title: COVID-19 patients presenting with afebrile acute abdominal pain.

text: IMPORTANCE With the surge in COVID-19 cases worldwide, the medical community should be aware of atypical clinical presentations to help with correct diagnosis, to take the proper measures to place the patient in isolation and to avoid healthcare professionals being infected by coronavirus (SARS-CoV-2). OBJECTIVE To report that patients who subsequently test positive for COVID-19 may present with acute abdominal pain and no pulmonary symptoms, although they already have typical lung lesions on computed tomography (CT) scan. DESIGN, SETTING AND PARTICIPANTS This case series is about three patients who presented to the emergency department of a community hospital in Montpellier, France, with acute abdominal pain. RESULTS The three patients had an elevated C-reactive protein level. CT scans demonstrated no abdominal anomaly, but bilateral lung lesions at the lung bases, typical of COVID-19 lesions, were observed. COVID-19 RT-PCR tests were positive for the three patients.The patients were transferred to the COVID-19 centre for disease control at Montpellier University Hospital. As of 29 March 2020, two of those patients are still intubated in the intensive care unit (ICU) and the third was discharged home. CONCLUSION AND RELEVANCE COVID-19 infections may present as an acute abdominal pain. In our case series, CT scan findings helped us to suspect the correct diagnosis, which was subsequently confirmed with COVID-19 RT-PCR tests.


title: Prevalence of Escherichia coli adhesion-related genes in neonatal calf diarrhea in Uruguay.

text: INTRODUCTION Neonatal calf diarrhea (NCD), one of the most important diseases of neonatal dairy and beef calves in Uruguay, has become relevant in association with intensive systems. This disease generates substantial economic losses every year worldwide as a result of increased morbidity and mortality. Escherichia coli, one of the pathogens associated with NCD, can express several fimbrial and afimbrial adhesins. The objective of this study was to assess the presence of clpG, f5, f17A, f17G(II), and f17G(I) genes that encode three important adhesins expressed in diarrheagenic E. coli: F5, F17 and CS31A, isolated from feces of calves in Uruguay. METHODOLOGY Feces of 86 (70 diarrheic and 16 healthy) calves, from 15 animal facilities in Uruguay, were collected between 2012 and 2013. Biochemical and molecular identification were performed to finally obtain 298 E. coli isolates. Partial amplification of adhesion-related genes was performed by polymerase chain reaction. RESULTS The most prevalent gene was f17A (31.2%), followed by f17G(II), clpG, f17G(I) and f5 (25.8%, 17.5%, 3.7% and 0.7%, respectively). All genes were present in diarrheic and healthy animals except f5 and f17G(I); these genes were present only in affected calves, although in low numbers. CONCLUSIONS This is the first report of the presence of F5, F17, and CS31A genes in E. coli strains from NCD cases in Uruguay. Prevalence values of the genes, except f5, were in accordance with regional findings. It is expected that further characterization of locally transmitted strains will contribute to control a problem of regional and international magnitude.


title: Radiofrequency ablation for the treatment of gastric antral vascular ectasia.

text: BACKGROUND AND STUDY AIMS The traditional endoscopic treatment for gastric antral vascular ectasia (GAVE) is argon plasma coagulation, but results are not always positive. Radiofrequency ablation (RFA) is a new endoscopic therapy that may be an attractive option for the treatment of GAVE. The aim of this study was to assess the efficacy and safety of RFA for the treatment of GAVE. PATIENTS AND METHODS This was an open-label, retrospective, case series study. The main outcome measures were number of red blood cell (RBC) packs transfused (transfusion requirement) and hemoglobin concentrations (g/dL) in the 6 months prior to and after RFA. Success was defined as a decrease in transfusion requirement in the 6 months after RFA compared with before treatment. RESULTS A total of 24 patients underwent a mean of 1.8 ± 0.8 RFA sessions. No complications were reported. One patient was referred for additional argon plasma coagulation during follow-up. The mean number of RBC packs decreased in all 23 transfusion-dependent patients, from a mean of 10.6 ± 12.1 during the 6 months prior to RFA, to a mean of 2.5 ± 5.9 during the 6 months after RFA treatment (P < 0.001), and 15 patients (65.2 %) were weaned off transfusions completely. An increase in the hemoglobin concentration was reported in all patients after RFA (from 6.8 ± 1.4 g/dL to 9.8 ± 1.8 g/dL; P < 0.001). CONCLUSION RFA for the treatment of GAVE seems feasible and safe, and significantly reduced the need for RBC transfusion and increased the hemoglobin level in this retrospective case series.


title: Are there positive lessons for Italy's NHS resulting from the Covid-19 pandemic?

text: The authors evaluate the importance of prevention measures and health care from their own experience and briefly analyse the factors that may have contributed to the rapid spread of Covid-19 in Italy, and hope this will feed into appropriate and new and improved health policies.


title: Effects of Memantine in a Mouse Model of Postoperative Cognitive Dysfunction.

text: Persistent impairment in cognitive functioning postoperatively is reported by clinical and animal studies, and is labeled as postoperative cognitive dysfunction (POCD). Evidence points to an exaggerated neuroinflammatory response resulting from peripheral systemic inflammation after surgery, with subsequent cytokine-induced glutamatergic excitotoxicity and synaptic impairment. These immunological changes, among many others, are also observed in Alzheimer's disease. Memantine is an N-methyl-D-aspartate receptor (NMDAR) antagonist commonly used to treat Alzheimer's disease. Surprisingly, little research exists on the role of memantine in preventing POCD. The purpose of this study is to investigate the effects of memantine on a spectrum of cognitive functions postoperatively. Mice were divided into 3 groups and each received treatment for 4 weeks. Placebo groups received a placebo then underwent either a sham procedure or a laparotomy procedure. The memantine group received memantine hydrochloride then underwent a laparotomy procedure. Cognitive tests were performed on postoperative days (POD) 1 and 7. Compared to sham-operated mice, placebo groups that underwent a laparotomy procedure showed impaired memory in the Morris water maze test, higher anxiety-like behavior in the open field and the elevated plus maze tests, increased depression-like behavior in the tail suspension test, and lack of preference for social novelty in the three-chamber test. On the other hand, memantine-treated mice that underwent a laparotomy procedure showed enhanced memory on POD7, improved depression-like behavior on POD1 and POD7, enhanced preference for social novelty on POD1, and no improvement in anxiety-like behavior. These findings suggest a potential protective effect of memantine in mice postoperatively on memory, depression-like behavior, and preference for social novelty.


Tele-Neuro-Ophthalmology During the Age of COVID-19.


title: Respiratory depression in low acuity hospital settings-Seeking answers from the PRODIGY trial.

text: Predicting episodes or severity of cardiorespiratory decompensation has proved to be challenging in patients with stable surgical or medical conditions, recovering on the general care floor (ward). Critical cardiorespiratory events on hospital floors may be prevented by early detection of deterioration using continuous, electronic cardiorespiratory monitoring (CEM). The PRediction of Opioid-induced Respiratory Depression In Patients Monitored by capnoGraphY (PRODIGY) trial investigates CEM using pulse oximetry and capnography in 1650 patients at 16 centers in North America, Europe, and Asia (ClinicalTrials.gov Identifier: NCT02811302). The primary goal of the study is to derive a risk prediction score for respiratory depression (RD) on the ward. The validation-derivation cohort design will derive this score from RD detected by continuous, blinded, multiparameter cardiorespiratory (heart rate, respiratory rate, end tidal carbon dioxide, and pulse oximetry) monitoring of patients on the ward receiving parenteral (including epidural) opioids for primary analgesia. This review provides a comprehensive synopsis on respiratory compromise in lower acuity hospital settings (ward) and describes the protocol of the PRODIGY trial as a means to enable prediction and early response to these events.


title: Nonpharmacological Interventions Addressing Pain, Sleep, and Quality of Life in Children and Adolescents with Primary Headache: A Systematic Review.

text: Purpose Children and adolescents with primary headache are at risk of persistent somatic symptoms and reduced quality of life (Qol) due to pain and pain-related behaviors, such as avoiding school and activities. Sleep is essential to health, and children and adolescents with primary headaches have more sleep complaints than do healthy controls. A treatment approach that addresses multifactorial causes is likely important. Nonpharmacological interventions seem promising. However, knowledge about effective strategies is limited. The objective of this review is to assess the effect of nonpharmacological interventions in randomized controlled trials (RCTs) among children and adolescents with primary headache in order to identify useful strategies. Patients and methods Outcome measures are pain, sleep, Qol, and coping versus no intervention or control intervention. Medline, CINAHL, EMBASE, and PsycINFO were searched for eligible trials. ClinicalTrials.gov. was searched for ongoing trials. Initial searches yielded 2588 publications. After initial screening and subsequent full-text review and quality assessment, 13 RCTs reported in 15 articles were selected for review. All reviewers independently assessed study quality using the CONSORT criteria for nonpharmacological interventions. Results Cognitive behavioral therapy (CBT), including education on pain-related topics, sleep, coping, and stress management, is an effective strategy for reducing headache and pain within groups over time. Fifteen studies assessed pain, 3 studies assessed sleep, 6 studies assessed Qol, and 11 studies assessed coping. Conclusion Strategies identified as useful were parts of CBT interventions. However, it was not possible to identify a single effective intervention addressing pain, sleep, Qol, and coping in children and adolescents with headache, primarily because sleep was infrequently addressed. Various aspects of Qol and coping strategies were assessed, rendering comparison difficult. Strategies for future interventions should include descriptions of theory-driven CBT interventions, depending on clinical setting and based on local resources, to promote a solid evidence base for nonpharmacological interventions.


title: Clinical Prognosis of Right-Sided Infective Endocarditis not Associated with Cardiac Devices or Intravenous Drug use: a Cohort Study and Meta-Analysis.

text: Right-sided infective endocarditis (RSIE), classically associated with intravenous drug use or intracardiac devices, is considered a good-prognosis infective endocarditis (IE) form. However, predisposing factors and prognosis for "NODID" RSIE (NOt associated with cardiac Devices or Intravenous Drug use) remain unclear. The aim of this study was to evaluate predisposing factors and prognosis of NODID RSIE compared to other RSIE forms. A retrospective cohort study (January 2008-January 2019) was conducted in a reference center on 300 patients diagnosed with IE. Endocarditis-related events were defined as related to IE in mortality or open-heart surgery during follow-up. A review and meta-analysis of associated literature (January 2008-January 2019) were also performed. Fifty-seven patients presented RSIE (19%), 22 of which were NODID RSIE (39%). Use of intravascular catheters (23% vs 3%; p = 0.027) and congenital heart diseases (18% vs 0%; p = 0.019) were associated with NODID RSIE. This group had a higher in-hospital mortality (23% vs 3%; p = 0.027) and endocarditis-related event rates (41% vs 6%; p = 0.001) than non-NODID RSIE. Furthermore, NODID RSIE was independently associated with in-hospital endocarditis-related events (OR = 19.29; 95%CI:2.23-167.16; p = 0.007). Our meta-analysis evaluated four studies and identified 96 cases (30%) of NODID RSIE from 320 total RSIE cases. NODID RSIE patients demonstrated higher in-hospital mortality (RR = 2.81; 95%CI:1.61-4.90; p < 0.001; I2 = 0.0%) and necessity of open-heart surgery (RR = 13.89; 95%CI:4.14-46.60; p < 0.001; I2 = 0.0%) than non-NODID RSIE cases. Our study suggests that NODID RSIE has the highest endocarditis-related event rate and in-hospital mortality among RSIE cases and therefore should not be considered a good-prognosis IE.


title: Responses of microbial capacity and community on the performance of mesophilic co-digestion of food waste and waste activated sludge in a high-frequency feeding CSTR.

text: To understand the relationship between microbes and digester performance of high-frequency feeding CSTR, which could achieve stable CH4 production at high OLR by easing instantaneous feeding shock, attentions were paid on the variations of methanogenic capacity (MC) and microbial community with OLR increasing. Results showed that the MC for feedstock degradation could satisfy the need of effective conversion from feedstock to CH4 when the OLR remained below 16.4 g-TS/L/d. Furthermore, the MC for acetate, propionate and butyrate degradation increased by 73.8%, 303%, and 164%, respectively, with OLR increasing from 3.03 g-TS/L/d 12.6 g-TS/L/d. The evolution of both bacterial and archaeal communities provided additional information on the adaptation of functional microbes to environmental factors. The significant increase of abundance of Methanoculleus and Methanomassiliicoccus likely promoted the utilization of H2, thus facilitating syntrophic methanogenesis, and consequently ensuring efficient CH4 production in stable stage.


title: The Difficult Airway and Aerosol-Generating Procedures in COVID-19: Timeless Principles for Uncertain Times.

text: The impact of the COVID-19 pandemic on otolaryngology practice is nowhere more evident than in acute airway management. Considerations of preventing SARS-CoV-2 transmission, conserving personal protective equipment, and prioritizing care delivery based on acuity have dictated clinical decision making in the acute phase of the pandemic. With transition to a more chronic state of pandemic, heightened vigilance is necessary to recognize how deferral of care in patients with tenuous airways and COVID-19 infection may lead to acute airway compromise. Furthermore, it is critical to respect the continuing importance of flexible laryngoscopy in diagnosis. Safely managing airways during the pandemic requires thoughtful multidisciplinary planning. Teams should consider trade-offs among aerosol-generating procedures involving direct laryngoscopy, supraglottic airway use, fiberoptic intubation, and tracheostomy. We share clinical cases that illustrate enduring principles of acute airway management. As algorithms evolve, time-honored approaches for diagnosis and management of acute airway pathology remain essential in ensuring patient safety.


A perspective on modern advances for COVID-19 (SARS-CoV-2) therapeutics.


title: An assessment of real-time RT-PCR kits for SARS-CoV-2 detection.

text: The COVID-19 outbreak caused by SARS-CoV-2 in Wuhan (China) in December 2019 is currently spreading rapidly and globally. We recently reported a laboratory diagnostic protocol for SARS-CoV-2 based on real-time RT-PCR assays using two primer sets, N and N2. On 30-31 January 2020, the protocol and reagents for these assays were distributed to local public health institutes and quarantine depots in Japan, and nationwide, SARS-CoV-2 diagnostic testing was started. For further validation, the assays were compared with the commercially available kits using SARS CoV-2 viral RNA and the clinical specimens obtained from COVID19-suspected individuals. The LightMix Modular SARS and Wuhan CoV E-gene (LN S&W-E) assay was highly sensitive for SARS-CoV-2, as was the N2 set, and both assays had perfectly consistent results with the clinical specimens. While the LM S&W-E set targets the highly conserved region of the E gene in SARS-CoV and SARS-CoV-2, the N2 set was designed to target the unique region in the SARS-CoV-2 N gene. Thus, the N2 set has high specificity and sensitivity for SARS-CoV-2 detection. These indicate that the protocol using the N and N2 sets is comparable to commercially available kits and is reliable for the laboratory diagnosis of COVID-19.


Annals Graphic Medicine - COVID Cataclysms: Coronavirus Through a Medical Student's Microscope.


title: A comprehensive review of laparoscopic redo fundoplication.

text: BACKGROUND The last decade has seen the publication of multiple case series investigating the feasibility of performing reoperative fundoplications using laparoscopic techniques. Most of these studies are small and reflect initial experiences with the procedure. To examine the collective experience with laparoscopic redo fundoplications, a systematic review was conducted. METHODS The MEDLINE, EMBASE, and Cochrane databases (January 1999 to March 2010) were reviewed. A total of 17 series representing 1,167 cases were selected. RESULTS The mean patient age was 51.8 years, and 42.8% of the patients were men. The most common indication for reoperation was recurrent gastroesophageal reflux disease (GERD), and the most common etiology of failure was herniation of the wrap. The mean operative time was 172 min, and the mean hospital stay was 2.8 days. Intraoperative complications occurred in 18.6% of cases, and the most common complication was gastrointestinal perforations (14.2%). The rate of conversion from laparoscopic to open surgery was 7.4%. The average postoperative follow-up period was 18 months. Postoperative complications were encountered with 16.9% of the patients, and the most common categorized complication was incisional hernia (1.6%). Success rates, defined variably, averaged 81%. CONCLUSIONS This review demonstrates that although technically challenging, redo laparoscopic fundoplication can be an effective tool in the operative management of clinically significant problems after primary fundoplication.


title: The Objective Use of Pulse Oximetry to Predict Respiratory Support Transition in Preterm Infants: An Observational Pilot Study.

text: BACKGROUND Preterm infants often require some form of respiratory support with supplemental oxygen and are monitored by continuous pulse oximetry (SpO2 ). The study objective was to determine whether the histogram distribution of SpO2 over a 24-h period will predict readiness for weaning respiratory support in preterm infants. We hypothesize that infants with ≥15% of time spent with SpO2 <86% before transitioning from CPAP or high-flow nasal cannula (HFNC) to low-flow nasal cannula, oxyhood, or room air are more likely to fail transitioning. METHODS The SpO2 histograms were downloaded daily for 31 infants, 24-32 weeks gestational age, before transition from CPAP or HFNC to low-flow nasal cannula, oxyhood, or room air. The SpO2 histogram downloads were continued for each infant for 1 week after transition or when the infant reached 36 weeks postmenstrual age or when SpO2 monitoring was discontinued. Failure was defined as an increase in respiratory support within 72 h of transitioning. We compared the percentage of time for each SpO2 quintile for the 24-h periods before and immediately following CPAP/HFNC transitioning between groups. RESULTS Twenty-four subjects transitioned successfully, but 7 subjects failed. Two of 7 subjects (28.6%) who failed transition experienced SpO2 <86% ≥15% of the time pretransition compared with none in the success group (P = .045). The failure group experienced SpO2 <86% 10.7 ± 11.9% of time pre-wean compared with 3.3 ± 4.7% of time in the success group (P = .02). In contrast, infants who were successfully weaned tended to experience a greater percentage of time with SpO2 >95% compared with the failure group, both pre-wean (54.3 ± 36.1% vs. 33 ± 27.7%, P = .16) and post-wean (52 ± 35.4% vs. 27.4 ± 27.7%, P = .10). CONCLUSIONS These data suggest that pulse oximetry histograms may be useful in assessing CPAP/HFNC support transition readiness.


title: Inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment.

text: The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hRSV). SH protein has a single α-helical transmembrane (TM) domain that forms pentameric ion channels. Herein, we report the first inhibitor of the SH protein channel, pyronin B, and we have mapped its binding site to a conserved surface of the RSV SH pentamer, at the C-terminal end of the transmembrane domain. The validity of the SH protein structural model used has been confirmed by using a bicellar membrane-mimicking environment. However, in bicelles the α-helical stretch of the TM domain extends up to His-51, and by comparison with previous models both His-22 and His-51 adopt an interhelical/lumenal orientation relative to the channel pore. Neither His residue was found to be essential for channel activity although His-51 protonation reduced channel activity at low pH, with His-22 adopting a more structural role. The latter results are in contrast with previous patch clamp data showing channel activation at low pH, which could not be reproduced in the present work. Overall, these results establish a solid ground for future drug development targeting this important viroporin. Importance: The human respiratory syncytial virus (hRSV) is responsible for 64 million reported cases of infection and 160,000 deaths each year. Lack of adequate antivirals fuels the search for new targets for treatment. The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by hRSV and other paramyxoviruses, and its absence leads to viral attenuation in vivo and early apoptosis in infected cells. SH protein forms pentameric ion channels that may constitute novel drug targets, but no inhibitor for this channel activity has been reported so far. A small-molecule inhibitor, pyronin B, can reduce SH channel activity, and its likely binding site on the SH protein channel has been identified. Black lipid membrane (BLM) experiments confirm that protonation of both histidine residues reduces stability and channel activity. These results contrast with previous patch clamp data that showed low-pH activation, which we have not been able to reproduce.


title: Echocardiographic screening to determine progression of latent rheumatic heart disease in endemic areas: A systematic review and meta-analysis.

text: BACKGROUND The World Health Organisation previously recommended routine screening in school-aged children in countries with a high prevalence of rheumatic heart disease (RHD); however, it is unclear if screening-detected (latent) valve disease will inevitably evolve to a pathological lesion. Understanding the natural history of latent RHD is essential prior to recommendation of screening in endemic areas. Studies documenting the progression of latent RHD have had contrasting conclusions about the pathogenicity of latent valvular lesions. This review provides estimates of rates of progression of latent RHD. METHODS AND FINDINGS In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, Global Index Medicus, Africa Wide, Cochrane Database of Systematic Reviews and Global Health Database for studies published before April 30, 2019. Study data were extracted from all studies which reported follow-up data on progression of latent valve lesions. Studies with control cohorts were used to calculate comparative prevalence ratios. This study is registered with PROSPERO, number CRD42019119427. We identified 12 studies reporting follow-up data on latent RHD for 950 people in 9 countries. The estimated pooled prevalence rate for progression per year of latent RHD was 5%/year (95% CI 2-8). Eight studies reported on the progression of borderline latent RHD with an estimated pooled prevalence of 2%/year (95% CI 0-4). Three studies included control groups. There was a significant increase in the risk of progression of valvular disease in the latent group compared with controls (RR = 3.57 (95%CI = 1.65-7.70, P = 0.001). The overall risk of bias was low. Given most studies included penicillin administration we were unable to document the natural history of latent RHD. Furthermore, we were unable to perform a sensitivity analysis to determine the effect of administering penicillin prophylaxis on progression of valve disease given prescription of penicillin was not standardised. CONCLUSION Latent RHD has a slow rate of progression but it is significantly higher compared to controls, with definite latent RHD having a higher rate of progression compared with borderline latent disease. There are a massive number of individuals at risk for RHD in the developing world as well as logistical challenges of screening and delivering penicillin prophylaxis. The low rate of progression from untargeted screening may be an important consideration in resource-constrained environments.


Lessons from the USA Delayed Response to the COVID-19 Pandemic.


title: Delivering psychotherapy by video conference in the time of COVID-19: some considerations.

text: In New Zealand we have been far less affected by Covid-19 than many other countries. To put our discussion in some context at the time of writing (May 10 2020) in a country of nearly 5 million people, we have had 1144 cases of Covid-19 with 1,371 people recovered and 21 deaths. At the same time the United Kingdom has had 215,000 cases and 31,587 deaths; and the USA has had 1,034,000 cases and 79,696 deaths. While our case numbers have not been particularly high the government's response has been to institute four types of lockdown.


title: NOSE laparoscopic gastrectomies for early gastric cancer may reduce morbidity and hospital stay: early results from a prospective nonrandomized study.

text: BACKGROUND Natural orifice specimen extraction - NOSE laparoscopy is a promising technique that avoids mini-laparotomy, possibly reducing postoperative pain, wound infections and hospital stay. Recent systematic reviews have shown that postoperative morbidity associated with laparoscopically assisted gastrectomies is similar to that after open gastrectomies. More specifically, there is no difference in wound infection rate. The study objective was to evaluate whether postoperative morbidity and hospital stay may be reduced by transoral specimen extraction after laparoscopically assisted gastrectomy for early gastric cancer (EGC). MATERIAL AND METHODS A prospective, nonrandomized study was carried out starting in August 2012. Data from all patients operated on during the first year, with minimum 18 months follow-up, were collected to assess feasibility, oncologic results, postoperative morbidity, hospital stay and functional results. Overall, 14 patients were included and followed-up. After gastric resection, a 3 cm opening was created on the gastric stump, and the specimen, divided into three segments stitched one to each other, was sutured to the gastric tube and retrieved through the mouth. RESULTS Postoperative morbidity was 7.14% (1/14): one case of pneumonia. No wound infection occurred. The mean postoperative hospital stay was 4.7 ± 1.0 days. CONCLUSIONS NOSE laparoscopic subtotal gastrectomy is feasible and safe, with similar oncologic results as LAG, but decreased morbidity and hospital stay.


title: On the incorporation of iron into hexagonal barium titanate: II. Magnetic moment, electron paramagnetic resonance (EPR) and optical transmission.

text: Systematic measurements of the magnetic moment in dependence on temperature and magnetic field of hexagonal 6H-BaTiO3+ 0.04 BaO + x/2 Fe2O3(0.005 ≤ x ≤ 0.05) ceramics were performed to study the influence of Fe ions on the magnetic properties. While the samples show Curie-Weiss paramagnetism for Fe concentrations ≤ 1.0 mol%, antiferromagnetic interactions become manifest for 2.0 and 5.0 mol% iron. With increasing Fe content the antiferromagnetic interaction, which is assumed to be caused by a superexchange mechanism Fe3+Ti(1)- O2-O(2)- Fe3+Ti(2), becomes stronger. At external magnetic fields smaller than 1 T a further, ferromagnetic interaction between Fe3+ions is detected below 200 K. The interactions between Fe3+ions in the samples with 2.0 and 5.0 mol% iron are also manifest in the EPR spectra by numerous lines with low intensity. Q-band EPR investigations of 5.0 mol% Fe doped single crystals confirm the existence of only one type of Fe3+- VOassociates in the samples.


title: Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells.

text: Cardiac progenitor cells including c-kit(+) cells and cardiosphere-derived cells (CDCs) play important roles in cardiac repair and regeneration. CDCs were reported to contain only small subpopulations of c-kit(+) cells and recent publications suggested that depletion of the c-kit(+) subpopulation of cells has no effect on regenerative properties of CDCs. However, our current study showed that the vast majority of CDCs from murine heart actually express c-kit, albeit, in an intracellular and non-glycosylated form. Immunostaining and flow cytometry showed that the fluorescent signal indicative of c-kit immunostaining significantly increased when cell membranes were permeabilized. Western blots further demonstrated that glycosylation of c-kit was increased during endothelial differentiation in a time dependent manner. Glycosylation inhibition by 1-deoxymannojirimycin hydrochloride (1-DMM) blocked c-kit glycosylation and reduced expression of endothelial cell markers such as Flk-1 and CD31 during differentiation. Pretreatment of these cells with a c-kit kinase inhibitor (imatinib mesylate) also attenuated Flk-1 and CD31 expression. These results suggest that c-kit glycosylation and its kinase activity are likely needed for these cells to differentiate into an endothelial lineage. In vivo, we found that intracellular c-kit expressing cells are located in the wall of cardiac blood vessels in mice subjected to myocardial infarction. In summary, our work demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage.


title: Insights into redox mediators-resource harvest/application with power production from waste activated sludge through freezing/thawing-assisted anaerobic acidogenesis coupling microbial fuel cells.

text: This first-attempted study demonstrated endogenous redox-mediators harvest/application from waste activated sludge (WAS) through freezing/thawing (F/T) pretreatment-enhanced anaerobic acidogenesis coupled with microbial fuel cells (MFCs). A total of 2.57 kWh electricity was produced from per kg soluble chemical oxygen demand (SCOD) via MFCs just in 2 d with about 90% organics removal, which contained 1.152 kWh/kg COD from F/T liquid together with 1.418 kWh/kg COD from fermentation liquid. The fermentation liquor-MFCs fostered higher anodic biodiversity and more power output as compared with the F/T liquid-MFCs. Essentially, the completely endogenous redox mediators-like substances with relatively high redox activities could be retained after MFC electrogenesis from F/T liquid and played electron shuttle-roles sufficiently in enlarging bio-energy production of MFCs, which seemed to be an effective option for harvesting endogenous redox mediators from sludge. This study might inspire progressive thinking toward aims of high-efficiency of resource recycle/bioenergy production from WAS.


Antirheumatic agents in covid-19: is IL-6 the right target?


A rare cause of gastric malignancy: Burkitt's lymphoma.


title: ABO blood group is a predictor of survival in patients undergoing surgery for renal cell carcinoma.

text: UNLABELLED What's known on the subject? and What does the study add? Some evidence suggests that ABO blood type may be a risk factor for cancer incidence and prognosis. For example, a large study recently discovered an increased incidence of pancreatic cancer in patients with non-O blood type; however, it is not known whether blood group correlates with outcomes in patients with RCC. We found a significant and independent association between ABO blood group and overall survival in patients undergoing surgery for locoregional RCC. Specifically, we identified non-O blood type as a predictor of mortality. OBJECTIVE • To determine whether ABO blood group is associated with survival after nephrectomy or partial nephrectomy for renal cell carcinoma (RCC). PATIENTS AND METHODS • We conducted a retrospective cohort study of 900 patients who underwent surgery for locoregional RCC between 1997 and 2008 at a single institution. • Covariates included age, gender, race, American Society of Anesthesiology Physical Status, preoperative anaemia and hypoalbuminemia, tumour characteristics, lymph node status, procedure performed, transfusion status and ABO blood group. • Primary outcomes were overall (OS) and disease-specific survival (DSS). • Univariable survival analyses were performed using the Kaplan-Meier and log-rank methods. Multivariable analysis was performed using a Cox proportional hazards model. RESULTS • The 3-year OS estimate was 75% (95%CI 70-79%) for O blood group and 68% (95% CI 63-73%) for non-O blood group (P= 0.072). The 3-year DSS was 81% (95% CI 76-85%) for O blood group and 76% (95%CI 71-80%) for non-O blood group (P= 0.053). • In the multivariable analysis for OS, non-O blood type was significantly associated with decreased OS (HR 1.68, 95%CI 1.18-2.39; P= 0.004) but not DSS (HR 1.53, 95%CI 0.97-2.41; P= 0.065). CONCLUSION • These data suggest that ABO blood group is independently associated with OS in patients undergoing surgery for locoregional RCC. ABO blood group has not been previously recognized as a predictor of survival in RCC.


Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence.


COVID-19 and Health Equity-A New Kind of "Herd Immunity".


title: The role of radioprotective spacers in clinical practice: a review.

text: The delivery of high dose radiotherapy to tumors is often limited by the proximity of the surrounding radiosensitive normal tissues, even using modern techniques such as intensity modulated radiation therapy (IMRT). Previous studies have reported that placement of a spacer can effectively displace normal tissues. So that they are some distance away from the lesion, thus allowing for the safe delivery of high-dose radiation. The application of radioprotective spacers was first reported 30 years ago regarding radiotherapy of tongue and abdominal cancers; more recently, they are increasingly being used in prostate cancer. This review focuses on the published data concerning the features of different types of spacers and their application in various tumor sites. Placement-related complications and the cost-effectiveness of the spacers are also discussed. With the increasing use of high-precision radiotherapy in clinical practice, especially the paradigm-changing stereotactic body radiotherapy (SBRT), more robust studies are warranted to further establish the role of radioprotective spacers through materials development and novel placement techniques.


A Good Death : A Pandemic Lesson.


title: Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection.

text: Newly emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome CoVs (MERS-CoV), and H7N9, cause fatal acute lung injury (ALI) by driving hypercytokinemia and aggressive inflammation through mechanisms that remain elusive. In SARS-CoV/macaque models, we determined that anti-spike IgG (S-IgG), in productively infected lungs, causes severe ALI by skewing inflammation-resolving response. Alveolar macrophages underwent functional polarization in acutely infected macaques, demonstrating simultaneously both proinflammatory and wound-healing characteristics. The presence of S-IgG prior to viral clearance, however, abrogated wound-healing responses and promoted MCP1 and IL-8 production and proinflammatory monocyte/macrophage recruitment and accumulation. Critically, patients who eventually died of SARS (hereafter referred to as deceased patients) displayed similarly accumulated pulmonary proinflammatory, absence of wound-healing macrophages, and faster neutralizing antibody responses. Their sera enhanced SARS-CoV-induced MCP1 and IL-8 production by human monocyte-derived wound-healing macrophages, whereas blockade of FcγR reduced such effects. Our findings reveal a mechanism responsible for virus-mediated ALI, define a pathological consequence of viral specific antibody response, and provide a potential target for treatment of SARS-CoV or other virus-mediated lung injury.


title: A refined technique for sciatic denervation in a golden-mantled ground squirrel (Callospermophilus lateralis) model of disuse atrophy.

text: Disuse atrophy of both muscle and bone can occur rapidly during periods of inactivity. In several rodent models developed for the study of disuse atrophy, immobilization is induced by prolonged cage restraint, hind limb unloading, tenotomy, sciatic nerve block or sciatic denervation. In less tractable species such as wild-caught hibernating rodents, the sciatic denervation model is superior in terms of both animal welfare and applicability to the characteristics of natural cases of disuse atrophy. The authors describe a refined surgical approach to sciatic denervation in golden-mantled ground squirrels (Callospermophilus lateralis), a hibernating species, that improves animal welfare and reduces the incidence of post-operative complications such as autotomy.


title: Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease.

text: RATIONALE There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. OBJECTIVES To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. METHODS PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. MEASUREMENTS AND MAIN RESULTS Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. CONCLUSIONS Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD.


title: Acute wound management: revisiting the approach to assessment, irrigation, and closure considerations.

text: BACKGROUND As millions of emergency department (ED) visits each year include wound care, emergency care providers must remain experts in acute wound management. The variety of acute wounds presenting to the ED challenge the physician to select the most appropriate management to facilitate healing. A complete wound history along with anatomic and specific medical considerations for each patient provides the basis of decision making for wound management. It is essential to apply an evidence-based approach and consider each wound individually in order to create the optimal conditions for wound healing. AIMS A comprehensive evidence-based approach to acute wound management is an essential skill set for any emergency physician or acute care practitioner. This review provides an overview of current evidence and addresses frequent pitfalls. METHODS A systematic review of the literature for acute wound management was performed. RESULTS A structured MEDLINE search was performed regarding acute wound management including established wound care guidelines. The data obtained provided the framework for evidence-based recommendations and current best practices for wound care. CONCLUSION Acute wound management varies based on the wound location and characteristics. No single approach can be applied to all wounds; however, a systematic approach to acute wound care integrated with current best practices provides the framework for exceptional wound management.


title: Exposures associated with infection with Cryptosporidium in industrialised countries: a systematic review protocol.

text: BACKGROUND Cryptosporidium is a protozoan parasite of humans and other animals worldwide and is one of the greatest contributors to human diarrhoeal illness. Transmission can occur indirectly via contaminated food or water, or directly via contact with animals or other infected people. Risk exposures are often identified from outbreak investigations, but a subset of cases remains unexplained, and sources for sporadic disease and pathways to infection are still unclear. Given the few systematic syntheses of reported evidence in industrialised populations, the aim of this review is to consolidate the literature to describe exposures associated with human cryptosporidiosis in industrialised countries, specifically including the UK, and describe any differences between outbreak-associated and sporadic disease. METHODS/DESIGN Where relevant, methods will follow the recommendations made in the Cochrane Handbook for Systematic Reviews of Interventions. Three steps will be used to identify the literature including electronic database searching using PubMed, Scopus, Embase and Web of Science; reference list trawling; and an exploration of the grey literature. Screening of results will be undertaken by two reviewers using pre-defined criteria. Studies conducted in industrialised countries and reporting on human subjects will be included. All observational studies will be included where they report exposures and relevant quantitative results. Data will be extracted using a standardised form. Study quality will be assessed using the ROBINS-I tool. Data will be summarised presenting the papers' main findings including population under study, outcomes, and exposures, and whether these were considered outbreak or sporadic cases. A narrative summary will also be included. Where populations are appropriate, available data will be pooled in a meta-analysis combining the significant exposures across studies. DISCUSSION This review aims to consolidate the evidence for transmission routes and exposures for Cryptosporidium in industrialised countries, with particular reference to how these may apply to the UK. In addition, the review will seek to describe differences between outbreak and sporadic cases. This will help to identify those most vulnerable, highlighting pathways where interventions and public health response may be appropriate. SYSTEMATIC REVIEW REGISTRATION PROSPERO number CRD42017056589 .


title: Is Sexting Associated with Sexual Behaviors During Adolescence? A Systematic Literature Review and Meta-Analysis.

text: INTRODUCTION A growing body of research has addressed adolescent use of mobile devices to exchange sexually explicit images and messages (sexting). Although there are legal consequences in some states for sexting among adolescents, research findings have also demonstrated associations between sexting and sexual activity. The purpose of this systematic review was to synthesize research examining the association between adolescent sexting and sexual activity. METHODS Five databases (CINAHL, Embase, Ovid MEDLINE, PsycINFO, and Scopus) were searched for studies measuring adolescent sexting and sexual behaviors. Studies were appraised for quality using a modified Downs and Black scale. Studies reporting frequencies or odds ratios were eligible for inclusion in random effects meta-analytic models. RESULTS Of 669 articles retrieved, 9 studies met inclusion criteria for systematic review; of these, 6 were included in meta-analysis. After pooling data from 9676 adolescents, the odds of reporting sexual activity were found to be 6.3 times higher (95% CI, 4.9-8.1; Q = 14.3; I2 = 65.1) for adolescents who sent sexts compared with those who did not. DISCUSSION These data suggest that adolescents who send sexually explicit text messages are more likely to report sexual activity than adolescents who do not. Midwives are well poised to integrate a discussion of sexting into sexual and reproductive health counseling with adolescent and young adult patients.


Correction: Vol. 22, No. 6.


title: Influenza in the elderly: a mini-review.

text: Influenza is an important cause of morbidity and mortality in the elderly population each year. The often subtle clinical manifestations in the frail geriatric patients may not be recognized initially, impeding timely administration of antiviral treatment. The effectiveness of current influenza vaccines in the elderly population is often diminished by immune senescence. Increasing immunization rates among health-care workers and elderly caregivers, and finding more effective vaccines for the elderly people are likely to significantly improve disease prevention in this population at risk.


The Meaning of Care and Ethics to Mitigate the Harshness of Triage in Second-Wave Scenario Planning During the COVID-19 Pandemic.


title: Mode of Delivery Does Not Influence Postpartum Hypercoagulability Measured by Thrombin Generation or Thromboelastometry.

text: Introduction Venous thromboembolism (VTE) is a significant cause of maternal mortality with the greatest risk postpartum. Mode of delivery influences VTE risk, with emergency caesarean section (CS) associated with the highest risk (CS). Thromboprophylaxis is recommended for selected women to reduce the risk of VTE. We aimed to investigate the impact of mode of delivery and thromboprophylaxis on hypercoagulability as measured by thromboelastometry (TEM) and thrombin generation (TG) in women at high VTE risk. Materials and Methods Blood was collected from 99 pregnant women with VTE risk factors at up to five time points from pre- (T1) and post (T2)-delivery to 6 weeks postpartum (T5). Multiple linear regression was utilised to compare TG and TEM between those with vaginal delivery (VD) and CS at each time point. Paired sample t -test with post hoc Bonferroni correction was utilised to compare laboratory markers over time. Results Women in both groups had a median of three postpartum VTE risk factors, with higher body mass index and parity post-VD. In both the groups, TG and TEM parameters suggested hypercoagulability at T2 compared with T1, with resolution at T5. There were minimal differences between groups, apart from T2 with shorter clot formation time and higher maximum clot firmness in the VD group. Conclusion TG and TEM illustrate hypercoagulability associated with pregnancy and delivery. The pattern of postpartum hypercoagulability seen in women with VTE risk factors was similar irrespective of mode of delivery. Further research is required to establish the effect of labour on TG/TEM in the absence of low molecular weight heparin use.


title: Evolutionary origins of hepatitis A virus in small mammals.

text: Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3D(pol) sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses.


title: Home monitoring for COVID-19.

text: Cleveland Clinic recognized the importance of mitigating community transmission of COVID-19 by keeping people at home. Patient-care activities quickly pivoted to remote touches, preserving continuity through a variety of digital and telephonic modalities. As the number of confirmed cases grew, standardizing home-based care became critical to managing high-risk patients, moderating the risk of exposure for healthcare workers, and reducing the amount of community spread through appropriate education on home-based care for exposed or infected individuals. This novel, team-based approach to caring for patients with COVID-19 incorporates a self-monitoring app for patient engagement, monitors symptoms for early intervention, and promotes a holistic view of care.


title: Population-based analysis of 4113 patients with acute cholecystitis: defining the optimal time-point for laparoscopic cholecystectomy.

text: OBJECTIVE To compare clinical outcomes after laparoscopic cholecystectomy (LC) for acute cholecystitis performed at various time-points after hospital admission. BACKGROUND Symptomatic gallstones represent an important public health problem with LC the treatment of choice. LC is increasingly offered for acute cholecystitis, however, the optimal time-point for LC in this setting remains a matter of debate. METHODS Analysis was based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery and included patients undergoing emergency LC for acute cholecystitis between 1995 and 2006, grouped according to the time-points of LC since hospital admission (admission day (d0), d1, d2, d3, d4/5, d ≥6). Linear and generalized linear regression models assessed the effect of timing of LC on intra- or postoperative complications, conversion and reoperation rates and length of postoperative hospital stay. RESULTS Of 4113 patients, 52.8% were female, median age was 59.8 years. Delaying LC resulted in significantly higher conversion rates (from 11.9% at d0 to 27.9% at d ≥6 days after admission, P < 0.001), surgical postoperative complications (5.7% to 13%, P < 0.001) and re-operation rates (0.9% to 3%, P = 0.007), with a significantly longer postoperative hospital stay (P < 0.001). CONCLUSIONS Delaying LC for acute cholecystitis has no advantages, resulting in significantly increased conversion/re-operation rate, postoperative complications and longer postoperative hospital stay. This investigation-one of the largest in the literature-provides compelling evidence that acute cholecystitis merits surgery within 48 hours of hospital admission if impact on the patient and health care system is to be minimized.


title: Overdiagnosis of pulmonary embolism: evaluation of a hypoxia algorithm designed to avoid this catastrophic problem.

text: BACKGROUND We observed a substantial increase in the incidence of pulmonary embolism (PE) after total joint arthroplasty (TJA) when multidetector computerized tomography (MDCT) replaced ventilation-perfusion (V/Q) scans as the diagnostic modality of choice. We questioned whether this resulted from the detection of clinically unimportant PE with the more sensitive MDCT and in 2007 instituted a hypoxia protocol to enhance the detection of PE. QUESTIONS/PURPOSES We determined whether this new hypoxia protocol increased the specificity of our workups for suspected clinically important PE in the immediate postoperative period without affecting patient morbidity and mortality. PATIENTS AND METHODS We compared the frequency of MDCT, V/Q scan and total investigations, incidence of PE, and overall mortality rates in the 3 years prior (January 2003 to December 2006) and 2 years after (January 2007 to November 2009) the implementation of the algorithm. RESULTS After instituting the protocol, we observed a trend toward a decrease in the number of patients worked up for PE (4.6 to 4.0 per 100 TJAs, 13.5% decrease). At the same time, there was an increase in the percent of positive findings of PE per workup for PE (23-33 positive PEs per 100 patients, 40.5% increase). All-cause mortality rates decreased for the 30-day period (3.1 to 1.4 per 1000 TJAs, 53.5% decrease) and the 90-day period (5.0 to 2.6 per 1000 TJAs, 48.3% decrease). CONCLUSIONS With the implementation of this algorithm, the specificity of our management of postoperative hypoxia and suspected clinically important PE improved without affecting patient morbidity or mortality.


title: Laparoscopic Roux-en-Y gastric bypass: comparison between hand-sewn and mechanical gastrojejunostomy.

text: The laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the ideal operations in the treatment of morbid obesity. There are several variations in the operation, especially during the construction of the gastrojejunostomy (GJA). From June 2006 to September 2008, 104 consecutive obese patients underwent LRYGB. The procedure was standardized, with the exception of the construction of the GJA, which was linear-stapled in 51 patients and hand-sewn in 53 other patients. A retrospective analysis was performed to compare the procedures. The series comprised 81 women and 23 men with a median age of 44 years, and a median BMI of 46.7 kg/m(2). There was no significant difference between the two groups of patients with respect to age, gender, BMI, ASA, and previously failed bariatric surgery. There was no significant difference between the two groups with respect to mortality, conversion, early reoperation, surgical complications, GJA leakage or stricture, and bariatric results. The only significant differences between the two groups were in regards to operating time (190 min for stapled GJA vs. 160 min for hand-sewn GJA, p value 0.029) and operating supply cost (100 Euros less for hand-sewn GJA). In our experience, hand-sewn GJA during LRYGB appears to be as safe as linear-stapled GJA and provides the same bariatric results while remaining slightly less expensive.


title: Even mild respiratory distress alters tissue oxygenation significantly in preterm infants during neonatal transition.

text: UNLABELLED Near-infrared spectroscopy (NIRS) enables continuous non-invasive measurements of regional oxygen saturation (rSO2). The aim was to evaluate the dynamics of rSO2 of the brain, preductal and postductal tissues during postnatal transition in preterm infants with and without respiratory support (RS). This single-centre study was designed as an exploratory prospective observational study. Fifty one preterm infants (≥ 30 + 0 and < 37 + 0 weeks) delivered by caesarean section were included. RS using a T-Piece-Resuscitator and supplemental oxygen were given according to guidelines. NIRS measurements were carried out by using Invos Monitor (Covidien; USA) for the first 15 min of life. Three NIRS transducers were attached on the forehead (rSO2brain), the right forearm (rSO2arm) and the left lower leg (rSO2leg). Two groups were compared based on need for RS: normal transition (NT) and RS group. RESULTS In NT group rSO2brain increased over time and was significantly higher than rSO2arm, whereas in RS group rSO2brain and rSO2arm increased without significant differences. Courses of rSO2arm and rSO2leg increased over time and showed a converging pattern with initially lower values of rSO2leg in NT group and a diverging pattern with lower levels of rSO2leg in RS group. Overall, rSO2 levels were higher in NT compared to RS group. CONCLUSION Our findings indicate that the decreased rSO2 levels in RS group compared to NT group are not only caused by lower arterial oxygen saturation levels, but also by a compromised perfusion even in infants with only mild respiratory distress.


title: Italian suggestions for pulmonary rehabilitation in COVID-19 patients recovering from acute respiratory failure: results of a Delphi process.

text: There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts' opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.


title: Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial.

text: BACKGROUND Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke. METHODS In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7-10 days and, when practical, again at 25-30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533. FINDINGS All patients were included in the analyses. The primary outcome occurred in 126 (10.0%) patients allocated to thigh-length GCS and in 133 (10.5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0.5% (95% CI -1.9% to 2.9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4.18, 95% CI 2.40-7.27). INTERPRETATION These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results. FUNDING Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.


title: Identification and characterization of a peptide with affinity to head and neck cancer.

text: UNLABELLED Combination therapy has improved the quality of life for patients with squamous cell carcinomas of the head and neck (HNSCCs) but has not decisively changed prognosis. Targeted therapies, which enhance accumulation of the drug in the tumor, may be realized using tumor-specific binding peptides. This paper identifies and characterizes an HNSCC affine peptide. METHODS From a phage library comprising 10(9) different displayed peptides, 1 peptide was enriched after 5 in vitro selection rounds on HNO223 tumor cells. Subsequently, the gained peptide sequence H(2)N-SPRGDLAVLGHKY-CONH(2) (HBP-1) was synthesized as an amide and labeled with (125)I. In vitro studies for binding kinetics and competition were performed with 5 different HNSCC cell lines. Furthermore, the stability of the peptide was evaluated in human serum. The in vivo biodistribution of (131)I-labeled peptide was determined in HNSCC tumor-bearing nude mice. The results were further validated in human HNSCC tumor tissue sections using fluorescence-labeled HBP-1. Competition experiments were performed to determine the binding sequence and validate the target. RESULTS The HBP-1 motif was enriched in 62% of all phages sequenced. Labeled (125)I-HBP-1 showed binding to 5 different HNSCC cell lines and a maximum binding to HNO97 cells, with 11% of the applied dose per 10(6) cells and an inhibitory concentration of 50% of 38.9 nM. Stability experiments in human serum showed a half-life of 55 min. In 2 different HNSCC tumor xenografts, (131)I-HBP-1 accumulated rapidly, with stable uptake until 45 min after intravenous application. Peptide immunohistochemistry of HNSCC tissue sections exhibited tumor staining by HBP-1, whereas normal tissue remained negative. Sequence mutation and competition experiments revealed that the intrinsic RGD motif in combination with the intrinsic LXXL motif is responsible for the binding ability of HBP1. The RGDLXXL sequence within this peptide is known and indicates that binding occurs via the alpha(v)beta(6) rather than the alpha(v)beta(3) integrin. CONCLUSION Within the sequence of HBP-1 is a RGDLXXL motif, and most likely it is targeting the alpha(v)beta(6) receptor of the integrin family of cell adhesion receptors. HBP-1 represents a promising lead structure for the development of targeted therapies or diagnostic procedures in patients with HNSCC.


title: Early oxygen-utilization and brain activity in preterm infants.

text: The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG) could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and quantitative aEEG/EEG parameters has not yet been investigated. Our aim was to study the association between oxygen utilization during the first 6 h after birth and simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty-four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS and aEEG/EEG data available and who did not receive morphine were included in the study. aEEG and NIRS monitoring started at NICU admission. The relation between regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE), and quantitative measurements of brain activity such as number of spontaneous activity transients (SAT) per minute (SAT rate), the interval in seconds (i.e. time) between SATs (ISI) and the minimum amplitude of the EEG in μV (min aEEG) were evaluated. rScO2 was negatively associated with SAT rate (β=-3.45 [CI=-5.76- -1.15], p=0.004) and positively associated with ISI (β=1.45 [CI=0.44-2.45], p=0.006). cFTOE was positively associated with SAT rate (β=0.034 [CI=0.009-0.059], p=0.008) and negatively associated with ISI (β=-0.015 [CI=-0.026- -0.004], p=0.007). Oxygen delivery and utilization, as indicated by rScO2 and cFTOE, are directly related to functional brain activity, expressed by SAT rate and ISI during the first hours after birth, showing an increase in oxygen extraction in preterm infants with increased early electro-cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain vulnerability in high-risk infants.


title: Polyester Preserves the Highest Breaking Point After Prolonged Incubation in Pancreatic Juice.

text: BACKGROUND The impact of suture materials on the development of pancreatic fistula after pancreaticoduodenectomy remains unclear. Thus, their choice among pancreatic surgeons is still mostly experience-based. Aim of the present study is to assess what is the best suture material to be used for pancreaticojejunostomy. MATERIALS AND METHODS The force needed to reach the breaking point of five widely used suture materials (polypropylene, polyester, polydioxanone, silk, and polyglactin 910) has been determined through a digital precision dynamometer at baseline and after 5 and 20 days of incubation in pancreatic juice, bile, or a mixture of both. RESULTS Regardless of the condition, polyglactin 910 has retained only 10% of its baseline force. Silk has maintained almost 90% of its initial force showing a very low baseline value of force. In pancreatic juice, polypropylene has lost less force compared to polyester (0.25 vs. 0.93 N; p = 0.03) and polydioxanone (0.25 vs. 3.67 N; p = 0.04). Polyester and polydioxanone have showed similar values of force. However, polydioxanone has lost a significant amount of force in pancreatic juice when compared to polyester (0.93 vs. 3.67 N; p = 0.03). Polyester has showed the highest value of force needed to reach the breaking point after 20 days of incubation in pancreatic juice. CONCLUSIONS After incubation in pancreaticobiliary secretions, polyglactin 910 loses almost all its force. Polypropylene preserves its characteristic, but polydioxanone and polyester show absolute higher breaking points, with polyester retaining the highest value of force needed to reach its breaking point after incubation in pancreatic juice.


title: Detection of rotavirus species A, B and C in domestic mammalian animals with diarrhoea and genotyping of bovine species A rotavirus strains.

text: Rotaviruses (RVs) are a major cause of neonatal diarrhoea in humans and animals worldwide. In this study, 425 faecal samples were collected between 1999 and 2013 from diarrhoeic livestock and companion animals at different locations in Germany and tested for RVs. A previously published real-time RT-PCR assay was optimized for detection of a larger variety of RV species A (RVA) strains, and real-time RT-PCR assays for detection of RV species B (RVB) and C (RVC) were newly developed. The detection limits of the assays were 1.54×10(2), 3.95×10(2) and 3.60×10(3) genome copies for RVA, RVB and RVC, respectively. RVA was identified in 85.2% of bovine samples, 51.2% of porcine samples, 50.0% of feline samples, 43.2% of equine samples and 39.7% of canine samples. RVB was found in 3.0% of bovine samples, 2.7% of equine samples and 1.6% of porcine samples. RVC was detected in 31.0% of porcine samples, 21.7% of feline samples, 9.0% of canine samples and 6.0% of bovine samples. For genotyping, 101 RVA-positive bovine samples were further analysed by semi-nested RT-PCR. Genotype combination G6P[5] was most frequently detected (67.3% of samples), followed by G6P[11] (13.9%), G10P[5] (4.0%), G8P[11] (3.0%), G6P[1] (1.0%), and G10P[11] (1.0%). Mixed RVA infections were detected in 5.9% of samples; no or incomplete typing was possible in 4.0% of the samples. This first overview on RV species and RVA genotypes in diarrhoeic livestock and companion animals from Germany indicates a broad circulation of a large variety of RVs.


title: PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine.

text: UNLABELLED The live attenuated measles virus vaccine is highly immunostimulatory. Identification and characterization of its components that activate the innate immune response might provide new strategies and agents for the rational design and development of chemically defined adjuvants. In this study, we report on the activation of type I interferon (IFN) production by a defective interfering (DI) RNA isolated from the Hu-191 vaccine strain of measles virus. We found that the Hu-191 virus induced IFN-β much more potently than the Edmonston strain. In the search for IFN-inducing species in Hu-191, we identified a DI RNA specifically expressed by this strain. This DI RNA, which was of the copy-back type, was predicted to fold into a hairpin structure with a long double-stranded stem region of 206 bp, and it potently induced the expression of IFN-β. Its IFN-β-inducing activity was further enhanced when both cytoplasmic RNA sensor RIG-I and its partner, PACT, were overexpressed. On the contrary, this activity was abrogated in cells deficient in PACT or RIG-I. The DI RNA was found to be associated with PACT in infected cells. In addition, both the 5'-di/triphosphate end and the double-stranded stem region on the DI RNA were essential for its activation of PACT and RIG-I. Taken together, our findings support a model in which a viral DI RNA is sensed by PACT and RIG-I to initiate an innate antiviral response. Our work might also provide a foundation for identifying physiological PACT ligands and developing novel adjuvants or antivirals. IMPORTANCE The live attenuated measles virus vaccine is one of the most successful human vaccines and has largely contained the devastating impact of a highly contagious virus. Identifying the components in this vaccine that stimulate the host immune response and understanding their mechanism of action might help to design and develop better adjuvants, vaccines, antivirals, and immunotherapeutic agents. We identified and characterized a defective interfering RNA from the Hu-191 vaccine strain of measles virus which has safely been used in millions of people for many years. We further demonstrated that this RNA potently induces an antiviral immune response through cellular sensors of viral RNA known as PACT and RIG-I. Similar types of viral RNA that bind with and activate PACT and RIG-I might retain the immunostimulatory property of measles virus vaccines but would not induce adaptive immunity. They are potentially useful as chemically defined vaccine adjuvants, antivirals, and immunostimulatory agents.


title: Where Are the Masks?

text: Shortages of vital PPE during the COVID-19 pandemic.


title: Accuracy of toric intraocular lens axis alignment using a 3-dimensional computer-guided visualization system.

text: PURPOSE To evaluate the accuracy of toric intraocular lens (IOL) alignment in femtosecond laser-assisted cataract surgery using the Truevision 3-dimensional (3-D) computer-guided visualization system compared with a manual marking method. SETTING Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA. DESIGN Retrospective comparative case series. METHODS Preoperatively, all patients had corneal topography measurements with a color light-emitting diode topographer. The 3-D system used the anterior keratometry values to create an optimized plan for the toric IOL alignment. Intrastromal marks were created by the femtosecond laser at the intended toric meridian, guided by manual ink marks placed at the 3 o'clock and 9 o'clock limbus with the patient sitting upright. Intraoperatively, the 3-D system was used to align the IOL and measure the angular position of the femtosecond marks relative to the IOL meridian. Three weeks postoperatively, the manifest refraction, corrected distance visual acuity, and toric IOL alignment were recorded. RESULTS The mean 3-D imaging error was -0.58 degrees ± 3.90 (SD) (range -9 to 5 degrees), and the mean manual ink error was -0.27 ± 3.65 degrees (range -8 to 5 degrees); neither was statistically significantly different from zero (P = .28 and P = .76, respectively). The mean absolute errors were 2.96 ± 2.54 degrees and 2.88 ± 2.18 degrees, respectively. CONCLUSION The 3-D computer-guided system and manual marking combined with femtosecond laser marks were similar in accuracy for toric alignment. FINANCIAL DISCLOSURES Dr. Wang received research support from Ziemer USA, Inc. Dr. Weikert is a consultant to Ziemer USA, Inc. Dr. Koch is a consultant to Alcon Laboratories, Inc., and Abbott Medical Optics, Inc., and received research support from Ziemer USA, Inc., i-Optics Corp, and Truevision Systems. None of the other authors has a financial or proprietary interest in any material or method mentioned.


title: Effects of Leak Compensation on Patient-Ventilator Synchrony During Premature/Neonatal Invasive and Noninvasive Ventilation: A Lung Model Study.

text: BACKGROUND During both nasal noninvasive ventilation (NIV) and invasive ventilation of neonates, the presence of air leaks causes triggering and cycling asynchrony. METHODS Five ICU ventilators (PB840, PB980, Servo-i, V500, and Avea) were compared in available invasive ventilation and NIV ventilator modes (pressure control continuous spontaneous ventilation [PC-CSV] and pressure control continuous mandatory ventilation [PC-CMV]). The V500 and Avea do not provide PC-CSV and PC-CMV in NIV. The Servo-i and Avea were tested with and without their proximal flow sensor. The ASL 5000 lung model (version 3.5) was used to simulate 4 neonatal scenarios (body weight 0.5, 1, 2, and 4 kg). The ASL 5000 was ventilated via endotracheal tube (invasive ventilation) or nasal cannula (NIV) with 4 different leaks. RESULTS The Avea (without flow sensor) during invasive ventilation and Servo-i and PB840 during NIV were not triggered by inspiratory efforts of the ASL 5000 at the baseline leak in the 0.5 kg scenario. In invasive ventilation, overall (median) asynchrony index was significantly lower with the PB980 (1%) and V500 (3%) than with the Servo-i (with flow sensor, 50%; without flow sensor, 50%) and Avea (with sensor, 50%; without sensor, 62%) (P < .05 for all comparisons). The PB840 (33%) was significantly different from all ventilators (P < .05). In NIV, the asynchrony index was significantly lower in PB980 (2%) than in the Servo-i (with sensor, 100%; without sensor, 100%) and PB840 (75%) (P < .05 for both). There was no difference in asynchrony index between PC-CSV and PC-CMV in all tested conditions and ventilators. CONCLUSIONS The ability of leak compensation to prevent asynchronous breathing varied widely between ventilators and lung mechanics. The PB980 and V500 were the only two ventilators to acclimate to all leak scenarios in invasive ventilation, and PB980 was the only ventilator to acclimate to all leak scenarios in NIV.


The COVID-19 Curriculum.


title: Congenital cranial ventral abdominal hernia, peritoneopericardial diaphragmatic hernia and sternal cleft in a 4-year-old multiparous pregnant queen.

text: Case summary Cranial ventral midline hernias, most often congenital, can be associated with other congenital abnormalities, such as sternal, diaphragmatic or cardiac malformations. A 4-year-old multiparous queen with a substernal hernia was admitted for evaluation of a mammary mass. During CT examination, a bifid sternum, the abdominal hernia containing the intestines, spleen, omentum, three fetuses, a mammary mass and an incidental peritoneopericardial diaphragmatic hernia were identified. Surgery consisted of a standard ovariohysterectomy and repair of the peritoneopericardial hernia. Primary closure of the abdominal hernia was attempted but deemed impossible even after the ovariohysterectomy, splenectomy and a partial omentectomy. An external abdominal oblique muscle flap was used to close with no tension on the cranial part of the hernia. One month postoperatively, the queen had no respiratory abnormalities and the herniorrhaphy was fully healed. Relevance and novel information This case is the first description of a 4-year-old multiparous pregnant queen with complex congenital malformations and surgical correction of a peritoneopericardial hernia and a 6 × 8 cmsubsternal hernia with an external abdominal oblique muscle flap. Life-threatening sequelae associated with large abdominal hernias can be attributed to space-occupying effects known as loss of domain and compartment syndrome, which is why a muscle flap was used in this case. The sternal cleft was not repaired because of the size of the cleft and the age of the cat.


title: Radiofrequency ablation: an assessment of clinical and cost efficacy.

text: BACKGROUND Varicose veins are common and frequently cause patient distress. In recent years, Radiofrequency ablation (RFA) has emerged as a minimally invasive alternative to traditional open venous ligation surgery. AIMS The aim of this study was to directly compare RFA and open saphenofemoral ligation. METHODS This was a single-centre retrospective cohort study. Consecutive patients undergoing surgical management over a 2-year period commencing from January 2011 were studied. Radiological success, peri-operative serological testing and hospital length of stay were documented. Procedural cost was calculated. A focused cohort analysis was undertaken to compare the initial 50 RFA procedures performed with the last 50. RESULTS During the study period, 296 patients underwent surgical intervention. A total of 204 patients underwent RFA. Sixty-six percent of all patients were female. RFA was associated with a reduction in overnight hospital stay (18 vs. 78 %, P = <0.001) when compared with open ligation with a success rate of 98 %. No significant inter-group difference was noted for 30-day readmission (p = 0.203). Focused cohort analysis identified an increase in hospital day case activity (74 vs. 90 %, p = 0.002), which contributed to a reduction in procedural cost (€1,024 vs. €971, p = 0.003) over the study period. CONCLUSIONS Radiofrequency ablation is a viable alternative to open repair offering excellent efficacy. It is however associated with a higher procedural cost than the open surgical option.


title: Modified Single Versus Double-Patch Technique for the Repair of Complete Atrioventricular Septal Defect.

text: OBJECTIVES We present our single center results of two commonly used surgical techniques, the modified single-patch and double-patch technique for the repair of the complete atrioventricular septal defect. METHODS We enrolled 49 patients with complete atrioventricular septal defect who were operated by a single surgeon between 2004 and 2014. The modified single-patch technique was performed in 32 cases (group S), whereas the defect was repaired with the double-patch technique in 17 patients (group D). RESULTS The mean age at the time of operation was 7.7 ± 8.6 (range 1-48) months and 9.9 ± 12.5 (range 1.5-48) months, in groups S and D, respectively. Mean body weight was 6.7 ± 3 (range 3.5-15.5) kilograms and 7.2 ± 3.8 (range 4.3-14.5) kilograms in groups S and D, respectively. Cross-clamp and cardiopulmonary bypass times were shorter in the modified single-patch group (65.6 ± 16.3 vs. 98.7 ± 19.8 minutes, p = 0.0001; 88.9 ± 23.3 vs. 128.9 ± 28.0 minutes, p = 0.0001). Postoperative atrioventricular valve function was improved in both groups. Mean follow-up period was 4.4 ± 3.2 (range 1.2-9.9) years. One patient in each group underwent reoperation for left atrioventricular valve insufficiency. We encountered two early and one late mortalities in modified single-patch group. One early mortality was experienced in the unmodified group. CONCLUSIONS The modified single-patch and two-patch techniques have comparable results; however, the modified single-patch technique is performed with significantly shorter cross-clamp and cardiopulmonary bypass times, therefore we have adopted this technique on a routine basis for the treatment of the complete atrioventricular septal defect in our institute.


title: A rat model of mild intestinal inflammation induced by Staphylococcus aureus enterotoxin B.

text: The epithelial barrier of the intestine and the gut-associated lymphoid tissue (GALT) protects the host against luminal pathogenic micro-organisms. This is important at weaning, when animals are exposed to infectious agents and stresses. We have developed a rat model of intestinal inflammation post weaning, based on the systemic administration of Staphylococcus aureus enterotoxin B (SEB). Since the inflammatory response obtained is mild, the food intake pattern is not affected, which makes this model useful for studies of nutritional therapies for intestinal inflammatory disease. SEB increased T-lymphocytes in Peyer's patches and the number of activated T-lymphocytes in mesenteric lymph nodes (organized GALT). In the lamina propria, SEB increased activated T-lymphocytes as well as cytotoxic and natural killer-cell populations of the diffuse GALT. It also increased pro-inflammatory cytokines and inflammatory mediators in both Peyer's patches and mucosa. Rats given SEB had higher paracellular permeability to macromolecules, which was associated with a reduction in epithelial tightness. This model was used to examine whether dietary supplementation with spray-dried animal plasma proteins affects intestinal inflammation. Results showed that dietary plasma proteins can attenuate the mucosal immune response in both organized and diffuse GALT and that these effects are mediated by a reduction in the production of pro-inflammatory cytokines.


title: The invisible victims - Impact of the pandemic on patients without COVID-19.

text: The coronavirus disease (COVID-19) pandemic has shocked the world to a standstill. Routine healthcare has been severely disrupted. Healthcare service is a finite resource and in the current pandemic situation the risks of providing care to individual patients, whether they be confirmed, probable or suspected cases, should be balanced against the ability to provide safe routine long-term care to others. But how far can the healthcare system protect itself and fear the unknown, before it starts causing harm by omission? Herein we provide a review of cases that were misdiagnosed, left stranded in the system or had to face unnecessary delays due to the lack of an organised pathway.


title: Single-incision laparoscopic total colectomy using an organ retractor: A case report.

text: Introduction Single-incision laparoscopic surgery (SILS) has benefits, including less postoperative pain, a shorter incision, and improved cosmesis. However, SILS is technically difficult because of the limited movement. An organ retractor is an instrument that has the potential to overcome these limitations. Presentation of case An 85-year-old woman with hematochezia was referred to our hospital. Emergency endoscopy showed diverticulosis of the entire colon and active bleeding from the ascending colon. Despite endoscopic clipping, the bleeding continued. SILS total colectomy using an organ retractor was performed due to uncontrollable diverticular bleeding. A 3-cm incision was placed in the umbilicus, and three conventional ports were inserted into the single umbilical incision. An organ retractor was used for hepatocolic ligament transection, transection of the ileocolic vessels, and transection of the mesentery of the sigmoid colon. For each transection, the tension was adjusted to provide a good operative view. The patient's postoperative course was uneventful. Conclusion An organ retractor was effective for SILS total colectomy to maintain an adequate operative view, which enabled safe dissection.


title: Therapeutic potential of glycyrrhetinic acids: a patent review (2010-2017).

text: INTRODUCTION Glycyrrhetinic acids (GAs) viz., 18β-glycyrrhetinic acid and 18α-glycyrrhetinic acid, are oleanane-type triterpenes having a carboxylic acid group at C-30, and are extracted from the Chines herbal medicine licorice (Glycyrrhiza uralensis). Although the pharmacological properties of GAs have long been known, attention to them has greatly increased in recent times due to their cytotoxic activity. AREAS COVERED This review represents the patents granted about natural and synthetic glycyrrhetinic acid analogs from January 2010 to December 2017, the advances made by research groups in conjunction with pharmaceutical companies in the discovery of new natural or synthetic glycyrrhetinic acid analogs. EXPERT OPINION GAs demonstrate excellent cytotoxic, antimicrobial, enzyme inhibitory, antiinflammatory, antioxidant, analgesic, and antiviral effects. It is interesting to note that the C-3(OH) and C30-CO2H functional groups make GAs very attractive lead structures for medicinal scientists since these functionalities allow the generation of further chemical diversity for improved pharmacological effects. Moreover, various GA analogues have been prepared via modification of the C30-CO2H. It is noteworthy that the C-30 amide of GA demonstrated better cytotoxic effects compared to the parent compounds. In addition, GAs have the capability to conjugate with other anticancer drugs or be converted into their halo or amino analogs which is expected to stimulate medicinal chemist to synthesize new lead compounds in cancer drug discovery.


title: Novel treatment with neuroprotective and antiviral properties against a neuroinvasive human respiratory virus.

text: Human coronaviruses (HCoVs) are recognized respiratory pathogens with neuroinvasive and neurotropic properties in mice and humans. HCoV strain OC43 (HCoV-OC43) can infect and persist in human neural cells and activate neuroinflammatory and neurodegenerative mechanisms, suggesting that it could be involved in neurological disease of unknown etiology in humans. Moreover, we have shown that HCoV-OC43 is neurovirulent in susceptible mice, causing encephalitis, and that a viral mutant with a single point mutation in the viral surface spike (S) protein induces a paralytic disease that involves glutamate excitotoxicity in susceptible mice. Herein, we show that glutamate recycling via the glial transporter 1 protein transporter and glutamine synthetase are central to the dysregulation of glutamate homeostasis and development of motor dysfunctions and paralytic disease in HCoV-OC43-infected mice. Moreover, memantine, an N-methyl-d-aspartate receptor antagonist widely used in the treatment of neurological diseases in humans, improved clinical scores related to paralytic disease and motor disabilities by partially restoring the physiological neurofilament phosphorylation state in virus-infected mice. Interestingly, memantine attenuated mortality rates and body weight loss and reduced HCoV-OC43 replication in the central nervous system in a dose-dependent manner. This novel action of memantine on viral replication strongly suggests that it could be used as an antiviral agent to directly limit viral replication while improving neurological symptoms in various neurological diseases with a viral involvement. Mutations in the surface spike (S) protein of human respiratory coronavirus OC43 appear after persistent infection of human cells of the central nervous system, a possible viral adaptation to this environment. Furthermore, a single amino acid change in the viral S protein modulated virus-induced neuropathology in mice from an encephalitis to a neuropathology characterized by flaccid paralysis, which involves glutamate excitotoxicity. We now show that memantine, a drug that is used for alleviating symptoms associated with neuropathology, such as Alzheimer's disease, can partially restore the physiological state of infected mice by limiting both neurodegeneration and viral replication. This suggests that memantine could be used as an antiviral agent while improving neurological symptoms in various neurological diseases with a viral involvement.


title: Implementation of Multi-Curie Production of (99m)Tc by Conventional Medical Cyclotrons.

text: UNLABELLED (99m)Tc is currently produced by an aging fleet of nuclear reactors, which require enriched uranium and generate nuclear waste. We report the development of a comprehensive solution to produce (99m)Tc in sufficient quantities to supply a large urban area using a single medical cyclotron. METHODS A new target system was designed for (99m)Tc production. Target plates made of tantalum were coated with a layer of (100)Mo by electrophoretic deposition followed by high-temperature sintering. The targets were irradiated with 18-MeV protons for up to 6 h, using a medical cyclotron. The targets were automatically retrieved and dissolved in 30% H2O2. (99m)Tc was purified by solid-phase extraction or biphasic exchange chromatography. RESULTS Between 1.04 and 1.5 g of (100)Mo were deposited on the tantalum plates. After high-temperature sintering, the (100)Mo formed a hard, adherent layer that bonded well with the backing surface. The targets were irradiated for 1-6.9 h at 20-240 μA of proton beam current, producing up to 348 GBq (9.4 Ci) of (99m)Tc. The resulting pertechnetate passed all standard quality control procedures and could be used to reconstitute typical anionic, cationic, and neutral technetium radiopharmaceutical kits. CONCLUSION The direct production of (99m)Tc via proton bombardment of (100)Mo can be practically achieved in high yields using conventional medical cyclotrons. With some modifications of existing cyclotron infrastructure, this approach can be used to implement a decentralized medical isotope production model. This method eliminates the need for enriched uranium and the radioactive waste associated with the processing of uranium targets.


title: Laparoscopic Total Gastrectomy in the Western Patient Population: Tips, Techniques, and Evidence-based Practice.

text: Gastric cancer is the second most common malignancy worldwide, and surgical resection is the only curative treatment. Traditionally, open total gastrectomy has been the procedure of choice for large and proximal carcinomas. Over the past decade, however, laparoscopic gastrectomy has emerged and an oncologically safe and feasible alternative to open surgery, and its use has become particularly widespread in Japan and Korea. Patients in the United States have important biological and anatomic distinctions from East Asian patients, and these become important factors when considering minimally invasive resection techniques. The goal of this paper is to describe the technique we have developed for laparoscopic total gastrectomy in our 10-year experience with a western patient population.


Prevention and control of methicillin-resistant Staphylococcus aureus: dealing with reality, resistance, and resistance to reality.


title: Challenges with Diagnosing and Managing Sepsis in Older Adults.

text: Sepsis in older adults has many challenges that affect rate of septic diagnosis, treatment, and monitoring parameters. Numerous age-related changes and comorbidities contribute to increased risk of infections in older adults, but also atypical symptomatology that delays diagnosis. Due to various pharmacokinetic/pharmacodynamic changes in the older adult, medications are absorbed, metabolized, and eliminated at different rates as compared to younger adults, which increases risk of adverse drug reactions due to use of drug therapy needed for sepsis management. This review provides information to aid in diagnosis and offers recommendations for monitoring and treating sepsis in the older adult population.


Cholangioscopic diagnosis of iatrogenic recurrent choledocholithiasis.


title: The Ottawa panel clinical practice guidelines for the management of knee osteoarthritis. Part one: introduction, and mind-body exercise programs.

text: OBJECTIVE To identify effective mind-body exercise programs and provide clinicians and patients with updated, high-quality recommendations concerning non-traditional land-based exercises for knee osteoarthritis. METHODS A systematic search and adapted selection criteria included comparative controlled trials with mind-body exercise programs for patients with knee osteoarthritis. A panel of experts reached consensus on the recommendations using a Delphi survey. A hierarchical alphabetical grading system (A, B, C+, C, D, D+, D-) was used, based on statistical significance ( P < 0.5) and clinical importance (⩾15% improvement). RESULTS The four high-quality studies identified demonstrated that various mind-body exercise programs are promising for improving the management of knee osteoarthritis. Hatha Yoga demonstrated significant improvement for pain relief (Grade B) and physical function (Grade C+). Tai Chi Qigong demonstrated significant improvement for quality of life (Grade B), pain relief (Grade C+) and physical function (Grade C+). Sun style Tai Chi gave significant improvement for pain relief (Grade B) and physical function (Grade B). CONCLUSION Mind-body exercises are promising approaches to reduce pain, as well as to improve physical function and quality of life for individuals with knee osteoarthritis.


title: The impacts of unstructured nature play on health in early childhood development: A systematic review.

text: BACKGROUND Nature play is growing in popularity as children's play spaces are transforming from traditional playgrounds into more nature-based play spaces with considerable financial and resource investment from government bodies. This has resulted in the re-development of children's play spaces to incorporate more natural elements such as trees, plants and rocks. Despite this, it is unclear whether there is empirical evidence to support claims that play in nature is beneficial for child health and development. AIM To conduct a systematic review examining the impacts of nature play on the health and developmental outcomes of children aged 2-12 years. METHODS Seven electronic databases were searched (MEDLINE, ERIC, Embase, PsycINFO, The Cochrane Library, The Joanna Briggs Institute and Emcare) from inception to July/August 2018 (search updated July/August 2019). The Inclusion criteria were children aged 2-12 years with no health/developmental conditions. The exposure/intervention of interest was unstructured, free play in nature. Critical appraisal of included studies was conducted using the McMaster Critical Appraisal Tool. Descriptive synthesis was then undertaken using the NHMRC FORM Framework. RESULTS Out of 2927 articles identified, 16 studies met the inclusion criteria. The nature play exposure/intervention was heterogeneously described, and a plethora of outcome measures were used. Nature play had consistent positive impacts on physical activity outcomes and cognitive play behaviours (imaginative and dramatic play). However, there remain some concerns regarding the quality of the evidence base, heterogeneity in intervention description and parameters in the outcome measures used. CONCLUSIONS While the positive impacts of nature play were encouraging in terms of physical activity and cognitive development, nature play stakeholders should focus on producing a universal definition for nature play, the development of standardised outcome measures and the conduct of robust research designs. Implications of these findings suggest the need for the development of standardised guidelines to inform practice and policy in the design of children's play spaces in different contexts.


Guidelines for non-invasive and invasive mechanical ventilation for treatment of chronic respiratory failure. Published by the German Society for Pneumology (DGP).


title: Composition of fibrin glues significantly influences axial vascularization and degradation in isolation chamber model.

text: In this study, different fibrin sealants with varying concentrations of the fibrin components were evaluated in terms of matrix degradation and vascularization in the arteriovenous loop (AVL) model of the rat. An AVL was placed in a Teflon isolation chamber filled with 500 μl fibrin gel. The matrix was composed of commercially available fibrin gels, namely Beriplast (Behring GmbH, Marburg, Germany) (group A), Evicel (Omrix Biopharmaceuticals S.A., Somerville, New Jersey, USA) (group B), Tisseel VH S/D (Baxter, Vienna, Austria) with a thrombin concentration of 4 IU/ml and a fibrinogen concentration of 80 mg/ml [Tisseel S F80 (Baxter), group C] and with an fibrinogen concentration of 20 mg/ml [Tisseel S F20 (Baxter), group D]. After 2 and 4 weeks, five constructs per group and time point were investigated using micro-computed tomography, and histological and morphometrical analysis techniques. The aprotinin, factor XIII and thrombin concentration did not affect the degree of clot degradation. An inverse relationship was found between fibrin matrix degradation and sprouting of blood vessels. By reducing the fibrinogen concentration in group D, a significantly decreased construct weight and an increased generation of vascularized connective tissue were detected. There was an inverse relationship between matrix degradation and vascularization detectable. Fibrinogen as the major matrix component showed a significant impact on the matrix properties. Alteration of fibrin gel properties might optimize formation of blood vessels.


Understanding COVID-19 new diagnostic guidelines - a message of reassurance from an internal medicine doctor in Shanghai.