title: Lessons learned from variation in response to therapy in clinical trials.

text: In the past, we viewed lack of response to asthma medications as a rare event. Based on recent studies, we now expect significant variation in treatment response for all asthma medications. However, little information is available about methods to predict favorable treatment response. Research conducted in the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network and Childhood Asthma Research and Education Network verified this variability in response to several long-term control medications, specifically inhaled corticosteroids and leukotriene receptor antagonists, in adults and children with mild-to-moderate persistent asthma. The networks also identified potential methods to use patients' characteristics, such as age and allergic status, and biomarkers, such as bronchodilator response, exhaled nitric oxide, and urinary leukotrienes, to help predict response to inhaled corticosteroids and leukotriene receptor antagonists and to determine which of the 2 treatments might be more effective in individual patients. This information now assists the clinician in personalizing asthma treatment at the time of initiating long-term control therapy.


title: Identification of Inhibitors for the DEDDh Family of Exonucleases and a Unique Inhibition Mechanism by Crystal Structure Analysis of CRN-4 Bound with 2-Morpholin-4-ylethanesulfonate (MES).

text: The DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors for DEDDh exonucleases. We further show that two of the inhibitors, ATA and PV6R, indeed inhibit the exonuclease activity of the viral protein NP exonuclease of Lassa fever virus in vitro. Moreover, we determine the crystal structure of CRN-4 in complex with MES that reveals a unique inhibition mechanism by inducing the general base His179 to shift out of the active site. Our results not only provide the structural basis for the inhibition mechanism but also suggest potential lead inhibitors for the DEDDh exonucleases that may pave the way for designing nuclease inhibitors for biochemical and biomedical applications.


title: Physical activity monitors to enhance amount of physical activity in older adults - a systematic review and meta-analysis.

text: Background The body of evidence related to the effect of physical activity monitor-based interventions has grown over the recent years. However, the effect of physical activity monitor-based interventions in older adults remains unclear and should be systematically reviewed. Objective The objective of this systematic review was to estimate the effect of physical activity monitor-based interventions on physical activity behavior in participants aged 65 and above. Subsequently we explored the effect on body mass index, physical capacity, and health-related quality of life and finally the impact of patient- and intervention characteristics. Methods Searches in MEDLINE, EMBASE, SPORTDiscus, CINAHL, and CENTRAL were performed on April 26, 2018. No publication date filters were applied. References of eligible studies were scrutinized and relevant journals were hand-searched. Randomized controlled trials and randomized cross-over trials investigating the effect of a physical activity monitor-based intervention on physical activity were included. Studies were included if the mean age of the participants was above 65 years, and participants could walk independently with or without walking aids. The Cochrane handbook was used as a template for extracting data and the RoB 2.0 tool was used to assess risk of bias. Random-effects meta-analysis using Hedges g, were used to pool the study results. The main outcome of this study was physical activity. Results Twenty-one studies with 2783 participants were included. The median participant age in the studies was 70.5 years, the median percentage of male participants was 42%, and the median baseline daily step count was 5268. Physical activity monitor-based interventions had a moderate effect (SMD = 0.54, 95% CI: 0.34 to 0.73) compared to control interventions, corresponding to an average increase of 1297 steps per day in the intervention groups. No impact of patient and intervention characteristics on the effect estimates were found. Short conclusion Low quality of evidence was found for a moderate effect of physical activity monitor-based interventions on physical activity compared with control interventions. More studies with higher research methodology standards are required. PROSPERO registration CRD42018083648.


The dangerous patient. Medical, legal, and public policy responses--a symposium introduction and overview.


title: Clinical characteristics and short-term outcomes of coronavirus disease 2019: retrospective, single-center experience of designated hospital in Poland.

text: INTRODUCTION Since the first reported case of coronavirus disease 19 (COVID-19) in Poland, the worldwide pandemic has spread throughout the country, leading to many hospital admissions. There has been urgent need to determine clinical characteristics of Polish patients with laboratory-confirmed SARS-CoV-2 infection in the clinical setting. OBJECTIVES The aim of this retrospective study was to outline characteristics and short-term outcomes of SARS-CoV-2-positive patients. PATIENTS AND METHODS We retrospectively characterized 169 consecutive patients with laboratory confirmed COVID-19, with regard to their: clinical manifestations, radiological findings, treatment, complications and outcomes. RESULTS Of the 169 patients, more than half was aged 65 (n=88, 52,1%) or above, 51,5% were male and 78,3% had comorbidities. Majority of patients (n=106, 62.7%) were transferred from outbreak locations in medical facilities. The most common symptoms on admission were fever (42%), shortness of breath (35%) and fatigue (33%). 27 (15.4%) of patients required intensive care unit admission. Overall mortality was 26.3% (n=46) and was significantly higher in patients transferred from other facilities (38 out of 106, 35.8%), than in patients admitted directly to the hospital (8 out of 63, 12.69%, p<0.001). 17 out of 29 patients admitted to ICU died (mortality = 58,6%), including 30 out of 41 patients with ARDS (73.2% mortality rate in ARDS patients). Conclusion: Polish COVID-19 patients have the similar characteristics and risk factors for adverse outcomes as already observed in countries in which outbreaks occurred earlier. Significantly higher mortality in patients transferred from other centers warrants special attention and transfer policy should be verified.


title: Percutaneous stereotactic radiofrequency ablation of colorectal liver metastases.

text: OBJECTIVES To evaluate the outcome of patients with colorectal liver metastasis (CRLM) treated with stereotactic radiofrequency ablation (SRFA). METHODS Following IRB approval, a retrospective evaluation of 98 SRFA treatment sessions of 189 CRLMs in 63 consecutive patients was performed. Local recurrence rate (LR), overall survival (OS) and disease-free survival (DFS) were analysed. RESULTS LR was identified in 16% of the tumours (31/189), with no significant differences (P = 0.635) when comparing tumour sizes <3 cm (17.7%), 3-5 cm (11.1%) and >5 cm (17.4%). The median OS from SRFA treatment was 33.2 months after a mean follow-up of 25 months (range 2-66); the corresponding 1-, 3- and 5- year survival rates were 87%, 44% and 27%. The median OS was significantly different when comparing unresectable and resectable patients (27 vs. 58 months, P = 0.002) with OS rates of 92%, 66% and 48% at 1, 3 and 5 years in resectable patients. Tumour size did not affect OS and DFS. CONCLUSION Due to the favourable outcome, SRFA challenges resection as first-line local treatment of patients with CRLM. As long as randomised studies are pending, we recommend entering an individual decision-making process with every patient. KEY POINTS Large colorectal liver metastases can be effectively treated by stereotactic radiofrequency ablation (SRFA). Using SRFA the overall survival is not affected by tumour size. SRFA achieves similar overall and disease-free survival rates as surgical resection. SRFA challenges surgical resection as the first-line treatment for colorectal liver metastases.


title: The Influence of Socioeconomic Status on Snacking and Weight among Adolescents: A Scoping Review.

text: Eating behaviors, including unhealthy snacking or excessive snacking leading to excess calorie consumption, may contribute to obesity among adolescents. Socioeconomic status (SES) also significantly influences eating behaviors, and low SES is associated with increased risk for obesity. However, little is known regarding the relationship between snacking behavior and SES among adolescents and how this may contribute to obesity-related outcomes. The primary objective of this scoping review was to review the literature to assess and characterize the relationship between SES and snacking in adolescents. The secondary objective was to assess weight-related outcomes and their relation to snacking habits. Included articles were published between January 2000 and May 2019; written in English, Portuguese, or Spanish; and focused on adolescents (13-17 years). In total, 14 bibliographic databases were searched, and seven studies met the inclusion criteria. Preliminary evidence from the seven included studies suggests a weak but potential link between SES and snacking. Additionally, these dietary patterns seemed to differ by sex and income type of country. Finally, only three of the included studies addressed weight-related outcomes, but the overall available evidence suggests that snacking does not significantly affect weight-related outcomes. Due to the small number of included studies, results should be interpreted with caution.


title: Absence of human bocavirus from deceased fetuses and their mothers.

text: BACKGROUND The human bocavirus (HBoV), a newly discovered parvovirus, is closely related to the bovine parvovirus and the canine minute virus, which are known to cause adverse pregnancy outcomes. Another human parvovirus, B19, can lead to fetal hydrops, miscarriage and intrauterine fetal death (IUFD). OBJECTIVES To determine the prevalence of HBoV DNA in aborted fetuses and IUFDs. The HBoV serology of the mothers was also studied. STUDY DESIGN We retrospectively studied all available fetuses (N=535) autopsied during 7/1992-12/1995, and 1/2003-12/2005 in Helsinki, Finland. All available formalin-fixed paraffin-embedded fetal tissues - placenta, heart and liver - of 120 miscarriages, 169 IUFDs, and 246 induced abortions were studied by quantitative PCR. We also measured the HBoV IgM and IgG antibodies in the corresponding maternal sera (N=462) mostly of the first trimester. The IgM-positive sera underwent HBoV PCR. RESULTS None of the fetal tissues harbored HBoV DNA. A total of 97% (448/462) of the mothers were positive for IgG antibodies to HBoV, while only 0.9% (4/462) exhibited HBoV-specific IgM antibodies without viremia or respiratory symptoms. One IgM-positive mother had an unexplained fetal loss. CONCLUSIONS We did not find HBoV DNA in any of the deceased fetuses. Almost all pregnant women were HBoV-IgG positive.


title: Laparoscopic partial nephrectomy.

text: Laparoscopic partial nephrectomy (LPN) compares favorably to traditional open nephron-sparing surgery (NSS) in terms of oncologic and surgical principles for kidney tumors. Studies have shown the modality to be feasible with similar oncologic efficacy and superior renal functional outcomes compared with laparoscopic radical nephrectomy (LRN) for tumors. The main advantages of LPN include marked improvements in estimated blood loss, decreased surgical site pain, shorter postoperative convalescence, better cosmesis, and nephron preservation. This review article evaluates the literature regarding LPN and discusses the main steps of the operation, the perioperative workup and management, surgical complications, and its role in the surgical management of kidney masses.


title: Near-infrared cholecysto-cholangiography with indocyanine green may secure cholecystectomy in difficult clinical situations: proof of the concept in a porcine model.

text: BACKGROUND Biliary injuries remain a major concern in laparoscopic cholecystectomy. New intraoperative guidance modalities, including near-infrared fluorescence cholangiography, are under evaluation. Initial results showed limitations in visualizing the biliary tree in specific clinical situations. The aim of this study was to examine the feasibility and potentiality of fluorescence cholecysto-cholangiography performed with a direct injection of indocyanine green (ICG) in the gallbladder and to compare it to systemic injection in such situations. MATERIALS AND METHODS Seven pigs were included in this non-survival study. In two pigs, the gallbladder was punctured by a percutaneous needle, and 1 mL of ICG in different concentrations (0.001, 0.01, 0.1, and 1 mg/mL) was sequentially injected. Visibility and pattern of the fluorescent signal around Calot's triangle were examined and compared with those of two control pigs receiving 2.5 mg of intravenous ICG, 30 min prior to the operation. Different scenarios of cholecystitis were modeled using an injection of a mixture of blood and agarose gel around Calot's triangle area in the remaining three pigs, and the applicability of direct intragallbladder injection methods was evaluated. RESULTS The fluorescent signal was identified immediately after intragallbladder injection, and the cystic duct became visible by 0.1 and 1 mg/mL of ICG. The whole cystic duct and the infundibulum of the gallbladder were clearly enhanced by intragallbladder ICG injection, but not by systemic injection. In the cholecystitis models, the cystic duct could be identified only after partial dissection, and fluorescence visualization of the gallbladder infundibulum provided crucial information to find the correct starting point of dissection. CONCLUSIONS Fluorescence cholecysto-cholangiography through direct intragallbladder ICG injection could rapidly provide an adequate visualization of gallbladder neck and cystic duct and might be a valid option to increase the safety of cholecystectomy in case of cholecystitis.


Genetic Roadmap for Kidney Involvement of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection.


title: CoViD-19 and stress in the pandemic: "sanity is not statistical".

text: CoViD-19 pandemic is causing serious consequences on mental health, consequences that are considered that bad that World Health Organization has affirmed that mental health defence is priority in this particular moment of development of pandemic. In light of this alertness, what we are interested in approaching in this work, is the specific stress condition caused by pandemic, which underlies and precedes the described classification of diseases and which is going towards an increase in the entire world, including . The stress caused by pandemic is a new condition in comparison with what is known in clinical practice and with what is included in the classification of mental disorder. The ongoing stress condition and the mixture of different types of unconventional stress, which not only hits the present but also disrupts the future, create an entirely new form of clinical condition given by pandemic.


Presidential Powers and Response to COVID-19.


title: IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes.

text: Type 1 IFNs (IFN-I) generally protect mammalian hosts from virus infections, but in some cases, IFN-I is pathogenic. Because IFN-I is protective, it is commonly used to treat virus infections for which no specific approved drug or vaccine is available. The Middle East respiratory syndrome-coronavirus (MERS-CoV) is such an infection, yet little is known about the role of IFN-I in this setting. Here, we show that IFN-I signaling is protective during MERS-CoV infection. Blocking IFN-I signaling resulted in delayed virus clearance, enhanced neutrophil infiltration, and impaired MERS-CoV-specific T cell responses. Notably, IFN-I administration within 1 day after infection (before virus titers peak) protected mice from lethal infection, despite a decrease in IFN-stimulated gene (ISG) and inflammatory cytokine gene expression. In contrast, delayed IFN-β treatment failed to effectively inhibit virus replication, increased infiltration and activation of monocytes, macrophages, and neutrophils in the lungs, and enhanced proinflammatory cytokine expression, resulting in fatal pneumonia in an otherwise sublethal infection. Together, these results suggest that the relative timing of the IFN-I response and maximal virus replication is key in determining outcomes, at least in infected mice. By extension, IFN-αβ or combination therapy may need to be used cautiously to treat viral infections in clinical settings.


title: Evaluation of Transport Media and Specimen Transport Conditions for the Detection of SARS-CoV-2 Using Real Time Reverse Transcription PCR.

text: The global COVID-19 pandemic has resulted in a worldwide shortage of viral transport media and raised questions about specimen stability. The objective of this study was to determine the stability of SARS-CoV-2 virus RNA in specimen transport media under various storage conditions. Transport medium tested included: VCM, UTM®-RT, ESwab™, M4 and saline (0.9% NaCl). Specimen types tested included Nasopharyngeal/Oropharyngeal (NP/OP) swabs in the above transport media, bronchoalveolar lavage (BAL) and Sputum. A high-titer SARS-CoV-2 remnant patient specimen was spiked into pooled SARS-CoV-2 RNA-negative specimen remnants for the various media types. Aliquots of samples were stored at 18°C to 25°C, 2°C to 8°C and -10°C to -30°C and then tested at time points up to 14 days. Specimens consistently yielded amplifiable RNA with mean Ct differences of <3 over the various conditions assayed, thus supporting the use and transport of alternative collection media and specimen types under a variety of temperature storage conditions.


title: Induction of mucosal immunity through systemic immunization: Phantom or reality?

text: Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity.


title: Outcome of endovascular treatment for acute basilar artery occlusion in the modern era: a single institution experience.

text: PURPOSE The beneficial effect of endovascular treatment (EVT) for patients with acute basilar artery occlusion (ABAO) remains uncertain. The purpose of the present study was to evaluate clinical outcome of EVT for patients with ABAO and analyze prognostic factors of good outcome. METHODS From our prospectively established database, we reviewed all patients with ABAO receiving EVT during January 2014 to December 2016. Baseline characteristics and outcomes were evaluated. Favorable functional outcome was defined as modified Rankin Scale score of 0 to 3 assessed at 3-month follow-up. The association between clinical and procedural characteristics and functional outcome was assessed. RESULTS Of the 68 patients included, 50 patients (73.5%) received mechanical thrombectomy with stent retriever device. Successful reperfusion (thrombolysis in cerebral infarction grades 2b-3) was achieved in 61 patients (89.7%). Overall favorable functional outcome was reached by 31 patients (45.6%). In univariate analysis, Glasgow Coma Scale sum score, baseline National Institutes of Health stroke scale score (NIHSS), and baseline glycemia level were identified predicting good clinical outcome. Multivariate analysis showed that lower NIHSS was the only independent risk factor of favorable functional outcome (OR 0.832; 95% CI, 0.715-0.968; p = 0.018). No difference of favorable outcomes was observed between the subgroups of time to EVT < 6 h and ≽ 6 h. CONCLUSIONS Data in the present study suggests that EVT for ABAO patients should be reasonable within 24 h of symptom onset. The most important factor determining clinical outcome is initial stroke severity.


title: Laparoendoscopic single-site surgery using conventional laparoscopic instruments and glove port technique in gynecology: a single surgeon's experience.

text: STUDY OBJECTIVE To report a single surgeon's experience with 120 laparoendoscopic single-site surgery (LESS) procedures using conventional laparoscopic instruments and a homemade glove port system to treat benign gynecologic diseases. DESIGN Retrospective chart analysis (Canadian Task Force classification III). SETTING Eulji University Hospital. PATIENTS One hundred twenty patients who underwent LESS performed by a single surgeon to treat benign gynecologic diseases between November 2010 and November 2012. INTERVENTION LESS using conventional instrumentation was performed using our specialized glove port technique, which consists of the combination of the homemade glove port system designed to minimalize collision of the trocar on the tip of the finger of the surgical glove, a sufficient rectus fasciotomy, the surgeon's position at the patient's head, and adequate positioning of the instruments. MEASUREMENTS AND MAIN RESULTS The LESS procedures performed were laparoscopically assisted vaginal hysterectomy (n = 50), ovarian cystectomy (n = 25), myomectomy (n = 14), oophorectomy (n = 11), salpingectomy (n = 9), fimbrioplasty or neosalpingstomy (n = 7), and adhesiolysis only (n = 4). Median patient age was 40 years, and median body mass index was 23. Median operative time was 100 minutes (range, 50-145 minutes) for laparoscopically assisted vaginal hysterectomy, 70 minutes (range, 30-150 minutes) for ovarian cystectomy, 107 minutes (range, 65-180 minutes) for myomectomy, 55 minutes (range, 25-130 minutes) for oophorectomy, 85 minutes (range, 35-110 minutes) for salpingectomy, 70 minutes (range, 25-140 minutes) for neosalpingostomy or fimbrioplasty, and 35 minutes (range, 30-60-minutes) for adhesiolysis only. All procedures were completed successfully without the need for additional ports or conversion to the standard laparoscopic approach. One perioperative complication occurred. The complication rate was 83% (1 of 120). Other postoperative complications were not observed at follow-up. CONCLUSION Our experience shows that LESS using conventional laparoscopic instruments and our glove port technique is a feasible and safe technique for the surgical management of various gynecologic conditions. Therefore, our homemade glove port laparoscopic system used in our specialized technique provides a simple, cost-effective approach to LESS and would probably make laparoscopic procedures using conventional instruments easier.


title: Nuclear Medicine Imaging of Neuroendocrine Tumors.

text: An important role is reserved for nuclear imaging techniques in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with (111)In-DTPA-octreotide is currently the most important tracer in the diagnosis, staging and selection for peptide receptor radionuclide therapy (PRRT). In the past decade, different positron-emitting tomography (PET) tracers have been developed. The largest group is the (68)Gallium-labeled somatostatin analogs ((68)Ga-SSA). Several studies have demonstrated their superiority compared to SRS in sensitivity and specificity. Furthermore, patient comfort and effective dose are favorable for (68)Ga-SSA. Other PET targets like β-[(11)C]-5-hydroxy-L-tryptophan ((11)C-5-HTP) and 6-(18)F-L-3,4-dihydroxyphenylalanine ((18)F-DOPA) were developed recently. For insulinomas, glucagon-like peptide-1 receptor imaging is a promising new technique. The evaluation of response after PRRT and other therapies is a challenge. Currently, the official follow-up is performed with radiological imaging techniques. The role of nuclear medicine may increase with the newest tracers for PET. In this review, the different nuclear imaging techniques and tracers for the imaging of NETs will be discussed.


Persistent Symptoms in Patients After Acute COVID-19.


title: Upregulation of CHOP/GADD153 during coronavirus infectious bronchitis virus infection modulates apoptosis by restricting activation of the extracellular signal-regulated kinase pathway.

text: Induction of the unfolded protein response (UPR) is an adaptive cellular response to endoplasmic reticulum (ER) stress that allows a cell to reestablish ER homeostasis. However, under severe and persistent ER stress, prolonged UPR may activate unique pathways that lead to cell death. In this study, we investigated the activation of the protein kinase R-like ER kinase (PERK) pathway of UPR in cells infected with the coronavirus infectious bronchitis virus (IBV) and its relationship with IBV-induced apoptosis. The results showed moderate induction of PERK phosphorylation in IBV-infected cells. Meanwhile, activating transcription factor 4 (ATF4) was upregulated at the protein level in the infected cells, resulting in the induction in trans of the transcription factor ATF3 and the proapoptotic growth arrest and DNA damage-inducible protein GADD153. Knockdown of PERK by small interfering RNA (siRNA) suppressed the activation of GADD153 and the IBV-induced apoptosis. Interestingly, knockdown of protein kinase R (PKR) by siRNA and inhibition of the PKR kinase activity by 2-aminopurine (2-AP) also reduced the IBV-induced upregulation of GADD153 and apoptosis induction. In GADD153-knockdown cells, IBV-induced apoptosis was suppressed and virus replication inhibited, revealing a key role of GADD153 in IBV-induced cell death and virus replication. Analysis of the pathways downstream of GADD153 revealed much more activation of the extracellular signal-related kinase (ERK) pathway in GADD153-knockdown cells during IBV infection, indicating that GADD153 may modulate apoptosis through suppression of the pathway. This study provides solid evidence that induction of GADD153 by PERK and PKR plays an important regulatory role in the apoptotic process triggered by IBV infection.


docid: xygpnpxc

title: Effect of endovascular reperfusion in relation to site of arterial occlusion.

text: OBJECTIVE To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL). METHODS We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions. RESULTS Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7). CONCLUSIONS The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.


title: The chronically critically ill patient: pediatric considerations.

text: Whether defined as chronically critically ill, long-term mechanical ventilator dependent (or otherwise chronically medically supported), or medically fragile, a population of infants and children with chronic illness clearly exists. Infants and children with chronic healthcare needs are at an increased risk for physical, developmental, behavioral, and/or emotional conditions and generally require healthcare services of a type or amount beyond that of a general pediatric or adult population. This review will focus on the specific management and psychosocial needs associated with the healthcare of this subgroup of infants and children with chronic illness. Attention will be paid to defining the population, describing trends over time, reviewing their special needs, and discussing outcomes. Increased focus and an increasing quantity of resources for this subgroup of infants and children are needed, as the number of such pediatric patients continues to grow.


title: Training With Curved Laparoscopic Instruments in Single-Port Setting Improves Performance Using Straight Instruments: A Prospective Randomized Simulation Study.

text: OBJECTIVE Lately single-port surgery is becoming a widespread procedure, but it is more difficult than conventional laparoscopy owing to the lack of triangulation. Although, these operations are also possible with standard laparoscopic instruments, curved instruments are being developed. The aims of the study were to identify the effect of training on a box trainer in single-port setting on the quality of acquired skills, and transferred with the straight and curved instruments for the basic laparoscopic tasks, and highlight the importance of a special laparoscopic training curriculum. DESIGN A prospective study on a box trainer in single-port setting was conducted using 2 groups. Each group performed 2 tasks on the box trainer in single-port setting. Group-S used conventional straight laparoscopic instruments, and Group-C used curved laparoscopic instruments. Learning curves were obtained by daily measurements recorded in 7-day sessions. On the last day, the 2 groups changed instruments between each other. SETTING 1st Department of Surgery, Semmelweis University of Medicine from Budapest, Hungary, a university teaching hospital. PARTICIPANTS In all, 20 fifth-year medical students were randomized into 2 groups. None of them had any laparoscopic or endoscopic experience. Participation was voluntary. RESULTS Although Group-S performed all tasks significantly faster than Group-C on the first day, the difference proved to be nonsignificant on the last day. All participants achieved significantly shorter task completion time on the last day than on the first day, regardless of the instrument they used. Group-S showed improvement of 63.5%, and Group-C 69.0% improvement by the end of the session. After swapping the instruments, Group-S reached significantly higher task completion time with curved instruments, whereas Group-C showed further progression of 8.9% with straight instruments. CONCLUSIONS Training with curved instruments in a single-port setting allows for a better acquisition of skills in a shorter period. For this reason, there is a need for proficiency-based conventional, but also for a single-port, laparoscopic training curriculum in general surgery residency education.


title: The genetic landscape of COVID-19: A South Asian perspective.

text: COVID-19 has taken the world by storm in the ongoing pandemic. The virus responsible for COVID-19 disease is 'severe acute respiratory syndrome coronavirus-2' SARS-CoV-2, an enveloped RNA beta-coronavirus from the family Coronaviridae. There have been similar beta-coronavirus disease outbreaks previously: Severe acute respiratory syndrome (SARS - 2002) and Middle East respiratory syndrome (MERS - 2012) epidemics. SARS-CoV-2 origins have been traced to bat reservoirs. A virus with a high capacity for mutation, SARS-CoV-2 poses unique challenges both in the current form of disease control and management, while also leaving the door open for future novel diseases and pandemics. An understanding of the virion structure and genomic organisation will help us in understanding their origins and likely course of future evolution. Moreover, novel cost-effective methodologies for genetic surveillance may help in mitigating the emergence of these viral infections in future. In this manuscript, the authors have detailed the unique aspects of the SARS-CoV-2 virus genome and its clinical implications.


Video consultations for covid-19.


title: Mortality After Paclitaxel-Coated Device Use in Patients With Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

text: PURPOSE To report the risk of all-cause mortality after treatment with paclitaxel-coated devices vs uncoated controls in patients with chronic limb-threatening ischemia (CLTI). MATERIALS AND METHODS A search of the PubMed, Embase, Cochrane, CINAHL, DARE, and PROSPERO databases was made on 5 November 2019 to identify randomized controlled trials (RCT) using intention-to-treat analysis to compare a paclitaxel-coated device to an uncoated device in PAD patients having clinical follow-up of at least 6 months. Half of the study population had to have CLTI or extractable data on the CLTI subgroup if <50%. The search identified 11 trials having 1450 patients randomized to a paclitaxel-coated device (n=866) or an uncoated control (n=584). There were 1367 (94.3%) patients with CLTI (range 10-429). The single endpoint was all-cause mortality, which was analyzed by pooling the mortality data in a DerSimonian and Laird random effects model. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI). RESULTS The mean follow-up was 25.6 months (range 6-60); 10 of 11 studies reported a minimum 12-month follow-up. There were 161 (18.6%) deaths among 866 subjects in the paclitaxel device group and 116 deaths among 584 (19.9%) subjects in the non-coated control group (RR 0.93, 95% CI 0.78 to 1.12, p=0.45). CONCLUSION There was no observed difference in short- to midterm mortality among a pooled patient population of predominately CLTI patients treated with paclitaxel-coated balloons or stents compared with uncoated controls.


title: Chemical and spectroscopic characterization of organic matter during the anaerobic digestion and successive composting of pig slurry.

text: In this work, anaerobic digestion of pig slurry and successive composting of the digestate after centrifugation were studied by means of chemical analysis, FTIR and fluorescence spectroscopy as excitation-emission matrix (EEM). Chemical analysis highlighted the organic matter transformation occurring during the processes. A decrease of volatile solids and total organic carbon were observed in the digestate with respect to the fresh pig slurry as a consequence of the consumption of sugars, proteins, amino acids and fatty acids used by microorganisms as a C source. Water Extractable Organic Matter (WEOM) was obtained for all samples and fractionated into a hydrophilic and a hydrophobic fraction. The highest WEOM value was found in the pig slurry indicating a high content of labile organic C. The digestate centrifuged and the digestate composted showed lower hydrophilic and higher hydrophobic contents because of the decrease of labile C. Total phenolic content was lower in the digestate with respect to fresh pig slurry sample (36.7%) as a consequence of phenolic compounds degradation. The strong decrease of total reducing sugars in the digestate (76.6%) as compared to pig slurry confirmed that anaerobic process proceed mainly through consumption of sugars which represent a readily available energy source for microbial activity. FTIR spectra of pig slurry showed bands indicative of proteins and carbohydrates. A drop of aliphatic structures and a decrease of polysaccharides was observed after the anaerobic process along with the increase of the peak in the aromatic region. The composted substrate showed an increase of aromatic and a relative decrease of polysaccharides. EEM spectra provided tryptophan:fulvic-like fluorescence ratios which increased from fresh substrate to digestate because of the OM decompostion. Composted substrate presented the lowest ratio due to the humification process.


docid: lrmoqmkq

title: Using social networks to deduce whether residents or dispersers spread parasites in a lizard population.

text: 1. Heterogeneity of host behaviour can play an important role in the spread of parasites and pathogens around wildlife populations. Social networks have previously been suggested to represent transmission pathways within a population, but where the dynamics of host-parasite interactions are difficult to observe, networks may also be used to provide insights into transmission processes. 2. Pygmy bluetongue lizards, Tiliqua adelaidensis, occupy individual territories, live exclusively in burrows constructed by spiders in Australian native grasslands and are hosts to a tick, Bothriocroton hydrosauri, and a nematode, Pharyngodon wandillahensis. 3. On five monthly occasions, the locations of all individual lizards in three study plots were used to construct weighted, undirected networks based on proximity of adjacent burrows. 4. The networks were used to explore alternative hypotheses about the spread of each parasite through the population: that stable population members that remained in the same burrow over the study period played a major role in influencing the pattern of infection or that dispersing individuals played a more significant role. 5. For ticks, host individuals that were infected were more connected in the network than uninfected hosts and this relationship remained significant for connections to residents in the population, but not for connections to dispersers. 6. For nematodes, infected and uninfected hosts did not differ in their overall strength of connection in the network, but infected hosts were more connected to dispersers than were uninfected hosts, suggesting that lizards moving across the population are the major agents for the transmission of nematodes. 7. This study shows how network analyses can provide new insights into alternative pathways of parasite spread in wildlife populations, where it is difficult to make direct observations of transmission-related behaviours.


title: Efficacy and complications of open and minimally invasive surgery in acute Achilles tendon rupture: a prospective randomised clinical study--preliminary report.

text: PURPOSE Surgical treatment of an acute Achilles tendon rupture can effectively reduce the risk of re-rupture, but it increases the probability of surgical complications. We postulated that a minimally invasive surgical treatment might reduce the number of complications related to open surgery and improve the functional results. METHOD We enrolled 47 patients with acute Achilles tendon ruptures in a prospective, randomised trial to compare clinical results and complications between a minimally invasive procedure with the Achillon(®) device and traditional open surgery with Krackow-type sutures. The average patient age was 46 years. The follow up time was 24 months. RESULTS No Achilles tendon re-rupture or nerve injury occurred in treated patients. There were two cases of wound infections in the open surgery group, and one superficial wound infection occurred in the minimally invasive group. The groups were not significantly different in the amount of pain, range of ankle movements, the single heel-rise test, calf circumference, or time to return to work and sports. CONCLUSION After a two year follow-up period, we found no significant differences in clinical outcomes between groups treated with traditional open surgery or minimally invasive surgery.


title: The effect of aerobic exercises on lipid profile of patients with human immunodeficiency virus infection undergoing highly active antiretroviral therapy: a protocol for a systematic review.

text: Patients living with human immunodeficiency virus (HIV) infection who are treated with highly active antiretroviral therapy (HAART) often experience metabolic changes that have an adverse effect on their over-all health status. This review will assess the effect of aerobic exercises on the lipid profile of individuals with HIV infection undergoing HAART. Cochrane Library, MEDLINE, CINAHL (Cumulative index to Nursing and Allied Health Literature), OVID, ProQuest, AMED (Allied and Complementary Medicine Database), PsycINFO, Web of Science Core Collection and Pedro databases will be searched until June 2018. Studies that investigated the effects of aerobic exercises on the lipid profile of HAART treated patients with HIV will be included. Two reviewers will screen all articles for eligibility and independently evaluate the risk of bias, complete quality assessment and extract data for all included articles. Homogenous quantitative outcome data will be analyzed using a random effect model of meta-analysis with results presented as relative risk for dichotomous variable and standardized mean for continuous variable. Heterogeneous qualitative data will be analyzed using narrative synthesis. This systematic review will provide evidence about the effectiveness of aerobic exercises in managing HAART related dyslipidemia in patients with HIV infection and thus provide the impetus for more structured exercise interventions.


title: Results of carotid artery stenting with distal embolic protection with improved systems: Protected Carotid Artery Stenting in Patients at High Risk for Carotid Endarterectomy (PROTECT) trial.

text: OBJECTIVE The Protected Carotid Artery Stenting in Patients at High Risk for Carotid Endarterectomy (PROTECT) study was performed to evaluate the safety and effectiveness of two devices for carotid artery stenting (CAS) in the treatment of carotid artery stenosis in patients at high risk for carotid endarterectomy (CEA): (1) a new embolic protection device, the Emboshield Pro (Abbott Vascular, Abbott Park, Ill), using the periprocedural composite end point of 30-day death, stroke, and myocardial infarction (DSMI), and (2) a carotid stent in conjunction with an embolic protection device (EPD) using the DSMI periprocedural composite end point plus ipsilateral stroke at up to 3 years for long-term evaluation. METHODS This prospective, multicenter clinical trial enrolled 220 consecutive participants between November 29, 2006, and January 14, 2008, followed by a second cohort of 102 participants between January 14 and June 18, 2008. Enrolled participants had carotid stenosis (symptomatic >50% or asymptomatic >80%). The first 220 subjects underwent distal EPD placement with a new large-diameter filter, and the second cohort of 102 underwent placement of an older EPD that is no longer manufactured. All 322 participants were to be treated with a dedicated carotid stent with a tapered, small, closed-cell design (Xact; Abbott Vascular) and were to be included in the long-term evaluation. Independent neurologic assessment was performed before CAS and at 1 day, 30 days, and annually after CAS. All primary end point events were independently adjudicated by a central committee. RESULTS The periprocedural composite end point of DSMI (95% confidence interval) in the first 220 participants was 2.3% (0.74%, 5.22%), with a combined death and stroke rate of 1.8% (0.50%, 4.59%) and a rate of death and major stroke of 0.5% (0.01%, 2.51%). As of January 3, 2011, the median follow-up for the entire 322-subject cohort for the long-term evaluation was 2.8 years. Freedom from the periprocedural composite of DSMI plus ipsilateral stroke thereafter was 95.4%, with an annualized ipsilateral stroke rate of 0.4%. CONCLUSIONS CAS outcomes in patients at high risk for CEA have improved from earlier carotid stent trials. With periprocedural rates of DSMI of 2.3%, death or stroke at 1.8%, and death or major stroke rate of 0.5%, PROTECT has the lowest rate of periprocedural complications among other comparable single-arm CAS trials in patients at high risk for CEA.


title: A novel porcine model of ventilator-associated pneumonia caused by oropharyngeal challenge with Pseudomonas aeruginosa.

text: BACKGROUND Animal models of ventilator-associated pneumonia (VAP) in primates, sheep, and pigs differ in the underlying pulmonary injury, etiology, bacterial inoculation methods, and time to onset. The most common ovine and porcine models do not reproduce the primary pathogenic mechanism of the disease, through the aspiration of oropharyngeal pathogens, or the most prevalent human etiology. Herein the authors characterize a novel porcine model of VAP due to aspiration of oropharyngeal secretions colonized by Pseudomonas aeruginosa. METHODS Ten healthy pigs were intubated, positioned in anti-Trendelenburg, and mechanically ventilated for 72 h. Three animals did not receive bacterial challenge, whereas in seven animals, a P. aeruginosa suspension was instilled into the oropharynx. Tracheal aspirates were cultured and respiratory mechanics were recorded. On autopsy, lobar samples were obtained to corroborate VAP through microbiological and histological studies. RESULTS In animals not challenged, diverse bacterial colonization of the airways was found and monolobar VAP rarely developed. In animals with P. aeruginosa challenge, colonization of tracheal secretion increased up to 6.39 ± 0.34 log colony-forming unit (cfu)/ml (P < 0.001). VAP was confirmed in six of seven pigs, in 78% of the cases developed in the dependent lung segments (right medium and lower lobes, P = 0.032). The static respiratory system elastance worsened to 41.5 ± 5.8 cm H2O/l (P = 0.001). CONCLUSIONS The authors devised a VAP model caused by aspiration of oropharyngeal P. aeruginosa, a frequent causative pathogen of human VAP. The model also overcomes the practical and legislative limitations associated with the use of primates. The authors' model could be employed to study pathophysiologic mechanisms, as well as novel diagnostic/preventive strategies.


Laparoscopic Isolated Resection of Caudate Lobe (Segment 1): A Safe and Versatile Technique.


title: Pulmonary drug toxicity: presentation of a case of recurrent diffuse alveolar damage caused by paroxetine.

text: Pulmonary drug toxicity is being diagnosed more often as a cause of acute and chronic lung disease. Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity. Recurrent diffuse alveolar damage is a rare manifestation of drug toxicity. We described an extremely rare case of recurrent diffuse alveolar damage caused by the antidepressant drug (paroxetine) resolved by a definitive suspension of the drug, after a recurrent respiratory failure because of inadvertently administering the drug.


title: Modified Phemister procedure for the surgical treatment of Rockwood types III, IV, V acute acromioclavicular joint dislocation.

text: Acromioclavicular (AC) joint dislocations are common in young, active patients. In case of surgical indications, Rockwood type IV, type V and selected type III dislocation, we use modified Phemister procedure. At mid-term follow-up, by an average of 35.1 months, we reassessed the records of 14 patients surgically treated for acute AC dislocation from February 2007 to November 2010. In patients with a diagnosis of grade III lesion, indication for surgery was given on the basis of the patient's functional demand. Full recovery was obtained on average 3 months after surgery. Constant Score accounted for 92.7 points, mean Disabilities of the Arm, Shoulder and Hand Score for 3.2 points, and mean Simple Shoulder Test Score for 11.4 points. X-ray findings were partial loss of reduction (9 cases), subclinic re-dislocation (2 cases), calcification (5 cases) and post-traumatic arthritis (2 cases). Modified Phemister is a reliable technique, technically easy, a low learning curve procedure and cheap with low hardware's costs.


title: Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing.

text: Apart from partial or total joint replacement, no surgical procedure is currently available to treat large and deep cartilage defects associated with advanced diseases such as osteoarthritis. In this work, we developed a perfusion bioreactor system to engineer human cartilage grafts in a size with clinical relevance for unicompartmental resurfacing of human knee joints (50 mm diameter × 3 mm thick). Computational fluid dynamics models were developed to optimize the flow profile when designing the perfusion chamber. Using the developed system, human chondrocytes could be seeded throughout large 50 mm diameter scaffolds with a uniform distribution. Following two weeks culture, tissues grown in the bioreactor were viable and homogeneously cartilaginous, with biomechanical properties approaching those of native cartilage. In contrast, tissues generated by conventional manual production procedures were highly inhomogeneous and contained large necrotic regions. The unprecedented engineering of human cartilage tissues in this large-scale opens the practical perspective of grafting functional biological substitutes for the clinical treatment for extensive cartilage defects, possibly in combination with surgical or pharmacological therapies to support durability of the implant. Ongoing efforts are aimed at integrating the up-scaled bioreactor based processes within a fully automated and closed manufacturing system for safe, standardized, and GMP compliant production of large-scale cartilage grafts.


Department of Error.


title: Vacuum-assisted adipose tissue suction technique (VAST) to optimize fat harvesting.

text: BACKGROUND Nowadays, fat grafting is a widespread technique that is commonly used in plastic and reconstructive surgery. The classical fat-harvesting method in which a 10-cc syringe and a 3.0-mm cannula are used, may be time-consuming when a large quantity of adipose tissue is required. We describe a novel technique to optimize fat harvesting, the vacuum-assisted adipose tissue suction technique (VAST), in which disposable sterile components are used. This study compares the adipose tissue harvesting speed and the adipocyte volume between the VAST and the 10-cc-syringe technique. METHODS From May 2010 to May 2012, a total of 32 patients who had structural fat grafting for breast reconstruction were enrolled in this prospective study. In 16 patients (control group) fat was harvested by the classical 10-cc-syringe technique, and in the other 16 patients (VAST group) fat was harvested by the VAST. Adipose tissue was harvested from the abdomen area in all patients. The volume of harvested adipose tissue was noted every minute during the operative procedure. The operative harvesting speed was calculated for each patient after 5 min. The volume harvested in 5 min was centrifuged, and the remaining adipocyte volume was noted after centrifugation. The operative harvesting speed and the remaining adipocyte rate were compared in both groups. RESULTS The average volume of harvested adipose tissue was 18.1 ml in the control group and 156.2 ml in the VAST group (p < 0.001). The average harvesting speed was 3.6 ml/min in the control group using a 10-cc syringe and 31.2 ml/min in the VAST group (p < 0.001). The average remaining adipocyte volume, after centrifugation, was 13.5 ml in the control group, and 118.2 ml in the VAST group (p < 0.001). The average remaining adipocyte rate, after centrifugation, was 74.3 % in the control group and 75.4 % in the VAST group (p = 0.27). CONCLUSIONS Adipose tissue harvesting can be optimized safely by using the VAST before structural fat grafting. Its quickness, low cost, and efficiency make us choose this method in breast reconstruction when a significant volume of adipocytes is required. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Standard and Guidelines: Intracranial Dural Arteriovenous Shunts.


Tribulations of stroke trials.


title: [Thoughts of the COVID-19 outbreak phases changed from emergency response to combination of emergency response and regular prevention and control].

text: Given the scope and speed of virus spread, the COVID-19 pandemic is complex and dangerous. Complicated objective factors such as the long-term existence of source of infection, difficulty in completely blocking the transmission route and a large susceptible population determined that the COVID-19 pandemic might stay with us for long term. Therefore, we should be ready for a tough and long battle against the COVID-19 epidemic. The strategy should adhere to the principle of combining emergency response with regular prevention and control measures, and all efforts should be well harnessed in a coordinated way to keep the epidemic under control while securing the economic and social development.


title: The high cost of fidelity.

text: The notoriously low fidelity of HIV-1 replication is largely responsible for the virus's rapid mutation rate, facilitating escape from immune or drug control. The error-prone activity of the viral reverse transcriptase (RT) is predicted to be the most influential mechanism for generating mutations. The low fidelity of RT has been successfully exploited by nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs) that halt viral replication upon incorporation. Consequently, drug-resistant strains have arisen in which the viral RT has an increased fidelity of replication, thus reducing analogue incorporation. Higher fidelity, however, impacts on viral fitness. The appearance of compensatory mutations in combination with higher fidelity NRTI resistance mutations and the subsequent reversion of NRTI-resistant mutations upon cessation of antiretroviral treatment lend support to the notion that higher fidelity exacts a fitness cost. Potential mechanisms for reduced viral fitness are a smaller pool of mutant strains available to respond to immune or drug pressure, slower rates of replication, and a limitation to the dNTP tropism of the virus. Unraveling the relationship between replication fidelity and fitness should lead to a greater understanding of the evolution and control of HIV.


Audio Interview: A Look at SARS-CoV-2 Transmission.


title: Quantitative proteomics using stable isotope labeling with amino acids in cell culture reveals changes in the cytoplasmic, nuclear, and nucleolar proteomes in Vero cells infected with the coronavirus infectious bronchitis virus.

text: Virus-host interactions involve complex interplay between viral and host factors, rendering them an ideal target for proteomic analysis. Here we detail a high throughput quantitative proteomics analysis of Vero cells infected with the coronavirus infectious bronchitis virus (IBV), a positive strand RNA virus that replicates in the cytoplasm. Stable isotope labeling with amino acids in cell culture (SILAC) was used in conjunction with LC-MS/MS to identify and quantify 1830 cellular and two viral proteins from IBV-infected cells. Fractionation of cells into cytoplasmic, nuclear, and nucleolar extracts was used to reduce sample complexity and provide information on the trafficking of proteins between the different compartments. Each fraction showed a proportion of proteins exhibiting >or=2-fold changes in abundance. Ingenuity Pathway Analysis revealed that proteins that changed in response to infection could be grouped into different functional categories. These included proteins regulated by NF-kappaB- and AP-1-dependent pathways and proteins involved in the cytoskeleton and molecular motors. A luciferase-based reporter gene assay was used to validate the up-regulation of AP-1- and NF-kappaB-dependent transcription in IBV-infected cells and confirmed using immunofluorescence. Immunofluorescence was used to validate changes in the subcellular localization of vimentin and myosin VI in IBV-infected cells. The proteomics analysis also confirmed the presence of the viral nucleocapsid protein as localizing in the cytoplasm, nucleus, and nucleolus and the viral membrane protein in the cytoplasmic fraction. This research is the first application of SILAC to study total host cell proteome changes in response to positive sense RNA virus infection and illustrates the versatility of this technique as applied to infectious disease research.


GATA3 and stemness of high-grade serous ovarian carcinoma: novel hope for the deadliest type of ovarian cancer.


title: Stent-thrombus interaction and the influence of aspiration on mechanical thrombectomy: evaluation of different stent retrievers in a circulation model.

text: INTRODUCTION Different devices and techniques are available for endovascular treatment of ischemic stroke. In this in vitro study, we examined the stent-thrombus interaction and the influence of additional aspiration on the efficiency of mechanical thrombectomy with established stent retrievers. METHODS Human blood thrombi were made in a Chandler loop. The thrombi were placed into the middle cerebral artery of a vascular silicon phantom. A programmable piston pump was used to acquire physiological flow in the model. Resistances were interposed to gain physiological pressure. The stent retrievers Trevo, Solitaire FR, Separator 3D, and Aperio were used to perform thrombectomy under direct visual control. For the additional aspiration, we used intermediate catheters. RESULTS Ten attempts per device were made with and without aspiration under standardized conditions, a total of n = 80. For all thrombectomy maneuvers, it was demonstrated that the thrombus was pushed by the stent struts against the vessel wall and was retracted along it. The stent-thrombus interaction was only superficial for all devices. Using additional distal aspiration, the amount of distal embolism and rate of embolism in new territories was significantly lower than without. Moreover, additional aspiration reduced the number of recanalization maneuvers and the recanalization time. CONCLUSION Distal aspiration with intermediate catheters increases the efficacy of mechanical thrombectomy with stent retrievers significantly. In contrary to earlier suggestions, the interaction between the thrombus and the stent retriever is only superficial, rather than an integration of the thrombus into the retriever. No significant differences between the proven devices could be shown in our model.


title: Current surgical management of pelvic organ prolapse: Strategies for the improvement of surgical outcomes.

text: There are a variety of surgical management strategies to help surgeons repair pelvic organ prolapse (POP). Surgical treatment for POP includes native tissue repair, augmentation with mesh, and minimally invasive surgeries. Currently, laparoscopic or robotic techniques for POP repair are increasing in popularity and continuing to evolve. The aim of this review is to present an up-to-date review of surgical techniques used for POP repair and to discuss ways to optimize surgical outcomes.


title: A novel astrovirus from dromedaries in the Middle East.

text: The recent emergence of Middle East respiratory syndrome coronavirus from the Middle East and its discovery from dromedary camels has boosted interest in the search for novel viruses in dromedaries. The existence of astroviruses (AstVs) in dromedaries was previously unknown. We describe the discovery of a novel dromedary camel AstV (DcAstV) from dromedaries in Dubai. Among 215 dromedaries, DcAstV was detected in faecal samples of four [three (1.5 %) adult dromedaries and one (8.3 %) dromedary calf] by reverse transcription-PCR. Sequencing of the four DcAstV genomes and phylogenetic analysis showed that the DcAstVs formed a distinct cluster. Although DcAstV was most closely related to a recently characterized porcine AstV 2, their capsid proteins only shared 60-66 % amino acid identity, with a mean amino acid genetic distance of 0.372. Notably, the N-terminal halves of the capsid proteins of DcAstV shared ≤ 85 % amino acid identity, but the C-terminal halves only shared ≤ 49 % amino acid identity compared with the corresponding proteins in other AstVs. A high variation of the genome sequences of DcAstV was also observed, with a mean amino acid genetic distance of 0.214 for ORF2 of the four strains. Recombination analysis revealed a possible recombination event in ORF2 of strain DcAstV-274. The low Ka/Ks ratios (number of non-synonymous substitutions per non-synonymous site to number of synonymous substitutions per synonymous site) of the four ORFs in the DcAstV genomes supported the suggestion that dromedaries are the natural reservoir where AstV is stably evolving. These results suggest that AstV is a novel species of the genus Mamastrovirus in the family Astroviridae. Further studies are important to understand the pathogenic potential of DcAstV.


title: Impact of Cardiovascular Disease on Clinical Characteristics and Outcomes of Coronavirus Disease 2019 (COVID-19).

text: BACKGROUND To investigate the effect of cardiovascular disease (CVD) on the global pandemic, coronavirus disease 2019 (COVID-19), we analyzed the cases of laboratory-confirmed COVID-19 patients in Wuhan.Methods and Results:Data were extracted from the medical records. SARS-CoV-2 RNA was confirmed by RT-PCR. A total of 33 (53.2%) of 62 cases with CVD, who had higher prevalence of severe COVID-19 compared with non-CVD patients (P=0.027). The median age of all patients was 66.0 (53.3, 73.0) years old. Coronary artery disease (11.3%) and hypertension (38.7%) were the common coexisting CVDs in COVID-19 patients. High-sensitivity cardiac troponin I (hs-cTnI), creatinine, high-density lipoprotein-cholesterol, interleukin-6, C-reactive protein, prothrombin time, and D-dimer levels in the severe COVID-19 with CVD group were higher than in the non-severe COVID-19 with CVD group (P<0.05). For all patients, chest computed tomography (CT) showed ground-glass opacity (66.1%), local (21.0%), bilateral (77.4%), and interstitial abnormalities (4.8%). In COVID-19 patients with CVD, 27 (81.8%) were cured and discharged. 6 (18.2%) remained in hospital, including 2 (3.2%) patients requiring intubation and mechanical ventilation. The hs-cTnI levels in the remaining hospitalized patients were higher than in the discharged patients (P=0.047). CONCLUSIONS CVDs play a vital role in the disease severity of COVID-19. COVID-19 could result in myocardial injury, which affects the prognosis of COVID-19.


Management of Patients With Severe Mental Illness During the Coronavirus Disease 2019 Pandemic.


title: Bronchial blocker versus double-lumen endobronchial tube in minimally invasive cardiac surgery.

text: BACKGROUND To compare the therapeutic value of a bronchial blocker (BB) with a double-lumen tube (DLT) in minimally invasive cardiac surgery (MICS). METHODS Sixty patients who underwent MICS were randomized to use either a DLT (Group D, n = 30) or a BB (Group B, n = 29; one failed was omitted). The following data were collected: time of intubation and tube localization; incidence of tube displacement; postoperative sore throat and hoarseness; time of cardiopulmonary bypass; maintenance time for SpO2 < 90% (PaCO2 < 60 mmHg); mean arterial pressure and heart rate; SpO2, PaO2, PaCO2, EtCO2, mean airway pressure, and airway peak pressure; surgeons' satisfaction with anesthesia; and short-term complications. RESULTS The times of intubation and tube localization were significantly longer in Group B than in Group D (P < 0.05). Patients in Group B exhibited significantly lower incidence of tube displacement, postoperative sore throat, and hoarseness when compared with patients in Group D (P < 0.05). Mean arterial pressure and heart rate were significantly lower in Group B than in Group D after tracheal intubation (P < 0.05). The mean airway pressure and airway peak pressure were significantly lower in Group B than in Group D after one-lung ventilation (P < 0.05). SpO2 and PaO2 in Group B were significantly higher than in group D after cardiopulmonary bypass (P < 0.05). No short-term postoperative complications were observed in patients of Groups B and D during 3 month follow-up. CONCLUSION BB can be a potential alternative to the conventional DLT for lung isolation in MICS. TRIAL REGISTRATION ChiCTR1900024250, July 2, 2019.


docid: vmmkqpks

title: Real-Time Characterization of Diminutive Colorectal Polyp Histology Using Narrow-Band Imaging: Implications for the Resect and Discard Strategy.

text: BACKGROUND & AIMS Narrow-band imaging (NBI) allows real-time histologic classification of colorectal polyps. We investigated whether endoscopists without prior training in NBI can achieve the following thresholds recommended by the American Society for Gastrointestinal Endoscopy: for diminutive colorectal polyps characterized with high confidence, a ≥90% negative predictive value for adenomas in the rectosigmoid and a ≥90% agreement in surveillance intervals. METHODS Twenty-six endoscopists from 2 tertiary care centers underwent standardized training in NBI interpretation. Endoscopists made real-time predictions of diminutive colorectal polyp histology and surveillance interval predictions based on NBI. Their performance was evaluated by comparing predicted with actual findings from histologic analysis. Multilevel logistic regression was used to assess predictors of performance. Cumulative summation analysis was used to characterize learning curves. RESULTS The endoscopists performed 1451 colonoscopies and made 3012 diminutive polyp predictions (74.3% high confidence) using NBI. They made 898 immediate post-procedure surveillance interval predictions. An additional 505 surveillance intervals were determined with histology input. The overall negative predictive value for high-confidence characterizations in the rectosigmoid was 94.7% (95% confidence interval: 92.6%-96.8%) and the surveillance interval agreement was 91.2% (95% confidence interval: 89.7%-92.7%). Overall, 97.0% of surveillance interval predictions would have brought patients back on time or early. High-confidence characterization was the strongest predictor of accuracy (odds ratio = 3.42; 95% confidence interval: 2.72-4.29; P < .001). Performance improved over time, however, according to cumulative summation analysis, only 7 participants (26.9%) identified adenomas with sufficient sensitivity such that further auditing is not required. CONCLUSIONS With standardized training, gastroenterologists without prior expertise in NBI were able to meet the negative predictive value and surveillance interval thresholds set forth by the American Society for Gastrointestinal Endoscopy. The majority of disagreement in surveillance interval brought patients back early. Performance improves with time, but most endoscopists will require ongoing auditing of performance. ClinicalTrials.gov ID NCT02441998.


title: [Guidelines for gastroenteropancreatic neuroendocrine tumors--what is new? What should be incorporated in daily therapeutic decisions?].

text: Neuroendocrine neoplasias are seldom, but increasing. This holds true for the incidence but even more for the prevalence, since patients are able to live with their disease for quite a long time. The European Neuroendocrine Tumor Society (ENETS) as well as other societies (NANETS: North American Neuroendocrine Tumor Society; NCCN: National Comprehensive Cancer Network; ESMO: European Society of Medical Oncology) have published diagnostic and therapeutic guidelines that we present in this review. We aim to summarize those actual guidelines in a practice-based diagnostic and therapeutic algorithm, but also wish to point to open questions that have to be discussed in a multidisciplinary approach.


title: Interference between surgical magnetic drapes and pacemakers: an observational study comparing commercially available devices and a new magnetically isolated drape.

text: BACKGROUND Magnetic fields may potentially interfere with the function of cardiovascular implantable electronic devices. Sterile magnetic drapes used to hold surgical instruments are often placed on the patient's thorax, and they are likely to interfere with the function of these devices. METHODS Thirty patients were recruited to compare a new prototype surgical magnetic drape (LT10G™ by Menodys) made with bottom-isolated ferrite magnets to the Covidien magnetic drape we used in a previous study. Twenty additional patients were recruited to compare the prototype drape with four commercially available surgical magnetic drapes. RESULTS Magnetic interference was found in 33 of the 50 total patients (70 %) when the Covidien drape was placed over the pacemaker. Of the 20 additional patients, 5 patients (25 %) displayed magnetic interference with a second type of surgical magnetic drape. A third magnetic drape caused interference in one patient (5 %), whereas a larger drape of the same model did not interfere in any patient. No patients demonstrated magnetic interference with the prototype drape. CONCLUSION Bottom isolation of magnets in the prototype magnetic drape (LT10G™) used during surgery prevents magnetic interference in all patients when placed over the pacemaker. Three of the four commercially available magnetic drapes tested demonstrated magnetic interference. Flipping the prototype drape is not recommended as it may expose non-isolated magnets to the cardiovascular implantable electronic device.


title: Signal quality of simultaneously recorded endovascular, subdural and epidural signals are comparable.

text: Recent work has demonstrated the feasibility of minimally-invasive implantation of electrodes into a cortical blood vessel. However, the effect of the dura and blood vessel on recording signal quality is not understood and may be a critical factor impacting implementation of a closed-loop endovascular neuromodulation system. The present work compares the performance and recording signal quality of a minimally-invasive endovascular neural interface with conventional subdural and epidural interfaces. We compared bandwidth, signal-to-noise ratio, and spatial resolution of recorded cortical signals using subdural, epidural and endovascular arrays four weeks after implantation in sheep. We show that the quality of the signals (bandwidth and signal-to-noise ratio) of the endovascular neural interface is not significantly different from conventional neural sensors. However, the spatial resolution depends on the array location and the frequency of recording. We also show that there is a direct correlation between the signal-noise-ratio and classification accuracy, and that decoding accuracy is comparable between electrode arrays. These results support the consideration for use of an endovascular neural interface in a clinical trial of a novel closed-loop neuromodulation technology.


Reflections from an emergency department junior doctor: the Covid legacy.


title: Iron oxide-filled micelles as ligands for fac-[M(CO)3]+ (M = (99m)Tc, Re).

text: Magnetite-filled micelles capture fac-[M(OH(2))(3)(CO)(3)](+) complexes (M = (99m)Tc, Re), creating versatile self-assembled constructs for multimodal SPECT/MR/optical imaging and radiopharmaceutical guided delivery.


title: High Iron Stores in the Low Malaria Season Increase Malaria Risk in the High Transmission Season in a Prospective Cohort of Rural Zambian Children.

text: Background: Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk.Objective: We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation.Methods: Data for this prospective study were collected from children aged 4-8 y (n = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively. Iron status was defined as deficient (corrected or uncorrected SF <12 or <15 μg/L, depending on age <5 or ≥5 y, respectively), moderate (<75 μg/L, excluding deficient), or high (≥75 μg/L). We used a modified Poisson regression to model the risk of malaria in the high transmission seasons (endline) as a function of iron status assessed in the low malaria seasons (baseline).Results: We observed an age-dependent, positive dose-response association between ferritin in the low malaria season and malaria incidence during the high malaria season in younger children. In children aged <6 y (but not older children), we observed a relative increase in malaria risk in the moderate iron status [incidence rate ratio (IRR) with SF: 1.56; 95% CI: 0.64, 3.86; IRR with inflammation-corrected SF: 1.92; 95% CI: 0.75, 4.93] and high iron status (IRR with SF: 2.66; 95% CI: 1.10, 6.43; or IRR with corrected SF: 2.93; 95% CI: 1.17, 7.33) categories compared with the deficient iron status category. The relative increase in malaria risk for children with high iron status was statistically significant only among those with a concurrently normal serum soluble transferrin receptor concentration (<8.3 mg/L; IRR: 1.97; 95% CI: 1.20, 7.37).Conclusions: Iron adequacy in 4- to 8-y-old children in rural Zambia was associated with increased malaria risk. Our findings underscore the need to integrate iron interventions with malaria control programs. This trial was registered at clinicaltrials.gov as NCT01695148.


title: Method for minimising rolling joint play in the steerable laparoscopic instrument prototype DragonFlex.

text: INTRODUCTION The steerable laparoscopic instrument prototype DragonFlex was recently developed with the vision of a minimalistic fully functional design, readily produced by additive manufacturing and requiring little assembly. Steering functionality is provided by rolling joints that, besides simplifying the assembly, help minimise cable fatigue and equalise force requirements on steering cables. However, the perfectly circular rolling joint design introduced some mechanism play, undermining the joint's bending stiffness. Hence, the aim of this paper is to present an innovative solution for play reduction in rolling joints. MATERIAL AND METHODS The original play-compensating mechanism, a shaft-embedded compression spring, proved unsatisfactory for play reduction. Therefore, a new non-circular rolling joint curvature was designed with the objective to compensate for any cable slack and thus minimise the joint play. The new rolling joint design was evaluated in several tip deflection experiments and compared to the original one. RESULTS AND CONCLUSIONS The experimental results proved that the optimised rolling joint curvature significantly minimises play, thus being a major improvement compared to the original design. The optimised rolling joint was implemented in a new real-scale DragonFlex prototype. The presented optimisation method enables elimination of a conventionally used cable tensioning device and it is generally applicable to steerable minimally invasive instruments that use a rolling joint.


title: The long view: 40 years of infectious bronchitis research.

text: The remit of this review is to provide the non-specialist reader of Avian Pathology with an overview of research carried out on infectious bronchitis over the 40 years since the journal was first published. In order to do this, we felt it necessary to summarize the knowledge acquired previously, since the since the disease was first identified in the 1930s. Infectious bronchitis virus is a significant pathogen in the domestic chicken, affecting the respiratory and renal systems as well as the female reproductive tract. The virus exists in the form of many, ever changing, serotypic or genotypic variants, some of which have global distribution whilst others are found only in more local areas. This review mentions the major discoveries concerning both the virus itself and the types of disease it causes and considers recent changes in its pathogenesis. It also discusses the impact of developments in the field of molecular biology and highlights possible areas for future work.


title: Gastroesophageal regurgitation during anesthesia and controlled ventilation with six airway devices.

text: STUDY OBJECTIVE To investigate the frequency of gastroesophageal regurgitation and respiratory mechanics during positive pressure ventilation using 5 supraglottic devices or an endotracheal tube (ETT). DESIGN Prospective, randomized study. SETTING Operating rooms in a university-affiliated hospital. PATIENTS 180 ASA physical status I and II patients, aged 18 to 65 years old, who underwent elective orthopedic, minor vascular, peripheral plastic, or urologic surgery during general anesthesia. INTERVENTIONS Patients were randomly allocated to one of 6 airway device groups (n = 30 each): (1) Cobra Perilaryngeal Airway; (2) Laryngeal Mask Airway (LMA) Classic; (3) LMA Fastrach; (4) LMA ProSeal; (5) laryngeal tube; and (6) ETT (SIMS Portex, Ltd, Hythe, Kent, UK). After insertion of the designated device, the lungs of each nonparalyzed patient were mechanically ventilated. MEASUREMENTS Hypopharyngeal pH, peak inspiratory pressures, sealing pressures, and lung compliance were measured. Hypopharyngeal pH lower than 4 was considered a regurgitation event. MAIN RESULTS Regurgitation (episodes of pH <4) occurred in between one and 5 patients of each study group, with no statistical difference. Sealing pressures were similar among all the airway device groups. CONCLUSIONS The frequency of gastroesophageal regurgitation in anesthetized, unparalyzed, mechanically ventilated patients was similar in patients whose lungs were ventilated with either the Cobra Perilaryngeal Airway, LMA Classic, Fastrach, ProSeal, laryngeal tube, or ETT.


A lion in our village--the unconscionable tragedy of cholera in Africa.


Electroconvulsive Therapy in a Time of Coronavirus Disease.


Dementia in the COVID-19 Period.


Athletes as community; athletes in community: covid-19, sporting mega-events and athlete health protection.


title: Development and characterization of clinical-grade 89Zr-trastuzumab for HER2/neu immunoPET imaging.

text: UNLABELLED The anti-human epidermal growth factor receptor 2 (HER2/neu) antibody trastuzumab is administered to patients with HER2/neu-overexpressing breast cancer. Whole-body noninvasive HER2/neu scintigraphy could help to assess and quantify the HER2/neu expression of all lesions, including nonaccessible metastases. The aims of this study were to develop clinical-grade radiolabeled trastuzumab for clinical HER2/neu immunoPET scintigraphy, to improve diagnostic imaging, to guide antibody-based therapy, and to support early antibody development. The PET radiopharmaceutical (89)Zr-trastuzumab was compared with the SPECT tracer (111)In-trastuzumab, which we have tested in the clinic already. METHODS Trastuzumab was labeled with (89)Zr and (for comparison) with (111)In. The minimal dose of trastuzumab required for optimal small-animal PET imaging and biodistribution was determined with human HER2/neu-positive or -negative tumor xenograft-bearing mice. RESULTS Trastuzumab was efficiently radiolabeled with (89)Zr at a high radiochemical purity and specific activity. The antigen-binding capacity was preserved, and the radiopharmaceutical proved to be stable for up to 7 d in solvent and human serum. Of the tested protein doses, the minimal dose of trastuzumab (100 microg) proved to be optimal for imaging. The comparative biodistribution study showed a higher level of (89)Zr-trastuzumab in HER2/neu-positive tumors than in HER2/neu-negative tumors, especially at day 6 (33.4 +/- 7.6 [mean +/- SEM] vs. 7.1 +/- 0.7 percentage injected dose per gram of tissue). There were good correlations between the small-animal PET images and the biodistribution data and between (89)Zr-trastuzumab and (111)In-trastuzumab uptake in tumors (R(2) = 0.972). CONCLUSION Clinical-grade (89)Zr-trastuzumab showed high and HER2/neu-specific tumor uptake at a good resolution.


title: Psychological and social consequences of non-invasive prenatal testing (NIPT): a scoping review.

text: BACKGROUND Genomics-based noninvasive prenatal tests (NIPT) allow screening for chromosomal anomalies such as Down syndrome (trisomy 21). The technique uses cell-free fetal DNA (cffDNA) that circulates in the maternal blood and is detectable from 5 weeks of gestation onwards. Parents who choose to undergo this relatively new test (introduced in 2011) might be aware of its positive features (i.e. clinical safety and ease of use); however, they might be less aware of the required decisions and accompanying internal conflicts following a potential positive test result. To show the evidence on psychological and social consequences of the use of NIPT, we conducted a scoping review. METHODS We systematically searched four electronic databases (MEDLINE (Ovid), Cochrane Library (Wiley), CINAHL (EBSCO) and PsychINFO (EBSCO)) for studies that investigated the psychological or social consequences of the use of NIPT by pregnant women or expecting parents. The search was limited to studies published between 2011 and August 8, 2018. We identified 2488 studies and, after removal of duplicates, screened 2007 titles and abstracts, and then assessed 99 articles in full text (both screenings were done independently in duplicate). We included 7 studies in our analysis. RESULTS Five studies assessed anxiety, psychological distress and/or decisional regret among women with validated psychological tests like the Spielberger State Trait-Anxiety Inventory (STAI), the Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R), the Kessler Psychological Distress Scale (K6) or the Decisional Regret Scale (DRS). Two studies assessed women's experiences with and feelings after NIPT in interviews or focus groups. The included studies were heterogeneous in location, study setting, inclusion criteria, outcome assessment, and other characteristics. CONCLUSIONS Only few studies on psychological consequences of NIPT have been identified. The studies assessed only short-term psychological consequences of NIPT at baseline and/or after receiving the results or after giving birth. Studies show that short term anxiety decreased when women received negative NIPT results and that decisional regret was generally low. We could not identify studies on long term consequences of NIPT, as well as studies on women's partners' short and long term outcomes, nor on social consequences of NIPT.


Covid-19: Cancer Research urges mass testing to enable care to continue during pandemic.


title: Case report: central venous catheterization via internal jugular vein with associated formation of perioperative venous thrombosis during surgery in the prone position.

text: An unusual case of central venous catheter (CVC)-related thrombosis during supine surgery in the prone position is presented. A 76-year-old woman was scheduled for elective surgery to repair a broken lumbar instrument. A single-lumen CVC was inserted via the right internal jugular vein. Surgery was performed in the prone position, with the patient's face directed downward in the standard median position (i.e., no rotation), but with slight forward flexion at the neck. After the surgery, the external jugular vein was dilated, and a postoperative X-ray revealed an infiltrative shadow in the right thoracic cavity. Because cervical echography showed dilated cervical veins with a "moyamoya-type" echo, possibly indicating a thrombus, contrast-enhanced computed tomography was performed, revealing a venous thrombus in the right internal jugular vein. An internal jugular venous-velocity measurement suggested that her slightly flexed neck position and her prone position during surgery may have kinked the internal jugular vein, causing engorgement with venous blood. The presence of the internal jugular venous catheter may have created thrombogenic conditions. A patient's position during surgery can reduce deep venous-flow velocity, and venous blood may stagnate, contributing greatly to thrombogenicity. We should consider a patient's position during surgery as a risk factor for thrombus formation, and a careful preoperative evaluation should be made as to which route should be chosen for CVC.


Temporoparietal fascia flap "sandwich" technique for repair of near-total traumatic auricle avulsion.


docid: yqjjndke

title: Household epidemics: modelling effects of early stage vaccination.

text: A Markovian susceptible --> infectious --> removed (SIR) epidemic model is considered in a community partitioned into households. A vaccination strategy, which is implemented during the early stages of the disease following the detection of infected individuals is proposed. In this strategy, the detection occurs while an individual is infectious and other susceptible household members are vaccinated without further delay. Expressions are derived for the influence on the reproduction numbers of this vaccination strategy for equal and unequal household sizes. We fit previously estimated parameters from influenza and use household distributions for Sweden and Tanzania census data. The results show that the reproduction number is much higher in Tanzania (6 compared with 2) due to larger households, and that infected individuals have to be detected (and household members vaccinated) after on average 5 days in Sweden and after 3.3 days in Tanzania, a much smaller difference.


title: Association between eczema and major cardiovascular outcomes in population-based studies: a systematic review protocol.

text: INTRODUCTION Chronic inflammatory diseases such as eczema (also known as atopic dermatitis) have been inconsistently linked to cardiovascular disease and stroke in both mechanistic and epidemiological studies. There is a need to review the existing epidemiological data examining the association between eczema and major cardiovascular outcomes, including angina, myocardial infarction, coronary revascularisation, heart failure, cardiac arrhythmias, stroke and cardiovascular death, in order to improve our understanding of the comorbidities of eczema. METHODS AND ANALYSIS We will systematically review population-based studies, including cohort, case-control and cross-sectional studies, reporting on the association between eczema and cardiovascular outcomes. We will search Medline, Embase and Global Health, from their date of inception to April 2017, using a comprehensive search strategy formulated with the help of a librarian. Two reviewers will independently screen titles and abstracts in duplicate, followed by independent data extraction and quality assessment. We will group studies by the cardiovascular outcome under study and synthesise them narratively. If sufficient numbers of homogeneous studies are returned, we will perform meta-analyses to obtain pooled effect estimates. Preferred Reporting Items for Systematic Review and Meta-Analysis will be used to inform the reporting of this study. TRIAL REGISTRATION NUMBER CRD42017060359.


COVID19 and Breastfeeding: Not That Simple.


docid: tjrlsagr

title: Nature Biotechnology's academic spinouts of 2019.


title: JNK and p38 mitogen-activated protein kinase pathways contribute to porcine circovirus type 2 infection.

text: Infection with a wide variety of viruses often perturbs host cell signaling pathways including the Jun NH(2)-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38/MAPK), which are important components of cellular signal transduction pathways. The present study demonstrated for the first time that porcine circovirus type 2 (PCV2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activate JNK1/2 and p38 MAPK pathways in PCV2-infected PK15 cells. However, PCV2 at an early stage of infection, as well as UV-irradiated PCV2, failed to activate these two MAPK families, which demonstrated that PCV2 replication was necessary for their activation. We further found that PCV2 activated the phosphorylation of JNK1/2 and p38 MAPK downstream targets c-Jun and ATF-2 with virus replication in the cultured cells. The roles of these kinases in PCV2 infection were further evaluated using specific inhibitors: the JNK inhibitor 1 for JNK1/2 and SB202190 for p38. Inhibition of JNK1/2 and p38 kinases by these specific inhibitors did result in significant reduction of PCV2 viral mRNA transcription and protein synthesis, viral progeny release, and blockage of PCV2-induced apoptotic caspase-3 activation in the infected cells. Taken together, these data suggest that JNK/SAPK and p38 MAPK pathways play important roles in the PCV2 replication and contribute to virus-mediated changes in host cells.


Respiratory Mechanics of COVID-19 vs. Non-COVID-19 Associated Acute Respiratory Distress Syndrome.


title: Hand-held medical robots.

text: Medical robots have evolved from autonomous systems to tele-operated platforms and mechanically-grounded, cooperatively-controlled robots. Whilst these approaches have seen both commercial and clinical success, uptake of these robots remains moderate because of their high cost, large physical footprint and long setup times. More recently, researchers have moved toward developing hand-held robots that are completely ungrounded and manipulated by surgeons in free space, in a similar manner to how conventional instruments are handled. These devices provide specific functions that assist the surgeon in accomplishing tasks that are otherwise challenging with manual manipulation. Hand-held robots have the advantages of being compact and easily integrated into the normal surgical workflow since there is typically little or no setup time. Hand-held devices can also have a significantly reduced cost to healthcare providers as they do not necessitate the complex, multi degree-of-freedom linkages that grounded robots require. However, the development of such devices is faced with many technical challenges, including miniaturization, cost and sterility, control stability, inertial and gravity compensation and robust instrument tracking. This review presents the emerging technical trends in hand-held medical robots and future development opportunities for promoting their wider clinical uptake.


Reply to: "HCV RNA kinetics on-treatment do not predict sustained virologic response in HCV genotype 3 patients receiving sofosbuvir and ribavirin".


title: QT interval and antidepressant use: a cross sectional study of electronic health records.

text: OBJECTIVE To quantify the impact of citalopram and other selective serotonin reuptake inhibitors on corrected QT interval (QTc), a marker of risk for ventricular arrhythmia, in a large and diverse clinical population. DESIGN A cross sectional study using electrocardiographic, prescribing, and clinical data from electronic health records to explore the relation between antidepressant dose and QTc. Methadone, an opioid known to prolong QT, was included to demonstrate assay sensitivity. SETTING A large New England healthcare system comprising two academic medical centres and outpatient clinics. PARTICIPANTS 38,397 adult patients with an electrocardiogram recorded after prescription of antidepressant or methadone between February 1990 and August 2011. MAIN OUTCOME MEASURES Relation between antidepressant dose and QTc interval in linear regression, adjusting for potential clinical and demographic confounding variables. For a subset of patients, change in QTc after drug dose was also examined. RESULTS Dose-response association with QTc prolongation was identified for citalopram (adjusted beta 0.10 (SE 0.04), P<0.01), escitalopram (adjusted beta 0.58 (0.15), P<0.001), and amitriptyline (adjusted beta 0.11 (0.03), P<0.001), but not for other antidepressants examined. An association with QTc shortening was identified for bupropion (adjusted beta 0.02 (0.01) P<0.05). Within-subject paired observations supported the QTc prolonging effect of citalopram (10 mg to 20 mg, mean QTc increase 7.8 (SE 3.6) ms, adjusted P<0.05; and 20 mg to 40 mg, mean QTc increase 10.3 (4.0) ms, adjusted P<0.01). CONCLUSIONS This study confirmed a modest prolongation of QT interval with citalopram, and identified additional antidepressants with similar observed risk. Pharmacovigilance studies using electronic health record data may be a useful method of identifying potential risk associated with treatments.


COVID-19 and emergency planning.


Training and Fit Testing of Health Care Personnel for Reusable Elastomeric Half-Mask Respirators Compared With Disposable N95 Respirators.


title: Hospital-acquired infection in public hospital buildings in the Philippines: Is the type of ventilation increasing the risk?

text: INTRODUCTION Hospital-acquired infections (HAIs) are associated with increased morbidity and mortality, especially in developing countries. However, limited information is available about the risk of HAIs in naturally ventilated wards (NVWs) and mechanically ventilated intensive care units (MVICUs) of public hospitals in the Philippines. We aimed to assess the association between HAIs and type of ventilation in an urban tertiary care hospital in the Philippines. METHODOLOGY A cross-sectional point-prevalence survey of infections was done in NVWs and MVICUs of a tertiary care hospital in December 2013. Multivariate analyses were done to examine the associations between HAIs and type of ventilation and other risk factors. RESULTS Of the 224 patients surveyed, 63 (28%) patients had 69 HAIs. Pneumonia was the most common HAI (35%). Wards near areas with high vehicular activity had more respiratory HAI cases. Being immunocompromised is a risk factor for HAI for pediatric and adult patients. Among pediatric patients, staying in MVICUs had a lower risk for HAIs (adjusted odds ratio [AOR]: 0.33; 95% confidence interval [CI]: 0.10-1.08) compared to staying in NVWs. For adult patients, a higher risk for HAIs (AOR: 2.41; 95% CI: 0.29-18.20) was observed in MVICUs compared to NVWs. CONCLUSIONS Type of ventilation is not a risk factor for HAIs. Patients who are immunocompromised may be at a higher risk for HAI. Indoor air pollution, proximity to congested main thoroughfare, and increased human foot traffic may contribute to the susceptibility of patients to HAIs. Hospital layout should be considered in infection control.


title: Genome-wide codon usage profiling of ocular infective Chlamydia trachomatis serovars and drug target identification.

text: Chlamydia trachomatis (C.t) is a Gram-negative obligate intracellular bacteria and is a major causative of infectious blindness and sexually transmitted diseases. Among the varied serovars of this organism, A, B and C are reported as prominent ocular pathogens. Genomic studies of these strains shall aid in deciphering potential drug targets and genomic influence on pathogenesis. Hence, in this study we performed deep statistical profiling of codon usage in these serovars. The overall base composition analysis reveals that these serovars are over biased to AU than GC. Similarly, relative synonymous codon usage also showed preference towards A/U ending codons. Parity Rule 2 analysis inferred unequal distribution of AT and GC, indicative of other unknown factors acting along with mutational pressure to influence codon usage bias (CUB). Moreover, absolute quantification of CUB also revealed lower bias across these serovars. The effect of natural selection on CUB was also confirmed by neutrality plot, reinforcing natural selection under mutational pressure turned to be a pivotal role in shaping the CUB in the strains studied. Correspondence analysis (COA) clarified that, C.t C/TW-3 to show a unique trend in codon usage variation. Host influence analysis on shaping the codon usage pattern also inferred some speculative relativity. In a nutshell, our finding suggests that mutational pressure is the dominating factor in shaping CUB in the strains studied, followed by natural selection. We also propose potential drug targets based on cumulative analysis of strand bias, CUB and human non-homologue screening.


The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction.


title: NMR metabolomics of human blood and urine in disease research.

text: This paper reviews the main applications of NMR metabolomics of blood and urine in disease research, over the last 5 years. The broad range of disease types addressed attests the increasing interest within the academic and medical communities to explore the recognised potential of metabolomics to (1) provide insight into underlying disease pathogenesis and (2) unveil new metabolic markers for disease diagnosis and follow up. Importantly, most recent studies reveal an increasing awareness of possible limitations and pitfalls of the metabolomics approach, together with efforts for improved study design and statistical validation, which are crucial requisites for the sound development of NMR metabolomics and its progress into the clinical setting.