title: [Clinical experience and critical issues.]

text: Bergamo is a rich and populous city of northern Italy and one of the epicentres of the worldwide pandemic CoViD-19. Despite the generosity of health workers, we are undergoing a severe humanitarian crisis that is stressing every aspect of daily life. From outside it is very hard to understand, because houses are closed for lockdown and are not destroyed as they would be in an earthquake. An outbreak is not "only" a sudden mass lethal incident, like a natural disaster, neither "only" a disease, to be treated by doctors, but a social phenomenon too. Historical and social elements are key factors for development (for example, intensive promiscuity between animals and humans) and spread of an epidemic (for example, health workers and ambulance rapidly become vector of the virus). Can medical responsibility change in times of pandemic? My answer, as anaesthetist and intensive care physician from Bergamo, is yes. When the global medical community is called on to face a pandemic of unprecedented scale, with little scientific evidence and "crazy numbers" describing the situation, honest and forthcoming advocacy is an ethical duty. Aim of this narrative report is to share a view point about the dilemma of moral responsibility.


title: Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial.

text: BACKGROUND The degree of antiplatelet response to clopidogrel has been associated with clinical outcomes. Studies have investigated whether adjustment of antiplatelet therapies based on a single platelet function test is beneficial. OBJECTIVES The aim of the study was to test the stability of platelet reactivity measurements over time among patients treated with standard and double doses of clopidogrel. METHODS The ELEVATE-TIMI 56 (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56) investigators genotyped 333 patients with coronary artery disease and randomized them to various clopidogrel regimens. Patients with at least 2 platelet function results on the same maintenance dose of clopidogrel (75 mg or 150 mg) were analyzed. Platelet aggregation was measured using P2Y12 reaction units (PRU). RESULTS In total, the mean platelet reactivity and the total number of nonresponders (PRU ≥230) with clopidogrel did not change between 2 periods for the 75-mg (22.4% vs. 21.9%; p = 0.86) and 150-mg doses of clopidogrel (11.5% vs. 11.5%; p = 1.00). In contrast, when evaluating each patient individually, 15.7% of patients taking clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their responder status when tested at 2 different time points (p < 0.001). Despite being treated with the same dose of clopidogrel, >40% of patients had a change in PRU >40 on serial sampling, which approximates the average PRU difference caused by increasing the clopidogrel dose from 75 mg to 150 mg. CONCLUSIONS Measurements of platelet reactivity vary over time in a significant proportion of patients. Thus, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy in clinical or research settings. (Escalating Clopidogrel by Involving a Genetic Strategy-Thrombolysis In Myocardial Infarction 56 [ELEVATE-TIMI 56]; NCT01235351).


title: The potential transmission of SARS-CoV-2 from patients with negative RT-PCR swab tests to others: two related clusters of COVID-19 outbreak.

text: In December 2019, a cluster of cases of acute respiratory illness, novel coronavirusinfected pneumonia, occurred in Wuhan, Hubei Province, China. The false-negative nasopharyngeal swabs of SARS-CoV-2 caused the delayed diagnosis of COVID-19 which hindered the prevention and control of the pandemic. The transmission risk of SARS-CoV-2 in negative nasopharyngeal swabs cases were little addressed previously. This study evaluated two clusters of COVID-19 in six patients. Four of six (66.7%) showed negative RNA of SARS-CoV-2 by nasopharyngeal swabs. All epidemiological, clinical and laboratory information was collected. The first cluster was a nosocomial infection of four health care providers at early January. One of them made sequential familial cluster of infection. All patients received either selfquarantined at home or were admitted to hospital for isolated treatment. All recovered and had anti-SARS-CoV-2 IgG and/or IgM positive (100%) for serological detection of SARS-CoV-2 at recovery stage. Our study provides a cautionary warning that negative results of nasopharyngeal swabs of suspected SARS-CoV-2 infection can increase the risk of nosocomial infection among health care providers. Serologic detection for anti-SARS-CoV-2 IgG and/or IgM is an important test in the assistant diagnosis of COVID-19.


title: Effect of chemical clarification of oral fluids on the detection of porcine reproductive and respiratory syndrome virus IgG.

text: Routine collection and testing of oral fluid (OF) samples facilitates porcine reproductive and respiratory syndrome virus (PRRSV) surveillance in commercial swine herds in a cost-effective, welfare-friendly fashion. However, OFs often contain environmental contaminants that may affect liquid handling and test performance. Traditional processing methods (e.g., filtration or centrifugation) are not compatible with high-throughput testing because of the burden of additional processing costs and time. OF "clarification" using chemical flocculants is an alternative approach not widely explored. Therefore, we evaluated the effect of chitosan-based clarification treatment on a commercial PRRSV OF ELISA. Serum and individual OFs were collected from vaccinated pigs ( n = 17) at -7 to 42 d post-vaccination and subdivided into 4 aliquots. Each aliquot was clarified (treatment A, B, C), with the 4th aliquot serving as untreated control. All samples were tested by PRRSV OF ELISA immediately after treatment and then were held at 4°C to be re-tested at 2, 4, 6, and 14 d post-treatment. Quantitative and qualitative treatment effects were evaluated. A Kruskal-Wallis test found no significant difference in ELISA S/P responses among treatments by days post-treatment. No difference was detected in the proportion of positive PRRSV antibody samples among treatments (Cochran Q, p > 0.05). Treatment of swine OFs using chitosan-based formulations did not affect the performance of a commercial PRRSV OF ELISA. Chitosan (or other flocculants) could improve OF characteristics and could be adapted for use in the field or in high-throughput laboratories.


Department of rehabilitation medicine in Shanghai response for coronavirus disease 2019: the impact and challenges.


title: Surface plasmon resonance for vaccine design and efficacy studies: recent applications and future trends.

text: The lack of a clear correlation between design and protection continues to present a barrier to progress in vaccine research. In this article, we outline how surface plasmon resonance (SPR) biosensors are emerging as tools to help resolve some of the key biophysical determinants of protection and, thereby, facilitate more rational vaccine design campaigns. SPR technology has contributed significantly to our understanding of the complex biophysical determinants of HIV neutralization and offers a platform for preclinical evaluation of vaccine candidates. In particular, the concept of reverse-engineering HIV vaccine targets based on known broadly neutralizing antibody modalities is explored and extended to include other infectious diseases, such as malaria and influenza, and other diseases such as cancer. The analytical capacity afforded by SPR includes serum screening to monitor immune responses and highly efficient quality-control surveillance measures. These are discussed alongside key technological advances, such as developments in sample throughput, and a perspective predicting continued growth and diversification of the role of SPR in vaccine development is proposed.


title: Driving improvements in emerging disease surveillance through locally relevant capacity strengthening.

text: Emerging infectious diseases (EIDs) threaten the health of people, animals, and crops globally, but our ability to predict their occurrence is limited. Current public health capacity and ability to detect and respond to EIDs is typically weakest in low- and middle-income countries (LMICs). Many known drivers of EID emergence also converge in LMICs. Strengthening capacity for surveillance of diseases of relevance to local populations can provide a mechanism for building the cross-cutting and flexible capacities needed to tackle both the burden of existing diseases and EID threats. A focus on locally relevant diseases in LMICs and the economic, social, and cultural contexts of surveillance can help address existing inequalities in health systems, improve the capacity to detect and contain EIDs, and contribute to broader global goals for development.


title: Will Coronavirus Disease 2019 Become Seasonal?

text: This manuscript explores the question of the seasonality of severe acute respiratory syndrome coronavirus 2 by reviewing 4 lines of evidence related to viral viability, transmission, ecological patterns, and observed epidemiology of coronavirus disease 2019 in the Southern Hemispheres' summer and early fall.


Therapeutic options for the 2019 novel coronavirus (2019-nCoV).


title: Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery.

text: The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a first step towards solution dosage form development. The parameters such as log P value were determined experimentally and compared with predicted values. The pH-dependent aqueous solubility and stability were investigated following standard protocols at 25°C and 37°C. Drug solubility enhancement was attempted utilizing both surfactants and cyclodextrins (CDs), and the drug/CD complexation was studied employing various techniques such as differential scanning calorimetry, Fourier transform infrared, nuclear magnetic resonance, and scanning electron microscopy. The experimental log P value suggested that the compound is fairly hydrophilic. Berberine chloride was found to be very stable up to 6 months at all pH and temperature conditions tested. Aqueous solubility of the drug was temperature dependent and exhibited highest solubility of 4.05 ± 0.09 mM in phosphate buffer (pH 7.0) at 25°C, demonstrating the effect of buffer salts on drug solubility. Decreased drug solubility was observed with increasing concentrations of ionic surfactants such as sodium lauryl sulfate and cetyl trimethyl ammonium bromide. Phase solubility studies demonstrated the formation of berberine chloride-HPβCD inclusion complex with 1:1 stoichiometry, and the aqueous solubility of the drug improved almost 4.5-fold in the presence of 20% HPβCD. The complexation efficiency values indicated that the drug has at least threefold greater affinity for hydroxypropyl-β-CD compared to randomly methylated-β-CD. The characterization techniques confirmed inclusion complex formation between berberine chloride and HPβCD and demonstrated the feasibility of developing an oral solution dosage form of the drug.


title: Antisperm antibodies and testicular blood flow after inguinal hernia mesh repair.

text: BACKGROUND Testicular flow studies after hernia mesh repair mostly showed different outcomes. The reason of infertility in some men after hernia repair is immunological factors. Aim of the study was to investigate the influence of mesh hernia repair on antisperm antibodies production and testicular blood flow and a connection among these parameters. MATERIALS AND METHODS A prospective interventional longitudinal cohort study was made on 82 male patients without exclusion criteria who had an inguinal hernia. Patients underwent laparoscopic TAPP or open tension-free hernia repair. Vascular ultrasound and antisperm antibodies were measured in the preoperative and postoperative periods. Main outcome measures were resistive index (RI), peak systolic velocity (PSV) cm/s, and end-diastolic velocity (EDV) cm/s in testicular blood flow measurement and the quantitative value of antisperm antibodies (ASA) in serum (IU/ml). RESULTS ASA significantly increased postoperatively only in patients who underwent open tension-free hernia repair (p < 0.001). ASA stayed in normal range in all patients except the one with postoperative complication. Friedman analysis showed significant change of the RI only on intratesticular (p < 0.001) and capsular artery level (0.02) in patients who underwent laparoscopic technique. PSV significantly changed on intratesticular (p < 0.001) and capsular artery level (p = 0.015) in the laparoscopic hernia repair. PSV showed significant change on intratesticular (p < 0.001) and testicular artery levels (p < 0.001) in the open tension-free hernia repair. EDV showed significant change only on testicular artery level (p = 0.032) in the patients who had open tension-free hernia repair. These blood flow parameters significantly increased in the early postoperative period and returned on basal value in the late postoperative period. Parameters of flow did not show any significant correlation with ASA. CONCLUSION Mesh hernia repairs without complication caused only a transitory change in testicular blood flow and no clinical significant autoimmune reaction.


title: Primary manual aspiration thrombectomy (MAT) for acute ischemic stroke: safety, feasibility and outcomes in 112 consecutive patients.

text: AIM To describe procedural aspects and clinical outcomes in a consecutive series of patients in whom manual aspiration thrombectomy (MAT) was performed as the first treatment modality with other techniques used only in case MAT did not yield recanalization. METHODS A retrospective review of a prospectively acquired acute stroke intervention database was performed. Primary MAT was carried out with a preference for the largest catheter considered to be trackable into the target occlusive lesion. The catheter was wedged into the thrombus followed by manual aspiration with a 20 ml syringe. RESULTS 112 consecutive patients were evaluated. The median age was 66 years and the median NIH Stroke Scale score was 17. Occlusion locations included the M1 (62%), M2 (8%), internal carotid artery terminus (19%) and the vertebrobasilar artery (11%). Patients with anterior occlusions had tandem extracranial/intracranial occlusive lesions in 18.7% Median time from symptom onset to groin puncture was 267 min, and from groin puncture to recanalization was 70 min. Successful recanalization (defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3) with primary MAT was 59% with a median of two passes. 41% of patients required the use of adjunctive therapy yielding an overall recanalization rate of TICI 2b/3 (86%) and TICI 3 (30.6%). Parenchymal hematoma of any type (PH1/PH2) was seen in 9.8% of patients, with symptomatic hemorrhage in 6%. Favorable outcomes (90-day modified Rankin Scale ≤2) were 46%. Mortality at 3 months was 31%. Primary MAT was associated with faster procedural times (mean 63 vs 97 min, p<0.0001) but not with higher rates of favorable outcomes. CONCLUSIONS Primary MAT is an alternative endovascular recanalization technique with reasonable first pass efficacy that will likely improve with technology and experience.


title: Comparison of four microwave ablation devices: an experimental study in ex vivo bovine liver.

text: PURPOSE To compare volume, sphericity, and short-axis diameter of the coagulation zone of four commercially available microwave ablation systems with three technical concepts in an ex vivo setting and to formulate mathematical models to predict these quantities. MATERIALS AND METHODS Two high-power systems (systems A and B), a system that enables simultaneous use of three antennas (system C), and a non-perfusion-cooled system that automatically adapts power and frequency (system D) were tested in ex vivo bovine livers (108 ablations). Coagulation volume, sphericity, and mean short-axis diameter were assessed, and mathematical functions were fitted for each system and assessed with the coefficient of determination (R(2)). Analysis of variance and Tukey post hoc tests were used for interdevice comparison after 5 and 10 minutes and after maximum recommended ablation time. RESULTS Volume and short-axis diameter were determined by using a mathematical model for every system, with coefficients of determination of 0.75-0.98 and 0.70-0.97, respectively. Correlation for determination of sphericity was lower (R(2) = 0.01-0.68). Mean results with ablation performed according to manufacturer recommendations were as follows: Volume, sphericity, and short-axis diameter were 57.5 cm(3), 0.75, and 43.4 mm, respectively, for system A; 72.3 cm(3), 0.68, and 45.5 mm, respectively, for system B; 17.1 cm(3), 0.58, and 26.8 mm, respectively, for system C (one antenna); 76.5 cm(3), 0.89, and 50.6 mm, respectively, for system C (three antennas); and 56.0 cm(3), 0.64, and 40.9 mm, respectively, for system D. Systems A (mean volume, 52.4 cm(3) ± 4.5 [standard deviation]) and B (39.4 cm(3) ± 1.7) reach large ablation zones with 5-minute ablation. CONCLUSION The largest ablation zone is obtained with systems B and C (three antennas) under maximum recommended ablation duration and with system A under short ablation time. The most spherical zone is obtained with system C (three antennas).


title: Louseborne Relapsing Fever among East African Refugees, Italy, 2015.

text: During June 9-September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.


title: Cancer and COVID-19: Unmasking their ties.

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and its clinical manifestation, the coronavirus disease 2019 (COVID19) have rapidly spread across the globe, leading to the declaration of a pandemic. While most present mild symptoms, it appears as though nearly 20% of confirmed patients develop significant complications. These include acute respiratory distress syndrome, septic shock and multi-organ failure, with a 3-6% mortality. A plethora of treatments has been or is being assessed, but to date, none has been proven effective. Management is mainly symptomatic, with organ support for the critically ill. Several reports, mainly case series, from across the world have concluded that patients with malignancy appear more susceptible to severe infection and mortality from COVID-19. This could be attributed to immunosuppression, co-existing medical conditions and underlying pulmonary compromise which is often the case in lung malignancy. Patients with haematological cancer and those who are receiving active chemotherapy treatment may be at greatest risk due to increased immunosuppression. This pandemic tested the resilience of worldwide health-care systems in an unprecedented manner. It has forced oncologists to rethink the entire diagnostic and therapeutic process, based on the local prevalence and impact of COVID-19. In this review we will discuss the impact of COVID-19 on patients affected by cancer, their diagnosis and management, as well as the pathophysiology of COVID-19 induced acute respiratory distress symptoms and currently investigated treatment approaches.


title: Continuous positive airway pressure and ventilation are more effective with a nasal mask than a full face mask in unconscious subjects: a randomized controlled trial.

text: INTRODUCTION Upper airway obstruction (UAO) is a major problem in unconscious subjects, making full face mask ventilation difficult. The mechanism of UAO in unconscious subjects shares many similarities with that of obstructive sleep apnea (OSA), especially the hypotonic upper airway seen during rapid eye movement sleep. Continuous positive airway pressure (CPAP) via nasal mask is more effective at maintaining airway patency than a full face mask in patients with OSA. We hypothesized that CPAP via nasal mask and ventilation (nCPAP) would be more effective than full face mask CPAP and ventilation (FmCPAP) for unconscious subjects, and we tested our hypothesis during induction of general anesthesia for elective surgery. METHODS In total, 73 adult subjects requiring general anesthesia were randomly assigned to one of four groups: nCPAP P0, nCPAP P5, FmCPAP P0, and FmCPAP P5, where P0 and P5 represent positive end-expiratory pressure (PEEP) 0 and 5 cm H2O applied prior to induction. After apnea, ventilation was initiated with pressure control ventilation at a peak inspiratory pressure over PEEP (PIP/PEEP) of 20/0, then 20/5, and finally 20/10 cm H2O, each applied for 1 min. At each pressure setting, expired tidal volume (Vte) was calculated by using a plethysmograph device. RESULTS The rate of effective tidal volume (Vte > estimated anatomical dead space) was higher (87.9% vs. 21.9%; P<0.01) and the median Vte was larger (6.9 vs. 0 mL/kg; P<0.01) with nCPAP than with FmCPAP. Application of CPAP prior to induction of general anesthesia did not affect Vte in either approach (nCPAP pre- vs. post-; 7.9 vs. 5.8 mL/kg, P = 0.07) (FmCPAP pre- vs. post-; 0 vs. 0 mL/kg, P = 0.11). CONCLUSIONS nCPAP produced more effective tidal volume than FmCPAP in unconscious subjects. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01524614.


title: Treatment options for symptomatic carotid stenosis: timing and approach.

text: Stroke is a major cause of morbidity and mortality and up to 15-20% of ischemic strokes can be attributed to atherosclerotic internal carotid artery disease. The treatment of carotid artery disease has been the subject of a wealth of literature in the past twenty years since the publication of the landmark randomized controlled trials, the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial, in the early 1990s. Although these landmark trials have helped establish the current guidelines for treatment of patients with symptomatic carotid artery disease, there have since been major advancements in the medical treatment of cardiovascular disease and there still remains a great deal of controversy regarding the timing and technical approach to carotid revascularization. In particular, there has been a wealth of literature to determine whether carotid endarterectomy or carotid stenting should be used for revascularization and when this revascularization should occur following onset of symptoms. This update offers an overview of the standards for diagnosis and medical treatment of patients with symptomatic carotid artery disease, the indications for surgical revascularization and a review of the most pertinent literature as it pertains to the more controversial issues of technical approach and timing of surgical revascularization following onset of symptoms in patients with carotid artery disease.


title: A novel liquid biopsy-based approach for highly specific cancer diagnostics: mitigating false responses in assaying patient plasma-derived circulating microRNAs through combined SERS and plasmon-enhanced fluorescence analyses.

text: Studies have shown that microRNAs, which are small noncoding RNAs, hold tremendous promise as next-generation circulating biomarkers for early cancer detection via liquid biopsies. A novel, solid-state nanoplasmonic sensor capable of assaying circulating microRNAs through a combined surface-enhanced Raman scattering (SERS) and plasmon-enhanced fluorescence (PEF) approach has been developed. Here, the unique localized surface plasmon resonance properties of chemically-synthesized gold triangular nanoprisms (Au TNPs) are utilized to create large SERS and PEF enhancements. With careful modification to the surface of Au TNPs, this sensing approach is capable of quantifying circulating microRNAs at femtogram/microliter concentrations. Uniquely, the multimodal analytical methods mitigate both false positive and false negative responses and demonstrate the high stability of our sensors within bodily fluids. As a proof of concept, microRNA-10b and microRNA-96 were directly assayed from the plasma of six bladder cancer patients. Results show potential for a highly specific liquid biopsy method that could be used in point-of-care clinical diagnostics to increase early cancer detection or any other diseases including SARS-CoV-2 in which RNAs can be used as biomarkers.


title: Daily Reportable Disease Spatiotemporal Cluster Detection, New York City, New York, USA, 2014-2015.

text: Each day, the New York City Department of Health and Mental Hygiene uses the free SaTScan software to apply prospective space-time permutation scan statistics to strengthen early outbreak detection for 35 reportable diseases. This method prompted early detection of outbreaks of community-acquired legionellosis and shigellosis.


title: Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies.

text: Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. 81mKr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99mTc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81mKr gas-ventilation and 99mTc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.


Erratum to: Porcine epidemic diarrhea virus: An emerging and re-emerging epizootic swine virus.


title: COVID-19: Notes From the Front Line, Singapore's Primary Health Care Perspective.

text: Coronavirus disease 2019 (COVID-19) is a rapidly progressing global pandemic against which nations are struggling for containment. Singapore is known to have promptly instituted aggressive public health and containment measures. A key pillar sustaining this is the response of its primary health care network. It is important for health care systems worldwide to recognize the value of a strong coordinated response to this crisis from a primary health perspective. There are best practices for early isolation and containment of suspect cases while protecting health care workers and limiting cross infections that are transferable across nations. We describe our framework for how our primary care clinics respond to this pandemic in the hope others may find solutions to their unique needs. Moving forward, there is a pressing need for more studies to enhance our understanding of the response of primary care during these public health crises.


title: Removal of emerging pollutants in aqueous phase by heterogeneous Fenton and photo-Fenton with Fe2O3-TiO2-clay heterostructures.

text: Fe2O3-TiO2-clay heterostructures have been prepared using an organo-bentonite as support, which organophilic character favored the fixation of TiO2. Furthermore, Fe2O3 was successfully anchored by wet impregnation. The resulting materials are characterized by a disordered layered structure and a mesoporous texture. The heterostructures were employed as catalysts for the removal of two pharmaceuticals, acetaminophen (ACE) and antipyrine (ANT), by heterogeneous Fenton and photo-Fenton processes. ACE removal under different operation conditions was studied in detail to establish structure-performance relationships, being the TiO2 formation and the developed texture the main factors controlling the activity. ANT showed a higher refractory behavior in oxidation by Fenton. Among the technologies studied, heterogeneous photo-Fenton achieved the best catalytic performance and higher kinetic rate and mineralization degree. Iron leaching was very low, lower than 5% of the initial iron load in all cases. This work demonstrates the potential application of these heterostructures for the removal of emerging pollutants of different nature.


title: Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination.

text: Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdown experiments further indicate that SMAD-mediated BMP signaling is largely required for differentiation-related processes rather than directly influencing self-renewal. Among the SMAD-associated genes, we further identified Dpysl2 (previously known as Crmp2) and the H3K27 demethylase Kdm6b (previously known as Jmjd3) as BMP4-modulated early neural differentiation regulators. Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators.


title: Serum cytokine responses in primary pneumonic plague patients.

text: The serum levels of interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10 of pneumonic plague patients were determined by enzyme-linked immunosorbent assay. IL-6 was the only elevated cytokine in the patients, and its level increased with a clear time course, indicating that IL-6 might be a prognostic marker for predicting the progression of plague.


title: Results of laparoscopic radiofrequency ablation for HCC. Could the location of the tumour influence a complete response to treatment? A single European centre experience.

text: INTRODUCTION In selected patients, radiofrequency ablation (RFA) is a well-established treatment for hepatocellular carcinoma (HCC). However, subcapsular or lesions close to adjacent viscera preclude a percutaneous approach. In this setting laparoscopic-RFA (LRFA) is a potential alternative. The aim of this study was to analyse the safety and feasibility of LRFA in patients with HCC. PATIENTS AND METHODS Retrospective study of patients with HCC meeting strict inclusion criteria who underwent LRFA at a single Institution from December 2000 to March 2013. RESULTS Forty-one patients underwent 42 LRFA of 51 nodules. The median size of the nodule was 2.5 (range 1.2-4.7) cm. Thirty-one tumours were subcapsular and 17 located near the gallbladder. Major complications occurred in 17 patients. The initial complete response (ICR) rate was 94% and was lower among tumours located adjacent to the gallbladder. At the end of the follow-up period, the sustained complete response (SCR) rate was 70% and was lower in tumours adjacent to the gallbladder while increased for subcapsular tumours. The 1-, 3- and 5-year overall survival rate was 92.6%, 64.5% and 43%, respectively. CONCLUSION LRFA of HCC is safe, feasible and achieves excellent results in selected patients. LRFA should be the first-line technique for subcapsular lesions as it minimizes the risk of tumoural seeding and improves ICR. Proximity to gallbladder interferes in treatment efficacy (lower rate of ICR and lower rate of SCR).


title: Mesenchymal stem cell-based angiotensin-converting enzyme 2 in treatment of acute lung injury rat induced by bleomycin.

text: BACKGROUND Acute lung injury (ALI) is a high incidence disease with no effective therapeutic method (mortality rate > 40%). The aim of this study was to find a new and effective therapeutic method for ALI. METHODS After the isolation of human umbilical cord mesenchymal stem cells (HUMSCs) from cesarean fetus, we transfected the HUMSCs with Lenti-ACE2 (angiotensin-converting enzyme 2) viral particles. Then we evaluated the therapeutic effect of HUMSCs harboring ACE2 on ALI, which induced by bleomycin (BLM) in rat model. RESULTS Our results showed that HUMSCs harboring ACE2 could attenuate ALI degree through reducing pulmonary inflammatory infiltration and degree of vascular permeability, repressing the mRNA level of pro-inflammatory cytokines, activating the mRNA level of anti-inflammatory cytokines and ACE2. Besides, results also demonstrated that HUMSCs harboring ACE2 gene had higher therapeutic effects to ALI than the single factor of HUMSCs or ACE2. CONCLUSIONS This research provided clues for the development of effective therapeutic methods to ALI using stem cell transplantation and gene therapy.


Psychological Distress and Loneliness Reported by US Adults in 2018 and April 2020.


title: Minimally invasive versus open surgery for acute Achilles tendon rupture: a systematic review.

text: INTRODUCTION This review provides a comprehensive description of clinical, functional outcomes, and complications after open and minimally invasive surgery for Achilles tendon ruptures. SOURCES OF DATA We systematically searched Medline (PubMED), EMBASE, CINHAL, Cochrane, Sports Discus and Google scholar databases using the combined keywords 'open repair', 'percutaneous surgery', 'minimally invasive surgery' 'Achilles tendon rupture', 'complications', 'infections', 'wound disorders' to identify articles published in English, Spanish, French and Italian. AREAS OF AGREEMENT Twelve studies fulfilled our inclusion criteria. Six studies were retrospective, five were randomized controlled trials and one was a prospective investigation. Of a total of 781 patients, 375 underwent open repair and 406 percutaneous surgery. Different procedures were performed for open and minimally invasive repair. AREAS OF CONTROVERSY The range of motion was significantly greater after percutaneous repair than open surgery. The number of complications that occurred after open surgery was higher than after minimally invasive surgery. GROWING POINTS Minimally invasive surgery is less expensive and less time demanding. AREAS TIMELY FOR DEVELOPING RESEARCH Minimally invasive and open surgery of the Achilles tendon are grossly equivalent. However, iatrogenic neurological complications are more frequent after percutaneous repair. Novel percutaneous repairs have been proposed to minimize the risk of sural nerve injury.


title: Fracture-induced changes in biomarkers CTX, PINP, OC, and BAP-a systematic review.

text: To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.


title: Does spinal excitability scale to the difficulty of the dual-task?

text: PURPOSE This study examined whether spinal excitability, as measured by the soleus Hoffmann reflex (H-reflex), is scaled to the difficulty level of the dual-task being performed. METHODS Twenty-two participants completed a combination of three balance task and three secondary cognitive (visuo-motor) task difficulty levels for a total of nine dual-task conditions. An additional eight participants were tested while performing the same three balance task difficulty levels on its own (i.e., single-tasking). The balance task required participants to maintain their balance on a fixed or rotating stabilometer while the visuo-motor task required participants to respond to moving targets presented on a monitor. Throughout each single- and dual-task trial, H-reflexes were elicited from the soleus. RESULTS Although dual-task performance, as quantified by visuo-motor task accuracy as well as the root mean square of the stabilometer position and velocity, decreased by 10-34% with increasing dual-task difficulty (p < 0.05), no changes in the soleus H-reflex amplitude were observed between dual-task conditions (p = 0.483-0.758). This contrasts to when participants performed the balance task as a single-task, where the H-reflex amplitude decreased by ~25% from the easy to the hard balance task difficulty level (p = 0.037). CONCLUSIONS In contrast to the commonly reported finding of a reduced soleus H-reflex amplitude when individuals perform a less posturally stable task by itself, the results indicate that spinal excitability is not modulated as a function of dual-task difficulty. It is possible that when an individual's attentional resource capacity is exceeded during dual-tasking, they become ineffective in regulating spinal excitability for balance control.


title: Vulnerable Children in a Dual Epidemic.

text: Two epidemics-Covid-19 and opioid use disorder (OUD) -are creating short- and long-term mental and physical health risks for vulnerable children and adolescents. Information about the risks to children from exposure to the coronavirus is still fragmentary, but even many healthy children are not getting appropriate health care, such as vaccinations or monitoring of developmental milestones during the Covid-19 pandemic. Children living in poverty are at heightened risk. Youngsters who are already dealing with OUD in their families-2.2 million as of 2017-face serious consequences stemming from trauma and stress. Although not officially designated by the Centers for Disease Control and Prevention as "adverse childhood experiences" ("ACEs"), these situations meet the CDC's criteria for inclusion, such as death or separation from a parent. It is important to recognize and meet the needs of all these children now and not just when the long-term consequences become apparent.


title: Impact of Pial Collaterals on Infarct Growth Rate in Experimental Acute Ischemic Stroke.

text: BACKGROUND AND PURPOSE Cerebral infarction evolves at different rates depending on available blood flow suggesting that treatment time windows vary depending on the degree of pial collateral recruitment. This work sought to mathematically model infarct growth and determine whether infarct volume growth can be predicted by angiographic assessment of pial collateral recruitment in an experimental MCA occlusion animal model. MATERIALS AND METHODS Pial collateral recruitment was quantified by using DSA, acquired 15 minutes following permanent MCA occlusion in 6 canines based on a scoring system (average pial collateral score) and arterial arrival time. MR imaging-based infarct volumes were measured 60, 90, 120, 180, 240 and 1440 minutes following MCA occlusion and were parameterized in terms of the growth rate index and final infarct volume (VFinal) as V(t) = VFinal [1 - e(-G × t)] (t = time). Correlations of the growth rate index and final infarct volume to the average pial collateral score and arterial arrival time were assessed by linear bivariate analysis. Correlations were used to generate asymptotic models of infarct growth for average pial collateral score or arterial arrival time values. Average pial collateral score- and arterial arrival time-based models were assessed by F tests and residual errors. RESULTS Evaluation of pial collateral recruitment at 15 minutes postocclusion was strongly correlated with 24-hour infarct volumes (average pial collateral score: r2 = 0.96, P < .003; arterial arrival time: r2 = 0.86, P < .008). Infarct growth and the growth rate index had strong and moderate linear relationships to the average pial collateral score (r2 = 0.89; P < .0033) and arterial arrival time (r2 = 0.69; P < .0419), respectively. Final infarct volume and the growth rate index were algebraically replaced by angiographically based collateral assessments to model infarct growth. The F test demonstrated no statistical advantage to using the average pial collateral score- over arterial arrival time-based predictive models, despite lower residual errors in the average pial collateral score-based model (P < .03). CONCLUSIONS In an experimental permanent MCA occlusion model, assessment of pial collaterals correlates with the infarct growth rate index and has the potential to predict asymptotic infarct volume growth.


title: A Patient with Eight Intracranial Aneurysms: Endovascular Treatment in Two Sessions.

text: The frequency of multiple intracranial aneurysms seen in patients with or without subarachnoid hemorrhage is high. The advancement of the endovascular technique and devices has ensured that endovascular treatment of intracranial aneurysms is the first choice in most cases, especially in unruptured ones. Different combinations of treatment modalities and techniques can be used in the management of multiple aneurysms. But in selected patients without subarachnoid hemorrhage, treatment of all aneurysms in one or more sessions with endovascular techniques is less traumatic than that with surgery. In the literature, the maximum number of aneurysms in one patient treated endovascularly and/or surgically is seven. In this case report, we present, with a review of the literature, a patient with eight intracranial aneurysms, all of which were treated in two sessions with various endovascular techniques. A 40-year-old female patient was admitted due to headache. Angiography showed eight aneurysms in the posterior circulation and, bilaterally, in the anterior circulation. All aneurysms were treated endovascularly in two sessions. In the treatment of the aneurysms, different endovascular techniques were used including flow diverters stents, stent-assisted coiling, Y-stent-assisted coiling, and coiling alone.


title: Angiotensin-converting enzyme 2: implications for blood pressure and kidney disease.

text: PURPOSE OF REVIEW Angiotensin-converting enzyme 2 (ACE 2), the main product of which is Ang 1-7, which binds to its receptor, Mas, is an important member of the renin-angiotensin system. RECENT FINDINGS A substantial body of research indicates that ACE2 is cardioprotective and renoprotective. ACE2 participates in a pathway that is counterregulatory to the effects of angiotensin II (Ang II). The mechanisms by which the protective effects of ACE2 occur are just beginning to be elucidated. SUMMARY As ACE2 appears to exert protective effects within the kidney and vasculature, recent data indicate that how it is expressed, what regulates it, and how it interacts with other biological systems may ultimately have clinical implications.


title: TRIM56 is an essential component of the TLR3 antiviral signaling pathway.

text: Members of the tripartite motif (TRIM) proteins are being recognized as important regulators of host innate immunity. However, specific TRIMs that contribute to TLR3-mediated antiviral defense have not been identified. We show here that TRIM56 is a positive regulator of TLR3 signaling. Overexpression of TRIM56 substantially potentiated extracellular dsRNA-induced expression of interferon (IFN)-β and interferon-stimulated genes (ISGs), while knockdown of TRIM56 greatly impaired activation of IRF3, induction of IFN-β and ISGs, and establishment of an antiviral state by TLR3 ligand and severely compromised TLR3-mediated chemokine induction following infection by hepatitis C virus. The ability to promote TLR3 signaling was independent of the E3 ubiquitin ligase activity of TRIM56. Rather, it correlated with a physical interaction between TRIM56 and TRIF. Deletion of the C-terminal portion of TRIM56 abrogated the TRIM56-TRIF interaction as well as the augmentation of TLR3-mediated IFN response. Together, our data demonstrate TRIM56 is an essential component of the TLR3 antiviral signaling pathway and reveal a novel role for TRIM56 in innate antiviral immunity.


title: Comparison of ED95 of Butorphanol and Sufentanil for gastrointestinal endoscopy sedation: a randomized controlled trial.

text: BACKGROUND Butorphanol, a synthetic opioid partial agonist analgesic, has been widely used to control perioperative pain. However, the ideal dose and availability of butorphanol for gastrointestinal (GI) endoscopy are not well known. The aim of this study was to evaluated the 95% effective dose (ED95) of butorphanol and sufentanil in GI endoscopy and compared their clinical efficacy, especially regarding the recovery time. METHODS The study was divided into two parts. For the first part, voluntary patients who needed GI endoscopy anesthesia were recruited to measure the ED95 of butorphanol and sufentanil needed to achieve successful sedation before GI endoscopy using the sequential method (the Dixon up-and-down method). The second part was a double-blind, randomized study. Two hundred cases of painless GI endoscopy patients were randomly divided into two groups (n = 100), including group B (butorphanol at the ED95 dose) and group S (sufentanil at the ED95 dose). Propofol was infused intravenously as the sedative in both groups. The recovery time, visual analogue scale (VAS) score, hand grip strength, fatigue severity scores, incidence of nausea and vomiting, and incidence of dizziness were recorded. RESULTS The ED95 of butorphanol for painless GI endoscopy was 9.07 μg/kg (95% confidence interval: 7.81-19.66 μg/kg). The ED95 of sufentanil was 0.1 μg/kg (95% CI, 0.079-0.422 μg/kg). Both butorphanol and sufentanil provided a good analgesic effect for GI endoscopy. However, the recovery time for butorphanol was significantly shorter than that for sufentanil (P < 0.05, group B vs. group S:21.26 ± 7.70 vs. 24.03 ± 7.80 min). CONCLUSIONS Butorphanol at 9.07 μg/kg was more effective than sufentanil for GI endoscopy sedation and notably reduced the recovery time. TRIAL REGISTRATION Chinese Clinical Trail Registry (Registration number # ChiCTR1900022780; Date of Registration on April 25rd, 2019).


title: A stochastic model for cancer stem cell origin in metastatic colon cancer.

text: Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.


title: Reversal agents: do we need to administer with neuromuscular monitoring - an observational study.

text: Background and Aims In clinical practice, in the majority of patients, recovery from the effect of muscle relaxants is assessed using subjective methods such as head lift, eye-opening, or by sustained hand grip after giving anticholinesterases (neostigmine) at the end of surgery. We planned a prospective observational cohort study to test the hypothesis that objective neuromuscular monitoring can help us in avoiding the use of anticholinesterases for reversal. Methods The patients posted for surgery of <2 h duration were included in the study. The cohort of patients was formed on the basis of those who were exposed to objective neuromuscular monitoring of recovery (train-of-four [TOF] ratio of 0.9 or more; exposed group) and the patients who were not exposed to objective neuromuscular monitoring (non-exposed group) acting as a control. Using objective neuromuscular monitoring, the time required for recovery from muscle relaxation when neostigmine was not given for reversal was noted and it was then compared with that of the control group. Results A total of 190 patients were enrolled over a period of 3 years. With the use of TOF ratio of 0.9 for extubation, patients safely recovered from neuromuscular blockade, without using neostigmine, with no difference in the mean recovery time (14.48 ± 1.138 min) as compared to the control group (12.14 ± 1.067 min, P = 0.139). There was no incidence of reintubation in post-operative period. Conclusion With objective neuromuscular monitoring, we can ensure complete recovery from the neuromuscular blockade while avoiding the use of anticholinesterases.


title: Real-time parameter estimation of Zika outbreaks using model averaging.

text: Early prediction of the final size of any epidemic and in particular for Zika disease outbreaks can be useful for health authorities in order to plan the response to the outbreak. The Richards model is often been used to estimate epidemiological parameters for arboviral diseases based on the reported cumulative cases in single- and multi-wave outbreaks. However, other non-linear models can also fit the data as well. Typically, one follows the so called post selection estimation procedure, i.e., selects the best fitting model out of the set of candidate models and ignores the model uncertainty in both estimation and inference since these procedures are based on a single model. In this paper we focus on the estimation of the final size and the turning point of the epidemic and conduct a real-time prediction for the final size of the outbreak using several non-linear models in which these parameters are estimated via model averaging. The proposed method is applied to Zika outbreak data in four cities from Colombia, during the outbreak ocurred in 2015-2016.


The Psychological Impact of COVID-19 Pandemic on Medical Staff in Guangdong, China: A Cross-Sectional Study.


title: Incidence of viral respiratory pathogens causing exacerbations in adult cystic fibrosis patients.

text: Respiratory infections caused by respiratory viruses are common in paediatric cystic fibrosis (CF) patients and are associated with increased morbidity. There is only little data on the incidence of viral respiratory pathogens causing exacerbations in the adult CF patient population. In this observational pilot study we show, by using molecular as well as conventional techniques for viral isolation, that during 1 y a viral pathogen could be isolated in 8/24 (33%) adult CF patients who presented with a pulmonary exacerbation. This result shows that there is a considerable incidence of viral pathogens in pulmonary exacerbations in adult CF patients. Newly identified viruses such as pandemic influenza A/H1N1, human metapneumovirus, human bocavirus, and human coronavirus NL63 were not detected in our population, except for 1 human coronavirus NL63.


WHO raises flu pandemic alert to level 5.


The challenging battle of mankind against COVID-19 outbreak: Is this global international biological catastrophe the beginning of a new era?


Efficacy of ventilation through a customized novel cuffed airway exchange catheter: a tracheal/lung model study.


title: Upregulation of endothelial cell adhesion molecules characterizes veins close to granulomatous infiltrates in the renal cortex of cats with feline infectious peritonitis and is indirectly triggered by feline infectious peritonitis virus-infected monocytes in vitro.

text: One of the most characteristic pathological changes in cats that have succumbed to feline infectious peritonitis (FIP) is a multifocal granulomatous phlebitis. Although it is now well established that leukocyte extravasation elicits the inflammation typically associated with FIP lesions, relatively few studies have aimed at elucidating this key pathogenic event. The upregulation of adhesion molecules on the endothelium is a prerequisite for stable leukocyte-endothelial cell (EC) adhesion that necessarily precedes leukocyte diapedesis. Therefore, the present work focused on the expression of the EC adhesion molecules and possible triggers of EC activation during the development of FIP. Immunofluorescence analysis revealed that the endothelial expression of P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was elevated in veins close to granulomatous infiltrates in the renal cortex of FIP patients compared to non-infiltrated regions and specimens from healthy cats. Next, we showed that feline venous ECs become activated when exposed to supernatant from feline infectious peritonitis virus (FIPV)-infected monocytes, as indicated by increased adhesion molecule expression. Active viral replication seemed to be required to induce the EC-stimulating activity in monocytes. Finally, adhesion assays revealed an increased adhesion of naive monocytes to ECs treated with supernatant from FIPV-infected monocytes. Taken together, our results strongly indicate that FIPV activates ECs to increase monocyte adhesion by an indirect route, in which proinflammatory factors released from virus-infected monocytes act as key intermediates.


title: Quinoxaline Derivatives as Antiviral Agents: A Systematic Review.

text: BACKGROUND In recent decades, several viruses have jumped from animals to humans, triggering sizable outbreaks. The current unprecedent outbreak SARS-COV-2 is prompting a search for new cost-effective therapies to combat this deadly pathogen. Suitably functionalized polysubstituted quinoxalines show very interesting biological properties (antiviral, anticancer, and antileishmanial), ensuring them a bright future in medicinal chemistry. OBJECTIVES Focusing on the promising development of new quinoxaline derivatives as antiviral drugs, this review forms part of our program on the anti-infectious activity of quinoxaline derivatives. METHODS Study compiles and discusses recently published studies concerning the therapeutic potential of the antiviral activity of quinoxaline derivatives, covering the literature between 2010 and 2020. RESULTS A final total of 20 studies included in this review. CONCLUSIONS This review points to a growing interest in the development of compounds bearing a quinoxaline moiety for antiviral treatment. This promising moiety with different molecular targets warrants further investigation, which may well yield even more encouraging results regarding this scaffold.


title: Peptide-modified optical filters for detecting protease activity.

text: The organic derivatization of silicon-based nanoporous photonic crystals is presented as a method to immobilize peptides for the detection of protease enzymes in solution. A narrow-line-width rugate filter, a one-dimensional photonic crystal, is fabricated that exhibits a high-reflectivity optical resonance that is sensitive to small changes in the refractive index at the pore walls. To immobilize peptide in the pore of the photonic crystal, the hydrogen-terminated silicon surface was first modified with the alkene 10-succinimidyl undecenoate via hydrosilylation. The monolayer with the succinimide ester moiety at the distal end served the dual function of protecting the underlying silicon from oxidation as well as providing a surface suitable for subsequent derivatization with amines. The surface was further modified with 1-aminohexa(ethylene glycol) (EG(6)) to resist nonspecific adsorption of proteins common in complex biological samples. The distal hydroxyl of the EG(6) is activated using the solid-phase coupling reagent disuccinimidyl carbonate for selective immobilization of peptides as protease recognition elements. X-ray photoelectron spectroscopy analysis reveals high activation and coupling efficiency at each stage of the functionalization. Exposure of the peptide-modified crystals to the protease subtilisin in solution causes a change in the refractive index, resulting in a shift of the resonance to shorter wavelengths, indicating cleavage of organic material within the pores. The lowest detected concentration of enzyme was 37 nM (7.4 pmol in 200 microL).


Supporting Organizational Workflow in Times of Crisis.


Secondary prevention after ischemic stroke.


title: Hospital Physician Engagement: A Scoping Review.

text: BACKGROUND Literature on health system transformation highlights the importance of physician engagement, suggesting that it is a critical factor for lowering costs while improving efficiency, quality of care, patient safety, physician satisfaction and retention. "Engagement" in health care is often defined as a positive, fulfilling work-related state of mind, which is characterized by vigor, dedication and absorption. The aim of this scoping review is to identify factors associated with, and tools used to measure physician engagement. METHODS MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and gray literature were searched. Supplementary articles were obtained by searching article references. All quantitative and qualitative study designs were eligible that described factors associated with, and tools used to measure, hospital physician engagement. Quantitative and qualitative analyses were conducted. Groupings and clustering were conducted to determine dominant groups or cluster of characteristics. Conceptual mapping was then conducted to identify patterns. RESULTS A total of 15 studies fulfilled the eligibility criteria. All were published between 2012 and 2017. Studies were predominantly conducted in Germany (n=8). Factors associated with physician engagement were synthesized into individual characteristics (n=7), work environment characteristics (n=7), and work outcomes (n=5). The Utrecht Work Engagement Scale was the most commonly used tool (n=14). CONCLUSIONS This scoping review provides a strong evidence-based platform to further advance knowledge in the area of physician engagement. The identification of environmental factors assists hospital administrative leaders in understanding how they might intervene to affect engagement, while the identification of individual characteristics enable identification of vulnerable physicians, permitting identification of the most pertinent targeted areas for focus.


title: Tissue oxygenation monitoring using resonance Raman spectroscopy during hemorrhage.

text: BACKGROUND The ability to monitor the patient of hemorrhage noninvasively remains a challenge. We examined the ability of resonance Raman spectroscopy to monitor tissue hemoglobin oxygenation (RRS-StO2) during hemorrhage and compared its performance with conventional invasive mixed venous (SmvO2) and central venous (ScvO2) hemoglobin oxygen saturation as well as with near-infrared spectroscopy tissue hemoglobin oxygenation (NIRS-StO2). METHODS Five male swine were anesthetized and instrumented followed by hemorrhage at a rate of 30 mL/min for 60 minutes. RRS-StO2 was continuously measured from the buccal mucosa, and NIRS-StO2 was continuously measured from the forelimb. Paired interval measures of SmvO2, ScvO2, and lactate were made. Pearson correlation was used to quantify the degree to which any two variables are related. Receiver operating characteristic (ROC) area under the curve values were used for pooled data for RRS-StO2, NIRS-StO2, SmvO2, and ScvO2 to compare performance in the ability of tissue oxygenation methods to predict the presence of an elevated arterial blood lactate level. RESULTS Sequential RRS-StO2 changes tracked changes in SmvO2 (r = 0.917; 95% confidence interval [CI], 0.867-0.949) and ScvO2 (r = 0.901; 95% CI, 0.828-0.944) during hemorrhage, while NIRS-StO2 failed to do so for SmvO2 (r = 0.283; 95% CI, 0.04919-0.4984) and ScvO2 (r = 0.142; 95% CI, -0.151 to 0.412). ROC curve performance of oxygenation measured to indicate lactate less than or greater than 3 mM yielded the following ROC area under the curve values: SmvO2 (1.0), ScvO2 (0.994), RRS-StO2 (0.972), and NIRS-StO2 (0.611). CONCLUSION RRS-StO2 seems to have significantly better ability to track central oxygenation measures during hemorrhage as well as to predict shock based on elevated lactate levels when compared with NIRS-StO2.


title: Fixed-target serial oscillation crystallography at room temperature.

text: A fixed-target approach to high-throughput room-temperature serial synchrotron crystallography with oscillation is described. Patterned silicon chips with microwells provide high crystal-loading density with an extremely high hit rate. The microfocus, undulator-fed beamline at CHESS, which has compound refractive optics and a fast-framing detector, was built and optimized for this experiment. The high-throughput oscillation method described here collects 1-5° of data per crystal at room temperature with fast (10° s-1) oscillation rates and translation times, giving a crystal-data collection rate of 2.5 Hz. Partial datasets collected by the oscillation method at a storage-ring source provide more complete data per crystal than still images, dramatically lowering the total number of crystals needed for a complete dataset suitable for structure solution and refinement - up to two orders of magnitude fewer being required. Thus, this method is particularly well suited to instances where crystal quantities are low. It is demonstrated, through comparison of first and last oscillation images of two systems, that dose and the effects of radiation damage can be minimized through fast rotation and low angular sweeps for each crystal.


title: Betulin-derived compounds as inhibitors of alphavirus replication.

text: This paper describes inhibition of Semliki Forest virus (SFV) replication by synthetic derivatives of naturally occurring triterpenoid betulin (1). Chemical modifications were made to OH groups at C-3 and C-28 and to the C-20-C-29 double bond. A set of heterocyclic betulin derivatives was also assayed. A free or acetylated OH group at C-3 was identified as an important structural contributor for anti-SFV activity, 3,28-di-O-acetylbetulin (4) being the most potent derivative (IC50 value 9.1 microM). Betulinic acid (13), 28-O-tetrahydropyranylbetulin (17), and a triazolidine derivative (41) were also shown to inhibit Sindbis virus, with IC50 values of 0.5, 1.9, and 6.1 microM, respectively. The latter three compounds also had significant synergistic effects against SFV when combined with 3'-amino-3'-deoxyadenosine. In contrast to previous work on other viruses, the antiviral activity of 13 was mapped to take place in virus replication phase. The efficacy was also shown to be independent of external guanosine supplementation.


title: Cell projections and extracellular matrix cross the interstitial interface within the renal stem/progenitor cell niche: accidental, structural or functional cues?

text: BACKGROUND During nephron induction, morphogenetic molecules are reciprocally exchanged between epithelial and mesenchymal stem/progenitor cells within the renal stem/progenitor cell niche. That these molecules remain concentrated, it is assumed that both cell populations stand in close contact to each other. However, recently published data illustrate that epithelial and mesenchymal cells are separated by an astonishingly wide interstitial interface. METHODS To gain deeper morphological insights into the spatial distribution of mesenchymal and epithelial stem/progenitor cells, the embryonic zone of neonatal rabbit kidney was fixed either with glutaraldehyde (GA) or in a combination with cupromeronic blue, ruthenium red or tannic acid. Transmission electron microscopy was then performed on exactly orientated sections. RESULTS Conventional fixation with GA illustrates that epithelial and mesenchymal stem/progenitor cells are separated by a bright but inconspicuously looking interstitial interface. In contrast, fixation of specimens in GA containing cupromeronic blue, ruthenium red or tannic acid elucidates that part of the interstitial interface exhibits a special extracellular matrix extending like woven strands between mesenchymal and epithelial stem/progenitor cells. In parallel, filigree projections from mesenchymal stem/progenitor cells cross the interstitial interface to penetrate the basal lamina of epithelial cells. Fusion of the plasma membranes cannot be observed. Instead, touching mesenchymal cell projections form a cone at the contact site with tunneling nanotubes. CONCLUSIONS The results demonstrate that the contact between mesenchymal and epithelial stem/progenitor cells does not form accidentally but physiologically and appears to belong to a suspected system involved in the exchange of morphogenetic information.


title: Heterogeneity of studies in anesthesiology systematic reviews: a meta-epidemiological review and proposal for evidence mapping.

text: Heterogeneity among the primary studies included in a systematic review (SR) is one of the most challenging considerations for systematic reviewers. Current practices in anaesthesiology SRs have not been evaluated, but traditional methods may not provide sufficient information to evaluate the true nature of these differences. We address these issues by examining the practices for evaluating heterogeneity in anesthesiology reviews. Also, we propose a mapping method for presenting heterogeneous aspects of the primary studies in SRs.We evaluated heterogeneity practices reported in SRs published in highly ranked anesthesiology journals and Cochrane reviews. Elements extracted from the SRs included heterogeneity tests, models used, analyses conducted, plots used, and I2 values. Additionally, we selected a SR to develop an evidence map in order to display clinical heterogeneity.Our statistical analysis showed 150/207 SRs reporting a test for statistical heterogeneity. Plots were used in 138 reviews to display heterogeneity. Subgroup analyses were the most commonly reported analysis (54%). Meta-regression and sensitivity analyses were used sparingly (25%; 23% respectively). A random effects model was most commonly reported (33%). Heterogeneity statistics across meta-analyses suggested that, in our sample, the majority (55%) did not present sufficient heterogeneity to be of great concern. Cochrane reviews (n=58) were also analysed. Plots were used in 88% of Cochrane reviews. Subgroup analysis was used in 59% Cochrane reviews, while sensitivity analysis was used in 62%.Many reviews did not provide sufficient detail regarding heterogeneity. We are calling for improvement to reporting practices.


Characteristics of Children With Reactivation of SARS-CoV-2 Infection After Hospital Discharge.


title: Pre-emptive scalp infiltration with dexamethasone plus ropivacaine for postoperative pain after craniotomy: a protocol for a prospective, randomized controlled trial.

text: Background: Approximately 55-87% of the patients undergoing craniotomy experience moderate to severe pain during the first 48 hrs after surgery, which negatively influences patients' postoperative rehabilitation. Recently, local infiltration of analgesia (LIA) has been widely performed clinically as a promising analgesic method that could avoid the side effects of analgesics but only has a short pain-free duration; researchers have clarified that the addition of dexamethasone to LIA could provide significant analgesic effects and significantly prolong the duration of analgesic effects without obvious complications for various types of surgeries. To date, no studies have evaluated the addition of dexamethasone to LIA for patients receiving craniotomy. The aim of the study was to test the hypothesis that pre-emptive scalp infiltration with a steroid (dexamethasone) plus a local anesthetic (ropivacaine) could achieve superior postoperative analgesic effects to a local anesthetic (ropivacaine) alone in adult patients undergoing a craniotomy. Study design and methods: This study is a randomized controlled trial that will include one intervention and one control group involving a total of 140 adults scheduled for elective craniotomy for resection of supratentorial tumors under general anesthesia and with an anticipated full recovery within 2 hrs postoperatively. The intervention will involve pre-emptive scalp infiltration with ropivacaine plus dexamethasone (the dexamethasone group) or ropivacaine alone (the control group), and the participants in both groups will complete a 6-month follow-up. The primary outcome will be the cumulative sufentanil consumption within 48 hrs postoperatively. Discussion: The intervention, if effective, this study will provide clinically important information on the role of dexamethasone in scalp infiltration for post-craniotomy pain management.


Bailout alternative use of re-entry device to achieve a chronically occluded superficial artery recanalization without detectable origin.


title: Treatment of Dissecting Distal Vertebral Artery (V4) Aneurysms With Flow Diverters.

text: BACKGROUND Dissecting aneurysms of the intracranial vertebral arteries are rare; however, treatment of these presents multiple challenges, including high risk of rebleeding, development of thromboembolic strokes, and progressive partial thrombosis. Flow diverters, such as Pipeline Endovascular Devices (PEDs; Covidien, Medtronic Inc, Dublin, Ireland), have emerged as a potential treatment option. OBJECTIVE To present our experience with patients treated at our institution with PEDs for dissecting distal vertebral artery (V4 segment) aneurysms. METHODS A retrospective search of our prospectively maintained database was performed between January 2014 and December 2016. We queried our database for all patients treated with PED for dissecting aneurysms of the V4 segment. Information was gathered including demographics, the location and morphology of the aneurysm, the clinical presentation, specific form of treatment, complications, antiplatelet medication regimen, and follow-up time. RESULTS There were a total of 9 patients with dissecting V4 aneurysms treated with PED during the study period. All were treated initially with an average of 1.2 PEDs. All patients were followed with at least one repeat diagnostic angiogram and there was no residual aneurysm seen in 8 of 9 cases. In those that presented with neurological deficits, there was an average improvement in modified Rankin Scale of 2.85 points. CONCLUSION PED is a safe and effective tool that can be used to treat ruptured dissecting aneurysms of this specific segment of the posterior circulation, but it does require close management of antiplatelet therapy in the setting of subarachnoid hemorrhage and close angiographic follow-up.


title: A Multicenter Study of the Presentation, Treatment, and Outcomes of Cervical Dural Tears.

text: STUDY DESIGN Retrospective multicenter case series study. OBJECTIVE Because cervical dural tears are rare, most surgeons have limited experience with this complication. A multicenter study was performed to better understand the presentation, treatment, and outcomes following cervical dural tears. METHODS Multiple surgeons from 23 institutions retrospectively identified 21 rare complications that occurred between 2005 and 2011, including unintentional cervical dural tears. Demographic data and surgical history were obtained. Clinical outcomes following surgery were assessed, and any reoperations were recorded. Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), Nurick classification (NuC), and Short-Form 36 (SF36) scores were recorded at baseline and final follow-up at certain centers. All data were collected, collated, and analyzed by a private research organization. RESULTS There were 109 cases of cervical dural tears among 18 463 surgeries performed. In 101 cases (93%) there was no clinical sequelae following successful dural tear repair. There were statistical improvements (P < .05) in mJOA and NuC scores, but not NDI or SF36 scores. No specific baseline or operative factors were found to be associated with the occurrence of dural tears. In most cases, no further postoperative treatments of the dural tear were required, while there were 13 patients (12%) that required subsequent treatment of cerebrospinal fluid drainage. Analysis of those requiring further treatments did not identify an optimum treatment strategy for cervical dural tears. CONCLUSIONS In this multicenter study, we report our findings on the largest reported series (n = 109) of cervical dural tears. In a vast majority of cases, no subsequent interventions were required and no clinical sequelae were observed.


title: Delusional infestation: neural correlates and antipsychotic therapy investigated by multimodal neuroimaging.

text: INTRODUCTION In delusional infestation (DI), as with other non-schizophrenic psychotic disorders, little is known about the neural basis and the mechanisms of antipsychotic treatment. We aimed at investigating the brain circuitry involved in DI and the role of postsynaptic D2 receptors in mediating the effects of antipsychotics by means of multimodal neuroimaging. METHODS In Case 1, a patient with DI (initially drug-induced), cerebral glucose metabolism and dopaminergic neurotransmission were studied in the untreated state (FDG-PET, FDOPA-PET, 123I-FP-CIT-SPECT, and IBZM-SPECT) and after effective aripiprazole treatment (FDG-PET and IBZM-SPECT), with negative drug screenings at both imaging sessions. In Case 2 (DI secondary to mild vascular encephalopathy) cerebral perfusion and gray matter volume changes were investigated in the untreated state and compared to N=8 [corrected] age-matched healthy controls (MRI-based CASL and VBM). RESULTS In Case 1, before treatment, glucose metabolism was left-dominant in the thalamus and the putamen. Pre- and postsynaptic dopaminergic neurotransmissions were altered in the striatum, again mainly the left putamen. Full remission to aripiprazole was associated with 63 to 78% striatal D2 receptor occupancy and glucose metabolism changes in the bilateral thalamus. In Case 2, significant perfusion and GMV changes were observed in the bilateral putamen, frontal and parietal somatosensory cortices as compared to controls. Symptoms partially remitted to ziprasidone therapy. DISCUSSION/CONCLUSION Six imaging techniques were first used to study the neural basis of DI and mechanisms of antipsychotic therapy. The study provides first low-level evidence in vivo evidence of fronto-striato-thalamo-parietal network to mediate core symptoms of DI, i.e. a priori brain regions involved in judgment (frontal cortex), sensory gating (thalamus) and body perception (dorsal striatum, thalamus and somatic cortices). This is also the first report of effective treatment with aripiprazole in drug-induced DI and with ziprasidone in organic DI, adding to existing limited evidence that SGAs are helpful in various forms of DI. Effective antipsychotic treatment seems to depend on blocking striatal D2 receptors with similar occupancy rates as in schizophrenia. Larger samples are needed to confirm our preliminary findings and further evaluate their relevance for the different forms of DI.


title: Single-port access prosthetic repair for primary and incisional ventral hernia: toward less parietal trauma.

text: BACKGROUND Although still under development, single-port access (SPA) approach may be of interest in patients prone to port-side incisional hernia, ensuring absence of increased fascial incision. This forms the basis for evaluating SPA for prosthetic ventral hernia repair. We report a new SPA technique of ventral hernia repair using working-channel endoscope, standard laparoscopic instruments, and 10-mm port. METHODS Prospective experience with SPA prosthetic repair of primary and incisional ventral hernia in 52 patients for 55 ventral hernias is presented. Median (range) patient age was 46 years (26-85 years), and BMI was 28 kg/m2 (20-38 kg/m2). Mean fascial defect was 16.2 cm2 for primary hernia (n=23) and 48.3 cm2 for incisional hernia (n=32). Intraperitoneal composite mesh repair was achieved through single 10-mm flank port using working-channel endoscope. Meshes were fixed using absorbable tackers and transfascial stitches. RESULTS SPA repair of primary and incisional ventral hernia was completed in all cases without conversion to standard laparoscopy. Median (range) operative time was 54 min (39-95 min). Mesh size ranged from 118 to 500 cm2. No intra- or postoperative complications were recorded, except two seromas. Median (range) hospital stay was 1 day (1-5 days). One patient presented prolonged postoperative pain on mesh fixation that resolved after 3 months. No recurrence or port-site incisional hernias have been recorded at median (range) follow-up of 16 months (3-28 months). CONCLUSIONS SPA prosthetic repair of primary and incisional ventral hernia is easily feasible according to natural exposition by pneumoperitoneum and gravity. In the present series, SPA ventral hernia repair appears to be safe for experienced SPA surgeons. It may decrease parietal trauma and scarring in patients prone to incisional hernia. SPA repair may be associated with a decrease in rate of port-site incisional hernia compared with multiport laparoscopy, but this has to be verified by randomized trial with standard laparoscopic approach on long-term follow-up.


title: [Machine learning-based method for interpreting the guidelines of the diagnosis and treatment of COVID-19].

text: The outbreak of pneumonia caused by novel coronavirus (COVID-19) at the end of 2019 was a major public health emergency in human history. In a short period of time, Chinese medical workers have experienced the gradual understanding, evidence accumulation and clinical practice of the unknown virus. So far, National Health Commission of the People's Republic of China has issued seven trial versions of the "Guidelines for the Diagnosis and Treatment of COVID-19". However, it is difficult for clinicians and laymen to quickly and accurately distinguish the similarities and differences among the different versions and locate the key points of the new version. This paper reports a computer-aided intelligent analysis method based on machine learning, which can automatically analyze the similarities and differences of different treatment plans, present the focus of the new version to doctors, reduce the difficulty in interpreting the "diagnosis and treatment plan" for the professional, and help the general public better understand the professional knowledge of medicine. Experimental results show that this method can achieve the topic prediction and matching of the new version of the program text through unsupervised learning of the previous versions of the program topic with an accuracy of 100%. It enables the computer interpretation of "diagnosis and treatment plan" automatically and intelligently.


title: Safety Analysis of Bariatric Patients Undergoing Outpatient Upper Endoscopy with Non-Anesthesia Administered Propofol Sedation.

text: BACKGROUND Non-anesthesia administered propofol (NAAP) has been shown to be a safe and effective method of sedation for patients undergoing gastrointestinal endoscopy. Bariatric surgery patients are potentially at a higher risk for sedation-related complications due to co-morbidities including obstructive sleep apnea. The outcomes of NAAP in bariatric patients have not been previously reported. METHODS In this retrospective cohort study, severely obese patients undergoing pre-surgical outpatient esophagogastroduodenoscopy (EGD) were compared to non-obese control patients (BMI ≤ 25 kg/m2) undergoing diagnostic EGD at our institution from March 2011-September 2015 using our endoscopy database. Patients' demographics and procedural and recovery data, including any airway interventions, were statistically analyzed. RESULTS We included 130 consecutive pre-operative bariatric surgical patients with average BMI 45.8 kg/m2 (range 34-80) and 265 control patients with average BMI 21.9 kg/m2 (range 14-25). The severely obese group had a higher prevalence of sleep apnea (62 vs 8%; p < 0.001), experienced more oxygen desaturations (22 vs 7%; p < 0.001), and received more chin lift maneuvers (20 vs 6%; p < 0.001). Advanced airway interventions were rarely required in either group and were not more frequent in the bariatric group. CONCLUSIONS With appropriate training of endoscopy personnel, NAAP is a safe method of sedation in severely obese patients undergoing outpatient upper endoscopy.


COVID-19 changes medical education in Italy: will other countries follow?


Let's not forget our COVID-19-free cirrhotic patients!


title: Safety protection of forensic examination during the epidemic of COVID-19.

text: Abstract


title: Postoperative delirium: etiology and management.

text: PURPOSE OF REVIEW Postoperative delirium is a pervasive and complicated process that poses numerous challenges for the perioperative physician and entails significant consequences for the patient. RECENT FINDINGS Postoperative delirium affects on average 36.8% of surgical patients, ranging from 9 to 87% depending on age, setting, type of surgery and other risk factors. This number may in fact be an underestimation based on the variation in screening practices. Meta-analyses show that in a mix of medical and surgical patients, a single episode of delirium resulted in a doubling of the odds ratio for death as well as an increase in the risk of admission to an institution and increase in dementia. It is also associated with an increase in length of mechanical ventilation in addition to total length of ICU and hospital length of stay. SUMMARY All told, the cost of delirium in the United States alone is estimated to be between US$ 38 and 152 billion. Thus, it is no surprise that there is considerable interest in understanding and treating the problem.


Patents, economics, and pandemics.


title: Cardiac cycle efficiency and dicrotic pressure variations: new parameters for fluid therapy: An observational study.

text: BACKGROUND During a fluid challenge, the changes in cardiac performance and peripheral circulatory tone are closely related to the position of the ventricle on the Frank-Starling curve. Some patients have a good haemodynamic response to a fluid challenge, others hardly any response. The early haemodynamic effects of a fluid challenge could predict the final response before the entire fluid volume has been administered. OBJECTIVE To assess whether a multivariate logistic regression model, including pulse pressure variation (PPV), cardiac cycle efficiency (CCE), arterial elastance and the difference between the dicrotic pressure and both systolic and mean arterial pressure (SAP - Pdic and MAP - Pdic) can predict cardiac responsiveness early during a fluid challenge in comparison with the standard procedure described elsewhere. DESIGN Observational study. SETTING Elective surgical patients undergoing laparotomy, enrolled in two Italian University Hospitals. PATIENTS Fifty adult surgical patients, ventilated with a lung protective strategy, were enrolled and data from 46 were analysed. INTERVENTIONS A fluid challenge consisting of 500 ml of crystalloid infused over 10 min. MAIN OUTCOME MEASURES AND ANALYSIS The changes in CCE, arterial elastance, SAP - Pdic and MAP - Pdic were compared using analysis of variance. A multivariate logistic regression analysis utilising baseline values and the first minute measuring a variation statistically significant for the considered variables. RESULTS At baseline, PPV correctly identified 70% of patients (89% of non-responders; 42% of responders). The model, including baseline PPV, ΔCCE and ΔSAP - Pdic, correctly identified the efficiency of fluid challenge in 87% of patients (84.2% of responders; 92.5 of non-responders) after 5 min from fluid challenge infusion. CONCLUSION In this pilot study conducted in a population of surgical patients mechanically ventilated with a VT less than 8 ml kg, a dynamic model of fluid challenge assessment, including PPV, ΔCCE and ΔSAP - Pdic, enhances the prediction of fluid challenge response after 5 min of a 10-min administration. TRIAL REGISTRATION ACTRN12616001479493.


title: Severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex involved in mitochondrial biogenesis and intracellular signaling.

text: The severe acute respiratory syndrome coronavirus (SARS-CoV) generates 16 nonstructural proteins (nsp's) through proteolytic cleavage of a large precursor protein. Although several nsp's exhibit catalytic activities that are important for viral replication and transcription, other nsp's have less clearly defined roles during an infection. In order to gain a better understanding of their functions, we attempted to identify host proteins that interact with nsp's during SARS-CoV infections. For nsp2, we identified an interaction with two host proteins, prohibitin 1 (PHB1) and PHB2. Our results suggest that nsp2 may be involved in the disruption of intracellular host signaling during SARS-CoV infections.


Impact of the COVID-19 outbreak on emergency medical system missions and emergency department visits in the Venice area.


title: The Nasopharyngeal Microbiota of Children With Respiratory Infections in Botswana.

text: BACKGROUND Nearly half of child pneumonia deaths occur in sub-Saharan Africa. Microbial communities in the nasopharynx are a reservoir for pneumonia pathogens and remain poorly described in African children. METHODS Nasopharyngeal swabs were collected from children with pneumonia (N = 204), children with upper respiratory infection symptoms (N = 55) and healthy children (N = 60) in Botswana between April 2012 and April 2014. We sequenced the V3 region of the bacterial 16S ribosomal RNA gene and used partitioning around medoids to cluster samples into microbiota biotypes. We then used multivariable logistic regression to examine whether microbiota biotypes were associated with pneumonia and upper respiratory infection symptoms. RESULTS Mean ages of children with pneumonia, children with upper respiratory infection symptoms and healthy children were 8.2, 11.4 and 8.0 months, respectively. Clustering of nasopharyngeal microbiota identified 5 distinct biotypes: Corynebacterium/Dolosigranulum-dominant (23%), Haemophilus-dominant (11%), Moraxella-dominant (24%), Staphylococcus-dominant (13%) and Streptococcus-dominant (28%). The Haemophilus-dominant [odds ratio (OR): 13.55; 95% confidence interval (CI): 2.10-87.26], the Staphylococcus-dominant (OR: 8.27; 95% CI: 2.13-32.14) and the Streptococcus-dominant (OR: 39.97; 95% CI: 6.63-241.00) biotypes were associated with pneumonia. The Moraxella-dominant (OR: 3.71; 95% CI: 1.09-12.64) and Streptococcus-dominant (OR: 12.26; 95% CI: 1.81-83.06) biotypes were associated with upper respiratory infection symptoms. In children with pneumonia, HIV infection was associated with a lower relative abundance of Dolosigranulum (P = 0.03). CONCLUSIONS Pneumonia and upper respiratory infection symptoms are associated with distinct nasopharyngeal microbiota biotypes in African children. A lower abundance of the commensal genus Dolosigranulum may contribute to the higher pneumonia risk of HIV-infected children.


Audio Interview: Practical Measures to Help Prevent Covid-19.


title: Intraoperatively Testing the Anastomotic Integrity of Esophagojejunostomy Using Methylene Blue.

text: BACKGROUND Intraoperative testing of gastrointestinal anastomosis effectively ensures anastomotic integrity. This study investigated whether the routine use of methylene blue intraoperatively identified leaks to reduce the postoperative proportion of clinical leaks. METHODS This study retrospectively analyzed consecutive total gastrectomies performed from January 2007 to December 2014 in a university hospital setting by a general surgical group that exclusively used the methylene blue test. All surgeries were performed for gastric or junctional cancers (n = 198). All reconstructions (Roux-en Y esophagojejunostomy) were performed using a stapler. The methylene blue test was used in 108 cases (group 1) via a nasojejunal tube. No test was performed for the other 90 cases (group 2). Intraoperative leakage rate, postoperative clinical leakage rate, length of hospitalization, and mortality rate were the outcome measures. RESULTS The intraoperative leakage rate was 7.4% in group 1. The postoperative clinical leakage rate was 8.6%. The postoperative clinical leakage rate was 3.7% in group 1 and 14.4% in group 2 (p = 0.007). There were no postoperative clinical leaks when an intraoperative leak led to concomitant intraoperative repair. The median length of hospital stay was 6 days in group 1 and 8 days in group 2 (p < 0.001). One death occurred in each group. No test-related complications were observed. CONCLUSION The methylene blue test for esophagojejunostomy is a safe and reliable method for the assessment of anastomosis integrity, especially in cases with difficult esophagojejunostomic construction.


Complete protection from covid-19 is possible for health workers.


title: Clinical Practice Update: Expert Review on Endoscopic Bariatric Therapies.

text: BACKGROUND & AIMS Multiple endoscopic bariatric therapies (EBTs) currently are being evaluated or are in clinical use in the United States. EBTs are well positioned to fill an important gap in the management of obesity and metabolic disease. The purpose of this expert review is to update gastroenterologists on these therapies and provide practice advice on how to incorporate them into clinical practice. METHODS The evidence reviewed in this work is a distillation of comprehensive search of several English-language databases and a manual review of relevant publications (including systematic reviews and meeting abstracts). Best Practice Advice 1: EBTs should be considered in patients with obesity who have been unsuccessful in losing or maintaining weight loss with lifestyle interventions. Best Practice Advice 2: EBTs can be used in patients with severe obesity as a bridge to traditional bariatric surgery. They also can be used as a bridge to allow unrelated interventions that are unable to be performed because of weight limits (ie, orthopedic surgery, organ transplantation). Best Practice Advice 3: Clinicians should use EBTs as part of a structured weight loss program that includes dietary intervention, exercise therapy, and behavior modification, in both the active weight loss phase and the long-term maintenance phase. Best Practice Advice 4: Clinicians should screen all potential EBT candidates with a comprehensive evaluation for medical conditions, comorbidities, and psychosocial or behavioral patterns that contribute to their condition before enrolling patients in a weight loss program that includes EBTs. Best Practice Advice 5: Clinicians incorporating EBTs into their clinical practice should follow up patients prospectively to capture the impact of the EBT program on weight and weight-related comorbidities, and all related adverse outcomes. Poor responders should be identified and offered a detailed evaluation and alternative therapy. Best Practice Advice 6: Clinicians embarking on incorporating EBTs into their clinical practice should have a comprehensive knowledge of the indications, contraindications, risks, benefits, and outcomes of individual EBTs, as well as a practical knowledge of the risks and benefits of alternative therapies for obesity. Best Practice Advice 7: Institutions should establish specific guidelines that are applied consistently across disciplines for granting privileges in EBTs that reflect the necessary knowledge and technical skill a clinician must achieve before being granted privileges to perform these procedures.


title: Colonic intussusception: clinical and radiographic features.

text: OBJECTIVE The purpose of this article is to comprehensively survey all CT-detected ileocolic and colocolic intussusceptions at a cancer institute. MATERIALS AND METHODS Using the free-text string "intus," the radiology information database of Memorial Sloan-Kettering Cancer Center was searched over a 13.5-year period for abdominopelvic CT scan reports. Images were rereviewed by an attending radiologist for the presence of a bowel-within-bowel appearance involving the colon. The reference standard for a lead point was histopathologic examination or, if the tumor was not resected, an identifiable mass persisting on follow-up CT scans. Transient intussusception was defined as intussusception that resolved on follow-up CT scan without surgical removal or as intussusception with an intermittent presence on serial CT scans. Idiopathic intussusception was defined as the absence of mass or mural thickening at CT or surgery. RESULTS Four hundred sixty-one CT scan reports were retrieved, 138 of which mentioned intussusception as a pertinent negative. From the remaining 323 scan reports, after all exclusions (small bowel-small bowel intussusception, incomplete imaging, pediatric patients, and misinterpretations on rereview), 33 patients were shown to have 34 intussusceptions, including ileocolic (n = 11) and colocolic (n = 23) intussusceptions, on 34 CT scans. Seven intussusceptions were transient (i.e., intermittent). No patient had idiopathic intussusception. Histopathologic results were available for 22 of 34 intussusceptions. Intussusceptions were caused by colorectal cancer (n = 12), lymphoma (n = 5), metastases to the colon (n = 8), colon polyps (n = 4), and nonneoplastic causes, including lipoma (n = 3), hematoma (n = 1), and edema (n = 1). CONCLUSION In patients with cancer, intussusceptions involving the colon are never idiopathic. Most are due to primary colon cancer or metastatic disease and most require surgical removal. Although seven intussusceptions were transient, six were caused by neoplasia.


title: An unresponsive COVID-19 patient.

text: Neurological manifestations and complications are increasingly reported in coronavirus disease-19 (COVID-19) patients. Although pulmonary manifestations are more common, patients with severe disease may present with neurological symptoms such as in our case. We describe a case report of a 50-year-old male without previous known comorbidity who was found unresponsive due to COVID-19-related neurological complications. During this pandemic, an emergency radiologist should be well acquainted with various neurological manifestations of COVID-19. In this article, we will discuss the pathogenesis, imaging findings, and differentials of this disease.


title: Pharmacokinetic characteristics, pharmacodynamic effect and in vivo antiviral efficacy of liver-targeted interferon alpha.

text: Interferon alpha (IFNα) is used for the treatment of hepatitis B virus infection, and whilst efficacious, it is associated with multiple adverse events caused by systemic exposure to interferon. We therefore hypothesise that targeting IFN directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. Furthermore we investigated whether directing IFN to the reservoir of infection in the liver may improve antiviral efficacy by increasing local concentration in target organs and tissues. Our previous results show that the mIFNα2 fused to an ASGPR specific liver targeting antibody, DOM26h-196-61, results in a fusion protein which retains the activity of both fusion partners when measured in vitro. In vivo targeting of the liver by mIFNα2-DOM26h-196-61, hereafter referred to as targeted mIFNα2, was observed in microSPECT imaging studies in mice. In this study we show by pharmacokinetic analysis that antibody mediated liver-targeting results in increased uptake and exposure of targeted mIFNα2 in target tissues, and correspondingly reduced uptake and exposure in systemic circulation, clearance organs and non-target tissues. We also show that cytokine activity and antiviral activity of liver-targeted IFN is observed in vivo, but that, contrary to expectations, liver-targeting of mIFNα2 using ASGPR specific dAbs actually leads to a reduced pharmacodynamic effect in target organs and lower antiviral activity in vivo when compared to non-targeted mIFNα2-dAb fusions.