title: Fully percutaneous transthoracic left atrial entry and closure as a potential access route for transcatheter mitral valve interventions.

text: BACKGROUND Percutaneous access for mitral interventions is currently limited to transapical and transseptal routes, both of which have shortcomings. We hypothesized that the left atrium could be accessed directly through the posterior chest wall under imaging guidance. METHODS AND RESULTS We tested percutaneous transthoracic left atrial access in 12 animals (10 pigs and 2 sheep) under real-time magnetic resonance imaging or x-ray fluoroscopy plus C-arm computed tomographic guidance. The pleural space was insufflated with CO2 to displace the lung, an 18F sheath was delivered to the left atrium, and the left atrial port was closed using an off-the-shelf nitinol cardiac occluder. Animals were survived for a minimum of 7 days. The left atrial was accessed, and the port was closed successfully in 12/12 animals. There was no procedural mortality and only 1 hemodynamically insignificant pericardial effusion was observed at follow-up. We also successfully performed the procedure on 3 human cadavers. A simulated trajectory to the left atrium was present in all of 10 human cardiac computed tomographic angiograms analyzed. CONCLUSIONS Percutaneous transthoracic left atrial access is feasible without instrumenting the left ventricular myocardium. In our experience, magnetic resonance imaging offers superb visualization of anatomic structures with the ability to monitor and address complications in real-time, although x-ray guidance seems feasible. Clinical translation seems realistic based on human cardiac computed tomographic analysis and cadaver testing. This technique could provide a direct nonsurgical access route for future transcatheter mitral implantation.


title: Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis.

text: BACKGROUND Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses. OBJECTIVE AND RATIONALE The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses. SEARCH METHODS Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale. OUTCOMES From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79-1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86-1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55-1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06-4.56). WIDER IMPLICATIONS A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.


title: Drone aggregation behavior in the social wasp Vespula germanica (Hymenoptera: Vespidae): Effect of kinship and density.

text: Inbreeding can have negative consequences on population viability because of the reduced fitness of the progeny. In general, most species have developed mechanisms to minimize inbreeding such as dispersal and kin avoidance behavior. In the eusocial Hymenoptera, related individuals typically share a common nest and have relatively short mating periods, this could lead to inbreeding, and because of their single-locus complementary sex determination system, it may generate diploid males that could result in infertile triploid progeny representing a cost for the colony. Vespula germanica, is an eusocial wasp that has invaded many parts of the world, despite likely facing a reduced genetic pool during the arrival phases. We ask whether male wasp display specific aggregation behavior that favors genetic diversity, key to reduce inbreeding. Through a set of laboratory experiments, we investigated the effects of drone nestmateship and density on the aggregation behavior of V. germanica drones. We show that drones avoid aggregating with their nestmates at all densities while non-nestmates are avoided only at high densities. This suggests that lek genetic diversity and density could be regulated through drone behavior and in the long run minimize inbreeding favoring invasion success.


title: The rapid shallow breathing index as a predictor of successful mechanical ventilation weaning: clinical utility when calculated from ventilator data.

text: OBJECTIVE The use of the rapid shallow breathing index (RSBI) is recommended in ICUs, where it is used as a predictor of mechanical ventilation (MV) weaning success. The aim of this study was to compare the performance of the RSBI calculated by the traditional method (described in 1991) with that of the RSBI calculated directly from MV parameters. METHODS This was a prospective observational study involving patients who had been on MV for more than 24 h and were candidates for weaning. The RSBI was obtained by the same examiner using the two different methods (employing a spirometer and the parameters from the ventilator display) at random. In comparing the values obtained with the two methods, we used the Mann-Whitney test, Pearson's linear correlation test, and Bland-Altman plots. The performance of the methods was compared by evaluation of the areas under the ROC curves. RESULTS Of the 109 selected patients (60 males; mean age, 62 ± 20 years), 65 were successfully weaned, and 36 died. There were statistically significant differences between the two methods for respiratory rate, tidal volume, and RSBI (p < 0.001 for all). However, when the two methods were compared, the concordance and the intra-observer variation coefficient were 0.94 (0.92-0.96) and 11.16%, respectively. The area under the ROC curve was similar for both methods (0.81 ± 0.04 vs. 0.82 ± 0.04; p = 0.935), which is relevant in the context of this study. CONCLUSIONS The satisfactory performance of the RSBI as a predictor of weaning success, regardless of the method employed, demonstrates the utility of the method using the mechanical ventilator.


title: Probiotic use in an infectious disease setting.

text: INTRODUCTION The lethality of infectious diseases and deep concern over growing antimicrobial resistance make it essential that alternative or adjunct therapies be developed. Areas covered: Using papers published in PubMed, a case is presented to consider beneficial microbes as a means to improve management of infectious diseases. Clinical evidence is mounting that certain probiotic microbes can contribute to this armamentarium. These could have an immediate effect against necrotizing enterocolitis, pre- and post-surgical procedures, antibiotic-associated infections, urogenital infections in women and for reducing the severity and duration of respiratory infections. While further studies will always be warranted irrespective of the intervention, and quality assurance and patient safety must remain a priority, the main barrier to implementation may well be unwarranted hesitation amongst physicians, healthcare administrators and regulators. Meanwhile, patients are already taking things into their own hands at a time when their knowledge of product selection is poor and clinical guidance is invariably missing. Expert commentary: Until vaccines and other alternatives emerge, it would be foolhardy to not use best practices to bring probiotics into mainstream infectious disease management. Our ability to manipulate microbial-host interactions offers hope before the last antibiotic stops being effective.


title: Patients With Intermittent Claudication and Chronic Widespread Pain Improves in Health-Related Quality of Life After Invasive but Not After Noninvasive Treatment.

text: Background Intermittent claudication (IC) is traditionally managed with risk factor modification, best medical treatment (BMT), and exercise training. Comorbidities such as diabetes and ischemic heart disease affect both results of invasive treatment and health-related quality of life (HRQoL) negatively. It is unknown how chronic widespread pain (CWP) influences the results of invasive treatment. We evaluated the influence of CWP on HRQoL in patients undergoing invasive (open surgery or endovascular treatment) and noninvasive BMT of IC. Methods A total of 242 patients with IC treated with invasive or noninvasive methods responded to the validated HRQoL questionnaires Short Form 36 Health Survey, EuroQoL 5-dimensions, and distribution of pain with the Epipain questionnaire at baseline and after 12 months. Results Invasively treated patients without CWP improved in all primary outcome measures. Patients with CWP reported significant improvements in most of the HRQoL-related outcome measures after invasive treatment, but patients with CWP in the noninvasive treatment group did not improve in any HRQoL-related outcome measure. Conclusions The presence of CWP not should be a cause to withhold invasive treatment in patients with IC.


title: Efficacy of interleukin 10 gene hydrofection in pig liver vascular isolated 'in vivo' by surgical procedure with interest in liver transplantation.

text: AIM Liver transplantation is the only curative strategy for final stage liver diseases. Despite the great advances achieved during the last 20 years, the recipient immune response after transplantation is not entirely controlled. This results in high rates of acute cell rejection and, approximately, 10% of early mortality. Therapeutic treatment could be improved by efficiently transfecting genes that encode natural immunosuppressant proteins, employing safe procedures that could be transferred to clinical setting. In this sense, interleukin 10 plays a central role in immune tolerance response by acting at different levels. METHODS hIL10 gene was hydrofected by retrograde hydrodynamic injection in pig liver with complete vascular exclusion mediated by an 'in vivo' surgical procedure. Levels of IL10 DNA, RNA and protein were determined within liver tissue 1 and 10 days after the injection and, more frequently, also the interleukin-10 protein in peripheral blood. RESULTS The procedure was safe for the animals and neither hemodynamic parameters nor liver function determinations showed relevant alterations. The hIL10 hydrofection in watertight liver mediated efficient gene transfer and this was transcribed and translated to protein, achieving up to 110 pg/ml of IL10 in peripheral blood. This value is close to that considered able to reduce the activity of TNFα by half (IL10 IC50 for TNFα = 124 pg/ml). CONCLUSIONS Results of this work suggest that IL10 liver hydrofection with vascular exclusion in vivo is a safe and transferable procedure that mediates plasma protein levels with potential clinical interest in immune modulation after transplantation.


title: Video-assisted thoracoscopic left upper lobe sleeve lobectomy combined with pulmonary arterioplasty via two-port approach.

text: Here we report a case of left upper lobe sleeve lobectomy with pulmonary arterioplasty via video-assisted thoracoscopy surgery (VATS) two-port approach. A squamous cell carcinoma with stage T3N1M0 was identified on pathological examination. The bronchial anastomosis was performed using running suture with a 3-0 prolene. Two bulldog clamps were used to gain adequate vascular control. Partial pulmonary artery resection was achieved tangentially with a stapler. The postoperative course was uneventful.


title: Medical students' knowledge of and attitudes towards LGBT people and their health care needs: Impact of a lecture on LGBT health.

text: OBJECTIVES Lesbian, gay, bisexual, and transgender (LGBT) adolescents have specific health care needs and are susceptible to health care disparities. Lack of skills and knowledge on the part of health care providers have a negative effect on their access to care and health outcomes. This study 1) explores the knowledge and attitudes of medical students regarding LGBT people, and 2) assesses the impact of a one-hour lecture targeting adolescent LGBT health needs. METHODS Fourth-year medical students attended a compulsory one-hour lecture on sexual orientation and gender identity development in adolescence, highlighting health issues. We created a questionnaire with items to elicit students' knowledge and attitudes about LGBT health issues. Students were invited to complete this questionnaire online anonymously one week before the lecture and one month after the lecture. RESULTS Out of a total of 157 students, 107 (68.2%) responded to the pre-intervention questionnaire and 96 (61.1%) to the post-intervention questionnaire. A significant proportion-13.7% of all respondents-identified as LGBT or questioning. Our results show that most medical students already show favorable attitudes towards LGBT people and a certain degree of knowledge of LGBT health needs. They demonstrated a large and significant increase in knowledge of LGBT health issues one month after the lecture. DISCUSSION A single one-hour lecture on sexual orientation and LGBT health issues may increase knowledge among medical students. Medical students and professionals should receive such training to increase their knowledge about LGBT patients as it, together with favorable attitudes, has the potential to improve health outcomes among this vulnerable population.


title: New coronavirus outbreak: Framing questions for pandemic prevention.

text: We need to understand and quantify the dominant variables that govern the SARS-CoV-2 outbreak, rather than relying exclusively on confirmed cases and their geospatial spread.


title: Combined proximal balloon occlusion and distal aspiration: a new approach to prevent distal embolization during neurothrombectomy.

text: BACKGROUND AND PURPOSE Embolization of thrombus fragments in a new vascular territory is a potential adverse event in neurothrombectomy. This study was performed to evaluate the safety and feasibility of a novel approach combining proximal balloon occlusion and distal aspiration to prevent distal thrombembolic complications. METHODS Patients with ischemic stroke meeting the following inclusion criteria were eligible: occlusion in the anterior circulation, neurothrombectomy using a balloon catheter for proximal flow arrest, and an intermediate catheter for distal aspiration. Pre- and post-interventional Thrombolysis In Cerebral Infarction (TICI) scores were assessed. Clinical presentation at admission and discharge and after 3 months was also evaluated and complications (particularly new thrombembolic events) were recorded. RESULTS We retrospectively identified 31 patients from our prospectively collected stroke database who met the inclusion criteria. In all patients the initial TICI was 0. A TICI score of ≥2b was achieved in 96.8%. No new thrombembolic complications occurred. The median NIH Stroke Scale score was 19 at admission and 4.5 at discharge. After 3 months, 51.6% of the patients had a favorable clinical outcome (modified Rankin Scale score 0-2) and 19.3% had died. CONCLUSIONS A combination of proximal internal carotid artery occlusion using a balloon catheter and distal aspiration through an intermediate catheter represents a safe and efficient adjunct to mechanical thrombectomy with stent retrievers. In our patient cohort, no new thrombembolic complications were detected.


title: Medical termination for pregnancy in early first trimester (≤ 63 days) using combination of mifepristone and misoprostol or misoprostol alone: a systematic review.

text: BACKGROUND A wide range of drugs have been studied for first trimester medical abortion. Studies evaluating different regimens, including combination mifepristone and misoprostol and misoprostol alone regimens, show varying results related to safety, efficacy and other outcomes. Thus, the objectives of this systematic review were to compare the safety, effectiveness and acceptability of medical abortion and to compare medical with surgical methods of abortion ≤63 days of gestation. METHODS Pubmed and EMBASE were systematically searched from database inception through January 2019 using a combination of MeSH, keywords and text words. Randomized controlled trials on induced abortion at ≤63 days that compared different regimens of medical abortion using mifepristone and/or misoprostol and trials that compared medical with surgical methods of abortion were included. We extracted data into a pre-designed form, calculated effect estimates, and performed meta-analyses where possible. The primary outcomes were ongoing pregnancy and successful abortion. RESULTS Thirty-three studies composed of 22,275 participants were included in this review. Combined regimens using mifepristone and misoprostol had lower rates of ongoing pregnancy, higher rates of successful abortion and satisfaction compared to misoprostol only regimens. In combined regimens, misoprostol 800 μg was more effective than 400 μg. There was no significant difference in dosing intervals between mifepristone and misoprostol and routes of misoprostol administration in combination or misoprostol alone regimens. The rate of serious adverse events was generally low. CONCLUSION In this systematic review, we find that medical methods of abortion utilizing combination mifepristone and misoprostol or misoprostol alone are effective, safe and acceptable. More robust studies evaluating both the different combination and misoprostol alone regimens are needed to strengthen existing evidence as well as assess patient perspectives towards a particular regimen.


title: Manual aspiration thrombectomy using a Penumbra catheter in patients with acute migrated MCA occlusion.

text: Background We retrospectively assessed the efficacy and safety of manual aspiration thrombectomy (MAT) using a Penumbra catheter in patients with acute migrated middle cerebral artery (MCA) occlusion. Methods We conducted a retrospective review of patients who underwent MAT using Penumbra 4 or 5 MAX reperfusion catheters for the treatment of acute MCA occlusion between January 2012 and December 2015. A migrated thrombus was defined as distal migration greater than ≥1 cm on initial cerebral angiography compared with preprocedural angiographic findings. We evaluated immediate angiographic results and clinical outcomes through a review of electronic medical records and compared clinical outcomes between migrated and non-migrated MCA occlusions. Results During this period, 98 patients underwent MAT using Penumbra catheters for treatment of acute MCA occlusions. Of these, 19 (19.4%) had a migrated MCA thrombus on initial cerebral angiography compared with preprocedural angiographic findings. The overall rate of successful recanalization (TICI grade ≥ 2b) was 90.8%. The rate of successful recanalization in the migrated thrombus group was 94.7% (18/19). Overall procedure time for recanalization in the migrated thrombus group was significantly shorter than that in the non-migrated thrombus group ( p = 0.001). Although the difference was not significant, there was a trend toward more favorable clinical outcomes in the migrated thrombus group compared to the non-migrated thrombus groups (78.9% versus 60.8%, p = 0.231). Conclusion MAT appears to be safe and can achieve a high rate of successful recanalization and favorable clinical outcomes with short procedure time and without serious complications in patients with acute migrated MCA occlusion.


'Do not attempt cardiopulmonary resuscitation' or 'allowing natural death'? The time for resuscitation community to review its boundaries and its terminology.


title: Pylorus preserving loop duodeno-enterostomy with sleeve gastrectomy - preliminary results.

text: BACKGROUND Bariatric operations mostly combine a restrictive gastric component with a rerouting of the intestinal passage. The pylorus can thereby be alternatively preserved or excluded. With the aim of performing a "pylorus-preserving gastric bypass", we present early results of a proximal postpyloric loop duodeno-jejunostomy associated with a sleeve gastrectomy (LSG) compared to results of a parallel, but distal LSG with a loop duodeno-ileostomy as a two-step procedure. METHODS 16 patients underwent either a two-step LSG with a distal loop duodeno-ileostomy (DIOS) as revisional bariatric surgery or a combined single step operation with a proximal duodeno-jejunostomy (DJOS). Total small intestinal length was determined to account for inter-individual differences. RESULTS Mean operative time for the second-step of the DIOS operation was 121 min and 147 min for the combined DJOS operation. The overall intestinal length was 750.8 cm (range 600-900 cm) with a bypassed limb length of 235.7 cm in DJOS patients. The mean length of the common channel in DIOS patients measured 245.6 cm. Overall excess weight loss (%EWL) of the two-step DIOS procedure came to 38.31% and 49.60%, DJOS patients experienced an %EWL of 19.75% and 46.53% at 1 and 6 months, resp. No complication related to the duodeno-enterostomy occurred. CONCLUSIONS Loop duodeno-enterosomies with sleeve gastrectomy can be safely performed and may open new alternatives in bariatric surgery with the possibility for inter-individual adaptation.


title: Travel-related fever in the time of COVID-19 travel restrictions.

text: Travel-related infections with prolonged incubation periods should be considered in febrile patients despite the current epidemiological situation, especially if alternative more frequent diagnoses, such as COVID-19, are not confirmed.


Labor and Delivery Visitor Policies During the COVID-19 Pandemic: Balancing Risks and Benefits.


title: Is acute reperfusion therapy safe in acute ischemic stroke patients who harbor unruptured intracranial aneurysm?

text: BACKGROUND Intracranial aneurysms are currently considered as contraindication for intravenous thrombolysis in acute ischemic stroke, very likely due to a possible increase in the risk of bleeding from aneurysm rupture; however, there is limited data available on whether intravenous thrombolysis is safe for acute ischemic stroke patients with pre-existing intracranial aneurysms. AIMS AND/OR HYPOTHESIS To find out the safety of intravenous thrombolysis in acute ischemic stroke patients who harbor unruptured intracranial aneurysms. METHODS We retrospectively reviewed the medical records and cerebrovascular images of all the patients treated with intravenous thrombolysis for acute ischemic stroke in our center from the beginning of 2006 till the end of April 2014. Those with unruptured intracranial aneurysm present on cerebrovascular images prior to acute reperfusion therapy were identified. Post-thrombolysis brain imaging was reviewed to evaluate for any intraparenchymal or subarachnoid hemorrhage related or unrelated to the aneurysm. RESULTS A total of 637 patients received intravenous thrombolysis for acute ischemic stroke in our center during an 8·3-year period. Thirty-three (5·2%) were found to have at least one intracranial aneurysms. Twenty-three (70%) of those received only intravenous thrombolysis, and 10 patients received combination of intravenous and intra-arterial thrombolysis. The size of the largest aneurysm was 10 mm in maximum diameter (range: 2-10 mm). The mean size of aneurysms was 4·8 mm. No symptomatic intracranial hemorrhage occurred among the 23 patients receiving only intravenous thrombolysis. Out of those who received a combination of intravenous and intra-arterial thrombolysis, one developed symptomatic intracranial hemorrhage in the location of acute infarct, distant to the aneurysm location. CONCLUSION Our findings suggest that neither intravenous thrombolysis nor combination of intravenous and intra-arterial thrombolysis increases the risk of aneurysmal hemorrhage in acute ischemic stroke patients who harbor unruptured intracranial aneurysms less than 10 mm in diameter. Their listing in exclusion criteria for intravenous thrombolysis should be reconsidered to assure appropriate use of acute reperfusion therapy in this group of patients.


title: Charting a Research Agenda for the Advancement of Nursing Organizations' Influence on Health Systems and Policy.

text: Nursing organizations across Canada play a significant role in influencing and shaping public policy. 2020, the Year of the Nurse and the Midwife, is an opportune time not only to support nurses in building policy leadership but also to explore opportunities to better understand and strengthen the policy advocacy work of nursing organizations. Given various social, political, and economic forces, the nature of organized nursing across Canada is changing significantly. We draw on recent key national and global events including our systematic inquiry into the Canada's 2019 federal election, the Year of the Nurse and Midwife, and the Coronavirus pandemic to examine how Canadian nursing organizations respond in highly complex and evolving contexts. We use our observations to offer a vision and chart a research agenda for the advancement of nursing organizations' influence on health systems and policy. Specifically, we focus on three key areas including examining nursing organizations' policy agendas and spheres of influence; nursing organizations' decision-making around policy advocacy tactics and engagement approaches; and the impact of policy advocacy coalitions and networks on nursing organizations' influence.


title: Effects of chicken anaemia virus and infectious bursal disease virus-induced immunodeficiency on infectious bronchitis virus replication and genotypic drift.

text: We followed changes in a portion of the S1 gene sequence of the dominant populations of an infectious bronchitis virus (IBV) Arkansas (Ark) vaccine strain during serial passage in chickens infected with the immunosuppressive chicken anaemia virus (CAV) and/or infectious bursal disease virus (IBDV) as well as in immunocompetent chickens. The IBV-Ark vaccine was applied ocularly and tears were collected from infected chickens for subsequent ocular inoculation in later passages. The experiment was performed twice. In both experiments the dominant S1 genotype of the vaccine strain was rapidly and negatively selected in all chicken groups (CAV, IBDV, CAV+IBDV and immunocompetent). Based on the S1 genotype, the same IBV subpopulations previously reported in immunocompetent chickens and named component (C) 1 to C5 emerged both in immunocompetent and immunodeficient chickens. During the first passage different subpopulations emerged, followed by the establishment of one or two predominant populations after further passages. Only when the subpopulation designated C2 became established in either CAV-infected or IBDV-infected chickens was IBV maintained for more than four passages. These results indicate that selection does not cease in immunodeficient chickens and that phenotype C2 may show a distinct adaptation to this environment. Subpopulations C1 or C4 initially became established in immunocompetent birds but became extinct after only a few succeeding passages. A similar result was observed in chickens co-infected with CAV+IBDV. These results suggest that the generation of genetic diversity in IBV is constrained. This finding constitutes further evidence for phenotypic drift occurring mainly as a result of selection.


Managing patients with COVID-19 infections: a first-hand experience from the Wuhan Mobile Cabin Hospital.


title: Preventing Cleavage of the Respiratory Syncytial Virus Attachment Protein in Vero Cells Rescues the Infectivity of Progeny Virus for Primary Human Airway Cultures.

text: UNLABELLED All live attenuated respiratory syncytial virus (RSV) vaccines that have advanced to clinical trials have been produced in Vero cells. The attachment (G) glycoprotein in virions produced in these cells is smaller than that produced in other immortalized cells due to cleavage. These virions are 5-fold less infectious for primary well-differentiated human airway epithelial (HAE) cell cultures. Because HAE cells are isolated directly from human airways, Vero cell-grown vaccine virus would very likely be similarly inefficient at initiating infection of the nasal epithelium following vaccination, and therefore, a larger inoculum would be required for effective vaccination. We hypothesized that Vero cell-derived virus containing an intact G protein would be more infectious for HAE cell cultures. Using protease inhibitors with increasing specificity, we identified cathepsin L to be the protease responsible for cleavage. Our evidence suggests that cleavage occurs in the late endosome or lysosome during endocytic recycling. Cathepsin L activity was 100-fold greater in Vero cells than in HeLa cells. In addition, cathepsin L was able to cleave the G protein in Vero cell-grown virions but not in HeLa cell-grown virions, suggesting a difference in G-protein posttranslational modification in the two cell lines. We identified by mutagenesis amino acids important for cleavage, and these amino acids included a likely cathepsin L cleavage site. Virus containing a modified, noncleavable G protein produced in Vero cells was 5-fold more infectious for HAE cells in culture, confirming our hypothesis and indicating the value of including such a mutation in future live attenuated RSV vaccines. IMPORTANCE Worldwide, RSV is the second leading infectious cause of infant death, but no vaccine is available. Experimental live attenuated RSV vaccines are grown in Vero cells, but during production the virion attachment (G) glycoprotein is cleaved. Virions containing a cleaved G protein are less infectious for primary airway epithelial cells, the natural RSV target. In the study described here we identified the protease responsible, located the cleavage site, and demonstrated that cleavage likely occurs during endocytic recycling. Moreover, we showed that the infectivity of Vero cell-derived virus for primary airway epithelial cells is increased 5-fold if the virus contains a mutation in the G protein that prevents cleavage. The blocking of cleavage should improve RSV vaccine yield, consequently reducing production costs. Posttranslational cleavage of the fusion glycoprotein of many viruses plays an essential role in activation; however, cleavage of the RSV G protein is a novel example of a detrimental effect of cleavage on virus infectivity.


title: A conserved RNA pseudoknot in a putative molecular switch domain of the 3'-untranslated region of coronaviruses is only marginally stable.

text: The 3'-untranslated region (UTR) of the group 2 coronavirus mouse hepatitis virus (MHV) genome contains a predicted bulged stem-loop (designated P0ab), a conserved cis-acting pseudoknot (PK), and a more distal stem-loop (designated P2). Base-pairing to create the pseudoknot-forming stem (P1(pk)) is mutually exclusive with formation of stem P0a at the base of the bulged stem-loop; as a result, the two structures cannot be present simultaneously. Herein, we use thermodynamic methods to evaluate the ability of individual subdomains of the 3' UTR to adopt a pseudoknotted conformation. We find that an RNA capable of forming only the predicted PK (58 nt; 3' nucleotides 241-185) adopts the P2 stem-loop with little evidence for P1(pk) pairing in 0.1 M KCl and the absence of Mg(2+); as Mg(2+) or 1 M KCl is added, a new thermal unfolding transition is induced and assignable to P1(pk) pairing. The P1(pk) helix is only marginally stable, ΔG(25) ≈ 1.2 ± 0.3 kcal/mol (5.0 mM Mg(2+), 100 mM K(+)), and unfolded at 37°C. Similar findings characterize an RNA 5' extended through the P0b helix only (89 nt; 294-185). In contrast, an RNA capable of forming either the P0a helix or the pseudoknot (97 nt; 301-185) forms no P1(pk) helix. Thermal unfolding simulations are fully consistent with these experimental findings. These data reveal that the PK forms weakly and only when the competing double-hairpin structure cannot form; in the UTR RNA, the double hairpin is the predominant conformer under all solution conditions.


Clinical characteristics of foreign-imported COVID-19 cases in Shanghai, China.


title: The effect of narrowed gastric conduits on anastomotic leakage following minimally invasive oesophagectomy.

text: OBJECTIVES Anastomotic leakage remains a major complication following minimally invasive oesophagectomy (MIO). In this study, our objective was to determine whether a narrower gastric conduit would lead to lower incidence of anastomotic leakage following MIO. METHODS In this retrospective study, patients with oesophageal cancer undergoing MIO were assigned to receive 5-cm-wide gastric conduits (from May 2011 to February 2012, Group W) and then 3-cm-wide gastric conduits (from March 2012 to December 2012, Group N) for gastro-oesophageal anastomosis. The length of the gastric conduit and the anastomotic details were recorded during surgery. Perfusion status of the conduit was analysed before and after anastomosis using a laser Doppler perfusion monitor. Following surgery, the incidence of anastomotic leakage in the two groups was statistically compared to identify differences between the two methods of gastric formation. RESULTS There were 126 patients in Group N and 133 patients in Group W. Patient demographics and surgical observations were comparable between the two groups. In Group N, the length of gastric conduit was significantly greater than in Group W (39.1 ± 2.7 vs 35.6 ± 4.4 cm, P = 0.0021). Lower reduction of perfusion units was recorded in Group N after gastro-oesophageal anastomosis (45.7 vs 28.1%, P = 0.004). Postoperatively, a total of 34 cases (13.13%) of anastomotic leakage was observed, and the incidence of anastomotic leakage was significantly lower in Group N than in Group W (8.7 vs 17.3%, P = 0.041). CONCLUSIONS Narrow gastric tubes were longer and less interfered in perfusion, which contributed to lower incidence of anastomotic leakage following minimally invasive oesophagectomy. Further study of the long-term effects of such treatment is required to confirm the advantages of this technique.


title: In vitro chemoresponse analysis of cervical cancer patient specimens.

text: PURPOSE The objective of this study was to report the results of in vitro chemoresponse analysis of primary, metastatic, and recurrent human cervical cancers. METHODS There were 557 tumor specimens submitted for testing from August 2006 to June 2010. Single agents tested were cisplatin, carboplatin, paclitaxel, docetaxel, epirubicin, fluorouracil, 4-hydroxy ifosfamide (active metabolite of ifosfamide), SN-38 (active metabolite of irinotecan), topotecan, and vinorelbine. Doublets tested were carboplatin/paclitaxel and cisplatin/topotecan. Tumor response was determined from dose-response curves. Results were scored as responsive, intermediate, or nonresponsive. Chemoresponse was reported as the combined responsive and intermediate results. RESULTS Three hundred fifty-three (63.4%) of 557 submitted specimens were successfully assayed. Confirmation of histology and tumor status (primary, metastatic, or recurrent) was available for 273 specimens. The chemoresponse of the most active agents in primary cancers (n = 151) was 75% for SN-38, 71% for 4-hydroxy ifosfamide, 62% for topotecan, and 73% for carboplatin/paclitaxel. The chemoresponse of metastatic cancers (n = 66) was 54% for SN-38, 51% for 4-hydroxy ifosfamide, 44% for epirubicin, and 53% for carboplatin/paclitaxel. The chemoresponse for recurrent cancers (n = 56) was 44% for epirubicin, 41% for 4-hydroxy ifosfamide, 39% for vinorelbine, 39% for paclitaxel, 36% for topotecan, 46% for carboplatin/paclitaxel, and 35% for cisplatin/topotecan. The overall chemoresponse was greater in primary cancers (58%) than in recurrent cancers (35%) (P < 0.0001). CONCLUSIONS In vitro chemoresponse analysis of cervical cancer biospecimens is feasible. Chemoresponse results are variable depending on tumor status. Clinical studies of assay-directed therapy should be developed.


title: Surgical outcomes according to the type of monopolar electrocautery device used in laparoscopic surgery for right colon cancer: a comparison of endo-hook versus endo-shears.

text: BACKGROUND Although monopolar electrocautery is preferred by many laparoscopic surgeons and is more cost-effective than bipolar or ultrasonic scissors, few studies have compared these outcomes between different monopolar electrocautery devices used in laparoscopic surgery. Therefore, this study compared the surgical outcomes between monopolar endo-hook versus endo-shears during laparoscopic right hemicolectomy for right colon cancer. METHODS Using a prospective database of patients treated at our institute, we analyzed the surgical outcomes of 358 consecutive patients with right colon cancer who underwent curative laparoscopic surgery with a monopolar endo-hook (n = 164) or endo-shears (n = 194) between March 2009 and March 2017. RESULTS There were no differences in age, sex, body mass index, American Society of Anesthesiologists' grade, previous operative history, or clinical stage between the endo-hook and endo-shears groups. The estimated blood loss was similar between the endo-hook and endo-shears groups (90.9 ± 60.3 vs. 92.0 ± 89.3 mL; P = 0.893). The number of harvested lymph nodes was greater in the endo-hook group (53.5 ± 20.3 vs. 48.1 ± 18.5; P = 0.008). Hospital stay was shorter in the endo-hook group (6.8 ± 2.2 vs. 7.8 ± 4.8 days; P = 0.013). Although chylous ascites was more frequent in the endo-hook group (21.3% vs. 7.7%, P < 0.001), the postoperative morbidity rate was lower in this group (9.8% vs. 18.0%; P = 0.025). All instances of chylous ascites healed spontaneously without intervention. CONCLUSIONS This study showed that the use of a monopolar endo-hook during laparoscopic right hemicolectomy might permit more meticulous lymph-node dissection and reduce morbidity compared with the use of monopolar endo-shears. Therefore, we suggest that the outcomes of laparoscopic surgery might be associated with the type of electrocautery device used.


title: Complication analysis of distal pancreatectomy based on early personal experience.

text: BACKGROUNDS/AIMS The objective of this study was to evaluate the relationship between initial personal experiences with distal pancreatectomy and perioperative risk factors, outcomes, and management of pancreatic fistulas. METHODS Between May, 2007 and May, 2010, a total of 28 patients who had undergone elective distal pancreatectomy were evaluated for this study. Perioperative factors and the occurrence of pancreatic fistula were analyzed on the basis of International Study Group of Pancreatic Fistula (ISGPF) criteria. RESULTS There were sixteen cases of benign neoplasms and twelve cases of malignant tumors. The remnant pancreas was manually sutured with ligation of the pancreatic duct (n=14), auto-suture stapling along with manual sutures (n=12), or stapling alone (n=2). According to the ISGPF classification, morbidity and mortality associated with pancreatic fistulas was 42.9% (n=12) and 0%, respectively. These pancreatic fistulae were classified as grade A in 8 cases (28.6%), grade B in 3 cases (10.7%), and grade C in one case (3.6%). All patients with pancreatic fistula were treated conservatively. CONCLUSIONS Perioperative factors do not affect the risk of pancreatic fistula. Adequate drainage is the most effective method for management of a pancreatic fistula after distal pancreatectomy.


title: Comparative analysis of Laparoscopic versus open surgical radiofrequency ablation for malignant liver tumors.

text: BACKGROUNDS/AIMS This study aims to evaluate the comparative effectiveness of two surgical approaches on the treatment outcomes of radiofrequency ablation (RFA) for malignant liver tumors. METHODS Fifty-seven patients with malignant liver tumors, hepatocellular carcinoma, cholangiocarcinoma and liver metastases, who were candidates for RFA, underwent laparoscopic or open surgical treatments. RESULTS The patients' characteristics were comparable in the two groups that received open (n=33, 57.9%) and laparoscopic (n=24, 42.1%) surgical treatments. There were no statistically significant differences between the two groups in terms of recurrence rate (p=0.337) and overall survival (p=0.423). However, patients in the laparoscopic RFA group had significantly shorter hospital stay (14.1 vs. 5.9 days, p<0.05) and experienced fewer complications (Grade I: 62.5% vs. 26.3%, p=0.102). CONCLUSIONS Laparoscopic RFA can be performed for malignant liver tumors with lower morbidity rates, less invasiveness and lower expense compared to open surgical approach.


Covid-19: UK deaths approach 50 000, but rate declines.


title: Rare inborn errors associated with chronic hepatitis B virus infection.

text: UNLABELLED Chronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB and 40 controls who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls. The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB, with P values of <1.0 × 10(-7) , 2.76 × 10(-5) , 5.08 × 10(-5) , 2.78 × 10(-4) and odds ratios (ORs) of 2.45, 4.08, 2.34, and 1.97, respectively. The combined P value was <2.0 × 10(-16) . As there has been no indication of immunological functions for the associated gene, transmembrane protein 2, we further studied its expression by immunohistochemistry, real-time polymerase chain reaction, and western blotting. Our results showed that it was strongly expressed by healthy hepatocytes, but its expression was reduced in liver tissues with CHB, hepatitis B viral (HBV) genome-containing HepG2.2.15 cells, as compared with healthy liver tissues and non-HBV genome-containing HepG2 cells (P = 0.022 and 0.0036, respectively). CONCLUSION We identified four missense mutations associated with CHB, our results providing evidence for rare inborn genetic defects that contribute to increased host susceptibility to CHB.


UK ACHD response to COVID-19: Which adult patients are being advised to follow shielding by UK centres?


title: Vitamin D and asthma.

text: PURPOSE OF REVIEW asthma is a disease that continues to carry a significant health burden on humanity. Vitamin D is thought to play a role in many chronic diseases as it may possess immunomodulatory properties. This article will review the role of vitamin D regulation on the immune system and its potential implication in the pathophysiology of asthma. RECENT FINDINGS vitamin D receptors are present on many cells in the body, specifically peripheral blood mononuclear cells. Vitamin D has been shown to regulate the balance of several pro-inflammatory and anti-inflammatory responses in the immune system. Studies have suggested that prenatal vitamin D intake has an effect on childhood wheezing and asthma. Additionally, vitamin D may play a role in asthma exacerbations, and recent evidence also suggests its importance in steroid resistant asthma. SUMMARY vitamin D has a complex role on the immune system and its regulation of various aspects of immunity has allowed speculation on its potential role in asthma. However, the net effect of vitamin D on the immune system and its role in asthma still remains unanswered. More research needs to address the diagnostic and therapeutic implications vitamin D may have in the future of asthma management.


title: Recommendations for Dental Care during COVID-19 Pandemic.

text: Dental clinics were suspected to be a hotspot for nosocomial transmission of coronavirus disease 19 (COVID-19), yet there has been no clear recommendation about emergency dental care and appropriate personal protective equipment during pandemics. In this paper, we aim to summarize recommendations for (i) patient risk assessment, (ii) patient triage, and (iii) measures to prevent infection of health professionals and nosocomial transmission in dental clinics. The available evidence was collected by performing searches on PubMed, Embase, and Cochrane databases. We reviewed papers on COVID-19, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, and related respiratory viral diseases. Legal and ethical frameworks, as well as international (e.g., World Health Organization (WHO)) and national (e.g., public health institutes, dental associations) guidelines were screened to summarize recommendations related to dental emergency care. To assess the patient risk, a questionnaire was developed to classify patients at unknown, high, and very high risk. Patient triage recommendations were summarized in a flow chart that graded the emergency level of treatments (i.e., urgent, as soon as possible, and postpone). Measures to prevent disease transmission based on current evidence were grouped for dental health professionals, dental clinics, and patients. The present recommendations may support health professionals implement preventative measures during the pandemic.


title: Functional and genetic studies of the substrate specificity of coronavirus infectious bronchitis virus 3C-like proteinase.

text: Coronavirus (CoV) 3C-like proteinase (3CLpro), located in nonstructural protein 5 (nsp5), processes the replicase polyproteins 1a and 1ab (pp1a and pp1ab) at 11 specific sites to produce 12 mature nonstructural proteins (nsp5 to nsp16). Structural and biochemical studies suggest that a conserved Gln residue at the P1 position is absolutely required for efficient cleavage. Here, we investigate the effects of amino acid substitution at the P1 position of 3CLpro cleavage sites of infectious bronchitis virus (IBV) on the cleavage efficiency and viral replication by in vitro cleavage assays and reverse genetic approaches. Our results demonstrated that a P1-Asn substitution at the nsp4-5/Q2779, nsp5-6/Q3086, nsp7-8/Q3462, nsp8-9/Q3672, and nsp9-10/Q3783 sites, a P1-Glu substitution at the nsp8-9/Q3672 site, and a P1-His substitution at the nsp15-16/Q6327 site were tolerated and allowed recovery of infectious mutant viruses, albeit with variable degrees of growth defects. In contrast, a P1-Asn substitution at the nsp6-7/Q3379, nsp12-13/Q4868, nsp13-14/Q5468, and nsp14-15/Q5989 sites, as well as a P1-Pro substitution at the nsp15-16/Q6327 site, abolished 3CLpro-mediated cleavage at the corresponding position and blocked the recovery of infectious viruses. Analysis of the effects of these lethal mutations on RNA synthesis suggested that processing intermediates, such as the nsp6-7, nsp12-13, nsp13-14, nsp14-15, and nsp15-16 precursors, may function in negative-stranded genomic RNA replication, whereas mature proteins may be required for subgenomic RNA (sgRNA) transcription. More interestingly, a mutant 3CLpro with either a P166S or P166L mutation was selected when an IBV infectious cDNA clone carrying the Q6327N mutation at the nsp15-16 site was introduced into cells. Either of the two mutations was proved to enhance significantly the 3CLpro-mediated cleavage efficiency at the nsp15-16 site with a P1-Asn substitution and compensate for the detrimental effects on recovery of infectious virus.


title: Convection enhanced delivery of cisplatin-loaded brain penetrating nanoparticles cures malignant glioma in rats.

text: Glioblastoma multiforme (GBM) is highly invasive and uniformly fatal, with median survival<20months after diagnosis even with the most aggressive treatment that includes surgery, radiation, and systemic chemotherapy. Cisplatin is a particularly potent chemotherapeutic agent, but its use to treat GBM is limited by severe systemic toxicity and inefficient penetration of brain tumor tissue even when it is placed directly in the brain within standard delivery systems. We describe the development of cisplatin-loaded nanoparticles that are small enough (70nm in diameter) to move within the porous extracellular matrix between cells and that possess a dense polyethylene glycol (PEG) corona that prevents them from being trapped by adhesion as they move through the brain tumor parenchyma. As a result, these "brain penetrating nanoparticles" penetrate much deeper into brain tumor tissue compared to nanoparticles without a dense PEG corona following local administration by either manual injection or convection enhanced delivery. The nanoparticles also provide controlled release of cisplatin in effective concentrations to kill the tumor cells that they reach without causing toxicity-related deaths that were observed when cisplatin was infused into the brain without a delivery system. Median survival time of rats bearing orthotopic glioma was significantly enhanced when cisplatin was delivered in brain penetrating nanoparticles (median survival not reached; 80% long-term survivors) compared to cisplatin in conventional un-PEGylated particles (median survival=40days), cisplatin alone (median survival=12days) or saline-treated controls (median survival=28days).


title: Laparoendoscopic single-site (LESS) surgery versus conventional laparoscopic surgery: comparison of surgical port performance in a surgical simulator with novices.

text: BACKGROUND Although laparoendoscopic single-site (LESS) surgery is feasible, it poses many technical challenges not seen in conventional laparoscopy. Recent interest and widespread implementation of LESS stems from advancements in commercially available access port technology. Consequently, this study objectively compared the technical performance between conventional laparoscopic and LESS surgical ports in a modified Fundamentals of Laparoscopic Surgery (FLS) simulator. METHODS The 24 novice participants in this study performed the FLS peg transfer task using two conventional laparoscopic 12-mm working ports, the SILS port, the TriPort access system, and the GelPOINT system with two standard length 5-mm graspers. Each participant completed the task using conventional laparoscopy first for familiarization, followed by each of the three LESS surgical ports in random order. Task completion time, errors, and subjective questionnaire ratings were used to compare conventional laparoscopy and the single-port devices. Congruent with FLS scoring procedures, task completion time and errors were used to compute a standardized task score for each port. RESULTS The task score did not differ significantly between conventional laparoscopy and the single-port devices. Additionally, there were no task score differences between trials for either the SILS port or the GelPOINT system. There was a significant performance decrement starting with the TriPort versus starting with either the SILS port or the GelPOINT, which resulted in the lowest overall trial task score (p<0.05). Task completion difficulty and instrument maneuverability resulted in no significant differences between ports. Ease of use and overall rank were significant, with conventional laparoscopy rated as the easiest to use and the highest overall followed by the GelPOINT system. CONCLUSIONS Overall, the TriPort may be more challenging for novices to use in learning the LESS procedure than either the SILS port or the GelPOINT system. The GelPOINT system may offer the most consistent platform for LESS performance and novice skill acquisition.


title: Bridging the past and the future of virology: surface plasmon resonance as a powerful tool to investigate virus/host interactions.

text: Despite decades of antiviral drug research and development, viruses still remain a top global healthcare problem. Compared to eukaryotic cells, viruses are composed by a limited numbers of proteins that, nevertheless, set up multiple interactions with cellular components, allowing the virus to take control of the infected cell. Each virus/host interaction can be considered as a therapeutical target for new antiviral drugs but, unfortunately, the systematic study of a so huge number of interactions is time-consuming and expensive, calling for models overcoming these drawbacks. Surface plasmon resonance (SPR) is a label-free optical technique to study biomolecular interactions in real time by detecting reflected light from a prism-gold film interface. Launched 20 years ago, SPR has become a nearly irreplaceable technology for the study of biomolecular interactions. Accordingly, SPR is increasingly used in the field of virology, spanning from the study of biological interactions to the identification of putative antiviral drugs. From the literature available, SPR emerges as an ideal link between conventional biological experimentation and system biology studies functional to the identification of highly connected viral or host proteins that act as nodal points in virus life cycle and thus considerable as therapeutical targets for the development of innovative antiviral strategies.


title: One-lung ventilation in infants and small children: blood gas values.

text: PURPOSE We investigated one-lung ventilation (OLV) in pediatric patients under 10 kg. The feasibility of OLV using either Arndt endobronchial blocker (AEB) or mainstem intubation technique is analyzed. Arterial blood gases (ABG) monitored throughout the procedures are presented. METHODS Following IRB approval, a retrospective chart review was conducted on 9 patients ≤6 months of age and 2 patients ≥12 months of age undergoing lung resections or aortic coarctations. For right thoracotomy, a conventional, cuffed, endotracheal tube (ETT) was inserted and guided into the left mainstem bronchus with a bronchoscope and the left lung was ventilated. For left thoracotomy, an AEB was inserted into the trachea 2 cm past the vocal cords and an ETT was placed through the cords adjacent to the blockers (extraluminal). A bronchoscope was then inserted through the ETT to visualize and manipulate the blocker into the left mainstem bronchus. The blocker cuff was inflated slowly under direct vision while the ETT continued to ventilate the right, dependent lung. ABG values were collected intraoperatively in all cases. RESULTS One-lung ventilation could be accomplished within 15 min in all cases, and lung isolation was successful in all patients. All patients were extubated within 12 h of surgery and had an uneventful recovery. ABG values revealed modest arterial acidosis and hypercarbia and mild acute ventilatory insufficiency. CONCLUSION The use of extraluminal AEB or mainstem intubation for OLV can be successfully completed in infants weighing less than 10 kg. OLV may induce acute respiratory pathology; therefore we recommend routine intraoperative ABG monitoring for pediatric patients.


title: Mediastinal teratoma with hydrops fetalis in a newborn and development of chronic respiratory insufficiency.

text: BACKGROUND Mediastinal fetal teratoma can be detected as a mass in the chest during a routine prenatal ultra-sound screening. Because of the pressure on mediastinal structures it can be the cause of non-immune hydrops fetalis and polyhydramnion. The development of hydrops fetalis leads to fetal death or premature delivery in most reported cases. Early surgical removal is important, but, the result of treatment depends on the stage of development of mediastinal organs and complications in the postoperative period. CASE REPORT A 31-year-old gravida carrying twins, with spontaneous membrane rupture at 32 weeks gestation underwent urgent caesarean section after antenatal ultrasound revealed severe polyhydramnion and hydrops fetalis in geminus A. The child was intubated immediately after birth due to severe respiratory distress. Ultrasound and X-ray revealed a tumour mass in the right hemithorax. Tumour resection was performed at the age of 7 days. Histology examination revealed an encapsulated immature teratoma. The postoperative course was complicated with respiratory insufficiency which turned into chronic at the age of eight months. CONCLUSION This is the fifth reported child with fetal mediastinal teratoma and severe hydrops fetalis that survived the neonatal period. Additional diagnostic search revealed abnormal course of both pulmonary arteries, which was probably one of the main causes of respiratory insufficiency.


title: A non-human primate model of bipedal locomotion under restrained condition allowing gait studies and single unit brain recordings.

text: For decades, several animal models of locomotion have allowed a better understanding of the basic physiological mechanisms of gait. However, unlike most of the mammals, the Order Primates is characterized by fundamental changes in locomotor behaviour. In particular, some primates use a specific pattern of locomotion and are able to naturally walk bipedally due possibly to a specific supra-spinal control of locomotion. These features must be taken into account when one considers to study the intrinsic properties of human gait. Thus, an experimental model of bipedal locomotion allowing precise and reproducible analysis of gait in non-human primate is still lacking. This study describes a non-human primate model of bipedal locomotion under restrained condition. We undertook a kinematic and biomechanic study in three Macaca fascicularis trained to walk bipedally on a treadmill. One of the primate was evaluated in complete head fixation. Gait visual analysis and electromyographic recordings provided pertinent description of the gait pattern. Step frequencies, step lengths, cycle and stance phase durations were correlated with Froude number (dimensionless velocity), whereas swing phase durations remained non-correlated. Gait patterns observed in our model were similar to those obtained in freely bipedal Macaca fuscata and to a lesser extend to Humans. Gait pattern was not modified by head fixation thereby allowing us to perform precise and repetitive micro electrode recordings of deep cerebral structures. Thus, the present model could provide a pertinent pre-clinical tool to study gait parameters and their neuronal control but also could be helpful to validate new therapeutics interventions.


US healthcare workers march against racism despite the risks.


title: Organophosphate ester (OPE) flame retardants and plasticizers in the open Mediterranean and Black Seas atmosphere.

text: The presence of organophosphate ester (OPE) flame retardants and plasticizers has been confirmed for the first time in the atmosphere over the Mediterranean and Black Seas. Atmospheric aerosol samples were collected during two West-East oceanographic cruises across the Mediterranean and in the southwest Black Sea. This comprehensive assessment of baseline concentrations of aerosol phase OPEs, spatial distribution, and related deposition fluxes reveals levels ranging from 0.4 to 6.0 ng m(-3) for the ∑14OPEs and a lack of significant differences among sub-basins. Levels measured across the Mediterranean Sea and in the Black Sea are in the upper range or higher than those from previous reports for the marine atmosphere, presumably due to proximity to sources. From 13 to 260 tons of OPEs are estimated to be annually loaded to the Mediterranean Sea open waters from the atmosphere. Tris-(1-chloro-2-propyl)phosphate (TCPP) was the most abundant compound over the atmosphere of all the Mediterranean and Black Sea sub-basins, and therefore the chemical reaching surface waters at a higher extent by dry deposition. The atmospheric deposition fluxes of phosphorus due to OPE deposition is a significant fraction of known atmospheric inputs of new organic phosphorus (P), suggesting the relevant role that anthropogenic organic pollutants could play in the P cycle.


title: The Influence of Liver Resection on Intrahepatic Tumor Growth.

text: The high incidence of tumor recurrence after resection of metastatic liver lesions remains an unsolved problem. Small tumor cell deposits, which are not detectable by routine clinical imaging, may be stimulated by hepatic regeneration factors after liver resection. It is not entirely clear, however, which factors are crucial for tumor recurrence. The presented mouse model may be useful to explore the mechanisms that play a role in the development of recurrent malignant lesions after liver resection. The model combines the easy-to-perform and reproducible techniques of defined amounts of liver tissue removal and tumor induction (by injection) in mice. The animals were treated with either a single laparotomy, a 30% liver resection, or a 70% liver resection. All animals subsequently received a tumor cell injection into the remaining liver tissue. After two weeks of observation, the livers and tumors were evaluated for size and weight and examined by immunohistochemistry. After a 70% liver resection, the tumor volume and weight were significantly increased compared to a laparotomy alone (p <0.05). In addition, immunohistochemistry (Ki67) showed an increased tumor proliferation rate in the resection group (p <0.05). These findings demonstrate the influence of hepatic regeneration mechanisms on intrahepatic tumor growth. Combined with methods like histological workup or RNA analysis, the described mouse model could serve as foundation for a close examination of different factors involved in tumor growth and metastatic disease recurrence within the liver. A considerable number of variables like the length of postoperative observation, the cell line used for injection or the timing of injection and liver resection offer multiple angles when exploring a specific question in the context of post-hepatectomy metastases. The limitations of this procedure are the authorization to perform the procedure on animals, access to an appropriate animal testing facility and acquisition of certain equipment.


title: Geospatial approaches for disease risk communication in marginalized communities.

text: BACKGROUND After Hurricane Katrina, Louisiana State University (LSU) collaborated with the Federal Emergency Management Agency (FEMA) to create the LSU GIS Clearinghouse Cooperative (LGCC) to disseminate geospatial data. From this experience of serving community geospatial data needs for risk communication, particularly in marginalized areas, and through working with the World Health Organization Collaborating Center for Remote Sensing and GIS for Public Health (WHOCC), we identified several useful geospatial technologies (GT) and methods for their implementation in risk communication strategies. OBJECTIVES This article provides an assessment of the benefits and limitations of these technologies for risk communication in marginalized communities. METHODS Several GT have been employed for risk communication and general data dissemination in communities throughout rural coastal Louisiana. From experimentation with these technologies for risk communication, they can be classed into three groups: lightweight GIS, map dissemination tools, and interactive GT. RESULTS Lightweight GIS and map dissemination tools will, at some point in their application, require the assistance of a GIS expert or GIS data provider to develop and customize the tool for its intended uses. Interactive GT, however, has rapidly developed options that allow user-friendly operation without reliance on expert assistance. Google Maps, however, is showing the greatest potential for community-based health participation. CONCLUSIONS Classifying the available GT based on functionality is critical to help specialists provide the most effective method for spatial risk communication and to assist community users in creating accessible data for their local health needs.


title: A naturally occurring human adenovirus type 7 variant with a 1743 bp deletion in the E3 cassette.

text: Human adenovirus type 7 (HAdV-7) is an important cause of acute respiratory disease (ARD). Different genomic variants of HAdV-7 have been described, designated 7a-7l. In a previous study to investigate risk factors for ARD and wheezing, nasopharyngeal samples were collected from 90 ill children seeking medical attention in Ribeirão Preto, São Paulo, Brazil. HAdVs were identified in 31 samples and were characterized by serum neutralization and genome restriction analysis. Eleven HAdVs were identified as being HAdV-7, five of which were classified as being of genome type 7p (Gomen). Six other HAdV-7 isolates gave new restriction profiles with all enzymes used and were classified as being a new genomic variant, 7m. These isolates were further characterized by sequencing. The hexon and fiber genes of the 7m variant were nearly identical to the prototype, 7p. However, nucleotide sequences from the E3 cassette revealed a 1743 bp deletion affecting the 16.1K, 19K, 20.1K and 20.5K ORFs.


title: Excellent rates of recanalization and good functional outcome after stent-based thrombectomy for acute middle cerebral artery occlusion. Is it time for a paradigm shift?

text: The natural history of untreated acute middle cerebral artery (MCA) occlusion is poor, with high rates of mortality (5-33%) and severe long-term disability (40-80% of survivors), despite therapy with intravenous tissue plasminogen activator. We analyzed outcomes in 31 consecutive patients with major ischemic stroke due to acute proximal MCA occlusion who were treated at the Hadassah-Hebrew University Medical Center from February 2010 to October 2012 by endovascular means, using the Solitaire stent (Covidien, Irvine, CA, USA) as a thrombectomy device. Patients had a mean age of 63.3±16.2 years (range, 26-92). The admission National Institutes of Health Stroke Scale score was 19.5±4.3 (median 20). Mean time from symptom onset to femoral artery puncture was 3.8±1.1 hours (median 4 hours). Mean time to recanalization was 46.9±11.1 minutes. Successful recanalization by means of stent-based thrombectomy alone was achieved in 90% of cases and reached 100% after combining definitive stent implantation in three patients. There was no arterial rupture or subarachnoid hemorrhage. Hemorrhagic transformation developed in seven patients (23%), but was symptomatic in only one. Post-procedure CT scan or MRI demonstrated >90% sparing of cortex at risk in all patients. Functional outcome at 90 day follow-up was modified Rankin Score 0-2 in 77% of all patients and 88% of patients younger than 80 years. Three patients (10%) died during hospitalization due to mesenteric event, sepsis, or pulmonary embolism. Our experience suggests that stent-based thrombectomy in selected patients for acute MCA occlusions is safe, very effective in terms of arterial recanalization, and associated with improved neurological outcome. If validated by other groups, endovascular treatment may be proposed as the therapy of choice for MCA occlusion.


title: Molecular characterization of Canine minute virus associated with neonatal mortality in a litter of Jack Russell terrier dogs.

text: The molecular characterization of a strain of Canine minute virus (CnMV) associated with neonatal death is reported. Three newborn puppies of a litter of Jack Russell terrier dogs died after displaying systemic disease, whereas 2 surviving puppies showed no clinical signs with the exception of transient cardiac abnormalities that were evident by electrocardiography. Necropsy of 1 dead puppy revealed severe lesions in the internal organs. A strain of Canine minute virus was detected in tissue samples collected from the puppy, and virus circulation was demonstrated by molecular or serological testing in the dam, puppies of the same litter, and other puppies in the same kennel. By sequence and phylogenetic analysis of the gene encoding for the VP2 capsid protein, the strain circulating in the kennel was found to be related to recent Asian CnMV isolates. Continuous molecular surveillance for CnMV in kennels, shelters, and rescue centers would expand the knowledge base on the epidemiological and pathogenetic features of CnMV, which has been known for several decades but still poorly understood.


title: Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - a position paper endorsed by ESMINT and ESNR : part II: methodology of future trials.

text: Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.


title: Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk.

text: Obesity-related sub-acute chronic inflammation has been associated with incident type 2 diabetes and atherosclerotic cardiovascular disease. Inflammation is increasingly considered to be a pathologic mediator of these commonly co-occurring diseases. A growing number of preclinical and clinical studies support the inflammatory hypothesis, but clinical trials to confirm the therapeutic potential to target inflammation to treat or prevent cardiometabolic conditions are still ongoing. There are multiple inflammatory signaling pathways. Regulation is complex, with substantial crosstalk across these multiple pathways. The activity of select pathways may be differentially regulated in different tissues. Pharmacologic approaches to diabetes management may have direct or indirect antiinflammatory effects, the latter potentially attributable to an improved metabolic state. Conversely, some antiinflammatory approaches may affect glucose metabolism and cardiovascular health. To date, clinical trials suggest that targeting one portion of the inflammatory cascade may differentially affect dysglycemia and atherothrombosis. Understanding the underlying biological processes may contribute to the development of safe and effective therapies, although a single approach may not be sufficient for optimal management of both metabolic and athrothrombotic disease states.


title: A Simple Microbiome in the European Common Cuttlefish, Sepia officinalis.

text: The European common cuttlefish, Sepia officinalis, is used extensively in biological and biomedical research, yet its microbiome remains poorly characterized. We analyzed the microbiota of the digestive tract, gills, and skin in mariculture-raised S. officinalis using a combination of 16S rRNA amplicon sequencing, quantitative PCR (qPCR), and fluorescence spectral imaging. Sequencing revealed a highly simplified microbiota consisting largely of two single bacterial amplicon sequence variants (ASVs) of Vibrionaceae and Piscirickettsiaceae. The esophagus was dominated by a single ASV of the genus Vibrio. Imaging revealed bacteria in the family Vibrionaceae distributed in a discrete layer that lines the esophagus. This Vibrio was also the primary ASV found in the microbiota of the stomach, cecum, and intestine, but occurred at lower abundance, as determined by qPCR, and was found only scattered in the lumen rather than in a discrete layer via imaging analysis. Treatment of animals with the commonly used antibiotic enrofloxacin led to a nearly 80% reduction of the dominant Vibrio ASV in the esophagus but did not significantly alter the relative abundance of bacteria overall between treated versus control animals. Data from the gills were dominated by a single ASV in the family Piscirickettsiaceae, which imaging visualized as small clusters of cells. We conclude that bacteria belonging to the Gammaproteobacteria are the major symbionts of the cuttlefish Sepia officinalis cultured from eggs in captivity and that the esophagus and gills are major colonization sites. IMPORTANCE Microbes can play critical roles in the physiology of their animal hosts, as evidenced in cephalopods by the role of Vibrio (Aliivibrio) fischeri in the light organ of the bobtail squid and the role of Alpha- and Gammaproteobacteria in the reproductive system and egg defense in a variety of cephalopods. We sampled the cuttlefish microbiome throughout the digestive tract, gills, and skin and found dense colonization of an unexpected site, the esophagus, by a microbe of the genus Vibrio, as well as colonization of gills by Piscirickettsiaceae. This finding expands the range of organisms and body sites known to be associated with Vibrio and is of potential significance for understanding host-symbiont associations, as well as for understanding and maintaining the health of cephalopods in mariculture.


Pandemic Adaptive Measures in a Major Trauma Center: Coping With COVID-19.


title: [Analysis of property and efficacy of traditional Chinese medicine in staging revention and treatment of coronavirus disease 2019].

text: Coronavirus disease 2019(COVID-19) triggered a severe and complicated epidemic situation, and it is of great significance to discuss the rules and characteristics of the prescription of COVID-19 in traditional Chinese medicine. This study collected prevention and treatment approaches of traditional Chinese medicine for COVID-19 released from the National Health Committee of China, 7 provinces and municipal health committees, the Chinese Medicine Administration and Handbook of Traditional Chinese Medicine Diagnosis and Treatment of COVID-19 between January 1 and February 18, 2020, and prescriptions prepared by 3 masters of Chinese medicine and 4 well-known Chinese medicine experts. These information were selected according to the inclusion and exclusion criteria, and EpiData 3.0 software was used to establish the "Traditional Chinese Medicine Prescription Library for the Prevention and Treatment of COVID-19" and the "Common Database of Traditional Chinese Medicine for the Prevention and Treatment of COVID-19". A total of 93 effective Chinese medicine prescriptions and a total of 157 kinds of constituent medicines were collected. Data analysis was performed by SPSS 18.0 software. The results showed that: ①most of the medicines are with cold and warm properties, 69 with cold medicines, accounting for 43.95%, 57 with warm medicines, accounting for 36.31%, and less with hot medicines, taking up 1.27%; ②there are many pungent, bitter and sweet medicines, and the distribution of medicinal flavors is different at different disease stage. The pungent medicines are mostly found in the early stage, the bitter drugs are the main flavor in the middle and severe stage, and the sweet medicines are mostly used in the recovery stage; ③the meridian of the drug is more concentrated at the lung, stomach, and heart, and most of drugs are into the lung meridian, accounting for 24.55%; these medicines are mostly into the lungs and stomach in the initial and middle stages, and into the heart and kidney in severe stages; ④oral drugs are mostly non-toxic, among which only 6 kinds are toxic, namely Armeniacae Semen Amarum, Dryopteridis Crassirhizomatis Rhizoma, Paridis Rhizoma, Pinelliae Rhizoma, Aconiti Lateralis Radix Praeparaia; ⑤most of the drugs have five types of functions: treating exterior syndromes, resolving dampness, clearing heat, replenishing deficiency, resolving phlegm, cough, and asthma. In the early stage, both drugs for treating exterior syndromes and heat clearing drugs were equally used, accounting for 18.81% each. In the middle stage, drugs resolving phlegm, cough, and asthma drugs are more often used, accounting for 29.61%. In the severe stage, heat clearing drugs are mostly used, accounting for 33.33%. During the recovery period, tonic deficiency drugs are used the most, accounting for 36.47%. The medical characteristics and efficacy of Chinese medicine in preventing and treating COVID-19 are closely related to the understanding of the etiology of Chinese medicine and the location and pathogenesis of the disease. Staged medication and local conditions need attention during the identification and treatment of COVID-19 clinical syndromes.


title: Effect of the Pulsatile Extracorporeal Membrane Oxygenation on Hemodynamic Energy and Systemic Microcirculation in a Piglet Model of Acute Cardiac Failure.

text: The objective of this study was to compare the effects of pulsatile and nonpulsatile extracorporeal membrane oxygenation (ECMO) on hemodynamic energy and systemic microcirculation in an acute cardiac failure model in piglets. Fourteen piglets with a mean body weight of 6.08 ± 0.86 kg were divided into pulsatile (N = 7) and nonpulsatile (N = 7) ECMO groups. The experimental ECMO circuit consisted of a centrifugal pump, a membrane oxygenator, and a pneumatic pulsatile flow generator system developed in-house. Nonpulsatile ECMO was initiated at a flow rate of 140 mL/kg/min for the first 30 min with normal heart beating, with rectal temperature maintained at 36°C. Ventricular fibrillation was then induced with a 3.5-V alternating current to generate a cardiac dysfunction model. Using this model, we collected the data on pulsatile and nonpulsatile groups. The piglets were weaned off ECMO at the end of the experiment (180 min after ECMO was initiated). The animals did not receive blood transfusions, inotropic drugs, or vasoactive drugs. Blood samples were collected to measure hemoglobin, methemoglobin, blood gases, electrolytes, and lactic acid levels. Hemodynamic energy was calculated using the Shepard's energy equivalent pressure. Near-infrared spectroscopy was used to monitor brain and kidney perfusion. The pulsatile ECMO group had a higher atrial pressure (systolic and mean), and significantly higher regional saturation at the brain level, than the nonpulsatile group (for both, P < 0.05). Additionally, the pulsatile ECMO group had higher methemoglobin levels within the normal range than the nonpulsatile group. Our study demonstrated that pulsatile ECMO produces significantly higher hemodynamic energy and improves systemic microcirculation, compared with nonpulsatile ECMO in acute cardiac failure.


title: Alteration in the lower limit of autoregulation with elevations in cephalic venous pressure.

text: OBJECTIVES Recent studies suggest that elevated intracranial pressure (ICP), created by hydrocephalus, can alter the lower limit of cerebrovascular autoregulation (LLA). Our objective in the present study was to determine if ICP elevation from cerebral venous outflow obstruction would result in comparable alterations in the LLA. METHODS Anesthetized juvenile pigs were assigned to one of two groups: naïve ICP (n = 15) or high ICP (>20 mmHg; n = 20). To elevate ICP through venous obstruction, a modified 5F esophageal balloon catheter was inserted via the right external jugular vein into the superior vena cava (SVC) and inflated to maintain an ICP of >20 mmHg. To calculate the LLA, gradual hypotension was induced by continuous hemorrhage from a catheter in the femoral vein. The LLA was determined by monitoring cortical laser Doppler flux (LDF). RESULTS The naïve and high ICP groups had LLAs of 45 mmHg (95% CI: 41-49 mmHg) and 71 mmHg (95% CI: 66-77 mmHg) respectively by LDF. The LLA was significantly different between the two groups and correlated significantly with ICP. DISCUSSION Elevated ICP from cephalic venous engorgement leads to an increase in the LLA. These findings suggest that pathologic processes resulting in cephalic venous outflow obstruction and intracranial venous congestion can acutely elevate ICP and may place the brain at risk for impaired cerebrovascular autoregulation.


Coronavirus Disease 2019 (COVID-19) and Firearms in the United States: Will an Epidemic of Suicide Follow?


title: Meaningful assessment method for laparoscopic suturing training in augmented reality.

text: BACKGROUND To be an effective training tool, a laparoscopic simulator has to provide metrics that are meaningful and informative to the trainee. Time, path length and smoothness are often used parameters, but are not very informative on the quality of the performance. This study aims to validate a newly developed assessment method for laparoscopic suturing on the ProMIS augmented reality simulator, and compares it with scores of objective observers. METHODS Twenty-four participants practised their suturing skills on the augmented reality suturing module: experienced participants (n = 10), >50 clinical laparoscopic suturing experience; and novice participants (n = 14), without laparoscopic experience. The performances were recorded and assessed by two unrelated observers and compared with the assessment scores. The assessment score was a calculation of time spent in the correct area and quality (strength) of the knot. To test the accuracy of the individual assessment parameters, we compared these with each other. RESULTS The experienced participants had significantly higher performance scores than the novice participants in the beginner-level mode (mean 95.73 vs. 60.89, standard deviation 2.63 vs. 17.09, p < 0.001, independent t-test). The performance scores of the assessment method (n = 43) correlated significantly with the scorings of the objective observers (Spearman's rho 0.672; p < 0.001). The parameter time spent in correct area had a calculated significant correlation with the strength of the knot (n = 229, Spearman's rho 0.257, p < 0.001), but this was clinically irrelevant. CONCLUSION This assessment method is a valid tool for objectively assessing laparoscopic suturing skills. Although assessment parameters can correlate, to provide informative feedback it is important to combine meaningful measurements in the assessment of suturing skills.


Abortion during the Covid-19 Pandemic - Ensuring Access to an Essential Health Service.


title: Evolving changes of minimally invasive esophagectomy: a single-institution experience.

text: BACKGROUND Initial adoption of minimally invasive esophagectomy (MIE) began in the late 1990s but its surgical technique, perioperative management, and outcome continues to evolve. METHODS The aim of this study was to examine the evolving changes in the technique, outcome, and new strategies in management of postoperative leaks after MIE was performed at a single institution over a two-decade period. A retrospective chart review of 75 MIE operations was performed between November 2011 and September 2018 and this was compared to the initial series of 104 MIE operations performed by the same group between 1998 and 2007. Operative technique, outcomes, and management strategies of leaks were compared. RESULTS There were 65 males (86.7%) with an average age of 61 years. The laparoscopic/thoracoscopic Ivor Lewis esophagectomy became the preferred MIE approach (49% of cases in the initial vs. 95% in the current series). Compared to the initial case series, there was no significant difference in median length of stay (8 vs. 8 days), major complications (12.5% vs. 14.7%, p = 0.68), incidence of leak (9.6% vs. 10.6%, p = 0.82), anastomotic stricture (26% vs. 32.0%, p = 0.38), or in-hospital mortality (2.9% vs. 2.6%, p = 0.47). Management of esophageal leaks has changed from primarily thoracotomy ± diversion initially (50% of leak cases) to endoscopic stenting ± laparoscopy/thoracoscopy currently (87.5% of leak cases). CONCLUSION In a single-institutional series of MIE over two decades, there was a shift toward a preference for the laparoscopic/thoracoscopic Ivor Lewis approach with similar outcomes. The management of postoperative leaks drastically changed with predilection toward minimally invasive option with endoscopic drainage and stenting.


title: Interleukin-29 suppresses hepatitis A and C viral internal ribosomal entry site-mediated translation.

text: Our aim was to investigate the effects of interferons (IFNs)-λ (interleukin-29 [IL-29], IL-28A, and IL-28B) on hepatitis C virus (HCV) and hepatitis A virus (HAV) internal ribosomal entry site (IRES)-mediated translation. The effects of these IFNs on HCV/HAV translation from HAV/HCV IRES were investigated using bicistronic reporter constructs. We transfected HCV/HAV IRES constructs into these IFN-expressing cell lines. IL-29 showed stronger inhibition of their IRES-mediated translation. Combining IL-29 with IFN-α or amantadine resulted in stronger inhibition of HAV IRES activity. Our findings demonstrated a novel antiviral effect of IFNs-λ against HAV and HCV through the suppression of IRES-mediated translation.


title: Development of a poliovirus neutralization test with poliovirus pseudovirus for measurement of neutralizing antibody titer in human serum.

text: In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical role by isolating and identifying poliovirus (PV) from the stool samples from acute flaccid paralysis (AFP) cases. In recent years, reestablishment of PV circulation in countries where PV was previously eliminated has occurred because of decreased herd immunity, possibly due to poor vaccination coverage. To monitor the vulnerability of countries to PV circulation, surveillance of neutralizing-antibody titers against PV in susceptible populations is essential in the end game of the polio eradication program. In this study, we have developed a PV neutralization test with type 1, 2, and 3 PV pseudoviruses to determine the neutralizing-antibody titer against PV in human serum samples. With this test, the neutralizing-antibody titer against PV could be determined within 2 days by automated interpretation of luciferase signals without using infectious PV strains. We validated the pseudovirus PV neutralization test with 131 human serum samples collected from a wide range of age groups (ages 1 to >60 years) by comparison with a conventional neutralization test. We found good correlation in the neutralizing-antibody titers determined by these tests. These results suggest that a pseudovirus PV neutralization test would serve as a safe and simple procedure for the measurement of the neutralizing-antibody titer against PV.


title: Detection and genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in Southwest China.

text: Human metapneumovirus (hMPV) is the main pathogen causing respiratory tract infection in susceptible populations, particularly in children and the elderly. Specimens were collected from hospitalized children with acute lower respiratory tract infections (ALRTI), and the hMPV was detected by using real-time reverse transcription-PCR (RT-PCR). The full-length G gene of hMPV was amplified by RT-PCR. A total of 1,410 nasopharyngeal aspirates (NPAs) were collected from April 2008 to March 2011, and 114 (10.2%) were positive for hMPV. Most hMPV-positive children were <5 years of age. The hMPV infection rate peaked in the spring-summer season of 2008 to 2009 and 2009 to 2010, while hMPV circulated predominantly during the winter-spring season of 2010 to 2011. The full-length G gene of 23 hMPV strains was amplified, and group A and B viruses accounted for 95.7% (22/23) and 4.3% (1/23), respectively. Genotype A2b of hMPV appeared to be predominant during the study period. Three genotypes (A2b, A1, and B1) were prevalent in the epidemic season of 2008 to 2009, and only genotype A2b was identified in the other two seasons (2009 to 2010 and 2010 to 2011). The G gene of hMPV was predicted to encode proteins with four different lengths, in which one with 210 amino acids was first identified in China. These findings suggest that hMPV was an important pathogen of ALRTI in pediatric patients, especially those <5 years of age. Genotype A2b of hMPV likely predominates in Southwest China, where other genotypes also circulate.


Are COVID-19 patients with hypertension at higher risk in China?


title: Direct comparison of 111In-labelled two-helix and three-helix Affibody molecules for in vivo molecular imaging.

text: PURPOSE Radiolabelled Affibody molecules have demonstrated a potential for visualization of tumour-associated molecular targets. Affibody molecules (7 kDa) are composed of three alpha-helices. Recently, a smaller two-helix variant of Affibody molecules (5.1 kDa) was developed. The aim of this study was to compare two- and three-helix HER2-targeting Affibody molecules directly in vivo. METHODS The three-helix Affibody molecule ABY-002 and the two-helix Affibody molecule PEP09239 were labelled with (111)In at the N-termini via DOTA chelator. Tumour-targeting properties were directly compared at 1 and 4 h after injection in mice bearing SKOV-3 xenografts with high HER2 expression and LS174T xenografts with low HER2 expression. RESULTS The dissociation constants (K(D)) for HER2 binding were 78 pM for the three-helix Affibody molecule and 2.1 nM for the two-helix Affibody molecule. (111)In-PEP09239 cleared more rapidly from the blood. In xenografts with high HER2 expression, the uptake of (111)In-ABY-002 was significantly higher than that of (111)In-PEP09239. The tumour-to-blood ratio was higher for (111)In-PEP09239 at 4 h after injection, while there was no significant difference in other tumour-to-organ ratios. The tumour uptake of (111)In-ABY-002 was eightfold higher than that of (111)In-PEP09239 in xenografts with low expression. Tumour-to-blood ratios were equal in this case, but other tumour-to-organ ratios were appreciably higher for the three-helix variant. CONCLUSION For tumours with high HER2 expression, two-helix HER2-targeting Affibody molecules can provide higher tumour-to-blood ratio at the cost of lower tumour uptake. In the case of low expression, both tumour uptake and tumour-to-organ ratios are appreciably higher for three-helix than for two-helix HER2-targeting Affibody molecules.


title: Anesthetic management of a patient with sodium-channel myotonia: a case report.

text: BACKGROUND Sodium-channel myotonia (SCM) is a nondystrophic myotonia, characterized by pure myotonia without muscle weakness or paramyotonia. The prevalence of skeletal muscle channelopathies is approximately 1 in 100,000, and the prevalence of SCM is much lower. To our knowledge, this is the first report on anesthetic management of a patient with SCM. CASE PRESENTATION A 23-year-old woman with congenital nasal dysplasia and SCM was scheduled to undergo rhinoplasty with autologous costal cartilage. Total intravenous anesthesia without muscle relaxants was administered followed by continuous intercostal nerve block. Although transient elevation of potassium level in the blood was observed during surgery, the patient did not show exacerbation of myotonic or paralytic symptoms in the postoperative period. CONCLUSION Total intravenous anesthesia and peripheral nerve block can be administered safely to a patient with SCM. However, careful monitoring of the symptoms and electrolytes is recommended.


title: Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent.

text: PURPOSE To compare changes in signal intensity (SI) ratios of the dentate nucleus (DN) and the globus pallidus (GP) to those of other structures on unenhanced T1-weighted magnetic resonance (MR) images between linear and macrocyclic gadolinium-based contrast agents (GBCAs). MATERIALS AND METHODS The study was approved by the ethical committee of the University of Heidelberg (reference no. S-324/2014). Owing to the retrospective character of the study, the ethical committee did not require any written informed consent. Two groups of 50 patients who underwent at least six consecutive MR imaging examinations with the exclusive use of either a linear GBCA (gadopentetate dimeglumine) or a macrocyclic GBCA (gadoterate meglumine) were analyzed retrospectively. The difference in mean SI ratios of DN to pons and GP to thalamus on unenhanced T1-weighted images from the last and first examinations was calculated. One-sample and independent-sample t tests were used to assess the difference in SI ratios for both groups, and regression analysis was performed to account for potential confounders. RESULTS The SI ratio difference in the linear group was greater than 0 (mean DN difference ± standard deviation, 0.0407 ± 0.0398 [P < .001]; GP, 0.0287 ± 0.0275 [P < .001]) and significantly larger (DN, P < .001 and standardized difference of 1.16; GP, P < .001 and standardized difference of 0.81) than that in the macrocyclic group, which did not differ from 0 (DN, 0.0016 ± 0.0266 [P = .680]; GP, 0.0031 ± 0.0354 [P = .538]). The SI ratio difference between the last and first examinations for the DN remained significantly different between the two groups in the regression analysis (P < .001). CONCLUSION This study indicates that an SI increase in the DN and GP on T1-weighted images is caused by serial application of the linear GBCA gadopentetate dimeglumine but not by the macrocyclic GBCA gadoterate meglumine. Clinical implications of this observation remain unclear.


Radiation risk from coronary artery disease imaging: how do different diagnostic tests compare?


title: Impact of postoperative complications on survival after oesophagectomy for oesophageal cancer.

text: BACKGROUND Recent evidence suggests that complications after oesophagectomy may decrease short- and long-term survival of patients with oesophageal cancer. This study aimed to analyse the impact of complications on survival in a Western cohort. METHODS Complications after oesophagectomy were recorded for all patients operated on between January 2006 and February 2017, with severity defined using the Clavien-Dindo classification. Associations between complications and overall and recurrence-free survival were assessed using univariable and multivariable Cox regression models. RESULTS Of 430 patients, 292 (67·9 per cent) developed postoperative complications, with 128 (39·8 per cent) classified as Clavien-Dindo grade III or IV. No significant associations were detected between Clavien-Dindo grade and either tumour (T) (P = 0·071) or nodal (N) status (P = 0·882). There was a significant correlation between Clavien-Dindo grade and ASA fitness grade (P = 0·032). In multivariable analysis, overall survival in patients with Clavien-Dindo grade I complications was similar to that in patients with no complications (hazard ratio (HR) 0·97, P = 0·915). However, patients with grade II and IV complications had significantly shorter overall survival than those with no complications: HR 1·64 (P = 0·007) and 1·74 (P = 0·013) respectively. CONCLUSION Increasing severity of complications after oesophagectomy was associated with decreased overall survival. Prevention of complications should improve survival.


title: RNA-based viral vectors.

text: The advent of reverse genetic approaches to manipulate the genomes of both positive (+) and negative (-) sense RNA viruses allowed researchers to harness these genomes for basic research. Manipulation of positive sense RNA virus genomes occurred first largely because infectious RNA could be transcribed directly from cDNA versions of the RNA genomes. Manipulation of negative strand RNA virus genomes rapidly followed as more sophisticated approaches to provide RNA-dependent RNA polymerase complexes coupled with negative-strand RNA templates were developed. These advances have driven an explosion of RNA virus vaccine vector development. That is, development of approaches to exploit the basic replication and expression strategies of RNA viruses to produce vaccine antigens that have been engineered into their genomes. This study has led to significant preclinical testing of many RNA virus vectors against a wide range of pathogens as well as cancer targets. Multiple RNA virus vectors have advanced through preclinical testing to human clinical evaluation. This review will focus on RNA virus vectors designed to express heterologous genes that are packaged into viral particles and have progressed to clinical testing.