS relapse occurrence was 6.5 times more likely to be very high (95% CI 1.8-24.0) and 7.1 times more likely to be moderately high (95% CI 1.5-33.2). An increase in MS relapse counts also followed Epstein-Barr virus (EBV) infections (OR 4.4, 95% CI 1.3-15.1), but we found no significant association with adenovirus infections and MS relapses. The MS relapse occurrence was lowest in the summer months July-August (Chi-square test, p<0.01). CONCLUSIONS Our findings suggest that influenza A and EBV viral infections in the general population are associated with a higher occurrence of exacerbations in MS patients, and thus environmental infection data should be included in epidemiological models on MS relapses.


title: [Critical illness polyneuropathy and myopathy as neurological complications of sepsis].

text: Intensive care unit acquired weakness (ICUAW) is a frequent and severe complication of intensive care management. Within ICUAW critical illness polyneuropathy (CIP) and myopathy (CIM) can be differentiated. The major symptom of ICUAW is progressive quadriparesis, which makes weaning from the respirator more difficult, can appear early after admission to an ICU and can often be detected several months after discharge from the ICU. The pathophysiology of ICUAW is multifactorial and complex. Potential therapeutic approaches are the early and sufficient therapy of mulitorgan dysfunction, optimal control of glucose levels as well as early and intensive physiotherapy. This review article discusses the data on incidence, pathophysiology, diagnostic approaches and prognosis of ICUAW.


title: Expression and prognostic significance of pyruvate dehydrogenase kinase 1 in bladder urothelial carcinoma.

text: Muscular infiltrating bladder urothelial carcinoma (MIBC) is a highly malignant disease with a poor prognosis. Radical cystectomy is the standard treatment. However, due to surgery and postoperative complications, the quality of life of patients is seriously affected. Therefore, it is increasingly important to find prognostic markers and new therapeutic targets for MIBC. Here, we investigated the expression of PDK1, a key regulator of glucose metabolism, in bladder urothelial carcinoma (BLCA) and its effect on prognosis. The expression pattern of PDK1 was examined by bioinformatics analysis and immunohistochemistry. A total of 101 cases of BLCA were selected for tissue microarrays (TMAs) that contained both tumour and paired normal tissues. We demonstrated that PDK1 expression was correlated with tumour grade and Ki67expression in our TMA cohort (all p values < 0.05). Kaplan-Meier survival analysis showed that patients with MIBC with high PDK1 expression had a worse prognosis than patients with low PDK1 expression (p = 0.016). Multifactor risk analysis showed that increased PDK1 expression was an independent prognostic factor affecting the overall survival of MIBC patients. GSEA showed that the mTOR pathway, HIF pathway, glycolysis, PI3K/AKT/mTOR signalling, etc. were differentially enriched in the PDK1 high expression phenotype. Hence, PDK1 may be a prognostic and therapeutic target for MIBC.


title: Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease.

text: RATIONALE The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear. OBJECTIVES To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues. METHODS Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay. MEASUREMENTS AND MAIN RESULTS CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P < 0.001), IL-13 (P < 0.001), eotaxin-2 (P < 0.001), and monocyte chemoattractant protein (MCP)-4 (P < 0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not different among the chronic rhinosinusitis subtypes examined. Compared with CRSwNP, AERD NP had elevated protein levels of eosinophil cationic protein (ECP) (P < 0.001), granulocyte-macrophage colony-stimulating factor (GM-CSF) (P < 0.01), and MCP-1 (P = 0.01), as well as decreased gene expression of tissue plasminogen activator (tPA) (P = 0.02). Despite the higher eosinophilia in AERD, there was no associated increase in type 2 mediator protein levels observed. CONCLUSIONS CRSwNP was characterized by a predominant type 2 inflammatory environment, whereas CRSsNP did not reflect a classic type 1 milieu, as has been suggested previously. AERD can be distinguished from CRSwNP by elevated ECP levels, but this enhanced eosinophilia is not associated with elevations in traditional type 2 inflammatory mediators associated with eosinophil proliferation and recruitment. However, other factors, including GM-CSF, MCP-1, and tPA, may be important contributors to AERD pathogenesis.


title: Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs.

text: SUMMARYPatients undergoing solid-organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (HCT) are at increased risk for infectious complications. Community-acquired respiratory viruses (CARVs) pose a particular challenge due to the frequent exposure pre-, peri-, and posttransplantation. Although influenza A and B viruses have a top priority regarding prevention and treatment, recent molecular diagnostic tests detecting an array of other CARVs in real time have dramatically expanded our knowledge about the epidemiology, diversity, and impact of CARV infections in the general population and in allogeneic HCT and SOT patients. These data have demonstrated that non-influenza CARVs independently contribute to morbidity and mortality of transplant patients. However, effective vaccination and antiviral treatment is only emerging for non-influenza CARVs, placing emphasis on infection control and supportive measures. Here, we review the current knowledge about CARVs in SOT and allogeneic HCT patients to better define the magnitude of this unmet clinical need and to discuss some of the lessons learned from human influenza virus, respiratory syncytial virus, parainfluenzavirus, rhinovirus, coronavirus, adenovirus, and bocavirus regarding diagnosis, prevention, and treatment.


title: Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor.

text: Cytoplasmic RNA receptors are important in the detection of and response to viral infections. We analyzed ligand recognition by the retinoic acid-inducible protein I (RIG-I) protein in biochemical assays and in transiently transfected cells and characterized the requirements for both single- and double-stranded RNA agonists for RIG-I activation of signaling. RIG-I mutants such as K270A and T409A/S411A that were defective in signaling with triphosphorylated single-stranded RNAs were perfectly capable of signaling with dsRNAs. Furthermore, phosphorothioated oligodeoxynucleotides were found to antagonize RIG-I signaling. Both agonists and antagonist bind purified RIG-I protein and a truncated RIG-I protein that lacked the signaling domain. The agonists were necessary to activate RIG-I ATPase activity in vitro, whereas antagonist inhibited ATPase activity. Differential scanning fluorometry showed that RIG-I bound to agonists, and antagonists have different denaturation properties, suggesting a difference in protein conformations. Last, single particle reconstruction was used to generate three-dimensional models of the RIG-I dimers in complex with an agonist and an antagonist. The two complexes exhibited dramatically different structures.


title: Treatment of Insulinomas by Laparoscopic Radiofrequency Ablation: Case Reports and Literature Review.

text: Despite its rarity, insulinoma is the most common type of pancreatic endocrine neoplasm, with an occurrence of 1 to 5 per million per year in the population. Surgical resection or enucleation is the first line of curative treatment choice for insulinoma. Eight patients with symptomatic insulinomas treated by radiofrequency ablation have been described since 2009. In the past two years, we treated two patients with symptomatic insulinomas (one in the pancreatic tail and the other in the pancreatic neck) successfully using laparoscopic radiofrequency ablation. Both patients achieved complete elimination without any significant complications. Our study suggests laparoscopic radiofrequency ablation could be developed as a safe and effective alternative treatment to surgery for the patients with insulinomas who refuse or are not eligible for surgery.


title: Banxia Xiexin Decoction () Treats Diabetic Gastroparesis through PLC-IP3-Ca2+/NO-cGMP-PKG Signal Pathway.

text: OBJECTIVE To test the effect of Banxia Xiexin Decoction (, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro. METHODS Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP3), neuronal nitric oxide synthase (nNOS), and cyclic guanosine monophosphate (cGMP) dependent protein kinase G (PKG) were detected by reverse transcription-polymerase chain reaction and Western blot, respectively, while nitric oxide (NO) and cGMP expressions were detected by enzyme-linked immunosorbent assay. Gastric tissues were obtained from rats for primary cell culture preparation. Gastric SM cells were treated with 0.8 µmol/L of STZ or STZ plus 1,000, 500 and 200 µg/mL of BXD or STZ plus 2.5 µmol/mL of domperidone for 24, 48, 72 or 96 h, respectively. The length of gastric SM cells and intracellular Ca2+ concentration ([Ca2+]i) before and after BXD treatment was measured. RESULTS Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP3, NO, nNOS, cGMP and PKG in rat's gastric tissue (P<0.01). Gastric SM cells treated with BXD showed a time- and dose-dependent increase in cell viability (P<0.01). The treatment with high- and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased [Ca2+]i compared with the model cells (P<0.01). CONCLUSIONS Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca2+/NO-cGMP-PKG signal pathway.


title: Inhibition of Cytosolic Phospholipase A2α Impairs an Early Step of Coronavirus Replication in Cell Culture.

text: Coronavirus replication is associated with intracellular membrane rearrangements in infected cells, resulting in the formation of double-membrane vesicles (DMVs) and other membranous structures that are referred to as replicative organelles (ROs). The latter provide a structural scaffold for viral replication/transcription complexes (RTCs) and help to sequester RTC components from recognition by cellular factors involved in antiviral host responses. There is increasing evidence that plus-strand RNA (+RNA) virus replication, including RO formation and virion morphogenesis, affects cellular lipid metabolism and critically depends on enzymes involved in lipid synthesis and processing. Here, we investigated the role of cytosolic phospholipase A2α (cPLA2α) in coronavirus replication using a low-molecular-weight nonpeptidic inhibitor, pyrrolidine-2 (Py-2). The inhibition of cPLA2α activity, which produces lysophospholipids (LPLs) by cleaving at the sn-2 position of phospholipids, had profound effects on viral RNA and protein accumulation in human coronavirus 229E-infected Huh-7 cells. Transmission electron microscopy revealed that DMV formation in infected cells was significantly reduced in the presence of the inhibitor. Furthermore, we found that (i) viral RTCs colocalized with LPL-containing membranes, (ii) cellular LPL concentrations were increased in coronavirus-infected cells, and (iii) this increase was diminished in the presence of the cPLA2α inhibitor Py-2. Py-2 also displayed antiviral activities against other viruses representing the Coronaviridae and Togaviridae families, while members of the Picornaviridae were not affected. Taken together, the study provides evidence that cPLA2α activity is critically involved in the replication of various +RNA virus families and may thus represent a candidate target for broad-spectrum antiviral drug development.IMPORTANCE Examples of highly conserved RNA virus proteins that qualify as drug targets for broad-spectrum antivirals remain scarce, resulting in increased efforts to identify and specifically inhibit cellular functions that are essential for the replication of RNA viruses belonging to different genera and families. The present study supports and extends previous conclusions that enzymes involved in cellular lipid metabolism may be tractable targets for broad-spectrum antivirals. We obtained evidence to show that a cellular phospholipase, cPLA2α, which releases fatty acid from the sn-2 position of membrane-associated glycerophospholipids, is critically involved in coronavirus replication, most likely by producing lysophospholipids that are required to form the specialized membrane compartments in which viral RNA synthesis takes place. The importance of this enzyme in coronavirus replication and DMV formation is supported by several lines of evidence, including confocal and electron microscopy, viral replication, and lipidomics studies of coronavirus-infected cells treated with a highly specific cPLA2α inhibitor.


title: Effectiveness of an Eight-Week Web-Based Mindfulness Virtual Community Intervention for University Students on Symptoms of Stress, Anxiety, and Depression: A Randomized Controlled Trial.

text: BACKGROUND A student mental health crisis is increasingly acknowledged and will only intensify with the COVID-19 crisis. Given accessibility of methods with demonstrated efficacy in reducing depression and anxiety (e.g., mindfulness meditation and cognitive behavioural therapy [CBT]) and limitations imposed by geographic obstructions and localized expertise, web-based alternatives have become vehicles for scaled-up delivery of benefits at modest cost. Mindfulness Virtual Community (MVC), a web-based program informed by cognitive behavioral therapy (CBT) constructs and featuring online videos, discussion forums, and videoconferencing was developed to target depression, anxiety, and experiences of excess stress among university students. OBJECTIVE Assessment of an eight-week web-based mindfulness and cognitive behavioural therapy (CBT) program in reducing symptoms of depression, anxiety, and stress (primary outcomes) and increasing mindfulness (secondary outcome) within a randomized controlled trial (RCT) with undergraduate students at a large Canadian university. METHODS An RCT was designed to assess undergraduate students (n = 160) who were randomly allocated to a web-based guided mindfulness-CBT condition (n = 80) or to a waitlist control condition (WLC) (n = 80). The eight-week intervention consisted of a web-based platform consisting of (1) 12 video-based modules with psycho-education on students' preidentified life challenges and applied mindfulness practice; (2) anonymous peer-to-peer discussion forums; and (3) anonymous, group-based, professionally guided 20-minute live videoconferences. The outcomes (depression, anxiety, stress, and mindfulness) were measured via online survey at baseline and at eight weeks post-intervention using the Patient Health Questionniare-9 (PHQ9), the Beck Anxiety Inventory (BAI), the Perceived Stress Scale (PSS), and the Five Facets Mindfulness Questionnaire Short Form (FFMQ-SF). Analyses employed generalized estimation equation (GEE) methods with AR(1) covariance structures and were adjusted for possible covariates (gender, age, country of birth, ethnicity, English as first language, paid work, unpaid work, relationship status, physical exercise, self-rated health, and access to private mental health counselling). RESULTS Of the 159 students who provided T1 data, 32 were males and 125 were females with a mean age of 22.55 years. Participants in the MVC (n = 79) and WLC (n = 80) groups were similar in sociodemographic characteristics at T1 with the exception of gender and weekly hours of unpaid volunteer work. At post-intervention follow-up, per the adjusted comparisons, there were statistically significant between-group reductions in depression scores (β = -2.21, P = .01) and anxiety scores (β = -4.82, P = .006) and a significant increase in mindfulness scores (β = 4.84, P = .02) compared to WLC. There were no statistically significant differences in perceived stress for MVC (β = .64, P = .48) compared to WLC. CONCLUSIONS With MVC intervention, there were significantly reduced depression and anxiety symptoms but no significant effect on perceived stress. Online mindfulness interventions can be effective in addressing common mental health conditions among post-secondary populations on a large scale, simultaneously reducing the current burden on traditional counselling services. CLINICALTRIAL https://doi.org/10.1186/ISRCTN12249616.


title: [Partial Nephrectomy in cT1 Renal Tumours: Conventional Laparoscopic Partial Nephrectomy Compared with LESS Partial Nephrectomy in SITUS Technique].

text: BACKGROUND Partial nephrectomy is the treatment of choice for clinical stage 1 renal tumours. Open partial nephrectomy is the standard operative technique. The use of minimally-invasive strategies such as laparoscopic, robot-assisted partial nephrectomy or laparoendoscopic single site (LESS) partial nephrectomy has increased in recent years. PATIENTS/MATERIAL AND METHODS In this retrospective study, patients undergoing laparoscopic partial nephrectomy between December 2008 and November 2013 were evaluated. All patients presented with renal lesions suspicious for malignancy. Operations were performed as conventional laparoscopic transperitoneal partial nephrectomies (cLPN) or LESS partial nephrectomies (LESS-PN) in SITUS technique (single incision transumbilical surgery). The aim of the study was to compare perioperative outcome parameters such as duration of surgery, time of ischaemia, complications, need for transfusion, conversion rates, changes in renal function and duration of hospital stay in both groups. RESULTS A total of 85 laparoscopic partial nephrectomies were performed in this study (72 cLPN and 13 LESS-PN). The average tumour size was 2.68±1.47 cm (cLPN) vs. 2.46±1.11 cm (LESS-PN). The mean duration of surgery was 175.17±50.026 min (cLPN) and 185.77±35.991 min (LESS-PN). 45 (62.5%) operations (cLPN) vs. 10 (76.9%) (LESS-PN) were performed in zero-ischaemia technique. There were no significant differences in perioperative outcome parameters between both groups. Postoperative complication rates (Clavien-Dindo≥3) were 11.1% (cLPN) vs. 7.7% (LESS-PN). CONCLUSIONS LESS partial nephrectomy in SITUS technique is an attractive alternative to conventional laparoscopic and open partial nephrectomy.


title: Recent progress in laparoscopic liver resection.

text: Laparoscopic liver resection has been performed in a limited number of centers, but worldwide the adoption and worldwide progress of the procedure have been slow since the 1990s, mainly because of the difficulty of controlling the hemorrhage during dissection of the hepatic parenchyma. In the late 2000s, technological innovations, improvement in surgical technique, and surgeons' accumulation of experience have led to more rapid progress of laparoscopic liver resection. Now, laparoscopic liver resection is able to be done by several approaches, for all locations of the tumors, for several diseases, with several types of resection, not only for tumors but for liver transplantation, with equivalent or better results compared with open surgery. Laparoscopic liver resection has been a standard procedure for left lateral sectionectomy or peripheral resection of the anterior liver, and other types of laparoscopic liver resection are expected to be standard in the near future.


title: Isolation and molecular characterization of porcine epidemic diarrhea viruses collected in Japan in 2014.

text: Porcine epidemic diarrhea virus (PEDV) is the etiological agent of porcine epidemic diarrhea (PED), which is threatening the swine industry all over the world. In Japan, although there were no reported PED cases from 2007 to 2012, a large-scale PED outbreak started in 2013, causing severe economic losses. Although several PEDV studies have been conducted in Japan, more PEDV isolates and sequence information are needed to understand the molecular biology and epidemiology of PEDV. Here, we isolated seven Japanese PEDV strains from intestinal tissue samples collected in 2014 and determined the spike gene sequences of 13 Japanese PEDV strains, including the above seven isolates. Phylogenetic analysis shows that all of the strains are genetically distinct from classical Japanese PEDV strains isolated prior to 2013 and can be classified into two different genotypes: 12 strains belong to the North American clade composed of recent highly pathogenic PEDV strains, and the remaining one strain belongs to the so-called insertion deletion (INDEL) clade. These data suggest multiple PEDV invasions from abroad to Japan. Notably, compared to classical Japanese strains, all of the recent Japanese strains have two amino acid substitutions in a known neutralizing epitope. In addition, one of the strains acquired an additional mutation in another neutralizing epitope that is highly conserved among PEDVs, including the classical and recent isolates. Our isolates and findings will be useful for future investigations aimed at understanding, controlling, and preventing PED.


title: A genetic score can identify men at high risk for prostate cancer among men with prostate-specific antigen of 1-3 ng/ml.

text: BACKGROUND The diagnostic performance of a genetic score based on single nucleotide polymorphisms (SNPs) is unknown in the prostate-specific antigen (PSA) range of 1-3 ng/ml. A substantial proportion of men in this PSA span have prostate cancer (PCa), but biomarkers to determine who should undergo a prostate biopsy are lacking. OBJECTIVE To evaluate whether a genetic risk score identifies men in the PSA range of 1-3 ng/ml who are at higher risk for PCa. DESIGN, SETTING, AND PARTICIPANTS Men aged 50-69 yr with PSA 1-3 ng/ml and without a previous prostate biopsy were selected from the STHLM2 cohort. Of 2696 men, 49 SNPs were genotyped, and a polygenic risk score was calculated. Of these men, 860 were invited according to risk score, and 172 underwent biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The risk of PCa was assessed using univariate and multivariate logistic regression analysis. RESULTS AND LIMITATIONS PCa was diagnosed in 47 of 172 participants (27%), with Gleason sum 6 in 36 of 47 men (77%) and Gleason sum ≥7 in 10 of 47 men (21%); one man had intraductal cancer. The genetic score was a significant predictor of a positive biopsy (p=0.028), even after adjusting for PSA, ratio of free to total PSA, prostate volume, age, and family history. There was an increase in the odds ratio of 1.60 (95% confidence interval, 1.05-2.45) with increasing genetic risk score. The absolute risk difference of positive biopsy was 19 percentage points, comparing the high and low genetic risk group (37% vs 18%). CONCLUSIONS A risk score based on SNPs predicts biopsy outcome in previously unbiopsied men with PSA 1-3 ng/ml. Introducing a genetic-based risk stratification tool can increase the proportion of men being classified in line with their true risk of PCa.


title: Prevention of influenza at Hajj: applications for mass gatherings.

text: Outbreaks of infectious diseases that spread via respiratory route, e.g. influenza, are common amongst Hajj congregation in Mecca, Saudi Arabia. The Saudi Arabian authority successfully organized the Hajj 2009 amidst fear of pandemic influenza. While severe influenza A(H1N1)pdm09 was rare, the true burden of pandemic influenza at Hajj that year remains speculative. In this article we review the latest evidence on influenza control and discuss our experience of influenza and its prevention at Hajj and possible application to other mass gatherings. Depending on study design the attack rate of seasonal influenza at Hajj has ranged from 6% in polymerase chain reaction or culture confirmed studies to 38% in serological surveillance. No significant effect of influenza vaccine or the use of personal protective measures against influenza has been established from observational studies, although the uptake of the vaccine and adherence to face masks and hand hygiene has been low. In all, there is a relatively poor evidence base for control of influenza. Until better evidence is obtained, vaccination coupled with rapid antiviral treatment of symptomatic individuals remains the mainstay of prevention at Hajj and other mass gatherings. Hajj pilgrimage provides a unique opportunity to test the effectiveness of various preventive measures that require a large sample size, such as testing the efficacy of plain surgical masks against laboratory-confirmed influenza. After successful completion of a pilot trial conducted among Australian pilgrims at the 2011 Hajj, a large multinational cluster randomized controlled trial is being planned. This will require effective international collaboration.


The role of the environment and its pollution in the prevalence of COVID-19.


title: Reviewing clinical guideline development tools: features and characteristics.

text: BACKGROUND To improve consistency and streamline development and publication of clinical guidelines (GL), there is a need for appropriate software support. We have found few specific tools for the actual authoring and maintaining of GLs, and correspondingly few analyses or reviews of GL development tool functionality. In order to assist GL developers in selecting and evaluating tools, this study tries to address the perceived gap by pursuing four goals: 1) identifying available tools, 2) reviewing a representative group of tools and their supported functionalities, 3) uncovering themes of features that the studied tools support, and 4) compare the selected tools with respect to the themes. METHODS We conducted a literature search using PubMed and Google Scholar in order to find GL development tools (GDT). We also explored tools and Content Management Systems (CMS) used in representative organisations and international communities that develop and maintain GLs. By reading a selected representative group of five GL tool manuals, exploring tools hands-on, we uncovered 8 themes of features. All found tools were compared according to these themes in order to identify the level of functionality they offer to support the GL development and publishing process. In order to limit the scope, tools for designing computer-interpretable/executable GL are excluded. RESULTS After finding 1552 published papers, contacting 7 organizations and international communities, we identified a total of 19 unique tools, of which 5 tools were selected as representative in this paper. We uncovered a total of 8 themes of features according to the identified functionalities that each tool provides. Four features were common among tools: Collaborative authoring process support, user access control, GL repository management, electronic publishing. We found that the GRADE methodology was supported by three of the reviewed tools, while only two tools support annotating GL with MeSH terms. We also identified that monitoring progress, reference management, Managing versions (version control), and Change control (tracking) were often the missing features. CONCLUSION The results can promote sector discussion and eventual agreement on important tool functionality. It may aid tool and GL developers towards more efficient, and effective, GL authoring.


title: Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review.

text: IMPORTANCE Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm. OBJECTIVE To evaluate the clinical effectiveness of a perioperative, cardiac output-guided hemodynamic therapy algorithm. DESIGN, SETTING, AND PARTICIPANTS OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014. INTERVENTIONS Patients were randomly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366). MAIN OUTCOMES AND MEASURES The primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care-free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay. RESULTS Baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, -0.3% to 13.9%]; P = .07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]). CONCLUSIONS AND RELEVANCE In a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rates. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN04386758.


title: Family Presence During Resuscitation: A Double-Edged Sword.

text: PURPOSE To illuminate the meaning of the lived experiences of resuscitation team members with the presence of the patient's family during resuscitation in the cultural context of Iran. DESIGN An interpretative phenomenology was used to discover the lived experiences of the nurses and physicians of Tabriz hospitals, Iran, with family presence during resuscitation (FPDR). A total of 12 nurses and 9 physicians were interviewed over a 6-month period. METHODS The interviews were audio recorded and semistructured, and were transcribed verbatim. Van Manen's technique was used for data analysis. FINDINGS Two major themes and 10 subthemes emerged, including destructive presence (cessation of resuscitation, interference in resuscitation, disruption to the resuscitation team's focus, argument with the resuscitation team, and adverse mental image in the family) and supportive presence (trust in the resuscitation team, collaboration with the resuscitation team, alleviating the family's concern and settling their nerves, increasing the family's satisfaction, and reducing conflict with resuscitation team members). CONCLUSIONS Participants stated that FPDR may work as a double-edged sword for the family and resuscitation team, hurting or preserving quality. It is thus recommended that guidelines be created to protect patients' and families' rights, while considering the positive aspects of the phenomenon for hospitals. CLINICAL RELEVANCE A liaison support person would act to decrease family anxiety levels and would be able to de-escalate any potentially aggressive or confrontational events during resuscitation. Well-trained and expert cardiopulmonary resuscitation team members do not have any stress in the presence of family during resuscitation. Resuscitation events tend to be prolonged when family members are allowed to be present.


title: Basic Immunology may lead to translational therapeutic rationale:: SARS-CoV-2 and Rheumatic Diseases.

text: COVID-19 pandemia is a major concern for patients and health care systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analyzing the basic biology of single diseases, the data suggest that there is an "immunological umbrella" that seems to protect against the infection, through IFN type 1 and NK cell function. To date, reports from China, US and Europe, did not reveal an higher risk of infection, either for Rheumatoid Arthritis, Juvenile Idiopathic Arthritis nor for Lupus Erythematosus. Antimalarials, anti-IL6-Anti-IL6-receptor, anti-IL1, anti-GM-CSF-receptor , JAK1/2/3 inhibitors, are under investigation in COVID-dedicated clinical trials to control the inflammation raised by SARS-CoV-2 infection. Initial reports on the occurrence of autoimmune phenomena in the convalescence phase of SARS-CoV-2 infection, suggests that the immunological consequences of the infection need to be strictly understood.


title: Recruitment and retention of underrepresented populations in Alzheimer's disease research: A systematic review.

text: Introduction Alzheimer's disease and related dementias (ADRD) disproportionately impact racial and ethnic minority and socioeconomically disadvantaged adults. Yet, these populations are significantly underrepresented in research. Methods We systematically reviewed the literature for published reports describing recruitment and retention of individuals from underrepresented backgrounds in ADRD research or underrepresented participants' perspectives regarding ADRD research participation. Relevant evidence was synthesized and evaluated for quality. Results We identified 22 eligible studies. Seven studies focused on recruitment/retention approaches, all of which included multifaceted efforts and at least one community outreach component. There was considerable heterogeneity in approaches used, specific activities and strategies, outcome measurement, and conclusions regarding effectiveness. Despite limited use of prospective evaluation strategies, most authors reported improvements in diverse representation in ADRD cohorts. Studies evaluating participant views focused largely on predetermined explanations of participation including attitudes, barriers/facilitators, education, trust, and religiosity. Across all studies, the strength of evidence was low. Discussion Overall, the quantity and quality of available evidence to inform best practices in recruitment, retention, and inclusion of underrepresented populations in ADRD research are low. Further efforts to systematically evaluate the success of existing and emergent approaches will require improved methodological standards and uniform measures for evaluating recruitment, participation, and inclusivity.


title: Percutaneous radiofrequency ablation of a bleeding pseudoaneurysm during CT-guided renal cancer treatment. A case report.

text: We describe a new emergency interventional radiology approach in percutaneous procedure complications. We present the case of an 81-year-old male with small renal cancer, approached with percutaneous radiofrequency ablation (RTA) and complicated by pseudoaneurysm bleeding of a renal artery branch. In the emergency setting, pseudoaneurysm was treated in the CT room by the same RTA needle, without any complications or local tumor recurrence during the next 6-month follow-up.


A historical personal perspective on human retroviruses and their infection of T cells.


title: Update: Public Health Response to the Coronavirus Disease 2019 Outbreak - United States, February 24, 2020.

text: An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in Wuhan, Hubei Province, China in December 2019, and has spread throughout China and to 31 other countries and territories, including the United States (1). As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China (1). There have been 2,462 associated deaths worldwide; no deaths have been reported in the United States. Fourteen cases have been diagnosed in the United States, and an additional 39 cases have occurred among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. This report summarizes the aggressive measures (2,3) that CDC, state and local health departments, multiple other federal agencies, and other partners are implementing to slow and try to contain transmission of COVID-19 in the United States. These measures require the identification of cases and contacts of persons with COVID-19 in the United States and the recommended assessment, monitoring, and care of travelers arriving from areas with substantial COVID-19 transmission. Although these measures might not prevent widespread transmission of the virus in the United States, they are being implemented to 1) slow the spread of illness; 2) provide time to better prepare state and local health departments, health care systems, businesses, educational organizations, and the general public in the event that widespread transmission occurs; and 3) better characterize COVID-19 to guide public health recommendations and the development and deployment of medical countermeasures, including diagnostics, therapeutics, and vaccines. U.S. public health authorities are monitoring the situation closely, and CDC is coordinating efforts with the World Health Organization (WHO) and other global partners. Interim guidance is available at https://www.cdc.gov/coronavirus/index.html. As more is learned about this novel virus and this outbreak, CDC will rapidly incorporate new knowledge into guidance for action by CDC, state and local health departments, health care providers, and communities.


title: Antibacterial, Antitubercular and Antiviral Activity Evaluations of Some Arylidenehydrazide Derivatives Bearing Imidazo[2,1-b]thiazole Moiety.

text: Objectives The aim of this study was to determine the probable antibacterial, antitubercular, and antiviral activities of some N2 -arylidene-(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl) acetic acid hydrazides (3a-j). Further structural optimization of the identified lead structures can lead us to new more active potential antibacterial, antitubercular, and antiviral agents. Materials and Methods Antibacterial activities of the title compounds against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922. These molecules were also evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) using the BACTEC 460 radiometric system and BACTEC 12B medium. Moreover, all the compounds (3a-j) were also evaluated against some DNA and RNA viruses in Madin-Darby Canine Kidney, Crandell-Rees Feline Kidney (CRFK), Vero, human embryonic lung (HEL) and HeLa cells. Results Among the tested compounds, 3i displayed the highest efficacy against S. aureus and E. coli. Compound 3j, 5-nitro-2-furfurylidene derivative showed the highest antituberculosis activity (IC50: 6.16 µg/mL and IC90: 14.390 µg/mL). Compound 3i showed the most potent antiviral activity against feline corona virus in CRFK cell cultures (antiviral EC50: 7.5 µM and SI>13). Furthermore, compounds 3c and 3g displayed activity against herpes simplex virus-1 and vaccinia virus in HEL cell cultures (antiviral EC50 values of 9; 16 and 20; 14 µM, respectively). Conclusion On the basis of aforementioned results, it can be conluded that imidazo[2,1-b]thiazole derivatives bearing hydrazone moieties serve as promising chemical probes to design therapeutic agents with antibacterial, antitubercular, and antiviral properties.


title: Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis.

text: UNLABELLED ♦ BACKGROUND Peritoneal dialysis (PD) solutions containing icodextrin as the osmotic agent have advantages during long dwells. The glucose polymers that constitute icodextrin are a heterogeneous mix of molecules with a polydispersity [ratio of weight-average to number-average molecular weight (Mw/Mn)] of approximately 2.6. The present study evaluates whether modifications in the polydispersity and concentration of glucose polymers can improve ultrafiltration (UF) without an associated increase in carbohydrate absorption (CA). ♦ METHODS Computer simulations using a three-pore model of peritoneal transport during a long dwell in PD patients predict that, in general, compared with 7.5% icodextrin, glucose polymers with a Mw greater than or equal to 7.5 kDa, a polydispersity less than 2.6, and concentrations greater than 7% could achieve higher UF without higher CA. Based on the simulations, we hypothesized that, compared with 7.5% icodextrin, glucose polymers with a Mw of 18 - 19 kDa and a polydispersity of 2.0 at 11% concentration could achieve higher UF without a higher CA. We tested this hypothesis in experimental studies using 8-hour dwells in New Zealand White rabbits. In those studies, UF was measured by complete fluid collection, and CA was measured by subtracting the total carbohydrate in the collected fluid from the carbohydrate initially infused. ♦ RESULTS The UF was higher with 11% 19 kDa glucose polymer than with 7.5% icodextrin (mean ± standard deviation: 89 ± 31 mL vs 49 ± 15 mL; p = 0.004) without higher CA (5.2 ± 0.9 g vs 5.0 ± 0.9 g, p = 0.7). Similar results were seen with the 11% 18 kDa glucose polymer, which, compared with 7.5% icodextrin, resulted in higher UF (mean ± standard deviation: 96 ± 18 mL vs 66 ± 17 mL; p < 0.001) without higher CA (4.8 ± 0.7 g vs 5.2 ± 0.6 g, p = 0.2). ♦ CONCLUSIONS The findings demonstrate that, compared with 7.5% icodextrin solution, long-dwell PD solutions containing 11% glucose polymers with a Mw of 18-19 kDa and a polydispersity of 2.0 can provide higher UF without higher CA.


title: Using gene transcription patterns (bar coding scans) to guide wound debridement and healing.

text: PURPOSE To acquaint wound care practitioners with new information related to debridement of chronic wounds. TARGET AUDIENCE This continuing education activity is intended for physicians and nurses with an interest in wound care. OBJECTIVES After reading this article and taking this test, the reader should be able to: 1. Explain the role of keratinocytes in wound healing. 2. Discuss new research findings on the physiological differences between healing and nonhealing wounds.3. Identify implications of the new research for debridement of chronic wounds.


Commentary: Evolving understanding of coronavirus disease 2019: Molecular biology, immunology, and surgery.


title: Bringing stroke clinical guidelines to life.

text: Clinical practice guidelines are essential for driving evidence-based clinical care to patients. In an era of ever-increasing research evidence, keeping guidelines up to date is a challenging and resource-intensive process. Advances in technological platforms provide opportunities to develop new models of guideline development that will allow for continuous, rapid updates to recommendations as new evidence emerges. As Australia and other countries begin to develop these models, we have an opportunity to work more closely together to ensure the most efficient use of resources.


title: Stress detection using ECG and EMG signals: A comprehensive study.

text: BACKGROUND AND OBJECTIVE In recent years, stress and mental health have been considered as important worldwide concerns. Stress detection using physiological signals such as electrocardiogram (ECG), skin conductance (SC), electromyogram (EMG) and electroencephalogram (EEG) is a traditional approach. However, the effect of stress on the EMG signal of different muscles and the efficacy of combination of the EMG and other biological signals for stress detection have not been taken into account yet. This paper presents a comprehensive review of the EMG signal of the right and left trapezius and right and left erector spinae muscles for multi-level stress recognition. Also, the ECG signal was employed to evaluate the efficacy of EMG signals for stress detection. METHODS Both EMG and ECG signals were acquired simultaneously from 34 healthy students (23 females and 11 males, aged 20-37 years). Mental arithmetic, Stroop color-word test, time pressure, and stressful environment were employed to induce stress in the laboratory. RESULTS The accuracies of stress recognition in two, three and four levels were 100%, 97.6%, and 96.2%, respectively, obtained from the distinct combination of feature selection and machine learning algorithms. CONCLUSIONS The comparison of stress detection accuracies resulted from EMG and ECG indicators demonstrated the strong ability and the effectiveness of EMG signal for multi-level stress detection.


title: Laparoscopic right hemicolectomy.

text: Over the past 20 years, laparoscopic colectomy has become a well-established technique in the surgical armamentarium of colorectal operations, with proven reductions in postoperative pain, time to return of bowel function, and length of hospital stay. After early concerns over its oncologic effects, large prospective, multicenter trials have proven its safety in colorectal adenocarcinoma, with equivalence in nodal harvest, recurrence rates, disease-free survival, and overall survival. Laparoscopic right hemicolectomy in particular is a relatively accessible technique which may be performed by a single surgeon and an assistant/camera operator; this operation serves as an excellent method to develop laparoscopic skills for more complicated colorectal procedures. In this article, we describe the technical aspects of our approach to laparoscopic right hemicolectomy, which utilizes a medial-to-lateral, no-touch technique and either an intracorporeal or extracorporeal anastomosis.


title: Comparison between breast MRI and contrast-enhanced spectral mammography.

text: BACKGROUND The main goal of this study was to compare contrast-enhanced spectral mammography (CESM) and breast magnetic resonance imaging (MRI) with histopathological results and to compare the sensitivity, accuracy, and positive and negative predictive values for both imaging modalities. MATERIAL/METHODS After ethics approval, CESM and MRI examinations were performed in 102 patients who had suspicious lesions described in conventional mammography. All visible lesions were evaluated independently by 2 experienced radiologists using BI-RADS classifications (scale 1-5). Dimensions of lesions measured with each modality were compared to postoperative histopathology results. RESULTS There were 102 patients entered into CESM/MRI studies and 118 lesions were identified by the combination of CESM and breast MRI. Histopathology confirmed that 81 of 118 lesions were malignant and 37 were benign. Of the 81 malignant lesions, 72 were invasive cancers and 9 were in situ cancers. Sensitivity was 100% with CESM and 93% with breast MRI. Accuracy was 79% with CESM and 73% with breast MRI. ROC curve areas based on BI-RADS were 0.83 for CESM and 0.84 for breast MRI. Lesion size estimates on CESM and breast MRI were similar, both slightly larger than those from histopathology. CONCLUSIONS Our results indicate that CESM has the potential to be a valuable diagnostic method that enables accurate detection of malignant breast lesions, has high negative predictive value, and a false-positive rate similar to that of breast MRI.


title: AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA.

text: Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melanoma 2 (AIM2)-like receptors (ALRs) have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production. AIM2 antagonizes IFI205-mediated IFN induction activity by sequestering it from STING. We also found that the complement of genes located in the ALR locus in C57BL/6 and AIM2 knockout mice are different and unique, which has implications for interpretation of the sensing of pathogens in different mouse strains. Our data suggest that members of the ALR family are critical to the host IFN response to endogenous DNA.IMPORTANCE Autoimmune diseases like Aicardi-Goutières syndrome and lupus erythematosus arise when cells of the immune system become activated and attack host cells and tissues. We found that DNA generated by endogenous retroviruses and retroelements in inbred mice and mouse cells is recognized by several host proteins found in macrophages that are members of the ALR family and that these proteins both suppress and activate the pathways leading to the generation of cytokines and IFNs. We also show that there is great genetic diversity between different inbred mouse strains in the ALR genes, which might contribute to differential susceptibility to autoimmunity. Understanding how immune cells become activated is important to the control of disease.


APIC Strategic Partner Program.


title: Efficacy and safety of intravascular lithotripsy for the treatment of peripheral arterial disease: An individual patient-level pooled data analysis.

text: BACKGROUND Peripheral arterial disease (PAD) is one of the most common manifestations of atherosclerotic disease worldwide. Peripheral arterial calcification reduces acute success and long-term patency of endovascular therapy for PAD. Several calcium modification devices are available for use in peripheral interventions. Outcomes after peripheral intravascular lithotripsy (IVL), a novel approach using pulsatile sonic waves to treat luminal and medial calcium in patients with PAD, have not been extensively characterized. Therefore, we sought to perform an individual patient-level data (IPD) pooled analysis of available studies to evaluate the efficacy and safety of IVL in the treatment of PAD. METHODS AND RESULTS We pooled IPD, including baseline and procedural variables, from five prospective studies which assessed IVL in the treatment of patients with extensive peripheral artery calcification. Final postprocedural percent diameter stenosis (%DS) and procedural angiographic complications were assessed by independent core laboratory. Efficacy endpoints were analyzed using linear mixed effects models and safety endpoints were tabulated overall and by vascular bed. Among 336 patients who underwent endovascular revascularization with use of IVL, there was a significant reduction between pre-procedural and final %DS of 55.1% (95% confidence interval 53.3-57.0%, p < .0001). Core-laboratory assessed lesion-level complications, including flow-limiting dissections (Types D-F), vessel perforation, distal embolization, thrombus, abrupt closure, and no reflow, occurred in 4/328 (1.22%) of treated lesions. CONCLUSIONS The present IPD of five prospective studies, marking the largest analysis to date evaluating the use of IVL in significantly calcified PAD lesions, demonstrates this treatment strategy to be both effective and safe.


title: The energetic cost of mounting an immune response for Pallas's long-tongued bat (Glossophaga soricina).

text: The acute phase response (APR) is the first line of defense of the vertebrate immune system against pathogens. Mounting an immune response is believed to be energetically costly but direct measures of metabolic rate during immune challenges contradict this assumption. The energetic cost of APR for birds is higher than for rodents, suggesting that this response is less expensive for mammals. However, the particularly large increase in metabolic rate after APR activation for a piscivorous bat (Myotis vivesi) suggests that immune response might be unusually costly for bats. Here we quantified the energetic cost and body mass change associated with APR for the nectarivorous Pallas's long-tongued bat (Glossophaga soricina). Activation of the APR resulted in a short-term decrease in body mass and an increase in resting metabolic rate (RMR) with a total energy cost of only 2% of the total energy expenditure estimated for G. soricina. This increase in RMR was far from the large increase measured for piscivorous bats; rather, it was similar to the highest values reported for birds. Overall, our results suggest that the costs of APR for bats may vary interspecifically. Measurement of the energy cost of vertebrate immune response is limited to a few species and further work is warranted to evaluate its significance for an animal's energy budget.


title: Simulation as a Tool to Facilitate Practice Changes in Teams Taking Care of Patients Under Investigation for Ebola Virus Disease in Spain.

text: INTRODUCTION We analyzed the impact of simulation-based training on clinical practice and work processes on teams caring for patients with possible Ebola virus disease (EVD) in Cantabria, Spain. METHODS The Government of Spain set up a special committee for the management of EVD, and the Spanish Ministry of Health and foreign health services created an action protocol. Each region is responsible for selecting a reference hospital and an in-house care team to care for patients under investigation. Laboratory-confirmed cases of EVD have to be transferred to the Carlos III Health Institute in Madrid. Predeployment training and follow-up support are required to help personnel work safely and effectively. Simulation-based scenarios were designed to give staff the opportunity to practice before encountering a real-life situation. Lessons learned by each team during debriefings were listed, and a survey administered 3 months later assessed the implementation of practice and system changes. RESULTS Implemented changes were related to clinical practice (eg, teamwork principles application), protocol implementation (eg, addition of new processes and rewriting of confusing parts), and system and workflow (eg, change of shift schedule and rearrangement of room equipment). CONCLUSIONS Simulation can be used to detect needed changes in protocol or guidelines or can be adapted to meet the needs of a specific team.


title: Varicella zoster meningitis: an atypical case of zoster reactivation in immunocompetent young adult.

text: Varicella virus is a neurotropic virus that can reactivate later in life to cause zoster or shingles. Typically, it affects elderly, immunocompromised population. We report an unusual case of an immunocompetent young adult presenting with occipital headache and zoster rash, without preherpetic and postherpetic neuralgia, who was diagnosed with varicella meningitis on Polymerase chain reaction (PCR). He was treated with intravenous acyclovir and later discharged on famciclovir. Diagnosis of varicella meningitis is difficult in the absence of typical features of zoster rash and requires high index of suspicion. Rapid diagnostic tests including varicella PCR and antithecal antibody testing can help in the confirmation of varicella zoster meningitis.


title: Fear of Ebola: The Influence of Collectivism on Xenophobic Threat Responses.

text: In response to the Ebola scare in 2014, many people evinced strong fear and xenophobia. The present study, informed by the pathogen-prevalence hypothesis, tested the influence of individualism and collectivism on xenophobic response to the threat of Ebola. A nationally representative sample of 1,000 Americans completed a survey, indicating their perceptions of their vulnerability to Ebola, ability to protect themselves from Ebola (protection efficacy), and xenophobic tendencies. Overall, the more vulnerable people felt, the more they exhibited xenophobic responses, but this relationship was moderated by individualism and collectivism. The increase in xenophobia associated with increased vulnerability was especially pronounced among people with high individualism scores and those with low collectivism scores. These relationships were mediated by protection efficacy. State-level collectivism had the same moderating effect on the association between perceived vulnerability and xenophobia that individual-level value orientation did. Collectivism-and the set of practices and rituals associated with collectivistic cultures-may serve as psychological protection against the threat of disease.


JCVI response on hepatitis B vaccination.


title: Clinical Indicators of the Need for Telemetry Postoperative Monitoring in Patients With Suspected Obstructive Sleep Apnea Undergoing Total Knee Arthroplasty.

text: BACKGROUND AND OBJECTIVES Obstructive sleep apnea is associated with increased complication rates postoperatively. Current literature does not provide adequate guidance on management of these patients. This study used the STOP-Bang questionnaire to diagnose patients with possible obstructive sleep apnea (score ≥3). We hypothesized that a STOP-Bang score of 3 or greater would significantly correlate with the number of oxygen desaturation episodes during the first 48 hours after total knee arthroscopy. METHODS The STOP-Bang questionnaire was administered to 110 patients preoperatively. All patients underwent spinal-epidural anesthesia with a saphenous nerve block and sedation and were connected to the Nellcor OxiMax N-600x pulse oximeter for 48 hours postoperatively. RESULTS Final analysis included 98 patients. There was no significant difference in the total number of desaturation events between STOP-Bang groups (score <3 vs ≥3 and score <5 vs ≥5). The total number of desaturation events on postoperative day 1 was greater than that on day 0 (32.8 ± 42.7 vs 4.1 ± 10.0, P < 0.0001). The total number of desaturation events correlated with length of hospital stay (r = 0.329, P = 0.0001). Patients with a preoperative serum CO2 of 30 mmol/L or greater had significantly longer episodes of desaturation on postoperative day 0 compared with CO2 of less than 30 mmol/L (233.7 ± 410.1 vs 82.0 ± 126.2 seconds, P = 0.044). CONCLUSIONS A high preoperative value of CO2 should be a warning for possible prolonged episodes of desaturation postoperatively. An attempt to limit postoperative desaturation events should be made to minimize length of stay.


title: Endovascular therapy after intravenous t-PA versus t-PA alone for stroke.

text: BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8-19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P=0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.).


title: The COVID-19 Epidemic and the Prison System in Italy.

text: The Italian Ministry of Justice and that of Health have established two strategies to limit the spread of COVID-19 in prisons: progressive isolation from the external world and adoption of practices to identify possible cases and to treat infected subjects. After the announcement of regulations revolts erupted in numerous Italian prisons. The motivations and effects of these strategy are discussed critically into the search for a balance between the right to health and other rights of prisoners in Italian prisons with the problem of an occupancy level of 121.75%.


title: TransForm occlusion balloon catheter for the treatment of intracranial aneurysms, initial experience.

text: INTRODUCTION The technique of balloon remodeling allows the endovascular treatment of wide-neck intracranial aneurysms. For many years the only available devices were the Hyperform and the Hyperglide balloon catheters. Recently, other companies have developed newer devices, single or dual-lumen. We present our initial experience with the TransForm occlusion balloon catheter for the treatment of intracranial aneurysms. METHODS We retrospectively analysed from our prospectively gathered aneurysm database all aneurysms that were treated with balloon remodelling using TransForm occlusion balloon catheters from January 2013 to February 2014. We assessed patient demographics, morphological features of the aneurysms, procedure feasibility, technical and clinical complications. RESULTS Thirty-three patients harbouring 36 intracranial saccular aneurysms were treated during 33 procedures. Clinical finding were: 15 incidental discovery, 13 subarachnoid haemorrhage (SAH), five aneurysms with mass effect, one ruptured aneurysm with SAH and mass effect, one recanalisation and one intraparenchymal haematoma. Thirty-five aneurysms were in the anterior and one in the posterior circulation. Mean dome and neck size were, respectively, 5.8 mm and 3.6 mm. Twenty-three aneurysms were treated with TransForm C and 13 with TransForm SC. We had two procedural thromboembolic complications, without permanent clinical events. No early rebleeding occurred. CONCLUSIONS In our small series, the TransForm occlusion balloon catheter seems to be safe and effective for the treatment of intracranial aneurysms, in ruptured and unruptured cases.


title: Comparison of thromboelastography parameters between different catheter lumen diameters in an uncontrolled haemorrhagic shock model in swine.

text: Sampling technique is a concern for standardization of thromboelastography (TEG), as it contributes towards preanalytical variation in TEG tracings. The objective of this study was to assess the influence of catheter lumen diameter on TEG parameters with kaolin-activated native blood in a swine haemorrhagic shock model, using standardized sampling techniques. We hypothesized that one or more TEG parameters will differ between venous samples collected from catheters with different diameter lumens. Ten male landrace swine were included in the study. Standard cut-down techniques on both femoral veins were performed and catheterized with a 14-gauge (14G) and a 20-gauge (20G) catheter of the same length. Blood withdrawal times were standardized to 3 s and TEG parameters (R, K, α, maximum amplitude, G and coagulation index) were measured or calculated. Significant differences were detected for R (14G < 20G; P = 0.002), K (14G < 20G; P = 0.026), maximum amplitude (14G > 20G; P = 0.02), G (14G > 20G; P = 0.001) and coagulation index (14G > 20G; P < 0.001). No significant differences were measured for α (P = 0.058). Bias values (method A: 20G; method B: 14G) for R, K, α, maximum amplitude, G and coagulation index were 1.00, 0.14, -1.88, -1.56, -1.39 and -1.07, respectively. Using TEG analysis, kaolin-activated native whole blood samples obtained from 14G catheters are hypercoagulable (clotted faster and stronger clot) compared with samples obtained from 20G catheters. Sampling methodology should be standardized and systematic when comparing TEG parameters.


title: Detection of Nipah virus RNA in fruit bat (Pteropus giganteus) from India.

text: The study deals with the survey of different bat populations (Pteropus giganteus, Cynopterus sphinx, and Megaderma lyra) in India for highly pathogenic Nipah virus (NiV), Reston Ebola virus, and Marburg virus. Bats (n = 140) from two states in India (Maharashtra and West Bengal) were tested for IgG (serum samples) against these viruses and for virus RNAs. Only NiV RNA was detected in a liver homogenate of P. giganteus captured in Myanaguri, West Bengal. Partial sequence analysis of nucleocapsid, glycoprotein, fusion, and phosphoprotein genes showed similarity with the NiV sequences from earlier outbreaks in India. A serum sample of this bat was also positive by enzyme-linked immunosorbent assay for NiV-specific IgG. This is the first report on confirmation of Nipah viral RNA in Pteropus bat from India and suggests the possible role of this species in transmission of NiV in India.


title: Principled leadership in public health: integrating ethics into practice and management.

text: Public health officials frequently face ethical tensions and conflicting obligations when making decisions and managing health departments. Leadership requires an ongoing approach to ethics that focuses on two dimensions of practice: the professional relationships of officials developed over time with their communities and the ethical aspects of day-to-day public health activities. Education and competencies in ethics may be helpful in practice, by providing, at a minimum, frameworks and ethical principles to help structure analysis, discussion, and decision making in health departments and with community stakeholders. Such a "practical ethics" approach in public health practice begins with a focus on public health values and an agency mission statement and integrates ethics throughout the organization by, for example, setting performance measures based on them. Using a case in emergency preparedness, this article describes ways in which ethical frameworks and the Code of Ethics can be used as tools for education and to integrate ethics into agency activities and programs.


title: Sex differences in the traumatic stress response: PTSD symptoms in women recapitulated in female rats.

text: BACKGROUND Post-traumatic stress disorder (PTSD) affects men and women differently. Not only are women twice as likely as men to develop PTSD, they experience different symptoms and comorbidities associated with PTSD. Yet the dearth of preclinical research on females leaves a notable gap in understanding the underlying neuropathology of this sex difference. METHODS Using two standard measures of PTSD-like responses in rats, the acoustic startle response (ASR) and dexamethasone suppression test (DST), we tested the effects of traumatic stress in adult male and female rats using two rodent models of PTSD, single prolonged stress and predator exposure. We then examined the neural correlates underlying these responses with cFos and glucocorticoid receptor immunohistochemistry in brain regions implicated in the traumatic stress response. RESULTS We now report that adult male and female rats across two models of PTSD show consistent sex-specific responses that recapitulate fundamental differences of PTSD in men and women. Trauma-exposed males showed the well-established hyper-responsive phenotype of enhanced ASR and exaggerated negative feedback control of the hypothalamic-pituitary-adrenal axis, while the same traumatic event had little effect on these same measures in females. Dramatic sex differences in how trauma affected cFos and glucocorticoid receptor expression in the brain lend further support to the idea that the trauma response of male and female rats is fundamentally different. CONCLUSIONS Two standard measures, ASR and DST, might suggest that females are resilient to the effects of traumatic stress, but other measures make it clear that females are not resilient, but simply respond differently to trauma. The next important question to answer is why. We conclude that males and females show fundamentally different responses to trauma that do not simply reflect differences in resilience. The divergent effects of trauma in the brains of males and females begin to shed light on the neurobiological underpinnings of these sex differences, paving the way for improved diagnostics and therapeutics that effectively treat both men and women.


title: Finding Camel-ot: A Holy Grail against pandemic SARS-CoV-2?

text: Engineered camelid antibody multimers can potently block SARS-CoV-2 viral entry.


title: Laparoscopic hernia complexity predicts operative time and length of stay.

text: PURPOSE Laparoscopic ventral hernia repair (LVHR) is associated with shorter hospitalization and lower complication rates compared to open ventral hernia repair. We sought to determine if hernia-related factors, such as defect size and re-operative status correlate with postoperative complications, operative times and length of stay (LOS). METHODS The study is a retrospective review of 30-day perioperative outcomes following LVHR in 91 patients who underwent surgery at a single institution from August 2009 through June 2012. A single surgeon performed all procedures. RESULTS Indications for surgery were recurrent incisional hernia in 33 % of patients and primary incisional or ventral abdominal hernias in the rest. Coated polyester mesh with an average size of 348 cm(2) (±214; range 113-1,036) was used. Mean operative time was 132 min (±66.1; range 53-412). The mean LOS was 4.0 days (±3.5; range 1-22). Complications occurred in 13 patients for overall morbidity of 16.5 % and no mortality. There was one recurrence in 30 days (1.1 %). Patients who had a surgery >120 min or a LOS >1 day were statistically more likely to have multiple hernias, larger defect sizes (>40 cm(2)), larger mesh sizes (>300 cm(2)) or a history of recurrent hernia (P < 0.05). No other clinical or demographic variable evaluated in this study correlated with operative time or LOS. CONCLUSIONS LVHR is safe with a low incidence of perioperative complications. Patients with multiple, larger and recurrent hernias have longer operative times and LOS. This information can be used to guide preoperative planning for the patient, surgeon and treating institution.


title: Effectiveness of Revive SE in the RAPID registry : Revive Acute Ischemic Stroke Patients ImmeDiately (RAPID) Prospective Multicenter Trial.

text: PURPOSE The prospective, multicenter Revive Acute ischemic stroke Patients ImmeDiately (RAPID) trial was carried out to evaluate the real-world safety and efficacy of the Revive SE stent retriever. METHODS From January 2017 the study planned to enroll 100 patients with acute ischemic stroke who were treated with the Revive SE as a first pass. The study primary outcomes were rates of favorable reperfusion using the modified thrombolysis in cerebral infarction score [mTICI] 2b/3 and rates of favorable outcome with the modified Rankin Scale (mRS) ≤2 at 3 months. The secondary outcomes were time interval from puncture to vascular reperfusion, number of passes by Revive SE stent-retriever, incidence of distal embolization and into new territories and rate of symptomatic intracranial hemorrhage (SICH) within 24 h post intervention. RESULTS A total of 100 treated patients (mean age: 65.6 ± 11.3 years) were enrolled. The median National Institutes of Health Stroke Scale before the procedure was 16. Target vessel occlusions were as follows: middle cerebral artery (MCA) M1 in 48, M2 in 6, anterior cerebral artery (ACA) in 3, internal carotid artery (ICA) in 22, basilar artery (BA) in 17, and vertebral artery (VA) in 4. Reperfusion rate with Revive SE without rescue devices was 69%. Reperfusion rate with Revive SE only was 83.3% in MCA M2, followed by 82.4% in BA. Thromboembolic complications and SICH developed in 10% and 2% of patients, respectively. Overall, a satisfactory reperfusion was achieved in 92% and a favorable outcome at 90 days in 48%. CONCLUSION Use of the Revive SE for thrombectomy appeared to be effective and safe but these findings need be confirmed in larger clinical trials (RAPID ClinicalTrials.gov number, NCT03007082).


title: Use of failure modes, effects, and criticality analysis to compare the vulnerabilities of laparoscopic versus open appendectomy.

text: PURPOSE To measure the feasibility of using FMECA applied to the surgery and then compare the vulnerabilities of laparoscopic versus open appendectomy by using FMECA. METHODS The FMECA study was performed on each single selected phase of appendectomy and on complication-related data during the period January 1, 2009, to December 31, 2010. The risk analysis phase was completed by evaluation of the criticality index (CI) of each appendectomy-related failure mode (FM). The CI is calculated by multiplying the estimated frequency of occurrence (O) of the FM, by the expected severity of the injury to the patient (S), and the detectability (D) of the FM. RESULTS In the first year of analysis (2009), 177 appendectomies were performed, 110 open and 67 laparoscopic. Eleven adverse events were related to the open appendectomy: 1 bleeding (CI: 8) and 10 postoperative infections (CI: 32). Three adverse events related to the laparoscopic approach were recorded: 1 postoperative infection (CI: 8) and 2 incorrect extractions of the appendix through the umbilical port (CI: 6). In the second year of analysis (2010), 158 appendectomies were performed, 69 open and 89 laparoscopic. Four adverse events were related to the open appendectomy: 1 incorrect management of the histological specimen (CI: 2), 1 dehiscence of the surgical wound (CI: 6), and 2 infections (CI: 6). No adverse events were recorded in laparoscopic approach. CONCLUSION FMECA helped the staff compare the 2 approaches through an accurate step-by-step analysis, highlighting that laparoscopic appendectomy is feasible and safe, associated with a lower incidence of infection and other complications, reduced length of hospital stay, and an apparent lower procedure-related risk.


title: Successful laparoscopic gastric resection and safe introduction of a single-incision technique for gastric submucosal tumors located near the esophagogastric junction.

text: PURPOSE Laparoscopic gastric resection cannot be easily applied for submucosal tumors near the esophagogastric junction (NEJ-SMTs). Furthermore, there have been no reports of single-incision laparoscopic surgery (SILS) for NEJ-SMTs. We evaluated our laparoscopic surgical outcomes for NEJ-SMTs, including a newly introduced phase of SILS. METHODS We retrospectively reviewed a total of 18 patients diagnosed with NEJ-SMTs who underwent laparoscopic surgery between April 2002 and September 2013. RESULTS All patients underwent laparoscopic gastric resection without local complications and with a negative surgical margin, including 12 patients treated with conventional laparoscopic surgery (CLS) and six patients treated with SILS. The mean length of the operation was 184.3 ± 52.3 min, and the mean blood loss was 19.2 ± 17.7 mL. All patients underwent complete resection. There were no statistically significant differences between the CLS and SILS groups in terms of the surgical outcomes. CONCLUSION Despite this challenging location of the tumor, laparoscopic gastric resection for NEJ-SMTs is safe and feasible. Furthermore, SILS can provide a better cosmetic result, which can lead to better global patient satisfaction in carefully selected patients with NEJ-SMTs.


title: The hepatitis C virus RNA-dependent RNA polymerase directs incoming nucleotides to its active site through magnesium-dependent dynamics within its F motif.

text: RNA viruses synthesize new genomes in the infected host thanks to dedicated, virally-encoded RNA-dependent RNA polymerases (RdRps). As such, these enzymes are prime targets for antiviral therapy, as has recently been demonstrated for hepatitis C virus (HCV). However, peculiarities in the architecture and dynamics of RdRps raise fundamental questions about access to their active site during RNA polymerization. Here, we used molecular modeling and molecular dynamics simulations, starting from the available crystal structures of HCV NS5B in ternary complex with template-primer duplexes and nucleotides, to address the question of ribonucleotide entry into the active site of viral RdRp. Tracing the possible passage of incoming UTP or GTP through the RdRp-specific entry tunnel, we found two successive checkpoints that regulate nucleotide traffic to the active site. We observed that a magnesium-bound nucleotide first binds next to the tunnel entry, and interactions with the triphosphate moiety orient it such that its base moiety enters first. Dynamics of RdRp motifs F1 + F3 then allow the nucleotide to interrogate the RNA template base prior to nucleotide insertion into the active site. These dynamics are finely regulated by a second magnesium dication, thus coordinating the entry of a magnesium-bound nucleotide with shuttling of the second magnesium necessary for the two-metal ion catalysis. The findings of our work suggest that at least some of these features are general to viral RdRps and provide further details on the original nucleotide selection mechanism operating in RdRps of RNA viruses.


title: The mechanism and energetics of a ligand-controlled hydrophobic gate in a mammalian two pore channel.

text: In the last decade two-pore intracellular channels (TPCs) attracted the interest of researchers, still some key questions remain open. Their importance for vacuolar (plants) and endo-lysosomal (animals) function highlights them as a very attractive system to study, both theoretically and experimentally. Indicated as key players in the trafficking of the cell, today they are considered a new potential target for avoiding virus infections, including those from coronaviruses. A particular boost for theoretical examinations has been made with recent high-resolution X-ray and cryo-EM structures. These findings have opened the way for efficient and precise computational studies at the atomistic level. Here we report a set of multiscale-calculations performed on the mTPC1, a ligand- and voltage-gated sodium selective channel. The molecular dynamics and enhanced molecular dynamics simulations were used for a thorough analysis of the mammalian TPC1 behaviour in the presence and absence of the ligand molecule, with a special accent on the supposed bottleneck, the hydrophobic gate. Moreover, from the reconstructed free energy obtained from enhanced simulations, we have calculated the macroscopic conductance of sodium ions through the mTPC1, which we compared with measured single-channel conductance values. The hydrophobic gate works as a steric barrier and the key parameters are its flexibility and the dimension of the sodium first hydration shell.


title: Effects of sleep disordered breathing on functional capacity and quality of life in chronic kidney disease Egyptian patients.

text: PURPOSE We assessed the prevalence of sleep disordered breathing (SDB) and investigated its effects on the muscle functional capacity and quality of life (QoL) among chronic kidney disease (CKD) Egyptian patients, either maintained or not maintained on hemodialysis (HD). METHODS The study population comprised 100 CKD patients who were divided into patients maintained on HD (n = 60; M/F = 28:32) and patients not maintained on HD (n = 40; M/F = 24:16). Patients were observed overnight using the pulse-oximetry technique and further subdivided into patients with SDB and patients without SDB, according to their calculated oxygen desaturation index (cutoff 5). All patients were subjected also to estimation of Kt/V ratio (which is a measure for the efficiency of HD), body-composition analysis, biochemical analysis, muscle functional capacity, and QoL measurements using standard methods and questionnaires, respectively. RESULTS Primary outcomes were intergroup differences regarding physical capacity and muscle performance, QoL, and body-composition measurements. CKD patients in general, either maintained on HD or not, suffer from SDB, and the levels of urea and creatinine may increase the incidence of SDB in CKD patients not maintained on HD. CKD patients maintained on HD with SDB had poorer functional capacity, physical performance, and muscle composition, in comparison with those without SDB. CONCLUSIONS Overall, SDB appears to partly contribute to the total diminished functional capacity of HD patients. Thus, CKD patients maintained on HD with SDB had significantly lower sleep quality and QoL as compared to those not maintained on HD with or without SDB.


title: A randomised controlled trial of the effect of laryngeal mask airway manometry on postoperative sore throat in spontaneously breathing adult patients presenting for surgery at a university teaching hospital.

text: Background Laryngeal mask airways (LMAs) are widely used in anaesthesia and are considered to be generally safe. Postoperative sore throat (POST) is a frequent complication following LMA use and can be very distressing to patients. The use of an LMA cuff pressure of between 30 and 32cm of H2O in alleviating post-operative sore throat has not been investigated. Objective To compare the occurrence of POST between the intervention group in which LMA cuff pressures were adjusted to 30-32cm of H2O and the control group in which only monitoring of LMA cuff pressures was done, to compare the severity of POST between the two study groups and to compare the LMA cuff pressures between the two study groups. Methods Eighty consenting adult patients scheduled to receive general anaesthesia with use of an LMA were randomized into two groups of 40 patients each. Intervention group: LMA airway cuff pressures were adjusted to 30 to 32cm of H2O. Control group: Only had LMA cuff pressures monitored throughout the surgery. All patients were interviewed postoperatively at two, six and twelve hours. Data of their baseline characteristics, occurrence and severity of POST was collected. If POST was present; a Numerical Rating Scale (NRS) was used to assess the severity. Cuff pressures between the two study groups were also determined. Results The baseline demographic characteristics of the participants were similar. The use of manometry to limit LMA AMBU® AuraOnce™ intracuff pressure to 30-32cm H2O reduced POST in surgical patient's by 62% at 2 hours and 6 hours (Risk Ratio 0.38 95%CI 0.21-0.69)in the intervention group. The median POST pain score in the intervention group was significantly lower than the control group with scores of 0 at 2, 6 and 12 hours post operatively. Routine practice of LMA cuff inflation by anesthesiologists is variable, and the intracuff pressures in the control group were higher than in the intervention group. (P<0.001). Conclusion Among this population, reduction of LMA AMBU® AuraOnce™ intracuff pressure to 30-32cm H2O reduces the occurrence and severity of POST. The LMA cuff pressures should be measured routinely using manometry and reducing the intracuff pressures to 30-32 cm of H2O recommended as best practice.


title: High-throughput, luciferase-based reverse genetics systems for identifying inhibitors of Marburg and Ebola viruses.

text: Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant challenge to global public health. Currently, no licensed therapies exist to treat filovirus infections, which cause up to 90% mortality in human cases. To facilitate development of antivirals against these viruses, we established two distinct screening platforms based on MARV and EBOV reverse genetics systems that express secreted Gaussia luciferase (gLuc). The first platform is a mini-genome replicon to screen viral replication inhibitors using gLuc quantification in a BSL-2 setting. The second platform is complementary to the first and expresses gLuc as a reporter gene product encoded in recombinant infectious MARV and EBOV, thereby allowing for rapid quantification of viral growth during treatment with antiviral compounds. We characterized these viruses by comparing luciferase activity to virus production, and validated luciferase activity as an authentic real-time measure of viral growth. As proof of concept, we adapt both mini-genome and infectious virus platforms to high-throughput formats, and demonstrate efficacy of several antiviral compounds. We anticipate that both approaches will prove highly useful in the development of anti-filovirus therapies, as well as in basic research on the filovirus life cycle.