title: DC-SIGN and L-SIGN Are Attachment Factors That Promote Infection of Target Cells by Human Metapneumovirus in the Presence or Absence of Cellular Glycosaminoglycans.

text: UNLABELLED It is well established that glycosaminoglycans (GAGs) function as attachment factors for human metapneumovirus (HMPV), concentrating virions at the cell surface to promote interaction with other receptors for virus entry and infection. There is increasing evidence to suggest that multiple receptors may exhibit the capacity to promote infectious entry of HMPV into host cells; however, definitive identification of specific transmembrane receptors for HMPV attachment and entry is complicated by the widespread expression of cell surface GAGs. pgsA745 Chinese hamster ovary (CHO) cells are deficient in the expression of cell surface GAGs and resistant to HMPV infection. Here, we demonstrate that the expression of the Ca(2+)-dependent C-type lectin receptor (CLR) DC-SIGN (CD209L) or L-SIGN (CD209L) rendered pgsA745 cells permissive to HMPV infection. Unlike infection of parental CHO cells, HMPV infection of pgsA745 cells expressing DC-SIGN or L-SIGN was dynamin dependent and inhibited by mannan but not by pretreatment with bacterial heparinase. Parental CHO cells expressing DC-SIGN/L-SIGN also showed enhanced susceptibility to dynamin-dependent HMPV infection, confirming that CLRs can promote HMPV infection in the presence or absence of GAGs. Comparison of pgsA745 cells expressing wild-type and endocytosis-defective mutants of DC-SIGN/L-SIGN indicated that the endocytic function of CLRs was not essential but could contribute to HMPV infection of GAG-deficient cells. Together, these studies confirm a role for CLRs as attachment factors and entry receptors for HMPV infection. Moreover, they define an experimental system that can be exploited to identify transmembrane receptors and entry pathways where permissivity to HMPV infection can be rescued following the expression of a single cell surface receptor. IMPORTANCE On the surface of CHO cells, glycosaminoglycans (GAGs) function as the major attachment factor for human metapneumoviruses (HMPV), promoting dynamin-independent infection. Consistent with this, GAG-deficient pgaA745 CHO cells are resistant to HMPV. However, expression of DC-SIGN or L-SIGN rendered pgsA745 cells permissive to dynamin-dependent infection by HMPV, although the endocytic function of DC-SIGN/L-SIGN was not essential for, but could contribute to, enhanced infection. These studies provide direct evidence implicating DC-SIGN/L-SIGN as an alternate attachment factor for HMPV attachment, promoting dynamin-dependent infection via other unknown receptors in the absence of GAGs. Moreover, we describe a unique experimental system for the assessment of putative attachment and entry receptors for HMPV.


title: Epidemiology of Respiratory Pathogens in Children with Lower Respiratory Tract Infections in Shanghai, China, from 2013 to 2015.

text: This study aimed to explore the epidemiology of pathogens in children who were hospitalized with lower respiratory tract infections (LRTIs) at the Children's Hospital of Fudan University, Shanghai, China. Children aged less than 18 years who were hospitalized with LRTIs were enrolled from January 2013 to December 2015. Respiratory specimens were collected for the detection of common respiratory viruses, atypical bacteria, and other bacteria using current laboratory diagnostic tests. The epidemiological characteristics of the respiratory pathogens were analyzed. Of the 10,123 specimens obtained from the patients, 5,966 (58.7%) were positive for at least 1 pathogen. Mycoplasma pneumoniae (M.pneumoniae) was the most commonly detected pathogen (15.7%), followed by respiratory syncytial virus (RSV) (13.9%). Co-infections were found in 11.4% of patients. Of these co-infections, viral-bacterial co-infections were the most common. The detection rates for the respiratory pathogens varied considerably by age. RSV was the most common pathogen in children aged less than 24 months. Clear seasonal peaks were observed for RSV, M. pneumoniae, parainfluenza virus, human metapneumovirus, Moraxella catarrhalis, and Haemophilus influenza infections. Our findings demonstrate specific epidemiological patterns in children with LRTIs in Shanghai, China.


title: Laparoscopic surgery for obese patients with colon cancer: a case-matched control study.

text: PURPOSE This study compared the results of laparoscopic surgery for colon cancer in obese patients with a body-mass index (BMI) of 25 kg/m(2) or higher with those in nonobese patients (BMI <25 kg/m(2)) who were matched for clinicohistopathological factors. METHODS The oncologic outcomes were compared between 140 patients with a BMI of 25 kg/m(2) or higher (obese group) and 140 patients with a BMI of <25 kg/m(2) (nonobese group) that were matched for sex, tumor location, date of operation, and pTNM stage. RESULTS The proportion of patients with postoperative complications was significantly higher in the obese group (15 %) than in the nonobese group (6 %). The disease-free survival rate and overall survival rate in patients with stage I or II disease were similar in the obese group (98.6 and 98.8 %, respectively) and the nonobese group (97.8 and 97.8 %, respectively). The disease-free survival rate and overall survival rate in patients with stage III disease also did not differ significantly between the obese group (77.2 and 79.4 %, respectively) and the nonobese group (83.4 and 84.9 %, respectively). CONCLUSIONS Postoperative complications and long-term oncologic outcomes were similar in obese and nonobese patients who underwent laparoscopic colectomy for colon cancer in this hospital.


title: Structural dynamics as a contributor to error-prone replication by an RNA-dependent RNA polymerase.

text: RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp) are attenuated. The ability to predict residues of the RdRp required for faithful incorporation of nucleotides represents an essential step in any pipeline intended to exploit perturbed fidelity as the basis for rational design of vaccine candidates. We used x-ray crystallography, molecular dynamics simulations, NMR spectroscopy, and pre-steady-state kinetics to compare a mutator (H273R) RdRp from poliovirus to the wild-type (WT) enzyme. We show that the nucleotide-binding site toggles between the nucleotide binding-occluded and nucleotide binding-competent states. The conformational dynamics between these states were enhanced by binding to primed template RNA. For the WT, the occluded conformation was favored; for H273R, the competent conformation was favored. The resonance for Met-187 in our NMR spectra reported on the ability of the enzyme to check the correctness of the bound nucleotide. Kinetic experiments were consistent with the conformational dynamics contributing to the established pre-incorporation conformational change and fidelity checkpoint. For H273R, residues comprising the active site spent more time in the catalytically competent conformation and were more positively correlated than the WT. We propose that by linking the equilibrium between the binding-occluded and binding-competent conformations of the nucleotide-binding pocket and other active-site dynamics to the correctness of the bound nucleotide, faithful nucleotide incorporation is achieved. These studies underscore the need to apply multiple biophysical and biochemical approaches to the elucidation of the physical basis for polymerase fidelity.


title: Requirements for independent community-based quality assessment and accountability practices in humanitarian assistance and disaster relief activities.

text: During responses to disasters, the credibility of humanitarian agencies can be threatened by perceptions of poor quality of the responses. Many initiatives have been introduced over the last two decades to help address these issues and enhance the overall quality of humanitarian response, often with limited success. There remain important gaps and deficiencies in quality assurance efforts, including potential conflicts of interest. While many definitions for quality exist, a common component is that meeting the needs of the "beneficiary" or "client" is the ultimate determinant of quality. This paper examines the current status of assessment and accountability practices in the humanitarian response community, identifies gaps, and recommends timely, concise, and population-based assessments to elicit the perspective of quality performance and accountability to the affected populations. Direct and independent surveys of the disaster-affected population will help to redirect ongoing aid efforts, and generate more effective and comparable methods for assessing the quality of humanitarian practices and assistance activities.


title: Performance Characteristics of Xpert Flu/RSV XC Assay.

text: The Xpert Flu/RSV XC assay was compared to laboratory-developed tests (LDTs) (n = 207) and the Xpert Flu assay (n = 147) using archived nasopharyngeal swabs. The percentages of positive agreements with LDTs were 97.8% for influenza A, 97.2% for influenza B, and 89.3% for RSV. The sensitivity of influenza detection was improved with the Xpert Flu/RSV XC assay compared to the Xpert Flu assay.


title: Massive splenomegaly in children: laparoscopic versus open splenectomy.

text: BACKGROUND AND OBJECTIVES Laparoscopic splenectomy for massive splenomegaly is still a controversial procedure as compared with open splenectomy. We aimed to compare the feasibility of laparoscopic splenectomy versus open splenectomy for massive splenomegaly from different surgical aspects in children. METHODS The data of children aged <12 years with massive splenomegaly who underwent splenectomy for hematologic disorders were retrospectively reviewed in 2 pediatric surgery centers from June 2004 until July 2012. RESULTS The study included 32 patients, 12 who underwent laparoscopic splenectomy versus 20 who underwent open splenectomy. The mean ages were 8.5 years and 8 years in the laparoscopic splenectomy group and open splenectomy group, respectively. The mean operative time was 180 minutes for laparoscopic splenectomy and 120 minutes for open splenectomy. The conversion rate was 8%. The mean amount of intraoperative blood loss was 60 mL in the laparoscopic splenectomy group versus 110 mL in the open splenectomy group. Postoperative atelectasis developed in 2 cases in the open splenectomy group (10%) and 1 case in the laparoscopic splenectomy group (8%). Oral feeding postoperatively resumed at a mean of 7.5 hours in the laparoscopic splenectomy group versus 30 hours in the open splenectomy group. The mean hospital stay was 36 hours in the laparoscopic splenectomy group versus 96 hours in the open splenectomy group. Postoperative pain was less in the laparoscopic splenectomy group. CONCLUSION Laparoscopic splenectomy for massive splenomegaly in children is safe and feasible. Although the operative time was significantly greater in the laparoscopic splenectomy group, laparoscopic splenectomy was associated with statistically significantly less pain, less blood loss, better recovery, and shorter hospital stay. Laparoscopic splenectomy for pediatric hematologic disorders should be the gold-standard approach regardless of the size of the spleen.


title: Lavage-induced Surfactant Depletion in Pigs As a Model of the Acute Respiratory Distress Syndrome (ARDS).

text: Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future therapies. Severe lung injury with a reproducible deterioration of pulmonary gas exchange and hemodynamics can be induced in anesthetized pigs using repeated lung lavages with warmed 0.9% saline (50 ml/kg body weight). Including standard respiratory and hemodynamic monitoring with clinically applied devices in this model allows the evaluation of novel therapeutic strategies (drugs, modern ventilators, extracorporeal membrane oxygenators, ECMO), and bridges the gap between bench and bedside. Furthermore, induction of lung injury with lung lavages does not require the injection of pathogens/endotoxins that impact on measurements of pro- and anti-inflammatory cytokines. A disadvantage of the model is the high recruitability of atelectatic lung tissue. Standardization of the model helps to avoid pitfalls, to ensure comparability between experiments, and to reduce the number of animals needed.


title: Long-term anatomic and functional results of laparoscopic sacrocolpopexy: a prospective study.

text: PURPOSE The aim of our study was to assess the impact of laparoscopic sacrocolpopexy on pelvic symptoms, quality of life and sexual function in patients with symptomatic pelvic organ prolapse. Secondary goals included the assessment of anatomical correction, recurrence and complication rates. METHODS This is a prospective, single-center study that included 82 patients between 2009 and 2016. A clinical evaluation took place before surgery, and was repeated at 3, 12, 36 and 60 months postoperatively. Patients routinely received an anterior prosthesis, associated with a posterior prosthesis in case of symptomatic rectocele. Patients included self-administered questionnaires for functional pelvic problems (PFDI-20), quality of life (PFIQ-7), and sexual function (PISQ-12), and a clinical examination with POP-Q staging, at each medical visit. RESULTS Functional pelvic problems derived from prolapse (PFDI-20 scores) and their impact on patients' quality of life (PFIQ-7 score) significantly improved at 3, 12, 36 and 60 months postoperatively. Improvement on sexual activity was significant at 3 and 60 months postoperatively. Effective prolapse anatomical correction (POP-Q score < 2) was found in 94.4% and 97.2% of patients at the anterior and middle stages, respectively, at the end of follow-up, but only in 80.3% at the posterior stage. Symptomatic recurrence required surgical intervention in 4 patients (5.3%). CONCLUSIONS This long-term follow-up prospective analysis confirms the good functional and anatomical results of laparoscopic sacrocolpopexy for pelvic organ prolapse.


title: Lymphoma Risk and Overall Safety Profile of Adalimumab in Patients With Crohn's Disease With up to 6 Years of Follow-Up in the Pyramid Registry.

text: OBJECTIVES Real-world, prospective, long-term studies in Crohn's disease (CD) characterizing adalimumab safety data and lymphoma risk were lacking. We present the final results from the PYRAMID registry, which was designed to rule out a doubling of lymphoma risk in adalimumab-treated patients with CD. METHODS Patients with moderately to severely active CD newly prescribed or currently receiving adalimumab according to local product labels were followed for up to 6 years and analyzed for adverse events (AEs). The registry exposure-adjusted observed rate of lymphoma was compared with the estimated background lymphoma rate from a sex-matched general population in the Surveillance, Epidemiology, and End Results 17 Registry database adjusted for anticipated prior or concurrent thiopurine use in a CD population. RESULTS A total of 5025 patients were evaluated (16680.4 PY of adalimumab registry exposure, ≈3 years/patient mean follow-up). Registry treatment-emergent AEs included 4129 serious AEs (n = 1853 [36.9%]; 24.8 E/100 PY), 792 serious infections (n = 556 [11.1%]; 4.7 E/100 PY), and 134 malignancies (n = 116 [2.3%]; 0.8 E/100 PY), including ten lymphomas. The observed lymphoma rate (0.060 E/100 PY) was lower than the estimated background rate (0.084 E/100 PY), and the upper bound of the one-sided 95% CI of the observed rate (0.102 E/100 PY) was lower than double the estimated rate (0.168 E/100 PY). CONCLUSIONS PYRAMID is the longest prospective adalimumab study in routine clinical practice, with up to 6 years of follow-up. No new safety signals were reported. The pre-specified registry objective of ruling out a doubling of lymphoma risk with adalimumab was met.


title: [Role of cyclophilin A during coronavirus replication and the antiviral activities of its inhibitors].

text: Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.


title: CT correlation with outcomes in 15 patients with acute Middle East respiratory syndrome coronavirus.

text: OBJECTIVE The purpose of this article is to retrospectively analyze chest CT findings for 15 patients with Middle East respiratory syndrome coronavirus and to identify features associated with survival. MATERIALS AND METHODS Patients were assigned to group 1 if they died (n=9) and to group 2 if they made a full recovery (n=6). Two reviewers scored chest radiographs and CT examinations for segmental involvement, ground-glass opacities, consolidation, and interstitial thickening. RESULTS Eight patients had ground-glass opacity (53%), five had ground-glass and consolidation in combination (33%), five had pleural effusion (33%), and four patients had interlobular thickening (27%). Of 281 CT findings, 151 (54%) were peripheral, 68 (24%) were central, and 62 (22%) had a mixed location. The number of involved lung segments was higher in group 1. The lower lobe was more commonly involved (mean, 12.2 segments) than in the upper and middle lobes combined (mean, 6.3 segments). The mean number of lung segments involved was 12.3 segments in group 1 and 3.4 segments in group 2. The CT lung score (mean±SD, 15.78±7.9 vs 7.3±5.7, p=0.003), chest radiographic score (20.8±1.7 vs 5.6±5.4; p=0.001), and mechanical ventilation duration (13.11±8.3 vs 0.5±1.2 days; p=0.002) were higher in group 1. All nine group 1 patients and three of six group 2 patients had pleural effusion (p=0.52). CONCLUSION CT of patients with Middle East respiratory syndrome coronavirus predominantly showed ground-glass opacities, with peripheral lower lobe preference. Pleural effusion and higher CT lung and chest radiographic scores correlate with poor prognosis and short-term mortality.


title: Retrieval of migrated coils with stent retrievers: an animal study.

text: BACKGROUND AND PURPOSE Coil migration is a potentially serious complication of endovascular aneurysm treatment. The aim of the study was to systematically investigate the effectiveness of coil retrieval with a stent retriever in an animal model. MATERIALS AND METHODS A total of 148 coils of various types and sizes were placed into arteries of varying diameters in a porcine in vivo model. Coil retrieval was performed by placing a Trevo ProVue stent retriever over the coil and trying to trap a part of the platinum coil within the stent mesh by advancing the microcatheter over the stent or simply by retrieving the stent without trying to trap the coil by advancing the microcatheter. RESULTS Coil retrieval was successful in 101 of 102 cases (99%), in which trapping of the coil within the stent retriever by advancing the microcathter was applied. When we only pulled back the stent without trapping the coil, retrieval was successful in only 5 of 46 cases (11%). Coil type, coil structure (2D versus 3D), actual coil shape in the affected vessel, investigator experience, aspiration, coil localization, and vessel diameter had no significant influence on retrieval outcome. There was no case of vessel perforation. CONCLUSIONS Retrieval of migrated platinum coils with a stent retriever is an effective treatment option for migrated coils when the correct technique is applied.


title: Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection.

text: During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic viruses, iDCs are essential for re-stimulating virus-specific CD8(+) T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. Lack of iDCs in Toso-deficient (Toso(-/-)) mice reduced CD8(+) T-cell function in the liver and resulted in virus persistence. Furthermore, Toso(-/-) DCs failed to induce autoimmune diabetes in the rat insulin promoter-glycoprotein (RIP-GP) autoimmune diabetes model. In conclusion, we found that Toso has an essential role in the differentiation and maturation of iDCs, a process that is required for the control of persistence-prone virus infection.


title: Inflammation of left atrial epicardial adipose tissue is associated with paroxysmal atrial fibrillation.

text: BACKGROUND Although an increased epicardial adipose tissue (EAT) volume around the left atrium (LA) is related to the atrial fibrillation (AF) burden, the role of EAT inflammation in AF is unclear. We investigated the association between AF and inflammation of the EAT around the LA. METHODS We retrospectively identified regions of EAT around the LA and measured the density of these areas using computed tomography (CT). RESULTS A total of 32 patients who underwent their first catheter ablation for paroxysmal AF (PAF) were enrolled (mean age 62.5±11.1 years). Patients without a history of AF (n=32), but who underwent cardiac CT and were matched by age, sex, and metabolic risk factors, were enrolled in the control group (62.2±12.1 years). The mean EAT density around the LA was significantly higher in the PAF group than in the control group (-108.1±6.7 vs. -111.6±5.5 Hounsfield units; p=0.02), while the densities of subcutaneous adipose tissue (SAT) in the abdomen and thorax did not differ between the two groups. In a multiple logistic regression analysis, a higher EAT density was significantly associated with the presence of PAF after adjusting for other risk factors (odds ratio: 1.25; 95% confidence interval: 1.08-1.45, p=0.003). CONCLUSIONS This study supports the hypothesis that inflammation of EAT around the LA, but not SAT, is related to the presence of PAF.


title: Behavior of a new long-chain cyanoacrylate tissue adhesive used for mesh fixation in hernia repair.

text: BACKGROUND Synthetic tissue adhesives (TA) are sometimes used in hernia repair surgery. This study compares the use of a new, noncommercial, long-chain cyanoacrylate (n-octyl) TA and Ifabond for mesh fixation. MATERIALS AND METHODS In two implant models in the rabbit, expanded polytetrafluorethylene meshes were fixed to the parietal peritoneum using a TA or tacks (intraperitoneal model), or polypropylene meshes used to repair partial abdominal wall defects were fixed with a TA or sutures (extraperitoneal model). Animals were euthanized 14 or 90 d postsurgery and implant specimens were processed for microscopy (labeling of macrophages and apoptotic cells), peritoneal fluid and biomechanical strength testing. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determinated in peritoneal fluid. RESULTS Mesothelial cell deposition on the intraperitoneal implants fixed using the new TA and Ifabond was adequate and similar IL-6 and TNF-α levels were detected in these implants. Intraperitoneal meshes fixed with tacks showed IL-6 overexpression. Three months after surgery, macrophage and apoptotic cell rates were higher for the intraperitoneal implants fixed with Ifabond versus the new TA or tacks. In the extraperitoneal model, reduced macrophage and cell damage responses were observed in the meshes fixed with sutures versus both TA. Tensile strengths were greater for the tacks versus TA in the intraperitoneal implants and similar for the sutures and TA in the extraperitoneal implants (90 d). CONCLUSIONS Both TA showed a good cell response in both models. Their use in an intraperitoneal location resulted in reduced tensile strength compared with the tacks. However, strengths were comparable when extraperitoneal implants were fixed with these adhesives or sutures.


title: The operation of cost-effective on-site process for the bio-treatment of mixed municipal solid waste in rural areas.

text: The application of on-site waste treatment significantly reduces the need for expensive waste collection and transportation in rural areas; hence, it is considered of fundamental importance in developing countries. In this study, the effects of in-field operation of two types of mini-scale on-site solid waste treatment facilities on de-centralized communities, one using mesophilic two-phase anaerobic digestion combined with composting (TPAD, 50 kg/d) and another using decentralized composting (DC, 0.6-2 t/d), were investigated. Source-separated collection was applied to provide organic waste for combined process, in which the amount of waste showed significant seasonal variation. The highest collection amount was 0.18 kg/capital day and 0.6 kg/household day. Both sites showed good performance after operating for more than 6 months, with peak waste reduction rates of 53.5% in TPAD process and 63.2% in DC process. Additionally, the windrow temperature exceeded 55 °C for >5 days, indicating that the composting products from both facilities were safe. These results were supported by 4 days aerobic static respiration rate tests. The emissions were low enough to avoid any impact on nearby communities (distance <100 m). Partial energy could be recovered by the combined process but with complicated operation. Hence, the choice of process must be considered in case separately.


title: Generation of Full-length Infectious cDNA Clones of Middle East Respiratory Syndrome Coronavirus.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 and its infection has been reported over 20 countries. Roughly 10,000 human cases were reported and fatality reaches up to 40%. The majority of cases occurred in Saudi Arabia and mostly sporadic outside the country except the outbreak in South Korea in 2015. The Korean MERS-CoV isolate was isolated from the second Korean patient and its genome was fully sequenced and deposited. To develop virus-specific protective and therapeutic agents against the Korean isolate and to investigate molecular determinants of virus-host interactions, it is of paramount importance to generate its full-length cDNA. Here we report that two full-length cDNA's of a Korean patient-isolated MERS-CoV strain are generated by combination of the conventional cloning techniques and efficient Gibson assembly reactions. The full-length cDNA's were validated by restriction analysis and its sequence was verified by Sanger method. Resulting cDNA was efficiently transcribed in vitro and showing the T7 promoter-driven expression is robust. The resulting reverse genetic system will add to the published list of MERS-CoV cDNA's and facilitate the development of Korean isolate-specific antiviral measures.


title: Outcomes of children with severe bronchopulmonary dysplasia who were ventilator dependent at home.

text: OBJECTIVE To describe the incidence and outcomes of children with chronic respiratory failure secondary to severe bronchopulmonary dysplasia (BPD) on chronic positive pressure ventilation (PPV) via tracheostomy at home. METHODS We retrospectively reviewed medical charts of patients with severe BPD who were PPV dependent at home and who were enrolled in a university-affiliated home ventilator program between 1984 and 2010. We excluded patients with other comorbidities that could contribute to the development of chronic respiratory failure. We reported the incidence of these children in Indiana and cumulative incidences of survival, liberation from PPV, and decannulation. RESULTS Over 27 years, 628 children were cared for in our home ventilator program. Of these, 102 patients met inclusion criteria: 83 (81.4%) were alive and 19 (18.6%) were deceased. Sixty-nine patients (67.6%) were liberated from PPV, and 97.1% of them were weaned before their fifth birthday, with a median age at liberation of 24 months (interquartile range, 19-33). Similarly, 60 patients (58.8%) were decannulated, of which 96.7% completed this process before their sixth birthday, with a median age at decannulation of 37.5 months (interquartile range, 31.5-45). The incidence of children with chronic respiratory failure secondary to BPD who were PPV-dependent at home in Indiana was 1.23 per 100 000 live births in 1984 and increased to 4.77 per 100 000 live births in 2010. CONCLUSIONS Although extreme prematurity associated with severe BPD necessitating PPV at home carries significant risks of morbidity and mortality, successful liberation from mechanical ventilation and decannulation are likely to occur.


title: Applying Gerontological Social Work Perspectives to the Coronavirus Pandemic.

text: Social workers are familiar with the challenges brought on by the coronavirus pandemic; and we apply three gerontological social work perspectives that might increase our chances of minimizing negative outcomes and improving health and quality of life for everyone. First, the reality that the older population is very heterogeneous challenges ageism and age-stereotyping that has surfaced with COVID-19. Second, concepts of cumulative disadvantage and intersectionality offer clear explanations of the disparities that are being illuminated and lead us to advocate for fundamental changes to reduce disparities in later life and for people across the life course. Third, a strength-based perspective highlights the assets of the older population and the opportunities for positive developments coming out of the crisis. We can capitalize on momentum to increase advance care planning, to reduce social isolation, and expand the use of on-line technology for service provision. We can bolster our arguments to support older workers, volunteers, and caregivers. The fact that these social work perspectives are so applicable to the coronavirus situation reminds us of their fundamental relevance. Gerontological social work has much to offer in our roles as researchers, educators, practitioners, and advocates during this crisis, and our foundational principles serve us well.


title: SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype.

text: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The relentless spread and pathogenicity of the virus have become a global public health emergency. One of the striking features of this pandemic is the pronounced impact on specific regions and ethnic groups. In particular, compared with East Asia, where the virus first emerged, SARS-CoV-2 has caused high rates of morbidity and mortality in Europe. This has not been experienced in past global viral infections, such as influenza, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and is unique to SARS-CoV-2. For this reason, we investigated the involvement of genetic factors associated with SARS-CoV-2 infection with a focus on angiotensin-converting enzyme (ACE)-related genes, because ACE2 is a receptor for SARS-CoV-2. We found that the ACE1 II genotype frequency in a population was significantly negatively correlated with the number of SARS-CoV-2 cases. Similarly, the ACE1 II genotype was negatively correlated with the number of deaths due to SARS-CoV-2 infection. These data suggest that the ACE1 II genotype may influence the prevalence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.


title: Preliminary in vitro angiographic comparison of the flow diversion behavior of Evolve and Pipeline devices.

text: BACKGROUND AND PURPOSE Flow diverters are increasingly used to treat a broad category of cerebral aneurysms. We conducted an in vitro study to angiographically compare the flow diversion effect of Surpass Evolve from Stryker Neurovascular with the Pipeline Shield Embolization Device from Medtronic Neurovascular. METHODS Three copies each of three carotid aneurysm geometries were manufactured from silicone. Evolve and Pipeline flow diverters were deployed in one copy of each geometry; the third copy was used as Control. High-speed angiography was acquired under pulsatile flow in each replica, contrast concentration-time curves within the aneurysms were recorded, and the curves were quantified with six parameters. The parameters were statistically evaluated to compare the flow diversion effect of both devices. RESULTS The Evolve showed greater flow diversion trends in almost all intra-geometry comparisons than the Pipeline. When aggregated over the three geometries, the Evolve was statistically significantly better than the Pipeline in four of the six parameters, and about the same or better (not statistically significant) than the Pipeline in the other two parameters. CONCLUSIONS The Evolve device demonstrated greater in vitro flow diversion effects than Pipeline. Comparative efficacy of the devices will need to be adjudicated based on clinical outcomes.


title: Refractoriness in bipolar disorder: definitions and evidence-based treatment.

text: Defining refractoriness in bipolar disorder is complex and should concern and include either every phase and pole or the disorder as a whole. The data on the treatment of refractory bipolar patients are sparse. Combination and add-on studies suggest that in acutely manic patients partial responders to lithium, valproate, or carbamazepine, a good strategy would be to add haloperidol, risperidone, olanzapine, quetiapine, or aripiprazole. Adding oxcarbazepine to lithium is also a choice. There are no reliable data concerning the treatment of refractory bipolar depressives and also there is no compelling data for the maintenance treatment of refractory patients. It seems that patients stabilized on combination treatment might do worse if shifted from combination. Conclusively there are only limited and sometimes confusing data on the treatment of refractory bipolar patients. Further focused research is necessary on this group of patients.


title: Minimally Invasive Surgical Repair for Congenital Bronchobiliary Fistula in an Adult.

text: Congenital bronchobiliary fistula (CBBF) is a very rare disease and usually requires surgical intervention at a young age. We report a case of CBBF in an adult who was treated successfully with a minimally invasive endoscopic operation.


Shortening treatment of tuberculosis: lessons from fluoroquinolone trials.


title: Life-Saving Esophageal Intubation in Neonate With Undiagnosed Tracheal Agenesis: A Case Report.

text: A 3-day-old, 2.2-kg former 34-week premature infant with imperforate anus required loop ileostomy surgery. At delivery, the child had respiratory distress. Endotracheal intubation was "confirmed" by detection of exhaled carbon dioxide with a Pedi-Cap (Covidien, Dublin, Ireland) and subsequent chest x-ray. On arrival to the operating room, the pulse oximeter reading was 100% despite a large leak around the endotracheal tube and high-airway pressures. Packing the throat reduced the leak and increased the tidal volume. Intraoperative bronchospasm occurred during the surgery. On postoperative day 1, fiberoptic examination by an otolaryngologist revealed esophageal intubation and the absence of laryngeal opening. Subsequent computed tomography scan revealed Floyd type II tracheal agenesis. To our knowledge, this is the only case of tracheal agenesis diagnosed after a non-airway related procedure. We discussed how the diagnosis was missed.


title: Impact of ambient air pollution and wheeze-associated disorders in children in Southeast Asia: a systematic review and meta-analysis.

text: Several systematic reviews have been conducted so far to examine the effect of air pollution on respiratory diseases, but there has not been a corresponding meta-analysis to estimate the effect sizes for wheeze-associated diseases/disorders, which is one of the leading causes of emergency department visits and hospitalizations for children worldwide. The aim of this review is to systematically evaluate the relationship between air pollution and risk of wheeze-associated disorders in children in Southeast Asia. We searched the relevant computerized databases (PubMed, EMBASE, Web of Science, Scopus and Cochrane library) for indexed publications up to July 2018. Finally, eight studies were qualified for performing a random-effect meta-analysis to compute the pooled effect sizes. The results show that each increase of 10 μg/m3 in concentrations of PM2.5, PM1 was associated with 1-2% increase in risk of wheeze-associated disorders. Positive associations were found for PM10, SO2, NO2, NOx but no association was found for CO and O3. We confirmed the strong effect of fine particulate matters on respiratory health and recommend an updated meta-analysis should be done when more studies are available.


title: [Analysis of gastrointestinal symptoms in 80 patients with coronavirus disease 2019].

text: OBJECTIVE To investigate the clinical characteristics of gastrointestinal symptoms in patients with coronavirus disease 2019 (COVID-19) during the whole disease process, and provide reference for etiological diagnosis and treatment. METHODS The clinical data of patients with COVID-19 admitted in the Infectious Diseases Branch of the First Affiliated Hospital of University of Science and Technology of China from January 22nd, 2020 to March 8th, 2020 were analyzed retrospectively. According to whether there were gastrointestinal symptoms (poor appetite, nausea/vomiting and diarrhea), all patients were divided into gastrointestinal symptom group and asymptomatic group. The characteristics of gastrointestinal symptoms, such as poor appetite, nausea, vomiting and diarrhea were counted and analyzed, and the correlation between gastrointestinal symptoms and gender, age, basic diseases, disease severity, laboratory examination and drug treatment were analyzed. RESULTS A total of 80 COVID-19 patients were involved, 43 cases (53.8%) presented with poor appetite, 17 cases (21.3%) had nausea and vomiting, and 33 cases (41.3%) had diarrhea. Among them, 5 cases, 1 case and 4 cases respectively preformed poor appetite, nausea/vomiting and diarrhea before admission, while the others experienced gastrointestinal symptoms within 48 hours after admission. Duration of poor appetite, nausea/vomiting and diarrhea (days) of all patients were 5.3±2.1, 2.2±1.0 and 1.4±0.9, respectively. The patients with poor appetite were older than those without symptoms (years old: 48.2±17.6 vs. 39.3±15.1), albumin (Alb) level and the lymphocytes ratio were lower than those in asymptomatic group [Alb (g/L): 39.8 (35.7, 45.1) vs. 46.1 (42.6, 49.4), lymphocytes ratio: 0.19 (0.09, 0.28) vs. 0.28 (0.17, 0.35)], while the neutrophil ratio, the levels of C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) were higher than those in asymptomatic group [the neutrophil ratio: 0.74 (0.61, 0.85) vs. 0.64 (0.52, 0.76), CRP (mg/L): 21.4 (3.9, 52.9) vs. 5.6 (2.4, 14.0), D-dimer (mg/L): 0.2 (0.2, 0.5) vs. 0.2 (0.1, 0.3), LDH (μmol×s-1×L-1): 4.49 (3.59, 5.19) vs. 3.12 (2.77, 4.90)]; at the same time, more traditional Chinese medicine was used in the patients with gastrointestinal symptoms [65.1% (28/43) vs. 40.5% (15/37), all P < 0.05]. In addition, 14 cases of 18 patients with cardiovascular diseases presented with poor appetite, 7 patients had nausea and vomiting symptoms. All of the 3 patients with chronic kidney disease presented with poor appetite, nausea and vomiting, and 2 of them had diarrhea. CONCLUSIONS The gastrointestinal symptoms in patients with COVID-19 are common. Whether it is caused by the virus or related drugs, diet and mental conditions, clinicians should analyze the causes of these symptoms timely, and then provide a better treatment for patients with COVID-19.


title: A case report with COVID-19 during perioperative period of lobectomy.

text: RATIONALE Currently, COVID-19 has made a significant impact on many countries in the world. However, there have been no reported cases of pulmonary lobectomy with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) infection. We are the first to report such a case. PATIENT CONCERNS We report a 63-year-old Wuhan male patient with smoking history of 40 cigarettes per day for 40 years. He sought medical consultation for right lower lung nodules found by CT scan. DIAGNOSES AND INTERVENTIONS The patient's postoperative pathological diagnosis was squamous cell carcinoma of the right lower lung. On the fourth day after the operation, the real-time reverse transcription polymerase chain reaction test showed a positive result. After the operation, we routinely give symptomatic treatments such as anti-infection, nebulization and oxygen inhalation. We also change antibiotics several times depending on the patient's condition. OUTCOMES The patient's condition continued to deteriorate. On the fifth day after surgery, the patient died despite medical treatment. LESSONS We are the first to report the diagnosis and treatment process of patients with COVID-19 during perioperative period of lobectomy. It provides a case for the postoperative management of such patients.


title: COVID-19 Epidemic: Clinical Characteristics of Patients in Pediatric Isolation Ward.

text: In order to accurately admit children with COVID-19 to an isolation ward, our study retrospectively analyzed the clinical characteristics of children in isolation wards during the COVID-19 epidemic. It was found that 55 cases (83.3%) had fever and 48 cases (72.7%) coughed in the isolated area, 31 cases (47%) had a history of exposure, 26 cases (39.4%) had a decrease in lymphocytes (LYM), more than half had an increase in lactate dehydrogenase and creatine kinase isoenzyme, 14 cases (21.2%) had positive SARS-CoV-2 nucleic acid, 58 cases (87.9%) had abnormal chest computed tomography (CT), and 11 cases (16.7%) had sinus arrhythmia. Therefore, for some suspected children with COVID-19, we can make a comprehensive judgment through clinical symptoms, epidemiological history, LYM number, myocardial enzyme spectrum, chest CT, and electrocardiogram; put these children in an isolation ward for treatment; and then transfer them to a general ward for treatment after excluding COVID-19.


Schistosomiasis in cattle in Corsica, France.


title: Enhanced antiviral T cell function in the absence of B7-H1 is insufficient to prevent persistence but exacerbates axonal bystander damage during viral encephalomyelitis.

text: The T cell inhibitory ligand B7-H1 hinders T cell-mediated virus control, but also ameliorates clinical disease during autoimmune and virus-induced CNS disease. In mice infected with gliatropic demyelinating coronavirus, B7-H1 expression on oligodendroglia delays virus control, but also dampens clinical disease. To define the mechanisms by which B7-H1 alters pathogenic outcome, virus-infected B7-H1-deficient (B7-H1(-/-)) mice were analyzed for altered peripheral and CNS immune responses. B7-H1 deficiency did not affect peripheral T or B cell activation or alter the magnitude or composition of CNS-infiltrating cells. However, higher levels of IFN-γ mRNA in CNS-infiltrating virus-specific CD8 T cells as well as CD4 T cells contributed to elevated IFN-γ protein in the B7-H1(-/-) CNS. Increased effector function at the single-cell level was also evident by elevated granzyme B expression specifically in virus-specific CNS CD8 T cells. Although enhanced T cell activity accelerated virus control, 50% of mice succumbed to infection. Despite enhanced clinical recovery, surviving B7-H1(-/-) mice still harbored persisting viral mRNA, albeit at reduced levels compared with wild-type mice. B7-H1(-/-) mice exhibited extensive loss of axonal integrity, although demyelination, a hallmark of virus-induced tissue damage, was not increased. The results suggest that B7-H1 hinders viral control in B7-H1 expressing glia cells, but does not mediate resistance to CD8 T cell-mediated cytolysis. These data are the first, to our knowledge, to demonstrate that B7-H1-mediated protection from viral-induced immune pathology associated with encephalomyelitis resides in limiting T cell-mediated axonal bystander damage rather than direct elimination of infected myelinating cells.


PERSEVERE OR PERIL: DIABETES CARE IN TIMES OF COVID-19.


title: Glutamate excitotoxicity is involved in the induction of paralysis in mice after infection by a human coronavirus with a single point mutation in its spike protein.

text: Human coronaviruses (HCoV) are recognized respiratory pathogens, and some strains, including HCoV-OC43, can infect human neuronal and glial cells of the central nervous system (CNS) and activate neuroinflammatory mechanisms. Moreover, HCoV-OC43 is neuroinvasive, neurotropic, and neurovirulent in susceptible mice, where it induces chronic encephalitis. Herein, we show that a single point mutation in the viral spike (S) glycoprotein (Y241H), acquired during viral persistence in human neural cells, led to a hind-limb paralytic disease in infected mice. Inhibition of glutamate excitotoxicity using a 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propranoic acid (AMPA) receptor antagonist (GYKI-52466) improved clinical scores related to the paralysis and motor disabilities in S mutant virus-infected mice, as well as protected the CNS from neuronal dysfunctions, as illustrated by restoration of the phosphorylation state of neurofilaments. Expression of the glial glutamate transporter GLT-1, responsible for glutamate homeostasis, was downregulated following infection, and GYKI-52466 also significantly restored its steady-state expression level. Finally, GYKI-52466 treatment of S mutant virus-infected mice led to reduced microglial activation, which may lead to improvement in the regulation of CNS glutamate homeostasis. Taken together, our results strongly suggest an involvement of excitotoxicity in the paralysis-associated neuropathology induced by an HCoV-OC43 mutant which harbors a single point mutation in its spike protein that is acquired upon persistent virus infection.


title: China bans sale of wildlife following coronavirus.

text: Josh Loeb reports on the action China is taking to prevent the spread of coronavirus.


Rationale and necessity for delivery of RRx-001, a Myc and CD47 antagonist, by intravenous blood mix.


title: Extracorporeal Hand-Sewn Anastomosis Through a Minilaparotomy in Laparoscopic Distal Gastrectomy.

text: BACKGROUND Various methods of reconstruction after laparoscopic distal gastrectomy (LDG) have been developed and reported. In open gastrectomy, gastroduodenostomy or gastroenterostomy is often performed with the hand-sewn technique. Therefore, hand-sewn anastomosis was performed through a small incision in LDG. The aim of this study was to evaluate the feasibility and safety of LDG with hand-sewn anastomosis. METHODS Between June 2009 and December 2015, we assessed 263 consecutive patients who underwent LDG in our institution. In all patients, the reconstruction procedures were performed extracorporeally with the hand-sewn technique. The clinical characteristics, surgical outcomes, and operation cost related to anastomosis were evaluated and compared with the other methods. RESULTS The average operation time was 157.5 minutes, and average blood loss was 38.8 mL. The types of reconstruction were Billroth I, 95 cases (36.1%); Billroth II, 165 cases (62.7%); and Roux-en-Y, 3 cases (1.1%). The overall incidence of postoperative complications (Clavien-Dindo classification≧Grade II) was 8.0%. Anastomotic leakage was observed in 1 patient (0.4%) and anastomotic bleeding and anastomotic stenosis in 2 patients each (0.8%). There was no postoperative mortality. The cost of the absorbable threads used in anastomosis is less than the cost of a linear or circular stapler, which is often used in intracorporeal anastomosis. CONCLUSION This procedure is similar to conventional open surgery, and it is feasible, safe, and cost-effective. In addition, in an institution that plans to introduce LDG, the use of our method during the introductory phase of LDG has many advantages.


title: Delivery, stabilization, and spatiotemporal activation of cargo molecules in cells with positively charged nanoparticles.

text: Positively charged photodegradable nanoparticles that simultaneously encapsulated various compounds including small and large molecules were prepared. The nanoparticles were internalized to the cell by endocytosis and were stable within the cells for at least 4 days. The encapsulated molecules were released into the cytosol using light stimuli.


title: Chronic posterior sternoclavicular dislocation.

text: SUMMARY Posterior sternoclavicular dislocation is a rare injury that involves a risk of concomitant injuries to mediastinal structures. We report a 23-year-old man who underwent open reduction and fixation with a plantaris tendon graft after 13 weeks. The clinical and radiologic outcome was good.


title: Productive replication and evolution of HIV-1 in ferret cells.

text: A rodent or other small animal model for HIV-1 has not been forthcoming, with the principal obstacles being species-specific restriction mechanisms and deficits in HIV-1 dependency factors. Some Carnivorans may harbor comparatively fewer impediments. For example, in contrast to mice, the domestic cat genome encodes essential nonreceptor HIV-1 dependency factors. All Feliformia species and at least one Caniformia species also lack a major lentiviral restriction mechanism (TRIM5α/TRIMCyp proteins). Here we investigated cells from two species in another carnivore family, the Mustelidae, for permissiveness to the HIV-1 life cycle. Mustela putorius furo (domesticated ferret) primary cells and cell lines did not restrict HIV-1, feline immunodeficiency virus (FIV), equine infectious anemia virus (EIAV), or N-tropic murine leukemia virus (MLV) postentry and supported late HIV-1 life cycle steps comparably to human cells. The ferret TRIM5α gene exon 8, which encodes the B30.2 domain, was found to be pseudogenized. Strikingly, ferret (but not mink) cells engineered to express human HIV-1 entry receptors supported productive spreading replication, amplification, and serial passage of wild-type HIV-1. Nevertheless, produced virions had relatively reduced infectivity and the virus accrued G→A hypermutations, consistent with APOBEC3 protein pressure. Ferret cell-passaged HIV-1 also evolved amino acid changes in the capsid cyclophilin A binding loop. We conclude that the genome of this carnivore can provide essential nonreceptor HIV-1 dependency factors and that ferret APOBEC3 proteins with activity against HIV-1 are likely. Even so, unlike in cat cells, HIV-1 can replicate in ferret cells without vif substitution. The virus evolves in this novel nonprimate cell adaptive landscape. We suggest that further characterization of HIV-1 adaptation in ferret cells and delineation of Mustelidae restriction factor repertoires are warranted, with a view to the potential for an HIV-1 animal model.


title: A protective technique for retraction of the liver during laparoscopic gastrectomy for gastric adenocarcinoma: using a Penrose drain.

text: BACKGROUND Retraction of the liver is necessary to ensure an adequate working space in laparoscopic surgery, but the retraction force applied may cause transient liver dysfunction. We have introduced the technique using a Penrose drain to suspend the liver with the performance of laparoscopic gastrectomy for gastric adenocarcinoma. METHODS 111 patients with gastric adenocarcinoma underwent laparoscopic gastrectomy using either a Penrose drain (n = 47) or a Nathanson's retractor (n = 64) for displacement of the liver. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP) and albumin were compared among the groups at baseline, immediately after operation, and on postoperative days (POD) 1, 2, 3, 5, and 7. RESULTS The levels of ALT on POD 2, 3, and 5 were significant higher in the Nathanson's retractor group than in the Penrose drain group. Levels of AST on POD 2 and 3 were also higher in the Nathanson's retractor group than in the Penrose drain group. There was no significant difference in total bilirubin, ALP, and serum albumin levels between groups. CONCLUSIONS The use of the Penrose drain for retraction of the liver appears to attenuate postoperative liver dysfunction during laparoscopic gastrectomy for gastric adenocarcinoma.


title: Issues of Cardiovascular Risk Management in People With Diabetes in the COVID-19 Era.

text: People with diabetes compared with people without exhibit worse prognosis if affected by coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly when compromising metabolic control and concomitant cardiovascular disorders are present. This Perspective seeks to explore newly occurring cardio-renal-pulmonary organ damage induced or aggravated by the disease process of COVID-19 and its implications for the cardiovascular risk management of people with diabetes, especially taking into account potential interactions with mechanisms of cellular intrusion of SARS-CoV-2. Severe infection with SARS-CoV-2 can precipitate myocardial infarction, myocarditis, heart failure, and arrhythmias as well as an acute respiratory distress syndrome and renal failure. They may evolve along with multiorgan failure directly due to SARS-CoV-2-infected endothelial cells and resulting endotheliitis. This complex pathology may bear challenges for the use of most diabetes medications in terms of emerging contraindications that need close monitoring of all people with diabetes diagnosed with SARS-CoV-2 infection. Whenever possible, continuous glucose monitoring should be implemented to ensure stable metabolic compensation. Patients in the intensive care unit requiring therapy for glycemic control should be handled solely by intravenous insulin using exact dosing with a perfusion device. Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19. In conclusion, COVID-19 and related cardio-renal-pulmonary damage can profoundly affect cardiovascular risk management of people with diabetes.


title: Simulations reveal how M-currents and memory-based inputs from CA3 enable single neuron mismatch detection for EC3 inputs to the CA1 subfield of hippocampus.

text: Significant evidence has accumulated to support the hypothesis that hippocampal region CA1 operates as an associative mismatch detector (e.g., Hasselmo et al., 1995; Lörincz & Buzsáki, 2000; Lisman & Otmakhova, 2001; Vinogradova, 2001; Meeter et al., 2004; Lisman & Grace, 2005; Kumaran & Maguire, 2007; Duncan et al., 2009; Schiffer et al., 2012). CA1 compares predictive synaptic signals from CA3 with synaptic signals from EC3, which reflect actual sensory inputs. The new CA1 pyramidal model presented here shows that the distal-proximal segregation of synaptic inputs from EC3 versus CA3, along with other biophysical features, enable such pyramids to serve as comparators that switch output encoding from a brief burst, for a match, to prolonged tonic spiking, for a mismatch. By including often-overlooked features of CA1 pyramidal neurons, this new model allows simulation of pharmacological effects that can eliminate either the match (phasic mode) response or the mismatch (tonic mode) response. These simulations reveal that dysfunctions can arise from either too much or too little ACh stimulation of the muscarinic receptors that control KCNQ channels. Additionally, a dysfunction caused by administration of an NMDA antagonist could be rescued by simultaneous administration of a KCNQ channel agonist, such as retigabine.


title: The effect of tissue compression on circular stapler line failure.

text: BACKGROUND Anastomotic leak after gastrointestinal anastomosis is a well-known and serious complication, yet there is no standardized approach to reliably create an anastomosis with sufficient mechanical properties to consistently avoid an anastomotic leak. The purpose of this study was to evaluate the relationships among combined tissue thickness, tissue compression, closed staple limb length, and mechanical strength of an anastomosis created with a circular stapler, as measured by maximum intraluminal pressure obtained at the time of leakage. METHODS Using 27 porcine stomachs and 27 porcine small-intestine segments, we measured tissue thickness and assessed the tissue compression at three different anvil closure distances created by a circular stapling device. Maximum intraluminal pressure was determined by infusing colored water into the porcine materials and increasing the pressure until leakage from the anastomosis occurred. RESULTS Tissue compression increased as the closure distance narrowed between the anvil and circular stapler (p < .0001). A tissue compression of ≥6 PSI correlated strongly with a maximum intraluminal pressure of ≥18 mmHg (43% for <6 PSI vs. 90% for ≥6 PSI; p = .02); tissue compression ≥12 PSI was necessary to obtain an acute maximum intraluminal pressure of ≥22 mmHg in 13 of 15 of our samples (p = .04). CONCLUSIONS Maximum intraluminal pressure of an anastomosis in this porcine model correlated most strongly with the compression of the tissue involved in the anastomosis. This experimental model provides a framework for constructing a systematic approach to creating an anastomosis with sufficient mechanical strength. However, this study was not intended to establish the upper range of tissue compression beyond which a permanent tissue injury may occur.


title: Pseudoaneurysm of the Petrosal Internal Carotid Artery in the Middle Ear as a Complication of Middle Ear Cholesteatoma.

text: We report the case of a 66-year-old man who had significant otorrhagia caused by a ruptured pseudoaneurysm in the petrous internal carotid artery (ICA). The patient had middle ear cholesteatoma, and computed tomography (CT) showed bony erosion and exposure of the ICA into the middle ear cavity. Further angiography of the right carotid artery revealed a pseudoaneurysm protruding from the petrosal ICA into the middle ear cavity. The pseudoaneurysm was promptly treated with coil embolization and stenting. The patient continues to be monitored regularly with clinical follow-up, and carotid angiography and temporal bone CT revealed no interval changes at the embolized site 3 years after the procedure.


title: Pure laparoscopic subsegmentectomy of the liver using a puncture method for the target portal branch under percutaneous ultrasound with artificial ascites.

text: PURPOSE It is important to minimize surgical invasiveness in the therapy of patients with hepatocellular carcinoma (HCC) and, consequently, laparoscopic hepatic resection is widely performed. However, most anatomic resections, except left lateral sectionectomy, are still difficult technically and, as an alternative approach, laparoscopy-assisted procedures also have been introduced because of the safety and curative success of the operation. Herein, we describe pure laparoscopic subsegmentectomy of the liver using puncture of the portal branch under percutaneous ultrasound (US) with artificial ascites. METHODS Pure laparoscopic subsegmentectomy of segment 6 (S6) was planned for a patient with HCC of S6 of the liver. The identification of the segment was performed by dye injection under percutaneous US guidance with artificial ascites. RESULTS The procedure was completed successfully in a minimally invasive manner with an operative time of 260 minutes and with intraoperative blood loss of 10 mL. The difference between the size of the resected specimen and that estimated by 3-dimensional computed tomography was very small. The postoperative course was uneventful and the patient was discharged 10 days after surgery. CONCLUSIONS Pure laparoscopic subsegmentectomy for HCC with a conventional puncture technique under percutaneous US with artificial ascites is considered to be a useful procedure featuring both low invasiveness and curative success.


title: A reverse genetics approach to study feline infectious peritonitis.

text: Feline infectious peritonitis (FIP) is a lethal immunopathological disease caused by feline coronaviruses (FCoVs). Here, we describe a reverse genetics approach to study FIP by assessing the pathogenicity of recombinant type I and type II and chimeric type I/type II FCoVs. All recombinant FCoVs established productive infection in cats, and recombinant type II FCoV (strain 79-1146) induced FIP. Virus sequence analyses from FIP-diseased cats revealed that the 3c gene stop codon of strain 79-1146 has changed to restore a full-length open reading frame (ORF).


title: Effect of Smoking on Infarct Size and Major Adverse Cardiac Events in Patients With Large Anterior ST-Elevation Myocardial Infarction (from the INFUSE-AMI Trial).

text: We sought to investigate the effect of smoking on infarct size (IS) and major adverse cardiac events (MACE) in patients with large anterior ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Participants from the Intracoronary Abciximab and Aspiration Thrombectomy in Patients with Large Anterior Myocardial Infarction study were categorized according to smoking status (current or previous smoking vs no history of smoking). The primary imaging outcome was cardiac magnetic resonance imaging-assessed IS of left ventricular mass (%) at 30 days. The primary clinical outcome was the rate of MACE at 30 days and 1 year, defined as the composite of death, reinfarction, new-onset heart failure, or rehospitalization. Of 447 patients enrolled in Intracoronary Abciximab and Aspiration Thrombectomy in Patients with Large Anterior Myocardial Infarction, 271 (60.6%) were current or past smokers. Compared with nonsmokers, smokers were almost 10 years younger and had a lower prevalence of clinical co-morbidities. Smokers had better procedural success and angiographic reperfusion compared with nonsmokers. At 30 days, there were no differences between smokers and nonsmokers in median IS (16.8% vs 17.4%, p = 0.67) or metrics of left ventricular function. By multivariable linear regression analysis, smoking was not significantly associated with IS at 30 days (beta coefficient: 0.83, p = 0.42). At 1 year, smokers had lower crude rates of MACE (7.6% vs 15%, p = 0.01). After multivariable adjustment, there were no significant differences in 1-year MACE between smokers and nonsmokers (adjusted hazard ratio 0.73, 95% CI 0.40 to 1.33, p = 0.30). In conclusion, smoking history had no significant effect on IS at 30 days. Although current or previous smokers had lower rates of 1-year MACE than those with no history of smoking, adjustment for baseline characteristics rendered this association nonsignificant. These findings support the hypothesis that the smoker's paradox is largely attributable to differences in demographic and clinical baseline risk, rather than differences in IS after primary percutaneous coronary intervention.


title: Synthetic polyglycomer short-term absorbable sutures vs. polydioxanone long-term absorbable sutures for preventing incisional hernia and wound dehiscence after abdominal wall closure: a comparative randomized study of patients treated for gastric or colon cancer.

text: PURPOSE To compare the results of abdominal wall closure using interrupted synthetic short-term vs. long-term tensile strength-retaining absorbable sutures. METHODS The subjects were 55 patients undergoing elective laparotomy through a midline vertical incision for gastric or colon cancer surgery between November 2008 and August 2010, at our hospital. After providing informed consent, the patients were randomized for suturing with Polysorb(®), which provides short-term tensile strength, or with PDS(®)II, which provides long-term strength. The primary outcome analyzed was the incidence of incisional hernia or wound dehiscence. RESULT There were 28 patients allocated to the Polysorb group and 27 to the PDS II group. Postoperative wound dehiscence was noted in two patients (3.6%). Five of 51 patients (9.8%) suffered incisional hernia within 1 year after surgery, 6 of 41 patients (14.6%) within 2 years, and 6 of 35 patients (17.1%) within 3 years. There was no significant per year difference in the incidence of incisional hernia or wound dehiscence between the groups. CONCLUSION Outcomes were favorable in both groups and not inferior to reported outcomes of larger-scale studies. Verification of the equivalence between the two types of suture material necessitates larger-scale studies that adopt the same suture methods.


title: Reversible high affinity inhibition of phosphofructokinase-1 by acyl-CoA: a mechanism integrating glycolytic flux with lipid metabolism.

text: The enzyme phosphofructokinase-1 (PFK-1) catalyzes the first committed step of glycolysis and is regulated by a complex array of allosteric effectors that integrate glycolytic flux with cellular bioenergetics. Here, we demonstrate the direct, potent, and reversible inhibition of purified rabbit muscle PFK-1 by low micromolar concentrations of long chain fatty acyl-CoAs (apparent Ki∼1 μM). In sharp contrast, short chain acyl-CoAs, palmitoylcarnitine, and palmitic acid in the presence of CoASH were without effect. Remarkably, MgAMP and MgADP but not MgATP protected PFK-1 against inhibition by palmitoyl-CoA indicating that acyl-CoAs regulate PFK-1 activity in concert with cellular high energy phosphate status. Furthermore, incubation of PFK-1 with [1-(14)C]palmitoyl-CoA resulted in robust acylation of the enzyme that was reversible by incubation with acyl-protein thioesterase-1 (APT1). Importantly, APT1 reversed palmitoyl-CoA-mediated inhibition of PFK-1 activity. Mass spectrometric analyses of palmitoylated PFK-1 revealed four sites of acylation, including Cys-114, Cys-170, Cys-351, and Cys-577. PFK-1 in both skeletal muscle extracts and in purified form was inhibited by S-hexadecyl-CoA, a nonhydrolyzable palmitoyl-CoA analog, demonstrating that covalent acylation of PFK-1 was not required for inhibition. Tryptic footprinting suggested that S-hexadecyl-CoA induced a conformational change in PFK-1. Both palmitoyl-CoA and S-hexadecyl-CoA increased the association of PFK-1 with Ca2+/calmodulin, which attenuated the binding of palmitoylated PFK-1 to membrane vesicles. Collectively, these results demonstrate that fatty acyl-CoA modulates phosphofructokinase activity through both covalent and noncovalent interactions to regulate glycolytic flux and enzyme membrane localization via the branch point metabolic node that mediates lipid flux through anabolic and catabolic pathways.


title: Association between bariatric surgery and long-term survival.

text: IMPORTANCE Accumulating evidence suggests that bariatric surgery improves survival among patients with severe obesity, but research among veterans has shown no evidence of benefit. OBJECTIVE To examine long-term survival in a large multisite cohort of patients who underwent bariatric surgery compared with matched control patients. DESIGN, SETTING, AND PARTICIPANTS In a retrospective cohort study, we identified 2500 patients (74% men) who underwent bariatric surgery in Veterans Affairs (VA) bariatric centers from 2000-2011 and matched them to 7462 control patients using sequential stratification and an algorithm that included age, sex, geographic region, body mass index, diabetes, and Diagnostic Cost Group. Survival was compared across patients who underwent bariatric surgery and matched controls using Kaplan-Meier estimators and stratified, adjusted Cox regression analyses. EXPOSURES Bariatric procedures, which included 74% gastric bypass, 15% sleeve gastrectomy, 10% adjustable gastric banding, and 1% other. MAIN OUTCOMES AND MEASURES All-cause mortality through December 2013. RESULTS Surgical patients (n = 2500) had a mean age of 52 years and a mean BMI of 47. Matched control patients (n = 7462) had a mean age of 53 years and a mean BMI of 46. At the end of the 14-year study period, there were a total of 263 deaths in the surgical group (mean follow-up, 6.9 years) and 1277 deaths in the matched control group (mean follow-up, 6.6 years). Kaplan-Meier estimated mortality rates were 2.4% at 1 year, 6.4% at 5 years, and 13.8% at 10 years for surgical patients; for matched control patients, 1.7% at 1 year, 10.4% at 5 years, and 23.9% at 10 years. Adjusted analysis showed no significant association between bariatric surgery and all-cause mortality in the first year of follow-up (adjusted hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]), but significantly lower mortality after 1 to 5 years (HR, 0.45 [95% CI, 0.36-0.56]) and 5 to 14 years (HR, 0.47 [95% CI, 0.39-0.58]). The midterm (>1-5 years) and long-term (>5 years) relationships between surgery and survival were not significantly different across subgroups defined by diabetes diagnosis, sex, and period of surgery. CONCLUSIONS AND RELEVANCE Among obese patients receiving care in the VA health system, those who underwent bariatric surgery compared with matched control patients who did not have surgery had lower all-cause mortality at 5 years and up to 10 years following the procedure. These results provide further evidence for the beneficial relationship between surgery and survival that has been demonstrated in younger, predominantly female populations.


MR RESCUE: is the glass half-full or half-empty?


title: Treatment of direct carotid-cavernous fistulas with flow diversion - does it work?

text: Direct carotid-cavernous fistulas (CCFs) are high flow lesions that can be challenging to treat. A number of recent reports suggest that flow diversion may be a viable treatment option. We present a case of a post-traumatic CCF successfully treated with flow diversion and provide a review of the literature. Our results suggest that flow diversion is a potentially effective treatment option for CCFs and is most successful when used as an adjunctive therapy.


title: Neurophysiologic predictors of response to atomoxetine in young adults with attention deficit hyperactivity disorder: a pilot project.

text: Atomoxetine is a non-stimulant medication with sustained benefit throughout the day, and is a useful pharmacologic treatment option for young adults with Attention-Deficit/Hyperactivity Disorder (ADHD). It is difficult to determine, however, those patients for whom atomoxetine will be both effective and advantageous. Patients may need to take the medication for several weeks before therapeutic benefit is apparent, so a biomarker that could predict atomoxetine effectiveness early in the course of treatment could be clinically useful. There has been increased interest in the study of thalamocortical oscillatory activity using quantitative electroencephalography (qEEG) as a biomarker in ADHD. In this study, we investigated qEEG absolute power, relative power, and cordance, which have been shown to predict response to reuptake inhibitor antidepressants in Major Depressive Disorder (MDD), as potential predictors of response to atomoxetine. Forty-four young adults with ADHD (ages 18-30) enrolled in a multi-site, double-blind placebo-controlled study of the effectiveness of atomoxetine and underwent serial qEEG recordings at pretreatment baseline and one week after the start of medication. qEEG measures were calculated from a subset of the sample (N = 29) that provided useable qEEG recordings. Left temporoparietal cordance in the theta frequency band after one week of treatment was associated with ADHD symptom improvement and quality of life measured at 12 weeks in atomoxetine-treated subjects, but not in those treated with placebo. Neither absolute nor relative power measures selectively predicted improvement in medication-treated subjects. Measuring theta cordance after one week of treatment could be useful in predicting atomoxetine treatment response in adult ADHD.


China coronavirus should be on "everybody's agenda," says vaccine expert.


title: Lower Circulating C1q/TNF-Related Protein-3 (CTRP3) Levels Are Associated with Obesity: A Cross-Sectional Study.

text: PURPOSE C1q/TNF-related protein-3 (CTRP3) is a novel adipokine that lowers blood glucose levels, reduces liver triglyceride synthesis, and is protective against hepatic steatosis in diet-induced obese mouse models. We hypothesized that higher circulating serum levels of CTRP3 would be associated with a lean body mass index (BMI) and a more favorable metabolic profile in humans. The aim of this study was to investigate CTRP3 levels in lean individuals compared to obese individuals. METHODS This was a cross-sectional study of obese (n=44) and lean control patients (n=60). Fasting metabolic parameters were measured in all patients and serum CTRP3 levels were measured by ELISA. RESULTS BMI of the lean group was 21.9 ± 0.2 kg/m2 and obese group was 45.2 ± 1.1 kg/m2. We found significantly lower circulating levels of CTRP3 in obese individuals (405 ± 8.3 vs. 436 ± 6.7 ng/mL, p=0.004) compared to the lean group. Serum CTRP3 levels were inversely correlated with BMI (p=0.001), and triglycerides (p<0.001), and significantly associated with gender (p<0.01), ethnicity (p=0.05), HDL-cholesterol (p<0.01), and adiponectin (p<0.01). We found BMI (p<0.01), gender (p<0.01), and ethnicity (p<0.05) to be significant predictors of CTRP3 levels when controlling for age in multiple regression analysis. CONCLUSIONS CTRP3 is a beneficial adipokine whose circulating levels are significantly lower in obese individuals. Obesity causes dysregulation in adipokine production, including the down-regulation of CTRP3. Lower CTRP3 levels may contribute to the pathophysiology of metabolic disorders associated with obesity. Optimizing CTRP3 levels through novel therapies may improve obesity and its comorbidities.


Interim Guidance for Basic and Advanced Life Support in Children and Neonates With Suspected or Confirmed COVID-19.


Is the COVID-19 Pandemic an Opportunity to Enlarge the Telemedicine Boundaries? (Re: Telemed J E Health 2020;26:571-573).


title: Metabolic Impacts of Confinement during the COVID-19 Pandemic Due to Modified Diet and Physical Activity Habits.

text: While the detrimental effects of a chronic positive energy balance due to a sedentary lifestyle have been well established, the impacts of a short period of abruptly reduced physical activity and overeating arising from strict confinement due to the COVID-19 pandemic will soon start to emerge. To reasonably anticipate major consequences according to the available evidence, we hereby review the literature for studies that have explored the health impacts of several weeks of a reduction in physical activity and daily step-count combined with modified eating habits. These studies identify as main metabolic consequences increases in insulin resistance, total body fat, abdominal fat and inflammatory cytokines. All these factors have been strongly associated with the development of metabolic syndrome, which in turn increases the risk of multiple chronic diseases. A plausible mechanism involved in these impacts could be a positive energy balance promoted by maintaining usual dietary intake while reducing energy expenditure. This means that just as calorie intake restriction could help mitigate the deleterious impacts of a bout of physical inactivity, overeating under conditions of home confinement is very likely to exacerbate these consequences. Moreover, hypertension, diabetes, and cardiovascular disease have been identified as potential risk factors for more severely ill patients with COVID-19. Thus, adequate control of metabolic disorders could be important to reduce the risk of severe COVID-19.


Airport screening for Ebola.


title: Discovery of the first series of small molecule H5N1 entry inhibitors.

text: The occurrence of highly pathogenic avian influenza virus H5N1 highlights the urgent need for new classes of antiviral drugs. Inhibition of H5N1 entry into cells may be an effective strategy. We report the first three small molecule inhibitors saponins with 3-O-beta-chacotriosyl residue, which showed potent inhibitory activity with IC(50) of 7.22-9.25 microM. The subsequent SAR studies showed the 3-O-beta-chacotriosyl residue was essential for the activity, and the aglycone structure also affected the activity.


title: An Update on Methods for Revascularization and Expansion of the TASC Lesion Classification to Include Below-the-Knee Arteries: A Supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II): The TASC Steering Comittee(.).

text: The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today.


title: Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases.

text: BACKGROUND Anti-tumour necrosis factor (anti-TNF) monoclonal antibodies have shown efficacy in inflammatory bowel diseases (IBD). As these therapies lose patent protection, biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13; however, some uncertainty exists regarding their pharmacology in IBD. AIM To review the literature on anti-TNF biosimilars focusing on pharmacokinetics, pharmacodynamic properties and comparative effectiveness, related to their use in IBD. METHODS A PubMed literature search was performed using the following terms individually or in combination: 'biosimilars,' 'CT-P13,' 'Crohn's disease,' 'inflammatory bowel disease,' 'ulcerative colitis,' 'anti-TNFα therapy,' 'infliximab,' 'adalimumab,' 'pharmacokinetics,' 'immunogenicity.' RESULTS Bioequivalence of CT-P13 and infliximab was shown in ankylosing spondylitis (AS) and therapeutic equivalence in rheumatoid arthritis (RA). Preliminary results of CT-P13 in IBD come from small post-marketing registries and case series with a relatively short-term follow-up period and suggest comparable efficacy and safety to infliximab. Inter- and intra-individual differences in exposure and response are well known for the original molecules but dosing regimens and concomitant medications are different for RA compared to IBD, limiting the ability to translate some of the pharmacology data in RA to IBD. Uncertainty exists about cross-reactivity of anti-drug antibodies and whether similar exposure-response relationships will be observed for biosimilars and efficacy thresholds for therapeutic drug monitoring can be used interchangeably. CONCLUSIONS It is likely that biosimilars will be widely used for the treatment of IBD due to their cost savings and comparable efficacy. Nevertheless, robust post-marketing studies and pharmacovigilance are warranted in the coming years.


title: All India Ophthalmological Society - Preferred practice in refractive surgery during the COVID-19 pandemic.

text: Coronavirus pandemic has strained the healthcare system with mortality and morbidity. A number of elective surgeries have come to standstill due to lockdown and movement restrictions. Refractive surgery being a purely elective procedure and quite a fresh subset of ophthalmology, there is a lack of unanimity as to what precautions should be followed to resume the practice of same. This article attempts to highlight simple guidelines in accordance with an expert panel, which can be followed by all those involved directly or indirectly in refractive surgery services while addressing safety of doctors, supporting staff as well as patients as a primary concern.


title: The effect of passive heat stress on distress andself-control in male smokers and non-smokers.

text: In the current study, we tested the effects of core body temperature increases (e.g. heat stress) on affect, self-reported physical discomfort, and subsequent self-control in male smokers and nonsmokers using a novel passive heat stress paradigm, within a distress tolerance framework. Twenty-eight men (14 smokers), completed both heat stress and control sessions in randomized order. Results revealed that increases in core body temperature were associated with increased anxiety, irritability, and body discomfort as well as decreased happiness, with stronger effects for smokers. Smokers and nonsmokers both evidenced less self-control during the heat session and did not differ on this measure, nor on a measure of interoceptive sensitivity. The current study indicates that heat stress is a viable method for studying distress tolerance in men, and suggests the value in examining dynamic changes in self-control as a function of distress. Implications will be discussed for distress tolerance in general and smokers in specific.


title: Automation of a suturing device for minimally invasive surgery.

text: BACKGROUND In minimally invasive surgery, hand suturing is categorized as a challenge in technique as well as in its duration. This calls for an easily manageable tool, permitting an all-purpose, cost-efficient, and secure viscerosynthesis. Such a tool for this field already exists: the Autosuture EndoStitch(®). In a series of studies the potential for the EndoStitch to accelerate suturing has been proven. However, its ergonomics still limits its applicability. The goal of this study was twofold: propose an optimized and partially automated EndoStitch and compare the conventional EndoStitch to the optimized and partially automated EndoStitch with respect to the speed and precision of suturing. METHODS Based on the EndoStitch, a partially automated suturing tool has been developed. With the aid of a DC motor, triggered by a button, one can suture by one-fingered handling. Using the partially automated suturing manipulator, 20 surgeons with different levels of laparoscopic experience successfully completed a continuous suture with 10 stitches using the conventional and the partially automated suture manipulator. Before that, each participant was given 1 min of instruction and 1 min for training. Absolute suturing time and stitch accuracy were measured. The quality of the automated EndoStitch with respect to manipulation was tested with the aid of a standardized questionnaire. RESULTS To compare the two instruments, t tests were used for suturing accuracy and time. Of the 20 surgeons with laparoscopic experience (fewer than 5 laparoscopic interventions, n=9; fewer than 20 laparoscopic interventions, n=7; more than 20 laparoscopic interventions, n=4), there was no significant difference between the two tested systems with respect to stitching accuracy. However, the suturing time was significantly shorter with the Autostitch (P=0.01). The difference in accuracy and speed was not statistically significant considering the laparoscopic experience of the surgeons. The weight and size of the Autostitch have been criticized as well as its cable. However, the comfortable handhold, automatic needle change, and ergonomic manipulation have been rated positive. CONCLUSION Partially automated suturing in minimally invasive surgery offers advantages with respect to the speed of operation and ergonomics. Ongoing work in this field has to concentrate on minimization, implementation in robotic systems, and development of new operation methods (NOTES).


title: False sense of safety by daily QTc interval monitoring during methadone IVPCA titration in a patient with chronic pain.

text: It has been proposed that some deaths attributed to methadone are related to prolongation of the QTc interval; however, there are no clear recommendations on electrocardiogram (ECG) monitoring in patients undergoing intravenous methadone infusion. This is a report on a patient receiving methadone intravenous patient-controlled analgesia titration for the treatment of chronic pain. Initially, her daily ECGs showed QTc intervals within normal limits; however, she experienced a rapid increase in QTc interval from 317 ms to 784 ms within a 24-hour period after methadone had been discontinued for excessive sedation. QTc interval greater than 500 ms is considered to be high risk for the fatal arrhythmia Torsades de Pointes. Daily ECGs did not detect a gradual increase in the QTc interval that would have alerted the medical staff of the need to decrease or stop the methadone before reaching a prolonged QTc interval associated with cardiotoxicity. In selected cases where aggressive methadone titration is required, more intensive monitoring, such as telemetry or ECG determinations every 12 hours, might help detect changes in QTc interval duration that might otherwise be missed by daily ECG determinations.


Measles Outbreak among Adults, Northeastern China, 2014.


title: The Effectiveness of Additional Treatment Modalities after the Failure of Recanalization by Thrombectomy Alone in Acute Vertebrobasilar Arterial Occlusion.

text: OBJECTIVE Acute vertebrobasilar artery occlusion (AVBAO) is a devastating disease with a high mortality rate. One of the most important factors affecting favorable clinical outcome is early recanalization. Mechanical thrombectomy is an emerging treatment strategy for achieving a high recanalization rates. However, thrombectomy alone can be insufficient to complete recanalization, especially for acute stroke involving large artery atheromatous disease. The purpose of this study is to investigate the safety and efficacy of mechanical thrombectomy in AVBAO. METHODS Fourteen consecutive patients with AVBAO were treated with mechanical thrombectomy. Additional multimodal treatments were intra-arterial (IA) thrombolysis, balloon angioplasty, or permanent stent placement. Recanalization by thrombectomy alone and multimodal treatments were assessed by the Thrombolysis in Cerebral Infarction (TICI) score. Clinical outcome was determined using the National Institutes of Health Stroke Scale (NIHSS) at 7 days and the modified Rankin Scale (mRS) at 3 months. RESULTS Thrombectomy alone and multimodal treatments were performed in 10 patients (71.4%) and 4 patients (28.6%), respectively. Successful recanalization (TICI 2b-3) was achieved in 11 (78.6%). Among these 11 patients, 3 (27.3%) underwent multimodal treatment due to underlying atherosclerotic stenosis. Ten (71.4%) of the 14 showed NIHSS score improvement of >10. Overall mortality was 3 (21.4%) of 14. CONCLUSION We suggest that mechanical thrombectomy is safe and effective for improving recanalization rates in AVBAO, with low complication rates. Also, in carefully selected patients after the failure of recanalization by thrombectomy alone, additional multimodal treatment such as IA thrombolysis, balloons, or stents can be needed to achieve successful recanalization.


title: Optimizing resilience and wellbeing for healthcare professions trainees and healthcare professionals during public health crises - Practical tips for an 'integrative resilience' approach.

text: Public health crises, including pandemics, are associated with significant health risk and concomitant stress, fear, decreased sense of control, and uncertainty. Deleterious impact on both physical and mental health can result, including for healthcare professionals and health professions trainees. Changes in governmental policies and hospital protocols for healthcare professionals as well as disruption of educational formats and requirements for trainees can ensue. Difficult anxiety-provoking realities of public health crises including pandemics which involve caring for many seriously ill patients, moral distress including difficult care decisions, personal health risk, and/or potential risk to one's family can take a dire toll on the mental health of healthcare professionals at all stages of the professional lifecycle. Educational disruptions can create significant anxiety for trainees about completing requirements and achieving competencies. Within this, coping skills may be challenged and strengths may be elucidated as well. Such crises create an imperative for medical educators to support trainees' wellbeing through adaptive flexibility for curriculum innovation and culturally sensitive resilience and wellbeing interventions. Strategies ('tips') to optimize resilience and wellbeing with an integrative resilience approach of individual, learning environment, and organization/systems factors are presented.


Commentary: Message in a Bottle - Sending out an SOS to the World.


title: Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism.

text: BACKGROUND It is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. This is an update of the review first published in 2008. OBJECTIVES The aim of this review was to assess the efficacy of combined intermittent pneumatic leg compression (IPC) and pharmacological prophylaxis versus single modalities in preventing venous thromboembolism. SEARCH METHODS For this update the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (May 2016). In addition the CIS searched the Cochrane Register of Studies (CENTRAL (2016, Issue 4)). Clinical trials databases were searched for details of ongoing or unpublished studies. SELECTION CRITERIA Randomized controlled trials (RCTs) or controlled clinical trials (CCTs) of combined IPC and pharmacological interventions used to prevent VTE. DATA COLLECTION AND ANALYSIS We independently selected trials and extracted data. Disagreements were resolved by discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. MAIN RESULTS We included a total of 22 trials (9137 participants) of which 15 were randomized trials (7762 participants). The overall risk of bias was mostly unclear or high due to selection and performance bias. We used GRADE to assess the quality of the evidence and this was downgraded from high to moderate or very low due to the risk of bias, imprecision or indirectness.The rate of PE in the studies comparing IPC alone with combined IPC and pharmacological prophylaxis was low, underpowering the analyses. The incidence of symptomatic PE was 0.79% with IPC, but ranged between 0.1 to 1% with combined IPC and pharmacological prophylaxis (OR 0.49, 95% CI 0.18 to 1.34; 12 studies, 3017 participants, moderate quality evidence). The incidence of DVT was 4.10% in the IPC group and 2.19% in the combined group showing a reduced incidence of DVT in favour of the combined group (OR 0.52, 95% CI 0.33 to 0.82; 11 studies, 2934 participants, moderate quality evidence). The addition of an anticoagulant to IPC, however, increased the risk of any bleeding compared to IPC alone; 0.66% (7/1053) in the IPC group and 4.0% (44/1102) in the combined group (OR 5.04, 95% CI 2.36 to 10.77; 7 studies, 2155 participants, moderate quality evidence). Major bleeding followed a similar pattern; 0.1% (1/1053) in the IPC group to 1.5% (17/1102) in the combined group (OR 6.81, 95% CI 1.99 to 23.28; 7 studies, 2155 participants, moderate quality evidence).We detected no difference between the type of surgery subgroups such as orthopedic and non-orthopedic participants for DVT incidence (P = 0.16). Tests for differences between type of surgery subgroups were not possible for PE incidence.Compared with pharmacological prophylaxis alone, the use of combined IPC and pharmacological prophylaxis modalities reduced the incidence of symptomatic PE from 2.92% to 1.20% (OR 0.39, 95% CI 0.23 to 0.64; 10 studies, 3544 participants, moderate quality evidence). The incidence of DVT was 6.2% in the pharmacological prophylaxis group and 2.9% in the combined group showing no difference between the combined and pharmacological prophylaxis groups (OR 0.42, 95% CI 0.18 to 1.03; 11 studies, 2866 participants, moderate quality evidence). Increased bleeding side effects were not observed for IPC when it was added to anticoagulation (bleeding: OR 0.80, 95% CI 0.30 to 2.14, very low quality evidence; major bleeding: OR 1.21, 95% CI 0.35 to 4.18, very low quality evidence, 3 studies, 244 participants).No difference was detected between the type of surgery subgroups for PE incidence (P = 0.68) or for DVT incidence (P = 0.10). AUTHORS' CONCLUSIONS Moderate quality evidence suggests that combining IPC and pharmacological prophylaxis, compared with IPC or pharmacological prophylaxis alone, decreases the incidence of DVT when compared to compression, and incidence of PE when compared to anticoagulation. Moderate quality evidence suggests that there is no difference between combined and single modalities in the incidence of PE when compared with compression alone and DVT when compared with anticoagulation alone. The quality of evidence for PE or DVT was downgraded to moderate due to imprecision or risk of bias in study methodology, highlighting the need for further research. Moderate quality evidence suggests the addition of pharmacological prophylaxis to IPC, increased the risk of bleeding compared to IPC alone, a side effect not observed for IPC when added to pharmacological prophylaxis (very low quality evidence), as expected for a physical method of thromboprophylaxis. The quality of evidence for bleeding was downgraded to moderate due to indirectness or very low due to risk of bias in study methodology, indirectness and imprecision highlighting the need for further research. Nevertheless, the results of the current review agree with current guideline recommendations, which support the use of combined modalities in hospitalised patients (limited to those with trauma or undergoing surgery) at risk of developing VTE. More studies on the role of combined modalities in VTE prevention are needed.


title: Does the 5-Aminosalicylate Concentration Correlate with the Efficacy of Oral 5-Aminosalicylate and Predict Response in Patients with Inflammatory Bowel Disease? A Systematic Review.

text: BACKGROUND Oral 5-aminosalicylic acid (5-ASA, mesalazine) is the first choice therapeutic agent for treating mild-to-moderate ulcerative colitis (UC). Unfortunately a significant group of patients fail to respond. Therapeutic drug monitoring might help to maintain or induce remission by providing a tool for optimization of 5-ASA therapy. However, plasma and urine concentrations of 5-ASA reflect systemic uptake and are not useful to evaluate therapeutic effect. OBJECTIVES To explore if mucosal and faecal 5-ASA values correlate with disease activity and/or therapeutic effects in patients with inflammatory bowel disease, especially UC. METHOD We identified studies that analysed 5-ASA in faeces or mucosa of humans using an oral 5-ASA formulation, using PubMed and Embase. RESULTS In total, 39 studies (n = 939) were included, 27 on faecal 5-ASA, 9 on mucosal concentrations, and 3 on both faecal and mucosal values. We included 33 cross-sectional studies, 3 randomised clinical trials, 2 longitudinal cohorts and 1 randomized cross-over study. Mucosal 5-ASA concentrations in healthy subjects and patients on equivalent doses of 5-ASA were not found to differ remarkably. In the sub-analysis of mucosal 5-ASA concentrations in patients with active or quiescent UC, a higher concentration was seen during remission. Faecal concentrations were associated with 5-ASA doses but not with disease activity. Differences in faecal or mucosal 5-ASA values could not be ascribed to different 5-ASA formulations. CONCLUSIONS An increase of the mucosal 5-ASA concentrations was observed during remission in patients with UC. No clear relationship between the faecal 5-ASA excretion and the therapeutic efficacy was identified.


Laparoscopy at all costs? Not now during COVID-19 and not for acute care surgery and emergency colorectal surgery: a practical algorithm from a Hub Tertiary teaching hospital in Northern Lombardy, Italy.


title: Development of a specific AFLP-based SCAR marker for Chinese Race 34MKG of Puccinia graminis f. sp. tritici.

text: Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is a fungus that causes the devastating fungalwheat stem rust disease in wheat production. Rapid identification of the physiological races of Pgt are very importance for the prevention of wheat stem rust. In this paper we developed a molecular method to identify the most prevalent race of Pgt, as a supplement for traditionally used host-specific methods. Amplified fragment length polymorphism (AFLP) was employed as a means of analyzing DNA polymorphisms in six common physiological races of Pgt in China and Ug99. In total, 64 pairs of primers were used for AFLP screening of race-specific molecular markers. One primer pair-namely, E7/M7 (5'-GACTGCGTACCAATTCG G-3'/5'-GATGAGTCCTGAGTAACGG-3')-yielded a unique band for the race 34MKG that was purified and cloned into the pGEM-T vector for sequencing. We then designed a new primer pairs (sequence-characterized amplified region marker) to amplify the 171-bp fragment and confirmed that the marker was highly specific for 34MKG. These results provide a new tool for monitoring different races of Pgt for improved control of wheat stem rust in China.