title: Smell and taste dysfunctions in COVID-19 are associated with younger age in ambulatory settings - a multicenter cross-sectional study.

text: BACKGROUND AND OBJECTIVE Since China's initial anecdotal reports of coronavirus disease 2019 (COVID-19), there have been a growing number of studies describing smell and/or taste dysfunction (STD). Objective: The aim was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers. METHODS A multicenter cross-sectional study on SARS-CoV-2 positive patients (n=846) and controls (n=143) from 15 Spanish Hospitals. Data of STD with an in-person survey was collected prospectively. STD severity was categorized by visual analogue scale. STD onset time, recovery rate, time to recovery, hospital admission, pneumonia diagnosis, comorbidities, smoking and symptoms were analyzed. RESULTS STD were at least 2-fold more common in COVID-19-positive compared to controls. In COVID-19-positive, hospitalized patients were older, with lower frequency of STD and recovered earlier than out-patients. Stratified analysis by severity of STD showed that more than a half of COVID-19 subjects presented severe loss of smell (53.7%) or taste (52.2%), in >90% this impairment was of both senses. In the multivariate analysis, an older age (>60yo), being hospitalized and an increased level of C-reactive protein were factors associated with a better sense of smell and/or taste. COVID-19-positive patients reported improvement of smell (45.6%) and taste (46.1%) at the time of the survey, 90.6% in less than two weeks' post-infection. CONCLUSIONS STD is a common symptom in COVID-19, and mainly present in young and non-hospitalized patients. More studies are needed to evaluate the follow-up of the chemosensory impairment.


title: Coronavirus Disease (COVID-19): A Machine Learning Bibliometric Analysis.

text: BACKGROUND/AIM To evaluate the research trends in coronavirus disease (COVID-19). MATERIALS AND METHODS A bibliometric analysis was performed using a machine learning bibliometric methodology. Information regarding publication outputs, countries, institutions, journals, keywords, funding and citation counts was retrieved from Scopus database. RESULTS A total of 1883 eligible papers were returned. An exponential increase in the COVID-19 publications occurred in the last months. As expected, China produced the majority of articles, followed by the United States of America, the United Kingdom and Italy. There is greater collaboration between highly contributing authors and institutions. The "BMJ" published the highest number of papers (n=129) and "The Lancet" had the most citations (n=1439). The most ubiquitous topic was COVID-19 clinical features. CONCLUSION This bibliometric analysis presents the most influential references related to COVID-19 during this time and could be useful to improve understanding and management of COVID-19.


title: Reusable and Recyclable Graphene Masks with Outstanding Superhydrophobic and Photothermal Performances.

text: The 2019 coronavirus outbreak (COVID-19) is affecting over 210 countries and territories, and it is spreading mainly by respiratory droplets. The use of disposable surgical masks is common for patients, doctors, and even the general public in highly risky areas. However, the current surgical masks cannot self-sterilize in order to reuse or be recycled for other applications. The resulting high economic and environmental costs are further damaging societies worldwide. Herein, we reported a unique method for functionalizing commercially available surgical masks with outstanding self-cleaning and photothermal properties. A dual-mode laser-induced forward transfer method was developed for depositing few-layer graphene onto low-melting temperature nonwoven masks. Superhydrophobic states were observed on the treated masks' surfaces, which can cause the incoming aqueous droplets to bounce off. Under sunlight illumination, the surface temperature of the functional mask can quickly increase to over 80 °C, making the masks reusable after sunlight sterilization. In addition, this graphene-coated mask can be recycled directly for use in solar-driven desalination with outstanding salt-rejection performance for long-term use. These roll-to-roll production-line-compatible masks can provide us with better protection against this severe virus. The environment can also benefit from the direct recycling of these masks, which can be used for desalinating seawater.


title: The '-omics' revolution and oesophageal adenocarcinoma.

text: Oesophageal adenocarcinoma (OAC) is the eighth most common cancer type worldwide with a dismal 5-year survival. Barrett oesophagus, the replacement of the normal squamous epithelia with glandular cells, is the first step in the pathway towards OAC. Although most patients with OAC present de novo, the presence of the easily detectable OAC precursor lesion, Barrett oesophagus, enables the possibility of early detection of high-risk patients who are more likely to progress. Currently, identification of high-risk patients depends on histopathological assessment of dysplasia with no regards to molecular pathogenesis. In the future, screening and risk stratification initiatives for Barrett oesophagus that incorporate molecular profiles might permit improved early diagnosis and intervention strategies with the possibility of preventing OAC. For the majority of patients presenting de novo at an advanced stage, combining so-called -omics datasets with current clinical staging algorithms might enable OACs to be better classified according to distinct molecular programmes, thereby leading to better targeted treatment strategies as well as cancer monitoring regimes. This Review discusses how the latest advances in -omics technologies have improved our understanding of the development and biology of OAC, and how this development might alter patient management in the future.


title: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2.

text: The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (KD of 39 and 12 nM, respectively) and block its interaction with ACE2. Single-particle cryo-EM revealed that both nanobodies bind to all three RBDs in the spike trimer. Crystal structures of each nanobody-RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD-ACE2 interaction. Nanobody-Fc fusions showed neutralizing activity against SARS-CoV-2 (4-6 nM for H11-H4, 18 nM for H11-D4) and additive neutralization with the SARS-CoV-1/2 antibody CR3022.


title: Estimating the Burden of Pandemic Infectious Disease: The Case of the Second Wave of Pandemic Influenza H1N1 in Forsyth County, North Carolina.

text: BACKGROUND Understanding the burden of influenza A(H1N1)pdm09 virus during the second wave of 2009-2010 is important for future pandemic planning. METHODS Persons who presented to the emergency department (ED) or were hospitalized with fever and/or acute respiratory symptoms at the academic medical center in Forsyth County, North Carolina were prospectively enrolled and underwent nasal/throat swab testing for influenza A(H1N1)pdm09. Laboratory-confirmed cases of influenza A(H1N1)pdm09 virus identified through active surveillance were compared by capture-recapture analysis to those identified through independent, passive surveillance (physician-ordered influenza testing). This approach estimated the number of total cases, including those not captured by either surveillance method. A second analysis estimated the total number of influenza A(H1N1)pdm09 cases by multiplying weekly influenza percentages determined via active surveillance by weekly counts of influenza-associated discharge diagnoses from administrative data. Market share adjustments were used to estimate influenza A(H1N1)pdm09 virus ED visits or hospitalizations per 1,000 residents. RESULTS Capture-recapture analysis estimated that 753 residents (95% confidence interval [CI], 424-2,735) with influenza A(H1N1)pdm09 virus were seen in the academic medical center from September 2009 through mid-April 2010; this result yielded an estimated 4.7 (95% CI, 2.6-16.9) influenza A(H1N1)pdm09 virus ED visits or hospitalizations per 1,000 residents. Similarly, 708 visits were estimated using weekly influenza percentages and influenza-associated discharge diagnoses, yielding an estimated 4.4 influenza A(H1N1)pdm09 virus ED visits or hospitalizations per 1,000 residents. CONCLUSION This study demonstrates that the burden of influenza A(H1N1)pdm09 virus in ED and inpatient settings by capture-recapture analysis was 4-5 per 1,000 residents; this rate was approximately 8-fold higher than that detected by physician-ordered influenza testing.


title: Laparoscopic long sleeve pancreaticogastrostomy (LPG): a novel pancreatic anastomosis following central pancreatectomy.

text: BACKGROUND Central pancreatectomy (CP) is preferred to distal pancreatectomy (DP) for the excision of benign tumours at the neck or body of the pancreas, in order to preserve pancreatic function and the spleen. However, the pancreaticoenterostomy is technically difficult to perform laparoscopically and the postoperative pancreatic fistula (POPF) rate is high. METHODS A novel laparoscopic reconstruction of the pancreatic stump during CP is described, the laparoscopic long sleeve pancreaticogastrostomy (LPG). RESULTS Two males and two females with a median age of 49 years had a laparoscopic CP with LPG. After a median follow-up of 27.5 months, there was no mortality. One patient had a grade A POPF, managed conservatively. CONCLUSIONS The LPG is a safe and technically less demanding method to reconstruct pancreatic drainage laparoscopically.


title: Hand-assisted laparoscopic colorectal surgery.

text: The use of laparoscopic techniques in the treatment of colorectal diseases was first described in the early 1990s. Even though its clinical benefits have been well documented, laparoscopic colorectal surgery has been slow to gain adoption in the surgical community, given its technical demands. To help overcome these challenges while preserving the clinical benefits derived from a minimally invasive approach, hand-assisted laparoscopic surgery (HALS) was proposed. HALS can decrease the learning curve by restoring tactile sensation and improving proprioception, and it may be more accessible for surgeons already in practice. A meta-analysis of the 3 published RCTs comparing hand-assisted laparoscopic to conventional laparoscopic colorectal resection showed a significantly lower rate of conversion in the hand-assist patients, while morbidity rates were equivalent. The meta-analysis further indicated that short-term postoperative benefits of conventional laparoscopic colectomies were preserved and costs were likely to be offset by reduced operative time and specific need of laparoscopic equipment. HALS represents a valuable option for performing colorectal resections.


title: Environmental safety: Air pollution while using MIRUS™ for short-term sedation in the ICU.

text: BACKGROUND MIRUS™ is a device for target-controlled inhalational sedation in the ICU in combination with use of isoflurane, or sevoflurane, or desflurane. The feasibility of this device has recently been proven; however, ICU staff exposure may restrict its application. We investigated ICU ambient room pollution during daily work to estimate ICU personnel exposure while using MIRUS™. METHODS This observational study assessed pollution levels around 15 adult surgical patients who received volatile anaesthetics-based sedation for a median of 11 hours. Measurements were performed by photoacoustic gas monitoring in real-time at different positions near the patient and in the personnel's breathing zone. Additionally, the impact of the Clean Air™ open reservoir scavenging system on volatile agent pollution was evaluated. RESULTS Baseline concentrations [ppm] during intervention and rest periods were isoflurane c ¯ mean = 0.58 ± 0.49, c ¯ max = 5.72; sevoflurane c ¯ mean = 0.22 ± 0.20, c ¯ max = 7.93; and desflurane c ¯ mean = 0.65 ± 0.57, c ¯ max = 6.65. Refilling MIRUS™ with liquid anaesthetic yielded gas concentrations of c ¯ mean = 2.18 ± 1.48 ppm and c ¯ max = 13.03 ± 9.37 ppm in the personnel's breathing zone. Air pollution in the patient's room was approximately five times higher without a scavenging system. CONCLUSION Ambient room pollution was minimal in most cases, and the measured values were within or below the recommended exposure limits. Caution should be taken during refilling of the MIRUS™ system, as this was accompanied by higher pollution levels. The combined use of air-conditioning and gas scavenging systems is strongly recommended.


title: Hepatoprotective effect and its possible mechanism of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced chronic liver hepatotoxicity in rats.

text: ETHNOPHARMACOLOGICAL RELEVANCE Coptidis rhizoma is traditionally used for heat-clearing and toxic-scavenging and it belongs to liver meridian in Chinese medicine practice. Clinically, Coptidis rhizoma can be used for hepatic and biliary disorders, yet details in the therapies of liver diseases and underlying mechanism(s) remain unclear. Our previous study demonstrated that Coptidis rhizoma aqueous extract (CRAE) against CCl(4)-induced acute liver damage was related to antioxidant property. In the present study, the protection of CRAE on chronic liver damage induced by carbon tetrachloride (CCl(4)) in rats and its related mechanism were explored. MATERIALS AND METHODS The CCl(4)-induced chronic liver damage model was established, and CRAE's protective effect was examined. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, serum and liver superoxide dismutase (SOD) activity were then measured. The histological changes were observed under microscopy and then computed in numerical score. The normal or damaged cells were isolated and related signaling pathway was evaluated. RESULT Serum AST and ALT activities were significantly decreased in rats treated with different doses of CRAE, indicating its protective effect against CCl(4)-induced chronic liver damage. Observation on serum SOD activity revealed that CRAE might act as an anti-oxidant agent against CCl(4)-induced chronic oxide stress. Histological study supported these observations. Erk1/2 inhibition may take part into CRAE's effect on preventing hepatocyte from apoptosis when exposed to oxidative stress. CONCLUSION CRAE showed protective effect against CCl(4)-induced chronic liver damage in rats and its potential as an agent in the treatment of chronic liver diseases by protecting hepatocyte from injury.


Atypical pneumonia diagnosed as COVID-19 by serologic test (patient #1 in Poland).


title: Lockean superaddition and Lockean humility.

text: This paper offers a new approach to an old debate about superaddition in Locke. Did Locke claim that some objects have powers that are unrelated to their natures or real essences? The question has split commentators. Some (Wilson, Stuart, Langton) claim the answer is yes and others (Ayers, Downing, Ott) claim the answer is no. This paper argues that both of these positions may be mistaken. I show that Locke embraced a robust epistemic humility. This epistemic humility includes ignorance of the real essences of bodies, of the causal processes underlying the production of natural phenomena, and of God's method of creation. I show how this epistemic humility offers strong support for an agnostic response to the question of superaddition. Locke did not intend to claim that bodies either do or do not have properties unrelated to their real essences. Instead, his primary goal in discussing the topic was to emphasize the strict limits to human knowledge.


title: [Interpretation of "Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection by the National Health Commission (Trial Version 5)"].

text: 国家卫生健康委员会（以下简称卫健委）发布了新型冠状病毒肺炎诊疗指南（试行第五版），随着对疾病不断地认识和了解，诊疗指南也随之进行修订。诊疗指南（以下简称指南）的发布指导我们认识疾病、治疗疾病、预防疾病。那么，卫健委发布的第五版指南较第四版指南具体更新了哪些内容，本文进行了解读。.


Coronavirus Disease 2019 (COVID-19) and Cardiac Injury-Reply.


title: Management of Breast Cancer During the COVID-19 Pandemic: A Stage- and Subtype-Specific Approach.

text: The COVID-19 pandemic has rapidly changed delivery of cancer care. Many nonurgent surgeries are delayed to preserve hospital resources, and patient visits to health care settings are limited to reduce exposure to SARS-CoV-2. Providers must carefully weigh risks and benefits of delivering immunosuppressive therapy during the pandemic. For breast cancer, a key difference is increased use of neoadjuvant systemic therapy due to deferral of many breast surgeries during the pandemic. In some cases, this necessitates increased use of genomic tumor profiling on core biopsy specimens to guide neoadjuvant therapy decisions. Breast cancer treatment during the pandemic requires multidisciplinary input and varies according to stage, tumor biology, comorbidities, age, patient preferences, and available hospital resources. We present here the Johns Hopkins Women's Malignancies Program approach to breast cancer management during the COVID-19 pandemic. We include algorithms based on tumor biology and extent of disease that guide management decisions during the pandemic. These algorithms emphasize medical oncology treatment decisions and demonstrate how we have operationalized the general treatment recommendations during the pandemic proposed by national groups, such as the COVID-19 Pandemic Breast Cancer Consortium. Our recommendations can be adapted by other institutions and medical oncology practices in accordance with local conditions and resources. Guidelines such as these will be important as we continue to balance treatment of breast cancer against risk of SARS-CoV-2 exposure and infection until approval of a vaccine.


title: Structure-based virtual screening and experimental validation of the discovery of inhibitors targeted towards the human coronavirus nucleocapsid protein.

text: Nucleocapsid protein (NP), an essential RNA-binding viral protein in human coronavirus (CoV)-infected cells, is required for the replication and transcription of viral RNA. Recent studies suggested that human CoV NP is a valid target for antiviral drug development. Based on this aspect, structure-based virtual screening targeting nucleocapsid protein (NP) was performed to identify good chemical starting points for medicinal chemistry. The present study utilized structure-based virtual screening against human CoV-OC43 using the Zinc database, which is performed through docking with varying precisions and computational intensities to identify eight potential compounds. The chosen potential leads were further validated experimentally using biophysical means. Surface plasmon resonance (SPR) analysis indicated that one among the potential leads, 6-chloro-7-(2-morpholin-4-yl-ethylamino) quinoxaline-5,8-dione (small-compound H3), exhibited a significant decrease of RNA-binding capacity of NP by more than 20%. The loss of binding activity was manifested as a 20% decrease in the minimum on-rate accompanied with a 70% increase in the maximum off-rate. Fluorescence titration and X-ray crystallography studies indicated that H3 antagonizes the binding between HCoV-OC43 NP and RNA by interacting with the N-terminal domain of the NP. Our findings provide insight into the development of new therapeutics that disrupt the interaction between RNA and viral NP in the HCoV. The discovery of the new compound would be an impetus to design novel NP inhibitors against human CoV.


docid: yfyhkxxs

title: Covid-19: Can France's ethical support units help doctors make challenging decisions?


A Canadian framework for managing prostate cancer during the COVID-19 pandemic: Recommendations from the Canadian Urologic Oncology Group and the Canadian Urological Association.


Promoting Physical Activity During the COVID-19 Pandemic: Implications for Obesity and Chronic Disease Management.


title: Complications of cerebral angiography in children younger than 3 years of age.

text: OBJECT The therapeutic potential for cerebral angiography (CA) in young children is expanding. However, its use in this patient population is limited by presumed higher complication rates among children. Therefore, to improve the accuracy of counseling of the parents/guardians of these patients and to identify modifiable risk factors, the authors evaluated complications after CA in young children. METHODS The authors reviewed data for 309 consecutive cerebral angiograms obtained in 87 children younger than 36 months of age from 2004 to 2010 at a single institution. They analyzed demographics, diagnosis, angiographic findings, and complications. RESULTS The patient population comprised 40 boys and 47 girls; mean age was 14.36 months (range 1-36 months) and mean weight was 10.8 kg (range 3.7-21.0 kg). For 292 of the 309 procedures, intraarterial chemotherapy was administered; the remaining 17 procedures were for vascular malformations, stroke, tumor embolization, and intracranial hemorrhage. The rate of neurological complications was 0.0%. The rate of nonneurological complications was 2.9%: 7 cases of contrast allergy or bronchospasm, 1 groin hematoma (body weight 7 kg), and 1 transient femoral artery occlusion (body weight 10.8 kg). The rate of radiographic complications was 1.3%: 1 case of transient asymptomatic intraarterial dissection and 3 cases of asymptomatic vasospasm. Postprocedural MRI was performed for 33.3% of patients with no evidence of ischemia. There were no delayed complications. Mean follow-up time was 16.6 months. No association was found between complications and age, duration of anesthesia, number of vessels catheterized, size of the sheath, or diagnostic versus interventional procedures. Despite a trend toward a higher rate of complications for patients who weighed less than 15 kg, this finding was not significant (p = 0.35). CONCLUSIONS The rate of complications for CA in young children is comparable to rates reported for older children and lower than rates reported for adults. When appropriately indicated, CA should not be omitted from the therapeutic strategy of children younger than 36 months of age.


A new varietal of DNA interstrand crosslink repair.


[Single port distal pancreatectomy without spleen preserving].


Emergency Medicine Physician Burnout and Wellness in Canada prior to COVID19: A National Survey.


title: Web-Based Surveillance of Illness in Childcare Centers.

text: School absenteeism is an inefficient and unspecific metric for measuring community illness and does not provide surveillance during summertime. Web-based biosurveillance of childcare centers may represent a novel way to efficiently monitor illness outbreaks year-round. A web-based biosurveillance program ( sickchildcare.org ) was created and implemented in 4 childcare centers in a single Michigan county. Childcare providers were trained to report sick children who required exclusion or had parent-reported absences due to illness. Deidentified data on age range, number of illnesses, and illness categories were collected. Weekly electronic reports were sent to the county public health department. Data for reports were gathered beginning in December 2013 and were summarized using descriptive statistics. A total of 385 individual episodes of illness occurred during the study period. Children with reported illness were infants (16%, n = 61), toddlers (38%, n = 148), and preschoolers (46%, n = 176). Illness categories included: fever (30%, n = 116), gastroenteritis (30%, n = 115), influenzalike illness (8%, n = 32), cold without fever (13%, n = 51), rash (7%, n = 26), conjunctivitis (1%, n = 3), ear infection (1%, n = 5), and other (10%, n = 37). The majority of reports were center exclusions (55%, n = 214); others were absences (45%, n = 171). The detection of a gastroenteritis outbreak by web-based surveillance during winter 2013-14 preceded county health reports by 3 weeks; an additional outbreak of hand-foot-mouth disease was detected during June 2014 when standard school-based surveillance was not available. Web-based biosurveillance of illness in childcare centers represents a novel and feasible method to detect disease trends earlier and year-round compared to standard school-based disease surveillance.


title: Impact of COVID -19 on children: special focus on the psychosocial aspect.

text: Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.


NIH move to ax bat coronavirus grant draws fire.


title: An enhancement strategy for integration of population health into medical school education: employing the framework developed by the Healthy People Curriculum Task Force.

text: The authors describe an enhancement strategy for integration of population health content into the medical school curriculum at The Brody School of Medicine at East Carolina University conducted in 2005-2006. The Clinical Prevention and Population Health Curriculum Framework developed by the Healthy People Curriculum Task Force served as the planning template for curriculum analysis. Key to success was the incorporation of population health as a "curriculum enhancement," as opposed to curricular expansion or substitution. Strategies included introduction of a Case-Based Series in Population-Oriented Prevention (C-POP) in the preclinical years; community assessments, home visits, and public health assignments in the family medicine and pediatrics clinical clerkships; and prevention history-taking. The Brody integrated curriculum included a wide range of topics and clinical experiences specific to prevention and population health; however, the coverage was uneven. Hybrid teaching cases were developed from four C-POP cases which were adapted to existing instructional materials. Students learned to define the determinants of health, disease burden in their community settings, and community strengths and obstacles specific to dealing with chronic conditions. Factors contributing to the successful integration of population health included a receptive primary care medical school, use of the Framework, analysis of gaps between the Framework and the existing curriculum, providing enhancements to the existing curriculum, employment of patient cases, and integrating population health into a variety of classroom and community medical learning experiences. This approach, as opposed to a separate and distinct course, seeks to reinforce the interconnectedness of communities, families, and individuals.


title: Integrating nutrition into health systems: What the evidence advocates.

text: There is considerable evidence of positive health and nutrition outcomes resulting from integrating nutrition-specific interventions into health systems; however, current knowledge on establishing and sustaining effective integration of nutrition into health systems is limited. The objective of this review is to map the existing types of integration platforms and review the evidence on integrated health and nutrition programmes' impacts on specific nutrition outcomes. A literature search was conducted, and integrated nutrition programmes were examined through the lens of the six World Health Organization (WHO) building blocks, including the demand side. Forty-five studies were included in this review, outlining the integration of nutrition-specific interventions with various programmes, including integrated community case management and Integrated Management of Childhood Illness, Child Health Days, immunization, early child development, and cash transfers. Limited quantitative data were suggestive of some positive impact on nutrition and non-nutrition outcomes with no adverse effects on primary programme delivery. Through the lens of the six WHO building blocks, service delivery and health workforce were found to be well-integrated, but governance, information systems, finance and supplies and technology were less well-integrated. Integrating nutrition-specific interventions into health systems may ensure efficient service delivery while having an impact on nutrition outcomes. There is no single successful model of integration; it varies according to the context and demands of the particular setting in which integration occurs. There is a need for more well-planned programmes considering all the health systems building blocks to ensure compliance and sustainability.


title: Channel-Inactivating Mutations and Their Revertant Mutants in the Envelope Protein of Infectious Bronchitis Virus.

text: It has been shown previously in the severe acute respiratory syndrome coronavirus (SARS-CoV) that two point mutations, N15A and V25F, in the transmembrane domain (TMD) of the envelope (E) protein abolished channel activity and led to in vivo attenuation. Pathogenicity was recovered in mutants that also regained E protein channel activity. In particular, V25F was rapidly compensated by changes at multiple V25F-facing TMD residues located on a neighboring monomer, consistent with a recovery of oligomerization. Here, we show using infected cells that the same mutations, T16A and A26F, in the gamma-CoV infectious bronchitis virus (IBV) lead to, in principle, similar results. However, IBV E A26F did not abolish oligomer formation and was compensated by mutations at N- and C-terminal extramembrane domains (EMDs). The C-terminal EMD mutations clustered along an insertion sequence specific to gamma-CoVs. Nuclear magnetic resonance data are consistent with the presence of only one TMD in IBV E, suggesting that recovery of channel activity and fitness in these IBV E revertant mutants is through an allosteric interaction between EMDs and TMD. The present results are important for the development of IBV live attenuated vaccines when channel-inactivating mutations are introduced in the E protein.IMPORTANCE The ion channel activity of SARS-CoV E protein is a determinant of virulence, and abolishment of channel activity leads to viral attenuation. E deletion may be a strategy for generating live attenuated vaccines but can trigger undesirable compensatory mechanisms through modifications of other viral proteins to regain virulence. Therefore, a more suitable approach may be to introduce small but critical attenuating mutations. For this, the stability of attenuating mutations should be examined to understand the mechanisms of reversion. Here, we show that channel-inactivating mutations of the avian infectious bronchitis virus E protein introduced in a recombinant virus system are deficient in viral release and fitness and that revertant mutations also restored channel activity. Unexpectedly, most of the revertant mutations appeared at extramembrane domains, particularly along an insertion specific for gammacoronaviruses. Our structural data propose a single transmembrane domain in IBV E, suggesting an allosteric interaction between extramembrane and transmembrane domains.


title: Single port laparoscopic myomectomy with intracorporeal suture-tying and transumbilical morcellation.

text: OBJECTIVE To evaluate the feasibility of single-port laparoscopic myomectomy (SPLM) with intracoporeal suture-tying and transumbilical morcellation. STUDY DESIGN We retrospectively reviewed the medical records of 100 consecutive women who underwent SPLM without any combined surgery between January 2010 and July 2011. The medical records were reviewed and the clinical outcomes were analyzed. Single port entry was established using a wound retractor and a surgical glove. After myoma was enucleated from myometrium, intracorporeal suturing and knot tying was done for myometrium repair. Enucleated myoma was extracted through umbilicus using tissue morcellator. Factors investigated included operation time, blood loss, postoperative hospital stay and complications. RESULTS Mean patient age and BMI were 40.4±7.1 years and 23.1±3.5kg/m(2). Mean diameter of largest myoma and number of myomas were 6.6±2.2 (range 2-12) cm and 1.6±1.2 (range 1-7), respectively. Mean weight of myoma was 136.9±118.4 (range 4-684)g. Type of the main myomas were intramural (80/100), submucosal (5/100), subserosal (12/100), and intraligamentary (3/100). Location of the main myomas were anterior (36/100), posterior (24/100), fundal (30/100), and lateral (10/100). Mean operation time and estimated blood loss were 116.3±36.8min and 94.6±74.5mL. Mean hospital stay after the operation was 2±0.4 days. Conversion to double port surgery (one more trocar inserted on suprapubic site) was occurred in 1 patient due to severe pelvic adhesion. No patient experienced major complications, including bowel, ureter, or bladder injuries, or incisional hernia. CONCLUSION SPLM is safe and acceptable for various myoma sites and sizes up to 12cm. Intracorporeal suture-tying and transumbilical morcellation are key technical points of SPLM.


title: Image-guided thermal ablation of lung malignancies.

text: Primary and secondary lung malignancies are often treated with surgery. Many patients are poor surgical candidates owing to advanced age or medical comorbidities. Alternatives to surgery for localized disease include radiation therapy and the newer treatments known as image-guided thermal ablation. Image-guided thermal ablation involves the use of needlelike applicators that are placed directly into tumors by using imaging guidance. Tumors are destroyed by the application of either intense heat or cold. The specific ablative modalities of radiofrequency ablation, microwave ablation, laser ablation, and cryoablation are reviewed with respect to the various clinical indications for treatment of both primary and secondary lung malignancies.


title: Is Roux-Y binding pancreaticojejunal anastomosis feasible for patients undergoing left pancreatectomy? Results from a prospective randomized trial.

text: BACKGROUND After pancreaticoduodenectomy, the Finnish binding pancreaticojejunal anastomosis (FBPJ) seems to reduce the risk for pancreatic fistula (POPF). Our aim was to investigate whether FBPJ is feasible and prevents the risk for POPF even after left pancreatectomy (LP). PATIENTS AND METHODS 47 consecutive patients underwent LP. 27 patients were recruited on the basis of CT and, of these, 16 patients were randomized on the basis of findings during surgery (transection line must be left of portal vein, as 2-3 cm pancreatic mobilization is required for FBPJ) to receive either Roux-Y FBPJ or hand-sewn closure of the pancreatic remnant. RESULTS Only 34% (16/47) of the patients met the randomization criteria. Clinically significant POPF rate was higher in FBPJ group (60%) compared to thand-sewn closure group (13%; P<0.05). POPF rate in FBPJ group was higher even when compared to all patients with hand-sewn closure (60% versus 37%; P<0.05). Overall, FBPJ was technically feasible for only 28% of patients. CONCLUSION FBPJ cannot be recommended for the routine closure of the pancreatic remnant after LP, as it was not technically achievable in 72% of the cases. Moreover, the technique does not seem to reduce the risk for POPF compared to the hand-sewn closure.


title: From lab to bedside: emerging clinical applications of thymosin alpha 1.

text: BACKGROUND Thymosin alpha(1) (Talpha(1)), a synthetic version of a thymic-derived biological response modifier was the first of the thymosins in clinical use. Talpha(1) is approved in over 35 countries for the treatment of hepatitis B and C, and as an immune stimulant and adjuvant. Talpha(1) is also in late-stage clinical testing in the United States and Europe for hepatitis C and stage IV melanoma. OBJECTIVE/METHODS Novel applications and other recently completed trials point to much broader clinical applications of Talpha(1) in the treatment of life-threatening and chronic diseases, and are the subject of this review. RESULT/CONCLUSIONS The most recent reports of clinical trials with Talpha(1) are pointing to important, hitherto unrecognized, applications in a number of diseases and disorders, including septic shock, acute respiratory distress syndrome, peritonitis, acute cytomegalovirus infection, TB, severe acute respiratory syndrome, and lung infections in critically ill patients. It is also emerging as a promising chemoprotection agent in patients undergoing chemotherapy.


title: Failed Mask Ventilation due to Air Leakage around the Orbit in a Patient with a History of Radical Maxillofacial Surgery with Orbital Exenteration.

text: A 72-year-old male (height: 160 cm, weight: 53 kg) was scheduled to undergo left renal and male with ans uterine tract resection. The patient had previously undergone right radical maxillofacial surgery with orbital exenteration 14 years before the present operation to treat squamous cell carcinoma of the right maxillary sinus, with tumour invasion to the orbital floor. An anaesthesiologist encountered difficulty in performing mask ventilation during the induction of anaesthesia in the patient, despite a good mask fit on the face, because the adhesive tape around the orbit had moved. Urgent endotracheal intubation was successful without desaturation. A postoperative examination revealed that a communication between the nasal cavity and the orbit was visible on computed tomograms obtained nine years before the surgery. The patient felt the air leakage around the adhesive tape. The anaesthesiologist should have removed the adhesive tape to directly observe the lesion and should have realised that the communication might cause difficulty in mask ventilation. Careful examination of the airways using computed tomography and precise interviews may improve the understanding of patients' airways and may help avoid similar events.


title: Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection.

text: UNLABELLED Severe acute respiratory syndrome coronavirus (SARS-CoV) caused an acute human respiratory illness with high morbidity and mortality in 2002-2003. Several studies have demonstrated the role of neutralizing antibodies induced by the spike (S) glycoprotein in protecting susceptible hosts from lethal infection. However, the anti-SARS-CoV antibody response is short-lived in patients who have recovered from SARS, making it critical to develop additional vaccine strategies. SARS-CoV-specific memory CD8 T cells persisted for up to 6 years after SARS-CoV infection, a time at which memory B cells and antivirus antibodies were undetectable in individuals who had recovered from SARS. In this study, we assessed the ability of virus-specific memory CD8 T cells to mediate protection against infection in the absence of SARS-CoV-specific memory CD4 T or B cells. We demonstrate that memory CD8 T cells specific for a single immunodominant epitope (S436 or S525) substantially protected 8- to 10-month-old mice from lethal SARS-CoV infection. Intravenous immunization with peptide-loaded dendritic cells (DCs) followed by intranasal boosting with recombinant vaccinia virus (rVV) encoding S436 or S525 resulted in accumulation of virus-specific memory CD8 T cells in bronchoalveolar lavage fluid (BAL), lungs, and spleen. Upon challenge with a lethal dose of SARS-CoV, virus-specific memory CD8 T cells efficiently produced multiple effector cytokines (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin 2 [IL-2]) and cytolytic molecules (granzyme B) and reduced lung viral loads. Overall, our results show that SARS-CoV-specific memory CD8 T cells protect susceptible hosts from lethal SARS-CoV infection, but they also suggest that SARS-CoV-specific CD4 T cell and antibody responses are necessary for complete protection. IMPORTANCE Virus-specific CD8 T cells are required for pathogen clearance following primary SARS-CoV infection. However, the role of SARS-CoV-specific memory CD8 T cells in mediating protection after SARS-CoV challenge has not been previously investigated. In this study, using a prime-boost immunization approach, we showed that virus-specific CD8 T cells protect susceptible 8- to 10-month-old mice from lethal SARS-CoV challenge. Thus, future vaccines against emerging coronaviruses should emphasize the generation of a memory CD8 T cell response for optimal protection.


title: Real-time observations of the impact of COVID-19 on underwater noise.

text: A slowdown in global trade activity due to COVID-19 has led to a reduction in commercial shipping traffic into the Port of Vancouver. The Ocean Networks Canada observatory system provides researchers real-time access to oceanographic data from a wide range of instruments including hydrophones located along the offshore and inshore approaches to Vancouver. Measurements of power spectral density at 100 Hz from four of these bottom mounted hydrophones are presented, along with AIS data and shipping and trade statistics to assess to what extent the economic impact of COVID-19 can be observed acoustically and in near real-time. The quarterly trend in median weekly noise power in the shipping band of frequencies shows that a reduction in noise commensurate with the economic slowdown has been observed at three of the four hydrophone stations.


title: Long-term outcomes of preoperative docetaxel with cisplatin plus S-1 therapy for gastric cancer with extensive nodal metastasis (JCOG1002).

text: BACKGROUND Preoperative chemotherapy with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis. In the JCOG1002, we added docetaxel to CS (DCS) to further improve long-term outcomes. However, the primary endpoint, clinical response rate (RR), did not reach the expected level (Ito et al. in Gastric Cancer 20:322-31, 2017). Herein, we report our long-term survival results. METHODS Patients with BN and/or PAN metastasis received 2 or 3 cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1 and S-1 at 80 mg/m2 per day for 2 weeks, followed by a 2-week rest) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. RESULTS Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% had both PAN and BN metastasis, and the rest had either PAN (26.4%) or BN (56.6%) metastasis. Among all eligible patients, the 5-year overall survival was 54.9% (95% confidence interval 40.3-67.3%) at the last follow-up in May 2018. Among 44 eligible patients with R0 resection, the 5-year relapse-free survival was 47.7% (95% confidence interval 32.5-61.5%). CONCLUSIONS Adding docetaxel to CS in preoperative chemotherapy for extensive nodal metastasis improved neither short-term outcomes nor long-term survival. Preoperative chemotherapy with CS followed by D2 + PAN dissection and postoperative S-1 remains the standard of care for patients with extensive nodal metastasis.


title: COVID-19: COMO TRANSFORMAR UN VENTILADOR DE NO INVASIVA EN UN VENTILADOR DE CRITICOS

text: Resumen La pandemia del COVID-19 ha hecho estragos, no solo en el número de víctimas fatales sino también en la infraestructura de los hospitales y unidades de cuidados intensivos. El número limitado de respiradores es una preocupación de toda la comunidad dada la demanda masiva y a muy corto plazo de estos equipos. Esta presentación tiene como fin dar soluciones sencillas para ventilar pacientes intubados de modo mandatorio utilizando equipos de ventilación no invasiva. Las soluciones propuestas permiten dos estrategias claras frente al COVID-19: Reemplazar las máquinas de anestesia para disponer de ellas en pacientes. Usar la opción de equipos de ventilación no invasiva para pacientes con COVID-19 a modo de “puente” y a la espera de la liberación de un respirador específico en la unidad de cuidados críticos. Abstract COVID-19 pandemic caused not only many deaths around the world but also made evident technical limitations of hospital and intensive care units (ICU). The growing demand of ICU ventilators in a short lapse of time constitutes one of the main community concerns. The main goal of this communication is to give simple solutions to transform a noninvasive ventilator in an invasive one for intubated patients. The proposal can be applied in two well defined strategies for the COVID-19 pandemic: To replace anesthesia workstations, leaving those machines to be used in patients. To apply this option in COVID-19 patients by way of a therapeutic “bridge”, waiting for the release of a ventilator in the ICU.


title: Angiotensin II downregulates ACE2-mediated enhancement of MMP-2 activity in human cardiofibroblasts.

text: Angiotensin converting enzyme II (ACE2) is a component of the renin-angiotensin system (RAS) that negatively regulates angiotensin II (Ang II). Ang II, in turn, affects the expression of matrix metalloproteinases (MMPs) to induce heart remodeling. The specific mechanisms by which ACE2 regulates MMP-2, however, remain unclear. The aim of this study was to investigate the regulatory relationships between Ang II, ACE2, and MMP-2. ACE2 expression was upregulated and downregulated in human cardiofibroblasts (HCFs) by lentiviral infection. Effects on MMP-2 activity, shed ACE2 activity, extracellular signal-regulated kinase (ERK) signaling pathway, and ADAM metallopeptidase domain 17 (ADAM17) expression were assessed. ACE2 increased MMP-2 activity, and Ang II inhibited this effect through the Ang II type-1 receptor (AT1R) and ERK1/2 signaling pathway. Ang II also reduced the effect of ACE2 on ERK1/2 levels, the activity of shed ACE2, and adam17 expression in HCFs. Additionally, these Ang II-mediated reductions could be attenuated by AT1R antagonist valsartan. In conclusion, these data help to clarify how ACE2 and Ang II interact to regulate MMP-2 and control tissue remodeling in heart disease.


The science of team science: assessing the value of transdisciplinary research.


docid: nrnliehg

title: Diabetes mellitus and carotid artery plaques exhibiting high-intensity signals on MR angiography are related to increased platelet reactivity after carotid artery stenting.

text: BACKGROUND Increased platelet reactivity after carotid artery stenting (CAS) may cause thromboembolic complications. OBJECTIVE This study aimed to investigate the incidence of increased platelet reactivity after CAS and to determine the factors related to it. METHODS Patients who underwent CAS were recruited prospectively. They received pre-procedural antiplatelet therapy comprising some combination of aspirin (100 mg/day), clopidogrel (75 mg/day), and/or cilostazol (200 mg/day) for a minimum of 7 days. ADP- and collagen-induced platelet aggregation were measured before and 4 days after CAS. Changes in platelet reactivity were reported as changes in the categorized platelet reactivity grade based on the effective dose 50%. Clinical characteristics of patients with and without increased platelet reactivity were compared. RESULTS Among 38 consecutive patients who underwent CAS, 18 (47%) exhibited increased platelet reactivity. Diabetes mellitus (OR 15.0; 95% CI 2.1 to 106.5; p=0.007) and carotid artery plaques exhibiting high-intensity signals (HIS) on time-of-flight MR angiography (TOF-MRA) (OR 25.2; 95% CI 2.0 to 316.2; p=0.013) were independently associated with increased platelet reactivity in a multivariate analysis. CONCLUSIONS Increased platelet reactivity occurred in nearly half of the studied patients subjected to CAS and was independently associated with diabetes mellitus and carotid artery plaques exhibiting HIS on TOF-MRA.


title: Estimates of the Potential Impact of the COVID-19 Pandemic on Sexual and Reproductive Health In Low- and Middle-Income Countries.

text: The novel coronavirus (SARS-CoV-2) that causes COVID-19 has spread rapidly since emerging in late 2019, leading the World Health Organization (WHO) to declare the disease a global pandemic on March 11, 2020. Governments around the world have had to quickly adapt and respond to curb transmission of the virus and to provide care for the many who have been infected. The strain that the outbreak imposes on health systems will undoubtedly impact the sexual and reproductive health of individuals living in low- and middle-income countries (LMICs); however, sexual and reproductive health will also be affected by societal responses to the pandemic, such as local or national lockdowns that force health services to shut down if they are not deemed essential, as well as the consequences of physical distancing, travel restrictions and economic slowdowns.


Allergic contact dermatitis due to a surgical marker.


title: Superior mesenteric artery stenting using embolic protection device for treatment of acute or chronic mesenteric ischemia.

text: OBJECTIVE The objective of the study was to report the feasibility and results of superior mesenteric artery (SMA) stenting using embolic protection devices (EPDs) to treat acute mesenteric ischemia (AMI) and chronic mesenteric ischemia (CMI). METHODS A retrospective review was conducted of consecutive patients who underwent SMA stenting with EPDs from 2007 to 2016. EPDs were used selectively in patients with occlusions, severe calcification, or acute thrombus. A two-wire technique with SpiderFX 0.014-inch filter wire (Medtronic, Minneapolis, Minn) combined with a 0.018-inch wire was used to provide support and to facilitate stenting and EPD retrieval. Presence of macroscopic debris in the EPD was recorded and graded as minor (minimal debris) or major (large thrombus or plaque). End points were technical success, presence of EPD debris, embolization, early morbidity, and mortality. RESULTS SMA stenting was performed in 179 patients, of whom 65 (36%) had EPDs. The mean age was 73 ± 11 years, and 49 were female (75%). Clinical presentation was CMI in 48 patients (74%) and AMI or acute-on-CMI in 17 (26%). Indications for EPD were severe calcification in 22 patients (34%), acute thrombus in 18 (28%), and total occlusion in 16 (25%). Bare-metal stents were used in 33 patients, covered stents in 26, and both types in 6. Adjunctive therapy included thrombolysis in seven patients, thrombectomy in four, and atherectomy in three. Technical success was 100%. There were no instances of filter retention or arterial trauma due to filter manipulation. Distal embolization was noted in four patients (6%), of whom two had AMI. All large emboli were retrieved using catheter aspiration devices, but one small distal embolus was left untreated with no clinical consequences. Two patients had vessel spasm treated by nitroglycerin. Macroscopic debris was noted in 43 patients (66%) and was major in 21 (49%) or minor in 22 (51%). Of the patients with AMI, five (29%) required exploratory laparotomy and four (23%) had bowel resection. Eight additional patients (12%) had early complications (five CMI, three AMI), including cardiac complications, brachial hematoma, acute cholecystitis, and acute respiratory distress syndrome in two patients each. There were no deaths among CMI patients and two early deaths (12%) among those who had AMI. CONCLUSIONS Use of EPDs during SMA stenting is safe and feasible with a two-wire technique. Large macroscopic debris was noted in one-third of the patients when the filter was applied selectively in patients with acute symptoms, occlusions, or severely calcified lesions. Despite the use of EPD, distal embolization occurred in 6% of patients and was successfully treated using catheter aspiration devices.


title: Predictive factors of maternal hypothermia during Cesarean delivery: a prospective cohort study.

text: PURPOSE Although perioperative hypothermia may increase maternal morbidity, active warming is infrequently performed to maintain normothermia during Cesarean delivery (CD). The aim of this prospective observational study was to determine the factors associated with maternal hypothermia in this setting. METHODS Women scheduled for elective or emergency CD were consecutively included in this study from November 2014 to October 2015. Maternal temperature was measured using an infrared tympanic thermometer on the patient's arrival in the operating room, at skin incision, and at the end of skin suture. Maternal hypothermia was defined by tympanic temperature < 36°C at the end of skin suture. Univariate analysis was performed, followed by multivariate logistic regression analysis, in order to determine the factors associated with maternal hypothermia at the end of the surgery. RESULTS Three hundred fifty-nine women were included and analyzed during this study. The incidence of hypothermia was 23% (95% confidence interval, 18 to 27) among the total population included. According to multivariate analysis, obesity, oxytocin augmentation of labour, and use of active forced-air warming were associated with a decreased risk of maternal hypothermia, while maternal temperature < 37.1°C on arrival in the operating room, maternal temperature < 36.6°C at skin incision, and an infused volume of fluids > 650 mL were significantly associated with maternal hypothermia. Both goodness of fit and predictive value of multivariate analysis were high. CONCLUSION Several predictive factors for maternal hypothermia during CD were identified. These factors should be taken into account to help prevent maternal hypothermia during CD.


title: Does depth of the frontal sinus affect near-infrared spectroscopy measurement?

text: Near-infrared spectroscopy (NIRS) is a non-invasive method that reflects real-time cerebral oxygenation (rSO2) by the use of two adhesive optodes placed on the forehead of the patient. Frontal sinuses vary anatomically and a large frontal sinus might compromise the NIRS signal since the NIRS optodes are placed at the skin surface superficial to the underlying frontal sinus. The aim of this case-series was to elucidate whether there is a difference in the obligate changes in rSO2 during cardiac surgery between patients with a small as opposed to a large anterior-posterior distance of the frontal sinus based on magnetic resonance imaging. Two matched groups with small (n = 5) vs. large (n = 5) frontal sinus (3.2 vs. 18.1 millimeters) in this case-series showed no difference in obligate changes of rSO2 (p = 0.54).


title: Diabetes and COVID-19: evidence, current status and unanswered research questions.

text: Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.


title: Efficacy of magnetic thermoablation using SPIO in the treatment of osteoid osteoma in a bovine model compared to radiofrequency and microwave ablation.

text: PURPOSE To evaluate heating efficacy of superparamagnetic iron oxide nanoparticles (SPIO) for electromagnetic ablation (EMA) of osteoid osteoma (OO) using an ex vivo model compared to radiofrequency ablation (RFA) and microwave ablation (MWA). METHODS A model for OO using sliced bovine tibia and sliced muscle tissue was developed. A bone cavity filled with either a mixture of SPIO and agarose or pure agarose (control group) was established. EMA was performed using an experimental system, RFA and MWA using clinically approved systems, and the ablation protocols recommended by the vendor. For temperature measurements, fiberoptic temperature probes were inserted inside the cavity, on the outside of the periosteum, and at a 5 mm distance to the periosteum. RESULTS Maximum temperatures with or without SPIO in the nidus were as follows: EMA: 79.9 ± 2.5/22.3 ± 0.7 °C; RFA: 95.1 ± 1.8/98.6 ± 0.9 °C; MWA: 85.1 ± 10.8/83.4 ± 9.62 °C. In RFA with or without SPIO significantly higher temperatures were achieved in the nidus compared to all other groups (p < 0.05). In MWA significantly higher temperatures were observed in the 5 mm distance to the periosteum compared to EMA and RFA with or without SPIO (p < 0.05). In MWA temperature decrease between nidus and the 5 mm distance to the periosteum was significantly lower than in RFA with or without SPIO (p < 0.0001). In MWA without SPIO temperature decrease was significantly lower than in the EMA group (p < 0.05). CONCLUSION In the experimental setting, ablation of OO is safe and effective using EMA. It is less invasive than RFA and MWA, and it theoretically allows repeated treatments without repeated punctures. In comparison, the highest temperatures in the nidus are reached using RFA.


title: The efficacy of surface electromyographic biofeedback assisted stretching for the treatment of chronic low back pain: a case-series.

text: Individuals with low back pain (LBP) commonly present with an impaired flexion-relaxation (FR) response, characterised as continued lumbar muscle activation at maximal voluntary flexion. The aim of the present investigation was to explore the effectiveness of a surface electromyographic assisted stretching (SEMGAS) programme in improving FR. Nine volunteers with chronic LBP and an impaired FR took part in weekly biofeedback SEMGAS sessions and performed a home-based stretching programme, for 5 weeks. FR, Oswestry Disability Index, Numeric Pain Rating Scale and Sit and Reach were recorded pre and post-intervention as well as at a 4-6-week follow-up. Of the nine participants included, three improved FR to statistically significant levels. These three participants also achieved a clinically important change in pain intensity scores. The results suggest that SEMGAS may provide benefits to some individuals with chronic LBP and impaired FR, although larger scale investigation of SEMGAS alone is indicated.


docid: uyjjjurf

title: Delayed laparoscopic management of placenta increta.

text: BACKGROUND Traditional methods of management of abnormal placentation are often associated with significant maternal morbidity. In an attempt to decrease such morbidity, we present a novel approach: delayed laparoscopic management. CASE A patient with placenta increta was delivered by Caesarean section, followed by closure of the uterine incision, with the placenta left in situ. The patient underwent total laparoscopic hysterectomy three weeks later. She did not receive any blood product transfusions, either at the time of Caesarean section or at the time of hysterectomy. CONCLUSION A laparoscopic approach may be considered for delayed surgical management of abnormal placentation. Key factors for success consist of a multi-disciplinary approach, the availability of skilled laparoscopic surgeons and advanced endoscopic equipment, and the availability of resources in the event of complications.


title: Endocrine Conditions and COVID-19.

text: COVID-19 was declared a global pandemic by the WHO and has affected millions of patients around the world. COVID-19 disproportionately affects persons with endocrine conditions, thus putting them at an increased risk for severe disease. We discuss the mechanisms that place persons with endocrine conditions at an additional risk for severe COVID-19 and review the evidence. We also suggest precautions and management of endocrine conditions in the setting of global curfews being imposed and offer practical tips for uninterrupted endocrine care.


Is the United Nations catching up with Ebola at last?


Erratum to: First detection, clinical presentation and phylogenetic characterization of Porcine epidemic diarrhea virus in Austria.


Alcohol consumption in the Covid-19 Era.


title: Different Impact of the Number of Organ Failures and Graft-Versus-Host Disease on the Outcome of Allogeneic Stem Cell Transplantation Recipients Requiring Intensive Care.

text: BACKGROUND Admission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) remains controversial, especially when graft-versus-host disease (GVHD) is present. METHODS We performed a retrospective study to assess prognostic factors of survival in all allogeneic SCT recipients admitted to the ICU between 2002 and 2013 in our center which has flexible admission criteria, especially regarding GVHD. RESULTS Of 349 patients who underwent allogeneic SCT during the study period, 92 patients (26%) were admitted to the ICU. Intensive care unit and hospital discharge rates were 66% and 46%, respectively, whereas 1 year survival was 24%. Acute GVHD, either grade III to IV (30 patients, 33%) or refractory (12 patients, 13%) had a nonsignificant impact on hospital mortality (odds ratio [OR], 2.1; P = 0.1; OR, 5, P = 0.05, respectively). Fifty percent of patients required invasive mechanical ventilation, 30% required vasopressors, 17% required renal replacement therapy, and 28% had liver impairment (bilirubin >34 μmol/L), each of these parameters defining organ failure. Mortality was closely associated with the number of organ failures as hospital discharge rates were 69%, 50%, 42%, and 0% among patients with 0 (26 patients), 1 (26 patients), 2 (26 patients), and 3 to 4 (14 patients) organ failures, respectively (OR, 2.7; 95% confidence interval, 1.6-4.6; P < 0.001 according to the number of organ failures). CONCLUSIONS Early mortality of allogeneic SCT recipients admitted to the ICU is especially influenced by the number of organ failures and therefore patients with 0 to 2 organ failures should be considered if required. Refractory GVHD affects survival but not within the confined ICU admission.


Three-dimensional rotational angiography in murine models: a technical note.


COVID-19 testing.


title: Sapheon: the solution?

text: Less invasive endovenous techniques have been shown to be as effective as open surgery in the treatment of varicose veins. Furthermore, they cause less postoperative bruising and pain and enable early return to normal activities and work. Tumescent anaesthesia is safe and obviates complications of general or spinal anaesthesia. Drawbacks are a steep learning curve and painful administration during treatment. Tumescentless techniques like Clarivein™ or VenaSeal™ Sapheon Closure System are recently under investigation. Short-term results of VenaSeal™ are comparable with thermal ablation. The procedure is safe without serious adverse events. Perioperative pain and patient discomfort with this tumescentless approach is minimal but postoperative recovery is temporarily hindered by thrombophlebitis in 14-15 % of patients. One-year results in a small feasibility study has demonstrated durable closure at this endpoint. No longer-term results are available. A randomized control trial between VenaSeal™ and Covidien ClosureFast™ is in a preparatory phase.


title: Imaging visceral adhesion to polymeric mesh using pneumoperitoneal-MRI in an experimental rat model.

text: BACKGROUND Intraperitoneal mesh implantation is often associated with formation of adhesion to the mesh. This experimental study examines the potential of minimally invasive pneumoperitoneal-MRI to assess these adhesions in a preclinical context. METHODS Uncoated polyethylene terephthalate meshes were placed intraperitoneally in rats, in regard to the caecum previously scraped to promote petechial bleeding and subsequent adhesions. Examinations were performed 2-weeks post mesh implantation using a rodent dedicated high field MRI. Respiratory-triggered T2-weighted images were acquired prior to and after intraperitoneal injection of ~8-10 mL gas to induce a mechanical stress on the abdominal wall. RESULTS Adhesions are occasionally seen in sham-operated rats as opposed to rats receiving polyethylene terephthalate meshes. On high-resolution images, meshes can be detected due to their characteristic net shape. However, evidence of adherence is only found if intraperitoneal gas injection is performed, when a ~1-cm elevation of the abdominal wall is observed. When adherence occurs between the mesh and the caecum, the latter remains in contact with the wall. Looser adherences between visceral tissue and meshes are also observed. CONCLUSIONS T2-weighted pneumoperitoneal-MRI is a powerful tool for assessing adherence after intraperitoneal mesh implantation. According to the mini-invasive procedure adopted here, this approach may allow a temporal follow-up of adherence fate.


title: Factors in the technical quality of gadolinium enhanced magnetic resonance angiography for pulmonary embolism in PIOPED III.

text: In a multi-center trial, gadolinium enhanced magnetic resonance angiography (MRA) for diagnosis of acute pulmonary embolism (PE) had a high rate of technically inadequate images. Accordingly, we evaluated the reasons for poor quality MRA of the pulmonary arteries in these patients. We performed a retrospective analysis of the data collected in the PIOPED III study. We assessed the relationship to the proportion of examinations deemed "uninterpretable" by central readers to the clinical centers, MR equipment platform and vendors, degree of vascular opacification in different orders of pulmonary arteries; type, frequency and severity of image artifacts; patient co-morbidities, symptoms and signs; and reader characteristics. Centers, MR equipment vendor and platform, degree of vascular opacification, and motion artifacts influenced the likelihood of central reader determinations that images were "uninterpretable". Neither the reader nor patient characteristics (age, body mass index, respiratory rate, heart rate) correlated with the likelihood of determining examinations "uninterpretable". Vascular opacification and motion artifact are the principal factors influencing MRA interpretability. Some centers obtain better images more consistently, but the reasons for differences between centers are unclear.


title: [Quick review: air pollution and morbi-mortality by Covid-19].

text: OBJECTIVE To analyze the evidence on the relationship between air pollution and an increased risk of morbidity and mortality from Covid-19. MATERIALS AND METHODS An adaptation of the Cochrane rapid review methodology was used. The search was performed in PubMed and MedRxiv and was limited until April 28 and 26, respectively. The titles and abstracts were reviewed by five researchers who, in turn, reviewed the full texts of the final selection. RESULTS 450 manuscripts were found, 15 met the inclusion criteria. The evidence reports that the incidence and risk of morbidity and mortality from Covid-19 increase with chronic and acute exposure to air pollution, particularly to particulate matter (PM2.5, PM10) and nitrogen dioxide. CONCLUSIONS More studies are required especially in Latin American cities. It is necessary to strengthen the recommendations in cities with higher levels of pollutants and to reduce their emissions.


title: Systematic reviews: guidance relevant for studies of older people.

text: Systematic reviews and meta-analyses are increasingly common. This article aims to provide guidance for people conducting systematic reviews relevant to the healthcare of older people. An awareness of these issues will also help people reading systematic reviews to determine whether the results will influence their clinical practice. It is essential that systematic reviews are performed by a team which includes the required technical and clinical expertise. Those performing reviews for the first time should ensure they have appropriate training and support. They must be planned and performed in a transparent and methodologically robust way: guidelines are available. The protocol should be written-and if possible published-before starting the review. Geriatricians will be interested in a table of baseline characteristics, which will help to determine if the studied samples or populations are similar to their patients. Reviews of studies of older people should consider how they will manage issues such as different age cut-offs; non-specific presentations; multiple predictors and outcomes; potential biases and confounders. Systematic reviews and meta-analyses may provide evidence to improve older people's care, or determine where new evidence is required. Newer methodologies, such as meta-analyses of individual level data, network meta-analyses and umbrella reviews, and realist synthesis, may improve the reliability and clinical utility of systematic reviews.


title: Explainable Deep Learning for Pulmonary Disease and Coronavirus COVID-19 Detection from X-rays.

text: BACKGROUND AND OBJECTIVE Coronavirus disease (COVID-19) is an infectious disease caused by a new virus never identified before in humans. This virus causes respiratory disease (for instance, flu) with symptoms such as cough, fever and, in severe cases, pneumonia. The test to detect the presence of this virus in humans is performed on sputum or blood samples and the outcome is generally available within a few hours or, at most, days. Analysing biomedical imaging the patient shows signs of pneumonia. In this paper, with the aim of providing a fully automatic and faster diagnosis, we propose the adoption of deep learning for COVID-19 detection from X-rays. METHOD In particular, we propose an approach composed by three phases: the first one to detect if in a chest X-ray there is the presence of a pneumonia. The second one to discern between COVID-19 and pneumonia. The last step is aimed to localise the areas in the X-ray symptomatic of the COVID-19 presence. RESULTS AND CONCLUSION Experimental analysis on 6,523 chest X-rays belonging to different institutions demonstrated the effectiveness of the proposed approach, with an average time for COVID-19 detection of approximately 2.5 seconds and an average accuracy equal to 0.97.


title: 3-D endoscope using a single CCD camera and pneumatic vibration mechanism.

text: BACKGROUND During endoscopic surgical procedures, surgeons must manipulate an endoscope inside the body cavity to observe a surgical area while estimating the distance between that area and the surgical instruments by reference to a monitor on which the movement and size of the surgical instruments are displayed in 2-D endoscopic images. Therefore, there is a risk of the endoscope or instruments physically damaging body tissues. To overcome this problem, we developed a Ø5-mm, 3-D endoscope using a single 1/10-inch CCD camera and pneumatic vibration mechanism. METHODS The 3-D endoscope proposed in this paper consists of an outer and inner sleeve, a 1/10-inch CCD camera attached to its distal end, and a pneumatic vibration mechanism attached to its proximal end. This endoscope can acquire left and right endoscopic images for stereovision in synchrony with the periodical motion generated by the vibration mechanism. We measured the displacement at the proximal and distal end of the 3-D endoscope simultaneously, and evaluated the feasibility of its use in vivo. RESULTS The displacement at the distal end of the endoscope to which the CCD camera is attached was approximately ±0.25 mm. The timing when the displacement of the CCD camera was at maximal amplitude coincided with the timing when the displacement of its proximal end was at maximal amplitude. In the in vivo experiment, this 3-D endoscope can provide clear 3-D images of the surgical area. CONCLUSIONS The developed 3-D endoscope that uses a single CCD camera and pneumatic vibration mechanism can successfully visualize internal organs inside the body even though the CCD camera is moved by the vibration. Therefore, the risk of damage to fragile body tissues can be significantly decreased.


title: Ty-raps in trauma: a novel closing technique of extremity fasciotomy wounds.

text: The challenge of closing extremity fasciotomy wounds is well known to every trauma and orthopedic surgeon. We developed a new, easy, and inexpensive dermatotraction technique based on the simple use of Ty-Raps and report on the first pilot study using this novel technique for the closure of 23 extremity fasciotomy wounds. The Ty-Rap system consists of several combinations of two Ty-Raps and four surgical staples. Immediately after fasciotomy, the system is secured to the skin by the surgical staples, and once the swelling of the affected limb is subsided, the Ty-Raps are tightened every 24 hours to 48 hours until full approximation of the skin edges is achieved. We recorded the time to closure of the wound, the time to removal of the Ty-Raps, and the complications related to the procedure. Also, a cost analyses was calculated. The mean time of approximation of the skin was 6.3 days, and after a further 9.4 days, the Ty-Raps could be removed. The majority of the wounds (91%) healed without complications, and only one patient in our series required a secondary surgical procedure for the closure of one fasciotomy wound. The total cost to close a fasciotomy wound of 30 cm with the use of Ty-Raps is US dollar 23.33. We regard the use of Ty-Raps a good alternative for the current closing techniques of extremity fasciotomy wounds. We value its low cost, general availability, effectiveness, and the fact that, in this pilot study, both the application and the tightening of the Ty-Raps were well tolerated by our patients with a minimal need for secondary procedures. Knowledge of this technique is a useful adjunct to the existing surgical array for every trauma and orthopedic surgeon for the closure of extremity fasciotomy wounds, especially in austere or military environments.


title: Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy, and surgical stripping for great saphenous varicose veins with 3-year follow-up.

text: INTRODUCTION This study compares the outcome 3 years after treatment of varicose veins by endovenous laser ablation (EVLA), radiofrequency ablation, ultrasound-guided foam sclerotherapy (UGFS), or surgery by assessing recurrence, Venous Clinical Severity Score (VCSS), and quality of life (QOL). METHODS A total of 500 patients (580 legs) were randomized to one of the three endovenous treatments or high ligation and stripping of the great saphenous vein (GSV). Follow-up included clinical and duplex ultrasound examinations and VCSS and QOL questionnaires. Kaplan-Meier (KM) life-table analysis was used. P values below .05 were considered statistically significant. RESULTS At 3 years, eight (KM estimate, 7%), eight (KM estimate, 6.8%), 31 (KM estimate, 26.4%), and eight (KM estimate, 6.5%) of GSVs recanalized or had a failed stripping procedure (more than 10 cm open refluxing part of the treated GSV; CLF, EVLA, UGFS, and stripping, respectively; P < .01). Seventeen (KM estimate, 14.9%), 24 (KM estimate, 20%), 20 (KM estimate, 19.1%), and 22 (KM estimate, 20.2%) legs developed recurrent varicose veins (P = NS). The patterns of reflux and location of recurrent varicose veins were not different between the groups. Within 3 years after treatment, 12 (KM estimate, 11.1%), 14 (KM estimate, 12.5%), 37 (KM estimate, 31.6%), and 18 (KM estimate, 15.5%) legs were retreated in the CLF, EVLA, UGFS, and stripping groups, respectively (P < .01). VCSS, SF-36, and Aberdeen QOL scores improved significantly in all the groups with no difference between the groups. CONCLUSIONS All treatment modalities were efficacious and resulted in a similar improvement in VCSS and QOL. However, more recanalization and reoperations were seen after UGFS.


title: Reliability of administrative data to identify sexually transmitted infections for population health: a systematic review.

text: INTRODUCTION International Classification of Diseases (ICD) codes in administrative health data are used to identify cases of disease, including sexually transmitted infections (STIs), for population health research. The purpose of this review is to examine the extant literature on the reliability of ICD codes to correctly identify STIs. METHODS We conducted a systematic review of empirical articles in which ICD codes were validated with respect to their ability to identify cases of chlamydia, gonorrhoea, syphilis or pelvic inflammatory disease (PID). Articles that included sensitivity, specificity and positive predictive value of ICD codes were the target. In addition to keyword searches in PubMed and Scopus databases, we further examined bibliographies of articles selected for full review to maximise yield. RESULTS From a total of 1779 articles identified, only two studies measured the reliability of ICD codes to identify cases of STIs. Both articles targeted PID, a serious complication of chlamydia and gonorrhoea. Neither article directly assessed the validity of ICD codes to identify cases of chlamydia, gonorrhoea or syphilis independent of PID. Using ICD codes alone, the positive predictive value for PID was mixed (range: 18%-79%). DISCUSSION AND CONCLUSION While existing studies have used ICD codes to identify STI cases, their reliability is unclear. Further, available evidence from studies of PID suggests potentially large variation in the accuracy of ICD codes indicating the need for primary studies to evaluate ICD codes for use in STI-related public health research.


Covid-19: Deaths in care home deaths in England and Wales rise sharply.


title: Modified uterine allotransplantation and immunosuppression procedure in the sheep model.

text: OBJECTIVE To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. METHODS In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. RESULTS Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. CONCLUSION We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.


title: SPE Approach for Robust Estimation of SIR Model with Limited and Noisy Data: The Case for COVID-19.

text: The SIR model and its variants are widely used to predict the progress of COVID-19 worldwide, despite their rather simplistic nature. Nevertheless, robust estimation of the SIR model presents a significant challenge, particularly with limited and possibly noisy data in the initial phase of the pandemic. K-means algorithm is used to perform a cluster analysis of the top ten countries with the highest number of COVID-19 cases, to observe if there are any significant differences among countries in terms of robustness. As a result of model variation tests, the robustness of parameter estimates is found to be particularly problematic in developing countries. The incompatibility of parameter estimates with the observed characteristics of COVID-19 is another potential problem. Hence, a series of research questions are visited. We propose a SPE ("Single Parameter Estimation") approach to circumvent these potential problems if the basic SIR is the model of choice, and we check the robustness of this new approach by model variation and structured permutation tests. Dissemination of quality predictions is critical for policy and decision-makers in shedding light on the next phases of the pandemic.


ACP Journal Club. In acute ischemic stroke, rapid intraarterial treatment plus usual care improved functional independence.


title: A comparative study of magnetic resonance venography techniques for the evaluation of the internal jugular veins in multiple sclerosis patients.

text: BACKGROUND AND PURPOSE The use of magnetic resonance imaging (MRI) to assess the vascular nature of diseases such as multiple sclerosis (MS) is a growing field of research. This work reports on the application of MR angiographic (MRA) and venographic (MRV) techniques in assessing the extracranial vasculature in MS patients. MATERIALS AND METHODS A standardized MRI protocol containing 2D TOF-MRV and dynamic 3D contrast-enhanced (CE) MRAV was run for 170 MS patients and 40 healthy controls (HC). The cross-sectional area (CSA) of the internal jugular veins (IJVs) was measured at three neck levels in all subjects for both MRV techniques to determine the presence of venous stenoses. All data were analyzed retrospectively. RESULTS For the values where both methods showed signal, the 3D method showed larger CSA measurement values compared to 2D methods in both IJVs, in both MS and HC subjects which was confirmed with student paired t-tests. Of the 170 MS patients, 93 (55%) in CE-MRAV and 103 (61%) in TOF-MRV showed stenosis in at least one IJV. The corresponding numbers for the 40 HC subjects were 2 (5%) and 4 (10%), respectively. Carotid ectasias with IJV stenosis were seen in 26 cases (15%) with 3D CE-MRAV and were not observable with 2D TOF-MRV. Carotid ectasias were not seen in the HC group. In the 2D TOF-MRV data, banding of the IJVs related to slow flow was seen in 58 (34%) MS cases and in no HC cases. MS patients showed lower average CSAs than the HC subjects. CONCLUSION The 3D CE MRAV depicted the vascular anatomy more completely than the 2D TOF-MRV. However, the 3D CE MRAV does not provide any information about the flow characteristics which are indirectly available in the 2D TOF-MRV in those cases where there is slow flow.


President's message: the impact of the COVID-19 public health emergency on the practice of addiction medicine.


title: Allicin enhances the radiosensitivity of colorectal cancer cells via inhibition of NF-κB signaling pathway.

text: Radioresistance is an important factor affecting the radiotherapy effect of colorectal cancer (CRC). Allicin is a versatile sulfur-containing organic compound extracted from garlic (Allium sativum L.), which has many pharmacological effects. However, the effect of allicin on the sensitivity of CRC radiotherapy has not been confirmed. The present study is to observe the radiosensitivity effects of allicin and to explore its mechanism in CRC radiotherapy. The proliferation inhibition effects of allicin combined with X-ray radiotherapy in HCT116 cells were measured by growth curve of cell and colony formation assays. The cell apoptosis was detected by Hoechst 33258 nucleus staining assay. The migration ability of cells was detected by Transwell chamber migration assay. The animal model of CRC was established in BALB/c mice via transplantation of CT26 cell, and the radiosensitization effect of allicin on CRC was detected in vivo. The mRNA expressions of NF-κB, IKKβ, and IκBα were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of NF-κB, p-NF-κB, IKKβ, p-IKKβ, IκBα, and p-IκBα were detected by western blotting. Our results showed that allicin improves the sensitivity of X-ray radiotherapy in CRC, and its mechanism may be associated with inhibition of NF-κB signaling pathway. These findings suggest that allicin may be used as a potential sensitizer for tumor radiotherapy in the clinic.


title: Immunolocalization of succinate dehydrogenase in the esophagus epithelium of domesticated mammals.

text: Using immunohistochemistry and transmission electron microscopy (TEM), the esophagus epithelia of seven domesticated mammals (horse, cattle, goat, pig, dog, laboratory rat, cat) of three nutrition groups (herbivorous, omnivorous, carnivorous) were studied to get first information about energy generation, as demonstrated by succinate dehydrogenase (SDH) activities. Distinct reaction intensities could be observed in all esophageal cell layers of the different species studied reflecting moderate to strong metabolic activities. The generally strong staining in the stratum basale indicated that new cells are continuously produced. The latter feature was confirmed by a thick, and in the horse generally highly active stratum spinosum. Only in the pig, reaction intensity variations occurred, obviously related to differences in physical feed quality or restricted feed allocation. The immunohistochemical results were corroborated by the presence of intact mitochondria in the esophageal cells of all species and nutrition types studied, except for the horse. Possible relationships between SDH reaction intensities and feed structure, mass or consistency are discussed.


title: Selection of proteins with desired properties from natural proteome libraries using mRNA display.

text: mRNA display is a powerful yet challenging in vitro selection technique that can be used to identify proteins with desired properties from both natural proteome and combinatorial polypeptide libraries. The physical conjugation between a protein and its own RNA presents unique challenges in manipulating the displayed proteins at a low nanomolar scale in an RNase-free environment. The following protocol outlines the generation of cDNA libraries derived from natural organisms as well as the steps required for generation of mRNA-protein fusion molecules, in vitro functional selection and regeneration of the selected cDNA library. The selection procedures for the identification of protease substrates and Ca(2+)-dependent calmodulin-binding proteins from natural cDNA libraries are presented as examples. The method can be generally applied to the identification of protein sequences with desired properties from various natural proteome libraries. One round of mRNA display-based selection can be accomplished in ~7 d.


title: Castanea sativa (European Chestnut) Leaf Extracts Rich in Ursene and Oleanene Derivatives Block Staphylococcus aureus Virulence and Pathogenesis without Detectable Resistance.

text: The Mediterranean is home to a rich history of medical traditions that have developed under the influence of diverse cultures over millennia. Today, many such traditions are still alive in the folk medical practices of local people. Investigation of botanical folk medicines used in the treatment of skin and soft tissue infections led us to study Castanea sativa (European Chestnut) for its potential antibacterial activity. Here, we report the quorum sensing inhibitory activity of refined and chemically characterized European Chestnut leaf extracts, rich in oleanene and ursene derivatives (pentacyclic triterpenes), against all Staphylococcus aureus accessory gene regulator (agr) alleles. We present layers of evidence of agr blocking activity (IC50 1.56-25 μg mL-1), as measured in toxin outputs, reporter assays hemolytic activity, cytotoxicity studies, and an in vivo abscess model. We demonstrate the extract's lack of cytotoxicity to human keratinocytes and murine skin, as well as lack of growth inhibitory activity against S. aureus and a panel of skin commensals. Lastly, we demonstrate that serial passaging of the extract does not result in acquisition of resistance to the quorum quenching composition. In conclusion, through disruption of quorum sensing in the absence of growth inhibition, this study provides insight into the role that non-biocide inhibitors of virulence may play in future antibiotic therapies.


title: Automatic tailoring and transplanting: a practical method that makes virtual screening more useful.

text: Docking-based virtual screening of large compound libraries has been widely applied to lead discovery in structure-based drug design. However, subsequent lead optimizations often rely on other types of computational methods, such as de novo design methods. We have developed an automatic method, namely automatic tailoring and transplanting (AutoT&T), which can effectively utilize the outcomes of virtual screening in lead optimization. This method detects suitable fragments on virtual screening hits and then transplants them onto a lead compound to generate new ligand molecules. Binding affinities, synthetic feasibilities, and drug-likeness properties are considered in the selection of final designs. In this study, our AutoT&T program was tested on three different target proteins, including p38 MAP kinase, PPAR-α, and Mcl-1. In the first two cases, AutoT&T was able to produce molecules identical or similar to known inhibitors with better potency than the given lead compound. In the third case, we demonstrated how to apply AutoT&T to design novel ligand molecules from scratch. Compared to the solutions generated by other two de novo design methods, i.e., LUDI and EA-Inventor, the solutions generated by AutoT&T were structurally more diverse and more promising in terms of binding scores in all three cases. AutoT&T also completed the assigned jobs more efficiently than LUDI and EA-Inventor by several folds. Our AutoT&T method has certain technical advantages over de novo design methods. Importantly, it expands the application of virtual screening from lead discovery to lead optimization and thus may serve as a valuable tool for many researchers.


title: Videolaryngoscopy increases 'mouth-to-mouth' distance compared with direct laryngoscopy.

text: The COVID-19 outbreak has resulted in the consideration of videolaryngoscopy (VL) for tracheal intubation of patients during an outbreak [1,2]. Benefits of VL compared with a standard curved Macintosh (MAC) blade include postural advantages, improved view for the laryngoscopist and assistants, enhanced supervision and easier management of unanticipated difficult airways [3].


title: Small interfering RNA expression inhibits avian infectious bronchitis virus replication and inflammatory response.

text: BACKGROUND Avian infectious bronchitis virus (IBV) is a major cause of poor weight gain and mortality among chicks. METHODS A lentivirus vector was used to generate transgenic chickens expressing small interfering RNA (siRNA) targeting the M protein of IBV. Offspring of generation 0 (G0) were screened to identify G1 transgenic chickens (Tg). Monocytes from G1 Tg were stimulated with IBV in vitro. RESULTS Monocytes producing siRNA efficiently inhibit IBV replication. Expression of inflammatory cytokines, Mx protein and nitric oxide levels were lower in early IBV infection in Tg. In vivo experiments show that siRNA expression inhibits IBV replication, significantly decreases mortality and increases weight gain. Inflammatory responses and oxidative damage were significantly decreased, yielding minimal tissue injury. The inflammatory responses indicate that the cellular immune response is most effective during the initial stage, while the humoral immune response is more significant in later stages of infection. CONCLUSIONS Small interfering RNA expression inhibits avian IBV replication and inflammatory response.


title: Radiological manifestations of COVID-19: key points for the physician.

text: The emergence of the SARS-CoV-2 virus at the end of 2019 has led to unprecedented demand on healthcare systems around the world. Healthcare workers, including doctors, have found themselves having to work in unfamiliar environments in the effort to control this pandemic. This article gives the hospital physician an overview of the radiological manifestations of COVID-19 disease, to improve knowledge and increase familiarity when reviewing radiographic images.


title: Comparison of Venous Thromboembolism Risks Between COVID-19 Pneumonia and Community-Acquired Pneumonia Patients.

text: OBJECTIVE The objectives were to investigate and compare the risks and incidences of venous thromboembolism (VTE) between the 2 groups of patients with coronavirus disease 2019 (COVID-19) pneumonia and community-acquired pneumonia (CAP). Approach and Results: Medical records of 616 pneumonia patients who were admitted to the Yichang Central People's Hospital in Hubei, China, from January 1 to March 23, 2020, were retrospectively reviewed. The patients with COVID-19 pneumonia were treated in the dedicated COVID-19 units, and the patients with CAP were admitted to regular hospital campus. Risks of VTE were assessed using the Padua prediction score. All the patients received pharmaceutical or mechanical VTE prophylaxis. VTE was diagnosed using Duplex ultrasound or computed tomography pulmonary angiogram. Differences between COVID-19 and CAP groups were compared statistically. All statistical tests were 2 sided, and P<0.05 was considered as statistically significant. All data managements and analyses were performed by IBM SPSS, version 24, software (SPSS, Inc, Chicago, IL). Of the 616 patients, 256 had COVID-19 pneumonia and 360 patients had CAP. The overall rate of VTE was 2% in COVID-19 pneumonia group and 3.6% in CAP group, respectively (P=0.229). 15.6% of the COVID-19 pneumonia patients and 10% of the CAP patients were categorized as high risk for VTE (Padua score, >4), which were significantly different (P=0.036). In those high-risk patients, the incidence of VTE was 12.5% in COVID-19 pneumonia group and 16.7% in CAP group (P=0.606). Subgroup analysis of the critically ill patients showed that VTE rate was 6.7% in COVID-19 group versus 13% in CAP group (P=0.484). In-hospital mortality of COVID-19 and CAP was 6.3% and 3.9%, respectively (P=0.180). CONCLUSIONS Our study suggested that COVID-19 pneumonia was associated with hypercoagulable state. However, the rate of VTE in COVID-19 pneumonia patients was not significantly higher than that in CAP patients.


title: Safety and efficacy of target vessel catheterization with the new steerable microcatheter Direxion compared with a standard microcatheter: a prospective, preclinical trial.

text: PURPOSE To assess the potential of a steerable microcatheter in a comparative preclinical trial. METHODS A total of 100 small target vessels of the lower limbs with a maximum diameter of 3 mm were prospectively randomized to catheterize with either the preshaped torqueable Direxion™ (J tip shape; Boston Scientific, Natick, MA) or a similarly steam-shaped Renegade™ microcatheter (Boston Scientific) in a porcine model. Catheterization was first performed in combination with a microguidewire and afterwards without. RESULTS No significant differences were found for the mean vessel diameter in the Direxion (1.53 ± 0.44 mm; n = 50) or Renegade (1.62 ± 0.43 mm; n = 50; p = 0.35) group. Guidewire-assisted catheterization was successful in all target vessels, whereas access was achieved in most cases with the guidewire alone. However, when it became necessary to steer the Direxion actively, this was regarded as key to obtain vessel access in three of four target vessels (75 %). Vessel catheterization without guidewire was significantly more successful with the Direxion (88 %; n = 44) compared with the Renegade (32 %; n = 16; p < 0.0001). In addition, this catheterization technique was also significantly faster with the Direxion compared with guidewire-assisted vessel catheterization with the Renegade (16.1 ± 14.4 sec compared with 27.1 ± 24.7 sec; p = 0.011). CONCLUSIONS The Direxion microcatheter demonstrated unique steerability characteristics, which makes it a promising new tool especially for complex coaxial endovascular procedures.