title: Neonatal Pneumothorax Pressures Surpass Higher Threshold in Lung Recruitment Maneuvers: An In Vivo Interventional Study.

text: BACKGROUND Causing pneumothorax is one of the main concerns of lung recruitment maneuvers in pediatric patients, especially newborns. Therefore, these maneuvers are not performed routinely during anesthesia. Our objective was to determine the pressures that cause pneumothorax in healthy newborns by a prospective experimental study of 10 newborn piglets (<48 h old) with healthy lungs under general anesthesia. METHODS The primary outcome was peak inspiratory pressure (PIP) causing pneumothorax. Animals under anesthesia and bilateral chest tube catheterization were randomly allocated to 2 groups: one with PEEP and fixed inspiratory driving pressure of 15 cm H2O (PEEP group) and the second one with PEEP = 0 cm H2O and non-fixed inspiratory driving pressure (zero PEEP group). In both groups, the ventilation mode was pressure-controlled, and PIP was raised at 2-min intervals, with steps of 5 cm H2O until air leak was observed through the chest tubes. The PEEP group raised PIP through 5-cm H2O PEEP increments, and the zero PEEP group raised PIP through 5-cm H2O inspiratory driving pressure increments. RESULTS Pneumothorax was observed with a PIP of 90.5 ± 15.7 cm H2O with no statistically significant differences between the PEEP group (92 ± 14.8 cm H2O) and the zero PEEP group (89 ± 18.2 cm H2O). The zero PEEP group had hypotension, with a PIP of 35 cm H2O; the PEEP group had hypotension, with a PIP of 60 cm H2O (P = .01). The zero PEEP group presented bradycardia, with PIP of 40 cm H2O; the PEEP group presented bradycardia, with PIP of 70 cm H2O (P = .002). CONCLUSIONS Performing recruitment maneuvers in newborns without lung disease is a safe procedure in terms of pneumothorax. Pneumothorax does not seem to occur in the clinically relevant PIPs of <50 cm H2O. Hemodynamic impairment may occur with high driving pressures. More studies are needed to determine the exact hemodynamic impact of these procedures and pneumothorax PIP in poorly compliant lungs.


title: SARS-like WIV1-CoV poised for human emergence.

text: Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.


title: Unerupted teeth associated with dentigerous cysts and treated with coronectomy: mini case series.

text: There is a resurgence of interest in coronectomy, but its appropriate application in the management of third molar teeth has yet to be defined. Dentigerous cysts associated with unerupted teeth are most commonly associated with mandibular third molars. In this case series we evaluate outcome after coronectomy of teeth with associated dentigerous cysts in cases where the inferior dental nerve was thought to be at risk, or there was an increased risk of mandibular fracture. We retrospectively studied 21 consecutive patients treated by coronectomy for dentigerous cysts at the Oral Surgery Department at Guy's Hospital. The most commonly affected teeth were mandibular third molars (20/21). One patient had permanent injury to the inferior dental nerve, but no mandibular fracture or recurrence of cyst was reported. One patient required secondary retrieval of the retained root because of eruption. Coronectomy of unerupted teeth associated with dentigerous cysts is an effective treatment when there is high risk of injury to the inferior dental nerve injury or potential for mandibular fracture. Further work with larger numbers and longer follow-up is required to discover the long-term outcome of the electively retained root.


How to Deal with COVID-19 Pandemic: A Radiologic Approach.


title: Amicus or Adversary Revisited: Platelets in Acute Lung Injury and Acute Respiratory Distress Syndrome.

text: Platelets are essential cellular effectors of hemostasis and contribute to disease as circulating effectors of pathologic thrombosis. These are their most widely known biologic activities. Nevertheless, recent observations demonstrate that platelets have a much more intricate repertoire beyond these traditional functions and that they are specialized for contributions to vascular barrier integrity, organ repair, antimicrobial host defense, inflammation, and activities across the immune continuum. Paradoxically, on the basis of clinical investigations and animal models of disease, some of these newly discovered activities of platelets appear to contribute to tissue injury. Studies in the last decade indicate unique interactions of platelets and their precursor, the megakaryocyte, in the lung and implicate platelets as essential effectors in experimental acute lung injury and clinical acute respiratory distress syndrome. Additional discoveries derived from evolving work will be required to precisely define the contributions of platelets to complex subphenotypes of acute lung injury and to determine if these remarkable and versatile blood cells are therapeutic targets in acute respiratory distress syndrome.


title: Inhibiting the Physiological Stress Effects of a Sustained Attention Task on Shoulder Muscle Activity.

text: OBJECTIVE The objective of this study was to investigate if a breathing technique could counteract the effects of hyperventilation due to a sustained attention task on shoulder muscle activity. BACKGROUND The trend towards higher levels of automation in industry is increasing. Consequently, manufacturing operators often monitor automated process for long periods of their work shift. Prolonged monitoring work requires sustained attention, which is a cognitive process that humans are typically poor at and find stressful. As sustained attention becomes an increasing requirement of manufacturing operators' job content, the resulting stress experienced could contribute to the onset of many health problems, including work related musculoskeletal disorders (WRMSDs). METHODS The SART attention test was completed by a group of participants before and after a breathing intervention exercise. The effects of the abdominal breathing intervention on breathing rate, upper trapezius muscle activity and end-tidal CO₂ were evaluated. RESULTS The breathing intervention reduced the moderation effect of end-tidal CO₂ on upper trapezius muscle activity. CONCLUSIONS Abdominal breathing could be a useful technique in reducing the effects of sustained attention work on muscular activity. APPLICATION This research can be applied to highly-automated manufacturing industries, where prolonged monitoring of work is widespread and could, in its role as a stressor, be a potential contributor to WRMSDs.


title: Results of the ALSTER BP real-world registry on renal denervation employing the Symplicity system.

text: AIMS To prove the efficacy and safety of renal sympathetic denervation as a new treatment option for patients suffering from resistant hypertension in a real-world setting. METHODS AND RESULTS This single-centre real-world registry included 93 patients who underwent renal denervation employing the Symplicity system. Patients were followed for six months. The patient cohort was divided into early responders with a reduction of office systolic blood pressure >10 mmHg three months after the procedure (n=53, 57%), late responders (six months after the procedure, n=16, 17%) and non-responders (n=24, 26%). After six months, systolic blood pressure was lowered by 46±2.9 mmHg (mean±SEM, p<0.001), 31±3.4 mmHg (p<0.001) and 7.1±3.3 mmHg (p=0.79, ns), respectively. Ambulatory blood pressure monitoring also showed a significant reduction in the early responder group (20±5.7 mmHg, p=0.002). We subjected eight patients to a re-do procedure which led to a significant reduction of blood pressure in another five patients after six months (63%). One patient in this cohort developed a one-sided renal artery stenosis associated with an increase in blood pressure. CONCLUSIONS This real-world analysis of renal sympathetic denervation confirms the procedure to be safe and efficient in the majority of patients. Non-responders may profit from a second ablation, arguing in favour of the hypothesis that the procedure did not destroy sufficient amounts of sympathetic innervation in these patients. However, repeated denervations may also increase side effects.


docid: qxtnuvvq

title: Psychological impact of COVID-19 on ophthalmologists-in-training and practising ophthalmologists in India.

text: Purpose To evaluate the psychological impact of the COVID 19 crisis on ophthalmologists-in-training and practising ophthalmologists during lockdown in India. Methods An online survey was completed by ophthalmologists and ophthalmology trainees during the lockdown. The information collected included demographics (age, gender), domicile (state, union territory), current professional status (in training or practising), type of practice (solo, group, institutional, governmental, non-governmental), marital status (married, single), impact of COVID-19 on their training or practice, and impact on income and ability to meet living expenses. Psychological distress was assessed using the Patient Health Questionnaire-9 (PHQ-9). Results In all, 2,355 ophthalmologists responded. Mean age was 42.5 (range, 25-82 years; SD, 12.05) years. Of these, 1,332 (56.7%) were males; 475 (20.2%) were still not in practice; 366 (15.5%) were single; 1,244 (52.8%) felt that COVID-19 would impact on their training or professional work; and 869 (37%) had difficulty in meeting their living expenses. The mean PHQ-9 score was 3.98 (range, 0-27; SD, 4.65). In terms of psychological impact, 768 (32.6%) had some degree of depression; mild in 504 (21.4%), moderate in 163 (6.9%), and severe in 101 (4.3%). Multivariable analysis showed that depression was significantly higher at younger age. The odds of depression decreased by 3% with 1 year increase in age. It was higher in non-practicing ophthalmologists, especially those who were considerably worried about their training or professional growth, and those with difficulty in meeting living expenses. Conclusion A strikingly high proportion of ophthalmologists are psychologically affected and may require personalized mental health care.


title: Proposal of a formal gynecologic endoscopy curriculum.

text: As minimally invasive surgery becomes the standard of care in the United States and around the world, the formal training of endoscopic surgeons is an issue of growing concern. With the implementation of the American Association of Gynecologic Laparoscopists/Society of Reproductive Surgeons (AAGL/SRS)-sponsored fellowship training in gynecologic endoscopy and a growing number of hands-on courses, we have the challenge of credentialing and certifying future gynecologic endoscopists. The objective of this article is to propose and to illustrate a uniform standardized core curriculum for obstetrics and gynecology residents, fellows in AAGL/SRS-sponsored fellowship programs, and participants in postgraduate courses. Consisting of 3 discrete parts, this proposal addresses formal laparoscopic training for gynecologists, already implemented and available to general surgeons, and a novel proposition for core training in hysteroscopy. The curriculum is distributed in a quarterly system with specific educational objectives in each quarter. After quarters 1 and 2, an online examination is given; after quarter 3, participants are required to take and pass a hands-on examination at a specified testing facility; and at the end of quarter 4, participants must demonstrate leadership skills in the operating room and in a teaching capacity, and promote the principles of the AAGL.


title: Arthroscopic Superior Capsular Reconstruction With a Minimally Invasive Harvested Fascia Lata Autograft Produces Good Clinical Results.

text: Background Painful dysfunctional shoulders with irreparable rotator cuff tears (IRCTs) in active patients are a challenge. Arthroscopic superior capsular reconstruction (ASCR) is a new treatment option originally described using a fascia lata autograft harvested through an open approach. However, concerns about donor site morbidity have discouraged surgeons from using this type of graft. Hypothesis ASCR using a minimally invasive harvested fascia lata autograft produces good 6-month and 2-year shoulder outcomes in IRCTs, with low-impact thigh morbidity at 2 years. Study Design Case series; Level of evidence, 4. Methods From 2015 to 2016, a total of 22 consecutive patients (mean age, 64.8 ± 8.6 years) with chronic IRCTs (Hamada grade 1-2; Goutallier cumulative grade ≥3; Patte stage 1: 2 patients; Patte stage 2: 6 patients; Patte stage 3: 14 patients) underwent ASCR using a minimally invasive harvested fascia lata autograft. All patients completed preoperative and 6-month evaluations consisting of the Simple Shoulder Test (SST), subjective shoulder value (SSV), Constant score (CS), range of motion (ROM), acromiohumeral interval (AHI), and magnetic resonance imaging. Twenty-one patients completed the 2-year shoulder and donor site morbidity assessments. Results The mean active ROMs improved significantly (P < .001): elevation, from 74.8° ± 55.5° to 104.5° ± 41.9° (6 months) and 143.8° ± 31.7° (2 years); abduction, from 53.2° ± 43.3° to 86.6° ± 32.9° (6 months) and 120.7° ± 37.7° (2 years); external rotation, from 13.2° ± 18.4° to 27.0° ± 16.1° (6 months) and 35.6° ± 17.3° (2 years); and internal rotation, from 1.2 ± 1.5 points to 2.6 ± 1.5 points (6 months) and 3.8 ± 1.2 points (2 years). The mean functional shoulder scores improved significantly (P < .001): SST, from 2.1 ± 2.9 to 6.8 ± 3.5 (6 months) and 8.6 ± 3.5 (2 years); SSV, from 33.0% ± 17.4% to 55.7% ± 25.6% (6 months) and 70.0% ± 23.0% (2 years); CS, from 17.5 ± 13.4 to 42.5 ± 14.9 (6 months) and 64.9 ± 18.0 (2 years). The mean shoulder abduction strength improved significantly (P < .001) from 0.0 to 1.1 ± 1.4 kg (6 months) and 2.8 ± 2.6 kg (2 years). The mean AHI improved from 6.4 ± 3.3 mm to 8.0 ± 2.5 mm (6 months) and decreased to 7.1 ± 2.5 mm (2 years). This 0.7 ± 1.5-mm overall decrease was statistically significant (P = .042). At 6 months, 20 of 22 patients (90.9%) had no graft tears. At 2 years, 12 of 21 patients (57.1%) were bothered by their harvested thigh, 16 (76.2%) noticed donor site changes, 16 (76.2%) considered that the shoulder surgery's end result compensated for the thigh's changes, and 18 (85.7%) would undergo the same surgery again. Conclusion ASCR using a minimally invasive harvested fascia lata autograft produced good 6-month and 2-year shoulder outcomes in IRCTs, with low-impact thigh morbidity at 2 years.


Implementing a structured digital-based online pathology curriculum for trainees at the time of COVID-19.


title: 10 pearls for safe endoscopic skull base surgery.

text: The introduction of the endoscopic endonasal approach for the management of lesions of the skull base has produced a paradigm shift in the way complicated lesions of this complex anatomic location are managed. The endonasal approach provides the most direct route to the anterior cranial base and adjacent skull base locations. This article presents the 10 most important tenets that have proved useful to the authors regarding postoperative patient management and surgical practice.


Immunomodulation and infection: back to the future.


Ebola Virus in Breast Milk in an Ebola Virus-Positive Mother with Twin Babies, Guinea, 2015.


title: Chimeric feline coronaviruses that encode type II spike protein on type I genetic background display accelerated viral growth and altered receptor usage.

text: Persistent infection of domestic cats with feline coronaviruses (FCoVs) can lead to a highly lethal, immunopathological disease termed feline infectious peritonitis (FIP). Interestingly, there are two serotypes, type I and type II FCoVs, that can cause both persistent infection and FIP, even though their main determinant of host cell tropism, the spike (S) protein, is of different phylogeny and displays limited sequence identity. In cell culture, however, there are apparent differences. Type II FCoVs can be propagated to high titers by employing feline aminopeptidase N (fAPN) as a cellular receptor, whereas the propagation of type I FCoVs is usually difficult, and the involvement of fAPN as a receptor is controversial. In this study we have analyzed the phenotypes of recombinant FCoVs that are based on the genetic background of type I FCoV strain Black but encode the type II FCoV strain 79-1146 S protein. Our data demonstrate that recombinant FCoVs expressing a type II FCoV S protein acquire the ability to efficiently use fAPN for host cell entry and corroborate the notion that type I FCoVs use another main host cell receptor. We also observed that recombinant FCoVs display a large-plaque phenotype and, unexpectedly, accelerated growth kinetics indistinguishable from that of type II FCoV strain 79-1146. Thus, the main phenotypic differences for type I and type II FCoVs in cell culture, namely, the growth kinetics and the efficient usage of fAPN as a cellular receptor, can be attributed solely to the FCoV S protein.


title: The associations of acceptance with quality of life and mental health following spinal cord injury: a systematic review.

text: STUDY DESIGN Systematic review. OBJECTIVES To identify, critically appraise, and synthesize research findings on the associations between acceptance, quality of life (QOL), and mental health outcomes in individuals living with spinal cord injury (SCI). METHODS Five databases (PubMed, PsycINFO, Embase, Web of Science, and Scopus) were systematically searched. Studies were included if they provided findings on the association between acceptance and QOL, mental health outcomes, or both in an SCI population aged 16 years or older. Only peer-reviewed original quantitative and qualitative studies were included. Screening, quality assessment, and data extraction were conducted independently by two researchers. Findings were tabulated and synthesized by outcome. RESULTS Forty-one studies were included. Greater acceptance was consistently associated with greater global and psychological QOL, life satisfaction, sense of well-being, mental health, and with lower levels of depression and anxiety. Inconsistent evidence was found with regards to social QOL and post-traumatic stress disorder. Acceptance was generally not associated with adjustment outcomes further than 2 years into the future. Study quality of the quantitative studies was mostly fair (n = 17) followed by good (n = 13), and poor (n = 9). CONCLUSION Health-care professionals may regard acceptance as a psychological resource they can aim to support in improving QOL and mental health following SCI. A range of methodological and conceptual limitations were present in the research. Future studies should prioritize longitudinal designs, consider dyadic effects, explore subjective meaning(s) of acceptance, and investigate the effectiveness of therapeutic approaches that stimulate the acceptance process.


title: Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

text: BACKGROUND In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. METHODS Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. FINDINGS Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. INTERPRETATION The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. FUNDING Bristol-Myers Squibb and Pfizer.


title: Qualitative systematic review of barriers and facilitators to patient-involved antipsychotic prescribing.

text: BACKGROUND Despite policy and practice mandates for patient involvement, people with serious mental illness often feel marginalised in decisions about antipsychotic medication. Aims To examine stakeholder perspectives of barriers and facilitators to involving people with serious mental illness in antipsychotic prescribing decisions. METHOD Systematic thematic synthesis. RESULTS Synthesis of 29 studies identified the following key influences on involvement: patient's capability, desire and expectation for involvement, organisational context, and the consultation setting and processes. CONCLUSIONS Optimal patient involvement in antipsychotic decisions demands that individual and contextual barriers are addressed. There was divergence in perceived barriers to involvement identified by patients and prescribers. For example, patients felt that lack of time in consultations was a barrier to involvement, something seldom raised by prescribers, who identified organisational barriers. Patients must understand their rights to involvement and the value of their expertise. Organisational initiatives should mandate prescriber responsibility to overcome barriers to involvement. Declaration of interest None.


title: Livestock infectious diseases and zoonoses.

text: Infectious diseases of livestock are a major threat to global animal health and welfare and their effective control is crucial for agronomic health, for safeguarding and securing national and international food supplies and for alleviating rural poverty in developing countries. Some devastating livestock diseases are endemic in many parts of the world and threats from old and new pathogens continue to emerge, with changes to global climate, agricultural practices and demography presenting conditions that are especially favourable for the spread of arthropod-borne diseases into new geographical areas. Zoonotic infections that are transmissible either directly or indirectly between animals and humans are on the increase and pose significant additional threats to human health and the current pandemic status of new influenza A (H1N1) is a topical example of the challenge presented by zoonotic viruses. In this article, we provide a brief overview of some of the issues relating to infectious diseases of livestock, which will be discussed in more detail in the papers that follow.


title: Catheter entrapment due to severe radial artery spasm during transradial approach.

text: BACKGROUND Catheter entrapment due to severe radial artery spasm (RAS) during transradial coronary catheterization has been rarely reported and its management is not precisely defined. The aim of this study was to determine the incidence, predictors and management of catheter entrapment due to severe RAS. METHODS A total of 723 patients undergoing transradial coronary catheterization at a single center were retrospectively enrolled in the present study. Patients were divided into two groups: those with catheter entrapment due to severe RAS and those without. RESULTS The incidence of catheter entrapment was 0.8%. Height (161.2 ± 9.1 cm vs. 169.6 ± ± 10 cm, p = 0.047) and body surface area (1.86 ± 0.04 vs. 1.95 ± 0.18, p = 0.002) were found to be lower, and total procedure time 33.2 ± 13.4 min vs. 15.2 ± 12.3 min, p < 0.001) was longer in the entrapment group. Multivariate logistic regression analysis demonstrated that total procedure time independently predicted catheter entrapment (odds ratio: 1.057, 95% confidence interval [CI] 1.004-1.114, p = 0.035). Receiver-operating characteristic curve demonstrated good diagnostic accuracy for prolonged total procedure time in predicting catheter entrapment (area under curve = 0.8, 95% CI 0.63-0.97, p = 0.01). Patients were effectively treated with stepwise administration of systemic vasodilators, forearm heating, sedation and as a last resort general anesthesia with no significant complication. CONCLUSIONS Catheter entrapment due to severe RAS during transradial approach was rare and prolonged total procedure time is an independent predictor of catheter entrapment. Treatment with stepwise administration of different treatment modalities is possible with no significant complication.


title: Two head positions for orotracheal intubation with the trachway videolight intubating stylet with manual in-line stabilization: A randomized controlled trial.

text: BACKGROUND The Trachway Videolight Intubating Stylet is a video-assisted system with a rigid but malleable intubating stylet that facilitates endotracheal intubation. Minimizing cervical spine movement with manual in-line stabilization is essential for patients with cervical spine injuries such as multiple trauma. However, the intubation time of the Trachway Videolight Intubating Stylet and complications associated with intubation in patients with manual in-line stabilization in the neutral-head and head-lift positions remain unclear. METHODS Patients (20-80 years old) who were scheduled to undergo surgery that required general anesthesia with tracheal intubation were randomly allocated to either a neutral-head (n = 62) or a head-lift position (n = 62) group. Manual in-line stabilization was performed to limit cervical spine mobility. We aimed to evaluate orotracheal intubation time and success rate in these 2 positions with the Trachway Videolight Intubating Stylet. RESULTS Intubation was faster in the head-lift than in the neutral-head position (20 ± 10 and 25 ± 13 seconds, respectively, P = .000); intubation was equally successful in the 2 positions (96.8% vs 96.8%). Responses to intubation did not differ between positions (heart rate, P = .142; visual analog scale scores for throat soreness, P = .54). The only significant predictor of intubation time was the body mass index in the head-lift position group (P = .005). CONCLUSIONS Intubation using the Trachway Videolight Intubating Stylet with manual in-line stabilization is faster in the head-lift position, and therefore preferable. However, if the head-lift position is not suitable, the neutral-head position is a sensible alternative, with comparable intubation success rate, heart rate change, and postoperative throat soreness.


title: Survival study of natural orifice translumenal endoscopic surgery for rectosigmoid resection using transanal endoscopic microsurgery with or without transgastric endoscopic assistance in a swine model.

text: BACKGROUND The feasibility of transanal rectosigmoid resection with transanal endoscopic microsurgery (TEM) was previously demonstrated in a swine nonsurvival model in which transgastric endoscopic assistance also was shown to extend the length of colon mobilized transanally. METHODS A 2-week survival study evaluating transanal endoscopic rectosigmoid resection with stapled colorectal anastomosis was conducted with swine using the transanal approach alone (TEM group, n = 10) or a transanal approach combined with transgastric endoscopic assistance (TEM + TG group, n = 10). Gastrotomies were created using a needleknife and balloon dilation, then closed using prototype T-tags. Outcomes were evaluated and compared between the groups using Student's t-test and Fisher's exact test. RESULTS Relative to the TEM group, the average length of rectosigmoid mobilized in the TEM + TG group was 15.6 versus 10.5 cm (p < 0.0005), the length of the resected specimen was 9 versus 6.2 cm (p < 0.0005), and the mean operative time was 254.5 versus 97.5 min (p < 0.0005). Intraoperatively, no organ injury or major bleeding was noted. Two T-tag misfires occurred during gastrotomy closure and four small staple line defects requiring transanal repair including one in the TEM group and three in the TEM + TG group (p = 0.2). Postoperatively, there was no mortality, and the animals gained an average of 3.4 lb. Two major complications (10%) were identified at necropsy in the TEM + TG group including an intraabdominal abscess and an abdominal wall hematoma related to T-tag misfire. Gastrotomy closure sites and colorectal anastomoses were all grossly healed, with adhesions noted in 60 and 70% and microabscesses in 50 and 20% of the gastrotomy sites and colorectal anastomoses, respectively. CONCLUSIONS Natural orifice translumenal endoscopic surgery (NOTES) for rectosigmoid resection using TEM with or without transgastric endoscopic assistance is feasible and associated with low morbidity in a porcine survival model. Transgastric assistance significantly prolongs the operative time but extends the length of the rectosigmoid mobilized transanally, with a nonsignificant increase in complication rates related to gastrotomy creation.


title: Lassa Fever-associated Stigmatization among Staff and Students of the University of Benin, Nigeria.

text: Lassa Fever (LF) remains a health burden in several endemic areas of Nigeria, and its toll remains unabated over several decades. Although most studies have focused on virological and clinical considerations, few studies have attempted to address the perceived psychosocial component of LF disease in Nigeria. Evaluation of stigmatization and discrimination faced by LF survivors is an important step in improving individual health and protecting public health. This study aimed to assess LF-associated stigmatization associated among staff and students of the University of Benin. Descriptive analyses of 600 consenting respondents (300 staff and 300 students) sampled using pretested questionnaires was conducted, and the Chi-square test was used to test for significant association between perceived LF stigmatization and predefined variables. LF was a potential cause of stigmatization in a higher proportion of student (n = 162, 57.9%) than staff (n = 112, 39.9%). LF-associated stigmatization among students was significantly associated with sex (p = 0.012) and poor knowledge (p = 0.013) of LF transmission and prevention. A greater tendency for stigmatization was observed among females than males. A comprehensive emergency response plan incorporating accurate knowledge dissemination about the disease may be a first step toward tackling perceived LF stigmatization.


title: Conservative Management of Invasive Placentation: Two Cases with Different Surgical Approaches.

text: Background When placenta accreta complicates a delivery, the typical management is to perform a cesarean hysterectomy. Other management strategies, including leaving the placenta in situ, have been attempted and supported in some cases. This may allow for an interval hysterectomy, which can potentially decrease average blood loss and/or allow a minimally invasive approach to the hysterectomy. Cases We present two cases of women with invasive placentation managed conservatively with interval hysterectomy. One woman was managed with robotic-assisted laparoscopic surgery and the other with an open surgical approach. Conclusion These cases highlight the successful use of conservative management for invasive placentation in two stable patients and showcase the novel use of a robotic-assisted laparoscopic surgery for management of invasive placentation.


docid: ylgyvxtd

title: COVID-19 associated central nervous system vasculopathy.


title: Acellular Hydrogels for Regenerative Burn Wound Healing: Translation from a Porcine Model.

text: Currently available skin grafts and skin substitutes for healing following third-degree burn injuries are fraught with complications, often resulting in long-term physical and psychological sequelae. Synthetic treatment that can promote wound healing in a regenerative manner would provide an off-the-shelf, non-immunogenic strategy to improve clinical care of severe burn wounds. Here, we demonstrate the vulnerary efficacy and accelerated healing mechanism of a dextran-based hydrogel in a third-degree porcine burn model. The model was optimized to allow examination of the hydrogel treatment for clinical translation and its regenerative response mechanisms. Hydrogel treatment accelerated third-degree burn wound healing by rapid wound closure, improved re-epithelialization, enhanced extracellular matrix remodeling, and greater nerve reinnervation, compared with the dressing-treated group. These effects appear to be mediated through the ability of the hydrogel to facilitate a rapid but brief initial inflammatory response that coherently stimulates neovascularization within the granulation tissue during the first week of treatment, followed by an efficient vascular regression to promote a regenerative healing process. Our results suggest that the dextran-based hydrogels may substantially improve healing quality and reduce skin grafting incidents and thus pave the way for clinical studies to improve the care of severe burn injury patients.


The Role of Lung Ultrasound in Diagnosis and Follow-Up of Children With Coronavirus Disease 2019.


title: Triterpene functional genomics in licorice for identification of CYP72A154 involved in the biosynthesis of glycyrrhizin.

text: Glycyrrhizin, a triterpenoid saponin derived from the underground parts of Glycyrrhiza plants (licorice), has several pharmacological activities and is also used worldwide as a natural sweetener. The biosynthesis of glycyrrhizin involves the initial cyclization of 2,3-oxidosqualene to the triterpene skeleton β-amyrin, followed by a series of oxidative reactions at positions C-11 and C-30, and glycosyl transfers to the C-3 hydroxyl group. We previously reported the identification of a cytochrome P450 monooxygenase (P450) gene encoding β-amyrin 11-oxidase (CYP88D6) as the initial P450 gene in glycyrrhizin biosynthesis. In this study, a second relevant P450 (CYP72A154) was identified and shown to be responsible for C-30 oxidation in the glycyrrhizin pathway. CYP72A154 expressed in an engineered yeast strain that endogenously produces 11-oxo-β-amyrin (a possible biosynthetic intermediate between β-amyrin and glycyrrhizin) catalyzed three sequential oxidation steps at C-30 of 11-oxo-β-amyrin supplied in situ to produce glycyrrhetinic acid, a glycyrrhizin aglycone. Furthermore, CYP72A63 of Medicago truncatula, which has high sequence similarity to CYP72A154, was able to catalyze C-30 oxidation of β-amyrin. These results reveal a function of CYP72A subfamily proteins as triterpene-oxidizing enzymes and provide a genetic tool for engineering the production of glycyrrhizin.


Hydrothermal duodenal mucosal resurfacing: a novel procedural therapy for metabolic disease.


title: Fundamental Use of Surgical Energy (FUSE) certification: validation and predictors of success.

text: INTRODUCTION The Fundamental Use of Surgical Energy (FUSE) program includes a Web-based didactic curriculum and a high-stakes multiple-choice question examination with the goal to provide certification of knowledge on the safe use of surgical energy-based devices. The purpose of this study was (1) to set a passing score through a psychometrically sound process and (2) to determine what pretest factors predicted passing the FUSE examination. METHODS Beta-testing of multiple-choice questions on 62 topics of importance to the safe use of surgical energy-based devices was performed. Eligible test takers were physicians with a minimum of 1 year of surgical training who were recruited by FUSE task force members. A pretest survey collected baseline information. RESULTS A total of 227 individuals completed the FUSE beta-test, and 208 completed the pretest survey. The passing/cut score for the first test form of the FUSE multiple-choice examination was determined using the modified Angoff methodology and for the second test form was determined using a linear equating methodology. The overall passing rate across the two examination forms was 81.5%. Self-reported time studying the FUSE Web-based curriculum for a minimum of >2 h was associated with a passing examination score (p < 0.001). Performance was not different based on increased years of surgical practice (p = 0.363), self-reported expertise on one or more types of energy-based devices (p = 0.683), participation in the FUSE postgraduate course (p = 0.426), or having reviewed the FUSE manual (p = 0.428). Logistic regression found that studying the FUSE didactics for >2 h predicted a passing score (OR 3.61; 95% CI 1.44-9.05; p = 0.006) independent of the other baseline characteristics recorded. CONCLUSION(S) The development of the FUSE examination, including the passing score, followed a psychometrically sound process. Self-reported time studying the FUSE curriculum predicted a passing score independent of other pretest characteristics such as years in practice and self-reported expertise.


title: Predictors for Symptomatic Intracranial Hemorrhage After Endovascular Treatment of Acute Ischemic Stroke.

text: BACKGROUND AND PURPOSE Symptomatic intracranial hemorrhage (SICH) pose a major safety concern for endovascular treatment of acute ischemic stroke. This study aimed to evaluate the risk and related factors of SICH after endovascular treatment in a real-world practice. METHODS Patients with stroke treated with stent-like retrievers for recanalizing a blocked artery in anterior circulation were enrolled from 21 stroke centers in China. Intracranial hemorrhage was classified as symptomatic and asymptomatic ones according to Heidelberg Bleeding Classification. Logistic regression was used to identify predictors for SICH. RESULTS Of the 632 enrolled patients, 101 (16.0%) were diagnosed with SICH within 72 hours after endovascular treatment. Ninety-day mortality was higher in patients with SICH than in patients without SICH (65.3% versus 18.8%; P<0.001). On multivariate analysis, baseline neutrophil ratio >0.83 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.24-3.46), pretreatment Alberta Stroke Program Early Computed Tomography Score of <6 (OR, 2.27; 95% CI, 1.24-4.14), stroke of cardioembolism type (OR, 1.91; 95% CI, 1.13-3.25), poor collateral circulation (OR, 1.97; 95% CI, 1.16-3.36), delay from symptoms onset to groin puncture >270 minutes (OR, 1.70; 95% CI, 1.03-2.80), >3 passes with retriever (OR, 2.55; 95% CI, 1.40-4.65) were associated with SICH after endovascular treatment. CONCLUSIONS Incidence of SICH after thrombectomy is higher in Asian patients with acute ischemic stroke. Cardioembolic stroke, poor collateral circulation, delayed endovascular treatment, multiple passes with stent retriever device, lower pretreatment Alberta Stroke Program Early Computed Tomography Score, higher baseline neutrophil ratio may increase the risk of SICH.


title: Conserved baculoviral ORFs 10 and 14 from Bombyx mori multiple nucleopolyhedrovirus.

text: ORFs 10 and 14 from Bombyx mori multiple nucleopolyhedrovirus (BmMNPV) were amplified, cloned and sequenced. Nucleotide analysis of these genes and those of other baculoviruses showed that these genes are highly conserved. The p10 protein from BmMNPV ORF10 has 70 amino acid residues similar to that of the four other known BmNPV strains. The BmMNPV ORF14 alignment showed a higher identity with the nucleopolyhedrovirus ORF14 from the baculovirus BmNPV and from Autographa californica multiple nucleopolyhedrovirus. The BmMNPV ORF14 protein has a putative transmembrane domain in the C-terminal region, which is similar to that of other baculoviruses. A phylogenetic analysis showed that BmMNPV ORF14 protein has higher similarity with BmNPV ORF14 and ORF23 of A. californica multicapsid nucleopolyhedrovirus (Ac23). We conclude that proteins produced by ORFs 10 and 14 from BmNPV and BmMNPV are highly conserved in NPVs and MNPVs. The high degree of conservation among members of these genera indicates the importance of these proteins, which could mean an important function that is active throughout the infection cycle.


title: Computed tomography lymphography for the detection of sentinel nodes in patients with gastric carcinoma.

text: The sentinel node (SN) concept has been found to be feasible in gastric cancer. However, the lymphatic network of gastric cancer may be more complex, and it may be difficult to visualize all the SN distributed in unexpected areas by conventional modalities. In this study, we evaluate the feasibility and efficacy of CT lymphography for the detection of SN in gastric cancer. A total 24 patients with early gastric cancer were enrolled in the study. Three modalities (CT lymphography, dye and radioisotope [RI] methods) were used for the detection of SN. The images of CT lymphography were obtained at 10 min after injection of contrast agents. The SN were successfully identified by CT lymphography in 83.3% of patients; detection rates by the dye and RI methods were 95% and 100%, respectively. Most patients, in whom SN were successfully detected by CT lymphography, had positive results at 5 min after injection of the contrast material. The SN stations detected by CT lymphography were consistent with or included those detected by dye and/or RI methods. In conclusion, CT lymphography for the detection of SN in gastric cancer is feasible and has several advantages. However, based on this initial experience, CT lymphography had a relatively low detection rate compared with conventional methods, and further efforts will be necessary to improve the detection rate and widen the clinical application of CT lymphography for the detection of SN in gastric cancer.


title: Combined cranionasal surgery for spheno-orbital meningiomas invading the paranasal sinuses, pterygopalatine, and infratemporal fossa.

text: OBJECTIVE To evaluate the efficacy of combining an endonasal endoscopic skull-base approach and repair with a transcranial orbitozygomatic approach for spheno-orbital meningiomas (SOMs). METHODS Three patients with recurrent SOMs underwent combined orbitozygomatic and endonasal endoscopic surgery. In 2 patients both procedures were done in 1 operation and in 1 patient the endonasal surgery was done 2.5 months after the craniotomy. Extent of resection, complications, morbidity, and mortality were evaluated. RESULTS Gross total resection was achieved in 1 patient and near total resection in the other 2 patients with tumor left in the cavernous sinus and parapharyngeal space. Two patients suffered cranial neuropathy from the transcranial surgery and the other developed a pseudomeningocele. There were no complications from the endonasal surgery. Patients having combined single setting cranionasal surgery were discharged on day 6 and 8, whereas the patient having only the endonasal component on a later date was discharged on day 2. CONCLUSIONS A combined cranionasal approach involving transcranial orbitozygomatic and endonasal endoscopic approaches is an effective 2-stage surgery for resecting SOMs invading into the sinuses and paranasal compartments. The ability to perform a multilayer closure involving a vascularized nasoseptal flap additionally decreases the risk of postoperative cerebrospinal fluid leak.


title: Diagnostic role of chest computed tomography in coronavirus disease 2019.

text: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a novel strain of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that appeared in China in December 2019 and spread globally, evolving into the currently observed pandemic. The laboratory diagnosis of SARS-CoV-2 infection is currently based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) testing, and imaging cannot replace genetic testing in patients suspected of COVID-19. However, with predominant respiratory manifestations of COVID-19, particularly in more severe cases, chest imaging using computed tomography (CT) plays a major role in detecting viral lung infection, evaluating the nature and extent of pulmonary lesions, and monitoring the disease activity. The role of chest CT as a diagnostic tool may be increased when the laboratory testing capacities using RT-PCR prove inaccurate or insufficient during a major outbreak of the disease. In these settings, a rapid presumptive diagnosis of COVID-19 potentially offered by CT might be an advantage, in addition to obvious benefits of delineating the nature and extent of pulmonary changes. In the present paper, we reviewed the diagnostic role of chest CT in COVID-19 patients.


The role of the medicine student in COVID-19 pandemic. A shared responsibility.


title: Antimicrobial Resistance in Escherichia coli.

text: Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.


title: Obituary: Pietro Cugini (13 December 1936 - 6 April 2020).

text: Chronobiology lost a great and distinguished physician-scientist, Pietro Cugini (Figure 1). He will be dearly missed by his family, his friends, and the field he helped shape and guide as he remained active until the end of his life at 83 years of age. In the middle of the worst pandemic the world has known in recent times, but not from COVID-19, Pietro passed away unexpectedly in front of his Rome apartment, on Via Latina, the same street where he was born and where he spent most of his life. He was buried shortly afterward in the Monumental cemetery of Marino. There was no formal ceremony as funerals were suspended because of the coronavirus. A proper ceremony will take place as soon as travel and congregation are possible. Pietro is survived by his three children, Silvia, Raffaella and Riccardo Cugini.


title: Survival after radiofrequency ablation and salvage transplantation in patients with hepatocellular carcinoma and Child-Pugh A cirrhosis.

text: BACKGROUND & AIMS In patients with hepatocellular carcinoma (HCC) within the Milan criteria, liver transplantation (LT) may be the best therapeutic option. However, the shortage of grafts, leads to attempt liver resection (LR) or radiofrequency ablation (RFA) as a first-line treatment for patients with Child-Pugh A cirrhosis. METHODS We report results, obtained between 2000 and 2007 from a single center, involving 67 patients (mean age: 57 years) eligible for LT, who were treated with RFA, followed by LT if there was recurrence or liver failure. RESULTS Eighty three tumors were treated (mean size: 29±9 mm; 16 binodular forms). RFA achieved complete ablation in 96% of nodules. No mortality occurred. During a post-RFA median follow-up of 48 months, 38 patients experienced recurrence, corresponding to a 5-year recurrence rate of 58%. Of these, 14 patients did not receive a transplant because they fell outside the Milan criteria, 21 were transplanted, and 3 were treated by RFA after refusing LT. Binodularity (95% CI HR=2, 1.0-4.0; p=0.049) was the unique risk factor for recurrence. By the study's end-point, 24 patients had undergone LT (21 for HCC recurrence and three for liver failure). No HCC recurrence occurred after LT. Among the 43 non-transplant patients, 12 died due to HCC progression, and 27 were alive without detectable viable tumor. The probability rates for 5-year overall and tumor-free survival were 74% and 69%, respectively. CONCLUSIONS First line RFA followed by salvage LT allows survival figures that are at least as good as a first-line LT, while limiting the number of grafts.


Air Hunger and Psychological Trauma in Ventilated COVID-19 Patients: An Urgent Problem.


Chloroquine and hydroxychloroquine repositioning in times of COVID-19 pandemics, all that glitters is not gold.


title: Closure of bronchopleural fistula with porcine dermal collagen and fibrin glue in an infant.

text: The management of an 11-month-old infant who developed a bronchopleural fistula (BPF) 3 weeks after video-assisted thoracic surgery for congenital cystic adenomatoid malformation of the right lower pulmonary lobe is presented. Being refractory to treatment with chest tubes, the BPF was managed using a bronchoscopic approach using porcine dermal collagen (PDC) combined with a fibrin glue plug. The single session was sufficient to manage the BPF and the postoperative course was uneventful. This case highlights the novelty in the successful management of BPF in infants after pulmonary surgery using PDC and fibrin glue using the minimal access bronchoscopic approach.


News and Views.


title: Nurses' perception of disaster: implications for disaster nursing curriculum.

text: AIMS AND OBJECTIVES The aims of the study were to identify nurses' perception of disaster, whether they considered some of the events that have occurred in Hong Kong to be disasters and the types of disastrous events that they considered likely in Hong Kong. BACKGROUND The frequent occurrence of disasters has caused concern internationally. When disaster strikes, the demands on nursing staff are much higher than those on other healthcare professionals. There is little understanding of the concept of disaster among nurses in Hong Kong. DESIGN This was a descriptive study. A questionnaire was used to explore nurses' perception of disaster. METHOD The questionnaire was distributed to all registered nurses studying in a master's degree programme in a university in Hong Kong. FINDINGS Only 123 out of the 164 respondents (75%) gave a description of disaster in the open-ended question. Sixty-one per cent of them described unfortunate events with large numbers of victims as disasters. The 'Lan Kwai Fong tragedy--stampede caused by over-crowdedness' (90.9%) and the severe acute respiratory syndrome outbreak (89.6%) were commonly referred to as disasters in Hong Kong. Fires in tall buildings (61.6%), infectious disease outbreaks (61%) and stampedes caused by overcrowding (48.8%) were rated as the events most likely to happen in Hong Kong. CONCLUSION Understanding how nurses perceive disaster and the likelihood of disastrous events is the initial step for disaster planning and the development of a disaster nursing curriculum in Hong Kong. RELEVANCE TO CLINICAL PRACTICE All nurses around the world should be equipped with knowledge and skills for disaster care. This study provides information and implications for related research and the development of a disaster nursing curriculum to meet the global demand for disaster preparedness.


title: Ski Boots Do Not Impair Standing Balance by Restricting Ankle-Joint Mobility.

text: OBJECTIVE This study was undertaken in order to provide new insight into sensorimotor control of posture when wearing high-shaft (HS) boots as ski boots. BACKGROUND Previous studies into the effects of HS boots on postural control have produced controversial results. Some studies reported postural control impairments with ski boots in bipedal postural tasks due to ankle movement restrictions without quantifying the actual restrictive effect of these boots and specifying the adaptations of the postural control system. METHOD Eighteen young healthy subjects took part in the experiment. Bilateral postural control was assessed on stable and unstable surfaces, while standing barefoot or wearing ski boots. Center of pressure (COP) parameters, ankle, knee, and hip joints movements were calculated and EMG activity from main postural muscles was recorded. RESULTS Ski boots did not restrict the amplitude of ankle angular movements and largely impacted COP parameters and EMG activity on stable ground. In conditions of mediolateral instability, COP data illustrated an enhanced postural control in the frontal plane when wearing ski boots. CONCLUSIONS Ski boots do not affect bipedal postural balance by restricting the ankle angular motions but induce complex adaptations of the postural control system which combine factors of a mechanical, motor, and sensorial nature. They impede postural control mainly when standing on stable ground without producing similar deleterious effects on unstable surfaces. APPLICATION Our results show that HS boots as ski boots can improve lateral balance on unstable surfaces, which can contribute to prevent fall risk and ankle sprain.


title: Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A.

text: Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species Betacoronavirus-1, and more closely related to bovine coronavirus (BCoV)-its presumptive ancestor-and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9-O-acetylated sialic acid (9-O-Ac-Sia). Receptor binding is mediated by spike protein S, the main determinant of coronavirus host specificity. For BCoV, a crystal structure for the receptor-binding domain S1A is available and for HKU1 a cryoelectron microscopy structure of the complete S ectodomain. However, the location of the receptor-binding site (RBS), arguably the single-most important piece of information, is unknown. Here we solved the 3.0-Å crystal structure of PHEV S1A We then took a comparative structural analysis approach to map the β1CoV S RBS, using the general design of 9-O-Ac-Sia-binding sites as blueprint, backed-up by automated ligand docking, structure-guided mutagenesis of OC43, BCoV, and PHEV S1A, and infectivity assays with BCoV-S-pseudotyped vesicular stomatitis viruses. The RBS is not exclusive to OC43 and related animal viruses, but is apparently conserved and functional also in HKU1 S1A The binding affinity of the HKU1 S RBS toward short sialoglycans is significantly lower than that of OC43, which we attribute to differences in local architecture and accessibility, and which may be indicative for differences between the two viruses in receptor fine-specificity. Our findings challenge reports that would map the OC43 RBS elsewhere in S1A and that of HKU1 in domain S1B.


docid: luyguguc

title: Prognostic impact of microscopic vessel invasion and visceral pleural invasion in non-small cell lung cancer: a retrospective analysis of 2657 patients.

text: OBJECTIVE We aimed to assess the prognostic significance of microscopic vessel invasion (MVI) and visceral pleural invasion (VPI) in non-small cell lung cancer (NSCLC). BACKGROUND VPI is included in the current tumor-node-metastasis (TNM) classification in NSCLC; however, MVI is not incorporated in TNM classification. METHODS From August 1992 to December 2009, 2657 consecutive patients with pathological T1-4N0-2M0 NSCLC underwent complete resection. In addition to conventional staging factors, we evaluated MVI histologically and analyzed its significance in NSCLC recurrence prognosis. The recurrence-free period in several NSCLC subgroups was analyzed using the Kaplan-Meier method and Cox regression analysis. RESULTS The proportion of patients with a 5-year recurrence-free period was 52.6% and 87.5%, respectively, in those with and without MVI (P < 0.001). Multivariate analysis showed that MVI, similarly to VPI, was found to be an independently significant predictor of recurrence [hazard ratio (HR): 2.78]. In particular, MVI and VPI were the 2 strongest significant independent predictors of recurrence in 1601 patients with pathological stage I disease treated without adjuvant chemotherapy (HR: 2.74 and 1.84, respectively). In each T subgroup analysis, evident and significant separation of the recurrence-free proportion curves were observed among the 3 groups (VPI and MVI absent, VPI or MVI present, and VPI and MVI present). CONCLUSIONS This study demonstrated that MVI was a significant independent risk factor for recurrence in patients with a resected T1-4N0-2M0 NSCLC. Further data on MVI prognostic impact should be collected for the next revision of the TNM staging system.


title: An ex vivo comparison of cuffed endotracheal tubes and self-sealing baffled endotracheal tubes.

text: AIMS To compare cuffed silicone endotracheal tubes with self-sealing baffled silicone endotracheal tubes in an ex vivo canine tracheal model, to determine whether the tubes differed in their maintenance of a seal and their effectiveness in removing fluid from the tracheal lumen, and whether the self-sealing endotracheal tubes would release pressure when a closed anaesthetic circuit reached ≥30 cm H2O. METHODS Twelve cadaver tracheae were randomly selected to be intubated with either cuffed or self-sealing baffled endotracheal tubes. To test tracheal seal efficacy, the tracheae were positioned vertically, 5 mL of water was instilled proximal to the tube cuff or baffles and they were monitored for leakage at 0, 15, 30, 45, and 60 minutes, recording the total volume leaked. To test fluid removal at extubation, the tracheae were intubated, then 5.6 g of 60% barium sulphate suspension was instilled proximal to the seal and left undisturbed for 5 minutes. The tubes were then extubated, with the cuffed endotracheal tubes being partially deflated before extubation, and the amount of barium recovered was weighed. These procedures were repeated on the same tracheae using the other endotracheal tubes. To test whether self-sealing baffled endotracheal tubes would release pressure at ≥30 cm H2O, the tracheae were intubated, connected to an anaesthetic machine and pressurised to 30 cm H2O for 5 minutes and then 50 cm H2O for 5 minutes. Release of pressure was defined as a decrease in pressure within the closed anaesthetic circuit. RESULTS More cuffed (7/12) than baffled (0/12) endotracheal tubes leaked water after 60 minutes (p=0.016). The mean amount of barium removed by the self-sealing baffled endotracheal tubes (4.9 (95% CI=3.8-4.4) g) was greater than that removed by the partially deflated cuffed endotracheal tubes (0.4 (95% CI=0.14-0.66) g) (p<0.001). None of the self-sealing baffled endotracheal tubes released pressure at ≥30 cm H2O in a closed anaesthetic circuit. CONCLUSIONS AND CLINICAL RELEVANCE Self-sealing baffled endotracheal tubes were more effective than cuffed endotracheal tubes at both preventing fluid leakage at the tracheal seal and removing fluid from the lumen of the trachea in cadaver tracheae. However they did not release pressure when the closed-circuit system was at ≥30 cm H2O in a canine cadaver model. The self-sealing baffled endotracheal tubes may be a suitable substitute for cuffed endotracheal tubes.


title: Fatal rupture of a brain arteriovenous malformation flow-related aneurysm during microcatheter removal: a rare complication.

text: Intracranial aneurysms are relatively frequently encountered in patients with brain arteriovenous malformations (BAVMs). They may be located on the circle of Willis, on arterial feeders, or even inside the nidus. Because BAVM-associated aneurysms represent a risk factor of bleeding, the question of the timing and modality of their management remains a matter of debate in unruptured BAVMs. The authors present a case of fatal periprocedural rupture of a flow-related aneurysm (FRA) during the removal of the microcatheter after injection of a liquid embolic agent. A 40-year-old man was treated at the authors' institution for the management of a Spetzler-Martin Grade III left unruptured frontal BAVM, revealed by seizures and a focal neurological deficit attributed to flow steal phenomenon. After a multidisciplinary meeting, endovascular treatment was considered to reduce the flow of the BAVM. A proximal FRA located on the feeding internal carotid artery (ICA) was purposely left untreated because it did not meet the criteria of the authors' institution for preventative treatment (i.e., small size [2.5 mm]). During embolization, at the time of microcatheter retrieval, and after glue injection, the aneurysm unexpectedly ruptured. The aneurysm's rupture was attributed to the stress (torsion/flexion) on the ICA caused by the microcatheter removal. Despite the attempts to manage the bleeding, the patient eventually died of the acute increase of intracranial pressure related to the massive subarachnoid hemorrhage. This case highlights a previously unreported mechanism of FRA rupture during BAVM embolization: the stress transmitted to the parent artery during the removal of the microcatheter.


title: Effect of an acute increase in central blood volume on cerebral hemodynamics.

text: Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV.


title: Genetic diversity and phenotypic associations of feline caliciviruses from cats in Switzerland.

text: Feline calicivirus (FCV) is a common viral pathogen in domestic cats worldwide. The variable regions of the capsid (VP1) gene of FCV have one of the highest recorded rates of molecular evolution. Understanding the genetic diversity and phylogeny of FCV is a prerequisite to exploring the epidemiology and pathogenesis of this virus and to the development of efficacious vaccine strategies. In this study, we undertook a nationwide molecular characterization of FCV using for the first time nearly complete capsid (VP1) gene sequences. Sequences from 66 FCV samples were used to investigate the correlation between viral phylogeny and several traits, including geographic origin, signalment, husbandry, FCV vaccination and co-infections. Codon-based nucleotide alignment showed that individual nucleotides and their corresponding amino acid sites were either invariant or highly variable. Using a threshold of 20 % genetic distance in variable region E, FCV samples were grouped into 52 strains, 10 of which comprised two to three samples. Significant associations between FCV phylogeny and host characteristics were found, specifically the pedigree status of the cats, and two well-supported lineages were identified in which the current FCV strain definition was confounded. No correlation between viral genetic distances and geographic distances was evident. The greater resolution of the FCV phylogeny in this study compared to previous studies can be attributed to our use of more conserved regions of the capsid (VP1) gene; nonetheless, our results were still hampered by sequence saturation. The study highlights the need for whole-genome sequences for FCV phylogeny studies.


Wildlife consumption ban is insufficient.


title: Eight-Hour Continuous Normothermic Ex Vivo Kidney Perfusion Is a Safe Preservation Technique for Kidney Transplantation: A New Opportunity for the Storage, Assessment, and Repair of Kidney Grafts.

text: BACKGROUND Hypothermic kidney storage causes preservation injury and is poorly tolerated by renal grafts. We investigated whether static cold storage (SCS) can be safely replaced with a novel technique of pressure-controlled normothermic ex vivo kidney perfusion (NEVKP) in heart-beating donor kidney transplantation. METHODS Right kidneys were removed from 30 kg Yorkshire pigs in a model of heart-beating donation and either preserved in cold histidine-tryptophan-ketoglutarate solution for 8 hours (n = 5), or subjected to 8 hours of pressure-controlled NEVKP (n = 5) followed by renal heterotopic autotransplantation. RESULTS During NEVKP, physiologic perfusion conditions were maintained with low intrarenal resistance and normal electrolyte and pH parameters. Aspartate aminotransferase and lactate dehydrogenase as injury markers were below the detectable analyzer range (<4 and <100 U/L, respectively). Perfusate lactate concentration decreased from baseline until the end of perfusion (10.38 ± 0.76 mmol/L vs 1.22 ± 0.26 mmol/L; P < 0.001). Posttransplantation, animals transplanted with NEVKP versus SCS grafts demonstrated similar serum creatinine peak levels (NEVKP, 2.0 ± 0.5 vs SCS 2.7 ± 0.7 mg/dL; P = 0.11) and creatinine clearance on day 10 (NEVKP, 65.9 ± 18.8 mL/min vs SCS 61.2 ± 15.6 mL/min; P = 0.74). After 10 days of follow-up, animals transplanted with NEVKP grafts had serum creatinine and blood urea nitrogen values comparable to their basal levels (P = 0.49 and P = 0.59), whereas animals transplanted with SCS grafts had persistently elevated serum creatinine and blood urea nitrogen when compared with basal levels (P = 0.01 and P = 0.03). CONCLUSIONS Continuous pressure-controlled NEVKP is feasible and safe in good quality heart-beating donor kidney grafts. It maintains a physiologic environment and excellent graft function ex vivo during preservation without causing graft injury.


title: Protective myoelectric activity at performing upper limb neurodynamic test 1 in breast cancer survivors. A cross-sectional observational study.

text: Myoelectric activity and range of motion during ULNT1 were recorded in 62 breast cancer (BC) survivors who had axillary lymph node dissection (n = 30) or sentinel lymph node biopsy (n = 32) within the previous 18 months, and 63 age-matched healthy women. BC survivors' symptoms were reproduced by ULNT1 and exhibited greater myoelectric activity in the biceps brachii than healthy women (MD (95% CI): 21,26 (10,83-31,70)). No differences between the axillary lymph node dissection and sentinel lymph node biopsy groups (MD (95% CI): 8,47 (-7,84-24,79)) were found. Myoelectric activity in the triceps brachii was greater in the sentinel lymph node biopsy group (MD (95% CI): 2,70 (-2,06-7,60)). BC survivors exhibited less shoulder and elbow range of motion during ULNT1 than healthy women. Increased upper limb nerve mechanosensitivity in BC survivors was associated with a greater protective muscle response during ULNT1.


title: Characterization of Epitope-Specific Anti-Respiratory Syncytial Virus (Anti-RSV) Antibody Responses after Natural Infection and after Vaccination with Formalin-Inactivated RSV.

text: UNLABELLED Antibodies against the fusion (F) protein of respiratory syncytial virus (RSV) play an important role in the protective immune response to this important respiratory virus. Little is known, however, about antibody levels against multiple F-specific epitopes induced by infection or after vaccination against RSV, while this is important to guide the evaluation of (novel) vaccines. In this study, we analyzed antibody levels against RSV proteins and F-specific epitopes in human sera and in sera of vaccinated and experimentally infected cotton rats and the correlation thereof with virus neutralization. Analysis of human sera revealed substantial diversity in antibody levels against F-, G (attachment)-, and F-specific epitopes between individuals. The highest correlation with virus neutralization was observed for antibodies recognizing prefusion-specific antigenic site Ø. Nevertheless, our results indicate that high levels of antibodies targeting other parts of the F protein can also mediate a potent antiviral antibody response. In agreement, sera of experimentally infected cotton rats contained high neutralizing activity despite lacking antigenic site Ø-specific antibodies. Strikingly, vaccination with formalin-inactivated RSV (FI-RSV) exclusively resulted in the induction of poorly neutralizing antibodies against postfusion-specific antigenic site I, although antigenic sites I, II, and IV were efficiently displayed in FI-RSV. The apparent immunodominance of antigenic site I in FI-RSV likely explains the low levels of neutralizing antibodies upon vaccination and challenge and may play a role in the vaccination-induced enhancement of disease observed with such preparations. IMPORTANCE RSV is an importance cause of hospitalization of infants. The development of a vaccine against RSV has been hampered by the disastrous results obtained with FI-RSV vaccine preparations in the 1960s that resulted in vaccination-induced enhancement of disease. To get a better understanding of the antibody repertoire induced after infection or after vaccination against RSV, we investigated antibody levels against fusion (F) protein, attachment (G) protein, and F-specific epitopes in human and animal sera. The results indicate the importance of prefusion-specific antigenic site Ø antibodies as well as of antibodies targeting other epitopes in virus neutralization. However, vaccination of cotton rats with FI-RSV specifically resulted in the induction of weakly neutralizing, antigenic site I-specific antibodies, which may play a role in the enhancement of disease observed after vaccination with such preparations.


Why G6PD Deficiency Should Be Screened Before COVID-19 Treatment With Hydroxychloroquine?


title: Variation in critical care services across North America and Western Europe.

text: OBJECTIVE Critical care represents a large percentage of healthcare spending in developed countries. Yet, little is known regarding international variation in critical care services. We sought to understand differences in critical care delivery by comparing data on the distribution of services in eight countries. DESIGN Retrospective review of existing national administrative data. We identified sources of data in each country to provide information on acute care hospitals and beds, intensive care units and beds, intensive care admissions, and definitions of intensive care beds. Data were all referenced and from as close to 2005 as possible. SETTING United States, France, United Kingdom, Canada, Belgium, Germany, The Netherlands, and Spain. PATIENTS Not available. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS No standard definition existed for acute care hospital or intensive care unit beds across countries. Hospital beds varied three-fold from 221/100,000 population in the United States to 593/100,000 in Germany. Adult intensive care unit beds also ranged seven-fold from 3.3/100,000 population in the United Kingdom to 24.0/100,000 in Germany. Volume of intensive care unit admissions per year varied ten-fold from 216/100,000 population in the United Kingdom to 2353/100,000 in Germany. The ratio of intensive care unit beds to hospital beds was highly correlated across all countries except the United States (r = .90). There was minimal correlation between the number of intensive care unit beds per capita and health care spending per capita (r = .45), but high inverse correlation between intensive care unit beds and hospital mortality for intensive care unit patients across countries (r = -.82). CONCLUSIONS Absolute critical care services vary dramatically between countries with wide differences in both numbers of beds and volume of admissions. The number of intensive care unit beds per capita is not strongly correlated with overall health expenditure, but does correlate strongly with mortality. These findings demonstrate the need for critical care data from all countries, as they are essential for interpretation of studies, and policy decisions regarding critical care services.


title: Transgene expression in the genome of Middle East respiratory syndrome coronavirus based on a novel reverse genetics system utilizing Red-mediated recombination cloning.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a high-priority pathogen in pandemic preparedness research. Reverse genetics systems are a valuable tool to study viral replication and pathogenesis, design attenuated vaccines and create defined viral assay systems for applications such as antiviral screening. Here we present a novel reverse genetics system for MERS-CoV that involves maintenance of the full-length viral genome as a cDNA copy inserted in a bacterial artificial chromosome amenable to manipulation by homologue recombination, based on the bacteriophage λ Red recombination system. Based on a full-length infectious MERS-CoV cDNA clone, optimal genomic insertion sites and expression strategies for GFP were identified and used to generate a reporter MERS-CoV expressing GFP in addition to the complete set of viral proteins. GFP was genetically fused to the N-terminal part of protein 4a, from which it is released during translation via porcine teschovirus 2A peptide activity. The resulting reporter virus achieved titres nearly identical to the wild-type virus 48 h after infection of Vero cells at m.o.i. 0.001 (1×105 p.f.u. ml-1 and 3×105 p.f.u. ml-1, respectively), and allowed determination of the 50 % inhibitory concentration for the known MERS-CoV inhibitor cyclosporine A based on fluorescence readout. The resulting value was 2.41 µM, which corresponds to values based on wild-type virus. The reverse genetics system described herein can be efficiently mutated by Red-mediated recombination. The GFP-expressing reporter virus contains the full set of MERS-CoV proteins and achieves wild-type titres in cell culture.


title: Thoracoscopic repair of recurrent bochdalek diaphragmatic hernias in children.

text: BACKGROUND Recurrent herniation is a well-known complication following the initial repair of congenital diaphragmatic hernias (CDHs). The role of minimally invasive surgical techniques in recurrent CDH remains undefined. The purpose of this study was to evaluate our early experience with thoracoscopic repair compared with traditional open repair in children with recurrent CDH. SUBJECTS AND METHODS We retrospectively reviewed all recurrent Bochdalek CDH cases (n=24) managed at a single tertiary-care referral center between January 1990 and March 2011. Children who underwent thoracoscopic repair for recurrent CDH were identified, and their data were compared by the unpaired t test and the two-sided Fisher's exact test, as appropriate, with those of children who underwent open repair. Significance was defined as P<.05. RESULTS Thoracoscopic repair was attempted in 6 (25%) children with recurrent CDH. Four (67%) repairs were successfully completed without conversion to an open procedure. The mean age at thoracoscopic repair was 11.5 months (range, 8.1-16.1 months). The mean operative time was 191 minutes (range, 94-296 minutes), and all children were extubated within 24 hours. The mean hospital length of stay was 3.75 days (range, 1-6 days). There were no deaths or subsequent recurrences after a mean follow-up of 26.5 months (range, 14.3-41.3 months). There were no statistical differences in any of the measured outcome variables when compared with the open repair group. CONCLUSIONS Our initial experience suggests that thoracoscopic repair is a feasible alternative to open repair in selected children with recurrent Bochdalek diaphragmatic hernias.


title: Application of Topic Modeling to Tweets as the Foundation for Health Disparity Research for COVID-19.

text: We randomly extracted publicly available Tweets mentioning COVID-19 related terms (n=2,558,474 Tweets) from Tweet corpora collected daily using an API from Jan 21st to May 3rd, 2020. We applied a clustering algorithm to publicly available Tweets authored by African Americans (n=1,763) to detect topics and sentiment applying natural language processing (NLP). We visualized fifteen topics (four themes) using network diagrams (Newman modularity 0.74). Compared to the COVID-19 related Tweets authored by others, positive sentiments, cohesively encouraging online discussions (e.g., Black strong 27.1%, growing up Blacks 22.8%, support Black business 17.0%, how to build resilience 7.8%), and COVID-19 prevention behaviors (e.g., masks 4.7%, encouraging social distancing 9.4%) were uniquely observed in African American Twitter communities. Application of topic modeling techniques to streaming social media Twitter provides the foundation for research team insights regarding information and future virtual based intervention and social media based health disparity research for COVID-19.


title: Multicenter, Prospective, Longitudinal Study of the Recurrence, Surgical Site Infection, and Quality of Life After Contaminated Ventral Hernia Repair Using Biosynthetic Absorbable Mesh: The COBRA Study.

text: OBJECTIVE The aim of the study was to evaluate biosynthetic absorbable mesh in single-staged contaminated (Centers for Disease Control class II and III) ventral hernia (CVH) repair over 24 months. BACKGROUND CVH has an increased risk of postoperative infection. CVH repair with synthetic or biologic meshes has reported chronic biomaterial infections and high hernia recurrence rates. METHODS Patients with a contaminated or clean-contaminated operative field and a hernia defect at least 9 cm had a biosynthetic mesh (open, sublay, retrorectus, or intraperitoneal) repair with fascial closure (n = 104). Endpoints included overall Kaplan-Meier estimates for hernia recurrence and postoperative wound infection rates at 24 months, and the EQ-5D and Short Form 12 Health Survey (SF-12). Analyses were conducted on the intent-to-treat population, and health outcome measures evaluated using paired t tests. RESULTS Patients had a mean age of 58 years, body mass index of 28 kg/m, 77% had contaminated wounds, and 84% completed 24-months follow-up. Concomitant procedures included fistula takedown (n = 24) or removal of infected previously placed mesh (n = 29). Hernia recurrence rate was 17% (n = 16). At the time of CVH repair, intraperitoneal placement of the biosynthetic mesh significantly increased the risk of recurrences (P ≤ 0.04). Surgical site infections (19/104) led to higher risk of recurrence (P < 0.01). Mean 24-month EQ-5D (index and visual analogue) and SF-12 physical component and mental scores improved from baseline (P < 0.05). CONCLUSIONS In this prospective longitudinal study, biosynthetic absorbable mesh showed efficacy in terms of long-term recurrence and quality of life for CVH repair patients and offers an alternative to biologic and permanent synthetic meshes in these complex situations.


title: A 14-year Prospective Study of Human Coronavirus Infections in Hospitalized Children: Comparison With Other Respiratory Viruses.

text: BACKGROUND Human coronaviruses (HCoVs) have been recognized as causative agents of respiratory tract infections.Our aim was to describe HCoV infections in hospitalized children in a prospective surveillance study for 14 years and compare them with other respiratory viruses. METHODS As a part of an ongoing prospective study to identify the etiology of viral respiratory infections in Spain, we performed the analysis of HCoV infections in children hospitalized in a secondary hospital in Madrid, between October 2005 and June 2018. Clinical data of HCoV patients were compared with those infected by rhinovirus, respiratory syncytial virus and influenza. RESULTS The study population consisted of 5131 hospitalizations for respiratory causes in children. A total of 3901 cases (75.9%) had a positive viral identification and 205 cases (4.1%) were positive for HCoV. Only 41 cases (20%) of HCoV infection were detected as single infections. Episodes of recurrent wheezing were the most common diagnosis, and 112 children (54%) had hypoxia. Clinical data in HCoV cases were similar to those associated with rhinovirus; however, patients with HCoV were younger. Other viruses were associated with hypoxia more frequently than cases with HCoV; high fever was more common in influenza infections and bronchiolitis in respiratory syncytial virus group. Although a slight peak of circulation appears mostly in winter, HCoV has been detected throughout the year as well. CONCLUSIONS HCoV infections represent a small fraction of respiratory infections that require hospitalization in children and their characteristics do not differ greatly from other respiratory viral infections.


title: GANP-mediated recruitment of activation-induced cytidine deaminase to cell nuclei and to immunoglobulin variable region DNA.

text: AID (activation-induced cytidine deaminase) catalyzes transcription-dependent deamination of C --> U in immunoglobulin variable (IgV) regions to initiate somatic hypermutation (SHM) in germinal center B-cells. SHM is essential in generating high affinity antibodies. Here we show that when coexpressed with GANP (germinal center-associated nuclear protein) in COS-7 cells, AID is transported from the cytoplasm and concentrated in the nucleus. GANP forms a complex with AID in cotransfected cells in vivo and in vitro. We have isolated AID mutants that bind with reduced affinity to GANP compared with wild type AID. One of these mutants, AID (D143A) binds GANP with a 10-fold lower affinity compared with wild type AID yet retains substantial C-deamination activity in vitro. Mutant AID (D143A) remains localized predominantly in the cytoplasm when coexpressed with GANP. Exogenous expression of GANP in Ramos B-cells promotes binding of AID to IgV DNA and mRNA and increases SHM frequency. These data suggest that GANP may serve as an essential link required to transport AID to B-cell nuclei and to target AID to actively transcribed IgV regions.


New WHO guidelines on emergency triage assessment and treatment.


title: Quantitative modeling of virus evolutionary dynamics and adaptation in serial passages using empirically inferred fitness landscapes.

text: We describe a stochastic virus evolution model representing genomic diversification and within-host selection during experimental serial passages under cell culture or live-host conditions. The model incorporates realistic descriptions of the virus genotypes in nucleotide and amino acid sequence spaces, as well as their diversification from error-prone replications. It quantitatively considers factors such as target cell number, bottleneck size, passage period, infection and cell death rates, and the replication rate of different genotypes, allowing for systematic examinations of how their changes affect the evolutionary dynamics of viruses during passages. The relative probability for a viral population to achieve adaptation under a new host environment, quantified by the rate with which a target sequence frequency rises above 50%, was found to be most sensitive to factors related to sequence structure (distance from the wild type to the target) and selection strength (host cell number and bottleneck size). For parameter values representative of RNA viruses, the likelihood of observing adaptations during passages became negligible as the required number of mutations rose above two amino acid sites. We modeled the specific adaptation process of influenza A H5N1 viruses in mammalian hosts by simulating the evolutionary dynamics of H5 strains under the fitness landscape inferred from multiple sequence alignments of H3 proteins. In light of comparisons with experimental findings, we observed that the evolutionary dynamics of adaptation is strongly affected not only by the tendency toward increasing fitness values but also by the accessibility of pathways between genotypes constrained by the genetic code.


title: Isolation of chicken astrovirus from specific pathogen-free chicken embryonated eggs.

text: Astroviruses have been associated with enteric disorders in many animal species, including chickens. Here, we describe the isolation, propagation, and pathological characteristics of chicken astrovirus (CAstV) in specific pathogen free (SPF) chicken embryonated eggs (CEE) from chickens with diarrhea and runting-stunting syndrome. The CEE were inoculated via the yolk sac route. Viral confirmation was carried out using PCR techniques and transmission electron microscopy negative staining with ammonium molybdate. The intestinal contents were screened for CAstV, and differential diagnostic testing was performed for avian nephritis virus, avian rotavirus, avian reovirus, chicken parvovirus, infectious bronchitis virus, and fowl adenovirus Group I to detect co-infection with other infectious agents. Seven- or 14-day-old CEEs presented with hemorrhages, edema, a gelatinous aspect, deformities, and dwarfism. The supporting membranes did not show any alterations. Here, we have described the isolation of CAstV and its pathological characteristics in SPF CEE.


title: Single-incision versus conventional laparoscopic sigmoid colectomy: a case-matched series.

text: BACKGROUND Single-incision laparoscopic surgery is an emerging modality that has proven to be safe and feasible for colon resection in multiple case reports and series. Nonetheless, comparative analyses with established techniques are limited in the published literature. We evaluated the efficacy of single-incision laparoscopic colectomy (SILC) for the treatment of sigmoid disease through a matched-case comparison with conventional laparoscopic colectomy (CLC). METHODS Twenty patients who underwent single-incision laparoscopic sigmoid resection for benign or malignant disease between July 2009 and September 2010 were matched to patients who underwent conventional laparoscopic sigmoid colectomy. Demographic, intraoperative, and postoperative data were assessed. RESULTS Twenty SILC and CLC cases each were paired based on gender (p < 1.0), age (p < 0.47), pathology (p < 1.0), and surgical procedure (p < 1.0). Ten patients (50%) in the SILC group and eight patients (40%) in the CLC group had a history of prior abdominal surgery (p < 0.53). There were no conversions to open surgery; however, one SILC procedure (5%) required conversion to CLC (p < 0.31). There was no significant difference in mean operating time between groups (p < 0.80). Mean estimated blood loss was significantly lower for SILC compared to CLC (p < 0.007). Mean lymph node extraction was comparable between groups in the subset of patients with malignant disease (p < 0.68). Two postoperative complications were encountered in each group. The mean length of hospital stay for SILC and CLC was 3.2 ± 1.0 and 3.8 ± 2.1 days, respectively (p < 0.25). There were no readmissions or reoperative interventions in either group. CONCLUSION Compared with conventional laparoscopic technique, single-incision laparoscopic surgery results in similar intraoperative and postoperative outcomes. The technique avoids use of multiple trocar sites and may safely be performed in patients with a history of previous abdominal surgery while maintaining a short length of hospital stay and low complication rate.


Tackling the threat of COVID-19 in Africa: an urgent need for practical planning.


title: Predictive performance of a new pharmacokinetic model for propofol in underweight patients during target-controlled infusion.

text: BACKGROUND In a previous study, the modified Marsh and Schnider models respectively showed negatively- and positively-biased predictions in underweight patients. To overcome this drawback, we developed a new pharmacokinetic propofol model-the Choi model-for use in underweight patients. In the present study, we evaluated the predictive performance of the Choi model. METHODS Twenty underweight patients undergoing elective surgery received propofol via TCI using the Choi model. The target effect-site concentrations (Ces) of propofol were 2.5, 3, 3.5, 4, 4.5, and 2 μg/mL. Arterial blood samples were obtained at least 10 minutes after achieving pseudo-steady-state. Predicted propofol concentrations with the modified Marsh, Schnider, and Eleveld pharmacokinetic models were obtained by simulation (Asan pump, version 2.1.3; Bionet Co. Ltd., Seoul, Korea). The predictive performance of each model was assessed by calculation of four parameters: inaccuracy, divergence, bias, and wobble. RESULTS A total of 119 plasma samples were used to determine the predictive performance of the Choi model. Our evaluation showed that the pooled median (95% CI) bias and inaccuracy were 4.0 (-4.2 to 12.2) and 23.9 (17.6-30.3), respectively. The pooled biases and inaccuracies of the modified Marsh, Schnider, and Eleveld models were clinically acceptable. However, the modified Marsh and Eleveld models consistently produced negatively biased predictions in underweight patients. In particular, the Schnider model showed greater inaccuracy at a target Ce ≥ 3 µg/mL. CONCLUSION The new propofol pharmacokinetic model (the Choi model) developed for underweight patient showed adequate performance for clinical use.


title: Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China.

text: UNLABELLED Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been identified in bats in China, Europe, and Africa, most have a genetic organization significantly distinct from human/civet SARS CoVs in the receptor-binding domain (RBD), which mediates receptor binding and determines the host spectrum, resulting in their failure to cause human infections and making them unlikely progenitors of human/civet SARS CoVs. Here, a viral metagenomic analysis of 268 bat rectal swabs collected from four counties in Yunnan Province has identified hundreds of sequences relating to alpha- and betacoronaviruses. Phylogenetic analysis based on a conserved region of the RNA-dependent RNA polymerase gene revealed that alphacoronaviruses had diversities with some obvious differences from those reported previously. Full genomic analysis of a new SARS-like CoV from Baoshan (LYRa11) showed that it was 29,805 nucleotides (nt) in length with 13 open reading frames (ORFs), sharing 91% nucleotide identity with human/civet SARS CoVs and the most recently reported SARS-like CoV Rs3367, while sharing 89% with other bat SARS-like CoVs. Notably, it showed the highest sequence identity with the S gene of SARS CoVs and Rs3367, especially in the RBD region. Antigenic analysis showed that the S1 domain of LYRa11 could be efficiently recognized by SARS-convalescent human serum, indicating that LYRa11 is a novel virus antigenically close to SARS CoV. Recombination analyses indicate that LYRa11 is likely a recombinant descended from parental lineages that had evolved into a number of bat SARS-like CoVs. IMPORTANCE Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been discovered in bats worldwide, there are significant different genic structures, particularly in the S1 domain, which are responsible for host tropism determination, between bat SARS-like CoVs and human SARS CoVs, indicating that most reported bat SARS-like CoVs are not the progenitors of human SARS CoV. We have identified diverse alphacoronaviruses and a close relative (LYRa11) to SARS CoV in bats collected in Yunnan, China. Further analysis showed that alpha- and betacoronaviruses have different circulation and transmission dynamics in bat populations. Notably, full genomic sequencing and antigenic study demonstrated that LYRa11 is phylogenetically and antigenically closely related to SARS CoV. Recombination analyses indicate that LYRa11 is a recombinant from certain bat SARS-like CoVs circulating in Yunnan Province.


title: Impact of lockdown measures during COVID-19 on air quality- A case study of India.

text: A novel infectious coronavirus disease (COVID-19) identified in late 2019 has now been labelled as a global pandemic by World Health Organization (WHO). The COVID-19 outbreak has shown some positive impacts on the natural environment. In present work, India is taken as a case study to evaluate the effect of lockdown on air quality of three Indian cities. The variation in concentration of key air pollutants including [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] during two phases, pre-lockdown and post-lockdown phases, was analysed. The concentration of [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] reduced by 55%, 49%, 60% and 19%, and 44%, 37%, 78% and 39% for Delhi and Mumbai, respectively, during post-lockdown phase. Overall, the findings in present study may provide confidence to the stakeholders involved in air quality policy development that a significant improvement in air quality can be achieved in future if better pollution control plans are strictly executed.