title: The efficacy of hepatic 90Y resin radioembolization for metastatic neuroendocrine tumors: a meta-analysis.

text: UNLABELLED (90)Y resin radioembolization is an emerging treatment in patients with liver-dominant metastatic neuroendocrine tumors (mNETs), despite the absence of level I data. The aim of this study was to evaluate the efficacy of this modality in a meta-analysis of the published literature. METHODS A comprehensive review protocol screened all reports in the literature. Strict selection criteria were applied to ensure consistency among the selected studies: human subjects, complete response data with time interval, resin microspheres, more than 5 patients, not a duplicate cohort, English language, and separate and complete data for resin-based (90)Y treatment of mNET if the study included multiple tumor and microsphere types. Selected studies were critically appraised on 50 study criteria, in accordance with the research reporting standards for radioembolization. Response data (Response Evaluation Criteria in Solid Tumors) were extracted and analyzed using both fixed and random-effects meta-analyses. RESULTS One hundred fifty-six studies were screened; 12 were selected, totaling 435 procedures for response assessment. Funnel plots showed no evidence of publication bias (P = 0.841). Critical appraisal revealed a median of 75% of desired criteria included in selected studies. Very high between-study heterogeneity ruled out a fixed-effects model. The random-effects weighted average objective response rate (complete and partial responses, CR and PR, respectively) was 50% (95% confidence interval, 38%-62%), and weighted average disease control rate (CR, PR, and stable disease) was 86% (95% confidence interval, 78%-92%). The percentage of patients with pancreatic mNET was marginally associated with poorer response (P = 0.030), accounting for approximately 23% of the heterogeneity among studies. The percentage of CR and PR correlated with median survival (R = 0.85; P = 0.008). CONCLUSION This meta-analysis confirms radioembolization to be an effective treatment option for patients with hepatic mNET. The pooled data demonstrated a high response rate and improved survival for patients responding to therapy.


title: Nasolaryngeal Distances in the Adult Population and an Evaluation of Commercially Available Nasotracheal Tubes.

text: BACKGROUND Preformed nasal endotracheal tubes (NETs) come with a predefined insertion depth due to their curved design. While size indication refers to internal diameter, there is a considerable variability in the corresponding lengths and proportions of same-sized tubes of different manufacturers which is probably based on the lack of data of nasolaryngeal distances (NLDs) in the adult population. Choosing the best-fitting NET is therefore difficult and carries the risk of endobronchial intubation or, on the contrary, cuff inflation at the vocal cord level. The aim of this study was to develop a prediction model for NLD and a selection guide to choose the appropriate NET based on a radiographic description of NLD in comparison to the measurements of available NETs of several manufacturers. METHODS After institutional ethics board review, 388 computed tomography (CT) scan images of head, neck, and upper thorax in a heterogeneous adult cohort were included. Mean distances from the nares to the lower border of the thyroid cartilage were measured. NETs from different manufacturers were measured and compared to the NLD derived from the radiographic analysis. The patients' sex, body height, and weight were considered as possible covariates in quantile regression models for predicting the NLD. RESULTS Data from 200 patients were analyzed. NLD was associated with sex, body height, and weight. A simple quantile regression model using the body height as the only covariate sufficed to achieve accurate predictions of NLD. Validation on independent test data showed that 92.8% of the NLD predictions were closer than ±20 mm to the observed NLD values. Measurements of equal-sized NETs varied considerably in outer diameter, proportion, the nasopharyngeal part, and guide marks. Length differences of the bend-to-cuff distance, containing the anatomically NLD, ranged between 218 and 270 mm at same sizes. CONCLUSIONS A reliable prediction of NLD can be obtained simply by body height, using the formula NLD (mm) = -13.2 + 1.1 × body height (cm). As manufacturers' tube lengths vary substantially, additional information about the bend-to-cuff distance as corresponding tube section would allow for more accurate tube selection.


Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing.


title: A SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Towards the Development of Point of Care Tests Using Commercially Available Reagents.

text: The SARS-CoV-2 pandemic has created an unprecedented need for rapid diagnostic testing to enable the efficient treatment and mitigation of COVID-19. The primary diagnostic tool currently employed is reverse transcription polymerase chain reaction (RT-PCR), which can have good sensitivity and excellent specificity. Unfortunately, implementation costs and logistical problems with reagents during the global SARS-CoV-2 pandemic have hindered its universal on demand adoption. Lateral flow assays (LFAs) represent a class of diagnostic that, if sufficiently clinically sensitive, may fill many of the gaps in the current RT-PCR testing regime, especially in low- and middle-income countries (LMICs). To date, many serology LFAs have been developed, though none meet the performance requirements necessary for diagnostic use cases, primarily due to the relatively long delay between infection and seroconversion. However, based on previously reported results from SARS-CoV-1, antigen-based SARS-CoV-2 assays may have significantly better clinical sensitivity than serology assays. To date, only a very small number of antigen-detecting LFAs have been developed. Development of a half-strip LFA is a useful first step in the development of any LFA format. In this paper we present a half-strip LFA using commercially available antibodies for the detection of SARS-CoV-2. We have tested this LFA in buffer and measured an LOD of 0.65 ng/ mL (95% CI of 0.53 to 0.77 ng/mL) ng/mL with recombinant antigen using an optical reader with sensitivity equivalent to a visual read. Further development, including evaluating the appropriate sample matrix, will be required for this assay approach to be made useful in a point of care setting, though this half-strip LFA may serve as a useful starting point for others developing similar tests.


title: Allergic contact dermatitis associated with Biosyn suture in a patient with gastroesophageal junction cancer.

text: A PUBMED literature review revealed no reports of allergic contact dermatitis to Biosyn(™) suture material. We present the first case of such an allergic reaction. The case emphasizes the need to remember that suture material can occasionally elicit an allergic dermatitis which may increase the complications and morbidity associated with any surgical procedure.


title: Ontogeny of a surgical technique: Robotic kidney transplantation with regional hypothermia.

text: INTRODUCTION Innovation is a hallmark of surgical practice. It is generally accepted that a new procedure will undergo technical changes during its evolution; however, quantitative accounts of the process are limited. METHODS Multiple groups, including our own, have recently described a minimally-invasive approach to conventional kidney transplantation (KT) operation. Unique to our experience is a structured development of the technique within the confines of a safe surgical innovation framework - the IDEAL framework (idea, development, exploration, assessment, long-term monitoring; stages 0-4). We here provide a first-hand narrative of the progress of robotic KT operation from preclinical trial to clinical application. RESULTS Overall, 54 patients underwent robotic KT with regional hypothermia successfully. Major technical changes including selection of optimal patient position (flank vs. lithotomy), robotic instrumentation, vascular occlusion method (bulldog vs. tourniquet) and suture material (prolene vs. GoreTex) occurred early during the procedure development (IDEAL stage 0, preclinical). Minor technical changes such as utilization of the aortic punch for arteriotomy (case 3), use of barbed suture during ureteroneocystostomy (case 6) and extraperitonealization of the graft kidney (case 6) that increased the efficiency and safety of the procedure continued throughout procedure development (IDEAL stages 1-2, clinical stages). CONCLUSIONS We demonstrate that a surgical technique evolves continually; although, the majority of technical alterations occur early in the life-cycle of the procedure. Development of a new technique within the confines a structured surgical innovation framework allows for evidence based progression of the technique and may minimize the risk of harm to the patient.


title: Dihydrocelastrol inhibits multiple myeloma cell proliferation and promotes apoptosis through ERK1/2 and IL-6/STAT3 pathways in vitro and in vivo.

text: Multiple myeloma (MM) is the second most frequent malignant hematological disease. Dihydrocelastrol (DHCE) is synthesized by hydrogenated celastrol, a treterpene isolated from Chinese medicinal plant Tripterygium regelii. In this study, we first reported the anti-tumor activity of DHCE on MM cells. We found that DHCE could inhibit cell proliferation and promote apoptosis through caspase-dependent way in vitro. In addition, DHCE could inactivate the expression of interleukin (IL)-6 and downregulate the phosphorylation of extracellular regulated protein kinases (ERK1/2) and the signal transducer and activator of transcription 3 (STAT3) in MM. It also retained its activity against MM cell lines in the presence of IL-6. Furthermore, treatment of MM cells with DHCE resulted in an accumulation of cells in G0/G1 phase of the cell cycle. Notably, DHCE reduced the expression of cyclin D1 and cyclin-dependent kinases 4 and 6 in MM cell lines. Additionally, its efficacy toward the MM cell lines could be enhanced in combination with the histone deacetylase inhibitor panobinostat (LBH589), which implied the possibility of the combination treatment of DHCE and LBH589 as a potential therapeutic strategy in MM. In addition, treatment of NCI-H929 tumor-bearing nude mice with DHCE (10 mg/kg/d, i.p., 1-14 days) resulted in 73% inhibition of the tumor growth in vivo. Taken together, the results of our present study indicated that DHCE could inhibit cellular proliferation and induce cell apoptosis in myeloma cells mediated through different mechanisms, possibly through inhibiting the IL-6/STAT3 and ERK1/2 pathways. And it may provide a new therapeutic option for MM patients.


title: Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens.

text: The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan low-density array (TLDA) cards for real-time PCR detection of 21 respiratory-pathogen targets. The performance of the TLDA was compared to that of individual real-time PCR (IRTP) assays with the same primers and probes using (i) nucleic acids extracted from the 21 pathogen strains and 66 closely related viruses and bacteria and (ii) 292 clinical respiratory specimens. With spiked samples, TLDA cards were about 10-fold less sensitive than IRTP assays. By using 292 clinical specimens to generate 2,238 paired individual assays, the TLDA card exhibited 89% sensitivity (95% confidence interval [CI], 86 to 92%; range per target, 47 to 100%) and 98% specificity (95% CI, 97 to 99%; range per target, 85 to 100%) overall compared to IRTP assays as the gold standard with a threshold cycle (C(T)) cutoff of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance.


title: Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability.

text: Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726-35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability.


title: Development of a dynamic model for ventral hernia mesh repair.

text: INTRODUCTION The adequate way of mesh fixation in laparoscopic ventral hernia repair is still subject to debate. So far, simulation has only been carried out in a static way, thereby omitting dynamic effects of coughing or vomiting. We developed a dynamic model of the anterior abdominal wall. MATERIALS AND METHODS An aluminium cylinder was equipped with a pressure controlled, fluid-filled plastic bag, simulating the abdominal viscera. A computer-controlled system allowed the control of influx and efflux, thus creating pressure peaks of up to 200 mmHg to simulate coughing and 290 mmHg to simulate vomiting. We tested fixation with tacks (Absorbatack, Covidien Deutschland, Neustadt a. D., Germany). The model was controlled for the friction coefficient of the tissue against the mesh and the physiologic elasticity of the abdominal wall surrogate. RESULTS The model was able to create pressure peaks equivalent to physiologic coughs or vomiting. Physiologic elasticity was thereby maintained. We could show that the friction coefficient is crucial to achieve a physiologic situation. The meshes showed a tendency to dislocate with an increasing number of coughs (Fig. 4). Nevertheless, when applied in a plain manner, the meshes withstood more cough cycles than when applied with a bulge as in laparoscopic surgery. CONCLUSIONS The dynamic movement of the abdominal wall, the friction between tissue and mesh and the way of mesh application are crucial factors that have to be controlled for in simulation of ventral abdominal hernia closure. We could demonstrate that patient specific factors such as the frequency of coughing as well as the application technique influence the long term stability of the mesh.


title: EVALUATION OF CHEMICAL IMMOBILIZATION IN CAPTIVE BLACK BEARS ( URSUS AMERICANUS) RECEIVING A COMBINATION OF NALBUPHINE, MEDETOMIDINE, AND AZAPERONE.

text: To assess potential seasonal differences in responses to immobilization, we sedated eight orphaned yearling black bears ( Ursus americanus) being held for rehabilitation at a wildlife facility in Colorado, US, using a premixed combination of nalbuphine (40 mg/mL), azaperone (10 mg/mL), and medetomidine (10 mg/mL; NalMed-A) in October (autumn) prior to hibernation and again after emergence in May (spring) prior to their release. We dosed all bears at 1 mL NalMed-A per estimated 45 kg body mass (1 mL NalMed-A/45 kg), delivered by intramuscular injection using a pole syringe, to facilitate routine examination and ear tagging. Arterial blood gases were measured to assess oxygenation and acid-base status of bears both pre and post oxygen supplementation. The mean (SE) dose calculated post hoc was 0.9 (0.04) mg nalbuphine/kg, 0.2 (0.01) mg azaperone/kg, and 0.2 (0.01) mg medetomidine/kg. The mean induction time was 8 (1) min for six of the bears in October and 6 (1) min for eight bears in May. The NalMed-A combination provided good sedation in captive yearling black bears in autumn and spring and was effectively antagonized with a combination of naltrexone and atipamezole. Mild hypoxemia (PaO2: 53.5-54.4 mmHg) was the most significant side effect and was corrected (PaO2: 68.4-150.1 mmHg) with supplemental oxygen administered at 2-5 L/min for 5 min (point of sampling).


title: Acute ischaemic stroke outcomes following mechanical thrombectomy in the elderly versus their younger counterpart: a retrospective cohort study.

text: OBJECTIVES Many physicians debate the efficacy of mechanical thrombectomy for ischaemic stroke, but most agree that to establish potential benefit, patient selection must be examined further. People >80 years are a growing population of patients with ischaemic stroke but are largely excluded from clinical trials. The benefit of thrombectomy for them may be greatly reduced due to diminishing neuroplasticity and a larger number of medical comorbidities. To address this knowledge gap, we examined clinical and economic outcomes after mechanical thrombectomy in the ischaemic stroke population from the Nationwide Inpatient Sample. Our null hypotheses were that elderly patients (>80 years) would have a similar rate of inpatient mortality in comparison to their younger counterparts and incur a similar economic expense. DESIGN Retrospective cohort study. SETTING A 20% stratified sample of US community hospitals within the Nationwide Inpatient Sample. PARTICIPANTS All patients from 2008 to 2010 with a primary diagnosis of ischaemic stroke that received mechanical thrombectomy were included. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome was inpatient mortality. Secondary outcomes included hospital charges and length of stay. RESULTS Less than 1% of all ischaemic stroke cases (9300) were treated with mechanical thrombectomy. Of these, 18% involved patients over 80 years of age. The odds of inpatient mortality in elderly patients treated with mechanical thrombectomy were approximately twice that of their younger counterparts (OR1.993, p < 0.001). The elderly experienced no significant difference in hospital charges (p=0.105) and length of stay (p=0.498). CONCLUSIONS The odds of inpatient mortality after mechanical thrombectomy in patients over 80 years of age were twice that of their younger counterparts. This is consistent with the overall worse prognosis seen in the natural history of this age group. Studies to better identify patients that would benefit from endovascular mechanical thrombectomy may improve outcomes and reduce the gap currently observed in age stratifications.


title: Identifying the probable timing and setting of respiratory virus infections.

text: OBJECTIVE Show how detailed incubation period estimates can be used to identify and investigate potential healthcare-associated infections and dangerous diseases. METHODS We used the incubation period of 9 respiratory viruses to derive decision rules for distinguishing between community- and hospital-acquired infection. We developed a method, implemented in a simple spreadsheet, that can be used to investigate the exposure history of an individual patient and more specifically to identify the probable time and location of infection. Illustrative examples are used to explain and evaluate this technique. RESULTS If the risks of hospital and community infection are equal, 95% of patients who develop symptoms of adenovirus infection within 5 days of hospital admission will have been infected in the community, as will 95% of patients who develop symptoms within 3 days for human-coronavirus infection, 2.5 days for severe acute respiratory syndrome, 1 day for influenza A, 0.5 day for influenza B, 12 days for measles, 2 days for parainfluenza, 4 days for respiratory syncytial virus infection, and 1.5 days for rhinovirus infection. Sources of infection suggested by analysis of the symptom onset times of individual patients are consistent with those from detailed investigations. CONCLUSIONS This work shows how a detailed understanding of the incubation period can be an effective tool for identifying the source of infection, ultimately ensuring patient safety.


title: Percutaneous Coronary Intervention of Saphenous Vein Graft.

text: BACKGROUND Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) has historically been associated with a high risk of adverse ischemic events, but there is a paucity of contemporary data on the second-generation drug-eluting stent use within SVG, and the relative importance of high platelet reactivity (HPR) in SVG PCI versus native lesion PCI is unknown. We studied ischemic and bleeding events after SVG PCI and their association with HPR. METHODS AND RESULTS Subjects in the prospective, multicenter ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) were stratified according to whether they had PCI of an SVG or a non-SVG lesion. Two-year outcomes were compared between groups using univariate and multivariable Cox proportional hazards models. HPR was defined as on-clopidogrel P2Y12 platelet reaction units >208 as measured by the VerifyNow assay; major adverse cardiac events were defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. Among 8582 subjects in ADAPT-DES, 405 (4.7%) had SVG PCI. SVG PCI was independently associated with a higher 2-year risk of major adverse cardiac events (adjusted hazard ratio, 2.34; 95% confidence interval, 1.69-3.23; P<0.0001), ischemia-driven target vessel revascularization (adjusted hazard ratio, 1.82; 95% confidence interval, 1.37-2.42; P<0.0001), and stent thrombosis (adjusted hazard ratio, 2.26; 95% confidence interval, 1.42-3.59; P=0.0006), but not of bleeding (adjusted hazard ratio, 0.99; 95% confidence interval, 0.68-1.46; P=0.97). There was no statistical interaction between HPR and SVG PCI in regard to major adverse cardiac events (adjusted Pinteraction=0.99). CONCLUSIONS SVG PCI is associated with a considerably higher risk of 2-year adverse ischemic events, with HPR conferring similar risk in SVG and non-SVG PCI. More potent and longer antiplatelet therapy may be beneficial for patients undergoing SVG PCI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.


Existing Drugs Might Treat COVID-19.


title: The association between severe COVID-19 and low platelet count: evidence from 31 observational studies involving 7613 participants.

text: A novel coronavirus disease 2019 (COVID-19) broke out at 2019 and had caused a pandemic around the world. This disease was found resulting from the infection of 2019 novel coronavirus (2019-nCoV) (Zhu, et al 2020). The severity of COVID-19 disease has a wide range and varies from asymptomatic to critical severe, clinical researches reported that 10-15% of the patients were in the severe situation and required a great deal of attention of treatment and nursing (WHO-China-Joint-Mission 2020).


Blood transfusion during haemodialysis improves systemic tissue oxygenation: A case report.


title: The effect of Adacolumn® on ulcerative colitis with COVID-19.

text: Crespo et al. comment on the influence of immunomodulators and biological drugs on ulcerative colitis and SARS-CoV-2 infection. Granulo-monocytoapheresis is a treatment used in ulcerative colitis outbreaks, whose mechanism of action is to selectively retain activated granulocytes and monocytes, in order to reduce the inflammatory process.


title: Comparison of serum neutralization and enzyme-linked immunosorbent assay on sera from porcine epidemic diarrhea virus vaccinated pigs.

text: BACKGROUND Porcine epidemic diarrhea virus (PEDV) is an economically important pathogen of swine. OBJECTIVE Serum neutralization (SN) and enzyme-linked immunosorbent assay (ELISA) test results as well as the utility of spike proteins S1, S2, and S3 and entire nucleocapsid protein were compared. ANIMALS AND METHODS Serum samples from 400 pigs vaccinated against PEDV strain SM98P were collected from 78 farms in Korea. SN test and ELISA were performed to confirm the presence of antibodies. For prokaryotic expression of partial fragments of spike protein the size and location of S1, S2, and S3, and full nucleocapsid protein, polymerase chain reaction was performed using specific primers. RESULTS Comparison of these results demonstrated that there was a correlation between the SN and ELISA results. Sera with higher neutralizing activity also had higher IgG titer. The antibody profiling data presented the correlation of neutralizing activity with the level of spike protein antibody. In particular, the S3 region may have an important role in neutralizing activity. CONCLUSIONS We confirmed that the carboxy-terminal region that includes the endodomain of the S protein induced stronger neutralizing activity than the region that includes the ectodomain. CLINICAL RELEVANCE The region of the S protein may have a stronger neutralizing KPEDV-9 epitope and could be useful for the evaluation of future PEDV vaccine efficacy.


title: The rise of adverse childhood experiences during the COVID-19 pandemic.

text: Adverse childhood experiences, which is defined by different forms of abuse, neglect, and household dysfunction occurring before the age of 18 years, is a major public health problem in the United States that has the potential to worsen in the current COVID-19 pandemic. Moreover, the challenge is even greater for children and youth from low-income communities and communities of color. Thus, there is a greater need for investments in youth-serving systems within and beyond health care and public health to effectively address adverse childhood experiences and prevent its short- and long-term negative health and social sequelae well beyond the current public health crisis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Harnessing behavioural science in public health campaigns to maintain 'social distancing' in response to the COVID-19 pandemic: key principles.


title: Impact of COVID-19 on Brazilian medical residencies in obstetrics and gynecology.

text: Brazil has become the epicenter for COVID-19 cases worldwide, after the United States, with more than 500 000 cases and almost 30 000 deaths as of June 1, 2020.[1] This pandemic has resulted in the need to modify all hospitals to be adapted for receiving patients with severe cases of COVID-19. In many institutions, postgraduate residents have experienced an interruption of their ordinary activities. Brazil is a vast country, with many structural inequalities and a postgraduate medical residency program sponsored within the public health system.


title: Analysis of Clinical Predictors of Resolution of Sleep Disturbance Related to Frequent Nighttime Heartburn and Acid Regurgitation Symptoms in Individuals Taking Esomeprazole 20 mg or Placebo.

text: BACKGROUND AND OBJECTIVE Sleep disturbances related to reflux symptoms have a significant impact on the daily lives of affected individuals. These analyses identified clinical factors related to resolution of reflux-related sleep disturbance in subjects treated with esomeprazole 20 mg for 14 days. METHODS Data from the first 14 days of 2 similar randomized, double-blind studies were pooled for subjects experiencing frequent heartburn and related sleep disturbances receiving esomeprazole 20 mg (n = 357) or placebo (n = 346). A stepwise logistic regression analysis was performed with pooled and individual study data to evaluate relationships between clinical factors [treatment (esomeprazole vs. placebo), run-in sleep disturbance frequency, occurrence (yes/no) of 24-h, daytime, and nighttime heartburn (yes: ≥1 episode in 14-day treatment period)] and complete sleep disturbance resolution (no disturbances for 7 consecutive days). RESULTS Absence of daytime (p = 0.0018) or nighttime (p < 0.0001) heartburn during treatment was a significant predictor of complete sleep disturbance resolution at 14 days for the total population, while higher run-in sleep disturbance frequency (p < 0.0001) was associated with a lower likelihood of resolution. Esomeprazole treatment was an independent significant predictor of improvement across all endpoints (p < 0.0001). A significant treatment by run-in sleep disturbance interaction was observed for complete resolution (p = 0.0231), indicating greater therapeutic benefit with esomeprazole in subgroups with higher run-in symptom frequency. CONCLUSIONS Lower run-in sleep disturbance frequency, no occurrence of daytime or nighttime heartburn during therapy, and esomeprazole treatment predicted complete reflux-related sleep disturbance resolution. The magnitude of therapeutic benefit for esomeprazole 20 mg over placebo increased with increasing baseline sleep disturbance.


title: Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity.

text: Influenza A and B viruses are a global threat to human health and increasing resistance to the existing antiviral drugs necessitates new concepts to expand the therapeutic options. Glycopeptide derivatives have emerged as a promising new class of antiviral agents. To avoid potential antibiotic resistance, these antiviral glycopeptides are preferably devoid of antibiotic activity. We prepared six vancomycin aglycone hexapeptide derivatives with the aim of obtaining compounds having anti-influenza virus but no antibacterial activity. Two of them exerted strong and selective inhibition of influenza A and B virus replication, while antibacterial activity was successfully eliminated by removing the critical N-terminal moiety. In addition, these two molecules offered protection against several other viruses, such as herpes simplex virus, yellow fever virus, Zika virus, and human coronavirus, classifying these glycopeptides as broad antiviral molecules with a favorable therapeutic index.


title: Allergenic immunotherapy and seasonal changes in nitric oxide concentration in exhaled air in seasonal rhinitis patients.

text: BACKGROUND Concentration of nitric oxide in exhaled air (FeNO) was revealed to decrease as a result of immunotherapy. However, individuals who are exposed to environmental allergens are characterized by elevated values of FeNO. The aim of this study was to analyze the effects of subcutaneous immunotherapy (SCIT) on the dynamics of FeNO determined during consecutive pollination seasons. METHODS This study, performed between 2005 and 2008, included 41 patients with confirmed sensitivity to grass pollens and predominating symptoms of seasonal allergic rhinitis, randomly assigned to desensitization by preseasonal or maintenance SCIT. FeNO was measured prior to and during each pollen season (November-January and May-July, respectively). The results were conferred to data on grass pollination intensity in 2006-2008 (air concentration of grass pollen grains, seasonal number of days when air concentration of grass pollen reached at least 50 grains per 1 m(3)). RESULTS Median content of FeNO in exhaled air was significantly higher in 2007 compared to 2006 and 2008 pollen seasons. During 2007 and 2008 pollen seasons, significant increase in FeNO was observed compared to the respective preseasonal values. Median number of days with air concentration of grass pollen ≥ 50 grains per 1 m(3) of air during 4 weeks preceding seasonal FeNO measurement was significantly higher in 2007, corresponding to higher FeNO value recorded during this pollen season. However, no significant correlation was observed between seasonal number of days with ≥ 50 grass pollen grains per 1 m(3) of air and FeNO in exhaled air (r=0.09, p=0.362). CONCLUSIONS Most seasonal allergic rhinitis patients show physiological levels of FeNO prior to the pollen seasons and a marked increase in this parameter, probably proportional to pollination intensity, is observed within the seasons. ISRCTN Registry: ISRCTN86562422.


title: Iterative Reconstruction Improves Both Objective and Subjective Image Quality in Acute Stroke CTP.

text: PURPOSE Computed tomography perfusion (CTP) imaging in acute ischemic stroke (AIS) suffers from measurement errors due to image noise. The purpose of this study was to investigate if iterative reconstruction (IR) algorithms can be used to improve the diagnostic value of standard-dose CTP in AIS. METHODS Twenty-three patients with AIS underwent CTP with standardized protocol and dose. Raw data were reconstructed with filtered back projection (FBP) and IR with intensity levels 3, 4, 5. Image quality was objectively (quantitative perfusion values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)) and subjectively (overall image quality) assessed. Ischemic core and perfusion mismatch were visually rated. Discriminative power for tissue outcome prediction was determined by the area under the receiver operating characteristic curve (AUC) resulting from the overlap between follow-up infarct lesions and stepwise thresholded CTP maps. RESULTS With increasing levels of IR, objective image quality (SNR and CNR in white matter and gray matter, elimination of error voxels) and subjective image quality improved. Using IR, mean transit time (MTT) was higher in ischemic lesions, while there was no significant change of cerebral blood volume (CBV) and cerebral blood flow (CBF). Visual assessments of perfusion mismatch changed in 4 patients, while the ischemic core remained constant in all cases. Discriminative power for infarct prediction as represented by AUC was not significantly changed in CBV, but increased in CBF and MTT (mean (95% CI)): 0.72 (0.67-0.76) vs. 0.74 (0.70-0.78) and 0.65 (0.62-0.67) vs 0.67 (0.64-0.70). CONCLUSION In acute stroke patients, IR improves objective and subjective image quality when applied to standard-dose CTP. This adds to the overall confidence of CTP in acute stroke triage.


title: Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19).

text: BACKGROUND There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.


title: Identification of the same polyomavirus species in different African horseshoe bat species is indicative of short-range host-switching events.

text: Polyomaviruses (PyVs) are considered to be highly host-specific in different mammalian species, with no well-supported evidence for host-switching events. We examined the species diversity and host specificity of PyVs in horseshoe bats (Rhinolophus spp.), a broadly distributed and highly speciose mammalian genus. We annotated six PyV genomes, comprising four new PyV species, based on pairwise identity within the large T antigen (LTAg) coding region. Phylogenetic comparisons revealed two instances of highly related PyV species, one in each of the Alphapolyomavirus and Betapolyomavirus genera, present in different horseshoe bat host species (Rhinolophus blasii and R. simulator), suggestive of short-range host-switching events. The two pairs of Rhinolophus PyVs in different horseshoe bat host species were 99.9 and 88.8 % identical with each other over their respective LTAg coding sequences and thus constitute the same virus species. To corroborate the species identification of the bat hosts, we analysed mitochondrial cytb and a large nuclear intron dataset derived from six independent and neutrally evolving loci for bat taxa of interest. Bayesian estimates of the ages of the most recent common ancestors suggested that the near-identical and more distantly related PyV species diverged approximately 9.1E4 (5E3-2.8E5) and 9.9E6 (4E6-18E6) years before the present, respectively, in contrast to the divergence times of the bat host species: 12.4E6 (10.4E6-15.4E6). Our findings provide evidence that short-range host-switching of PyVs is possible in horseshoe bats, suggesting that PyV transmission between closely related mammalian species can occur.


title: Widespread 3'-end uridylation in eukaryotic RNA viruses.

text: RNA 3' uridylation occurs pervasively in eukaryotes, but is poorly characterized in viruses. In this study, we demonstrate that a broad array of RNA viruses, including mycoviruses, plant viruses and animal viruses, possess a novel population of RNA species bearing nontemplated oligo(U) or (U)-rich tails, suggesting widespread 3' uridylation in eukaryotic viruses. Given the biological relevance of 3' uridylation to eukaryotic RNA degradation, we propose a conserved but as-yet-unknown mechanism in virus-host interaction.


title: Lost needle: a dilemma in robotic-assisted laparoscopic surgery.

text: A case is presented where a needle was lost in the assistant's port during a robotic-assisted radical prostatectomy. This complication generated a unique dilemma: whether or not to disengage the robot and search for the needle or to continue with the operation and look for the needle at the end of the operation.


title: Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort.

text: OBJECTIVE Comorbid conditions are associated with poor prognosis in COVID-19. Registry data show that patients with cirrhosis may be at high risk. However, outcome comparisons among patients with cirrhosis+COVID-19 versus patients with COVID-19 alone and cirrhosis alone are lacking. The aim of this study was to perform these comparisons. DESIGN A multicentre study of inpatients with cirrhosis+COVID-19 compared with age/gender-matched patients with COVID-19 alone and cirrhosis alone was performed. COVID-19 and cirrhosis characteristics, development of organ failures and acute-on-chronic liver failure (ACLF) and mortality (inpatient death+hospice) were compared. RESULTS 37 patients with cirrhosis+COVID-19 were matched with 108 patients with COVID-19 and 127 patients with cirrhosis from seven sites. Race/ethnicity were similar. Patients with cirrhosis+COVID-19 had higher mortality compared with patients with COVID-19 (30% vs 13%, p=0.03) but not between patients with cirrhosis+COVID-19 and patients with cirrhosis (30% vs 20%, p=0.16). Patients with cirrhosis+COVID-19 versus patients with COVID-19 alone had equivalent respiratory symptoms, chest findings and rates of intensive care unit transfer and ventilation. However, patients with cirrhosis+COVID-19 had worse Charlson Comorbidity Index (CCI 6.5±3.1 vs 3.3±2.5, p<0.001), lower presenting GI symptoms and higher lactate. Patients with cirrhosis alone had higher cirrhosis-related complications, maximum model for end-stage liver disease (MELD) score and lower BiPAP/ventilation requirement compared with patients with cirrhosis+COVID-19, but CCI and ACLF rates were similar. In the entire group, CCI (OR 1.23, 95% CI 1.11 to 1.37, p<0.0001) was the only variable predictive of mortality on multivariable regression. CONCLUSIONS In this multicentre North American contemporaneously enrolled study, age/gender-matched patients with cirrhosis+COVID-19 had similar mortality compared with patients with cirrhosis alone but higher than patients with COVID-19 alone. CCI was the only independent mortality predictor in the entire matched cohort.


title: Pharmacotherapy for lower respiratory tract infections.

text: INTRODUCTION Bacterial infections play an important role as etiological agents in acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and exacerbations of non-cystic fibrosis (CF) bronchiectasis. In acute bronchitis and asthma exacerbations their role is less well defined than with patients with COPD. The clinical features, causative pathogens and therapies of common acute respiratory tract infections are detailed in this review. AREAS COVERED This article covers medical literature published in any language from 2000 to 2014, on 'lower respiratory tract infections', identified using PubMed, MEDLINE and ClinicalTrial.gov. The search terms used were 'COPD exacerbations', 'bronchiectasis', 'macrolides' and 'inhaled antibiotics'. EXPERT OPINION Given that almost half of AECOPD are caused by bacteria, administration of antibacterial agents is recommended for patients with severe exacerbations or severe underlying COPD. Chronic prophylactic use of macrolides seems to be of benefit, particularly in patients with bronchiectasis and chronic mucous hypersecretion. In an effort to manage chronic airway infection non-CF bronchiectasis due to drug-resistant pathogens, aerosolized antibiotics may be of value, and the data from recent studies are examined to demonstrate the potential value of this therapy, which is often used as an adjunctive measure to systemic antimicrobial therapy.


title: [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China].

text: Objective: An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods: All COVID-19 cases reported through February 11, 2020 were extracted from China's Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results: A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions: The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic.


title: Safe abortion amid the COVID-19 pandemic: The case of Italy.

text: An estimated 56 million induced abortions occur globally every year, of which 54.9% are unsafe.[1] This is a major public health issue, especially where access to legal abortion is highly restricted, resulting in an estimated 7.9% of maternal deaths annually due to unsafe abortion.


title: Making the most of the first prenatal visit: The challenge of expanding prenatal genetic testing options and limited clinical encounter time.

text: OBJECTIVE Advances in prenatal genetics place additional challenges as patients must receive information about a growing array of screening and testing options. This raises concerns about how to achieve a shared decision-making process that prepares patients to make an informed decision about their choices about prenatal genetic screening and testing options, calling for a reconsideration of how healthcare providers approach the first prenatal visit. METHODS We conducted interviews with 40 pregnant women to identify components of decision-making regarding prenatal genetic screens and tests at this visit. Analysis was approached using grounded theory. RESULTS Participants brought distinct notions of risk to the visit, including skewed perceptions of baseline risk for a fetal genetic condition and the implications of screening and testing. Participants were very concerned about financial considerations associated with these options, ranking out-of-pocket costs on par with medical considerations. Participants noted diverging priorities at the first visit from those of their healthcare provider, leading to barriers to shared decision-making regarding screening and testing during this visit. CONCLUSION Research is needed to determine how to restructure the initiation of prenatal care in a way that best positions patients to make informed decisions about prenatal genetic screens and tests. This article is protected by copyright. All rights reserved.


title: Management of acute bacterial skin and skin structure infections with a focus on patients at high risk of treatment failure.

text: Over the last 25 years, the terminology of skin and soft tissue infections, as well as their classification for optimal management of patients, has changed. The so-called and recently introduced term 'acute bacterial skin and skin structure infections' (ABSSSIs), a cluster of fairly common types of infection, including abscesses, cellulitis, and wound infections, require an immediate effective antibacterial treatment as part of a timely and cautious management. The extreme level of resistance globally to many antibiotic drugs in the prevalent causative pathogens, the presence of risk factors of treatment failure, and the high epidemic of comorbidities (e.g. diabetes and obesity) make the appropriate selection of the antibiotic for physicians highly challenging. The selection of antibiotics is primarily empirical for ABSSSI patients which subsequently can be adjusted based on culture results, although rarely available in outpatient management. There is substantial evidence suggesting that inappropriate antibiotic treatment is given to approximately 20-25% of patients, potentially prolonging their hospital stay and increasing the risk of morbidity and mortality. The current review paper discusses the concerns related to the management of ABSSSI and the patient types who are most vulnerable to poor outcomes. It also highlights the key management time-points that treating physicians and surgeons must be aware of in order to achieve clinical success and to discharge patients from the hospital as early as possible.


title: Sequence identity between the genomes of humans and viruses.

text: OBJECTIVE People exposed to viruses usually do not develop diseases. Viruses cause diseases; however, most of the pathologic effects of these diseases are not caused directly by the viruses but by the side effects of the immune response. It is possible that sequence identity may exist between viruses and humans and may be biologically relevant to the infection of virus. The aim of this study was to find out whether sequence identity exists between viruses and humans. METHODS BLAST searches of virus genome sequences against human genome were performed using the resources of the National Center for Biotechnology Information (NCBI). RESULTS All the viruses that were compared to humans contain different numbers of short identical regions to the human genome. Each identical region was 20-30 nt and some were found at multiple sites within the human genome. CONCLUSION A new role of the virus in the relationship between viruses and humans was taken into account. We assume that viruses have brought their sequence into the human genome in the long past history of human-virus interaction. In the process, viruses play roles as carriers to transfer external sequence information into the human genome.


title: Dengue Virus Selectively Annexes Endoplasmic Reticulum-Associated Translation Machinery as a Strategy for Co-opting Host Cell Protein Synthesis.

text: A primary question in dengue virus (DENV) biology is the molecular strategy for recruitment of host cell protein synthesis machinery. Here, we combined cell fractionation, ribosome profiling, and transcriptome sequencing (RNA-seq) to investigate the subcellular organization of viral genome translation and replication as well as host cell translation and its response to DENV infection. We report that throughout the viral life cycle, DENV plus- and minus-strand RNAs were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as the primary site of DENV translation. DENV infection was accompanied by an ER compartment-specific remodeling of translation, where ER translation capacity was subverted from host transcripts to DENV plus-strand RNA, particularly at late stages of infection. Remarkably, translation levels and patterns in the cytosol compartment were only modestly affected throughout the experimental time course of infection. Comparisons of ribosome footprinting densities of the DENV plus-strand RNA and host mRNAs indicated that DENV plus-strand RNA was only sparsely loaded with ribosomes. Combined, these observations suggest a mechanism where ER-localized translation and translational control mechanisms, likely cis encoded, are used to repurpose the ER for DENV virion production. Consistent with this view, we found ER-linked cellular stress response pathways commonly associated with viral infection, namely, the interferon response and unfolded protein response, to be only modestly activated during DENV infection. These data support a model where DENV reprograms the ER protein synthesis and processing environment to promote viral survival and replication while minimizing the activation of antiviral and proteostatic stress response pathways.IMPORTANCE DENV, a prominent human health threat with no broadly effective or specific treatment, depends on host cell translation machinery for viral replication, immune evasion, and virion biogenesis. The molecular mechanism by which DENV commandeers the host cell protein synthesis machinery and the subcellular organization of DENV replication and viral protein synthesis is poorly understood. Here, we report that DENV has an almost exclusively ER-localized life cycle, with viral replication and translation largely restricted to the ER. Surprisingly, DENV infection largely affects only ER-associated translation, with relatively modest effects on host cell translation in the cytosol. DENV RNA translation is very inefficient, likely representing a strategy to minimize disruption of ER proteostasis. Overall these findings demonstrate that DENV has evolved an ER-compartmentalized life cycle; thus, targeting the molecular signatures and regulation of the DENV-ER interaction landscape may reveal strategies for therapeutic intervention.


docid: mzmphgru

title: The necessity of continuing to ban tobacco use in public places post-COVID-19.


Thoracic techniques: robotic thymectomy for thymoma.


Survival after bariatric surgery among high-risk patients.


title: Total laparoscopic partial pancreatoduodenectomy and reconstruction via laparoscopic pancreatogastrostomy.

text: INTRODUCTION Minimally invasive surgery has conquered almost all niches of abdominal surgery. Even though some surgeons have shown equal lymph node ratio and oncologic radicality for laparoscopic surgery of pancreatic cancer, oncologic surgeons still take reasonably conservative views of the use of minimally invasive techniques for the treatment of pancreatic cancer, especially if located in the head of the pancreas. Laparoscopic abdominal approaches on the other hand have a potential advantage of better visualization, decreased postoperative pain, decreased use of analgetics, and shorter hospital stay. We demonstrate in this technical surgical report the first description of a total laparoscopic pancreatoduodenectomy and reconstruction via laparoscopic pancreatogastrostomy in a 74-year-old female patient with a periampullary tumor. DISCUSSION After pylorus-preserving pancreatoduodenectomy by superior mesenteric artery, first approach including standard lymphadenectomy, the reconstruction involved total laparoscopic end-to-side running-suture hepaticojejunostomy, double-layer running-suture antecolic pylorojejunostomy to the first jejunal loop, and pancreatogastrostomy via posterior gastrotomy secured by two anchoring and purse-string sutures.


COVID-19 amidst Ebola's retreat.


title: Safe incorporation of new technologies in thyroid surgery.

text: The history of thyroid surgery starts with Billroth, Kocher and Halsted, who developed the technique for thyroidectomy between the years of 1873 and 1910. In general the essential objectives for thyroidectomy are: sparing the parathyroid glands, avoidance of injury to the laryngeal nerves, an accurate hemostasis and an excellent cosmesis. In the last 10 years, major improvements and new technologies have been proposed and applied in thyroid surgery. These include mini-invasive thyroidectomy, new devices for achieving hemostasis and dissection, regional anesthesia, intraoperative neuromonitoring, parathyroid hormone assay technology and genetic screening. This paper reviews the relevant medical literature published on the influence of these new technologies on the quality of thyroid surgery, as well as prevention of postoperative morbidity and mortality. Searches were last updated in April 2008.


title: Effect of a fever control protocol-based strategy on ventilator-associated pneumonia in severely brain-injured patients.

text: INTRODUCTION Fever is associated with a poor outcome in severely brain-injured patients, and its control is one of the therapies used in this condition. But, fever suppression may promote infection, and severely brain-injured patients are frequently exposed to infectious diseases, particularly ventilator-associated pneumonia (VAP). Therefore, we designed a study to explore the role of a fever control protocol in VAP development during neuro-intensive care. METHODS An observational study was performed on severely brain-injured patients hospitalized in a university ICU. The primary goal was to assess whether fever control was a risk factor for VAP in a prospective cohort in which a fever control protocol was applied and in a historical control group. Moreover, the density of VAP incidence was compared between the two groups. The statistical analysis was based on a competing risk model multivariate analysis. RESULTS The study included 189 brain-injured patients (intervention group, n = 98, and historical control group, n = 91). The use of a fever control protocol was an independent risk factor for VAP (hazard ratio 2.73, 95% confidence interval (1.38, 5.38; P = 0.005)). There was a significant increase in the incidence of VAP in patients treated with a fever control protocol (26.1 versus 12.5 VAP cases per 1000 days of mechanical ventilation). In cases in which a fever control protocol was applied for > 3 days, we observed a higher rate of VAP in comparison with the rate among patients treated for ≤ 3 days. CONCLUSIONS Fever control in brain-injured patients was a major risk factor for VAP occurrence, particularly when applied for > 3 days.


Coordinating a national clinical trials center: the German experience.


The world is changing fast!


title: Dissection of Ascending Aorta: A Complication of Transradial Artery Access of Coronary Procedure.

text: Iatrogenic acute dissection of ascending aorta following coronary angiography and percutaneous intervention is a rare complication. Most reports involve localized aortic dissections as a complication of cannulation of a coronary artery with propagation into the ascending aorta. It is usually treated by sealing the intima with a stent in the ostium of the coronary artery or conservative management, while extensive dissections may require a surgical intervention. We describe a case of the subclavian dissection extending into the ascending aorta that occurred during diagnostic catheterization using the radial approach. The patient was successfully treated utilizing conservative management.


Is Metformin ahead in the race as a repurposed host-directed therapy for patients with diabetes and COVID-19?


The FPM International Awards for Medical Writing in Social Media: a step in the right direction.


title: Chemotherapeutic Potential of Monensin as an Anti-microbial Agent.

text: Monensin is a lipid-soluble naturally occurring bioactive ionophore produced by Streptomyces spp. Its antimicrobial activity is mediated by its ability to exchange Na+ and K+ ions across the cell membrane thereby disrupting ionic gradients and altering cellular physiology. It is approved by Food and Drug Administration as a veterinary antibiotic to treat coccidiosis. Besides veterinary applications, monensin exhibits a broad spectrum activity against opportunistic pathogens of humans such as bacteria, virus, fungi and parasites in both drug sensitive and resistant strains. This ionophore can selectively kill pathogens with negligible toxic effect on mammalian cells. In this review, we discuss the therapeutic potential of monensin as a new broad-spectrum anti-microbial agent that warrants further studies for clinical use.


title: Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy.

text: In epilepsy, seizures can evoke cardiac rhythm disturbances such as heart rate changes, conduction blocks, asystoles, and arrhythmias, which can potentially increase risk of sudden unexpected death in epilepsy (SUDEP). Electroencephalography (EEG) and electrocardiography (ECG) are widely used clinical diagnostic tools to monitor for abnormal brain and cardiac rhythms in patients. Here, a technique to simultaneously record video, EEG, and ECG in mice to measure behavior, brain, and cardiac activities, respectively, is described. The technique described herein utilizes a tethered (i.e., wired) recording configuration in which the implanted electrode on the head of the mouse is hard-wired to the recording equipment. Compared to wireless telemetry recording systems, the tethered arrangement possesses several technical advantages such as a greater possible number of channels for recording EEG or other biopotentials; lower electrode costs; and greater frequency bandwidth (i.e., sampling rate) of recordings. The basics of this technique can also be easily modified to accommodate recording other biosignals, such as electromyography (EMG) or plethysmography for assessment of muscle and respiratory activity, respectively. In addition to describing how to perform the EEG-ECG recordings, we also detail methods to quantify the resulting data for seizures, EEG spectral power, cardiac function, and heart rate variability, which we demonstrate in an example experiment using a mouse with epilepsy due to Kcna1 gene deletion. Video-EEG-ECG monitoring in mouse models of epilepsy or other neurological disease provides a powerful tool to identify dysfunction at the level of the brain, heart, or brain-heart interactions.


Tissue reactions to polyethylene glycol and glutaraldehyde-based surgical sealants in a rabbit aorta model.


title: Differential expression of ADAM15 and ADAM17 metalloproteases in the rat brain after severe hypobaric hypoxia and hypoxic preconditioning.

text: The ADAMs (a disintegrin and metalloprotease) are a family of membrane-anchored glycoproteins capable of shedding a multitude of proteins from the cell surface. Although ADAMs are being considered as crucial modulators of physiological and pathophysiological processes, their roles in neuronal death/survival are largely unexplored. In the present study, changes in brain expression of ADAM15 and ADAM17 (TACE) have been quantitatively examined in rats in response to injurious severe hypoxia (SH) and in animals which acquired hypoxic tolerance through preconditioning to mild hypoxia prior SH. SH persistently up-regulated ADAM15 mRNA and protein levels in hippocampus and neocortex but not in thalamus or hypothalamus. This effect was not observed in the preconditioned rats tolerant to SH. In contrast, hippocampal levels of ADAM17 mRNA and neocortical levels of ADAM17 mRNA and protein were largely reduced following SH in non-preconditioned rats. Hypoxic preconditioning prevented down-regulation of the adam17 gene and considerably enhanced ADAM17 protein expression in hippocampus and neocortex in response to SH. The present findings implicate ADAM15 in the processes of neuronal hypoxic injury. On the other hand, these results also provide evidence for a pro-survival neuroprotective role of ADAM17 and its engagement in the process of preconditioning-induced hypoxic tolerance. The analysis of the protein levels of soluble and membrane-bound forms of APP in the neocortex and hippocampus of rats subjected to SH and SH with preconditioning has demonstrated that an increased ADAM17 expression in preconditioned animals 24h after hypoxia corresponded to a higher level of soluble form of APP and a reduction of the membrane bound fraction which reflects the role of ADAM17 in APP shedding.


title: Laboratory diagnosis of Ebola virus disease and corresponding biosafety considerations in the China Ebola Treatment Center.

text: Ebola virus disease (EVD), caused by Ebola virus (EBOV), is a potent acute infectious disease with a high case-fatality rate. Etiological and serological EBOV detection methods, including techniques that involve the detection of the viral genome, virus-specific antigens and anti-virus antibodies, are standard laboratory diagnostic tests that facilitate confirmation or exclusion of EBOV infection. In addition, routine blood tests, liver and kidney function tests, electrolytes and coagulation tests and other diagnostic examinations are important for the clinical diagnosis and treatment of EVD. Because of the viral load in body fluids and secretions from EVD patients, all body fluids are highly contagious. As a result, biosafety control measures during the collection, transport and testing of clinical specimens obtained from individuals scheduled to undergo EBOV infection testing (including suspected, probable and confirmed cases) are crucial. This report has been generated following extensive work experience in the China Ebola Treatment Center (ETC) in Liberia and incorporates important information pertaining to relevant diagnostic standards, clinical significance, operational procedures, safety controls and other issues related to laboratory testing of EVD. Relevant opinions and suggestions are presented in this report to provide contextual awareness associated with the development of standards and/or guidelines related to EVD laboratory testing.


title: Stent-assisted detachable coil embolization of wide-necked renal artery aneurysms.

text: Renal artery aneurysms (RAAs) are rare with an estimated incidence of 0.1% in the general population, and they represent approximately 25% of all visceral aneurysms. The gold standard of treatment is open surgery, but it is associated with a high risk of nephrectomy, mortality, and morbidity. Less invasive endovascular therapies are becoming increasingly common for the treatment of RAAs. Here, we aimed to report three cases of wide-necked complex renal artery aneurysms treated endovascularly using stent-assisted coil embolization with self-expandable stent nitinol Solitaire AB and Concerto Axium coils. In addition, we describe the use of the waffle-cone technique in a case of wide-necked saccular RAA involving the renal artery bifurcation. Technical success was achieved in all three cases with no early or late complications and no recurrences.


title: In COVID-19, adding lopinavir-ritonavir to usual care did not shorten time to clinical improvement.

text: SOURCE CITATION Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020;382:1787-99. 32187464.


title: Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles.

text: BACKGROUND Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality in women worldwide. Despite various attempts to improve the diagnosis and therapy of ovarian cancer patients, the survival rate for these patients is still dismal, mainly because most of them are diagnosed at a late stage. Up to 90% of ovarian cancers arise from neoplastic transformation of ovarian surface epithelial cells, and are usually referred to as epithelial ovarian cancer (EOC). Unlike most human cancers, which are disseminated through blood-borne metastatic routes, EOC has traditionally been thought to be disseminated through direct migration of ovarian tumor cells to the peritoneal cavity and omentum via peritoneal fluid. It has recently been shown, however, that EOC can also be disseminated through blood-borne metastatic routes, challenging previous thoughts about ovarian cancer metastasis. CONCLUSIONS Here, we review our current understanding of the most updated cellular and molecular mechanisms underlying EOC metastasis and discuss in more detail two main metastatic routes of EOC, i.e., transcoelomic metastasis and hematogenous metastasis. The emerging concept of blood-borne EOC metastasis has led to exploration of the significance of circulating tumor cells (CTCs) as novel and non-invasive prognostic markers in this daunting cancer. We also evaluate the role of tumor stroma, including cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs), endothelial cells, adipocytes, dendritic cells and extracellular matrix (ECM) components in EOC growth and metastasis. Lastly, we discuss therapeutic approaches for targeting EOC. Unraveling the mechanisms underlying EOC metastasis will open up avenues to the design of new therapeutic options. For instance, understanding the molecular mechanisms involved in the hematogenous metastasis of EOC, the biology of CTCs, and the detailed mechanisms through which EOC cells take advantage of stromal cells may help to find new opportunities for targeting EOC metastasis.


title: Endovascular stroke treatment's impact on malignant type of edema (ESTIMATE).

text: BACKGROUND AND PURPOSE In patients with acute ischemic stroke and large vessel occlusion, the prognosis has improved tremendously since the implementation of endovascular thrombectomy (EVT). The effect of EVT on the incidence of malignant middle cerebral artery infarctions (MMI) has not been studied before. METHODS ESTIMATE, a multicenter retrospective study, evaluates data of ischemic stroke patients with occlusion in the anterior circulation in the years of 2007-2015 comparing three treatment options (no therapy; IV-TPA; IV-TPA plus EVT or EVT only). Primary endpoint of the study was the incidence of MMI on follow-up imaging and mortality rates. Secondary endpoints were functional outcome, further clinical and imaging data. Logistic and Cox-regression models with a propensity score weighting approach were applied to evaluate differences between treatment groups. RESULTS In 2161 patients over 9 years, EVT reduced the MMI rates significantly: patients without acute stroke treatment had increased odds for MMI of 1.57 [95% confidence interval (CI) 1.49-1.65]. In contrast, after treatment with IV-TPA, only we observed an OR of 0.88 (95% CI 0.83-0.94, p < 0.001), and after EVT an OR of 0.80 (95% CI 0.76-0.85, p < 0.001). This was more pronounced in larger pretreatment infarctions (ASPECTS < 5, p < 0.01). IV-TPA also lowers the MMI rates but not to the same extent. EVT-treated patients had increased survival rates (p < 0.05) and the best functional outcome at discharge. CONCLUSIONS The findings of this study illustrate that occurrence of MMI and mortality rates was significantly reduced in patients treated with EVT.


title: Parent artery occlusion in large, giant, or fusiform aneurysms of the carotid siphon: clinical and imaging results.

text: BACKGROUND AND PURPOSE Parent artery occlusion has long been considered the reference treatment for large/giant or fusiform aneurysms of the carotid siphon. However, meager recent data exist on this technique, which tends to be replaced by stent-assisted reconstructive techniques. In our department since 2004, we have assessed the safety, efficacy, and complication risk factors of parent artery occlusion by using coils for trapping these aneurysms. MATERIALS AND METHODS We determined retrospectively the complication rate, factors associated with the occurrence of an ischemic event, changes in symptoms of mass effect, evolution of the aneurysmal size, and the growth of an additional aneurysm after treatment. RESULTS Fifty-six consecutive patients were included, with a median age of 54 years (range, 25-85 years; 92% women), 48% with giant aneurysms and 75% with infraclinoid aneurysms. There was a permanent morbidity rate of 5% exclusively due to ischemia, a zero mortality rate, an aneurysmal retraction rate of 91%, and an improvement rate for pain of 98% and for cranial nerve palsy of 72%, with a median follow-up of >3 years. Para-/supraclinoid topography of the aneurysm (P = .043) and the presence of cardiovascular risk factors (P = .024) were associated with an excessive risk of an ischemic event, whereas the presence of a mural thrombus had a protective role (P = .033). CONCLUSIONS In this study, parent artery occlusion by using coils to treat large/giant or fusiform aneurysms of the carotid siphon was safe and effective, especially for giant infraclinoid aneurysms. According to recent meta-analyses, these results suggest that the validation of stent-assisted reconstructive treatments for these aneurysms requires controlled studies with parent occlusion artery.


title: Comparison of Surgical Outcomes of Robotic and Conventional Approaches in Patients with Pre- and Poststyloid Parapharyngeal Space Tumors.

text: BACKGROUND Benefits and drawbacks of robotic surgical approaches for parapharyngeal space (PPS) tumors remain undetermined. The purpose of this study is to compare surgical outcomes of PPS tumor patients who underwent robotic surgery with those of patients who received conventional surgical treatment. PATIENTS AND METHODS We retrospectively analyzed clinicopathologic data from 136 patients who underwent surgical removal of PPS tumors via conventional or robotic approaches. RESULTS We identified PPS tumors in pre- and poststyloid regions in 87 (64%) and 49 (36%) patients, respectively. There were 48 (35.3%) pleomorphic adenomas, 36 (26.5%) schwannomas, and 24 (17.6%) paragangliomas. Conventional surgical techniques were performed in 83 patients, and robotic surgical approaches were administered to 53 patients. Transcervical-parotid and transcervical approaches were most commonly performed in conventional surgery, while transoral and retroauricular approaches were the preferred surgical methods in robotic surgery for pre- and poststyloid PPS tumors, respectively. Robotic surgery resulted in less estimated blood loss during poststyloid PPS tumor surgery. Postoperative cranial nerve complications were noted in 36 of 83 cases (43.4%) in the conventional surgery group and in 17 of 53 cases (32.1%) in the robotic surgery group. Intraoperative tumor spillage of pleomorphic adenoma showed no significant differences between the two groups (13.6% in conventional vs. 15.4% in robotic surgery). The mean follow-up time was 4.9 ± 3.4 years, and recurrences were observed in two patients during follow-up without a significant difference between the two groups (4.5% in conventional vs. 3.8% in robotic surgery). CONCLUSIONS Robotic surgery in PPS tumors is feasible through transoral, retroauricular, or combined approaches and provides treatment outcomes comparable to those of conventional open surgery.


title: Comparative Study of the Effect of Warming at Various Temperatures on Biochemical, Hematologic, and Hemodynamic Parameters During Spinal Fusion Surgery Under Intravenous Anesthesia.

text: Background Perioperative inadvertent hypothermia (PIH) commonly occurs after major surgical procedures under local or general anesthesia and increases the risk of complications such as organ failure, hypoperfusion, and peripheral vasoconstriction, as well as adverse postoperative outcomes, such as wound infection and increased surgical bleeding. Objectives We hypothesized that the intra-operative warming may affect these complications and thus, we aimed to compare the most appropriate temperature of the warmer to decrease patients' complications. Methods The present randomized clinical trial investigated 90 patients undergoing total intravenous anesthesia in posterior spinal fusion surgery, randomly divided into two groups of 45. The warmer was set at 38°C for group "A" during surgery and at 40°C for group "B." Patient's demographic characteristics, the serum level of hemoglobin, hematocrit, and platelet counts, mean core temperature, systolic blood pressure (BP), heart rate, and respiratory rate were recorded before and after the surgery. Variables were compared between the two groups at three time intervals (during induction, during operation, and during recovery). Results The mean temperature was not different between the two groups at the three time intervals. Other laboratory serum tests, vital signs, and oxygen consumption were maintained within the normal range although they did not improve significantly in two groups at the three time intervals. Conclusions There was no significant difference in warming of the patients during operation at 38 or 40°C to prevent hypothermia-induced complications during induction, operation, and recovery.


title: Navigating the Pandemic Response Life Cycle: Molecular Diagnostics and Immunoassays in the Context of COVID-19 Management.

text: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To counter COVID-19 spreading, an infrastructure to provide rapid and thorough molecular diagnostics and serology testing is the cornerstone of outbreak and pandemic management. We hereby review the clinical insights with regard to using molecular tests and immunoassays in the context of COVID-19 management life cycle: the preventive phase, the preparedness phase, the response phase and the recovery phase. The spatial and temporal distribution of viral RNA, antigens and antibodies during human infection is summarized to provide a biological foundation for accurate detection of the disease. We shared the lessons learned and the obstacles encountered during real world high-volume screening programs. Clinical needs are discussed to identify existing technology gaps in these tests. Leverage technologies, such as engineered polymerases, isothermal amplification, and direct amplification from complex matrices may improve the productivity of current infrastructure, while emerging technologies like CRISPR diagnostics, visual end point detection, and PCR free methods for nucleic acid sensing may lead to at-home tests. The lessons learned, and innovations spurred from the COVID-19 pandemic could upgrade our global public health infrastructure to better combat potential outbreaks in the future.


docid: vfbyqghs

title: Unbiased parallel detection of viral pathogens in clinical samples by use of a metagenomic approach.

text: Viral infectious diseases represent a major threat to public health and are among the greatest disease burdens worldwide. Rapid and accurate identification of viral agents is crucial for both outbreak control and estimating regional disease burdens. Recently developed metagenomic methods have proven to be powerful tools for simultaneous pathogen detection. Here, we performed a systematic study of the capability of the short-read-based metagenomic approach in the molecular detection of viral pathogens in nasopharyngeal aspirate samples from patients with acute lower respiratory tract infections (n = 16). Using the high-throughput capacity of ultradeep sequencing and a dedicated data interpretation method, we successfully identified seven species of known respiratory viral agents from 15 samples, a result that was consistent with results of conventional PCR assays. We also detected a coinfected case that was missed by regular PCR testing. Using the metagenomic data, 11 draft genomes of the abundantly detected viruses in the samples were reconstructed with 21.84% to 98.53% coverage. Our results show the power of the short-read-based metagenomic approach for accurate and parallel screening of viral pathogens. Although there are some inherent difficulties in applying this approach to clinical samples, including a lack of controls, limited specimen quantity, and high contamination rate, our work will facilitate further application of this unprecedented high-throughput method to clinical samples.


Management of COVID-19 Respiratory Distress.


Number needed to treat and cost-effectiveness in the prevention of ventilator-associated pneumonia.


title: Psychological effects and associated factors of COVID-19 in a Mexican sample.

text: OBJECTIVE The coronavirus disease 2019 (COVID 19) is a new viral zoonosis of global concern that could cause psychological sequelae. We examined the levels of psychological distress, anxiety, depression, and stress during the COVID-19 outbreak in a Mexican sample. METHODS An online survey was applied which collected information on demographic and financial status data, physical status, contact history, knowledge, concerns, and precautionary measures concerning COVID-19. Impact of Event Scale-Revised and Depression, Anxiety and Stress Scale were included. RESULTS 50.3% of respondents rated psychological distress as moderate-severe; 15.7% reported moderate-severe depressive symptoms; 22.6% reported moderate-severe anxiety symptoms; and 19.8% reported moderate-severe stress levels. Female gender, older age, divorced status, lack confidence related to security of the test, lower satisfaction of health information concerning COVID-19, history of direct or indirect contact with a COVID-19 confirmed case, live with just one other person and spent >9h per day at home were associated with greater psychological distress and/or higher levels of stress, anxiety, and depression. By contrast, precautionary measures as hand hygiene and wearing masks were associated with lower levels of psychological distress, depression, anxiety, and stress. CONCLUSIONS COVID-19 outbreak results in considerable psychological effects among the Mexican sample.


Letter from China: covid-19 on the grapevine, on the internet, and in commerce.


title: Addressing multiple gastroenterological aspects of COVID-19.

text: The outbreak of coronavirus disease 2019 (COVID-19) pandemic has become the biggest challenge for the whole human community since many years. It seems that the appropriate identification of all people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the best strategy to limit COVID-19 transmission. However, in a significant proportion of patients, there are no clinical manifestations of the disease, symptoms may be very mild or atypical. There is a growing body of evidence that digestive manifestations of COVID-19 are frequently reported and may precede typical respiratory symptoms. Moreover, the presence of SARS-CoV-2 particles was shown in the gastrointestinal epithelial cells, and viral RNA was detected in the feces of COVID-19 patients. These data suggest that gastrointestinal symptoms in COVID-19 are not an accidental finding, but they may result from direct digestive involvement. Patients with new-onset diarrhea, abdominal pain, nausea, vomiting without any other evident etiological factors should be tested for SARS-CoV-2 infection. Gastroenterologists and members of other medical specialties should also remember that the current epidemiological situation has changed diagnostic and therapeutic algorithms in several gastrointestinal and liver disorders. The paper summarizes the currently available data on multiple gastroenterological aspects of COVID-19 and provides practical recommendations and position statements submitted by the most prominent associations in the field of gastroenterology in response to the emergence of the pandemic.


Commentary: Revisiting the methods of corneal preservation in the COVID-19 era.


The new age of molecular diagnostics for microbial agents.


title: Collagen implants in inguinal and ventral hernia repair.

text: Collagen has been used in various medical fields and more recently serves as matrix for biomeshes in hernia repair. Meshes derived from organic sources have been designed to reduce foreign body reaction, seromas, adhesions, limited integration, and mesh infection that are frequently found with synthetic meshes. However, synthetic meshes made from polymer materials, e.g., polypropylene or polyester represent the standard of care in both open and laparoscopic inguinal and ventral hernia repair. This review aims to outline the current state of collagen implants and to investigate their potential to replace or compete with synthetic products. Unfortunately, literature reveals a discrepancy between cautious reports and a growing number of acclaiming studies. Special attention has therefore been paid to experimental data of adequate animal models, providing second look data and histology.


title: Time-Resolved C-Arm Computed Tomographic Angiography Derived From Computed Tomographic Perfusion Acquisition: New Capability for One-Stop-Shop Acute Ischemic Stroke Treatment in the Angiosuite.

text: BACKGROUND AND PURPOSE Multimodal imaging using cone beam C-arm computed tomography (CT) may shorten the delay from ictus to revascularization for acute ischemic stroke patients with a large vessel occlusion. Largely because of limited temporal resolution, reconstruction of time-resolved CT angiography (CTA) from these systems has not yielded satisfactory results. We evaluated the image quality and diagnostic value of time-resolved C-arm CTA reconstructed using novel image processing algorithms. METHODS Studies were done under an Institutional Review Board approved protocol. Postprocessing of data from 21 C-arm CT dynamic perfusion acquisitions from 17 patients with acute ischemic stroke were done to derive time-resolved C-arm CTA images. Two observers independently evaluated image quality and diagnostic content for each case. ICC and receiver-operating characteristic analysis were performed to evaluate interobserver agreement and diagnostic value of this novel imaging modality. RESULTS Time-resolved C-arm CTA images were successfully generated from 20 data sets (95.2%, 20/21). Two observers agreed well that the image quality for large cerebral arteries was good but was more limited for small cerebral arteries (distal to M1, A1, and P1). receiver-operating characteristic curves demonstrated excellent diagnostic value for detecting large vessel occlusions (area under the curve=0.987-1). CONCLUSIONS Time-resolved CTAs derived from C-arm CT perfusion acquisitions provide high quality images that allowed accurate diagnosis of large vessel occlusions. Although image quality of smaller arteries in this study was not optimal ongoing modifications of the postprocessing algorithm will likely remove this limitation. Adding time-resolved C-arm CTAs to the capabilities of the angiography suite further enhances its suitability as a one-stop shop for care for patients with acute ischemic stroke.


Doctors race to understand inflammatory condition in kids.


title: Effectiveness of Trevo stent retriever in acute ischemic stroke: Comparison with Solitaire stent.

text: Recently, mechanical thrombectomy with stent retriever has achieved faster and higher rates of recanalization for intracranial major vessel occlusion. However, comparative studies of the most widely used Solitaire and Trevo stents have been rarely published.The authors retrospectively reviewed a total of 200 patients who performed mechanical thrombectomy at our center during 4 years and divided patients into 2 groups: mechanical thrombectomy with Solitaire stent (Group 1: Solitaire) and mechanical thrombectomy with Trevo stent (Group 2: Trevo). All patients underwent a clinical assessment with National Institutes of Health Stroke Scale (NIHSS) score and underwent modified Rankin Scale (mRS) score. Radiologic results were evaluated using thrombolysis in cerebral infarction (TICI) score and number of stent passes. In addition, multiple time intervals were analyzed.There was no statistically significant difference in clinical outcome between the 2 groups. Trevo group revealed the shorter procedure time, less number of stent passage, and more one pass cases than Solitaire group with statistically significance (P = .009, P = .014, P = .030). In addition, Trevo group achieved higher successful recanalization (TICI 2b or 3) rate (89.7%) with statically significant than group1 (82.3%) (P = .018). In multivariate logistic regression analysis, the use of Trevo stent was a predictive for successful recanalization. (odds ratio 1.40, 95% confidence interval 1.250-1.550, P = .028).Our study suggests that the Trevo stent allows higher recanalization rate through the less number of stent passages and shorter procedure time than the Solitaire stent. More randomized control trials are needed to determine which stents are more effective.


title: Practical Considerations for Treating Patients With Cancer in the COVID-19 Pandemic.

text: Cancer has become a prevalent disease, affecting millions of new patients globally each year. The COVID-19 pandemic is having far-reaching impacts around the world, causing substantial disruptions to health and health care systems that are likely to last for a prolonged period. Early data have suggested that having cancer is a significant risk factor for mortality from severe COVID-19. A diverse group of medical oncologists met to formulate detailed practical advice on systemic anticancer treatments during this crisis. In the context of broad principles, issues including risks of treatment, principles of prioritizing resources, treatment of elderly patients, and psychosocial impact are discussed. Detailed treatment advice and options are given at a tumor stream level. We must maintain care for patients with cancer as best we can and recognize that COVID-19 poses a significant competing risk for death that changes conventional treatment paradigms.


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title: Porcine aminopeptidase N is not a cellular receptor of porcine epidemic diarrhea virus, but promotes its infectivity via aminopeptidase activity.

text: Porcine epidemic diarrhea virus (PEDV), a causative agent of pig diarrhoea, has recently caused significant economic damage worldwide. Porcine aminopeptidase N (pAPN) has been reported to be the receptor for PEDV, although robust evidence is lacking. In the present study, we explored whether pAPN functions as a receptor for PEDV. Human HeLa cells expressing pAPN and pAPN-positive porcine CPK cells failed to support PEDV infection, but were susceptible to infection by transmissible gastroenteritis virus (TGEV), which utilizes pAPN as a functional receptor. In contrast to TGEV, PEDV did not bind soluble porcine aminopeptidases (pAPs) and infection was not inhibited by the soluble form of pAPs. However, overexpression of pAPN in porcine CPK cells (CPK-pAPN cells) slightly increased the production of PEDV, and the increased replication in CPK-pAPN cells was inhibited by bestatin, an inhibitor of the protease activity of aminopeptidase N. These results suggest that pAPN is not a functional receptor for PEDV, but promotes the infection of PEDV through its protease activity.


title: From self-sorted coordination libraries to networking nanoswitches for catalysis.

text: This feature article sketches our long way from the development of dynamic heteroleptic coordination motifs to the self-sorting of multi-component libraries and finally the design of a new family of triangular nanomechanical switches, which are useful for ON-OFF control of catalysis and in bidirectional communication. Due to their orthogonal switching stations, the nanoswitches have evolved as powerful toggles to even control two catalytic processes in an alternate manner, ON-OFF photosensitization and redox-controlled communication in small networks. The near future will show whether these nanoswitches can be interdependently linked together in autonomously regulated catalytic networks.


title: Contemporary systematic review and meta-analysis of early outcomes with percutaneous treatment for infrapopliteal atherosclerotic disease.

text: PURPOSE The need for specialty devices to improve the technical outcome of endovascular interventions is dependent on the rate of early failure in such procedures. This meta-analysis assessed procedural outcomes of such interventions to elucidate the rate of early procedural failures and the need for such specialty devices. MATERIALS AND METHODS MEDLINE and EMBASE were searched for contemporary studies (2000-2012) reporting procedural or short-term outcomes for revascularization of infrapopliteal atherosclerotic lesions. A random-effects metaanalysis was performed, which included post hoc comparisons among treatment groups. RESULTS A total of 42 studies with 52 treatment arms representing 3,660 unique patients were included. Technical success rates were higher with bare metal stents (BMSs; 98.6%) than with atherectomy (92.2%; P < .05) or percutaneous transluminal angioplasty (PTA; 91.2%; P = .01), and higher with drug-eluting stents (DESs) than with PTA (P < .001). DES use had higher primary patency rates than atherectomy (P < .05), BMS use (P < .001), and PTA (P < .01). The 30-day rate of target lesion revascularization was significantly higher with PTA (8.1%) than with BMSs (2.2%; P < .05) and DESs (1.1%; P < .05). Thirty-day rates of major unplanned amputation (range, 1.5%-4.4%) and mortality (range, 0.9%-3.3%) were comparable among treatment groups. Significant heterogeneity among studies was noted for most PTA outcomes. Publication bias was evident for most PTA and DES outcomes. CONCLUSIONS Early failure of percutaneous therapies in patients with infrapopliteal atherosclerotic lesions is device- and technique-dependent. Specialty devices designed to reduce technical failure rates may therefore be of benefit in this selected group of patients. Study results are confounded by inconsistent data reporting, heterogeneity of treatment effects, and publication bias.


title: The whole truth and nothing but the truth: the need for full reporting of randomised trials.

text: The use of cardiac output monitoring to guide fluid and inotropic therapy in surgical patients has remained a controversial topic for more than 40 years. The reasons for this are numerous and complex, but key amongst them is the interplay between poor research methodology and the likely selective reporting of randomised trials. In this issue of Perioperative Medicine, we find a very unusual report, one which describes a randomised trial stopped for futility after the recruitment of only a small proportion of the target patient sample (Jammer et al. Periop Med). The authors offer no statistical analysis of their findings but simply an explanation of what went wrong. On the face of it, this exercise would seem to offer little of value to the general reader. How can publication of the findings of an unsuccessful trial contribute to the evidence base on this topic? To understand this, we must delve a little deeper into the evidence and see how these trials were designed.


A Towering Babel of Risk Information in the COVID-19 Pandemic: Trust and Credibility in Risk Perception and Positive Public Health Behaviors.


Comment on: comparison of endostapler performance in challenging tissue applications.


title: Northern Ireland disease surveillance report, October to December 2013.

text: • Otitis media associated with Mycoplasma bovis infection in calves. • Yew poisoning in a calf. • Jaagsiekte in sheep. • Fasciolosis and copper toxicity in sheep. These are among matters discussed in the Northern Ireland animal disease surveillance quarterly report for October to December 2013.


title: Severe acute respiratory syndrome coronavirus replication inhibitor that interferes with the nucleic acid unwinding of the viral helicase.

text: Severe acute respiratory syndrome (SARS) is a highly contagious disease, caused by SARS coronavirus (SARS-CoV), for which there are no approved treatments. We report the discovery of a potent inhibitor of SARS-CoV that blocks replication by inhibiting the unwinding activity of the SARS-CoV helicase (nsp13). We used a Förster resonance energy transfer (FRET)-based helicase assay to screen the Maybridge Hitfinder chemical library. We identified and validated a compound (SSYA10-001) that specifically blocks the double-stranded RNA (dsRNA) and dsDNA unwinding activities of nsp13, with 50% inhibitory concentrations (IC(50)s) of 5.70 and 5.30 μM, respectively. This compound also has inhibitory activity (50% effective concentration [EC(50)] = 8.95 μM) in a SARS-CoV replicon assay, with low cytotoxicity (50% cytotoxic concentration [CC(50)] = >250 μM), suggesting that the helicase plays a still unidentified critical role in the SARS-CoV life cycle. Enzyme kinetic studies on the mechanism of nsp13 inhibition revealed that SSYA10-001 acts as a noncompetitive inhibitor of nsp13 with respect to nucleic acid and ATP substrates. Moreover, SSYA10-001 does not affect ATP hydrolysis or nsp13 binding to the nucleic acid substrate. SSYA10-001 did not inhibit hepatitis C virus (HCV) helicase, other bacterial and viral RNA-dependent RNA polymerases, or reverse transcriptase. These results suggest that SSYA10-001 specifically blocks nsp13 through a novel mechanism and is less likely to interfere with the functions of cellular enzymes that process nucleic acids or ATP. Hence, it is possible that SSYA10-001 inhibits unwinding by nsp13 by affecting conformational changes during the course of the reaction or translocation on the nucleic acid. SSYA10-001 will be a valuable tool for studying the specific role of nsp13 in the SARS-CoV life cycle, which could be a model for other nidoviruses and also a candidate for further development as a SARS antiviral target.


In reply to: Helmich and Bloem (2020) "The Impact of the COVID-19 Pandemic on Parkinson's Disease: Hidden Sorrows and Emerging Opportunities".


title: Remodulation of neurosurgical activities in an Italian region (Emilia-Romagna) under COVID- 19 emergency: maintaining the standard of care during the crisis.

text: BACKGROUND The impact of COVID-19 outbreak in the neurosurgical practice has been dramatic, imposing several limitations. The aim of this study is to present how the neurosurgical departments of Emilia-Romagna, a northern Italian region, have re-set their organization to maintain the higher standard of care as possible. METHODS All OR and out-patients activities performed during the COVID-19 emergency in the neurosurgical department of Emilia-Romagna have been collected and compared to the means of the same timeframe in 2018 and 2019. RESULTS In 2020, 205 surgical procedures and 466 out-patients consultations have been performed, representing respectively 28.8% and 26.4% of the previous biennium. The most of OR procedures had been emergencies/urgencies and oncological patients (respectively 113 and 66 vs 164.5 and 84.5 of the previous biennium), while elective surgeries decrease up to -97.1%, as for spinal nerves and endoscopic skull base procedures. The patients phone contacts and telemedicine evaluations of their examinations have permitted to reduce the hospital access for outpatients of 75.6%, but these modalities have, also, permitted to follow-up a large number of cases. CONCLUSIONS The outbreak of COVID-19 has imposed several limits to our current practice, however this should not represent an excuse to reduce the standard of care. In our experience, the net integration of different local centers has permitted for each of them to effectively cope the crisis, managing the local cases requiring a prompt surgery and keeping the care continuity with already discharged patients.