title: Using wavelet coherence to characterize surface water infiltration into a low-lying karst aquifer.

text: Karstified carbonate aquifers may receive significant recharge contributions from losing streams, hence, the knowledge about surface water-groundwater (SW-GW) interactions is crucial with regard to water management (e.g. source protection zone delineation). The dynamics of SW-GW interactions may depend on factors such as the relative water levels between streams and aquifers, resulting in a temporal variation of exchange, which imposes complexity to the understanding of such dynamics. This study highlights the use of high-resolution time series and multi-resolution analysis to help to gain insights into such complex dynamics. Wavelet coherence (WTC) is applied on hourly time series of rainfall, stream and spring discharges of a low lying karstified spring catchment to yield a correlation in the time-frequency domain. This analysis provides comprehensive information on the overall impact of the river on the spring, which is supported by the cross-correlation function, as well as by more detailed information, including time-variant influences such as a threshold level of influence. Field observations of turbidity sampling at the spring appear to support this interpretation. This innovative approach relies on basic hydrological parameters, water level or discharge, and is therefore applicable to many other systems with such existing time series. This article is protected by copyright. All rights reserved.


title: Cardiac injury is associated with severe outcome and death in patients with Coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of observational studies.

text: Coronavirus disease 2019 (COVID-19) is a global pandemic impacting 213 countries/territories and more than 5,934,936 patients worldwide. Cardiac injury has been reported to occur in severe and death cases. This meta-analysis was done to summarize available findings on the association between cardiac injury and severity of COVID-19 infection. Online databases including Scopus, PubMed, Web of Science, Cochrane Library and Google Scholar were searched to detect relevant publications up to 20 May 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. In total, 22 studies with 3684 COVID-19 infected patients (severe cases=1095 and death cases=365) were included in this study. Higher serum levels of lactate dehydrogenase (weighted mean difference (WMD) =108.86 U/L, 95% confidence interval (CI)=75.93-141.79, p<0.001) and creatine kinase-MB (WMD=2.60 U/L, 95% CI=1.32-3.88, p<0.001) were associated with a significant increase in the severity of COVID-19 infection. Furthermore, higher serum levels of lactate dehydrogenase (WMD=213.44 U/L, 95% CI=129.97-296.92, p<0.001), cardiac troponin I (WMD=26.35 pg/mL, 95% CI=14.54-38.15, p<0.001), creatine kinase (WMD=48.10 U/L, 95% CI=0.27-95.94, p = 0.049) and myoglobin (WMD=159.77 ng/mL, 95% CI=99.54-220.01, p<0.001) were associated with a significant increase in the mortality of COVID-19 infection. Cardiac injury, as assessed by serum analysis (lactate dehydrogenase, cardiac troponin I, creatine kinase (-MB) and myoglobin), was associated with severe outcome and death from COVID-19 infection.


title: Methods of anorectal manometry vary widely in clinical practice: Results from an international survey.

text: BACKGROUND Ano-rectal manometry (ARM) is the most commonly performed investigation for assessment of anorectal dysfunction. Its use is supported by expert consensus documents and international guidelines. Variation in technology, data acquisition, and analysis affect results and clinical interpretation. This study examined variation in ARM between institutions to establish the status of current practice. METHODS A 50-item web-based questionnaire assessing analysis and interpretation of ARM was distributed by the International Anorectal Physiology Working Group via societies representing practitioners that perform ARM. Study methodology and performance characteristics between institutions were compared. KEY RESULTS One hundred and seven complete responses were included from 30 countries. Seventy-nine (74%) institutions performed at least two studies per week. Forty-nine centers (47%) applied conventional ARM (≤8 pressure sensors) and 57 (53%) high-resolution ARM (HR-ARM). Specialist centers were most likely to use HR-ARM compared to regional hospitals and office-based practice (63% vs 37%). Most conventional ARM systems used water-perfused technology (34/49); solid-state hardware was more frequently used in centers performing HR-ARM (44/57). All centers evaluated rest and squeeze. There was marked variation in the methods used to report results of maneuvers. No two centers had identical protocols for patient preparation, setup, study, and data interpretation, and no center fully complied with published guidelines. CONCLUSIONS & INFERENCES There is significant discrepancy in methods for data acquisition, analysis, and interpretation of ARM. This is likely to impact clinical interpretation, transfer of data between institutions, and research collaboration. There is a need for expert international co-operation to standardize ARM.


title: SARS-CoV-2 detection in formalin-fixed paraffin-embedded tissue specimens from surgical resection of tongue squamous cell carcinoma.

text: In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pathologists can be exposed to infection handling surgical specimens. Guidelines related to safety procedures in the laboratory have been released. However, there is a lack of studies performed on biopsy and surgical resection specimens. Here we report the detection of SARS-CoV-2 in formalin-fixed paraffin-embedded samples from surgical resection of tongue squamous cell carcinoma of a patient who developed COVID-19 postsurgery. RNA of SARS-CoV-2 strain was detected in the tumour and the normal submandibular gland samples using real-time PCR-based assay. No viral RNA was found in metastatic and reactive lymph nodes. We demonstrated that SARS-CoV-2 RNA can be detected in routine histopathological samples even before COVID-19 disease development. These findings may give important information on the possible sites of infection or virus reservoir, and highlight the necessity of proper handling and fixation before sample processing.


title: The Effect of Mobile App Interventions on Influencing Healthy Maternal Behavior and Improving Perinatal Health Outcomes: Systematic Review.

text: BACKGROUND Perinatal morbidity and mortality are significant public health issues with an enduring impact on the health and well-being of women and their families. Millions of pregnant women now download and use mobile applications to access, store, and share health information. However, little is known about the consequences. An investigation of their impact on perinatal health outcomes is particularly topical. OBJECTIVE To determine the effects of mobile app interventions during pregnancy on influencing healthy maternal behavior and improving perinatal health outcomes. METHODS Searches of PubMed, Embase, the Cochrane Library, CINAHL, WHO Global Health Library, POPLINE, and CABI Global Health were conducted with no date or language restrictions. Randomized and non-randomized studies were included if they reported perinatal health outcomes of interventions targeting pregnant women, using mobile apps compared with other communication modalities or with standard care. The primary outcome measure was the change in maternal behaviors (as defined by trial authors), by intervention goals. Two reviewers independently extracted data using standardized forms. RESULTS Four randomized controlled trials (RCTs) involving 456 participants were included. All studies targeted participants in early pregnancy; however, wide variation was evident in participant characteristics, intervention, and study outcomes measures. Three trials were based in hospital settings, comparing women using mobile apps with routine antenatal care. One community-based trial gave all participants a device to promote physical activity; the intervention arm was also given a mobile app. All studies reported data for the primary outcome measure, describing some benefit from the intervention compared with controls. However, few statistically significant primary or secondary outcomes were reported. Due to insufficient data, the planned meta-analysis and subgroup analyses were not performed. CONCLUSIONS Due to limited numbers, heterogeneity of interventions, comparators, and outcome measures, no firm conclusions can be drawn on the effects of mobile application interventions during pregnancy on maternal knowledge, behavior change, and perinatal health outcomes. As millions of women utilize mobile apps during pregnancy, rigorous studies are essential for health care and maternity care providers to optimally design, implement, and evaluate interventions.


title: Detection of Respiratory Viruses in the Clinical Outcome of Children With Fever and Neutropenia.

text: BACKGROUND Several evidence-based guidelines for the management of children with febrile neutropenia (FN) have been published, with special focus in bacterial and fungal infections. However, the role of acute respiratory infections caused by respiratory viruses (RV) has not been clearly established. The aim of this study was to evaluate the epidemiology, clinical presentation and outcome of acute respiratory infections in children with FN. METHODS Patients, <18 years of age admitted to the Pediatric Oncology-Hematology Unit after developing FN between November 2010 and December 2013, were prospectively included in the study. Children were evaluated by clinical examination and laboratory tests. Nasopharyngeal sample was obtained for detection of RV. RESULTS There was a total of 112 episodes of FN in 73 children admitted to the hospital during a 32-month period. According to disease severity, 33% of the episodes were considered moderate or severe. Rhinovirus was the most frequently detected RV (66.6%; 24/36), followed by parainfluenza. On regard to clinical outcome, RV-infected children developed fewer episodes of moderate or severe FN compared with non-RV infected children (16.7% vs. 33.3%; P = 0.08). CONCLUSIONS A great proportion of children with FN admitted to a tertiary hospital had a RV isolation. The rate of this RV isolation was significantly higher when a rapid molecular test was used compared with conventional microbiological methods. Rhinovirus was the most frequently isolated, although its role as an active agent of acute infection was not clear. Children with FN and a RV isolate had a lower rate of severe disease.


title: Radioimmunotherapy improves survival of rats with microscopic liver metastases of colorectal origin.

text: BACKGROUND Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. METHODS Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. RESULTS (111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). CONCLUSION This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors.


title: X-ray structure of the arenavirus glycoprotein GP2 in its postfusion hairpin conformation.

text: Arenaviruses are important agents of zoonotic disease worldwide. The virions expose a tripartite envelope glycoprotein complex at their surface, formed by the glycoprotein subunits GP1, GP2 and the stable signal peptide. This complex is responsible for binding to target cells and for the subsequent fusion of viral and host-cell membranes for entry. During this process, the acidic environment of the endosome triggers a fusogenic conformational change in the transmembrane GP2 subunit of the complex. We report here the crystal structure of the recombinant GP2 ectodomain of the lymphocytic choriomeningitis virus, the arenavirus type species, at 1.8-Å resolution. The structure shows the characteristic trimeric coiled coil present in class I viral fusion proteins, with a central stutter that allows a close structural alignment with most of the available structures of class I and III viral fusion proteins. The structure further shows a number of intrachain salt bridges stabilizing the postfusion hairpin conformation, one of which involves an aspartic acid that appears released from a critical interaction with the stable signal peptide upon low pH activation.


title: Implications of ventricular arrhythmia "bursts" with normal epicardial flow, myocardial blush, and ST-segment recovery in anterior ST-elevation myocardial infarction reperfusion: a biosignature of direct myocellular injury "downstream of downstream".

text: AIMS Establishing epicardial flow with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is necessary but not sufficient to ensure nutritive myocardial reperfusion. We evaluated whether adding myocardial blush grade (MBG) and quantitative reperfusion ventricular arrhythmia "bursts" (VABs) surrogates provide a more informative biosignature of optimal reperfusion in patients with Thrombolysis in Myocardial Infarction (TIMI) 3 flow and ST-segment recovery (STR). METHODS AND RESULTS Anterior STEMI patients with final TIMI 3 flow had protocol-blinded analyses of simultaneous MBG, continuous 12-lead electrocardiogram (ECG) STR, Holter VABs, and day 5-14 SPECT imaging infarct size (IS) assessments. Over 20 million cardiac cycles from >4500 h of continuous ECG monitoring in subjects with STR were obtained. IS and clinical outcomes were examined in patients stratified by MBG and VABs. VABs occurred in 51% (79/154) of subjects. Microcirculation (MBG 2/3) was restored in 75% (115/154) of subjects, of whom 53% (61/115) had VABs. No VABs were observed in subjects without microvascular flow (MBG of 0). Of 115 patients with TIMI 3 flow, STR, and MBG 2/3, those with VABs had significantly larger IS (median: 23.0% vs 6.0%, p=0.001). Multivariable analysis identified reperfusion VABs as a factor significantly associated with larger IS (p=0.015). CONCLUSIONS Despite restoration of normal epicardial flow, open microcirculation, and STR, concomitant VABs are associated with larger myocardial IS, possibly reflecting myocellular injury in reperfusion settings. Combining angiographic and ECG parameters of epicardial, microvascular, and cellular response to STEMI intervention provides a more predictive "biosignature" of optimal reperfusion than do single surrogate markers.


title: Cerebral oxygenation during different treatment strategies for a patent ductus arteriosus.

text: BACKGROUND Preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) are at risk for fluctuations in cerebral blood flow, but it is unclear how different hsPDA treatment strategies may affect cerebral oxygenation. OBJECTIVE To compare regional cerebral oxygen saturation (rSO(2)) as measured by near-infrared spectroscopy (NIRS) in very low birth weight (VLBW) infants with a hsPDA treated with conservative management, indomethacin, or surgical ligation. METHODS This prospective observational study enrolled 33 VLBW infants with a hsPDA diagnosed by echocardiogram and 12 control VLBW infants without a hsPDA. Infants had NIRS cerebral monitoring applied prior to conservative treatment, indomethacin, or surgical ligation. Cranial ultrasound and magnetic resonance imaging data were also collected. RESULTS Infants undergoing surgical ligation had a greater time period with >20% change in rSO(2) from baseline (30%) compared to those receiving indomethacin (7.4%, p = 0.001) or control infants without a hsPDA (2.6%, p = 0.0004). NIRS measures were not associated with abnormal neuroimaging in this small cohort. CONCLUSION These findings suggest that infants requiring surgical ligation for a hsPDA are at high risk for significant changes in cerebral oxygenation, whereas those receiving either indomethacin or conservative management maintain relatively stable cerebral oxygenation levels. Additional research is necessary to determine if NIRS monitoring identifies infants with a hsPDA at highest risk for brain injury.


title: Walking the dog: exploration of the contact networks between dogs in a community.

text: This study uses social network analysis to investigate potential contact among 214 dog-owning households in a UK community through their utilization of public space during walking. We identified a high level of potential contact between dog-owning households; most households walked their dogs in only a few areas but a small number visited many. Highly connected households were more likely to have multiple dogs, walk their dogs off lead, and own Working, Pastoral or some Terrier types. Similarly, most areas were only visited by a few households but a few were visited by many. Despite identification of subgroups of households and locations, we demonstrated high connectivity between dog-owning households, with minimum path lengths of two 'steps' (household-area-household, 74%) or four 'steps' (via two areas, 26%).


title: Virtual stenting of intracranial aneurysms: A pilot study for the prediction of treatment success based on hemodynamic simulations.

text: Endovascular treatment of intracranial aneurysms using flow-diverting devices has revolutionized the treatment of large and complex lesions due to its minimally invasive nature and potential clinical outcomes. However, incomplete or delayed occlusion and persistent intracranial aneurysm growth are still an issue for up to one-third of the patients. We evaluated two patients with intracranial aneurysm located at the internal carotid artery who were treated with flow-diverting devices and had opposite outcomes. Both patients presented with similar aneurysms and were treated with the same device, but after a 1-year follow-up, one case presented with complete occlusion (Case 1) and the other required further treatment (Case 2). To reproduce the interventions, virtual stents were deployed and blood flow simulations were carried out using the respective patient-specific geometries. Afterward, hemodynamic metrics such as aneurysmal inflow reduction, wall shear stresses, oscillatory shear, and inflow concentration indices were quantified. The hemodynamic simulations reveal that for both cases, the neck inflow was clearly reduced due to the therapy (Case 1: 19%, Case 2: 35%). In addition, relevant hemodynamic parameters such as time-averaged wall shear stress (Case 1: 35.6%, Case 2: 57%) and oscillatory shear (Case 1: 33.1%, Case 2: 26.7%) were decreased considerably. However, although stronger relative reductions occurred in the unsuccessful case, the absolute flow values in the successful case were approximately halved. The findings demonstrate that a high relative effect of endovascular devices is not necessarily associated with the desired treatment outcome. Instead, it appears that a successful intracranial aneurysm therapy requires a certain patient-specific inflow threshold.


title: Discovery of retroviral homologs in bats: implications for the origin of mammalian gammaretroviruses.

text: Gammaretroviruses infect a wide range of vertebrate species where they are associated with leukemias, neurological diseases and immunodeficiencies. However, the origin of these infectious agents is unknown. Through a phylogenetic analysis of viral gene sequences, we show that bats harbor an especially diverse set of gammaretroviruses. In particular, phylogenetic analysis places Rhinolophus ferrumequinum retrovirus (RfRV), a new gammaretrovirus identified by de novo analysis of the Rhinolophus ferrumequinum transcriptome, and six other gammaretroviruses from different bat species, as basal to other mammalian gammaretroviruses. An analysis of the similarity in the phylogenetic history between the gammaretroviruses and their bat hosts provided evidence for both host-virus codivergence and cross-species transmission. Taken together, these data provide new insights into the origin of the mammalian gammaretroviruses.


title: Application of a motion capture data glove for hand and wrist ergonomic analysis during laparoscopy.

text: OBJECTIVES This study aims to analyze the surgeons' hand spatial configuration during the use of two different instrument handles for laparoscopy, by obtaining information from the data glove CyberGlove®, and establishing existing risk levels for wrist disorders. MATERIAL AND METHODS Fifty surgeons participated in this study and were distributed into three groups (novices, intermediate and experts). Each subject carried out suturing and dissection tasks on a physical simulator, using axial-handled or ring-handled instruments, respectively. Hand and wrist positions were registered by the CyberGlove® and a modified RULA method was applied to establish appropriate risk levels for wrist disorders. RESULTS We found statistically significant differences in seven of the eleven glove sensors when comparing both tasks. RULA method showed that all subjects, with the exception of the experts using an axial-handled instrument, assume a prejudicial wrist posture during the practice of suturing and dissection tasks on the simulator. CONCLUSIONS Data glove CyberGlove® allows for the distinction between two laparoscopic exercises performed with different instruments. Also, laparoscopic intracorporeal suturing when performed with an axial-handled needle holder entails a more ergonomic posture for the wrist joint. Previous minimally invasive surgical experience is a positive influencing factor on the surgeons' wrist postures during laparoscopy.


title: How human factors affect escalation of care: a protocol for a qualitative evidence synthesis of studies.

text: INTRODUCTION Failure to rescue is defined as mortality after complications during hospital care. Incidence ranges 10.9%-13.3% and several national reports such as National Confidential Enquiry into Patient Outcomes and Death and National Institute of Clinical Excellence CG 50 highlight failure to rescue as a significant problem for safe patient care.To avoid failure to rescue events, there must be successful escalation of care. Studies indicate that human factors such as situational awareness, team working, communication and a culture promoting safety contribute to avoidance of failure to rescue events. Understanding human factors is essential to developing work systems that mitigate barriers and facilitate prompt escalation of care. This qualitative evidence synthesis will identify and synthesise what is known about the human factors that affect escalation of care. METHODS AND ANALYSIS We will search MEDLINE (Ovid), EMBASE (Ovid) and CINAHL, between database inception and 2018, for studies describing human factors affecting failure to rescue and/or care escalation. A search strategy was developed by two researchers and a medical librarian. Only studies exploring in-hospital (ward) populations using qualitative data collection methods will be included. Screening will be conducted by two researchers. We are likely to undertake a thematic synthesis, using the Thomas and Harden framework. Selected studies will be assessed for quality, rigour and limitations. Two researchers will extract and thematically synthesise codes using a piloted data extraction tool to develop analytical themes. ETHICS AND DISSEMINATION The qualitative evidence synthesis will use available published literature and no ethical approval is required. This synthesis will be limited by the quality of studies, rigour and reproducibility of study findings. Results will be published in a peer-reviewed journal, publicised at conferences and on social media. PROSPERO REGISTRATION NUMBER CRD42018104745.


title: Pemphigus autoantibodies generated through somatic mutations target the desmoglein-3 cis-interface.

text: Pemphigus vulgaris (PV) is an autoimmune blistering disease of skin and mucous membranes caused by autoantibodies to the desmoglein (DSG) family proteins DSG3 and DSG1, leading to loss of keratinocyte cell adhesion. To learn more about pathogenic PV autoantibodies, we isolated 15 IgG antibodies specific for DSG3 from 2 PV patients. Three antibodies disrupted keratinocyte monolayers in vitro, and 2 were pathogenic in a passive transfer model in neonatal mice. The epitopes recognized by the pathogenic antibodies were mapped to the DSG3 extracellular 1 (EC1) and EC2 subdomains, regions involved in cis-adhesive interactions. Using a site-specific serological assay, we found that the cis-adhesive interface on EC1 recognized by the pathogenic antibody PVA224 is the primary target of the autoantibodies present in the serum of PV patients. The autoantibodies isolated used different heavy- and light-chain variable region genes and carried high levels of somatic mutations in complementary-determining regions, consistent with antigenic selection. Remarkably, binding to DSG3 was lost when somatic mutations were reverted to the germline sequence. These findings identify the cis-adhesive interface of DSG3 as the immunodominant region targeted by pathogenic antibodies in PV and indicate that autoreactivity relies on somatic mutations generated in the response to an antigen unrelated to DSG3.


title: Skin to Skin: Transradial Carotid Angiography and Stenting.

text: Carotid artery stenting (CAS) is a proven alternative to carotid endarterectomy in patients with significant carotid disease. The femoral artery is the conventional access site for CAS procedures. However, this approach may be problematic because of peripheral vascular disease and anatomic variations. Access site complications are the most common adverse event after CAS from the transfemoral approach (TFA) and most technical failures are related to a complex aortic arch. The transradial approach has been evaluated to address the shortcomings of TFA. In cases involving a complex arch, transradial access may be a viable alternative strategy.


title: A sorting signal suppresses IFITM1 restriction of viral entry.

text: The interferon-induced transmembrane proteins (IFITMs) broadly inhibit virus infections, particularly at the viral entry level. However, despite this shared ability to inhibit fusion, IFITMs differ in the potency and breadth of viruses restricted, an anomaly that is not fully understood. Here, we show that differences in the range of viruses restricted by IFITM1 are regulated by a C-terminal non-canonical dibasic sorting signal KRXX that suppresses restriction of some viruses by governing its intracellular distribution. Replacing the two basic residues with alanine (KR/AA) increased restriction of jaagsiekte sheep retrovirus and 10A1 amphotropic murine leukemia virus. Deconvolution microscopy revealed an altered subcellular distribution for KR/AA, with fewer molecules in LAMP1-positive lysosomes balanced by increased levels in CD63-positive multivesicular bodies, where jaagsiekte sheep retrovirus pseudovirions are colocalized. IFITM1 binds to cellular adaptor protein complex 3 (AP-3), an association that is lost when the dibasic motif is altered. Although knockdown of AP-3 itself decreases some virus entry, expression of parental IFITM1, but not its KR/AA mutant, potentiates inhibition of viral infections in AP-3 knockdown cells. By using the substituted cysteine accessibility method, we provide evidence that IFITM1 adopts more than one membrane topology co-existing in cellular membranes. Because the C-terminal dibasic sorting signal is unique to human IFITM1, our results provide novel insight into understanding the species- and virus-specific antiviral effect of IFITMs.


title: Risk perception of musculoskeletal injury among critical care nurses.

text: BACKGROUND Nursing is known as an occupation with high risk of musculoskeletal injury. Nurses' perceptions about the risk of injury may have a role in preventing such injury. OBJECTIVES The aim of this study was to investigate how nurses perceived the risk of musculoskeletal injury from work and identify factors associated with their risk perception. METHODS In a cross-sectional study using a postal survey, 361 critical care nurses reported on risk perception, physical workload, psychosocial job factors, safety climate, musculoskeletal symptoms, and safe work behavior. RESULTS Of all critical care nurse respondents, 83% perceived that they were more likely than not to have a musculoskeletal injury within 1 year. On average, nurses perceived the risk of musculoskeletal injury as lower to themselves than to coworkers. This more positive perception of risk to self had stronger correlations with symptom experiences. Multiple linear regression analysis revealed that higher risk perception of injury was associated with greater job strain, greater physical workload, lack of availability of lifting devices or lifting teams, and more symptoms. DISCUSSION Study findings indicated that most critical care nurses were concerned about their ergonomic job risks. Their risk perceptions about musculoskeletal injury risk were affected by physical work exposures, psychosocial job stressors, and experience with musculoskeletal symptoms, but not by perceived workplace safety climate. The findings underscore the need for management efforts to improve physical and psychosocial working conditions and create a safe work environment.


title: Coronavirus disease 2019 (COVID-19) in children and/or adolescents: a meta-analysis.

text: BACKGROUND To assess the overall prevalence of clinical signs, symptoms, and radiological findings in children and/or adolescents with COVID-19. METHODS We systematically researched in PubMed, Scopus and Web of Science databases observational studies describing COVID-19 in children and/or adolescents until April 11, 2020. Data regarding clinical and radiological features were extracted from eligible studies and meta-analysis was performed using random-effects modeling. RESULTS We examined 19 eligible studies for a total of 2855 children and/or adolescents with COVID-19. Approximately 47% of subjects had fever (95% confidence interval [CI] 22-72%; I2 = 98.6%), 37% cough (95%CI 15-63%; I2 = 98.6%), 4% diarrhea (95%CI 0-12%; I2 = 92.2%), 2% nasal congestion (95%CI 0-7%; I2 = 87.7%), 1% dyspnea (95%CI 0-7%; I2 = 91.5%) and 0% abdominal pain (95%CI 0-1%; I2 = 76.3%). Subjects presented mild symptoms in 79% (95%CI 65-91%; I2 = 93.5%) of cases, whereas only 4% (95%CI 1-9%; I2 = 76.4%) were critical. Among those with pneumonia on computed tomography, 26.4% (95%CI 13-41%; I2 = 80.8%) presented a unilateral involvement, 16% (95%CI 5-29%, I2 = 81.2%) had bilateral involvement and 9% (95%CI 0-24%; I2 = 88.7%) had interstitial pneumonia. CONCLUSIONS Children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. IMPACT Compared to adults, children and/or adolescents tend to have a mild COVID-19 course with a good prognosis. This study provides new and consistence information on the clinical and radiological characteristics of COVID-19 in pediatrics. This study may help to fight COVID-19 in pediatric population.


title: Bronchial lumen is the safer route for an airway exchange catheter in double-lumen tube replacement: preventable complication in airway management for thoracic surgery.

text: There is no current consensus on which lumen an airway exchange catheter (AEC) should be passed through in double-lumen endotracheal tube (DLT) to exchange for a single-lumen endotracheal tube (SLT) after thoracic surgery. We report an unusual case to provide possible solution on this issue. A 71-year-old man with lung adenocarcinoma had an event of a broken exchange catheter used during a DLT replacement with a SLT, after a video-assisted thoracic surgery. The exchange catheter was impinged at the distal tracheal lumen and snapped during manipulation. All three segments of the catheter were retrieved without further airway compromises. Placement of airway tube exchanger into the tracheal lumen of double-lumen tube is a potential contributing factor of the unusual complication. We suggest an exchange catheter be inserted into the bronchial lumen in optimal depth with the adjunct of video laryngoscope, as the safe method for double-lumen tube exchange.


Harnessing multiple models for outbreak management.


Peripheral lymphocyte subset monitoring in COVID19 patients: a prospective Italian real-life case series.


title: Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle.

text: Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure-activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of 7ii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis.


title: Single-incision intragastric resection for upper and mid gastric submucosal tumors: a case-series study.

text: PURPOSE Laparoscopic gastric wedge resection is a standard treatment for removing gastric submucosal tumors (SMTs). So far, however, there have been few reports of single-incision laparoscopic intragastric wedge resection. Our aim was to describe this procedure and our experience with it. METHODS From January 2010 to December 2013, a total of 21 consecutive patients with gastric SMTs underwent single-incision intragastric resection at our institution. Their clinicopathologic data were analyzed retrospectively. RESULTS The patients consisted of nine men and 12 women with a mean age of 51.9 ± 12.9 years (22-69 years). Their mean body mass index was 22.6 ± 2.0 kg/m(2). Mean tumor size was 2.4 ± 0.7 cm, with the following anatomic distribution: esophagogastric junction in three patients, fundus in twelve, upper body in three, and lower body in two. Mean operating time was 68.6 ± 12.0 minutes. There were no conversions to open surgery and no major intraoperative complications. Time to resumption of water intake was 1.4 ± 0.5 days. Mean hospital stay was 4.9 ± 1.7 days. There were no recurrences or deaths during the mean 19-month follow-up. CONCLUSION Single-incision intragastric wedge resection is a feasible and safe procedure. It is especially efficient for treating small endophytic gastric SMTs located on the upper and mid portion of the stomach.


Audio Interview: A Covid-19-Related Syndrome in Children.


title: Modified frozen elephant trunk for acute type A aortic dissection: a comparative study with standard repair technique.

text: Objectives We hypothesized that antegrade open stent graft implantation in the descending aorta during acute type A aortic dissection surgery is safe and improves patient outcome compared with the standard repair technique. Methods Hundred and forty-one consecutive patients underwent surgery for acute type A aortic dissection at our institution from 2010 to 2016. Of those, 104 patients underwent ascending aorta and hemiarch repair under hypothermic circulatory arrest with antegrade cerebral perfusion (standard group). Since 2013, 37 patients have undergone the standard procedure combined with antegrade stent implantation in the descending aorta (stented group). A matched analysis using the logistic EuroSCORE (37 patients per group) was done. All data were collected prospectively. Results The mean logistic EuroSCORE was 29 in both groups, P = 1. Cardiopulmonary bypass time was 150 ± 57 (standard) vs 157 ± 48 (stented) min, P = 0.6; aortic clamping 99 ± 47 (standard) vs 100 ± 36 (stented) min, P = 1. Stented patients had longer circulatory arrest times with antegrade cerebral perfusion, 23 ± 7 vs 15 ± 7 min, P < 0.001. Stroke occurred in 24.3% (standard) vs 8.1% (stented), P = 0.1; paraplegia developed in 2.7% (standard) vs 0% (stented), P = 1. Abdominal intervention due to suspected visceral ischaemia was needed in 18.9% (standard) vs 5.4% (stented), P = 0.2. 30-day mortality was 13.5% (standard) vs 0% (stented), P = 0.05. Survival at 6-month was 100% and 86.5% in patients with implanted stents and standard repair, respectively, P = 0.02. Conclusions Antegrade, open stent graft implantation into the descending aorta during acute type A aortic dissection repair is safe and is associated with improved outcomes at 6 months postoperatively compared to the standard repair technique.


title: Clinical Performance of SARS-CoV-2 Molecular Testing.

text: Molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19), but the clinical performance of these tests is still poorly understood, particularly with regard to disease course, patient-specific factors, and viral shedding. From 3/10/2020-5/1/2020 NewYork-Presbyterian laboratories performed 27,377 SARS-CoV-2 molecular assays from 22,338 patients. Repeat testing was performed for 3,432 patients, of which 2,413 had initial negative and 802 had initial positive results. Repeat-tested patients were more likely to have severe disease and low viral loads. The negative predictive value of the first day result among repeat-tested patients was 81.3% The clinical sensitivity of SARS-CoV-2 molecular assays was estimated between 58 % and 96%, depending on the unknown number of false negative results in single-tested patients. Conversion to negative was unlikely to occur before 15 to 20 days after initial testing or 20-30 days after the onset of symptoms, with 50% conversion occurring at 28 days after initial testing. Conversion from first day negative to positive results increased linearly with each day of testing, reaching 25% probability in 20 days. Sixty patients fluctuated between positive and negative results over several weeks suggesting caution when acting on single results. In summary, our study provides estimates of the clinical performance of SARS-CoV-2 molecular assays and suggests time frames for appropriate repeat testing, namely 15 to 20 days after a positive test and the same or next 2 days after a negative test in patients with high suspicion for COVID-19.


title: Single incision laparoscopic TAPP with standard laparoscopic instruments and suturing of flaps: A continuing study.

text: BACKGROUND Single incision laparoscopic surgery, especially transumbilical, should be the closest to replicate the minimal access results achieved by natural orifice endoscopic surgery (NOTES). This study of single incision transabdominal preperitoneal (SITAPP) inguinal hernia repair is a continuing study exploring the peroperative variables and short and long term complications of this procedure. PATIENTS AND METHODS All the 183 patients were operated by the same surgeon through a horizontal transumbilical incision positioned across the lower third of the umbilicus. Port access was through three separate transfacial punctures. Routine rigid instruments were used and the peritoneal flaps were either tacked or sutured into place. Patients with irreducible hernia and obstructed hernia were included, while those with strangulated hernia were excluded. RESULTS All the patients were male with an average age of 41.4 years. Twenty four patients had bilateral hernia, 15 patients had irreducible and 6 patients had obstructed hernia. The mean operating time was 38.3 mins for unilateral hernias completed with tackers and 42.8 mins in those with intracorporeal suturing. The corresponding operating time for bilateral hernias was 53.2 and 62.7 minutes. There was minimal serous discharge from the umbilicus in 8 patients, port site infection in 1 patient and recurrence in 2 patients over a 36 months period. CONCLUSIONS SITAPP for groin hernias, performed with conventional instruments is feasible, easy to learn, has a very high patient acceptance and is cosmetically superior to conventional TAPP. The use of tackers reduces the operating time significantly.


title: Anti-frameshifting ligand reduces the conformational plasticity of the SARS virus pseudoknot.

text: Programmed -1 ribosomal frameshifting (-1 PRF) stimulated by mRNA pseudoknots regulates gene expression in many viruses, making pseudoknots potential targets for anti-viral drugs. The mechanism by which pseudoknots trigger -1 PRF, however, remains controversial, with several competing models. Recent work showed that high -1 PRF efficiency was linked to high pseudoknot conformational plasticity via the formation of alternate conformers. We tested whether pseudoknots bound with an anti-frameshifting ligand exhibited a similar correlation between conformational plasticity and -1 PRF efficiency by measuring the effects of a ligand that was found to inhibit -1 PRF in the SARS coronavirus on the conformational dynamics of the SARS pseudoknot. Using single-molecule force spectroscopy to unfold pseudoknots mechanically, we found that the ligand binding effectively abolished the formation of alternate conformers. This result extends the connection between -1 PRF and conformational dynamics and, moreover, suggests that targeting the conformational dynamics of pseudoknots may be an effective strategy for anti-viral drug design.


title: Gustatory Dysfunction as an Early Symptom in COVID-19 Screening.

text: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Wuhan, China in December 2019 leads to the present coronavirus disease 2019 (COVID-19) pandemic. The various symptoms identified for COVID-19 are fever, dry cough, sore throat, dyspnea, fatigue, myalgia, and headache. Olfactory and gustatory dysfunctions are emerging as a new symptom more in the European patients. Taste disturbances are common in various oral and systemic diseases. Varying severity and onset of taste disturbances are reported in COVID-19 positive patients in this pandemic. But a sudden onset of taste disturbances without an established and recognized cause should raise suspicion of COVID-19. This article will analyze the various studies focusing on taste disturbances as a reliable early symptom for COVID-19 screening.


title: Specific binding and uptake of 131I-MIBG and 111In-octreotide in metastatic paraganglioma--tools for choice of radionuclide therapy.

text: Tumor-specific uptake of the radiolabeled nor-epinephrine analogue meta-iodobenzylguanidine via norepinephrine transporter or radiolabeled somatostatin analogues octreotide/octreotate via somatostatin receptors offers possibilities to diagnose and treat metastatic pheochromocytoma/paraganglioma. High uptake of 123I-meta-iodobenzylguanidine is dependent on high expression of vesicular monoamine transporters responsible for mediating uptake of biogenic amines into dense core granules. A patient with metastatic paraganglioma (liver and bone metastases) underwent surgical removal of the primary after injection of 131I-meta-iodobenzylguanidine and 111In-octreotide. Radioactivity was determined in biopsies from tumor and normal tissue biopsies. The tumor/blood concentration value was high: 180 for 131I-meta-iodobenzylguanidine 3 h after injection and 590 for 111In-octreotide 27 h after injection. Studies of primary tumor cell cultures demonstrated increased cell membrane binding and internalization over time for 131I-meta-iodobenzylguanidine. The vesicular monoamine transporter antagonist reserpine and the norepinephrine transporter inhibitor clomipramine reduced internalization by 90% and 70%, respectively, after 46 h of incubation. The results demonstrated increased cell membrane binding and internalization over time also for 111In-octreotide. Internalization was highest for a low concentration of 111In-octreotide. Excess of octreotide reduced internalization of 111In-octreotide with 75% after 46 h of incubation. In conclusion, uptake and tumor/blood concentration values of radiolabeled meta-iodobenzylguanidine and somatostatin analogues can be determined for metastatic pheochromocytoma/paraganglioma to evaluate the possibility to use one or both agents for therapy. For this patient, the high tumor/blood values clearly demonstrated that therapy using both radiopharmaceuticals would be most beneficial. In vitro studies verified specific cell-membrane binding and internalization in tumor cells of both radiopharmaceuticals.


title: Public Health Response to COVID-19 Cases in Correctional and Detention Facilities - Louisiana, March-April 2020.

text: Correctional and detention facilities face unique challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1-3). Among >10 million annual admissions to U.S. jails, approximately 55% of detainees are released back into their communities each week (4); in addition, staff members at correctional and detention facilities are members of their local communities. Thus, high rates of COVID-19 in correctional and detention facilities also have the potential to influence broader community transmission. In March 2020, the Louisiana Department of Health (LDH) began implementing surveillance for COVID-19 among correctional and detention facilities in Louisiana and identified cases and outbreaks in many facilities. In response, LDH and CDC developed and deployed the COVID-19 Management Assessment and Response (CMAR) tool to guide technical assistance focused on infection prevention and control policies and case management with correctional and detention facilities. This report describes COVID-19 prevalence in correctional and detention facilities detected through surveillance and findings of the CMAR assessment. During March 25-April 22, 489 laboratory-confirmed COVID-19 cases, including 37 (7.6%) hospitalizations and 10 (2.0%) deaths among incarcerated or detained persons, and 253 cases, including 19 (7.5%) hospitalizations and four (1.6%) deaths among staff members were reported. During April 8-22, CMAR telephone-based assessments were conducted with 13 of 31 (42%) facilities with laboratory-confirmed cases and 11 of 113 (10%) facilities without known cases. Administrators had awareness and overall understanding of CDC guidance for prevention of transmission in these facilities but reported challenges in implementation, related to limited space to quarantine close contacts of COVID-19 patients and inability of incarcerated and detained persons to engage in social distancing, particularly in dormitory-style housing. CMAR was a useful tool that helped state and federal public health officials assist multiple correctional and detention facilities to better manage COVID-19 patients and guide control activities to prevent or mitigate transmission.


Central cannulation (aortic and pulmonary artery) and sequential clamping from distal to proximal in the surgical management of chronic type B dissection utilizing hypothermic circulatory arrest.


[COVID-19 coronavirus: what implications for Cardiology?]


title: Decellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds.

text: Decellularized biologic scaffolds are gaining popularity over synthetic biomaterials as naturally derived materials capable of promoting improved healing. Nevertheless, the most widely used biologic material - acellular dermal matrix (ADM) - exhibits slow repopulation and remodeling, which prevents integration. Additionally, engineering control of these materials is limited because they require a natural source for their production. In the current report, we demonstrate the feasibility of using genetically engineered animals to create decellularized biologic scaffolds with favorable extracellular matrix (ECM) properties. Specifically, we utilized skin from thrombospondin (TSP)-2 KO mice to derive various decellularized products. Scanning electron microscopy and mechanical testing showed that TSP-2 KO ADM exhibited an altered structure and a reduction in elastic modulus and ultimate tensile strength, respectively. When a powdered form of KO ADM was implanted subcutaneously, it was able to promote enhanced vascularization over WT. Additionally, when implanted subcutaneously, intact slabs of KO ADM were populated by higher number of host cells when compared to WT. In vitro studies confirmed the promigratory properties of KO ADM. Specifically, degradation products released by pepsin digestion of KO ADM induced greater cell migration than WT. Moreover, cell-derived ECM from TSP-2 null fibroblasts was more permissive to fibroblast migration. Finally, ADMs were implanted in a diabetic wound model to examine their ability to accelerate wound healing. KO ADM exhibited enhanced remodeling and vascular maturation, indicative of efficient integration. Overall, we demonstrate that genetic manipulation enables engineered ECM-based materials with increased regenerative potential.


title: Prone positioning in severe acute respiratory distress syndrome.

text: BACKGROUND Previous trials involving patients with the acute respiratory distress syndrome (ARDS) have failed to show a beneficial effect of prone positioning during mechanical ventilatory support on outcomes. We evaluated the effect of early application of prone positioning on outcomes in patients with severe ARDS. METHODS In this multicenter, prospective, randomized, controlled trial, we randomly assigned 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (FiO2) of less than 150 mm Hg, with an FiO2 of at least 0.6, a positive end-expiratory pressure of at least 5 cm of water, and a tidal volume close to 6 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died from any cause within 28 days after inclusion. RESULTS A total of 237 patients were assigned to the prone group, and 229 patients were assigned to the supine group. The 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (P<0.001). The hazard ratio for death with prone positioning was 0.39 (95% confidence interval [CI], 0.25 to 0.63). Unadjusted 90-day mortality was 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group. CONCLUSIONS In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique National 2006 and 2010 of the French Ministry of Health; PROSEVA ClinicalTrials.gov number, NCT00527813.).


title: STIs and the COVID-19 pandemic: the lockdown does not stop sexual infections.

text: In December 2019 a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China, responsible for an aggressive interstitial pneumonia. Italy was the first western country to be hit by the CoronaVIrus Disease 2019 (COVID-19) and on 9 March our Prime Minister announced a nationwide lockdown, strictly forbidding any contacts outside cohabitants, except for urgent or medical reasons. In compliance with the ministerial decree, all scheduled visits were suspended, maintaining hospital access only for emergencies.


What could coronavirus teach us?


title: Brain gadolinium deposition after administration of gadolinium-based contrast agents.

text: Gadolinium-based contrast agents (GBCAs) consist of gadolinium ions and a chelating agent that binds the gadolinium ion tightly so that its toxicity is not manifested. However, in 2013, an association between brain MRI abnormalities and a history of GBCA administration was first reported. Even in patients with normal renal function, increased signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images showed a positive correlation with previous exposure to linear chelate type GBCAs, but not to macrocyclic chelate type ones. This difference of GBCAs is speculated to reflect the stability of GBCAs, and de-chelated gadolinium deposition has been strongly suspected. Using inductively coupled plasma mass spectroscopy, gadolinium was detected from patients' brains with a history of repeated GBCA administration. In some cases, the gadolinium concentration of a patient's brain with normal renal function exceeded the gadolinium concentration of the skin in nephrogenic systemic fibrosis patients, but without any histological change. The actual risk has not been documented yet, but it seems important to consider the potential unknown risks of residual gadolinium in our decisions regarding GBCA administration, and to make efforts to minimize any residual gadolinium in the patient's body.


title: Recombinant probes for visualizing endogenous synaptic proteins in living neurons.

text: The ability to visualize endogenous proteins in living neurons provides a powerful means to interrogate neuronal structure and function. Here we generate recombinant antibody-like proteins, termed Fibronectin intrabodies generated with mRNA display (FingRs), that bind endogenous neuronal proteins PSD-95 and Gephyrin with high affinity and that, when fused to GFP, allow excitatory and inhibitory synapses to be visualized in living neurons. Design of the FingR incorporates a transcriptional regulation system that ties FingR expression to the level of the target and reduces background fluorescence. In dissociated neurons and brain slices, FingRs generated against PSD-95 and Gephyrin did not affect the expression patterns of their endogenous target proteins or the number or strength of synapses. Together, our data indicate that PSD-95 and Gephyrin FingRs can report the localization and amount of endogenous synaptic proteins in living neurons and thus may be used to study changes in synaptic strength in vivo.


title: Human respiratory syncytial virus infection is inhibited by IFN-induced transmembrane proteins.

text: The IFN immune system plays an essential role in protecting the host against most viral infections. In order to explore the interactions between the IFN pathway and human respiratory syncytial virus (RSV) infection, and to identify potential IFN-stimulated genes (ISGs) that may be involved in suppressing the replication of RSV, we utilized an IFN pathway-specific microarray to study the effects of RSV infection on the IFN pathway in HeLa cells. We showed that RSV infection enhanced the expression of a series of ISGs, including oligoadenylate synthetase 2, IFITM1 (IFN-induced transmembrane protein 1) and myxovirus resistance 2. Our results also showed that the IFITM proteins potently inhibited RSV infection mainly by interfering with both virus entry and the subsequent replication steps, but not the attachment process. The antiviral effect of IFITM3 was not affected by ubiquitination modification. Furthermore, knocking down the endogenous and IFN-induced expression of IFITM1 and 3 facilitated RSV infection. Expression of the IFITM proteins was found to delay the phosphorylation of IFN regulatory factor 3 through interfering with the detection of viral RNA by MDA5 (melanoma differentiation-associated gene 5) and RIG-I (retinoic acid-inducible gene I). These results demonstrated that the restriction of RSV infection by the IFITM proteins was achieved through the inhibition of virus entry and replication, and they provided further insight for exploring the mechanism of IFITM-protein-mediated virus restriction.


title: Endovenous thermal ablation for healing venous ulcers and preventing recurrence.

text: BACKGROUND Venous leg ulcers represent the worst extreme within the spectrum of chronic venous disease. Affecting up to 3% of the adult population, this typically chronic, recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The current mainstay of treatment for venous leg ulcers is compression therapy, which has been shown to enhance ulcer healing rates. Open surgery on the veins in the leg has been shown to reduce ulcer recurrence rates, but it is an unpopular option and many patients are unsuitable. The efficacy of the newer, minimally-invasive endovenous thermal techniques has been established in uncomplicated superficial venous disease, and these techniques are now beginning to be used in the management of venous ulceration, though the evidence for this treatment is currently unclear. It is hypothesised that, when used with compression, ablation may further reduce pressures in the leg veins, resulting in improved rates of healing. Furthermore, since long-term patient concordance with compression is relatively poor, it may prove more popular, effective and cost-effective to provide a single intervention to reduce recurrence, rather than life-long treatment with compression. OBJECTIVES To determine the effects of superficial endovenous thermal ablation on the healing, recurrence and quality of life of people with active or healed venous ulcers. SEARCH METHODS In August 2013 we searched Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions on the language of publication but there was a date restriction based on the fact that superficial endovenous thermal ablation is a comparatively new medical technology. SELECTION CRITERIA Randomised clinical trials comparing endovenous thermal ablative techniques with compression therapy alone for venous leg ulcers were eligible for inclusion. Trials had to report on at least one objective measure of ulcer healing (primary outcome) such as proportion of ulcers healed at a given time point, time to complete healing, change in ulcer size, proportion of ulcers recurring over a given time period, or at a specific point, and ulcer-free days. Secondary outcomes sought included patient-reported quality of life, economic data and adverse events. DATA COLLECTION AND ANALYSIS Details of potentially eligible studies were extracted and summarised using a data extraction table. Data extraction and validity assessment were performed independently by two review authors, and any disagreements resolved by consensus or by arbitration of a third review author. MAIN RESULTS No eligible randomised controlled trials were identified. There is an absence of evidence regarding the effects of superficial endovenous thermal ablation on ulcer healing, recurrence or quality of life of people with venous leg ulcer disease. AUTHORS' CONCLUSIONS The review identified no randomised controlled trials on the effects on ulcer healing, recurrence or quality of life, of superficial endovenous thermal ablation in people with active or healed venous leg ulcers. Adequately-powered, high quality randomised controlled trials comparing endovenous thermal ablative interventions with compression therapy are urgently required to explore this new treatment strategy. These should measure and report outcomes that include time to ulcer healing, ulcer recurrence, quality of life and cost-effectiveness.


title: COVID-19 preparedness and response at a large UK major trauma operating theatres department.

text: This article aims to describe the early experience of a large major trauma operating theatres department in the East of England during the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. To date and to our knowledge, a small amount of reports describing a surgical department's response to this unprecedented pandemic have been published, but a well-documented account from within the United Kingdom (UK) has not yet been reported in the literature. We describe our preparation and response, including: operating theatres management during the COVID-19 pandemic, operational aspects and communication, leadership and support. The process review of measures presented covers approximately the two-month period between March and May 2020 and emphasises the fluidity of procedures needed. We discuss how significant challenges were overcome to secure implementation and reliable oversight. The visible presence of clinical leads well sighted on every aspect of the response guaranteed standardisation of procedures, while sustaining a vital feedback loop. Finally, we conclude that an effective response requires rapid analysis of the complex problem that is of providing care for patients intraoperatively during the COVID-19 pandemic, and that retrospective sense-making is essential to maintain adaptability.


title: Correction: Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus.

text: [This corrects the article DOI: 10.1371/journal.pone.0227547.].


title: Pharmaceutical treatment of acute bipolar depression.

text: The treatment of bipolar depression is one of the most challenging fields in contemporary psychiatry. The best data concern the antipsychotics quetiapine and the olanzapine-fluoxetine combination. However, the usefulness of antidepressants in bipolar depression remains controversial; positive data are available for fluoxetine but negative results have been published for paroxetine. Accumulated knowledge so far suggests that bipolar patients need continuous administration of an antimanic agent even during the acute depressive phase. Although our knowledge is indeed limited, the development of guidelines for polypharmacy is necessary and should be done as soon as possible.


title: Impact of the intensity of microemboli on neurocognitive outcome following cardiopulmonary bypass.

text: BACKGROUND This study aimed to determine whether there was any association between the intensity of intraoperative gaseous microembolic signals (GME), neuropsychological testing and clinical outcome in high-risk patients undergoing coronary artery surgery (CABG). METHODS Over a 6-month period, GME activity was monitored in 102 Euroscore 6+ patients during cardiopulmonary bypass (CPB) with a conventional 32-micron arterial filter by non-invasive, real-time ultrasonic device. Cognitive tests; line bisection, the Stroop test, finger tapping, and the Rey Auditory Verbal Learning Test were performed at baseline, postoperative one week and postoperative one month. RESULTS The distribution of GME activity showed that there were three groups of patients: >500 total emboli (n = 38); 250 to 500 emboli (n = 30) and <250 emboli (n = 34) at a detection level of 2% of the circuit diameter on the arterial side. Line bisection, the Stroop test and finger tapping were impaired significantly in >500 emboli patients versus control (<250 emboli) in postoperative week one, but resolved in one month. CONCLUSIONS Correlation between intraoperative GME intensity and neurocognitive tests suggests that the level of GME might have a role in determining the psychological outcome after CABG with CPB.


title: Early Reverse Cardiac Remodeling Effect of Laparoscopic Sleeve Gastrectomy.

text: BACKGROUND This study evaluated the early postoperative benefits of laparoscopic sleeve gastrectomy (LSG) on the left ventricular (LV) function and left atrial (LA) structural, mechanical, and electrical functions in severely obese patients. METHODS Thirty-two patients with severe obesity who were consecutively scheduled for LSG and 30 healthy controls were included in the study. LV global longitudinal strain (LGS), peak atrial longitudinal strain (PALS), and strain rates (S-Sr, E-Sr, and A-Sr) of the lateral and septal LA walls, and intra- and interatrial dyssynchrony periods for all subjects were evaluated using strain echocardiography. The measurements were repeated in patients 1 month after surgery. RESULTS LGS of the LV was significantly depressed in the patient group compared with the control group (p < 0.001). LA peak septal and lateral wall strain values were significantly lower in patients than in controls (both p values <0.001). LA intra- and interatrial dyssynchrony periods were longer in patients than in controls (p = 0.012 and p = 0.004, respectively). LGS significantly improved after LSG (p < 0.001). Significant reductions were noted in the LA antero-posterior diameter (p < 0.001), LA volume index (LAVI, p = 0.001), and in the mitral velocity to the early diastolic velocity of the mitral annulus ratio (E/e' ratio, p = 0.046). The PALS of the septal and lateral LA walls significantly increased (p = 0.001 and p < 0.001, respectively). S-Sr, E-Sr, and A-Sr values of the septal LA wall (p = 0.049, p < 0.001, and p = 0.001, respectively) and the lateral LA wall (p = 0.009, p = 0.007, and p = 0.002, respectively) significantly improved postoperatively. Intra- and interatrial dyssynchrony significantly decreased (p = 0.001 and p < 0.001, respectively). Weight loss positively correlated with changes in LGS (R = 0.39, p = 0.039), LAVI (R = 0.39, p = 0.034), intra-atrial dyssynchrony (R = 0.45, p = 0.021), interatrial dyssynchrony (R = 0.42, p = 0.038), septal LA wall peak strain (R = 0.44, p = 0.027), lateral LA wall peak strain (R = 0.46, p = 0.017), septal LA wall A-Sr (R = 0.43, p = 0.028), and lateral LA wall A-Sr (R = 0.46, p = 0.019). The comparison of postoperative findings of the patients with controls revealed that the LA diameter, both LA volume and volume index (LAVI), E/e' ratio, S-Sr and E-Sr of both lateral and septal LA walls, intra- and interatrial LA dyssynchrony of the patient group became similar to the control group (all p value >0.05). Postoperative A-Sr values of both LA walls (both p value <0.001) were higher in patients than controls. CONCLUSION The benefits of LSG on LV and LA function may be observed even in the early postoperative phase. The resulting weight loss correlates with LV and LA reverse remodeling in severely obese patients.


title: Structural markers observed with endoscopic 3-dimensional optical coherence tomography correlating with Barrett's esophagus radiofrequency ablation treatment response (with videos).

text: BACKGROUND Radiofrequency ablation (RFA) is effective for treating Barrett's esophagus (BE) but often involves multiple endoscopy sessions over several months to achieve complete response. OBJECTIVE Identify structural markers that correlate with treatment response by using 3-dimensional (3-D) optical coherence tomography (OCT; 3-D OCT). DESIGN Cross-sectional. SETTING Single teaching hospital. PATIENTS Thirty-three patients, 32 male and 1 female, with short-segment (<3 cm) BE undergoing RFA treatment. INTERVENTION Patients were treated with focal RFA, and 3-D OCT was performed at the gastroesophageal junction before and immediately after the RFA treatment. Patients were re-examined with standard endoscopy 6 to 8 weeks later and had biopsies to rule out BE if not visibly evident. MAIN OUTCOME MEASUREMENTS The thickness of BE epithelium before RFA and the presence of residual gland-like structures immediately after RFA were determined by using 3-D OCT. The presence of BE at follow-up was assessed endoscopically. RESULTS BE mucosa was significantly thinner in patients who achieved complete eradication of intestinal metaplasia than in patients who did not achieve complete eradication of intestinal metaplasia at follow-up (257 ± 60 μm vs 403 ± 86 μm; P < .0001). A threshold thickness of 333 μm derived from receiver operating characteristic curves corresponded to a 92.3% sensitivity, 85% specificity, and 87.9% accuracy in predicting the presence of BE at follow-up. The presence of OCT-visible glands immediately after RFA also correlated with the presence of residual BE at follow-up (83.3% sensitivity, 95% specificity, 90.6% accuracy). LIMITATIONS Single center, cross-sectional study in which only patients with short-segment BE were examined. CONCLUSION Three-dimensional OCT assessment of BE thickness and residual glands during RFA sessions correlated with treatment response. Three-dimensional OCT may predict responses to RFA or aid in making real-time RFA retreatment decisions in the future.


title: Endovascular management of carotid and vertebral artery dissections with new generation double-mesh stent and protection systems - single-center early and midterm results.

text: Introduction Symptomatic dissections (SD) of cervical arteries are still a therapeutic problem. Although endovascular management (EM) is currently a preferred method of treatment of SD, complications associated with this method of treatment in published reports are quite frequent (3-16%). Aim In this retrospective study we analyzed the results of EM with novel, double-mesh stent and protection systems (PS) for SD of the internal carotid (IC) or vertebral arteries (VA) that coexisted with hemodynamically significant stenosis or aneurysmatic dilatation of the dissected artery. Material and methods We evaluated the results of EM in 19 patients (men 15, median age: 55, range: 25-83), presenting with SD of the IC or VA with coexisting stenosis and/or aneurysmatic dilatation of the artery in segments C1-C5 of IC or V0-V4 of VA. Twelve patients had a stroke, 6 TIA, and 3 patients a headache and/or a neck pain with Horner syndrome. Stents and PS were tailored according to the location, length of dissection and coexisting stenotic or aneurysmatic lesions. Results There were no new strokes, in-hospital deaths or other serious morbidities during the procedure and postprocedural hospital stay. There were no fatalities during 6-40 months of follow-up. In control angiographies performed after interventions all patients demonstrated a patent target artery, complete coverage of the dissection and aneurysm by stents and no new lesions in the area of the previous dissection. Conclusions The results of this study indicate that EM of SD of IC and VA with the new stents and PS is safe and effective with good early and midterm results.


title: Geometric morphometric shape analysis in an ovine model confirms that the upper esophageal sphincter is not round.

text: OBJECTIVES/HYPOTHESIS Dysfunction of the upper esophageal sphincter (UES) is a common cause of oral-pharyngeal dysphagia (OPD). Dilation is a primary treatment, although current techniques are subject to a high rate of failure and recurrence. Devices available for UES dilation are cylindrical and were designed to distend the round lumen of the esophagus. Our objective was to determine the cross-sectional dimension of the UES in an ovine model of OPD and compare it with that of the cervical esophagus. STUDY DESIGN Prospective cadaveric animal study. METHODS Three-dimensional casts of the upper aerodigestive tract of 10 fresh cadaveric ewes were constructed using a platinum-cured liquid silicone polymer. Cross-sections at the level of the UES and cervical esophagus were digitized and mathematically compared using geometric morphometric shape analysis. RESULTS Consensus shape among all 10 animals revealed that the narrowest region of the maximally distended UES has a cross-sectional shape that resembles a kidney, whereas the cervical esophagus approximates a circle. The shape of the UES and cervical esophagus were significantly different (P < .0001), and surface area calculations demonstrated that an inscribed circle significantly underestimated the area implied by the kidney-shaped UES model. CONCLUSIONS Current dilators used to treat UES dysfunction are cylindrical and based on the assumption that the UES is round. This is the first report to empirically analyze the cross-sectional area of the UES utilizing an established ovine model. The data suggest that the cross-sectional area of the UES is shaped like a kidney, and currently available cylindrical dilators are suboptimal for UES distention.


VIRAL TRANSPORTATION IN COVID-19 PANDEMIC: INACTIVATED VIRUS TRANSPORTATION SHOULD BE IMPLEMENTED FOR SAFE TRANSPORTATION AND HANDLING AT DIAGNOSTICS LABORATORIES.


Is Universal Testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Needed on All Labor and Delivery Units?


title: Effect of combining a recruitment maneuver with protective ventilation on inflammatory responses in video-assisted thoracoscopic lobectomy: a randomized controlled trial.

text: BACKGROUND We hypothesized that the addition of a recruitment maneuver to protective ventilation (PVRM) would result in lower pulmonary and systemic inflammatory responses than traditional ventilation or protective ventilation (PV) alone in patients undergoing lung surgery. METHODS Sixty patients who underwent scheduled thoracoscopic lobectomy were randomly assigned to three groups: traditional ventilation, PV, or PVRM. Ventilations were performed using a tidal volume of 10 mL/kg for the traditional ventilation group and either 8 mL/kg (two-lung) or 6 mL/kg (one-lung, OLV) with a positive end-expiratory pressure of 5 cm H2O for the PV and PVRM groups. The RM was performed 10 min after the start of OLV. Fiberoptic bronchoalveolar lavage (BAL) was performed twice in dependent and non-dependent lungs: before the start and immediately after the end of OLV. Blood samples were collected at the same time points. The levels of cytokines, including TNF-α, IL-1β, IL-6, IL-8, and IL-10, were measured. RESULTS After OLV, the level of TNF-α in the BAL fluid of dependent lungs was significantly higher in the PV than in the PVRM group (P = 0.049), whereas IL-1β, IL-6, IL-8, and IL-10 levels were not significantly different among the groups. In non-dependent lung BAL fluid, no cytokines were significantly different among the groups. After OLV, IL-10 serum levels were significantly higher in the traditional ventilation than in the PVRM group (P = 0.027). CONCLUSIONS Lower inflammatory responses in the ventilated lung and serum were observed with PVRM than with traditional ventilation or PV alone. Larger multi-center clinical trials are warranted to confirm the effects of different ventilatory strategies on postoperative outcomes.


title: EASAPS/ESPRAS Considerations in getting back to work in Plastic Surgery with the COVID-19 Pandemic - A European point of view.

text: The aim of this paper is to summarize the results of a consensus process and a European webinar of the two societies, European Association of Societies of Aesthetic Surgery (EASAPS) and the European Society of Plastic, Reconstructive and Aesthetic Societies (ESPRAS) on what is considered safe practice based on the scientific knowledge we have today. This review of the current situations gives considerations which have to be taken into account when getting back to work in plastic surgery with COVID-19 in Europe. At all times, one should be familiar the local and regional infection rates in the community, with particular emphasis on the emergence of second and third waves of the pandemic. Due to the fast-evolving nature of the COVID-19 pandemic the recommendations aim to be rather considerations than fixed guidelines and might need to be revised in near future.


title: Influenza in Brazil: surveillance pathways.

text: Influenza is a viral disease of global concern that has demanded the attention of health authorities. Since 1947, as a preventive measure, the World Health Organization monitors viral circulation to define the annual vaccine through a worldwide network of laboratories. This article presents the structuring of influenza surveillance in Brazil and highlights virological surveillance and the role of diagnostic laboratories as well as the expansion of actions to improve detection and expedite responses. The model set corresponds to sentinel surveillance complemented by the universal notification of severe acute respiratory syndrome investigating outbreaks, deaths, and unusual events and monitoring hospitalization and mortality in an expanded surveillance. In this review, we address aspects of influenza surveillance in animals, the need for interagency integration, and the sharing of information in many surveillance systems.


title: Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke.

text: INTRODUCTION Unfortunately, over 40% of stroke victims have pre-existing diabetes which not only increases their risk of stroke up to 2-6 fold, but also worsens both functional recovery and the severity of cognitive impairment. Our lab has recently linked the chronic inflammation in diabetes to poor functional outcomes and exacerbated cognitive impairment, also known as post-stroke cognitive impairment (PSCI). Although we have shown that the development of PSCI in diabetes is associated with the upregulation and the activation of pro-inflammatory microglia, we have not established direct causation between the two. To this end, we evaluated the role of microglia in the development of PSCI. METHODS At 13 weeks of age, diabetic animals received bilateral intracerebroventricular (ICV) injections of short hairpin RNA (shRNA) lentiviral particles targeting the colony stimulating factor 1 receptor (CSF1R). After 14 days, animals were subjected to 60 min middle cerebral artery occlusion (MCAO) or sham surgery. Adhesive removal task (ART), novel object recognition (NOR), and 2-trial Y-maze were utilized to evaluate sensorimotor and cognitive function. Tissue from freshly harvested brains was analyzed by flow cytometry and immunohistochemistry. RESULTS CSF1R silencing resulted in a 94% knockdown of residential microglia to relieve inflammation and improve myelination of white matter in the brain. This prevented cognitive decline in diabetic animals. CONCLUSION Microglial activation after stroke in diabetes may be causally related to the development of delayed neurodegeneration and PSCI.


title: Population pharmacokinetic analysis of propofol in underweight patients under general anaesthesia.

text: BACKGROUND The modified Marsh and Schnider pharmacokinetic models for propofol consistently produce negatively and positively biased predictions in underweight patients, respectively. We aimed to develop a new pharmacokinetic model of propofol in underweight patients. METHODS Twenty underweight (BMI<18.5 kg m-2) patients aged 20-68 yr were given an i.v. bolus of propofol (2 mg kg-1) for induction of anaesthesia. Anaesthesia was maintained with a zero-order infusion (8 mg kg-1 h-1) of propofol and target-controlled infusion of remifentanil. Arterial blood was sampled at preset intervals. A population pharmacokinetic analysis was performed using non-linear mixed effects modelling. The time to peak effect (tpeak, maximally reduced bispectral index) was measured in 28 additional underweight patients receiving propofol 2 mg kg-1. RESULTS In total, 455 plasma concentration measurements from the 20 patients were used to characterise the pharmacokinetics of propofol. A three-compartment mammillary model well described the propofol concentration time course. BMI and lean body mass (LBM) calculated using the Janmahasatian formula were significant covariates for the rapid peripheral volume of distribution and for the clearance of the final pharmacokinetic model of propofol, respectively. The parameter estimates were as follows: V1(L)=2.02, V2(L)=12.9(BMI/18.5), V3(L)=139, Cl (L⋅min-1)=1.66(LBM/40), Q1 (L⋅min-1)=1.44, Q2 (L⋅min-1)=0.87+0.0189×(LBM-40). The median tpeak of propofol was 1.32 min (n=48). CONCLUSIONS A three-compartment mammillary model can be used to administer propofol via target effect-site concentration-controlled infusion of propofol in underweight patients. CLINICAL TRIAL REGISTRATION KCT0001760.


title: Interventions to treat cutaneous leishmaniasis in children: A systematic review.

text: BACKGROUND Case management in children with cutaneous leishmaniasis (CL) is mainly based on studies performed in adults. We aimed to determine the efficacy and harms of interventions to treat CL in children. METHODS We conducted a systematic review of clinical trials and cohort studies, assessing treatments of CL in children (≤12 years old). We performed structured searches in PubMed, CENTRAL, LILACS, SciELO, Scopus, the International Clinical Trials Registry Platform (ICTRP), clinicaltrials.gov and Google Scholar. No restrictions regarding ethnicity, country, sex or year of publication were applied. Languages were limited to English, Spanish and Portuguese. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A qualitative summary of the included studies was performed. RESULTS We identified 1092 records, and included 8 manuscripts (6 Randomized Clinical Trials [RCT] and 2 non-randomized studies). Most of the articles excluded in full-text review did not report outcomes separately for children. In American CL (ACL), 5 studies evaluated miltefosine and/or meglumine antimoniate (MA). Their efficacy varied from 68-83% and 17-69%, respectively. In Old-World CL (OWCL), two studies evaluated systemic therapies: rifampicin and MA; and one study assessed efficacy of cryotherapy (42%, Per Protocol [PP]) vs intralesional MA (72%, PP). Few studies (4) provided information on adverse events (AEs) for children, and no serious AEs were reported in participants. Risk of bias was generally low to unclear in ACL studies, and unclear to high in OWCL studies. CONCLUSION Information on efficacy of treatment for CL in children is scarce. There is an unmet need to develop specific formulations, surveillance of AEs, and guidelines both for the management of CL and clinical trials involving the pediatric population. REGISTRATION The protocol of this review was registered in the PROSPERO International register of systematic reviews, number CRD42017062164.


title: Panmictic structure of the Cryptosporidium parvum population in Irish calves: influence of prevalence and host movement.

text: In total, 245 Cryptosporidium parvum specimens obtained from calves in 205 Irish herds between 2003 and 2005 were subtyped by sequencing the glycoprotein gene gp60 and performing multilocus analysis of seven markers. The transmission dynamics of C. parvum and the influence of temporal, spatial, parasitic, and host-related factors on the parasite (sub)populations were studied. The relationship of those factors to the risk of cryptosporidiosis was also investigated using results from 1,368 fecal specimens submitted to the veterinary laboratories for routine diagnosis during 2005. The prevalence was greatest in the northwest and midwest of the country and on farms that bought in calves. The panmixia (random mating) detected in the C. parvum population may relate to its high prevalence, the cattle density, and the frequent movement of cattle. However, local variations in these factors were reflected in the C. parvum subpopulations. This study demonstrated the importance of biosecurity in the control of bovine cryptosporidiosis (e.g., isolation and testing of calves before introduction into a herd). Furthermore, the zoonotic risk of C. parvum was confirmed, as most specimens possessed GP60 and MS1 subtypes previously described in humans.


title: Oxygen reduces tourniquet-associated pain: a double-blind, randomized, controlled trial for application in hand surgery.

text: BACKGROUND Why do limb tourniquets cause pain? If ischemia is the mechanism, can supplemental oxygen reduce pain? The Reducing Tourniquet Associated Pain study investigated whether this simple treatment could extend tourniquet tolerance time to facilitate hand surgery under local or regional anesthesia. METHODS The Reducing Tourniquet Associated Pain study was a double-blind, randomized, controlled trial of healthy volunteers. Participants received either 50% inhaled oxygen or air placebo via a face mask for 3 minutes before and up to 30 minutes after upper arm tourniquet inflation to 250 mmHg. Pain scores were recorded at 2-minute intervals using a validated 100-mm visual analogue scale. The primary outcomes were (1) difference in visual analogue scale score and (2) difference in time taken to reach visual analogue score of 40 mm or more in oxygen and air groups. RESULTS Fifty participants enrolled and, after exclusion criteria were applied, 46 were analyzed (oxygen, n = 23; air, n = 23). Oxygen supplementation was associated with a 29 percent mean reduction in pain on visual analogue scoring compared with air placebo over the entire period of inhalation (p = 0.027). Oxygen also extended the time to visual analogue scale score of 40 mm or more by a mean of 6½ minutes compared with air placebo (p = 0.008). CONCLUSIONS Oxygen is a readily available, low-risk, low-cost treatment that significantly reduced tourniquet-associated pain in this study and significantly increased the time taken to reach visual analogue scale score of 40 or more. The authors recommend oxygen to facilitate hand surgery under a tourniquet and when a regional block fails to control tourniquet pain.


title: Laparoscopic Low Anterior Resection of the Rectum with Transanal Prolapsing Specimen Extraction: Early Experience with 23 Patients.

text: OBJECTIVE For laparoscopic low anterior resection of the rectum, a small additional incision is needed to extract the specimen. We describe an adjustment technique, which inserted the anvil and extracted the specimen through transanal pathway. METHODS Between July 2010 and July 2012, 23 patients underwent laparoscopic rectal surgery with transanal anvil insertion and transanal prolapsing specimen extraction. All perioperative data and short-term outcomes were recorded in a database. RESULTS The mean patient age was 61.3 years (range 47-68 years). Of the 23 patients, 17 underwent resection for rectal carcinoma and 6 had tubulovillous adenomas. No intraoperative complications occurred. The mean operative time was 137 minutes (range 118-170 minutes). The distal margins, circumferential resection margins, and lymph node dissections were oncologically adequate for all malignancies. One patient experienced anastomotic leakage (4.3%), treated conservatively. One male patient with benign prostatic hyperplasia suffered from postoperative urinary retention. The average postoperative hospital stay was 11.3 days (range 7-21 days). No patients experienced anal dysfunction. At a median follow-up of 26 months, there were no tumor recurrences. CONCLUSION The technique of transanal prolapsing specimen extraction for laparoscopic low anterior resection of the rectum is feasible and safe for selected patients.


title: Benefit of Laparoendoscopic Repair of Hiatal Hernia in the Presence of Aberrant Left Hepatic Artery.

text: Background and Objectives An aberrant left hepatic artery (ALHA) limits the already confined operative field of laparoscopic antireflux surgery (LARS) and laparoscopic hiatal hernia repair (LHHR). The aim of this study is to provide a safe laparoendoscopic technique for hiatal hernia repair in the presence of an ALHA. Methods We conducted a retrospective chart review of patients who underwent LARS or LHHR between March 2016 and March 2018. We reviewed clinical and laboratory data and operative reports and images. Follow-up data included gastroesophageal reflux disease (GERD) questionnaire results and the results of esophagogastroduodenoscopy (EGD) and upper gastrointestinal studies. Results One hundred thirty-one LARS and LHHR procedures were performed by a single surgeon. Eight (6.1%) patients had an ALHA. There were 6 female and 2 male patients. The average age was 54.5 (±10.4) years, and the average body mass index was 28.1 (±5.5) kg/m2. The duration of their GERD symptoms was 16.6 (±6.9) years. Patients underwent LHHR followed by transoral incisionless fundoplication. Hiatoplasty was performed with extracorporeal sliding arthroscopic knots. The ALHA was preserved in all cases. There was no intraoperative bleeding, mortality or postoperative complications. All antireflux medications were discontinued with significant improvement of GERD questionnaires. All patients had EGD at 3 months postoperatively with no recurrence of hiatal hernia. Five patients who had the surgery longer than 1 year ago had an upper gastrointestinal study without evidence of hiatal hernia recurrence. Conclusion The laparoendoscopic technique of hiatal hernia repair, using extracorporeal arthroscopic sliding knots and concomitant transoral incisionless fundoplication, is safe, preserves an ALHA, and allows proper surgical techniques in a confined operative field.


title: SAHA-based novel HDAC inhibitor design by core hopping method.

text: The catalytic activity of the histone deacetylase (HDAC) is directly relevant to the pathogenesis of cancer, and HDAC inhibitors represented a promising strategy for cancer therapy. SAHA (suberoanilide hydroxamic acid), an effective HDAC inhibitor, is an anti-cancer agent against T-cell lymphoma. However, SAHA has adverse effects such as poor pharmacokinetic properties and severe toxicities in clinical use. In order to identify better HDAC inhibitors, a compound database was established by core hopping of SAHA, which was then docked into HDAC-8 (PDB ID: 1T69) active site to select a number of candidates with higher docking score and better interaction with catalytic zinc ion. Further ADMET prediction was done to give ten compounds. Molecular dynamics simulation of the representative compound 101 was performed to study the stability of HDAC8-inhibitor system. This work provided an approach to design novel high-efficiency HDAC inhibitors with better ADMET properties.


title: Submerged flapless technique vs. conventional flap approach for implant placement: experimental domestic pig study with 12-month follow-up.

text: OBJECTIVES The aim of our study was to compare osseointegration and peri-implant crestal bone resorption in submerged flapless and conventional flap surgery over a 12-month follow-up. MATERIALS AND METHODS The study used five domestic pigs. Implants were inserted 9 weeks after tooth extraction. Each animal received six implants in the mandible, following a split-mouth design: one side was treated using a flapless technique using mini-incisions, while a flap was raised on the other. The animals were sacrificed at 2 weeks, 1, 3, 6 and 12 months after implant placement. Radiographic images were taken to analyze crestal bone loss, and samples were extracted for histopathological and bone-to-implant contact (BIC) analyses. RESULTS Significantly, greater crestal bone loss (P = 0.005) was obtained in the flap group compared with the flapless group. The flapless group presented significantly higher percentages of BIC (P < 0.05) at 3, 6 and 12 months compared with the conventional flap group. CONCLUSIONS Within the limitations of this experimental animal study, it may be concluded that the type of surgery (flap or flapless) affects peri-implant bone preservation and osseointegration of regular platform implants. Flapless surgery is associated with peri-implant crestal bone preservation. Flapless surgery in combination with submerged implants allows higher osseointegration values.


title: Research: Continuous Surveillance of Sleep Apnea Patients in a Medical-Surgical Unit.

text: This report consists of two separate studies on the use of continuous capnography monitoring conducted in an effort to improve patient safety at Virtua Health System. The desire for improved patient safety is motivating continuous monitoring and improved surveillance in clinical areas not traditionally equipped for such monitoring. We explored the use of remote monitoring of capnography, using enterprise middleware, in patients recovering from surgery in a medical-surgical unit. Continuous monitoring traditionally has been used in higher-acuity settings, such as intensive care units. Patients diagnosed or suspected to have obstructive or central sleep apnea may benefit from the increased surveillance afforded by continuous monitoring. Pain management in this cohort of patients, recovering from bariatric, joint replacement, or other major surgery, often involves administration of opioids (e.g., hydromorphone, morphine sulfate), which are known to increase risk of respiratory depression. Continuous monitoring of these patients increases the likelihood of detecting adverse clinical events. Our goal was to implement continuous monitoring in order to identify alarm conditions caused by adverse clinical events requiring intervention (e.g., opioid-induced respiratory depression) and artifacts related to patient movement, suspect measurements, or other medical device-generated alarm signals.


title: Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice.

text: PURPOSE Iron overload accelerates bone loss in mice lacking the bone morphogenetic protein 6 (Bmp6) gene, which is the key endogenous regulator of hepcidin, iron homeostasis gene. We investigated involvement of other BMPs in preventing haemochromatosis and subsequent osteopenia in Bmp6-/- mice. METHODS Iron-treated wild-type (WT) and Bmp6-/- mice were analysed for hepcidin messenger RNA (mRNA) and tissue and blood BMP levels by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunohistochemistry, Western blot, enzyme-linked immunosorbent assay (ELISA) and proximity extension assay. BMPs labeled with technetium-99m were used in pharmacokinetic studies. RESULTS In WT mice, 4 h following iron challenge, liver Bmp6 and hepcidin expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that BMP6 circulates in WT mice and that iron increased the BMP6 serum level and the specific liver uptake of (99m)Tc-BMP6. In Bmp6-/- mice, iron challenge led to blunted activation of liver Smad signaling and hepcidin expression with a delay of 24 h, associated with increased Bmp5 and Bmp7 expression and increased Bmp2, 4, 5 and 9 expression in the duodenum. Liver Bmp7 expression and increased circulating BMP9 eventually contributed to the late hepcidin response. This was further supported by exogenous BMP7 therapy resulting in an effective hepcidin expression followed by a rapid normalisation of plasma iron values and restored osteopenia in Bmp6-/- mice. CONCLUSION In Bmp6-/- mice, iron activated endogenous compensatory mechanisms of other BMPs that were not sufficient for preventing hemochromatosis and bone loss. Administration of exogenous BMP7 was effective in correcting the plasma iron level and bone loss, indicating that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis.


title: COVID-19 pandemic and lacrimal practice: Multipronged resumption strategies and getting back on our feet.

text: The aim of this review was to propose multi-pronged resumption strategies for lacrimal practice in an effort to plan a sustainable recommencement of elective surgeries after we emerge from the peak of COVID-19 pandemic. The strategies for lacrimal practice were classified into 7 subtypes, and each of the blueprints were reassessed based on existing information on resumption strategies of elective surgeries from other specialties in COVID-19 era. The specific needs of lacrimal practice were then added to construct algorithms summarizing the resumption strategies. The basic principle of 'primum non nocere' needs to be followed. The overall proposed plan advocates the transition to a more sustainable health care reality in a world where we would still co-exist with COVID-19. A comprehensive effort involving screening, laboratory testing, appropriate triage, effective personal protection and specific precautionary measures for lacrimal clinics and operating room are needed to be able to safely resume elective surgery when the pandemic peak declines. To predict the timing of the resumption of elective surgeries is quite complex and influenced by several geographic, political and economic factors. It is equally important to remember that COVID-19 crisis is a dynamic situation and constantly evolving, hence the strategies provided are subject to change. Strict adherence to standard COVID-19 guidelines combined with effective testing and personal protection strategies can ensure slow yet smooth and safe return to full lacrimal practice after the COVID-19 pandemic calms down. The local government directives, individual and institutional discretion are advised.