title: Bovine coronavirus nonstructural protein 1 (p28) is an RNA binding protein that binds terminal genomic cis-replication elements.

text: Nonstructural protein 1 (nsp1), a 28-kDa protein in the bovine coronavirus (BCoV) and closely related mouse hepatitis coronavirus, is the first protein cleaved from the open reading frame 1 (ORF 1) polyprotein product of genome translation. Recently, a 30-nucleotide (nt) cis-replication stem-loop VI (SLVI) has been mapped at nt 101 to 130 within a 288-nt 5'-terminal segment of the 738-nt nsp1 cistron in a BCoV defective interfering (DI) RNA. Since a similar nsp1 coding region appears in all characterized groups 1 and 2 coronavirus DI RNAs and must be translated in cis for BCoV DI RNA replication, we hypothesized that nsp1 might regulate ORF 1 expression by binding this intra-nsp1 cistronic element. Here, we (i) establish by mutation analysis that the 72-nt intracistronic SLV immediately upstream of SLVI is also a DI RNA cis-replication signal, (ii) show by gel shift and UV-cross-linking analyses that cellular proteins of approximately 60 and 100 kDa, but not viral proteins, bind SLV and SLVI, (SLV-VI) and (iii) demonstrate by gel shift analysis that nsp1 purified from Escherichia coli does not bind SLV-VI but does bind three 5' untranslated region (UTR)- and one 3' UTR-located cis-replication SLs. Notably, nsp1 specifically binds SLIII and its flanking sequences in the 5' UTR with approximately 2.5 muM affinity. Additionally, under conditions enabling expression of nsp1 from DI RNA-encoded subgenomic mRNA, DI RNA levels were greatly reduced, but there was only a slight transient reduction in viral RNA levels. These results together indicate that nsp1 is an RNA-binding protein that may function to regulate viral genome translation or replication but not by binding SLV-VI within its own coding region.


title: Metagenomic sequencing for virus identification in a public-health setting.

text: The use of metagenomics for virus discovery in clinical samples has opened new opportunities for understanding the aetiology of unexplained illness. This study explores the potential of this sequence-independent approach in a public-health setting, by systematic analysis of samples cultured from patients with unexplained illness through a combination of PCR-based assays and viral metagenomics. In total, 1834 cell-culture isolates were collected between 1994 and 2007 through the Enterovirus Surveillance programme in the Netherlands. During the 13 year period, seven samples that exhibited reproducible cytopathogenic effects in cell culture tested negative in standard PCR assays for a range of viruses. In order to fill the diagnostic gap, viral metagenomics was applied to these culture supernatants, resulting in the rapid identification of viruses in all of the samples. The unexplained samples contained BK polyomavirus, herpes simplex virus, Newcastle disease virus and the recently discovered Saffold viruses (SAFV) (which dominated the unexplained samples; n=4). The full genomic sequences of four SAFV genotype 3 (SAFV-3) viruses, which share 88-93 % nucleotide identity with known SAFV-3 viruses, are reported. Further screening for SAFV in additional cultured, unidentified clinical isolates from 2008 and 2009 resulted in identification of another SAFV-positive sample. Although the pathogenicity of the identified viruses has not been established, this study demonstrates that viral metagenomics is a powerful tool that can be integrated into public-health monitoring efforts to investigate unidentified viruses in cell cultures from clinical isolates where standard PCR assays fail to detect viruses.


title: The Prevalence of Nonadherence in Patients With Resistant Hypertension: A Systematic Review Protocol.

text: Background Resistant hypertension, usually defined as blood pressure remaining above goal despite the concurrent use of 3 or more antihypertensive agents of different classes, is common (about 10% prevalence) and known to be a risk factor for cardiovascular events. These patients also undergo more screening intensity for secondary hypertension. However, not all patients with apparent treatment-resistant hypertension have true resistant hypertension, with some of them being nonadherent to prescribed pharmacotherapy. The prevalence of nonadherence varies from about 5% to 80% in the published literature. However, the relative contributions of intentional and nonintentional nonadherence are not well described. Nonintentional nonadherence refers to occasional forgetfulness and/or carelessness and can sometimes be related to an inability to follow instructions, because of either cognitive or physical limitations. Intentional nonadherence refers to an active process in which a patient may choose to alter the prescribed medication regimen by discontinuing medications, skipping doses, or modifying doses or dosing intervals. Objective Our objective is to establish the overall prevalence of nonadherence in the apparent treatment-resistant hypertension population and evaluate the relative contributions of nonintentional and intentional nonadherence subtypes. Design We will conduct a systematic review and meta-analysis. Setting We will include observational studies and randomized controlled trials where adherence to antihypertensive medications is measured using a test of adherence, either direct or indirect. Patients We will include adult human participants aged 18 years or older with a diagnosis of resistant hypertension. Measurements Data extracted from individual studies will include title, first author, design, country, publication year, funding body, method of assessing adherence to antihypertensive medication, prevalence of medication nonadherence, definition of resistant hypertension, sample size, sex, mean age, and coexistent comorbidities. Methods A librarian will search the databases Medline, EMBASE, Cochrane, CINAHL, and Web of Science for studies meeting criteria for inclusion. Two reviewers will independently screen the titles and abstracts retrieved and assess the methodological quality of eligible full-text articles using the Cochrane Risk of Bias tool for clinical trials and the Newcastle-Ottawa Scale for observational studies. Summary estimates of prevalence will be generated using pooled analysis using the random-effects method. Subgroup analyses, sensitivity analyses, and evaluation of publication bias will also be performed. Results The outcomes of interest are the pooled prevalence of nonadherence to antihypertensive medication in apparent treatment-resistant hypertension and the prevalence of nonadherence based on different methods of assessing nonadherence (indirect vs direct), which will allow us to estimate the relative proportion of unintentional and intentional nonadherence subtypes in the overall phenomenon of medication nonadherence. Limitations Possible limitations of this study include the finding of severe heterogeneity, the limitations of the literature search, publication bias, and the lack of granular data in the published studies for a study-level meta-analysis. Conclusions This systematic review will provide a synthesis of current evidence on the prevalence of medication nonadherence in apparent treatment-resistant hypertension and on the relative contributions of nonintentional and intentional nonadherence subtypes. These findings will provide clinicians with a better understanding of the factors underlying treatment-resistant hypertension and will serve as a strong research base to guide future research on interventions to address medication nonadherence as well as the nonintentional and intentional subtypes. Trial registration This protocol has been registered with PROSPERO. We will add registration details once available.


title: Safety and feasibility of single-incision laparoscopic cholecystectomy in obese patients.

text: BACKGROUND Current literature frequently indicates that experienced laparoscopic surgeons can safely perform single-incision laparoscopic cholecystectomy, but there have been few reports evaluating the feasibility and safety of performing single-incision laparoscopic cholecystectomy for obese patients. Therefore, a large single-center database was retrospectively reviewed to evaluate the feasibility and safety of single-incision laparoscopic cholecystectomy for obese patients by comparing the outcomes of normal-weight and obese patients undergoing single-incision laparoscopic cholecystectomy. METHODS A retrospective analysis of 608 patients undergoing SILC between May 2009 and May 2015 at Osaka Police Hospital was performed, and the outcomes of obese [body mass index (BMI) ≥ 30 kg/m2] and normal-weight patients (18.5 ≤ BMI < 25 kg/m2) were compared. RESULTS Thirty-eight obese patients (mean BMI 32.5 kg/m2) were compared to 362 normal-weight patients (mean BMI 22.0 kg/m2). The American Society of Anesthesiologists (ASA) scores of the obese patients were significantly higher than those of normal-weight patients. The mean operative times in the normal-weight and the obese groups were 110 min vs. 127 min, respectively (p < 0.05). There were no significant differences in the bleeding volume and the conversion rate to a different operative procedure. Perioperative complications were seen in 6% (23/362) of the patients in the normal-weight group and 8% (3/38) of the patients in the obese group (p = 0.7). The mean postoperative hospital stay was 4.5 days for the normal-weight group and 4.4 days for the obese group (p = 0.8). CONCLUSIONS Single-incision laparoscopic cholecystectomy, which offers good cosmetic outcomes, seems feasible and safe in obese patients.


docid: jymfbfau

title: New approaches to sepsis: molecular diagnostics and biomarkers.

text: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.


Did COVID-19 early lockdown actually lead to a higher rate of relapses in psychiatric patients?


title: Infectious pathogens and bronchiolitis outcomes.

text: Bronchiolitis is a common early childhood illness and an important cause of morbidity, it is the number one cause of hospitalization among US infants. Bronchiolitis is also an active area of research, and recent studies have advanced our understanding of this illness. Although it has long been the conventional wisdom that the infectious etiology of bronchiolitis does not affect outcomes, a growing number of studies have linked specific pathogens of bronchiolitis (e.g., rhinovirus) to short- and long-term outcomes, such as future risk of developing asthma. The authors review the advent of molecular diagnostic techniques that have demonstrated diverse pathogens in bronchiolitis, and they review recent studies on the complex link between infectious pathogens of bronchiolitis and the development of childhood asthma.


title: Study of the impact of tissue density heterogeneities on 3-dimensional abdominal dosimetry: comparison between dose kernel convolution and direct Monte Carlo methods.

text: UNLABELLED Dose kernel convolution (DK) methods have been proposed to speed up absorbed dose calculations in molecular radionuclide therapy. Our aim was to evaluate the impact of tissue density heterogeneities (TDH) on dosimetry when using a DK method and to propose a simple density-correction method. METHODS This study has been conducted on 3 clinical cases: case 1, non-Hodgkin lymphoma treated with (131)I-tositumomab; case 2, a neuroendocrine tumor treatment simulated with (177)Lu-peptides; and case 3, hepatocellular carcinoma treated with (90)Y-microspheres. Absorbed dose calculations were performed using a direct Monte Carlo approach accounting for TDH (3D-RD), and a DK approach (VoxelDose, or VD). For each individual voxel, the VD absorbed dose, D(VD), calculated assuming uniform density, was corrected for density, giving D(VDd). The average 3D-RD absorbed dose values, D(3DRD), were compared with D(VD) and D(VDd), using the relative difference Δ(VD/3DRD). At the voxel level, density-binned Δ(VD/3DRD) and Δ(VDd/3DRD) were plotted against ρ and fitted with a linear regression. RESULTS The D(VD) calculations showed a good agreement with D(3DRD). Δ(VD/3DRD) was less than 3.5%, except for the tumor of case 1 (5.9%) and the renal cortex of case 2 (5.6%). At the voxel level, the Δ(VD/3DRD) range was 0%-14% for cases 1 and 2, and -3% to 7% for case 3. All 3 cases showed a linear relationship between voxel bin-averaged Δ(VD/3DRD) and density, ρ: case 1 (Δ = -0.56ρ + 0.62, R(2) = 0.93), case 2 (Δ = -0.91ρ + 0.96, R(2) = 0.99), and case 3 (Δ = -0.69ρ + 0.72, R(2) = 0.91). The density correction improved the agreement of the DK method with the Monte Carlo approach (Δ(VDd/3DRD) < 1.1%), but with a lesser extent for the tumor of case 1 (3.1%). At the voxel level, the Δ(VDd/3DRD) range decreased for the 3 clinical cases (case 1, -1% to 4%; case 2, -0.5% to 1.5%, and -1.5% to 2%). No more linear regression existed for cases 2 and 3, contrary to case 1 (Δ = 0.41ρ - 0.38, R(2) = 0.88) although the slope in case 1 was less pronounced. CONCLUSION This study shows a small influence of TDH in the abdominal region for 3 representative clinical cases. A simple density-correction method was proposed and improved the comparison in the absorbed dose calculations when using our voxel S value implementation.


Public health and infections: Health in Sweden: The National Public Health Report 2012. Chapter 15.


title: Stereotactic Radiofrequency Ablation of Hepatocellular Carcinoma: a Histopathological Study in Explanted Livers.

text: This retrospective study was performed to evaluate the efficacy of three-dimensional (3D)-navigated multiprobe radiofrequency ablation (RFA) with intraprocedural image fusion for treatment of hepatocellular carcinoma (HCC) by histopathological examination. From 2009 to 2018, 97 patients (84 men, 13 women; median age, 60 years; range, 1-71) were transplanted after bridging therapy of 195 HCCs by stereotactic RFA (SRFA). The median interval between the first SRFA and transplantation was 6.8 months (range, 0-71). The rate of residual vital tissue (RVT) could be assessed in 188 of 195 lesions in 96 of 97 patients by histological examination of the explanted livers using hematoxylin and eosin (H&E) and Tdt-mediated UTP nick-end labeling (TUNEL) stains. Histopathological results were compared with the findings of the last computed tomography (CT) imaging before liver transplantation (LT). Median number and size of treated tumors were 1 (range, 1-8) and 2.5 cm (range, 1-8). Complete radiological response was achieved in 186 of 188 nodules (98.9%) and 94 of 96 patients (97.9%) and complete pathological response in the explanted liver specimen in 183 of 188 nodules (97.3%) and 91 of 96 patients (94.8%), respectively. In lesions ≥3 cm, complete tumor cell death was achieved in 50 of 52 nodules (96.2%). Residual tumor did not correlate with tumor size (P = 0.5). Conclusion: Multiprobe SRFA with intraprocedural image fusion represents an efficient, minimally invasive therapy for HCC, even with tumor sizes larger than 3 cm, and without the need of a combination with additional treatments. The results seem to justify the additional efforts related to the stereotactic approach.


Management of Care for Neonates Born to SARS-CoV-2 Positive Women with or without Clinical Symptoms (COVID-19).


title: Radiofrequency ablation for Barrett's dysplasia: past, present and the future?

text: Barrett's oesophagus is the only know pre-cursor to oesophageal adenocarcinoma. The incidence of OAC is growing rapidly in the western world with a poor prognosis for most with a 5-year survival of only 15%. The approach to treating patients with neoplasia arising within BE has dramatically changed in the past 5 years. Resection of visible lesions with endoscopic mucosal resection followed by field ablation with radio-frequency ablation is now the accepted standard of care in these patients worldwide. This combined approach has shown high rates of disease reversal in several high quality clinical trials but also large volume registry studies. As well as being a minimally invasive and oesophageal sparing interventions compared to surgery with oesophagectomy, endoscopic therapy has proved to be safe and emerging long-term data show sustained benefit in the majority of patients and low rates of cancer progression. However, in a sub-group of patients, recurrences have been reported after successful endoscopic therapy making it mandatory to follow these patients post therapy. Improvements in endoscopic imaging continue to aid early diagnosis, and in turn, this will allow clinicians the ability to offer patient's treatment at an early stage.


title: Single port access laparoscopic-assisted vaginal hysterectomy for large uterus weighing exceeding 500 grams: technique and initial report.

text: STUDY OBJECTIVE To present our initial experience with single-port access laparoscopic-assisted vaginal hysterectomy (SPA-LAVH) in a large uterus weighing in excess of 500 g. DESIGN A prospective single-center study (Canadian Task Force classification III). SETTING University hospital PATIENTS Fifteen patients with an extirpated uterine weight of more than 500 g were enrolled from May 2008 to September 2009. INTERVENTIONS SPA-LAVH. MEASUREMENTS AND MAIN RESULTS There were 11 cases with uterine myomas and 4 cases of adenomyosis. All patients had symptoms related to these diagnoses including menorrhagia, dysmenorrhea, and pelvic pressure symptoms such as urinary frequency. The median and range are used to describe data not distributed normally. The median operation time, weight of the uterus, and estimated blood loss were 125 minutes (80 to 236 minutes), 690 g (503 to 1260 g), and 500 mL (150 to 1000 mL), respectively. There was a significant linear correlation between the operation time and the extirpated uterine weight (p<.002). Thirteen procedures were successfully performed with SPA-LAVH. The SPA procedure failed in 2 cases: 1 (uterine weight, 732 g) required 1 ancillary 5-mm port to manipulate with a myoma screw, and in the other we inserted 1 additional 15-mm port to use for a laparoscopic morcellator. There were no umbilical complications, additional procedures, or surgical complications. CONCLUSION The SPA-LAVH procedure for a large uterus weighing in excess of 500 g was as safe and effective as the conventional LAVH. Additional experience and continued investigation are warranted.


docid: brwmgaim

title: The leader proteinase of foot-and-mouth disease virus: structure-function relationships in a proteolytic virulence factor.

text: The leader proteinase (Lpro) of the foot-and-mouth disease virus inhibits the host innate immune response by at least three different mechanisms. The most well-characterised of these is the prevention of the synthesis of cytokines such as interferons immediately after infection, brought about by specific proteolytic cleavage of the eukaryotic initiation factor 4G. This prevents the recruitment of capped cellular mRNA; however, the viral RNA can be translated under these conditions. The two other mechanisms are the induction of NF-κB cleavage and the deubiquitination of immune signalling molecules. This review focuses on the structure-function relationships in Lpro responsible for these widely divergent activities.


HIV and tuberculosis in Russia and eastern Europe: sounding the alarm.


Patient-centered medical homes offer a model for better, cheaper health care.


title: Initial Experience of ACE68 Reperfusion Catheter in Patients with Acute Ischemic Stroke Related to Internal Carotid Artery Occlusion.

text: OBJECTIVE Penumbra ACE68 reperfusion catheter is a new large bore aspiration catheter used for reperfusion of large vessel occlusion. The objective of this study was to investigate the efficacy of this catheter in comparison to that of previous Penumbra catheters in patients with acute ischemic stroke related to internal carotid artery (ICA) occlusion. METHODS Data of all eligible patients who received endovascular treatment (EVT) for ICA occlusion using Penumbra aspiration catheters between January 2015 and December 2018 were retrospectively reviewed. After dividing into two groups according to use of penumbra ACE68, baseline characteristics of patients, successful recanalization rate, puncture to recanalization time, and switch to stent base technique rate were assessed. Successful recanalization was defined by a thrombolysis in cerebral infarction (TICI) score ≥2b and favorable functional outcome was defined according to modified Rankin scale (score, 0-2). RESULTS ACE68 reperfusion catheter was used in 29 of 75 eligible patients (39%). The puncture to recanalization time was significantly shorter (26±18.2 minutes vs. 40±24.9 minutes, p=0.011) and the rate of switch to stent-based retrieval was significantly lower (3% vs. 20%, p=0.046) in ACE68 catheter group. Moreover, although not statistically significant, the successful recanalization rate was higher (83% vs. 76%, p=0.492) in ACE68 catheter group. Favorable functional outcome was observed in 48% of patients treated with ACE68 reperfusion catheter and in 30% of patients treated using other Penumbra systems (p=0.120). Baseline Alberta Stroke Program Early CT Scores ≥8 (odds ratio [OR], 9.74; 95% confidence interval [CI], 1.72-54.99; p=0.010) and successful recanalization (OR, 10.20; 95% CI, 1.13-92.46; p=0.039) were independent predictors of favorable outcome. CONCLUSION EVT using ACE68 reperfusion catheter can be considered a first-line therapy in patients with acute ICA occlusion as it can achieve rapid recanalization and reduce the frequency of conversion to stent-retrieve therapy.


title: Prevention of contrast-induced nephropathy: an overview.

text: Many unknowns remain concerning how best to reduce a patient's risk of contrast-induced nephropathy (CIN). Many interventions have been proposed, but few have gone unchallenged, and new questions have arisen from analysis of serum creatinine variations in patients who have not been exposed to radiographic iodinated contrast media (RICM). Use of alternate imaging tests that do not use RICM is the most direct way to avoid CIN. Hydration remains the bulwark of intervention when RICM must be administered. The administration of N-acetylcysteine is a popular pharmacologic prophylaxis against CIN but its efficacy is unclear. Hemodialysis has not been effective, but hemofiltration has shown good results in limited series.


Courses and Conferences.


title: Effects of a tissue sealing-cutting device versus monopolar electrocautery on early pilonidal wound healing: a prospective randomized controlled trial.

text: BACKGROUND Monopolar electrocauterization produces thermal effects on neighboring tissues, causing tissue damage. Recently, tissue sealing-cutting devices, which are easy to use and achieve simultaneous selective sealing and cutting with less production of heat, have been used. OBJECTIVE The aim of this study was to investigate the effects of a tissue sealing-cutting device vs monopolar electrocautery on wound healing in the early postoperative period after pilonidal sinus surgery. DESIGN This study was a prospective randomized clinical trial. SETTING This study was conducted at Military Hospital, Eskisehir, Turkey. PATIENTS In total, 128 patients with chronic pilonidal disease were randomly assigned into 2 clinically comparable groups between December 2009 and June 2010. INTERVENTION Pilonidal sinus excision was performed with monopolar electrocautery in the control group (n = 64) and with a tissue sealing-cutting device in the study group (n = 64). Data regarding wound healing, demographic variables, history, physical examination findings, defect dimensions, and scores for a visual analog scale were recorded. MAIN OUTCOME MEASURES The main outcomes measured were surgical site infection, early wound failure (dehiscence), and unhealed wound rate. RESULTS : Wound infection and dehiscence rates were significantly lower (P = .01 and .02), but the duration of surgery was significantly longer (P < .01) in the tissue sealing-cutting group. The unhealed wound rate was 12.5% in the electrocautery group and 4.7% in the tissue sealing-cutting group (P = .01). When the distance from the lowest margin to the anus was 5 cm or less, wound infection and dehiscence rates were lower in the tissue sealing-cutting group (P < .01 and .03). LIMITATIONS We could not obtain data regarding the cost-effectiveness of the instruments. CONCLUSIONS A tissue sealing-cutting device in pilonidal sinus surgery yields better wound healing than monopolar electrocautery.


title: Variations in pH sensitivity, acid stability, and fusogenicity of three influenza virus H3 subtypes.

text: UNLABELLED Influenza A virus strains adapt to achieve successful entry into host species. Entry is mediated by the viral membrane protein hemagglutinin (HA), which triggers membrane fusion and genome release under acidic conditions in the endosome. In addition to changes in the receptor binding domain, the acid stability of HA has been linked to the successful transmission of virus between avian and human hosts. However, to fully understand the connection between changes in HA and host tropism, additional factors relevant to HA structure-function and membrane fusion are also likely to be important. Using single-particle-tracking (SPT) techniques, individual membrane fusion events can be observed under specific conditions, which provide detailed information regarding HA pH sensitivity and acid stability and the rate and extent of membrane fusion. This provides a comparative way to characterize and distinguish influenza virus fusion properties among virus strains. We used SPT to quantify the fusion properties of three H3 influenza strains: A/Aichi/68/H3N2 (X:31), A/Udorn/72/H3N2 (Udorn), and A/Brisbane/07/H3N2 (Brisbane). The rate of fusion for the most clinically relevant strain, Brisbane, is generally insensitive to decreasing pH, while the fusion of the egg-adapted strains Udorn and X:31 is strongly dependent on pH (and is faster) as the pH decreases. All strains exhibit similar acid stability (the length of time that they remain fusogenic in an acidic environment) at higher pHs, but the egg-adapted strains become less acid stable at lower pHs. Thus, it appears that the laboratory-adapted H3 strains tested may have evolved to compensate for the faster HA deactivation at low pH, with a commensurate increase in the rate of fusion and number of proteins facilitating fusion, relative to the Brisbane strain. IMPORTANCE The ability of influenza virus to release its genome under different acidic conditions has recently been linked to the transmission of influenza virus between different species. However, it is yet to be determined how acid-induced membrane fusion varies with virus strain and influences tropism. The results presented here are the results of an intra-H3-subtype study of acid stability and fusion kinetics. Using a single-particle-tracking (SPT) technique, we show here that the highest pH that initiates fusion is not necessarily the pH at which the kinetics of fusion is fastest and most abundant for a given strain. Strains exhibit different fusion behaviors, as evidenced by their unique kinetic trends; pH sensitivities, as evidenced by the differences when the first fusion events commence; and HA stabilities, as evidenced by the length of time that virions can persist in an acidic environment and still be fusion competent.


title: Severe Coronavirus Infections in Pregnancy: A Systematic Review.

text: OBJECTIVE To inform the current coronavirus disease 2019 (COVID-19) outbreak, we conducted a systematic literature review of case reports of Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, during pregnancy and summarized clinical presentation, course of illness, and pregnancy and neonatal outcomes. DATA SOURCES We searched MEDLINE and ClinicalTrials.gov from inception to April 23, 2020. METHODS OF STUDY SELECTION We included articles reporting case-level data on MERS-CoV, SARS-CoV, and SARS-CoV-2 infection in pregnant women. Course of illness, indicators of severe illness, maternal health outcomes, and pregnancy outcomes were abstracted from included articles. TABULATION, INTEGRATION, AND RESULTS We identified 1,328 unique articles, and 1,253 articles were excluded by title and abstract review. We completed full-text review on 75, and 29 articles were excluded by full-text review. Among 46 publications reporting case-level data, eight described 12 cases of MERS-CoV infection, seven described 17 cases of SARS-CoV infection, and 31 described 98 cases of SARS-CoV-2 infection. Clinical presentation and course of illness ranged from asymptomatic to severe fatal disease, similar to the general population of patients. Severe morbidity and mortality among women with MERS-CoV, SARS-CoV, or SARS-CoV-2 infection in pregnancy and adverse pregnancy outcomes, including pregnancy loss, preterm delivery, and laboratory evidence of vertical transmission, were reported. CONCLUSION Understanding whether pregnant women may be at risk for adverse maternal and neonatal outcomes from severe coronavirus infections is imperative. Data from case reports of SARS-CoV, MERS-CoV, and SAR-CoV-2 infections during pregnancy are limited, but they may guide early public health actions and clinical decision-making for COVID-19 until more rigorous and systematically collected data are available. The capture of critical data is needed to better define how this infection affects pregnant women and neonates. This review was not registered with PROSPERO.


title: Two-dimensional difference gel electrophoresis (DiGE) analysis of plasmas from dengue fever patients.

text: Dengue fever is the world's most important arthropod-born viral disease affecting humans. To contribute to a better understanding of its pathogenesis, this study aims to identify proteins differentially expressed in plasmas from severe dengue fever patients relative to healthy donors. The use of 2-D Fluorescence Difference Gel Electrophoresis to analyze plasmas depleted of six high-abundance proteins (albumin, IgG, antitrypsin, IgA, transferrin and haptoglobin) allowed for the detection of 73 differentially expressed protein spots (n = 13, p < 0.01), of which 37 could be identified by mass spectrometry. These 37 spots comprised a total of 14 proteins, as follows: 7 had increased expression in plasmas from dengue fever patients (C1 inhibitor, alpha1-antichymotrypsin, vitamin D-binding protein, fibrinogen gamma-chain, alpha1-acid glycoprotein, apolipoprotein J and complement component C3c), while 7 others had decreased expression in the same samples (alpha-2 macroglobulin, prothrombin, histidine-rich glycoprotein, apolipoproteins A-IV and A-I, transthyretin and complement component C3b). The possible involvement of these proteins in the inflammatory process triggered by dengue virus infection and in the repair mechanisms of vascular damage occurring in this pathology is discussed in this study.


title: Emergency Intracranial Stenting in Acute Stroke: Predictors for Poor Outcome and for Complications.

text: Background Stent-retriever thrombectomy is the first-line therapy in acute stroke with intracranial large vessel occlusion. In case of failure of stent-retriever thrombectomy, rescue stent angioplasty might be the only treatment option to achieve permanent recanalization. This study aims at identifying predictors for poor outcome and complications in a large, multicenter cohort receiving rescue stent angioplasty. Methods and Results We performed a retrospective analysis of patients with large vessel occlusion who were treated with rescue stent angioplasty after stent-retriever thrombectomy between 2012 and 2018 in 7 neurovascular centers. We defined 2 binary outcomes: (1) functional clinical outcome (good modified Rankin Scale, 0-2; and poor modified Rankin Scale, 4-6) and (2) early symptomatic intracerebral hemorrhage. Impacts of clinical, radiological, and interventional parameters on outcomewere assessed in uni- and multivariable logistic regression models. Two hundred ten patients were included with target vessels located within the anterior circulation (136 of 210; 64.8%) and posterior circulation (74 of 210; 35.2%). Symptomatic intracerebral hemorrhage occured in 22 patients, 86.4% (19 of 22) after anterior and 13.6% (3 of 22) after posterior circulation large vessel occlusion. Good functional outcome was observed in 44.8% (73 of 163). A higher National Institutes of Health Stroke Scale on admission (adjusted odds ratio, 1.10; P=0.002), a higher premorbid modified Rankin Scale (adjusted odds ratio, 2.02; P=0.049), and a modified Thrombolysis in Cerebral Infarction score of 0 to 2a after stenting (adjusted odds ratio, 23.24; P<0.001) were independent predictors of poor functional outcome. Conclusions Use of rescue stent angioplasty can be considered for acute intracranial large vessel occlusion in cases after unsuccessful stent-retriever thrombectomy. Likelihood of symptomatic intracerebral hemorrhage is higher in anterior circulation stroke.


title: A propensity score-matched comparison of surgical precision obtained by using volumetric analysis between robot-assisted laparoscopic and open partial nephrectomy for T1 renal cell carcinoma: a retrospective non-randomized observational study of initial outcomes.

text: PURPOSE We compared surgical outcomes between robot-assisted laparoscopic partial nephrectomy (RAPN) and open partial nephrectomy (OPN) by using volumetric analysis in a propensity score-matched analysis. METHODS We analyzed the records of 279 patients with normal contralateral kidneys who underwent RAPN or OPN for T1 renal tumors between 2012 and 2014. Volumetric studies to assess the vascularized parenchymal volume of the operated kidney were performed 2 months preoperatively and 6 months postoperatively. Patient data, including age, body mass index, presence of hypertension and/or diabetes mellitus, American Society of Anesthesiologists score, tumor size, preoperative estimated glomerular filtration rate, and tumor complexity using the renal nephrometry score, were matched 1:1 using propensity score matching between groups. RESULTS This cohort included 100 patients who underwent RAPN and 179 who underwent OPN. After matching, 48 patients were included in each group. Mean tumor diameter was 31 mm, and about 14 % were high-complexity tumors (RENAL score 10-12). The RAPN and OPN groups showed no significant differences in the rate of preservation of global renal function (95 vs. 92 %) and parenchymal volume of the operated kidney (84 vs. 79 %). Similarly, urological complications did not significantly differ between groups. Surgical margins were negative in all tumors. Patients who underwent RAPN had lower estimated blood loss (p < 0.0001) and shorter postoperative length of hospital stay (p < 0.0001) than those who underwent OPN. CONCLUSION RAPN can offer acceptable surgical outcomes and precision, compared to OPN, with decreased estimated blood loss and hospital stay.


title: Comparison of no-touch multi-bipolar vs. monopolar radiofrequency ablation for small HCC.

text: BACKGROUND & AIMS The primary aim of this study was to compare the rate of global radiofrequency ablation (RFA) failure between monopolar RFA (MonoRFA) vs. no-touch multi-bipolar RFA (NTmbpRFA) for small hepatocellular carcinoma (HCC) ⩽5cm in cirrhotic patients. METHODS A total of 362 cirrhotic patients were included retrospectively across four French centres (181 per treatment group). Global RFA failure (primary RFA failure or local tumour progression) was analysed using the Kaplan-Meier method after coarsened exact matching. Cox regression models were used to identify factors associated with global RFA failure and overall survival (OS). RESULTS Patients were well matched according to tumour size (⩽30/>30mm); tumour number (one/several); tumour location (subcapsular and near large vessel); serum AFP (<10; 10-100; >100ng/ml); Child-Pugh score (A/B) and platelet count (⩾100G/L), p=1 for all. One case of perioperative mortality was observed in the NTmbpRFA group and the rate of major complications was 7.2% in both groups (p=1). The cumulative rates of global RFA failure at 1, 3 and 5years were respectively 13.3%, 31% and 36.7% for MonoRFA vs. 0.02%, 7.9% and 9.2% for NTmbpRFA, p<0.001. Monopolar RFA, tumour size >30mm and HCC near large vessel were independent factors associated with global RFA failure. Five-year OS was 37.2% following MonoRFA vs. 46.4% following NTmbpRFA p=0.378. CONCLUSIONS This large multicentre case-matched study showed that NTmbpRFA provided better primary RFA success and sustained local tumour response without increasing severe complications rates, for HCC ⩽5cm. LAY SUMMARY Using no-touch multi-bipolar radiofrequency ablation for hepatocellular carcinoma ⩽5cm provide a better sustained local tumour control compared to monopolar radiofrequency ablation.


title: The therapeutic potential of metal-based antimalarial agents: implications for the mechanism of action.

text: Despite recent encouraging advances against the disease, malaria remains a major public health problem affecting almost half a billion people and killing almost a million per annum. Due to a short arsenal of efficient antimalarial agents and the frequent appearance of resistance to the drugs in current use, which consequently reduce our means to treat patients, there is a very urgent and continuous need to develop new compounds. This perspective outlines a unique strategy for that purpose through the development of metal-based antimalarial agents. The examples presented here illustrate an attractive alternative to classical drugs.


An Interdisciplinary Working Group to Advocate Universal Palliative Care and Pain Relief Access.


Coagulation concerns in patients with COVID-19 proposed for regional anesthesia.


title: Contextual factors associated with life-space mobility in community-dwelling older adults based on International Classification of Functioning, Disability and Health: protocol for a systematic review.

text: INTRODUCTION Mobility decline compromises functionality and quality of life in old age. Life-Space Assessment (LSA) evaluates mobility considering interaction between person and environment. The International Classification of Functioning, Disability and Health (ICF) is a reference to identify and categorise the personal and environmental contextual factors associated to the LSA. Our objective is identifying contextual factors that may influence life-space mobility of older community-dwelling adults based on ICF. METHODS AND ANALYSIS A systematic review of literature will be performed to identify studies published between 1 January 2001 and 10 May 2017 which investigates life-space mobility among older adults. Keywords will be entered into the electronic databases of MEDLINE (PubMed), EMBASE (OVID), CINHAL (EBSCO), Cochrane Central Register of Controlled Trials Cochrane Central (OVID), PsycINFO (EBSCO) and COCH (OVID). Five investigators will work on search databases and standardised screening of the articles. Mobility predictors will be separated into personal and environmental aspects, according to the ICF model. The results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and then a meta-analysis will be performed, if applicable. DISCUSSION Knowledge about life-space mobility in community-dwelling older adults by examining related risk and protective aspects may help practitioners better approach older adults' mobility and prevent their decline in old age. Furthermore, researchers will have more clues for investigations into factors related to life-space mobility. TRIAL REGISTRATION NUMBER CRD42017064552.


Neuropalliative care essentials for the COVID-19 crisis.


title: Sesquiterpenoids with Various Carbocyclic Skeletons from the Flowers of Chrysanthemum indicum.

text: A phytochemical investigation of the flowers of Chrysanthemum indicum yielded sesquiterpenoids 1-25 with various carbocyclic skeletons, including 10 new (1-10) and 15 known (11-25) analogues. The structures were elucidated via their physical data, while the absolute configuration of compounds 6, 8, and 10 was assessed via electronic circular dichroism analysis. The evaluation of the effect of sesquiterpenoids on porcine epidemic diarrhea virus (PEDV) replication showed that compounds 1-5, 12, 14, 16, 17, 19, and 21 increased cell viability against cell death in PEDV-injected cells. Compounds 2, 12, and 17 were selected and investigated for their inhibition of proteins required for PEDV replication. Compounds 2 and 17 significantly reduced PEDV nucleocapsid and spike protein synthesis compared with azauridin as a positive control.


Tracking a Virus.


title: Searching for the most cost-effective strategy for controlling epidemics spreading on regular and small-world networks.

text: We present a combined epidemiological and economic model for control of diseases spreading on local and small-world networks. The disease is characterized by a pre-symptomatic infectious stage that makes detection and control of cases more difficult. The effectiveness of local (ring-vaccination or culling) and global control strategies is analysed by comparing the net present values of the combined cost of preventive treatment and illness. The optimal strategy is then selected by minimizing the total cost of the epidemic. We show that three main strategies emerge, with treating a large number of individuals (global strategy, GS), treating a small number of individuals in a well-defined neighbourhood of a detected case (local strategy) and allowing the disease to spread unchecked (null strategy, NS). The choice of the optimal strategy is governed mainly by a relative cost of palliative and preventive treatments. If the disease spreads within the well-defined neighbourhood, the local strategy is optimal unless the cost of a single vaccine is much higher than the cost associated with hospitalization. In the latter case, it is most cost-effective to refrain from prevention. Destruction of local correlations, either by long-range (small-world) links or by inclusion of many initial foci, expands the range of costs for which the NS is most cost-effective. The GS emerges for the case when the cost of prevention is much lower than the cost of treatment and there is a substantial non-local component in the disease spread. We also show that local treatment is only desirable if the disease spreads on a small-world network with sufficiently few long-range links; otherwise it is optimal to treat globally. In the mean-field case, there are only two optimal solutions, to treat all if the cost of the vaccine is low and to treat nobody if it is high. The basic reproduction ratio, R(0), does not depend on the rate of responsive treatment in this case and the disease always invades (but might be stopped afterwards). The details of the local control strategy, and in particular the optimal size of the control neighbourhood, are determined by the epidemiology of the disease. The properties of the pathogen might not be known in advance for emerging diseases, but the broad choice of the strategy can be made based on economic analysis only.


title: Attenuation of Acute Renal Injury After the Post-resuscitation Administration of Doxycycline in Surviving Newborn Piglets With Severe Hypoxia-Reoxygenation.

text: Background: Asphyxiated neonates often have myocardial dysfunction and renal insufficiency. Previously we demonstrated that doxycycline improved cardio-renal function through matrix metalloproteinase (MMP)-2 inhibition in an acute swine model of neonatal hypoxia-reoxygenation. The prolonged cardio-renal protective effects of doxycycline in neonates still remained unknown. We therefore hypothesized that the protective effects of doxycycline persisted in surviving subjects. Methods: Newborn piglets were instrumented and subjected to 1 h of hypoxia followed by reoxygenation with 21-25% oxygen and observed for 4 days. Intravenous doxycycline (30 mg/kg) or normal saline (1 mL, saline-control group) was given at 5 min of reoxygenation (n = 8/group) in a randomized, blinded fashion. Sham-operated piglets (n = 5) received no hypoxia-reoxygenation. At 96 h after reoxygenation, the left ventricular function was assessed by Millar® catheter. Renal injury was investigated by measuring plasma creatinine, urinary N-acetyl-D-glucosaminidase activity, renal tissue lactate and MMP-2 activity. Results: Both hypoxia-reoxygenation groups had similar hypoxic stress with severe lactate acidosis, and hemodynamic recovery. Doxycycline-treated piglets had higher urine output with lower urine N-acetyl-D-glucosaminidase, plasma creatinine, and renal MMP-2 activity (vs. saline-controls; all p < 0.05). These markers were all negatively correlated with urine output. Conclusions: In newborn piglets surviving hypoxia-reoxygenation, we observed a weak but significant and persistent attenuation of renal injury and improved recovery with the post-resuscitation administration of doxycycline.


title: Otolaryngology Residency Application during the SARS-CoV-2 (COVID-19) Pandemic.

text: The escalation of the COVID-19 pandemic has affected health care at every level, including medical education. As some fourth-year medical students graduate early to join the front lines, we must now turn our attention to those trainees in their penultimate year. In this commentary, we address the unique dilemmas facing otolaryngology residency candidates for the 2020-2021 cycle, with a focus on those applicants with no institutional otolaryngology department.


Socioeconomic gradient in health and the covid-19 outbreak.


title: Transarterial embolization of mandibular arteriovenous malformations using ONYX.

text: PURPOSE To document the efficacy of ethylene vinyl alcohol copolymer (ONYX; ev3/Covidien, Irvine, CA) in the treatment of arteriovenous malformations (AVMs) of the mandible. MATERIALS AND METHODS A retrospective consecutive series of patients with facial AVMs isolated to the mandible and immediate perimandibular tissue was identified at 2 institutions. The primary treatment modality of transarterial embolization using ONYX was performed by way of the external carotid artery branches. Staged procedures were accomplished until no arteriovenous shunt remained. A 1-year follow-up angiogram was obtained for each patient. RESULTS Three patients, aged 8 (patient 1), 16 (patient 2), and 17 (patient 3) years presented with bleeding from facial AVMs isolated to the mandible. Patient 1 was female and patients 2 and 3 were male. The 2 older patients had loose molar or canine dentition. Transarterial embolization with ONYX achieved complete angiographic closure of the arteriovenous shunt in each patient. A total of 1, 6, and 3 staged embolization procedures were performed in the 3 patients. Patient 2 had mild transient facial numbness after embolization that completely resolved. Patient 3 had loose molars associated with the AVM that were extracted for treatment of intraprocedural bleeding. The 1-year angiographic follow-up data demonstrated durable closure of all 3 lesions. CONCLUSIONS Transarterial embolization of high-flow intraosseus mandibular AVMs was safely accomplished with ONYX in our small retrospective cohort. Complete, durable occlusion was found on the angiogram at 1 year, with clinical stability extending to an average of 3 years. Surgical resection of the AVM was avoided in all 3 patients.


title: A novel double snare technique to retrieve embolized septal and left atrial appendage occluders.

text: BACKGROUND Device embolization is the most frequent procedural complication during transcatheter closure of congenital cardiac defects. Retrieval of an embolized device may often be complicated by failure to introduce the right atrial (RA) disk hub into the sheath or difficulty in securely grasping the hub pin of RA disk. We aimed to evaluate the efficiency and success rate of device retrieval using a novel double snare technique. METHODS We reviewed retrieval procedures of embolized atrial septal defect (ASD) or left atrial appendage (LAA) occluder using double snare technique reported from five tertiary referral centers in Korea, Japan, and Uzbekistan. A total of 16 retrieval procedures in 15 patients were reported, including 14 patients who were planned for ASD device closure while 1 patient was planned for LA appendage occlusion. RESULTS Retrieved devices included 15 ASD occluders from six different manufacturers and one Amplantzer cardiac plug. Success rate of retrieval procedure was 100% using the double snare technique. There were no complications related to device retrieval. Most (15/16, 93.8%) of these devices could be retrieved through their original delivery sheaths. In six patients for whom retrieval was unsuccessful with conventional single snare technique and switched to double snare technique, the retrieval time was shortened significantly (P = 0.004*) by using the double snare technique. CONCLUSIONS The double snare technique enables effective retrieval of various embolized devices. It abolishes the need of changing the sheath to a larger one in most patients.


title: Integrative Physiology of Pneumonia.

text: Pneumonia is a type of acute lower respiratory infection that is common and severe. The outcome of lower respiratory infection is determined by the degrees to which immunity is protective and inflammation is damaging. Intercellular and interorgan signaling networks coordinate these actions to fight infection and protect the tissue. Cells residing in the lung initiate and steer these responses, with additional immunity effectors recruited from the bloodstream. Responses of extrapulmonary tissues, including the liver, bone marrow, and others, are essential to resistance and resilience. Responses in the lung and extrapulmonary organs can also be counterproductive and drive acute and chronic comorbidities after respiratory infection. This review discusses cell-specific and organ-specific roles in the integrated physiological response to acute lung infection, and the mechanisms by which intercellular and interorgan signaling contribute to host defense and healthy respiratory physiology or to acute lung injury, chronic pulmonary disease, and adverse extrapulmonary sequelae. Pneumonia should no longer be perceived as simply an acute infection of the lung. Pneumonia susceptibility reflects ongoing and poorly understood chronic conditions, and pneumonia results in diverse and often persistent deleterious consequences for multiple physiological systems.


Germany hits science high.


title: Comparison of established and novel methods for the detection and enumeration of microparticles in canine stored erythrocyte concentrates for transfusion.

text: BACKGROUND Microparticles (MP) are submicron, phosphatidylserine (PS)-bearing lipid vesicles with physiologic and pathologic roles in coagulation and inflammation. Microparticles accumulate in packed RBC (pRBC) stored for transfusion, potentially increasing recipient morbidity. Historically, canine MP have been detected with the PS label annexin V in supernatant samples. Other detection methods are available but have not been evaluated in dogs. OBJECTIVES The purpose of the study was to detect and enumerate MP in canine pRBC using annexin V, lactadherin, and bio-maleimide to compare label performance and assess microparticle accumulation under standard storage conditions. METHODS Microparticles (0.5-1.0 μm) in canine dog erythrocyte antigen 1.1 positive, nonleukoreduced pRBC were labeled with FITC-annexin V, FITC-lactadherin, and the fluorescent dye bio-maleimide, and were counted using flow cytometry at 3 time points (days 7, 21, and 35) of storage. Unprocessed pRBC, rather than supernatant, were used. RESULTS Annexin V and bio-maleimide labeling produced comparable microparticle counts (P = .16), while lactadherin labeling resulted in higher microparticle counts than annexin V (P = .002) and bio-maleimide (P = .006), particularly on day 7. Bio-maleimide- and annexin V-based microparticle counts increased significantly from day 7 to 35 (P = .04), and increases from day 21 to 35 approached statistical significance (P = .05). CONCLUSIONS Bio-maleimide- and annexin V-mediated microparticle counts were comparable in unprocessed canine pRBC using flow cytometry. Whether the increased microparticle counts with lactadherin were due to increased sensitivity for small, PS-bearing MP or due to labeling of membrane fragments and debris requires further investigation.


title: A two-step control of secondary splenic pedicles using ligasure during laparoscopic splenectomy.

text: OBJECTIVE We modified the LigaSure vessel sealing into a two-step technique without using Endo-GIA stapler for the secondary splenic pedicle control in laparoscopic splenectomy (LS). This study evaluated the efficacy and safety outcomes of this technique. METHODS Patients (n = 105) scheduled for elective LS were consecutively and prospectively enrolled, including 24 males and 81 females, with a mean age of 43.6 (range 11-75) years. Following the mobilization of the spleen, the splenic inflow was interrupted by applying a Hem-o-lock clip. LigaSure was used to seal and transect the secondary splenic pedicles adjacent to the pancreatic tail and subsequently in proximity to the spleen. RESULTS Of 105 patients, 103 patients (98.1%) underwent successful LS, whereas two patients (1.9%) required the conversion to laparotomy. The mean operative time was 100 min, whilst the mean volume of blood loss was 500 mL. No clinically significant morbidities or mortality occurred following LS. An average of 8,000 RMB (range: 6900 to 9000; 1 USD = 6.5 RMB) was saved by using this two-step technique. CONCLUSION Secondary splenic pedicles can be successfully controlled in LS by using a two-step technique with the LigaSure vessel sealing system in an economically favorable way.


title: Poor utility of grading scales in acute intracerebral hemorrhage: results from the INTERACT2 trial.

text: BACKGROUND Several simple clinical grading scores have been developed for intracerebral hemorrhage, primarily to predict 30-day mortality. AIMS We aimed to determine the accuracy of three popular scores (original intracerebral hemorrhage, modified intracerebral hemorrhage, and intracerebral hemorrhage grading scale) on 30-day mortality and 90-day death or major disability, and whether the magnitude of benefit varies according to prognosis graded by the three predictive scores. METHODS Data from the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial which included 2839 intracerebral hemorrhage patients (<6 hours) and elevated systolic blood pressure (150-220 mmHg), randomized to intensive (target systolic blood pressure <140 mmHg) or guideline-based (<180 mmHg) blood pressure management. Discrimination of scales for predicting death and poor outcome (modified Rankin scale 3-6) was evaluated in area under receiver operator characteristic curves. RESULTS Among 2556 (90%) participants with available data, the modified intracerebral hemorrhage had the highest discrimination (receiver operator characteristic 0·75) for 90-day poor outcome compared with the original intracerebral hemorrhage (receiver operator characteristic 0·68) and intracerebral hemorrhage grading scale (receiver operator characteristic 0·69). All scores had good positive predictive value (approximately 80-90%) for poor outcome but poor sensitivity and positive predictive value for death. The scores do not clearly discriminate a patient group most likely to benefit from blood pressure lowering. CONCLUSIONS Intracerebral hemorrhage prognostic scores are not useful in defining patients at high probability of early death, but they are reliable for predicting poor outcome, defined by death or major disability. Potential benefits of early intensive blood pressure lowering are broadly applicable across grades of severity defined by such scores.


title: Viruses in cystic fibrosis patients' airways.

text: Although bacteria have historically been considered to play a major role in cystic fibrosis (CF) airway damage, a strong impact of respiratory viral infections (RVI) is also now recognized. Emerging evidence confirms that respiratory viruses are associated with deterioration of pulmonary function and exacerbation and facilitation of bacterial colonization in CF patients. The aim of this review is to provide an overview of the current knowledge on respiratory viruses in CF airways, to discuss the resulting inflammation and RVI response, to determine how to detect the viruses, and to assess their clinical consequences, prevalence, and interactions with bacteria. The most predominant are Rhinoviruses (RVs), significantly associated with CF exacerbation. Molecular techniques, and especially multiplex PCR, help to diagnose viral infections, and the coming rise of metagenomics will extend knowledge of viral populations in the complex ecosystem of CF airways. Prophylaxis and vaccination are currently available only for Respiratory syncytial and Influenza virus (IV), but antiviral molecules are being tested to improve CF patients' care. All the points raised in this review highlight the importance of taking account of RVIs and their potential impact on the CF airway ecosystem.


Infectious disease. Combating emerging viral threats.


Resurgence of sport in the wake of COVID-19: cardiac considerations in competitive athletes.


title: Effectiveness of N95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis.

text: BACKGROUND Conflicting recommendations exist related to which facial protection should be used by health care workers to prevent transmission of acute respiratory infections, including pandemic influenza. We performed a systematic review of both clinical and surrogate exposure data comparing N95 respirators and surgical masks for the prevention of transmissible acute respiratory infections. METHODS We searched various electronic databases and the grey literature for relevant studies published from January 1990 to December 2014. Randomized controlled trials (RCTs), cohort studies and case-control studies that included data on health care workers wearing N95 respirators and surgical masks to prevent acute respiratory infections were included in the meta-analysis. Surrogate exposure studies comparing N95 respirators and surgical masks using manikins or adult volunteers under simulated conditions were summarized separately. Outcomes from clinical studies were laboratory-confirmed respiratory infection, influenza-like illness and workplace absenteeism. Outcomes from surrogate exposure studies were filter penetration, face-seal leakage and total inward leakage. RESULTS We identified 6 clinical studies (3 RCTs, 1 cohort study and 2 case-control studies) and 23 surrogate exposure studies. In the meta-analysis of the clinical studies, we found no significant difference between N95 respirators and surgical masks in associated risk of (a) laboratory-confirmed respiratory infection (RCTs: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.64-1.24; cohort study: OR 0.43, 95% CI 0.03-6.41; case-control studies: OR 0.91, 95% CI 0.25-3.36); (b) influenza-like illness (RCTs: OR 0.51, 95% CI 0.19-1.41); or (c) reported workplace absenteeism (RCT: OR 0.92, 95% CI 0.57-1.50). In the surrogate exposure studies, N95 respirators were associated with less filter penetration, less face-seal leakage and less total inward leakage under laboratory experimental conditions, compared with surgical masks. INTERPRETATION Although N95 respirators appeared to have a protective advantage over surgical masks in laboratory settings, our meta-analysis showed that there were insufficient data to determine definitively whether N95 respirators are superior to surgical masks in protecting health care workers against transmissible acute respiratory infections in clinical settings.


title: Pretreatment of food waste for methane and hydrogen recovery: A review.

text: Food waste (FW) management by biological process is more attractive and eco-friendly approach than thermo-chemical conversion or landfilling. However, FW composition and physico-chemical and biological characteristics affect the overall biological process in terms of product yield and degradation rate. To overcome this major bottle-neck, the pretreatment of FW is proposed. Therefore this review aims to provide a comprehensive summary of the importance of pretreatment of FW with respect to FW management by anaerobic digestion (AD) and dark fermentation (DF). It also reviews the existing knowledge gaps and future research perspectives for better integration of FW pretreatments for AD and DF, which should include (i) the preservation of carbon mass through freeze and thaw, or drying; and (ii) improve the carbon accessibility through particle size reduction and thermal pretreatments for high-rate bioenergy recovery.


title: Surgical Considerations for an Awake Tracheotomy During the COVID-19 Pandemic.

text: Background: The current global COVID-19 pandemic is caused by the novel coronavirus Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Given that SARS-CoV-2 is highly transmissible, surgical societies have recommended that procedures with a high risk of aerosolization be avoided or delayed. However, some high-risk procedures, such as those related to head and neck malignancies, cannot always be delayed. Care must be taken during aerosol-generating procedures to minimize viral transmission as much as possible. Preoperative testing for COVID-19, limited operating room personnel, adequate personal protective equipment, and surgical technique are factors to consider for high-risk procedures. Methods: This article presents the case of an awake tracheotomy performed for a transglottic mass causing airway obstruction. Results: With detailed planning and specific techniques, the amount of aerosolization was reduced, and the procedure was performed as safely as possible. Conclusion: This case provides a template for future aerosol-generating procedures during respiratory pandemics.


title: Early secretory pathway localization and lack of processing for hepatitis E virus replication protein pORF1.

text: Hepatitis E virus (HEV) is a positive-strand RNA virus and a major causative agent of acute sporadic and epidemic hepatitis. HEV replication protein is encoded by ORF1 and contains the predicted domains of methyltransferase (MT), protease, macro domain, helicase (HEL) and polymerase (POL). In this study, the full-length protein pORF1 (1693 aa) and six truncated variants were expressed by in vitro translation and in human HeLa and hepatic Huh-7 cells by using several vector systems. The proteins were visualized by three specific antisera directed against the MT, HEL and POL domains. In vitro translation of full-length pORF1 yielded smaller quantities of two fragments. However, these fragments were not observed after pORF1 expression and pulse-chase studies in human cells, and their production was not dependent on the predicted protease domain in pORF1. The weight of evidence supports the proposition that pORF1 is not subjected to specific proteolytic processing, which is unusual among animal positive-strand RNA viruses but common for plant viruses. pORF1 was membrane associated in cells and localized to a perinuclear region, where it partially overlapped with localization of the endoplasmic reticulum (ER) marker BAP31 and was closely interspersed with staining of the ER-Golgi intermediate compartment marker protein ERGIC-53. Co-localization with BAP31 was enhanced by treatment with brefeldin A. Therefore, HEV may utilize modified early secretory pathway membranes for replication.


A Knotted Elemental Diet Tube in a Neonate: Serial Radiographs Demonstrating the Process of Loop Formation.


Goals of Care in the Dark: Guiding Families of Patients with "COVID-19 Encephalopathy".


title: Can quality improvement improve the quality of care? A systematic review of reported effects and methodological rigor in plan-do-study-act projects.

text: BACKGROUND The Plan-Do-Study-Act (PDSA) method is widely used in quality improvement (QI) strategies. However, previous studies have indicated that methodological problems are frequent in PDSA-based QI projects. Furthermore, it has been difficult to establish an association between the use of PDSA and improvements in clinical practices and patient outcomes. The aim of this systematic review was to examine whether recently published PDSA-based QI projects show self-reported effects and are conducted according to key features of the method. METHODS A systematic literature search was performed in the PubMed, Embase and CINAHL databases. QI projects using PDSA published in peer-reviewed journals in 2015 and 2016 were included. Projects were assessed to determine the reported effects and the use of the following key methodological features; iterative cyclic method, continuous data collection, small-scale testing and use of a theoretical rationale. RESULTS Of the 120 QI projects included, almost all reported improvement (98%). However, only 32 (27%) described a specific, quantitative aim and reached it. A total of 72 projects (60%) documented PDSA cycles sufficiently for inclusion in a full analysis of key features. Of these only three (4%) adhered to all four key methodological features. CONCLUSION Even though a majority of the QI projects reported improvements, the widespread challenges with low adherence to key methodological features in the individual projects pose a challenge for the legitimacy of PDSA-based QI. This review indicates that there is a continued need for improvement in quality improvement methodology.


title: Tackle the problem when it gets here: pandemic preparedness among small and medium businesses.

text: Globally, governments and health authorities are preparing for pandemic influenza and producing resources to promote preparedness planning; however, there is little information available to inform the design of strategies to promote preparedness. Three focus groups were conducted to identify and to describe beliefs and perceptions about pandemic influenza and response planning among small and medium business owners and managers. Most participants were not concerned about the risk of pandemic influenza, and none had engaged in any planning for a pandemic. Findings show that participants were uncertain of the modes of transmission of pandemic influenza and what precautions could be taken prior to, or in the event of, a pandemic. Among the most important findings was participants' perceived inability to effectively prevent or control the spread of influenza within their workplace. These findings have important implications for the design of communication strategies to promote preparedness.


I Can't Breathe - Race, Violence and COVID-19.


title: Comparison of Abbott ID Now and Abbott m2000 methods for the detection of SARS-CoV-2 from nasopharyngeal and nasal swabs from symptomatic patients.

text: The ID NOW COVID-19 (IDNCOV) assay performed on the ID Now Instrument (Abbott Diagnostics, Scarborough, Inc. Scarborough, ME) is a rapid diagnostic test that can be performed in a point of care setting equivalent to CLIA waived testing.….


title: Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial.

text: PURPOSE This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness. METHODS Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid. RESULTS Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 ± 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups. CONCLUSIONS Training in meditation or exercise may be effective in reducing ARI illness burden.


title: Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells.

text: The ability of extracellular vesicles (EVs) to regulate a broad range of cellular processes has recently been exploited for the treatment of diseases. For example, EVs secreted by stem cells injected into infarcted hearts can induce recovery through the delivery of stem-cell-specific miRNAs. However, the retention of the EVs and the therapeutic effects are short-lived. Here, we show that an engineered hydrogel patch capable of slowly releasing EVs secreted from cardiomyocytes derived from induced pluripotent stem (iPS) cells reduced arrhythmic burden, promoted ejection-fraction recovery, decreased cardiomyocyte apoptosis 24 hours after infarction, and reduced infarct size and cell hypertrophy 4 weeks post-infarction when implanted onto infarcted rat hearts. We also show that the EVs are enriched with cardiac-specific miRNAs known to modulate cardiomyocyte-specific processes. The extended delivery of EVs secreted from iPS-cell-derived cardiomyocytes into the heart may help understand heart recovery and treat heart injury.


title: COVID-19 and the renin, angiotensin, aldosterone system. A complex relationship.

text: The COVID-19 pandemic has had major negative health, psychological, social and economic repercussions for individuals, families, communities, countries and for humanity in general. The interrelation with age and the presence of chronic non-communicable diseases (hypertension, diabetes, obesity, smoking) seems to go further than what would be explained by the prevalence and distribution of both. The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue. This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. The response of practically all Scientific Societies was almost immediate, with the precise indication that treatment with these drugs should not be discontinued, since the evidence of their usefulness is based on very solid and high-quality evidence. Simultaneously, a different hypothesis also appeared, also based on very preliminary evidence, that these drugs are not only harmful but also beneficial, however these medicaments are not yet accepted as agents for the prevention or treatment of this disease or its complications. This review reports current knowledge on the relationship between COVID-19 and SRAA.


Middle East Respiratory Syndrome in Korea.


title: TICI and Age: What's the Score?

text: BACKGROUND AND PURPOSE Previous studies have suggested that advanced age predicts worse outcome following mechanical thrombectomy. We assessed outcomes from 2 recent large prospective studies to determine the association among TICI, age, and outcome. MATERIALS AND METHODS Data from the Solitaire FR Thrombectomy for Acute Revascularization (STAR) trial, an international multicenter prospective single-arm thrombectomy study and the Solitaire arm of the Solitaire FR With the Intention For Thrombectomy (SWIFT) trial were pooled. TICI was determined by core laboratory review. Good outcome was defined as an mRS score of 0-2 at 90 days. We analyzed the association among clinical outcome, successful-versus-unsuccessful reperfusion (TICI 2b-3 versus TICI 0-2a), and age (dichotomized across the median). RESULTS Two hundred sixty-nine of 291 patients treated with Solitaire in the STAR and SWIFT data bases for whom TICI and 90-day outcome data were available were included. The median age was 70 years (interquartile range, 60-76 years) with an age range of 25-88 years. The mean age of patients 70 years of age or younger was 59 years, and it was 77 years for patients older than 70 years. There was no significant difference between baseline NIHSS scores or procedure time metrics. Hemorrhage and device-related complications were more common in the younger age group but did not reach statistical significance. In absolute terms, the rate of good outcome was higher in the younger population (64% versus 44%, P < .001). However, the magnitude of benefit from successful reperfusion was higher in the 70 years of age and older group (OR, 4.82; 95% CI, 1.32-17.63 versus OR 7.32; 95% CI, 1.73-30.99). CONCLUSIONS Successful reperfusion is the strongest predictor of good outcome following mechanical thrombectomy, and the magnitude of benefit is highest in the patient population older than 70 years of age.


title: Large eddy simulation for predicting turbulent heat transfer in gas turbines.

text: Blade cooling technology will play a critical role in the next generation of propulsion and power generation gas turbines. Accurate prediction of blade metal temperature can avoid the use of excessive compressed bypass air and allow higher turbine inlet temperature, increasing fuel efficiency and decreasing emissions. Large eddy simulation (LES) has been established to predict heat transfer coefficients with good accuracy under various non-canonical flows, but is still limited to relatively simple geometries and low Reynolds numbers. It is envisioned that the projected increase in computational power combined with a drop in price-to-performance ratio will make system-level simulations using LES in complex blade geometries at engine conditions accessible to the design process in the coming one to two decades. In making this possible, two key challenges are addressed in this paper: working with complex intricate blade geometries and simulating high-Reynolds-number (Re) flows. It is proposed to use the immersed boundary method (IBM) combined with LES wall functions. A ribbed duct at Re=20 000 is simulated using the IBM, and a two-pass ribbed duct is simulated at Re=100 000 with and without rotation (rotation number Ro=0.2) using LES with wall functions. The results validate that the IBM is a viable alternative to body-conforming grids and that LES with wall functions reproduces experimental results at a much lower computational cost.


title: Extra-pulmonary complications of COVID-19: a multi-system disease?

text: The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS-CoV-2 may also adversely affect other organ systems. To date, however, there is very limited understanding of the extent and management of COVID-19-related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extra-pulmonary manifestations of COVID-19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes current understanding of the extra-pulmonary complications caused by COVID-19 in order to improve the management and prognosis of patients with COVID-19. This article is protected by copyright. All rights reserved.


Providing Safe and Effective Surgical Care During the COVID-19 Outbreak in the UK - Changing Strategies.


title: Acute alcohol intoxication in adolescents: frequency of respiratory depression.

text: BACKGROUND Adolescents and young adults are frequent users of alcohol. Younger patients may be more sensitive to the effects of alcohol than their adult counterparts, and toxicity has been known to occur at lower doses. Respiratory depression is a serious adverse effect of alcohol intoxication; however, current monitoring practices may not adequately detect respiratory depression. OBJECTIVE Our objective was to determine the frequency of hypoventilation as measured by capnography among adolescents with acute alcohol intoxication. Our secondary objective was to determine if an association exists between alcohol levels and incidence of hypoventilation. METHODS This was a prospective observational pilot study of patients 14-20 years of age with acute alcohol intoxication. Blood or breath alcohol measurements were obtained on arrival. Hourly measurements of vital signs including capnography were recorded. RESULTS Sixty-five subjects were analyzed. Mean alcohol level was 185 mg/dL. Twenty-eight percent of subjects had episodes of hypoventilation. Episodes occurred in similar proportions on arrival and during the first 5 h of measurements. There was no difference in alcohol levels between subjects who did and did not hypoventilate (185 mg/dL vs. 186 mg/dL; 95% confidence interval -29 to 25). Oxygen desaturations occurred in 14 subjects and were associated with hypoventilation (p = 0.015). CONCLUSIONS Hypoventilation is common among adolescents who are acutely intoxicated with alcohol. It is independent of alcohol level and occurs at a steady rate during the first several hours of intoxication. Capnography should be considered as an additional monitoring device to detect these episodes and enhance patient safety.


title: Feasibility and Safety of Repeat Instant Endovascular Interventions in Patients with Refractory Cerebral Vasospasms.

text: BACKGROUND AND PURPOSE For patients with cerebral vasospasm refractory to medical and hemodynamic therapies, endovascular therapies often remain the last resort. Data from studies in large cohorts on the efficacy and safety of multiple immediate endovascular interventions are sparse. Our aim was to assess the feasibility and safety of multiple repeat instant endovascular interventions in patients with cerebral vasospasm refractory to medical, hemodynamic, and initial endovascular interventions. MATERIALS AND METHODS This was a single-center retrospective study of prospectively collected data on patients with cerebral vasospasm refractory to therapies requiring ≥3 endovascular interventions during the course of treatment following aneurysmal subarachnoid hemorrhage. The primary end point was functional outcome at last follow-up (mRS ≤2). The secondary end point was angiographic response to endovascular therapies and the appearance of cerebral infarctions. RESULTS During a 4-year period, 365 patients with aneurysmal subarachnoid hemorrhage were treated at our institution. Thirty-one (8.5%) met the inclusion criteria. In 52 (14%) patients, ≤2 endovascular interventions were performed as rescue therapy for refractory cerebral vasospasm. At last follow-up, a good outcome was noted in 18 (58%) patients with ≥3 interventions compared with 31 (61%) of those with ≤2 interventions (P = .82). The initial Hunt and Hess score of ≤2 was a significant independent predictor of good outcome (OR, 4.7; 95% CI, 1.2-18.5; P = .03), whereas infarcts in eloquent brain areas were significantly associated with a poor outcome (mRS 3-6; OR, 13.5; 95% CI, 2.3-81.2; P = .004). CONCLUSIONS Repeat instant endovascular intervention is an aggressive but feasible last resort treatment strategy with a favorable outcome in two-thirds of patients with refractory cerebral vasospasm and in whom endovascular treatment has already been initiated.


Stop the Wuhan virus.


title: Community-acquired pneumonia requiring hospitalization among U.S. children.

text: BACKGROUND Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed. METHODS We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists. RESULTS From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%). CONCLUSIONS The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).


docid: eijpojog

title: Reduced length of hospital stay in colorectal surgery after implementation of an enhanced recovery protocol.

text: BACKGROUND Enhanced recovery after surgery (ERAS) is a multimodal approach to perioperative care that combines a range of interventions to enable early mobilization and feeding after surgery. We investigated the feasibility, clinical effectiveness, and cost savings of an ERAS program at a major U. S. teaching hospital. METHODS Data were collected from consecutive patients undergoing open or laparoscopic colorectal surgery during 2 time periods, before and after implementation of an ERAS protocol. Data collected included patient demographics, operative, and perioperative surgical and anesthesia data, need for analgesics, complications, inpatient medical costs, and 30-day readmission rates. RESULTS There were 99 patients in the traditional care group, and 142 in the ERAS group. The median length of stay (LOS) was 5 days in the ERAS group compared with 7 days in the traditional group (P < 0.001). The reduction in LOS was significant for both open procedures (median 6 vs 7 days, P = 0.01), and laparoscopic procedures (4 vs 6 days, P < 0.0001). ERAS patients had fewer urinary tract infections (13% vs 24%, P = 0.03). Readmission rates were lower in ERAS patients (9.8% vs 20.2%, P = 0.02). DISCUSSION Implementation of an enhanced recovery protocol for colorectal surgery at a tertiary medical center was associated with a significantly reduced LOS and incidence of urinary tract infection. This is consistent with that of other studies in the literature and suggests that enhanced recovery programs could be implemented successfully and should be considered in U.S. hospitals.


title: The pain quality response profile of pregabalin in the treatment of neuropathic pain.

text: OBJECTIVE To identify and describe the response profile of pregabalin on the qualities of pain associated with peripheral neuropathy. METHODS A post hoc analysis to examine the effects of pregabalin on pain quality in patients with moderate-to-severe peripheral neuropathic pain was performed using data from an enriched enrollment randomized withdrawal proof-of-concept study. Patients rated the quality of their pain experience using the Pain Quality Assessment Scale (PQAS) at baseline, after a 12-day titration period, after a 9-day maintenance period, and after a 19-day randomized withdrawal period. Pretitration to posttitration and prewithdrawal to postwithdrawal changes in PQAS paroxysmal, surface, and deep pain scale scores were examined. RESULTS PQAS data were available for 99 of the 104 participants who entered all phases of the study. There were significant (P<0.006, Bonferroni adjusted for multiple tests) improvements pretitration to posttitration in all 3 PQAS subscales, with a greater effect on paroxysmal and deep pain than on surface pain. During the withdrawal phase, pregabalin was significantly (P<0.006) more effective than placebo for improvements in paroxysmal and surface pain only, although the pregabalin group continued to show numerical improvement in deep pain relative to placebo. DISCUSSION Pregabalin had a greater effect on PQAS-assessed paroxysmal pain than on surface or deep pain in patients with peripheral neuropathy. The findings corroborate previous research demonstrating differential effects of analgesic drugs across pain qualities, further emphasizing the need to assess individual pain qualities in addition to overall pain intensity.


title: [Analysis of the first cluster of cases in a family of COVID-19 in Gansu Province].

text: The epidemiological history and clinical characteristics of 7 cases of COVID-19 and 1 case of close contact in the first family aggregation epidemic of COVID-19 in Gansu Province were analyzed. The first patient A developed on January 22, 2020, with a history of residence in Wuhan, and confirmed severe cases of NCP on January 24, 2020; patient B, on January 23, 2020, diagnosed on January 31, severe cases; patient C, asymptomatic, diagnosed on January 27; patient D, asymptomatic, diagnosed on January 27; patient E, on January 24, diagnosed on January 28; patient F, asymptomatic, diagnosed on January 31; Patient G was asymptomatic and was diagnosed on January 31. In close contact, H was asymptomatic, PCR test was negative and asymptomatic, and he was discharged early. Among the 7 patients, 1 case died of (B) aggravation, and the other patients' condition was effectively controlled after active treatment. Except for the discharged cases, 5 cases were positive for COVID-19 specific IgM antibody and 1 case was negative. In this clustering outbreak, 4 patients remained asymptomatic, but PCR and IgM antibodies were positive, indicating that asymptomatic patients may be the key point to control the epidemic. Specific IgM antibody screening for patients whose pharyngeal swab nucleic acid test is negative but with ground glass-like lung lesions is very important for early detection and early isolation.


title: Efficient Methods To Isolate Human Monoclonal Antibodies from Memory B Cells and Plasma Cells.

text: In this article, we highlight the advantages of isolating human monoclonal antibodies from the human memory B cells and plasma cell repertoires by using high-throughput cellular screens. Memory B cells are immortalized with high efficiency using Epstein-Barr virus (EBV) in the presence of a toll-like receptor (TLR) agonist, while plasma cells are maintained in single-cell cultures by using interleukin 6 (IL-6) or stromal cells. In both cases, multiple parallel assays, including functional assays, can be used to identify rare cells that produce antibodies with unique properties. Using these methods, we have isolated potent and broadly neutralizing antibodies against a variety of viruses, in particular, a pan-influenza-A-neutralizing antibody and an antibody that neutralizes four different paramyxoviruses. Given the high throughput and the possibility of directly screening for function (rather than just binding), these methods are instrumental to implement a target-agnostic approach to identify the most effective antibodies and, consequently, the most promising targets for vaccine design. This approach is exemplified by the identification of unusually potent cytomegalovirus-neutralizing antibodies that led to the identification of the target, a pentameric complex that we are developing as a candidate vaccine.


title: Fucoidans inhibit the formation of post-operative abdominal adhesions in a rat model.

text: PURPOSE Fibrin clot is essential for post-operative abdominal adhesion formation. Fucoidans, sulfated polysaccharides, inhibit fibrin clot formation. In addition, they inhibit inflammation and fibrosis, which also play important roles in adhesion formation. The purpose of this study was to evaluate fucoidans' potential for inhibiting post-operative abdominal adhesions and measure their effects on systemic coagulation parameters when administered intraperitoneally (IP). METHODS AND MATERIALS Female Sprague Dawley rats were studied. A 2.5x2.5cm full thickness segment of abdominal wall was excised. The skin edges were approximated. This model induces extensive adhesions and allows objective quantitation. Three fucoidans were evaluated- Sigma Fucoidan Crude (SFC), Fucus vesiculosis 95% (Sigma) and, Peridan. One protocol involved continuous infusion into the abdomen from a subcutaneous osmotic pump. Alternatively, boluses of the solutions were injected IP at the end of the operation. Rats were sacrificed a week later. Adhesion extent was scored. Systemic coagulation effects of fucoidans were also evaluated. INR and aPTT were measured following IP injection of the fucoidan solutions and after 7 days of continuous infusion. RESULTS Animals given a continuous infusion of either SFC or Peridan yielded adhesion reduction of 80 to 90% from control. Bolus Peridan had no discernable influence on adhesion formation, but a single bolus of SFC caused significant adhesion reductions. Peridan resulted in prompt aPTT elevations which fell to nearly normal by 5 hours. The maximum peak value after SFC injection was seen in 15 hours. The maximal INR elevations were around 2. Measurement of INR and aPTT after a week of continuous infusion of either Peridan or SFC, were always in the normal control range. The third agent, Sigma, frequently yielded intraperitoneal infection found at autopsy. CONCLUSIONS These findings indicate that selected fucoidans infused intraperitoneally for a week after abdominal operations reduce adhesion extent by up to 90%.


title: Polyclonal and monoclonal antibodies for the treatment of influenza.

text: PURPOSE OF REVIEW This review summarizes past and ongoing efforts for using polyclonal and monoclonal antibodies for the treatment of influenza, and is focused on products that have entered clinical trials. RECENT FINDINGS At least three polyclonal and eight monoclonal antibody products have been tested in clinical trials for the treatment of influenza. Considered across the two classes of therapeutics, these products appear to be safe and well tolerated. However, the efficacy results have been mixed and inconclusive. To date, no products have consistently shown superiority to currently available antivirals. SUMMARY No products within these two classes have been licensed, and several products appear to have stopped further clinical development. There are several ongoing studies that are anticipated to be completed or reported in the next 1-2 years which will be critical for understanding the value of polyclonal and monoclonal antibodies in the treatment of influenza.


Getting to the heart of the matter of COVID-19.


COVID-19 Research in Brief: 30 May to 5 June, 2020.


title: Constrained pupil balance compensation for specific lithographic illuminator settings.

text: Pupil energy balances have always been considered significant elements for emersion lithography generally due to the large angle of incidence and offset imaging field. Those imbalances impact on exposure uniformity and decay pattern resolution. To overcome such shortcomings, a study on pupil compensation is discussed in this manuscript. A computational method based on a constrained optimization solution is proposed. By using a self-designed optical model of a zoomed system incorporating axicon lenses, a series of computations are developed and discussed. Also, the validity of our compensation method has been fully verified by simulations under multiple illumination settings.


New analyses of standard physiological signals: the old pipes give the sweetest smoke.


title: Acute Pain in the African Prehospital Setting: A Scoping Review.

text: Background Acute pain is a common reason for seeking prehospital emergency care. Regrettably, acute pain is often underestimated and poorly managed in this setting. The scoping review was conducted to gain insight into existing research on the topic and to make recommendations for future work. Objectives To identify all available evidence related to acute pain assessment and management in the African prehospital setting, describe the extent of the evidence, encapsulate findings, and identify research gaps. Methods The scoping review considered primary and secondary research related to acute pain assessment and management of both medical and traumatic origins in all age groups in the African prehospital setting. The search strategy aimed to identify published, unpublished, and ongoing research which met the inclusion criteria. Potentially eligible studies were identified by a comprehensive search of electronic databases, trial registers, dissertation/thesis databases, grey literature databases, and conference proceedings. Screening and data extraction were conducted independently and in duplicate. Results The comprehensive search identified 3823 potential studies, duplicate titles were removed, and 3358 titles/abstracts were screened. Full text of 66 potentially eligible titles was screened, 60 were excluded, and six publications met the inclusion criteria. Despite recommendations for pain assessment during general patient care, most studies reported no/limited pain assessment. In general, pain management was concluded to be insufficient and not conforming to best practice. Conclusions Only six publications addressing prehospital acute pain care in Africa could be identified, possibly indicative of a knowledge gap. Future research is indicated to enable a better understanding of the epidemiology of acute pain and barriers and enablers of acute pain care and to develop evidence-based clinical practice guidelines (CPGs) catering for all EMS systems in Africa. Additionally, educational initiatives should be implemented to improve the quality of acute pain care and to monitor quality through continuous quality improvement (CQI) programs.


title: A practical system for recording instrument interactions during live robotic surgery.

text: We have developed a system for measuring and recording the high-frequency vibrations that characterize instrument interactions during minimally invasive robotic surgery. Consisting of simple circuitry and a DVD recorder, this system is low-cost and easily implementable, requires no sterilization, and enables measurement of a validated, objective technical skill metric in both the simulated setting and the operating room. The vibration recordings of fourteen sleeve gastrectomies were processed by segmenting the operation into seven phases and calculating the root mean square (RMS) vibration within each phase. Statistical analysis showed that the observed differences match expectations drawn from knowledge of the operation, substantiating the premise that RMS vibration provides a good measure of the intensity of instrument interactions during live robotic surgery.


docid: imdzxmau

title: Could the NHS ever be truly independent?