title: Identification of residual metabolic-active areas within NSCLC tumours using a pre-radiotherapy FDG-PET-CT scan: a prospective validation.

text: It was recently described that high FDG-uptake areas pre-radiotherapy largely correspond with residual metabolic-active areas post-radiotherapy. Here, an independent prospective validation of these results was performed using an overlap-fraction (OF) calculation of various FDG-uptake based thresholds. Data from twelve patients treated at Radboud University Nijmegen Medical Center with lung cancer were analyzed. All patients underwent two FDG-PET-CT scans, one pre-radiotherapy (pre-RT) and one approximately three months after treatment (post-RT). Of the twelve analyzed patients, eight patients showed residual FDG uptake on the post-RT scan and were included for analysis. One of these patients had a residue that was not clearly distinguishable from the surrounding tissue due to FDG avid inflammation. Therefore, seven patients remained for further analysis. The mean volume of the residual metabolic-active areas post-RT was 14.6±10.0% (mean±SD) of the mean volume of the gross tumour volume (GTV) pre-RT. The residual metabolic-active areas largely corresponded with the pre-RT GTV (OF=93.7±7.2%). The pre-RT-scan threshold delineations of 34%, 40% and 50% of the SUV(max) had a large OF with the residual region, 86.9±8.3%, 77.4±8.1% and 67.9±6.8%, respectively. In this independent dataset, we confirmed that the location of residual FDG-uptake areas after radiotherapy corresponds with the high FDG-uptake areas pre-radiotherapy. Therefore, a pre-radiotherapy FDG-PET-CT scan can potentially be used for radiotherapy dose redistribution.


title: How sequential studies inform drug development: evaluating the effect of food intake on optimal bioavailability of ziprasidone.

text: Determining a drug dosing regimen that produces consistent bioavailability and patient effects is one of the goals of the drug development process. Food consumption is one factor that can significantly alter the bioavailability of some drugs. This manuscript describes a research approach to determine what recommendations to give patients regarding taking oral ziprasidone in relation to food consumption. Four pharmacokinetic studies, the first three in volunteers and the fourth in patients at steady-state on the maximum recommended daily dose of ziprasidone, investigated the relationship between food intake and ziprasidone absorption. These studies illustrate how sequential studies are used in drug development to investigate increasingly precise questions using data from one study to refine the question being addressed by the next. In the first study, the absorption of ziprasidone was shown to double when taken following a high-calorie, high-fat meal versus the fasting state. The second study showed that the difference in absorption between the fasting and fed states increased with dose. The third study suggested that calorie rather than fat content was the critical variable. This finding was confirmed in the fourth study over a wider variety of meals and under clinically relevant dosing conditions. That study also found reduced pharmacokinetic variability (i.e., more consistent absorption) when ziprasidone was administered with 500-1000 kcal meals without regard to fat content rather than under fasting or low-calorie meal conditions. These results have several clinically important implications. First, the effect of taking ziprasidone in a fasting state cannot be overcome simply by increasing the dose. Second, significant swings in ziprasidone concentration and hence efficacy and tolerability may occur on a day-to-day basis if diet is not controlled. Third, patients should be advised to take ziprasidone with a meal containing at least 500 calories (without regard to fat content) to ensure adequate ziprasidone bioavailability and thus achieve optimal efficacy. These four studies illustrate the sequential and incremental nature of drug development research and what is meant by the concept of bioequivalence.


title: Utility of prenatal Doppler ultrasound to predict neonatal impaired cerebral autoregulation.

text: OBJECTIVE Determine if abnormal prenatal Doppler ultrasound indices are predictive of postnatal impaired cerebral autoregulation. STUDY DESIGN Prospective cohort study of 46 subjects, 240-296 weeks' gestation. Utilizing near-infrared spectroscopy and receiver-operating characteristic analysis, impaired cerebral autoregulation was defined as >16.5% time spent in a dysregulated state within 96 h of life. Normal and abnormal Doppler indices were compared for perinatal outcomes. RESULTS Subjects with abnormal cerebroplacental ratio (n = 12) and abnormal umbilical artery pulsatility index (n = 13) were likely to develop postnatal impaired cerebral autoregulation (p ≤ 0.02). Abnormal cerebroplacental ratio was associated with impaired cerebral autoregulation between 24 and 48 h of life (p = 0.016). These subjects have increased risk for fetal growth restriction, lower birth weight, lower Apgar scores, acidosis, and severe intraventricular hemorrhage and/or death (p < 0.05). CONCLUSION Abnormal cerebroplacental ratio and umbilical artery pulsatility index are associated with postnatal impairment in cerebral autoregulation and adverse outcome.


title: Laparoscopic nephroureterectomy with transvesical single-port distal ureter and bladder cuff dissection: points of technique and initial surgical outcomes with five patients.

text: Although a variety of techniques have been used to manage the distal ureter during laparoscopic radical nephroureterectomy (LNU), a consensus has not yet been established. Recently, some authors have used a single-port transvesical approach to excise the distal ureter and bladder cuff following LNU. The aim of the study was to present our initial experience in "en bloc" dissection of the distal ureter and bladder cuff during LNU, using a transvesical single-port approach (T-LESS) and standard laparoscopic instruments. From April to October 2012, 5 patients aged 45 to 73 years with upper urinary tract urothelial tumors were subjected to LNU/T-LESS. After a standard LNU was performed, a TriPort+(®) device was introduced into the bladder and the pneumovesicum was established. A bladder cuff with a distal ureter was dissected and put in the paravesical tissue. The bladder wall defect was closed with the V-loc(®) 3/0 suture. The LNU was then completed in the flank position. All procedures were completed successfully. No significant blood loss or complications were observed. The mean operative time was 250 min (range: 200-370) for a total procedure and 59 min (range: 42-80) for the T-LESS stage. The postoperative hospital stay was 5.2 days (range: 4-9). Pathologic examination revealed no positive margin in any of the cases. The LNU/T-LESS approach is an efficient and safe procedure. A well-visualized dissection of the distal ureter, closing the defect of the bladder, the use of standard laparoscopic instruments and a good cosmesis are advantages of the method.


title: Apelin is a positive regulator of ACE2 in failing hearts.

text: Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases.


title: Diagnosis of non-effusive feline infectious peritonitis by reverse transcriptase quantitative PCR from mesenteric lymph node fine-needle aspirates.

text: OBJECTIVES The aim of this study was to evaluate a feline coronavirus (FCoV) reverse transcriptase quantitative PCR (RT-qPCR) on fine-needle aspirates (FNAs) from mesenteric lymph nodes (MLNs) collected in sterile saline for the purpose of diagnosing non-effusive feline infectious peritonitis (FIP) in cats. METHODS First, the ability of the assay to detect viral RNA in MLN FNA preparations compared with MLN biopsy preparations was assessed in matched samples from eight cats. Second, a panel of MLN FNA samples was collected from a series of cats representing non-effusive FIP cases (n = 20), FCoV-seropositive individuals (n = 8) and FCoV seronegative individuals (n = 18). Disease status of the animals was determined using a combination of gross pathology, histopathology and/or 'FIP profile', consisting of serology, clinical pathology and clinical signs. RESULTS Viral RNA was detected in 18/20 non-effusive FIP cases; it was not detected in two cases that presented with neurological FIP. Samples from 18 seronegative non-FIP control cats and 7/8 samples from seropositive non-FIP control cats contained no detectable viral RNA. Thus, as a method for diagnosing non-effusive FIP, MLN FNA RT-qPCR had an overall sensitivity of 90.0% and specificity of 96.1%. CONCLUSIONS AND RELEVANCE In cases with a high index of suspicion of disease, RT-qPCR targeting FCoV in MLN FNA can provide important information to support the ante-mortem diagnosis of non-effusive FIP. Importantly, viral RNA can be reliably detected in MLN FNA samples in saline submitted via the national mail service. When applied in combination with biochemistry, haematology and serological tests in cases with a high index of suspicion of disease the results of this assay may be used to support a diagnosis of non-effusive FIP.


The H7N9 influenza virus in China--changes since SARS.


title: Overdiagnosis across medical disciplines: a scoping review.

text: OBJECTIVE To provide insight into how and in what clinical fields overdiagnosis is studied and give directions for further applied and methodological research. DESIGN Scoping review. DATA SOURCES Medline up to August 2017. STUDY SELECTION All English studies on humans, in which overdiagnosis was discussed as a dominant theme. DATA EXTRACTION Studies were assessed on clinical field, study aim (ie, methodological or non-methodological), article type (eg, primary study, review), the type and role of diagnostic test(s) studied and the context in which these studies discussed overdiagnosis. RESULTS From 4896 studies, 1851 were included for analysis. Half of all studies on overdiagnosis were performed in the field of oncology (50%). Other prevalent clinical fields included mental disorders, infectious diseases and cardiovascular diseases accounting for 9%, 8% and 6% of studies, respectively. Overdiagnosis was addressed from a methodological perspective in 20% of studies. Primary studies were the most common article type (58%). The type of diagnostic tests most commonly studied were imaging tests (32%), although these were predominantly seen in oncology and cardiovascular disease (84%). Diagnostic tests were studied in a screening setting in 43% of all studies, but as high as 75% of all oncological studies. The context in which studies addressed overdiagnosis related most frequently to its estimation, accounting for 53%. Methodology on overdiagnosis estimation and definition provided a source for extensive discussion. Other contexts of discussion included definition of disease, overdiagnosis communication, trends in increasing disease prevalence, drivers and consequences of overdiagnosis, incidental findings and genomics. CONCLUSIONS Overdiagnosis is discussed across virtually all clinical fields and in different contexts. The variability in characteristics between studies and lack of consensus on overdiagnosis definition indicate the need for a uniform typology to improve coherence and comparability of studies on overdiagnosis.


title: Single-Use Energy Sources and Operating Room Time for Laparoscopic Hysterectomy: A Randomized Controlled Trial.

text: STUDY OBJECTIVES To compare the intraoperative direct costs of a single-use energy device with reusable energy devices during laparoscopic hysterectomy. DESIGN A randomized controlled trial (Canadian Task Force Classification I). SETTING An academic hospital. PATIENTS Forty-six women who underwent laparoscopic hysterectomy from March 2013 to September 2013. INTERVENTIONS Each patient served as her own control. One side of the uterine attachments was desiccated and transected with the single-use device (Ligasure 5-mm Blunt Tip LF1537 with the Force Triad generator). The other side was desiccated and transected with reusable bipolar forceps (RoBi 5 mm), and transected with monopolar scissors using the same Covidien Force Triad generator. The instrument approach used was randomized to the attending physician who was always on the patient's left side. Resident physicians always operated on the patient's right side and used the converse instruments of the attending physician. MEASUREMENTS AND MAIN RESULTS Start time was recorded at the utero-ovarian pedicle and end time was recorded after transection of the uterine artery on the same side. Costs included the single-use device; amortized costs of the generator, reusable instruments, and cords; cleaning and packaging of reusable instruments; and disposal of the single-use device. Operating room time was $94.14/min. We estimated that our single use-device cost $630.14 and had a total time savings of 6.7 min per case, or 3.35 min per side, which could justify the expense of the device. The single-use energy device had significant median time savings (-4.7 min per side, p < .001) and total intraoperative direct cost savings ($254.16 per case). CONCLUSIONS A single-use energy device that both desiccates and cuts significantly reduced operating room time to justify its own cost, and it also reduced total intraoperative direct costs during laparoscopic hysterectomy in our institution. Operating room cost per minute varies between institutions and must be considered before generalizing our results.


title: A prospective, multicentre, randomised controlled study of human fibroblast-derived dermal substitute (Dermagraft) in patients with venous leg ulcers.

text: This was an open-label, prospective, multicentre, randomised controlled study to evaluate the efficacy and safety of human fibroblast-derived dermal substitute (HFDS) plus four-layer compression therapy compared with compression therapy alone in the treatment of venous leg ulcers. The primary outcome variable was the proportion of patients with completely healed study ulcers by 12 weeks. The number healed was further summarised by ulcer duration and baseline ulcer size. Sixty-four (34%) of 186 patients in the HFDS group experienced healing by week 12 compared with 56 (31%) of 180 patients in the control group (P = 0·235). For ulcers ≤ 12 months duration, 49 (52%) of 94 patients in the HFDS group versus 36 (37%) of 97 patients in the control group healed at 12 weeks (P = 0·029). For ulcers ≤ 10 cm(2), complete healing at week 12 was observed in 55 (47%) of 117 patients in the HFDS group compared with 47 (39%) of 120 patients in the control group (P = 0·223). The most common adverse events (AEs) were wound infection, cellulitis and skin ulcer. The frequency of AEs did not markedly differ between the treatment and control groups.


title: As We Went to Press: COVID-19 Continues to Spread.

text: Updates on the coronavirus.


title: Glycogen synthase kinase-3 regulates the phosphorylation of severe acute respiratory syndrome coronavirus nucleocapsid protein and viral replication.

text: Coronavirus (CoV) nucleocapsid (N) protein is a highly phosphorylated protein required for viral replication, but whether its phosphorylation and the related kinases are involved in the viral life cycle is unknown. We found the severe acute respiratory syndrome CoV N protein to be an appropriate system to address this issue. Using high resolution PAGE analysis, this protein could be separated into phosphorylated and unphosphorylated isoforms. Mass spectrometric analysis and deletion mapping showed that the major phosphorylation sites were located at the central serine-arginine (SR)-rich motif that contains several glycogen synthase kinase (GSK)-3 substrate consensus sequences. GSK-3-specific inhibitor treatment dephosphorylated the N protein, and this could be recovered by the constitutively active GSK-3 kinase. Immunoprecipitation brought down both N and GSK-3 proteins in the same complex, and the N protein could be phosphorylated directly at its SR-rich motif by GSK-3 using an in vitro kinase assay. Mutation of the two priming sites critical for GSK-3 phosphorylation in the SR-rich motif abolished N protein phosphorylation. Finally, GSK-3 inhibitor was found to reduce N phosphorylation in the severe acute respiratory syndrome CoV-infected VeroE6 cells and decrease the viral titer and cytopathic effects. The effect of GSK-3 inhibitor was reproduced in another coronavirus, the neurotropic JHM strain of mouse hepatitis virus. Our results indicate that GSK-3 is critical for CoV N protein phosphorylation and suggest that it plays a role in regulating the viral life cycle. This study, thus, provides new avenues to further investigate the specific role of N protein phosphorylation in CoV replication.


title: Distribution of CD10-positive epithelial and mesenchymal cells in human mid-term fetuses: a comparison with CD34 expression.

text: CD10, a marker of immature B lymphocytes, is expressed in the developing epithelium of mammary glands, hair follicles, and renal tubules of human fetuses. To assess mesenchymal and stromal expression of CD10, we performed immunohistochemical assays in whole body sections from eight fetuses of gestational ages 15-20 weeks. In addition to expression in urinary tract and intestinal epithelium, CD10 was strongly expressed at both gestational ages in fibrous tissues surrounding the airways from the larynx to lung alveoli, in the periosteum and ossification center, and in the glans of external genitalia. CD10 was not expressed, however, in other cavernous tissues. These findings suggest that mesenchymal, in addition to epithelial cells at specific sites, are likely to express CD10. The glomeruli, alveoli, and glans are all end products of budding or outgrowth processes in the epithelium or skin. However, in contrast to the CD34 marker of stromal stem cells, CD10 was not expressed in vascular progenitor cells and in differentiated vascular endothelium. The alternating pattern of CD10 and CD34 expression suggests that these factors play different roles in cellular differentiation and proliferation of the kidneys, airway and external genitalia.


title: Docking study of Chloroquine and Hydroxychloroquine interaction with SARS-CoV-2 spike glycoprotein-An in silico insight into the comparative efficacy of repurposing antiviral drugs.

text: Recent outbreak of novel Coronavirus disease (Covid-19) pandemic around the world is associated with severe acute respiratory syndrome. The death toll associated with the pandemic is increasing day by day. SARS-CoV-2 is an enveloped virus and there are ample evidences that its Spike protein (S-protein) is mainly associated with pathogenesis as it is surface-exposed and mediates entry into host cells by binding to angiotensin-converting enzyme-2 (ACE-2) receptor. Therefore, it is the main target of neutralizing antibodies upon infection and there is always a quest to inhibit the S-protein which in turn may help in controlling diseases caused by SARS-CoV-2 in humans. The role of Chloroquine and Hydroxychloroquine as potential treatments for Covid-19 is still under debate globally because of some side effects associated with it. This study involves the In silico interactions of Chloroquine and Hydroxychloroquine with the S-protein of SARS-CoV-2. With the help of various computational methods, we have re-explored the potential role of both of these antiviral drugs for the treatment of Covid-19 patients by comparing the efficacy of both of the drugs to bind to S-protein at its host receptor region. In our research Hydroxychloroquine exhibited potential inhibitory effectsof S-protein with binding energy -7.28 kcal/mol than Chloroquine (-6.30 kcal/mol) at SARS-CoV-2 receptor recognition of susceptible cells. The outcomes of this research strongly appeal for in vivo trials of Hydroxychloroquine for the patients infected with Covid-19. Furthermore, the recommended doses of Hydroxychloroquine may reduce the chances of catching Covid-19 to the healthcare workers and staff who are in contact with or delivering direct care to coronavirus patients as long as they have not been diagnosed with Covid-19. We further hypothesize that the comparative S-protein-drug docking interactions may help to understand the comparative efficacy of other candidate repurposing drugs until discovery of a proper vaccine.


title: Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane- and trastuzumab-naïve patients with HER2-positive, previously treated, advanced, or recurrent gastric cancer (JFMC45-1102).

text: Paclitaxel is a standard second-line gastric cancer treatment in Japan. Trastuzumab could be active as second-line chemotherapy for taxane/trastuzumab-naïve patients with epidermal growth factor 2 (HER2)-positive advanced gastric cancer. Patients aged ≥20 years with HER2-positive, previously treated (except for trastuzumab and taxane), unresectable or recurrent gastric adenocarcinoma underwent combined trastuzumab (first and subsequent doses of 8 and 6 mg kg-1 , respectively, every 3 weeks) and paclitaxel (days 1, 8, 15, every 4 weeks) treatment. Study endpoints were best overall response, progression-free survival, overall survival, and safety. From September 2011 to March 2012, 47 Japanese patients were enrolled. Forty patients discontinued treatment after a median of 128.5 (range 4-486) days. Complete and partial responses were obtained in one and 16 patients (response rate of 37% [95% CI 23-52]), respectively. Median progression-free survival and overall survival were 5.1 (95% CI 3.8-6.5) and 17.1 (95% CI 13.5-18.6) months, respectively. Grade 3/4 adverse events were neutropenia (32.6%), leukopenia (17.4%), anemia (15.2%) and hypoalbuminemia (8.7%). There was no clinically significant cardiotoxicity or cumulative toxicity. Three (disturbed consciousness, pulmonary fibrosis, and rapid disease progression) grade 5 events occurred. In conclusion, trastuzumab combined with paclitaxel was well tolerated and was a promising regimen for patients with HER2-positive, previously treated, advanced or recurrent gastric cancer.


title: What is the current evidence of the impact on quality of life whilst waiting for management/treatment of orthopaedic/musculoskeletal complaints? A systematic scoping review.

text: PURPOSE To describe quality of life (QoL) outcome measures that are reported in the literature in patients waiting for outpatient orthopaedic/musculoskeletal specialist care and how waiting impacts on QoL in these terms. METHODS A subset of studies reporting on QoL outcome measures were extracted from literature identified in a recent scoping search of Medline, Embase, Pubmed, NHS Economic Evaluation Database (Prospero registration CRD42016047332). The systematic scoping search examined impacts on patients waiting for orthopaedic specialist care. Two independent reviewers ranked study design using the National Health and Medical Research Council aetiology evidence hierarchy, and appraised study quality using Critical Appraisal Skills Programme tools. QoL measures were mapped against waiting period timepoints. RESULTS The scoping search yielded 142 articles, of which 18 reported on impact on QoL. These studies reported only on patients waiting for hip and/or knee replacement surgery. The most recent study reported on data collected in 2006/7. The Western Ontario and McMaster Universities Arthritis Index and the SF-36 were the most commonly reported QoL measures. QoL was measured at variable timepoints in the waiting period (from a few weeks to greater than 12 months). The impact of waiting on QoL was inconsistent. CONCLUSION The evidence base was over 10 years old, reported only on patients with hip and knee problems, and on limited QoL outcome measures, and with inconsistent findings. A better understanding of the impact on QoL for patients waiting for specialist care could be gained by using standard timepoints in the waiting period, patients with other orthopaedic conditions, comprehensive QoL measures, as well as expectations, choices and perspectives of patients waiting for specialist care.


title: The role of opioid receptor agonists in ischemic preconditioning.

text: Opioids and their receptor agonists have been widely used because of their beneficial effects on pain management and control. Over the past decade, there has been an increasing interest on the experimental use of opioid agonists in the laboratory setting of ischemia and reperfusion; existing data suggest that there is a potential association between opioid agonism and the reduction of infarct size in several animal models of regional ischemia similar to that following ischemic preconditioning. Most of these studies seem to attribute these beneficial and cardioprotective effects to the stimulation of a specific opioid receptor type, the delta (δ) opioid receptor. This review focuses on the role of the delta opioid receptor agonism in several models of ischemia and reperfusion, as well as on hemorrhagic shock models, on the potential mechanisms of action following delta opioid receptor activation and on the time window for opioid administration in various animal studies.


title: Telemedicine and Neurological Practice in the COVID-19 Era.

text: Background The COVID-19 pandemic has within months turned the world upside down. With personal distancing and shortage of personal protective equipment, face-to-face health care encounters are increasingly becoming problematic. Neurological manifestations are also being observed in clinical presentations. Objective Worldwide most countries, the World Health Organization (WHO) and Centre for Disease Control (USA) have recommended use of Telemedicine during the current pandemic.With acute shortage of neurologists and neurosurgeons and their lopsided distribution, it becomes more difficult to provide neurological care to those who need it the most, particularly with travel restrictions. The author has since 2002 been advocating use of Telemedicine in Neurosciences. Materials and Methods This article reviews the increasing deployment of Telemedicine in neurological practice in the last few years, particularly the radical exponential use in the last few months due to COVID-19. Conclusions With possible reduction in face-to-face consultations, remote evaluation may become mainstream. Webinars will play an increasing role. CME's and resident training will become more and more digital. The world will never be the same again. It is imperative that we accept and start deploying the "New Normal".


Impact of delayed diagnoses at the time of COVID-19: increased rate of preventable bilateral blindness in giant cell arteritis.


docid: syamuzwy

title: The impact of financial incentives on physical activity in adults: a systematic review protocol.

text: BACKGROUND Most adults fail to meet global physical activity guidelines set out by the World Health Organization. In recent years, behavioural economic principles have been used to design novel interventions that increase physical activity. Immediate financial rewards, for instance, can motivate an individual to change physical activity behaviour by lowering the opportunity costs of exercise. This systematic review will summarise the evidence about the effectiveness of financial incentive interventions for improving physical activity in adults. METHODS We will search MEDLINE, Embase, Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, PsycINFO, EconLit, SPORTDiscus, the National Health Service Economic Evaluation Database, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform from inception using a comprehensive, electronic search strategy. The search strategy will include terms related to 'financial incentive' and 'physical activity'. Only randomised controlled trials that investigate the effect of financial incentives on physical activity in adult populations and that are written in the English language will be included. Two review authors will independently screen abstracts and titles, complete full text reviews and extract data on objective and self-reported physical activity outcomes. The authors will also assess the study quality using the Cochrane risk of bias tool and provide a systematic presentation and synthesis of the included studies' characteristics and results. If more than two studies are sufficiently similar in population, settings and interventions, we will pool the data to conduct a meta-analysis. If we are unable to perform a meta-analysis, we will conduct a narrative synthesis of the results and produce forest plots for individual studies. Our subgroup analyses will examine the differential effects of an intervention in healthy populations compared to populations with disease pathology and compare the effects of interventions using financial rewards to interventions using financial penalties. DISCUSSION This systematic review will determine the effectiveness of positive and negative financial incentives on physical activity in adults. Findings will help inform the development of public health interventions and research in this field. SYSTEMATIC REVIEW REGISTRATION PROSPERO 2017: CRD42017068263.


title: Non-parametric frequency response function tissue modeling in bipolar electrosurgery.

text: High-frequency radio energy is applied to tissue therapeutically in a number of different medical applications. The ability to model the effects of RF energy on the collagen, elastin, and liquid content of the target tissue would allow for the refinement of the control of the energy in order to improve outcomes and reduce negative side-effects. In this paper, we study the time-varying impedance spectra of the circuit. It is expected that the collagen/elastin ratio does not change over time such that the time-varying impedance is a function of the liquid content. We apply a non-parametric model in which we characterize the measured impedance spectra by its frequency response function. The measurements indicate that the changing impedance as a function of time exhibit a polynomial shift which we characterize by a polynomial regression. Finally, we quantify the uncertainty to obtain prediction intervals for the estimated polynomial describing the time variation of the impedance spectra.


title: Induction of a type I interferon signature in normal human monocytes by gadolinium-based contrast agents: comparison of linear and macrocyclic agents.

text: The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between the magnitude of the measured response and the Gd chelate used. To explore the mechanisms responsible for GdBCA induction of fibrosis in nephrogenic systemic fibrosis (NSF) in vitro, normal human dermal fibroblasts were incubated with GdBCA-treated monocyte culture supernatants and the effects on profibrotic gene expression were examined. Supernatants from monocytes exposed to all GdBCA stimulated types I and III collagen, fibronectin and α-smooth muscle actin (α-SMA) expression in normal dermal fibroblasts. The results indicate that the monocyte activation induced by GdBCA may be the initial step in the development of GdBCA associated fibrosis in NSF.


Coronavirus and children, deep-sea microbes and a bold new climate law.


New rules for biosecurity.


title: SAFE ENDOUROLOGY PROCEDURE USING A C-ARM DRAPE DURING COVID-19 TIMES.

text: Healthcare providers are at the front line of the COVID-19 outbreak response and as such are exposed to hazards that put them at risk of infection. Hazards include pathogen exposure, long working hours, psychological distress, fatigue, occupational burnout, stigma, and physical and psychological violence. [1] Health care workers, particularly those involved in airway-related procedures such as endotracheal intubation are at high risk of infection.


title: Entry remnants in flow-diverted aneurysms: Does branch geometry influence aneurysm closure?

text: OBJECTIVE Numerous studies have suggested a relationship between delayed occlusion of intracranial aneurysms treated with the Pipeline Embolization Device (PED) and the presence of an incorporated branch. However, in some cases, flow diversion may still be the preferred treatment option. This study sought to determine whether geometric factors pertaining to relative size and angulation of branch vessel(s) can be measured in a reliable fashion and whether they are related to occlusion rates. METHODS Eighty aneurysms treated at a single neurovascular center from November 2008 to June 2014 were identified. Two blinded raters prospectively reviewed the imaging performed at the time of the procedure and measured the following geometric variables: inflow jet/incorporated branch direction angle and branch artery/ parent artery ratio. Delayed occlusion was defined as the absence of complete aneurysmal occlusion at one year. Analysis was performed using logistic regression and intra-class correlation co-efficient (ICC). RESULTS Twenty-four (30%) aneurysms with 28 incorporated branches were identified. A trend toward higher inflow jet/incorporated branch direction angle was found in the group of aneurysms demonstrating delayed occlusion when compared to the group with complete occlusion. ICC revealed high correlation. Overall lower one-year occlusion rates of 53% versus 73% for aneurysms with and without incorporated branches, respectively, were also noted. CONCLUSIONS The presence of an incorporated branch conferred a 20% absolute risk increase for delayed aneurysmal occlusion. Incorporated branches with a larger angle between the inflow jet and the incorporated branch direction exhibited a trend toward lower occlusion rates. This might be further investigated using a multicenter approach in conjunction with other potentially relevant clinical and angiographic variables.


title: The effect and safety of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in women: a protocol for systematic review and meta-analysis.

text: BACKGROUND The prevalence of menopause in women with or at risk of chronic kidney disease is increasing globally. Although international guidelines on menopause recommend the use of postmenopausal hormone therapy with or without selective estrogen receptor modulators for control of vasomotor symptoms, the effects of these treatments on kidney function and albuminuria are unclear. Furthermore, women with chronic kidney disease are at significantly increased risk of venous thromboembolism and malignancy, well-documented adverse effects of postmenopausal hormone therapy. Our study aims to establish the effect of these treatments on kidney function and albuminuria in women, as well as determine the safety of these treatments in the chronic kidney disease population. METHODS We will conduct a systematic review and meta-analysis addressing the effect and safety of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in women. We plan to search for published (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), tables of contents of relevant journals) and unpublished (ongoing studies, conference proceedings) studies in all languages examining the effect of postmenopausal hormone therapy, including selective estrogen receptor modulators, on kidney function and albuminuria, as well as the risk of adverse outcomes of these treatments in women with chronic kidney disease. Two independent investigators will screen identified abstracts and select studies that examine the effect of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in the general population or adverse outcomes in the chronic kidney disease population. Data on study population, intervention, outcomes, as well as study quality and risk of bias will be independently extracted from each eligible study. Along with descriptive presentation of data, outcome measures will be presented as meta-analyses using a random effects model. Planned subgroup analyses will be completed, and meta-regression will be performed if significant heterogeneity is noted. DISCUSSION By examining the effects of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney function and albuminuria, the results of this systematic review and meta-analysis will inform management of postmenopausal women in the general population. Furthermore, it will evaluate the safety, including the risks of known adverse outcomes of postmenopausal hormone therapy and selective estrogen receptor modulators, in the already vulnerable chronic kidney disease population. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42016050651.


title: Comparison of the i-gel and other supraglottic airways in adult manikin studies: Systematic review and meta-analysis.

text: BACKGROUND The i-gel has a gel-like cuff composed of thermoplastic elastomer that does not require cuff inflation. As the elimination of cuff inflation may shorten insertion time, the i-gel might be a useful tool in emergency situations requiring prompt airway care. This systematic review and meta-analysis of previous adult manikin studies for inexperienced personnel was performed to compare the i-gel with other supraglottic airways. METHODS We searched PubMed, the Cochrane Library, and EMBASE for eligible randomized controlled trials (RCTs) published before June 2015, including with a crossover design, using the following search terms: "i-gel," "igel," "simulation," "manikin," "manikins," "mannequin," and "mannequins." The primary outcomes of this review were device insertion time and the first-attempt success rate of insertion. RESULTS A total of 14 RCTs were included. At the initial assessment without difficult circumstances, the i-gel had a significantly shorter insertion time than the LMA Classic, LMA Fastrach, LMA Proseal, LMA Unique, laryngeal tube, Combitube, and EasyTube. However, a faster insertion time of the i-gel was not observed in comparisons with the LMA Supreme, aura-i, and air-Q. In addition, the i-gel did not show the better results for the insertion success rate when compared to other devices. CONCLUSION The findings of this meta-analysis indicated that inexperienced volunteers placed the i-gel more rapidly than other supraglottic airways with the exception of the LMA Supreme, aura-i, and air-Q in manikin studies. However, the quicker insertion time is clinically not relevant. The unapparent advantage regarding the insertion success rate and the inherent limitations of the simulation setting indicated that additional evidence is necessary to confirm these advantages of the i-gel in an emergency setting.


title: Impact of Helicobacter pylori on the growth of hepatic orthotopic graft tumors in mice.

text: Helicobacter pylori is a well-known causative organism of chronic gastric diseases and has been found in many hepatic carcinoma samples. To explore the expression of apoptosis-related proteins and carcinoma development in H. pylori-infected livers, we utilized BALB/cAnSlac mice to establish an H. pylori-infected model by oral inoculation and orthotopic grafts of hepatic tumors by H22 cells, respectively. We found that H. pylori colonies could not be cultured from all liver and tumor samples. However, its 16S rRNA was detectable in 85.3% of livers and 66.7% of tumors in the infected mice. Inflammatory cells were observed and thinly distributed in the lobule portions of the liver, and H. pylori mainly existed in the infected hepatic sinusoids and the necrotic areas of the infected tumors. No significant difference was found in liver to body weight ratio between the infected and uninfected. Moreover, the pathological tumor difference was unremarkable between the two. The proliferating cell nuclear antigen (PCNA) and Bcl-2-associated X protein (Bax) expression in the infected tumors was significantly higher and lower, respectively, than those of the uninfected tumors. However, no significant difference in Bcl-2 (B-cell lymphoma 2) expression existed. The results indicate that H. pylori found in the livers which were infected by H. pylori oral inoculation could contribute to the infiltration of inflammatory cells in livers. Although H. pylori has no significant impact on the liver to body weight ratio or tumor Bcl-2 expression, it may upregulate PCNA expression and downregulate Bax expression, respectively. All our findings show that H. pylori may promote proliferation and inhibit apoptosis of tumor cells.


title: Visualizing the autophagy pathway in avian cells and its application to studying infectious bronchitis virus.

text: Autophagy is a highly conserved cellular response to starvation that leads to the degradation of organelles and long-lived proteins in lysosomes and is important for cellular homeostasis, tissue development and as a defense against aggregated proteins, damaged organelles and infectious agents. Although autophagy has been studied in many animal species, reagents to study autophagy in avian systems are lacking. Microtubule-associated protein 1 light chain 3 (MAP1LC3/LC3) is an important marker for autophagy and is used to follow autophagosome formation. Here we report the cloning of avian LC3 paralogs A, B and C from the domestic chicken, Gallus gallus domesticus, and the production of replication-deficient, recombinant adenovirus vectors expressing these avian LC3s tagged with EGFP and FLAG-mCherry. An additional recombinant adenovirus expressing EGFP-tagged LC3B containing a G120A mutation was also generated. These vectors can be used as tools to visualize autophagosome formation and fusion with endosomes/lysosomes in avian cells and provide a valuable resource for studying autophagy in avian cells. We have used them to study autophagy during replication of infectious bronchitis virus (IBV). IBV induced autophagic signaling in mammalian Vero cells but not primary avian chick kidney cells or the avian DF1 cell line. Furthermore, induction or inhibition of autophagy did not affect IBV replication, suggesting that classical autophagy may not be important for virus replication. However, expression of IBV nonstructural protein 6 alone did induce autophagic signaling in avian cells, as seen previously in mammalian cells. This may suggest that IBV can inhibit or control autophagy in avian cells, although IBV did not appear to inhibit autophagy induced by starvation or rapamycin treatment.


Investigation and management of suspected appendicitis during the COVID-19 pandemic.


title: Structure of the infectious salmon anemia virus receptor complex illustrates a unique binding strategy for attachment.

text: Orthomyxoviruses are an important family of RNA viruses, which include the various influenza viruses. Despite global efforts to eradicate orthomyxoviral pathogens, these infections remain pervasive. One such orthomyxovirus, infectious salmon anemia virus (ISAV), spreads easily throughout farmed and wild salmonids, constituting a significant economic burden. ISAV entry requires the interplay of the virion-attached hemagglutinin-esterase and fusion glycoproteins. Preventing infections will rely on improved understanding of ISAV entry. Here, we present the crystal structures of ISAV hemagglutinin-esterase unbound and complexed with receptor. Several distinctive features observed in ISAV HE are not seen in any other viral glycoprotein. The structures reveal a unique mode of receptor binding that is dependent on the oligomeric assembly of hemagglutinin-esterase. Importantly, ISAV hemagglutinin-esterase receptor engagement does not initiate conformational rearrangements, suggesting a distinct viral entry mechanism. This work improves our understanding of ISAV pathogenesis and expands our knowledge on the overall diversity of viral glycoprotein-mediated entry mechanisms. Finally, it provides an atomic-resolution model of the primary neutralizing antigen critical for vaccine development.


title: Radiographic and CT Features of Viral Pneumonia.

text: Viruses are the most common causes of respiratory infection. The imaging findings of viral pneumonia are diverse and overlap with those of other nonviral infectious and inflammatory conditions. However, identification of the underlying viral pathogens may not always be easy. There are a number of indicators for identifying viral pathogens on the basis of imaging patterns, which are associated with the pathogenesis of viral infections. Viruses in the same viral family share a similar pathogenesis of pneumonia, and the imaging patterns have distinguishable characteristics. Although not all cases manifest with typical patterns, most typical imaging patterns of viral pneumonia can be classified according to viral families. Although a definite diagnosis cannot be achieved on the basis of imaging features alone, recognition of viral pneumonia patterns may aid in differentiating viral pathogens, thus reducing the use of antibiotics. Recently, new viruses associated with recent outbreaks including human metapneumovirus, severe acute respiratory syndrome coronavirus, and Middle East respiratory syndrome coronavirus have been discovered. The imaging findings of these emerging pathogens have been described in a few recent studies. This review focuses on the radiographic and computed tomographic patterns of viral pneumonia caused by different pathogens, including new pathogens. Clinical characteristics that could affect imaging, such as patient age and immune status, seasonal variation and community outbreaks, and pathogenesis, are also discussed. The first goal of this review is to indicate that there are imaging features that should raise the possibility of viral infections. Second, to help radiologists differentiate viral infections, viruses in the same viridae that have similar pathogenesis and can have similar imaging characteristics are shown. By considering both the clinical and radiologic characteristics, radiologists can suggest the diagnosis of viral pneumonia. ©RSNA, 2018.


Systemic Corticosteroid Therapy May Delay Viral Clearance in Patients with Middle East Respiratory Syndrome Coronavirus Infection.


title: Just-in-time learning is effective in helping first responders manage weapons of mass destruction events.

text: BACKGROUND Chemical, biologic, radiologic, nuclear, and explosive (CBRNE) incidents require specialized training. The low frequency of these events leads to significant skill decay among first responders. To address skill decay and lack of experience with these high-impact events, educational modules were developed for mobile devices to provide just-in-time training to first responders en route to a CBRNE event. This study assessed the efficacy and usability of the mobile training. METHODS Ninety first responders were randomized to a control or an intervention group. All participants completed a pretest to measure knowledge of CBRNE topics. The intervention group then viewed personal protective equipment and weapons of mass destruction field management videos as an overview. Both groups were briefed on a disaster scenario (chemical nerve agent, radiologic, or explosives) requiring them to triage, assess, and manage a patient. Intervention group participants watched a mobile training video corresponding to the scenario. The control group did not receive prescenario video training. Observers rated participant performance in each scenario. After completing the scenarios, all participants answered a cognitive posttest. Those in the intervention group also answered a questionnaire on their impressions of the training. RESULTS The intervention group outperformed the control group in the explosives and chemical nerve agent scenarios; the differences were statistically significant (explosives, mean of 26.32 for intervention and 22.85 for control, p < 0.01; nerve agent, mean of 23.14 for intervention and 16.61 for control, p < 0.01). There was no statistically significant difference between the groups in the radiologic scenario (mean, 12.7 for intervention and 11.8 for control; p = 0.51). The change in pretest to posttest cognitive scores was significantly higher in the intervention group than in the control group (t = 3.28, p < 0.05). CONCLUSION Mobile just-in-time training improved first-responder knowledge of CBRNE events and is an effective tool in helping first responders manage simulated explosive and chemical agent scenarios. LEVEL OF EVIDENCE Therapeutic/care management study, level II.


title: Neonatal outcome of preterm delivery.

text: Advances in perinatal and neonatal care over the last 30 years have contributed to improved survival among extremely low birth weight (ELBW) infants. As the rate of neonatal morbidity has remained stable, parents and health care professionals involved in the care of these infants often raise questions regarding the prevalence of adverse neurodevelopmental outcomes. Existing data in the literature is heterogeneous and the reported prevalence of disability varies more than survival rates do. One of the key issues toward a better clinical management of ELBW infants is the knowledge of the nature of mortality and disability in this population of infants. Studies from individual centers report outcomes of ELBW infants and demonstrate several limitations as to the ways babies were treated. Advice to parents and decisions to be made regarding the care of these infants should be based on reliable, unbiased, and representative data drawn from geographically defined populations. Such data have recently become available. This report gives an overview of existing literature on this issue.


Presence of Decreased Intraepidermal Nerve Fiber Density Consistent with Small Fiber Neuropathy in Patients with Central Post-Stroke Pain.


title: Potentially Modifiable Risk Factors for Long-Term Cognitive Impairment After Critical Illness: A Systematic Review.

text: Long-term cognitive impairment is common in survivors of critical illness. Little is known about the etiology of this serious complication. We sought to summarize current scientific knowledge about potentially modifiable risk factors during intensive care unit (ICU) treatment that may play a substantial role in the development of long-term cognitive impairment. All searches were run on October 1, 2017. The search strategy included Ovid MEDLINE, Ovid Embase, Ovid CDR, Cochrane Central Register of Controlled Trials and Database of Abstracts of Reviews of Effect, Scopus, and Web of Science, and included MeSH headings and keywords related to intensive care, critical care, and cognitive disorders. Searches were restricted to adult subjects. Inclusion required follow-up cognitive evaluation at least 2 months after ICU discharge. Studies assessing patients with cardiac arrest, traumatic brain injury, and cardiac surgery history were excluded. The search strategy resulted in 3180 studies. Of these, 28 studies (.88%) met our inclusion criteria and were analyzed. Delirium and duration of delirium were associated with long-term cognitive impairment after ICU admission in 6 of 9 studies in which this factor was analyzed. Weaker and more inconsistent associations have been reported with hypoglycemia, hyperglycemia, fluctuations in serum glucose levels, and in-hospital acute stress symptoms. Instead, most of the studies did not find significant associations between long-term cognitive impairment and mechanical ventilation; use of sedatives, vasopressors, or analgesic medications; enteral feeding; hypoxia; extracorporeal membrane oxygenation; systolic blood pressure; pulse rate; or length of ICU stay. Prolonged delirium may be a risk factor for long-term cognitive impairment after critical illness, though this association has not been entirely consistent across studies. Other potentially preventable factors have not been shown to have strong or consistent associations with long-term cognitive dysfunction in survivors of critical illness.


title: Acute haemodynamic effects of continuous positive airway pressure in awake patients with heart failure.

text: BACKGROUND AND OBJECTIVE Continuous positive airway pressure (CPAP) has been used to treat patients with chronic heart failure (CHF) and sleep-disordered breathing (SDB). CPAP treatment in severe CHF with concomitant SDB and atrial fibrillation has been linked to impairment of cardiac output (CO) as a potential cause for adverse outcome. The aim of the present study was to test whether incremental CPAP application in awake CHF patients with SDB, with and without atrial fibrillation, induces acute alterations of blood pressure (BP), heart rate (HR) and CO. METHODS During daytime, we applied incremental CPAP (4-10 cmH2O) in 37 stable patients with CHF and SDB. BP and HR were assessed after each 1 cmH2O CPAP increase in 5-min intervals in the entire sample, and CO was assessed at one centre (n = 11). RESULTS Neither mean BP, HR nor CO changed significantly with incremental CPAP (at 0 and 10 cmH2O: 85 ± 2 and 84 ± 2 mm Hg, P = 1.0, 63 ± 1 to 61 ± 2 b.p.m., P = 0.88 and 2.03 ± 0.5 and 2.35 ± 0.8 L/min/m2 , P = 0.92, respectively). No significant differences in maximum BP drop or HR drop between patients with sinus rhythm and atrial fibrillation were found. In 1 of 37 patients, a prespecified event of haemodynamic compromise (drop of mean BP >15 mm Hg) without clinical signs occurred. CONCLUSIONS These results contribute to the evidence that CPAP does not cause haemodynamic compromise in the vast majority of normotensive CHF patients with SDB.


title: Robotic transanal microsurgery for high early rectal neoplasia (T0-T1, N0 lesions), case series of 10 patients.

text: PURPOSE/BACKGROUND In 2017, an estimated 39 910 people will receive a new diagnosis of rectal cancer. Current surgical guidelines limit transanal excision of early rectal neoplasia to 8 cm from the anal verge. We report that R0 resection of higher rectal cancers is possible using transanal robotic microsurgery. METHODS/INTERVENTIONS Ten cases of robotic assisted transanal surgery for early stage disease (T0-T1, N0) between 2013 and 2016 were reviewed. RESULTS/OUTCOMES All cases were diagnosed preoperatively with colonoscopy, and the average distance from the anal verge was 11.1 cm. The average operative time was 167 minutes, and the average blood loss was 37.5 cc. Four cases required intraoperative conversion; one conversion required robotic abdominal access to repair a proctotomy. All margins were histologically negative, and 6-month follow-up showed no recurrences. CONCLUSION/DISCUSSION Transanal robotic surgery may provide the colorectal surgeon a method to address rectal lesions farther from the anal verge.


title: The stimulatory RNA of the Visna-Maedi retrovirus ribosomal frameshifting signal is an unusual pseudoknot with an interstem element.

text: The stimulatory RNA of the Visna-Maedi virus (VMV) -1 ribosomal frameshifting signal has not previously been characterized but can be modeled either as a two-stem helix, reminiscent of the HIV-1 frameshift-stimulatory RNA, or as an RNA pseudoknot. The pseudoknot is unusual in that it would include a 7 nucleotide loop (termed here an interstem element [ISE]) between the two stems. In almost all frameshift-promoting pseudoknots, ISEs are absent or comprise a single adenosine residue. Using a combination of RNA structure probing, site directed mutagenesis, NMR, and phylogenetic sequence comparisons, we show here that the VMV stimulatory RNA is indeed a pseudoknot, conforming closely to the modeled structure, and that the ISE is essential for frameshifting. Pseudoknot function was predictably sensitive to changes in the length of the ISE, yet altering its sequence to alternate pyrimidine/purine bases was also detrimental to frameshifting, perhaps through modulation of local tertiary interactions. How the ISE is placed in the context of an appropriate helical junction conformation is not known, but its presence impacts on other elements of the pseudoknot, for example, the necessity for a longer than expected loop 1. This may be required to accommodate an increased flexibility of the pseudoknot brought about by the ISE. In support of this, (1)H NMR analysis at increasing temperatures revealed that stem 2 of the VMV pseudoknot is more labile than stem 1, perhaps as a consequence of its connection to stem 1 solely via flexible single-stranded loops.


docid: dnbhovep

title: COVID-19 in solid organ transplant recipients: a single-center case series from Spain.

text: The clinical characteristics, management and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after solid organ transplantation (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%] and heart [22.2%]) recipients diagnosed with COVID-19 by March 23, 2020 at a tertiary-care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine [HCQ]) was used in 50.0% of patients, and had to be prematurely discontinued in two of them. Other antiviral regimens included HCQ monotherapy (27.8%) and interferon-β (16.7%). As of April 4, the case fatality rate was 27.8% (5/18). After a median follow-up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C reactive protein levels at various points were significantly higher among recipients that experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS-CoV-2 infection has a severe course in SOT recipients.


title: Characteristics of replacement breeding cattle trade in Great Britain.

text: The movements of replacement breeding cattle have been implicated in the spread of many economically important cattle diseases. In this analysis, records from the Cattle Tracing System database were used to investigate the frequency and characteristics of replacement breeding cattle trade in Great Britain. During the 2006 calendar year, an estimated 48.7 per cent of beef herds and 47.8 per cent of dairy herds purchased at least one replacement breeding animal. Open beef herds purchased an average of 7.2 replacement animals (median: 4, range: 1-819) from 3.6 source herds (median: 2, range: 1-114), while open dairy herds purchased an average of 13.7 replacement animals (median: 7, range: 1-827) from 5.2 source herds (median: 3, range: 1-146). The most common animal types purchased by beef and dairy herds were open heifers and open lactating cows, respectively. Although the movements of purchased replacement breeding cattle accounted for only 13 per cent of individual movements in the between-herd contact network, they had a disproportionately strong influence on the risk of disease spreading through the industry as evidenced by their high betweenness centrality scores. These results emphasise the importance of ensuring that good biosecurity programmes are in place to prevent disease transmission.


title: COVID 19: Designing and conducting an online mini-multiple interview (MMI) in a dynamic landscape.

text: Introduction: The COVID-19 pandemic presented numerous, significant challenges for medical schools, including how to select the best candidates from a pool of applicants when social distancing and other measures prevented "business as usual" admissions processes. However, selection into medical school is the gateway to medicine in many countries, and it is critical to use processes which are evidence-based, valid and reliable even under challenging circumstances. Our challenge was to plan and conduct a multiple-mini interview (MMI) in a dynamic and stringent safe distancing context.Methods: This paper reports a case study of how to plan, re-plan and conduct MMIs in an environment where substantially tighter safe distancing measures were introduced just before the MMI was due to be delivered.Results: We report on how to design and implement a fully remote, online MMI which ensured the safety of candidates and assessors.Discussion: We discuss the challenges of this approach and also reflect on broader issues associated with selection into medical school during a pandemic. The aim of the paper is to provide broadly generalizable guidance to other medical schools faced with the challenge of selecting future students under difficult conditions.


title: Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication.

text: Members of rhinovirus C (RV-C) species are more likely to cause wheezing illnesses and asthma exacerbations compared with other rhinoviruses. The cellular receptor for these viruses was heretofore unknown. We report here that expression of human cadherin-related family member 3 (CDHR3) enables the cells normally unsusceptible to RV-C infection to support both virus binding and replication. A coding single nucleotide polymorphism (rs6967330, C529Y) was previously linked to greater cell-surface expression of CDHR3 protein, and an increased risk of wheezing illnesses and hospitalizations for childhood asthma. Compared with wild-type CDHR3, cells transfected with the CDHR3-Y529 variant had about 10-fold increases in RV-C binding and progeny yields. We developed a transduced HeLa cell line (HeLa-E8) stably expressing CDHR3-Y529 that supports RV-C propagation in vitro. Modeling of CDHR3 structure identified potential binding sites that could impact the virus surface in regions that are highly conserved among all RV-C types. Our findings identify that the asthma susceptibility gene product CDHR3 mediates RV-C entry into host cells, and suggest that rs6967330 mutation could be a risk factor for RV-C wheezing illnesses.


Rapid on-site evaluation and the COVID-19 pandemic.


title: Effect of corneal contact lens wear on healing time and comfort post LGK for treatment of SCCEDs in boxers.

text: PURPOSE To determine whether dogs with spontaneous chronic corneal epithelial defects (SCCEDs) would heal faster and with an improved comfort score following linear grid keratotomy (LGK) combined with corneal contact lens (Acrivet(™) ) wear when compared to dogs having the LGK procedure alone. STUDY DESIGN Prospective study. METHODS Twenty-seven boxer dogs (27 eyes) diagnosed with a SCCEDs were enrolled in the study. A LGK was performed on all dogs under dexmedetomidine and butorphanol sedation. Fourteen eyes were randomly assigned to receive a corneal contact lens. The dogs were evaluated typically at 7, 10, and 14 days or until the ulceration was healed. Client surveys were completed by the owners to subjectively assess comfort level and contact lens retention. Statistical analyses were performed utilizing generalized linear models and survival analysis with the Wilcoxon-Gehan test to evaluate group differences. RESULTS All ulcers healed after the LGK procedure. Dogs with bandage contact lenses had a statistically significant (P = 0.035) decrease in median healing time (7 days (95% CI [7,9]) compared to those without contact lenses (10 days (95% CI [7,12])). There was no difference in subjective comfort score between treatment groups. Early contact loss occurred in 28.6% (95% CI [8.4%, 58.1%]) of dogs. All of the Acrivet(™) ruler corneal measurements agreed to within 1 mm (95% CI [87.2%, 100%]) of the Jameson caliper measurements of horizontal corneal diameter. CONCLUSIONS The use of corneal bandage contact lenses significantly decreased median healing time although there was no effect on subjective comfort score. The Acrivet(™) ruler measurements were accurate in determining corneal diameter and therefore contact lens size.


title: Qualitative Assessment of Rapid System Transformation to Primary Care Video Visits at an Academic Medical Center.

text: BACKGROUND The coronavirus disease 2019 pandemic spurred health systems across the world to quickly shift from in-person visits to safer video visits. OBJECTIVE To seek stakeholder perspectives on video visits' acceptability and effect 3 weeks after near-total transition to video visits. DESIGN Semistructured qualitative interviews. SETTING 6 Stanford general primary care and express care clinics at 6 northern California sites, with 81 providers, 123 staff, and 97 614 patient visits in 2019. PARTICIPANTS Fifty-three program participants (overlapping roles as medical providers [n = 20], medical assistants [n = 16], nurses [n = 4], technologists [n = 4], and administrators [n = 13]) were interviewed about video visit transition and challenges. INTERVENTION In 3 weeks, express care and primary care video visits increased from less than 10% to greater than 80% and from less than 10% to greater than 75%, respectively. New video visit providers received video visit training and care quality feedback. New system workflows were created to accommodate the new visit method. MEASUREMENTS Nine faculty, trained in qualitative research methods, conducted 53 stakeholder interviews in 4 days using purposeful (administrators and technologists) and convenience (medical assistant, nurses, and providers) sampling. A rapid qualitative analytic approach for thematic analysis was used. RESULTS The analysis revealed 12 themes, including Pandemic as Catalyst; Joy in Medicine; Safety in Medicine; Slipping Through the Cracks; My Role, Redefined; and The New Normal. Themes were analyzed using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to identify critical issues for continued program utilization. LIMITATIONS Evaluation was done immediately after deployment. Although viewpoints may have evolved later, immediate evaluation allowed for prompt program changes and identified broader issues to address for program sustainability. CONCLUSION After pandemic-related systems transformation at Stanford, critical issues to sustain video visit long-term viability were identified. Specifically, technology ease of use must improve and support multiparty videoconferencing. Providers should be able to care for their patients, regardless of geography. Providers need decision-making support with virtual examination training and home-based patient diagnostics. Finally, ongoing video visit reimbursement should be commensurate with value to the patients' health and well-being. PRIMARY FUNDING SOURCE Stanford Department of Medicine and Stanford Health Care.


title: Herbs and other dietary supplements: current regulations and recommendations for use to maintain health in the management of the common cold or other related infectious respiratory illnesses.

text: Herbal preparations are sold as dietary supplements in the United States and are subject to the rules and regulations of various health care and economic government agencies that monitor the sale of these products. One approach to assessing the usefulness of these substances is to focus on one particular disease state and then review both the primary literature and expert opinion. The common cold is an important illness due to its recurring nature, the number of people it afflicts, and its economic impact on patients. Dietary supplements have been shown to decrease the duration, the severity, and the frequency of symptoms of the common cold. The most commonly available supplements are zinc, ginseng, echinacea, and vitamin C. Data from expert opinion suggested that certain supplements are more beneficial than others to maintain one's health during episodes of the common cold. Expert opinion regarding the use of dietary supplements in other related infectious respiratory illnesses, such as the flu, when aggregated with expert opinion findings regarding the common cold were not contradictory. The primary literature provided insights into specific dosages and compounds that may be used in practice.


To control the covid-19 outbreak, young, healthy patients should avoid the emergency department.


title: Prolonged mechanical ventilation worsens sepsis-induced diaphragmatic dysfunction in the rat.

text: BACKGROUND Short-term mechanical ventilation (MV) protects against sepsis-induced diaphragmatic dysfunction. Prolonged MV induces diaphragmatic dysfunction in non-septic animals, but few reports describe the effects of prolonged MV in sepsis. We hypothesized that prolonged MV is not protective but worsens the diaphragmatic dysfunction induced by a mild sepsis, because MV and sepsis share key signaling mechanisms, such as cytokine upregulation. METHOD We studied the impact of prolonged MV (12 h) in four groups (n = 8) of male Wistar rats: 1) endotoxemia induced by intraperitoneal injection of Escherichia coli lipopolysaccharide, 2) MV without endotoxemia, 3) combination of endotoxemia and MV and 4) sham control. Diaphragm mechanical performance, pro-inflammatory cytokine concentrations (Tumor Necrosis Factor-α, Interleukin-1β, Interleukin-6) in plasma were measured. RESULTS Prolonged MV and sepsis independtly reduced maximum diaphragm force (-27%, P = 0.003; -37%, P<0.001; respectively). MV and sepsis acted additively to further decrease diaphragm force (-62%, P<0.001). Similar results were observed for diaphragm kinetics (maximum lengthening velocity -47%, P<0.001). Sepsis and MV reduced diaphragm cross sectional area of type I and IIx fibers, which was further increased by the combination of sepsis and MV (all P<0.05). Sepsis and MV were individually associated with the presence of a robust perimysial inflammatory infiltrate, which was more marked when sepsis and MV were both present (all P<0.05). Sepsis and, to a lesser extent, MV increased proinflammatory cytokine production in plasma and diaphragm (all P<0.05); proinflammatory cytokine expression in plasma was increased further by the combination of sepsis and MV (all P<0.05). Maximum diaphragm force correlated negatively with plasma and diaphragmatic cytokine production (all p<0.05). CONCLUSIONS Prolonged (12 h) MV exacerbated sepsis-induced decrease in diaphragm performance. Systemic and diaphragmatic overproduction of pro-inflammatory cytokines may contribute to diaphragm weakness.


Incentive spirometry to prevent acute chest syndrome in adults with sickle cell disease; a RCT.


title: Extrapulmonary manifestations of COVID-19.

text: Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.


Covid-19 pandemic: a public and global mental health opportunity for social transformation?


title: Prospective nonrandomized comparison of quality of life and recurrence between high ligation and stripping and radiofrequency ablation for varicose veins.

text: PURPOSE Varicose veins are a major problem worldwide and improvement in quality of life (QoL) is the ultimate goal after treatment of this benign disease. However QoL is highly dependent on personal and social factors. This study compares high ligation and stripping (HS) and radiofrequency ablation (RFA) in terms of QoL and recurrence in Korea. METHODS A retrospective analysis of prospectively collected data between August 2006 and October 2008 was performed for patients undergoing HS and RFA at a single institution. QoL was assessed with a questionnaire preoperatively, at 3 months postoperatively and annually thereafter. Recurrence was assessed by Duplex ultrasound annually after surgery. RESULTS A total of 272 patients completed the questionnaire at 3 months. Among these patients, 155 patients returned for their annual follow-up. There were no significant differences between HS and RFA in global QoL scores, although RFA showed less pain. However, paresthesia rates were also higher after RFA. Recurrence rates were similar between the two modalities, although technical failures were more common after RFA. CONCLUSION Overall QoL and recurrence rates were similar between the two modalities. The benefits of RFA do not seem to be enough to overcome the higher costs of HS in Korea.


title: Left atrial size and function as assessed by computed tomography in cardiac resynchronization therapy: Association to echocardiographic and clinical outcome.

text: To evaluate whether baseline left atrial (LA) volume and function were associated with clinical or echocardiographic response to cardiac resynchronization therapy (CRT), and to determine LA reverse remodeling as assessed by computed tomography (CT). We prospectively included patients receiving a CRT system who underwent dynamic cardiac CT with measurement of LA size and function before and 6 months after implantation. Patients alive not hospitalized for heart failure, and improving ≥1 NYHA class or ≥10% in 6-min walk test after 6 months follow-up were classified as clinical responders. Echocardiographic response was defined as ≥15% reduction in left ventricular (LV) end-systolic volume. We included 138 patients, of whom 95 (69%) were clinical responders and 114 (83%) were echocardiographic responders. We found no association between baseline measures of LA volume or function and clinical or echocardiographic response. Mean reduction in LA maximum and minimum volumes at 6 months were 3.3 ± 12.7 ml/m2 (p = 0.004) and 2.6 ± 11.4 ml/m2 (p = 0.01) corresponding to a relative reduction of 4.1 and 5.0%, respectively. LV end-systolic relative volume reduction was 35.2 ± 22.4% (p < 0.001). No measures of LA function changed significantly. Cardiac CT measures of baseline LA volume and function are not associated with clinical or echocardiographic response to CRT. Change in LA volume and function is marginal after 6 months despite pronounced LV reverse remodeling.


title: Alvimopan for recovery of bowel function after radical cystectomy.

text: BACKGROUND Alvimopan is used in abdominal surgery to reduce postoperative ileus in patients undergoing small bowel resections with primary anastomosis. The role and efficacy of alvimopan in patients undergoing radical cystectomy with urinary diversion is not well understood. OBJECTIVES To assess the effects of alvimopan in the context of enhanced recovery pathways compared to enhanced recovery pathways alone for perioperative bowel dysfunction in patients undergoing radical cystectomy. SEARCH METHODS The terms alvimopan and cystectomy were used to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We also reviewed abstracts from the past four years (2013 to 2016) of the American Urologic Association, Society of Urologic Oncology, and American Society of Clinical Oncology Genitourinary Cancers. SELECTION CRITERIA We searched for randomized controlled trials that compared alvimopan to placebo. DATA COLLECTION AND ANALYSIS This study was based on a published protocol. We performed a comprehensive search of multiple databases including CENTRAL in the Cochrane Library, MEDLINE, Embase, LILACS, Web of Science, Scopus and Biosis, which we last updated on 6 February 2017. We also searched abstract proceedings for major relevant meetings (2013 to 2016), databases of the grey literature, trial registries, citations of relevant reviews and contacted clinical experts and the drug manufacturer.Two independent reviewers screened the literature in two stages (title and abstract, full-text) using Covidence software. Two independent reviewers assessed the risk of bias on a 'per outcome' basis using the Cochrane 'Risk of bias; tool and rated the quality of evidence according to GRADE. Results of the single eligible trial were reported in a 'Summary of findings' table based on an intention-to-treat analysis. MAIN RESULTS Based on a single trial and moderate-quality evidence, alvimopan reduced the time to reach a composite endpoint of tolerance of solid food and documented bowel movements (hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.41 to 2.23). This represents 165 more patients (109 more to 207 more) per 1000 meeting this endpoint within 10 days of surgery. Based on moderate-quality evidence, alvimopan reduced the time to hospital discharge (HR 1.67, 95% CI 1.38 to 2.01). This represents 138 more patients (82 more to 198 more) per 1000 being discharged within 10 days of surgery. Also based on moderate-quality evidence, alvimopan was associated with a reduced risk of major adverse events (risk ratio (RR) 0.28, 95% CI 0.18 to 0.44) representing 355 fewer patients (404 fewer to 276 fewer) with major adverse events per 1000. We downgraded this outcome for indirectness as it included adverse events that we did not consider major.In terms of secondary outcomes, alvimopan did not appear to alter the rate of readmission (RR 0.89, 95% CI 0.59 to 1.33), change the rate of any cardiovascular event (RR 0.54, 95% CI 0.27 to 1.05) or alter the mean narcotic pain medication use (mean difference 0, 95% CI 14.08 fewer to 14.08 more morphine equivalents). The quality of evidence was moderate for all three outcomes. Based on high-quality evidence, alvimopan reduced the rate of nasogastric tube replacement (RR 0.31, 95% CI 0.16 to 0.59). We did not find evidence for the drug's impact on rates of parenteral nutrition. All outcomes were short term and limited to a 30-day time horizon.Based on the existence of only one trial, we were unable to perform any subgroup or sensitivity analyses. AUTHORS' CONCLUSIONS In patients undergoing radical cystectomy and urinary diversion, the use of alvimopan administered as part of an enhanced recovery pathway for a limited duration (up to 15 doses for up to seven days) probably reduces the time to tolerance of solid food, time to hospital discharge and rates of major adverse events. Readmission rates, rates of cardiovascular events and narcotic pain requirements are probably similar. The need for reinsertion of nasogastric tubes is reduced. We found no evidence for the impact on rates of parenteral nutrition within 30 postoperative days.


title: Preperitoneal herniation and bowel obstruction post laparoscopic inguinal hernia repair: case report and review of the literature.

text: Laparoscopic inguinal hernia repairs, both transabdominal preperitoneal (TAPP) and total extraperitoneal (TEP), are associated with peritoneal defects or tears. Nonclosure of the tears can lead to bowel obstruction. I present a case of an early (48 h) bowel obstruction related to a peritoneal defect post TAPP inguinal hernia repair. The literature on peritoneal closure and bowel obstruction related to laparoscopic inguinal hernia repair is reviewed as well as options for repairing defects.


title: Castration in the standing horse combining laparoscopic and conventional techniques.

text: BACKGROUND Standing laparoscopic castration without orchidectomy has been shown to be a reliable method of castration in animals with abdominal cryptorchidism, but it cannot be recommended as a method of castration in those with inguinal cryptorchidism or normal males. An alternative laparoscopic method for the castration of horses with descended testes was developed. OBJECTIVES To report the results of laparoscopy-assisted abdominal transection of the spermatic cord and a modified open method in the standing horse for castration of descended testes in unilateral abdominal cryptorchids. STUDY DESIGN Descriptive case series. METHODS Fifteen unilateral abdominal cryptorchids were castrated laparoscopically by performing intra-abdominal ligation of both spermatic cords. The spermatic cord of the cryptorchid testis was not transected. After intra-abdominal transection of the spermatic cord of the descended testis, the testis was removed by an open castration technique in the standing horse. Data collected included time taken to perform the surgical procedure, surgical complications and post-operative recovery. RESULTS Abdominal testes were located on the right side in eight horses and on the left in seven. The surgical procedure was easy to perform and few intra- or post-operative complications were seen. Pulse and respiration rates and rectal temperatures remained within normal limits during the evaluation period in all but one animal, which displayed transient pyrexia. The scrotal and laparoscopic incisional wounds healed well without any signs of swelling or exudate. In one Warmblood, there was prolapse of subcutaneous tissue the day after surgery, which retracted in 3 days. The owners were contacted by telephone at 2-3 months after discharge. Post-operative recovery had been uneventful in all horses. MAIN LIMITATIONS This study included a small number of cases in which all surgeries were performed by or under the supervision of the same surgeon. Follow-up was limited to telephone reports from owners. CONCLUSIONS A laparoscopic technique that is combined with an open scrotal incision to remove the descended testis in the standing horse was developed and shown to be a safe and reliable option for the castration of unilateral abdominal cryptorchids.


title: Changes in the electroencephalogram during anaesthesia and their physiological basis.

text: The use of EEG monitors to assess the level of hypnosis during anaesthesia has become widespread. Anaesthetists, however, do not usually observe the raw EEG data: they generally pay attention only to the Bispectral Index (BIS™) and other indices calculated by EEG monitors. This abstracted information only partially characterizes EEG features. To properly appreciate the availability and reliability of EEG-derived indices, it is necessary to understand how raw EEG changes during anaesthesia. With hemi-frontal lead EEGs obtained under volatile anaesthesia or propofol anaesthesia, the dominant EEG frequency decreases and the amplitude increases with increasing concentrations of anaesthetic. Looking more closely, the EEG changes are more complicated. At surgical concentrations of anaesthesia, spindle waves (alpha range) become dominant. At deeper levels, this activity decreases, and theta and delta waves predominate. At even deeper levels, EEG waveform changes into a burst and suppression pattern, and finally becomes flat. EEG waveforms vary in the presence of noxious stimuli (surgical skin incision), which is not always reflected in BIS™, or other processed EEG indices. Spindle waves are adequately sensitive, however, to noxious stimuli: under surgical anaesthesia they disappear when noxious stimuli are applied, and reappear when adequate analgesia is obtained. To prevent awareness during anaesthesia, I speculate that the most effective strategy is to administer anaesthetic agents in such a way as to maintain anaesthesia at a level where spindle waves predominate.


title: Response to "Comments on 'Zhang et al.: Clinical trial analysis of 2019-nCoV therapy registered in China '".

text: We thank Dr. Yang and colleagues for their attention to our article1,2 . And we appreciate their meaningful suggestions, which we highly agree with. With the purpose of letting the public know the overall situation of the clinical trials of new coronary pneumonia in China as soon as possible, we completed the data collection and brief analysis in a very short time. This article is protected by copyright. All rights reserved.


docid: ilmmvjxy

title: Mars walking simulation: An electromyographic analysis.

text: Context With a long duration return mission to Mars on the horizon, we must learn as much about the environment and its influence on the musculoskeletal system as possible to develop countermeasures and mitigate deleterious health effects and maladaptation. Aims To determine the influence of simulated Mars gravity on the activity of four locomotor muscles while walking, in comparison to 1 G, using lower body positive pressure (LBPP). Material and Methods A total of 14 male subjects (mean age: 20.6 ± 2.4 years) performed bouts of walking in both simulated Mars gravity (0.38 G) and Earth gravity (1 G) using an LBPP device. The dependent variables were the muscle activity evoked in the tibialis anterior, vastus lateralis, gluteus maximus and lateral portion of the gastrocnemius, measured using electromyography and expressed as percentages of maximum voluntary isometric contractions, and heart rate (HR). For statistical analysis, a paired t-test was performed. Statistical significance was defined as P < 0.05. Results No significant differences in muscle activity were found across conditions for any of the investigated muscles. A significant mean difference in the HR was identified between Earth (105.15 ± 8.1 bpm) and Mars (98.15 ± 10.44 bpm) conditions (P = 0.027), wherein the HR was lower during the Mars trial. Conclusions The Mars environment may not result in any deteriorative implications for the musculoskeletal system. However, if future research should report that stride frequency and thus activation frequency is decreased in the simulated Mars gravity, negative implications may be posed for muscle retention and reconditioning efforts on the Red Planet.


A Game Plan for the Resumption of Sport and Exercise After Coronavirus Disease 2019 (COVID-19) Infection.


title: The impact of viral respiratory infection on the severity and recovery from an asthma exacerbation.

text: BACKGROUND : Viral respiratory illness triggers asthma exacerbations, but the influence of respiratory illness on the acute severity and recovery of childhood asthma is unknown. Our objective was to evaluate the impact of a concurrent acute respiratory illness (based on a clinical definition and PCR detection of a panel of respiratory viruses, Mycoplasma pneumoniae and Chlamydia pneumoniae) on the severity and resolution of symptoms in children with a nonhospitalized exacerbation of asthma. METHODS : Subjects were children aged 2 to 15 years presenting to an emergency department for an acute asthma exacerbation and not hospitalized. Acute respiratory illness (ARI) was clinically defined. Nasopharyngeal aspirates (NPA) were examined for respiratory viruses, Chlamydia and Mycoplasma using PCR. The primary outcome was quality of life (QOL) on presentation, day 7 and day 14. Secondary outcomes were acute asthma severity score, asthma diary, and cough diary scores on days 5, 7, 10, and 14. RESULTS : On multivariate regression, presence of ARI was statistically but not clinically significantly associated with QOL score on presentation (B = -0.36, P = 0.025). By day 7 and 14, there was no difference between groups. Asthma diary score was significantly higher in children with ARI (B = 0.41, P = 0.039) on day 5 but not on presentation or subsequent days. Respiratory viruses were detected in 54% of the 78 NPAs obtained. There was no difference in the any of the asthma outcomes of children grouped by positive or negative NPA. CONCLUSIONS : The presence of a viral respiratory illness has a modest influence on asthma severity, and does not influence recovery from a nonhospitalized asthma exacerbation.


title: Septic shock, necrotizing pneumonitis, and meningoencephalitis caused by Mycoplasma pneumoniae in a child: a case report.

text: Mycoplasma pneumoniae is an important causative agent of respiratory infection in childhood. Although the infection caused by M. pneumoniae is classically described as benign, severe and life-threatening pulmonary and extrapulmonary complications can occur. This study describes the first case of septic shock related to M. pneumoniae in a child with necrotizing pneumonitis, severe encephalitis, and multiple organs involvement, with a favorable outcome after lobectomy and systemic corticosteroids.


title: X-ray Structural and Functional Studies of the Three Tandemly Linked Domains of Non-structural Protein 3 (nsp3) from Murine Hepatitis Virus Reveal Conserved Functions.

text: Murine hepatitis virus (MHV) has long served as a model system for the study of coronaviruses. Non-structural protein 3 (nsp3) is the largest nsp in the coronavirus genome, and it contains multiple functional domains that are required for coronavirus replication. Despite the numerous functional studies on MHV and its nsp3 domain, the structure of only one domain in nsp3, the small ubiquitin-like domain 1 (Ubl1), has been determined. We report here the x-ray structure of three tandemly linked domains of MHV nsp3, including the papain-like protease 2 (PLP2) catalytic domain, the ubiquitin-like domain 2 (Ubl2), and a third domain that we call the DPUP (domain preceding Ubl2 and PLP2) domain. DPUP has close structural similarity to the severe acute respiratory syndrome coronavirus unique domain C (SUD-C), suggesting that this domain may not be unique to the severe acute respiratory syndrome coronavirus. The PLP2 catalytic domain was found to have both deubiquitinating and deISGylating isopeptidase activities in addition to proteolytic activity. A computationally derived model of MHV PLP2 bound to ubiquitin was generated, and the potential interactions between ubiquitin and PLP2 were probed by site-directed mutagenesis. These studies extend substantially our structural knowledge of MHV nsp3, providing a platform for further investigation of the role of nsp3 domains in MHV viral replication.


title: Complete low-intensity endurance training programme in haemodialysis patients: improving the care of renal patients.

text: BACKGROUND Patients on haemodialysis (HD) have a decreased physical and functional capacity. Several studies have reported the beneficial effects of exercise on the physical, functional and psychological functioning of HD patients. Despite these results, exercise programmes on HD are not commonplace. OBJECTIVE To analyse the effect of an intradialysis endurance training programme on muscular strength and functional capacity in our HD patients. MATERIAL AND METHODS A 6-month single-centre prospective study. HD patients were non-randomly assigned to an exercise group (group E) or a control group (group C). Exercise training included complete endurance training using balls, weights and elastic bands in the first 2 h of an HD session; group C received standard HD care. Analysed data: (1) biochemical parameters; (2) biceps and quadriceps muscle tone, maximum quadriceps length strength (MQLS) and dominant hand grip (HG); (3) functional capacity tests: sit-to-stand-to-sit (STS10) and 6-min walking test (6MWT). RESULTS Forty patients were included, 55% were men; their mean age was 68.4 years; the patients were 61.6 months on HD; 16 patients were in group E and 24 in group C. In group E, muscular strength showed a significant improvement in MQLS (15.6 ± 10.7 vs. 17.7 ± 12.5 kg, p < 0.05) and HG (22.1 ± 13.2 vs. 24.1 ± 15.8 kg, p < 0.05) at the end of the programme, while a global decrease was reported in group C (MQLS 20.9 ± 9.3 vs. 16.2 ± 8.4 kg, p < 0.05; HG 25.1 ± 10.3 vs. 24.1 ± 11.1 kg). 6MWT significantly improved in group E (20%, 293.1 vs. 368 m, p < 0.001) and decreased in group C (10%, 350 vs. 315 m, p < 0.004). At the end of the programme, STS10 time was reduced in group E (2.1 ± 18.5 vs. 28.7 ± 20.6 s), while it rose in group C (31.5 ± 17.9 vs. 36.4 ± 19.8 s), though significant differences were not found. CONCLUSIONS (1) The intradialysis training programme improved muscular strength and functional capacity in our HD patients. (2) These results support the benefits of exercise training for HD patients. (3) Nephrologists should consider exercise training as a standard practice for the care of HD patients.


title: Robotic surgery in pediatric urology: Current status.

text: Robot-assisted laparoscopic surgery (RALS) has been increasingly embraced in the fields of adult and pediatric urology, especially in North America and Europe. The advantages of a stable magnified 3-D view, tremor filtering, and motion scaling allow for precise intracorporeal exposure and suturing. Because most surgeries are performed as reconstructive rather than excision procedures, the robotic platform is particularly feasible for the field of pediatric urology. In this review, we summarize the recent viewpoints on RALS, such as pyeloplasty, ureteral reimplantation, bladder neck reconstruction, bladder neck sling, appendicovesicostomy, bladder diverticulectomy, and treatments for ureterocele or ectopic ureters, and we also critically summarize the current status of the literature. Based on our initial experience, RALS is technically feasible for pediatric patients and may be achieved with comparable surgical outcomes. RALS is also associated with reduced morbidity compared to open surgery to conventional laparoscopic surgery. This evolution will offer an alternative in the treatment pediatric patients, along with improved care and patient quality of life. Further large case series and randomized controlled trials that investigate the robotic platform's technological improvements will help to expand indications of RALS in the field of pediatric urology.


docid: mtznfpfk

title: Covid-19: Guidance is urgently needed on who should be treated in event of shortages, say lawyers.


title: Transbronchial Cryobiopsies for Diagnosing Interstitial Lung Disease: Real-Life Experience from a Tertiary Referral Center for Interstitial Lung Disease.

text: BACKGROUND Transbronchial cryobiopsy (cTBB) may offer an alternative to surgical lung biopsy (SLB) for histopathological diagnosis of interstitial lung diseases (ILDs). However, real-life experience is limited, although case series are increasingly reported. OBJECTIVES We aimed to evaluate the value of cTBB performed under real-life conditions in a tertiary care center for ILDs. METHODS Data on all patients undergoing a cTBB for evaluation of suspected ILD between October 2015 and January 2017 were included in this retrospective case series. Procedure details, complication rates, histopathological results, and diagnostic consensus reached by a multidisciplinary team (MDT) discussion were collated and evaluated. RESULTS A total of 109 patients (mean age 64 years, range 19-85; 66% male, 38% never smokers) referred to our center with features suggestive of ILD underwent cTBB. The mean FVC% predicted was 77% (range 41-131), with a mean DLCO of 51% (range 20-86), and a 6-min walking test (6MWT) of 402 m (range 100-642). On average, 4 samples were taken from each patient (range 1-8), with a mean biopsy diameter of 5 mm (range 2-12). Complications included pneumothorax (11.9%), all treated with chest drain. Moderate bleeding occurred in 28.4% (all resolved without active measures). No acute disease exacerbations and no deaths occurred. A histopathological pattern diagnosis was possible in 80 cases (73.4%), and 26.6% of cases were considered nonspecific. An MDT consensus diagnosis was reached in 83.5% of cases. Subsequent SLB was proposed in 13 cases and performed in 8 cases. CONCLUSIONS In the real-world setting, cTBB has a meaningful diagnostic value in the context of a MDT approach and may enable histopathological assessment even in patients with more advanced disease unsuitable for SLB.