bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered Patterns of Compositional and Functional Disruption of the Gut Microbiota in Typhoid Fever and Nontyphoidal Febrile Illness
Authors: Haak Bastiaan W , de Jong Hanna K , Kostidis Sarantos , Giera Martin , Maude Rapeephan R , Samad Rasheda , Wijedoru Lalith , Ghose Aniruddha , Faiz Mohammed Abul , Parry Christopher M , Wiersinga W Joost
Published: June 2020

Background

Experimental murine models and human challenge studies of Salmonella Typhi infection have suggested that the gut microbiome plays an important protective role against the development of typhoid fever. Anaerobic bacterial communities have been hypothesized to mediate colonization resistance against Salmonella species by producing short-chain fatty acids, yet the composition and function of the intestinal microbiota in human patients with typhoid fever remain ill defined.

Methods

We prospectively collected fecal samples from 60 febrile patients admitted to Chittagong Medical College Hospital, Bangladesh, with typhoid fever or nontyphoidal febrile illness and from 36 healthy age-matched controls. The collected fecal samples were subjected to 16s rRNA sequencing followed by targeted metabolomics analysis.

Results

Patients with typhoid fever displayed compositional and functional disruption of the gut microbiota compared with patients with nontyphoidal febrile illness and healthy controls. Specifically, typhoid fever patients had lower microbiota richness and alpha diversity and a higher prevalence of potentially pathogenic bacterial taxa. In addition, a lower abundance of short-chain fatty acid–producing taxa was seen in typhoid fever patients. The differences between typhoid fever and nontyphoidal febrile illness could not be explained by a loss of colonization resistance after antibiotic treatment, as antibiotic exposure in both groups was similar.

Conclusions

his first report on the composition and function of the gut microbiota in patients with typhoid fever suggests that the restoration of these intestinal commensal microorganisms could be targeted using adjunctive, preventive, or therapeutic strategies.
Acute respiratory failure in an infant and thiamine deficiency in West Africa: a case report
Authors: Hiffler L , Escajadillo K , Rocaspana M , Janet S
Published: June 2020

In paediatrics, the overall clinical picture of thiamine deficiency (TD) is not easy to recognize, because it mimics or can be confused with other diseases even in cases of classic beriberi. Unsurprisingly, the likelihood of misdiagnosis of TD is even greater where beriberi has not been described.

Critically ill patients have increased thiamine body consumption and dextrose-based IV fluid increases thiamine cellular demand even further. Consequently, severe acute conditions may result in TD, or trigger TD signs in patients with borderline thiamine status, with life-threatening consequences.

Here, we describe the case of a young patient admitted to a West African hospital where TD is not well documented and diagnosed with severe pneumonia who responded dramatically to thiamine injection.

The lack of rapid diagnostic capacity and the severe outcome of TD justify the use of a therapeutic thiamine challenge in cases with high clinical suspicion. Increased awareness about TD and low threshold for thiamine use should guide clinicians in their practice.
Hydroxychloroquine-induced Stevens–Johnson syndrome in COVID-19: a rare case report
Authors: Davoodi Lotfollah , Jafarpour Hamed , Kazeminejad Armaghan , Soleymani Eissa , Akbari Zahra , Razavi Alireza
Published: June 2020

The international outbreak of respiratory illness termed coronavirus disease 2019 (COVID-19) began in December 2019 that has affected >0.8 million individuals. Self-limiting respiratory tract involvement, severe pneumonia, multiorgan failure and death are the spectrum of COVID-19. To date, there are no especial therapeutic agents for COVID-19 infections. One such medication includes the antimalarial hydroxychloroquine (HCQ), which recently reported as a possible therapy for shortening the duration of COVID-19 symptoms, reducing inflammatory reactions to infection, impairing the exacerbation of pneumonia and boosting lung imaging findings. Like all medications, HCQ has side effects and may occur in COVID-19 patients. Here, we report on the case of a 42-year-old woman, presented with fever and dry cough, who had COVID-19 and 2 days later presented with a pruritic erythematous maculopapular rash, which started from the distal of upper extremities and rapidly, involved the entire body.
Parliamentary Recruitment in the UK House of Commons: De-Gendering Workplace Structures, Gendering the Applicant
Authors: Miller Cherry M
Published: June 2020

Recruitment to key positions in institutions can be viewed as one way to introduce strategic reforms; however, little research has been conducted as to the effectiveness of the practice within parliaments. Even less has been written about the recruitment practices for non-elected parliamentary actors. Applying a feminist discursive institutionalist analysis, this article highlights the main discourses prominent in discussions around the recruitment to the Clerk of the House of Commons in 2014. It is argued that there are three discourses that rhetorically de-gendered career structures in the UK House of Commons, while two discourses explicitly gendered the applicant to the position of Clerk. The article discusses the broader significance of these insights for analysing parliaments as gendered workplaces, and for member engagement with parliamentary administrations.
Professional trustees: is it time to get on with the job? A discussion on whether Public Trustee v Cooper “blessing” applications are being abused by overly cautious trustees
Authors: Lindley Robert , O’Brien Wesley
Published: June 2020

Trustees are fortunate to have available a process where they can seek the Court’s blessing as to proposed actions and decisions, a remedy not widely available to decision-makers outside of a trusts context. However, with blessing applications becoming increasingly common (particularly in offshore jurisdictions), it is questionable whether trustees are being overly cautious in their approach. Are professional trustees who are paid for the performance of their duties too readily rushing to Court (often at great expense to the Trust Fund) in order to safeguard against remote hypothetical risks? Reviewing recent cases, this article will consider whether the industry has gone too far in its adoption of “blessing” applications, and whether Courts may seek to restrict the “momentous” circumstances that justify an application. We will consider the types of matters which may justify a “blessing” application, both from a legal and commercial perspective, and the alternative options which may be available to trustees when making significant decisions.
Extension Horses, Inc. experts act fast to create online resources to assist the horse industry during COVID-191
Authors: Greene Elizabeth A , Hein Wendy , Wickens Carissa L , Smarsh Danielle N
Published: June 2020

The COVID-19 pandemic and resulting stay-at-home directives, adopted out of necessity to protect human health, introduced significant challenges for horse owners and small equine businesses. Restricted access, and in many cases closure of barns, resulted in a multitude of questions and concerns within the equine community which needed to be addressed rapidly. Extension Horses, Inc. (EH) coordinated the development and delivery of a variety of educational resources utilizing a combination of online formats and dissemination through social media and EH member contact lists. A series of infographics, webinars, and podcasts (three in each category) were created to provide guidance on essential care of horses, emergency preparedness, financial assistance, legal concerns, and biosecurity during the crucial, initial weeks of the pandemic (March to April 2020). Web conferencing technology (Zoom) was used to facilitate discussion and task delegation among EH members and to conduct and record webinars and podcasts. Podcasts were hosted on Buzzsprout and infographics were created using Adobe InDesign. Live webinar participants were invited to participate in several polls during the webinar and were sent a brief survey to complete at the end of the webinar series. Analytics for all educational resources combined demonstrated a 32-d total direct reach of 135,563. Most live webinar participants identified themselves as horse owners and small equine business owners (55%). The majority of live webinar participants indicated the information was useful (99%), and they would utilize the resources they had learned about (80%). Survey respondents reported that Facebook, email, and word of mouth were key ways in which they learned about the webinars. The same survey found that the web-platform was an effective method to receive information (85% high satisfaction) and respondents were highly likely to recommend future EH webinars to others (88%). The three infographics had a total Facebook reach of 131,765, the webinars had 3,522 total views, and the three podcasts had 276 total downloads. The rapid response of EH and quick turnaround of products allowed a large online audience to receive vital information for coping with COVID-19. Having the established EH network, already familiar with virtual education, was a big asset in this effort. This can serve as a model for cooperative extension to utilize in future collaborative responses to industry issues.
“We understand our community”: implementation of the Healthy Eating Healthy Aging program among community-based organizations
Authors: Leong Judy , Jang Sou Hyun , Bishop Sonia K , Brown Emily V R , Lee Eun Jeong , Ko Linda K
Published: June 2020

Cardiovascular disease is the second leading cause of death in the USA among Asian Americans and Pacific Islanders (AAPIs) over the age of 65. Healthy Eating Healthy Aging (HEHA), an evidence-based heart health program, can provide culturally appropriate nutrition education to decrease the risk of cardiovascular disease. Community-based organizations (CBOs) are optimal settings to implement community-based programs. However, there is inadequate research on how evidence-based interventions like HEHA are implemented in CBOs. This study examined processes that facilitated the implementation of HEHA among CBOs serving older AAPIs. Twelve representatives from CBOs that implemented the HEHA program were recruited to participate in a semistructured interview. All the participants were CBO directors or senior managers. A semistructured interview guide was created and informed by the Consolidated Framework for Implementation Research (CFIR) to capture how HEHA played into the five domains of CFIR: (a) intervention characteristics, (b) outer setting, (c) inner setting, (d) characteristics of the individuals, and (e) process. Data analysis captured themes under the CFIR domains. All five CFIR domains emerged from the interviews. Under intervention characteristics, three constructs emerged as facilitating the implementation of HEHA: (a) the participant’s beliefs around the quality of the HEHA program and its ability to promote healthy eating, (b) HEHA’s adaptability to different AAPI subgroups, and (c) perceptions of how successfully HEHA was bundled and assembled. Under outer setting, the participants described the community’s need for healthy eating programs and how the HEHA program meets that need. Four constructs emerged under inner setting: (a) the CBO’s structural characteristics and social standing in the community; (b) resources dedicated to the implementation and ongoing operations, including funding, training, education, physical space, and time; (c) the culture of the CBO; and (d) the participant’s commitment and involvement in marketing, promotion, and implementation of HEHA. Under characteristics of individuals, participants’ described their desire to learn the content of HEHA and deliver them successfully. Under process, participants described strategies to engage relevant individuals to facilitate HEHA implementation. The interviews with CBO representatives provided insights into CFIR domain constructs that facilitated the implementation of HEHA. CBOs are key settings for community health education. Understanding processes that lead to the successful implementation of evidence-based interventions among CBOs is critical for accelerating the dissemination and implementation of best practices.
Topography influences species-specific patterns of seasonal primary productivity in a semiarid montane forest
Authors: Murphy Patrick C , Knowles John F , Moore David J P , Anchukaitis Kevin , Potts Daniel L , Barron-Gafford Greg A
Published: June 2020

Semiarid forests in the southwestern USA are generally restricted to mountain regions where complex terrain adds to the challenge of characterizing stand productivity. Among the heterogeneous features of these ecosystems, topography represents an important control on system-level processes including snow accumulation and melt. This basic relationship between geology and hydrology affects radiation and water balances within the forests, with implications for canopy structure and function across a range of spatial scales. In this study, we quantify the effect of topographic aspect on primary productivity by observing the response of two codominant native tree species to seasonal changes in the timing and magnitude of energy and water inputs throughout a montane headwater catchment in Arizona, USA. On average, soil moisture on north-facing aspects remained higher during the spring and early summer compared with south-facing aspects. Repeated measurements of net carbon assimilation (Anet) showed that Pinus ponderosa C. Lawson was sensitive to this difference, while Pseudotsuga menziesii (Mirb.) Franco was not. Irrespective of aspect, we observed seasonally divergent patterns at the species level where P. ponderosa maintained significantly greater Anet into the fall despite more efficient water use by P. menziesii individuals during that time. As a result, this study at the southern extent of the geographical P. menziesii distribution suggests that this species could increase water-use efficiency as a response to future warming and/or drying, but at lower rates of production relative to the more drought-adapted P. ponderosa. At the sub-landscape scale, opposing aspects served as a mesocosm of current versus anticipated climate conditions. In this way, these results also constrain the potential for changing carbon sequestration patterns from Pinus-dominated landscapes due to forecasted changes in seasonal moisture availability.
The longirostrine crocodyliforms from Bolivia and their evolution through the Cretaceous–Palaeogene boundary
Authors: Jouve Stéphane , de Muizon Christian , Cespedes-Paz Ricardo , Sossa-Soruco Víctor , Knoll Stephane
Published: June 2020

Numerous aquatic crocodyliforms have been found during the last four decades of fieldwork in the Maastrichtian El Molino and Palaeocene Santa Lucía Formations in Bolivia. We describe new material in detail and review previously described specimens. This work enables identification of at least three new Palaeocene dyrosaurid species and the reassignement of the Maastrichtian crocodylian Dolichochampsa minima to Gavialoidea. Dolichochampsa minima is thus the oldest known South American member of this clade; previously, gavialoids were known from this continent only since the late Eocene. A new phylogenetic analysis suggests that Vectisuchus leptognathus and Elosuchus are more closely related to Dyrosauridae, and a new name, Dyrosauroidea, is proposed for this clade. Several characters previously considered as typical for dyrosaurids are present in Elosuchus. Comparison of this phylogenetic analysis with geographical and temporal distributions helps to reveal a new scenario for dyrosaurid dispersal. A high number of intercontinental interchanges occurred during the Maastrichtian, whereas higher intracontinental diversification occurred during the lower Palaeocene.
Factors Associated With Pulmonary Embolism Among Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: A Multicenter Study Among 375 Patients
Authors: Soumagne Thibaud , Lascarrou Jean-Baptiste , Hraiech Sami , Horlait Geoffroy , Higny Julien , d’Hondt Alain , Grimaldi David , Gaudry Stéphane , Courcelle Romain , Carbutti Giuseppe , Blonz Gauthier , Aissaoui Nadia , Vinsonneau Christophe , Vandenbunder Benoit , Textoris Julien , Szychowiak Piotr , Serck Nicolas , Sauneuf Bertrand , Piagnerelli Michael , Ly Andre , Lejeune François , Lefebvre Laurent , Piton Gaël
Published: June 2020

Risk factors associated with pulmonary embolism in coronavirus disease 2019 acute respiratory distress syndrome patients deserve to be better known. We therefore performed a post hoc analysis from the COronaVirus-Associated DIsease Study (COVADIS) project, a multicenter observational study gathering 21 ICUs from France (n = 12) and Belgium (n = 9). Three-hundred seventy-five consecutive patients with moderate-to-severe acute respiratory distress syndrome and positive coronavirus disease 2019 were included in the study. At day 28, 15% were diagnosed with pulmonary embolism. Known risk factors for pulmonary embolism including cancer, obesity, diabetes, hypertension, and coronary artery disease were not associated with pulmonary embolism. In the multivariate analysis, younger age (< 65 yr) (odds ratio, 2.14; 1.17–4.03), time between onset of symptoms and antiviral administration greater than or equal to 7 days (odds ratio, 2.39; 1.27–4.73), and use of neuromuscular blockers greater than or equal to 7 days (odds ratio, 1.89; 1.05–3.43) were independently associated with pulmonary embolism. These new findings reinforce the need for prospective studies that will determine the predictors of pulmonary embolism among patients with severe coronavirus disease 2019.
Interventions in Post-Intensive Care Syndrome-Family: A Systematic Literature Review
Authors: Zante Bjoern , Camenisch Sabine A. , Schefold Joerg C.
Published: June 2020

Objectives:

Data show that family members of ICU patients may have high levels of anxiety, depression, posttraumatic stress disorders, and/or complicated grief. This was previously referred to as post-intensive care syndrome-family. We systematically review randomized controlled trials for post-intensive care syndrome-family.

Data Sources:

Systematic research in databases (Pubmed, EMBASE, PsycINFO, CINHAL for articles published between January 2000 and October 2019).

Study Selection:

Interventions in randomized controlled trials for post-intensive care syndrome-family in relatives of adult ICU patients.

Data Extraction:

Review, quality assessment, and risk assessment for bias of eligible publications were performed along recommended guidelines for each investigation. Quality assessment graded studies into “strong” (n = 5), “moderate” (n = 4), and “weak” (n = 2).

Data Synthesis:

Out of 2,399 publications, 11 investigations were found eligible (3,183 relatives of ICU patients). Studies addressed interventions during ICU stay (n = 6), during the post-ICU period (n = 4), or both (n = 1). Two studies included relatives of dying/deceased patients. One study implemented end-of-life conferences and showed reduced prevalence of posttraumatic stress disorder (45% vs 69%; p = 0.01), anxiety (45% vs 67%; p = 0.02), and depression (29% vs 56%; p = 0.003). Family conferences with a physician and proactive participation of a nurse reduced anxiety-scores (p = 0.01) without reducing anxiety prevalence (33.3% vs 52.3%; p = 0.08). Other studies failed to improve symptoms or reduce prevalence of post-intensive care syndrome-family. Interestingly, condolence letters may even increase prevalence of posttraumatic stress disorder (52.4% vs 37.1%; p = 0.03). Meetings without the presence of ICU physicians were shown to increase Impact of Event Scale-Revised scores (25.9 vs 21.3; p = 0.0495).

Conclusions:

Only few data are available on interventions for post-intensive care syndrome-family. It appears that proactive communication and provision of information seems pivotal for post-intensive care syndrome-family treatment. Interestingly, some interventions may even worsen post-intensive care syndrome-family. In the light of the relevance of post-intensive care syndrome-family in daily ICU care, more high-quality data seems urgently needed.
Trends, Cost, and Mortality From Sepsis After Trauma in the United States: An Evaluation of the National Inpatient Sample of Hospitalizations, 2012–2016
Authors: Eguia Emanuel , Bunn Corinne , Kulshrestha Sujay , Markossian Talar , Durazo-Arvizu Ramon , Baker Marshall S. , Gonzalez Richard , Behzadi Faraz , Churpek Matthew , Joyce Cara , Afshar Majid
Published: June 2020

Objectives:

Identification and outcomes in patients with sepsis have improved over the years, but little data are available in patients with trauma who develop sepsis. We aimed to examine the cost and epidemiology of sepsis in patients hospitalized after trauma.

Design:

Retrospective cohort study.

Patients:

National Inpatient Sample.

Interventions:

Sepsis was identified between 2012 and 2016 using implicit and explicit International Classification of Diseases, Ninth and Tenth Revision codes. Analyses were stratified by injury severity score greater than or equal to 15. Annual trends were modeled using generalized linear models. Survey-adjusted logistic regression was used to compare the odds for in-hospital mortality, and the average marginal effects were calculated to compare the cost of hospitalization with and without sepsis.

Measurements and Main Results:

There were 320,450 (se = 3,642) traumatic injury discharges from U.S. hospitals with sepsis between 2012 and 2016, representing 6.0% (95% CI, 5.9–6.0%) of the total trauma population (n = 5,329,714; se = 47,447). In-hospital mortality associated with sepsis after trauma did not change over the study period (p > 0.40). In adjusted analysis, severe (injury severity score ≥ 15) and nonsevere injured septic patients had an odds ratio of 1.39 (95% CI, 1.31–1.47) and 4.32 (95% CI, 4.06–4.59) for in-hospital mortality, respectively. The adjusted marginal cost for sepsis compared with nonsepsis was $16,646 (95% CI, $16,294–$16,997), and it was greater than the marginal cost for severe injury compared with nonsevere injury $8,851 (95% CI, $8,366–$8,796).

Conclusions:

While national trends for sepsis mortality have improved over the years, our analysis of National Inpatient Sample did not support this trend in the trauma population. The odds risk for death after sepsis and the cost of care remained high regardless of severity of injury. More rigor is needed in tracking sepsis after trauma and evaluating the effectiveness of hospital mandates and policies to improve sepsis care in patients after trauma.
Molecular Mechanisms of Gut Microbiota-Associated Colorectal Carcinogenesis
Authors: Shao Yichang , Zeng Xun
Published: June 2020

Colorectal cancer (CRC) is the cancer occurring in colon and rectum, and is the fourth leading cause of tumor-associated deaths worldwide. As a multi-etiological cancer, CRC could be induced by genetic and environmental factors, including unhealthy diet, irregular lifestyle, inappropriate inflammatory, and the dysbiosis of gut microbiota. Since immunotherapy has been the most popular cancer therapy nowadays, the relationships among gut microbiota, host immune cells and CRC pathogenesis are widely investigated. Scientists constantly tried to figure out the underlying mechanisms involved to support the further therapeutic studies. In this review, we discuss the component shifts of gut microbiota in CRC patients compared with healthy people, summarize how immune cells participate in protecting host from pathogenic microbes, elaborate the molecular mechanisms involved in gut microbiota-associated carcinogenesis of colonic epithelial cells and look into how gut microbiota influence the CRC therapy.
Longitudinal Effects of Left Ventricular Assist Device Implantation on Global and Domain-Specific Cognitive Function
Authors: Faulkner Kenneth M. , Chien Christopher V. , Denfeld Quin E. , Gelow Jill M. , Lyons Karen S. , Grady Kathleen L. , Mudd James O. , Lee Christopher S.
Published: June 2020

Background

Left ventricular assist devices (LVADs) are a common treatment of advanced heart failure, but cognitive dysfunction, which is common in heart failure, could limit the ability to perform postimplantation LVAD care. Implantation of an LVAD has been associated with improved cerebral perfusion and may improve cognitive function post implantation.

Objective

The aim of this study was to quantify longitudinal change in cognitive function after LVAD implantation.

Methods

A secondary analysis of data on 101 adults was completed to evaluate cognitive function before implantation and again at 1, 3, and 6 months post implantation of an LVAD. Latent growth curve modeling was conducted to characterize change over time. Serial versions of the Montreal Cognitive Assessment were used to measure overall (total) cognitive function and function in 6 cognitive domains.

Result

There was moderate, nonlinear improvement from preimplantation to 6 months post implantation in Montreal Cognitive Assessment total score (Hedges' g = 0.50) and in short-term memory (Hedges' g = 0.64). There also were small, nonlinear improvements in visuospatial ability, executive function, and attention from preimplantation to 6 months post implantation (Hedges' g = 0.20–0.28). The greatest improvements were observed in the first 3 months after implantation and were followed by smaller, sustained improvements or no additional significant change.

Conclusions

Implantation of an LVAD is associated with significant, nonlinear improvement in short-term memory and global cognitive function, with the most significant improvements occurring in the first 3 months after implantation. Clinicians should anticipate improvements in cognitive function after LVAD implantation and modify postimplantation education to maximize effectiveness of LVAD self-care.
Unplanned PICU Readmission in a Middle-Income Country: Who Is at Risk and What Is the Outcome?*
Authors: Mat Bah Mohd Nizam , Syed Mohamed Sharifah Adlena , Abdullah Nisah , Alias Emieliyuza Yusnita
Published: June 2020

Objectives:

To study the rate of unplanned PICU readmission, determine the risk factors and its impact on mortality.

Design:

A single-center retrospective cross-sectional study.

Setting:

Tertiary referral PICU in Johor, Malaysia.

Patients:

All children admitted to the PICU over 8 years were included. Patients readmitted into PICU after the first PICU discharge during the hospitalization period were categorized into “early” (within 48 hr) and “late” (after 48 hr), and factors linked to the readmissions were identified. The mortality rate was determined and compared between no, early, and late readmission.

Interventions:

None.

Measurements and Main Results:

There were 2,834 patients in the study with 70 early and 113 late readmissions. Therefore, the rate of early and late PICU readmission was 2.5% (95% CI, 1.9–3.0%) and 3.9% (95% CI, 3.2–4.7%), respectively. The median length of stay of the second PICU admission for early and late readmissions was 2.7 days (interquartile range, 1.1–7.0 d) and 3.2 days (interquartile range, 1.2–7.5 d), respectively. The majority of early and late readmissions had a similar diagnosis with their first PICU admission. Multivariable multinomial logistic regression revealed a Pediatric Index Mortality 2 score of greater than or equal to 15, chronic cardiovascular condition, and oxygen supplement upon discharge as independent risk factors for early PICU readmission. Meanwhile, an infant of less than 1 year old, having cardiovascular, other congenital and genetic chronic conditions and being discharged between 8 am and 5 pm was an independent risk factor for late readmission. There was no significant difference in the mortality rate of early (12.9%), late (13.3%), and no readmission (10.7%).

Conclusions:

Despite the lack of resources and expertise in lower- and middle-income countries, the rate and factors for PICU readmission are similar to those in high-income countries. However, PICU readmission has no statistically significant association with mortality.
Mobile Extracorporeal Membrane Oxygenation: 5-Year Experience of a French Pediatric and Neonatal Center
Authors: Soreze Yohan , Smagghue Gabriel , Hervieux Erik , Julliand Sabestien , Genuini Mathieu , Piloquet Jean-Eudes , Rapp Mélanie , Starck Julie , Léger Pierre-Louis , Rambaud Jérôme
Published: June 2020

Objectives:

Extracorporeal membrane oxygenation is an established therapy for refractory cardiac and/or pulmonary failure that is not available in all centers. When infants and children require extracorporeal membrane oxygenation, they are sometimes placed on extracorporeal membrane oxygenation support in peripheral centers where extracorporeal membrane oxygenation is not available and then transferred on extracorporeal membrane oxygenation to specialized centers. The objective of this study is to first describe one of the largest cohorts of infants and children transported by a mobile unit while on extracorporeal membrane oxygenation.

Design:

We undertook a single-center retrospective study that included patients transported while on extracorporeal membrane oxygenation between November 1, 2014, and May 31, 2019.

Patients:

All patients transported by our mobile extracorporeal membrane oxygenation unit during the study period were included. Computerized data collection was approved by the French Data Protection Authority (Commission nationale de l'informatique et des libertés n° 2121127V0).

Main Results:

Over the study period, our extracorporeal membrane oxygenation mobile team transported 80 patients on extracorporeal membrane oxygenation among which 20 were newborns (25%) and 60 were children of 1 month to 17 years old (75%); 57 patients were on venoarterial-extracorporeal membrane oxygenation (71%) and 23 on venovenous-extracorporeal membrane oxygenation (29%). The average duration of transport was 8.4 hours with a median of 8 hours; the average distance travelled was 189 ± 140 km. Transport was by air and then ground for 50% of the patients and by ground for 42%. We observed a significant decrease in the Vasoactive-Inotropic Score (125 vs 99; p = 0.005) and Paco
2 levels (67 vs 49 mm Hg; p = 0.0005) after arrival in our unit. Survival rate 6 months after PICU discharge was 46% (37). There was a statistically significant relationship between initial lactate level and mortality (p = 0.02). We observed minor adverse events in 39% of the transports and had no mortality during transport.

Conclusions:

We describe one of the largest cohorts of infants and children transported by a mobile unit while on extracorporeal membrane oxygenation. Our findings confirm that it is safe to start extracorporeal membrane oxygenation in a referring center and to transport patients using an extracorporeal membrane oxygenation mobile team. The only risk factor associated with higher mortality was an initially elevated lactate level.
A Quality Improvement Project to Improve First Case On-time Starts in the Pediatric Operating Room
Authors: Pashankar Dinesh S. , Zhao Anna M. , Bathrick Rebecca , Taylor Cindy , Boules Heidi , Cowles Robert A. , Grossman Matthew
Published: June 2020

Background:

Delays in the operating room (OR) can lead to increased hospital costs as well as patient and provider dissatisfaction. Starting the first case on time in the OR can potentially prevent subsequent delays. We designed a quality improvement project to improve the first case on-time starts in the pediatric OR at a tertiary care children’s hospital.

Methods:

Following the collection of baseline data, we formed an interdisciplinary team. We analyzed the causes of delay and used the Six Sigma methodology of Define, Measure, Analyze, Improve, and Control. We identified key drivers and implemented several low-cost interventions using Plan-Do-Study-Act cycles. Major interventions included preoperative care coordination, strategic staggering of OR cases, and introduction of “Wow Bucks” incentives. We monitored start times and the delay in minutes for all first cases weekly. The OR minutes saved per week were calculated and used to estimate cost savings.

Results:

We studied a total of 1981 first-start cases from May 2018 to October 2019. The first case on-time starts improved from 62% to 77% over the study period. There was a significant improvement in total minutes delayed for all the first cases from 197.9 minutes per week down to 133 minutes per week (P < 0.05). Estimated cost savings were $4,023 per week due to improved OR utilization.

Conclusions:

A multidisciplinary collaborative team approach using quality improvement tools can improve on-time starts in the pediatric OR.
Neural progenitor cells-secreted exosomal miR-210 induced by hypoxia influences cell viability
Authors: Zhao Ming , Gao Yan , Wang Fei , Cheng Xiang , Zhao Tong , Zhao Yongqi , Fan Ming , Zhu Lingling
Published: June 2020

Hypoxia as a microenvironment is essential for the development of neural stem/progenitor cells (NSCs/NPCs). Our previous studies showed that mild hypoxia can promote proliferation of NPCs. However, the underlying mechanisms are remaining unknown. In the present study, we explored the impact of hypoxia on miR-210 secretion and its effect on cell viability. We found that short time or long time of hypoxia treatment could increase the expression of miR-210, but also promoted its secretion into the medium. The results of exosomes isolation and quantitative real-time PCR showed that hypoxia increased the levels of miR-210 in the exosome enriched from the medium. In addition, the secreted miR-210 can be absorbed by recipient NPCs. The resutls of cell viability assay showed that low levels of secreted miR-210 slightly increased cell viability of NPCs. In contrast, high levels of secreted miR-210 exhibited an inhibitory effect on cell viability. These effects were blocked by an miR-210-specific inhibitor. Taken together, hypoxia increased secretion of miR-210 in exosomes and exhibited a differential effect on cell viability of recipient NPCs.

Video abstract: https://links.lww.com/WNR/A588.
socru: typing of genome-level order and orientation around ribosomal operons in bacteria
Authors: Page Andrew J. , Ainsworth Emma V. , Langridge Gemma C.
Published: June 2020

Rearrangements of large genome fragments occur in bacteria between repeat sequences and can impact on growth and gene expression. Homologous recombination resulting in inversion between indirect repeats and excision/translocation between direct repeats enables these structural changes. One form of rearrangement occurs around ribosomal operons, found in multiple copies across many bacteria, but identification of these rearrangements by sequencing requires reads of several thousand bases to span the ribosomal operons. With long-read sequencing aiding the routine generation of complete bacterial assemblies, we have developed socru, a typing method for the order and orientation of genome fragments between ribosomal operons. It allows for a single identifier to convey the order and orientation of genome-level structure and we have successfully applied this typing to 433 of the most common bacterial species. In a focused analysis, we observed the presence of multiple structural genotypes in nine bacterial pathogens, underscoring the importance of routinely assessing this form of variation alongside traditional single-nucleotide polymorphism (SNP) typing.
Lagging strand encoding promotes adaptive evolution
Authors: Merrikh Christopher N. , Harris Leonard A. , Mangiameli Sarah , Merrikh Houra
Published: June 2020

Cells may be able to promote adaptive evolution in a gene-specific and temporally-controlled manner. Genes encoded on the lagging strand have a higher mutation rate and evolve faster than genes on the leading strand. This effect is likely driven by head-on replication-transcription conflicts, which occur when lagging strand genes are transcribed during DNA replication. We previously suggested that the ability to selectively increase mutagenesis in a subset of genes may provide an adaptive advantage for cells. However, it is also possible that this effect could be neutral or even highly deleterious. Distinguishing between these models is important because, if the adaptive model is correct, it would indicate that 1) head-on conflicts, which are generally deleterious, can also provide a benefit to cells, and 2) cells possess the remarkable ability to fine-tune adaptive evolution. Furthermore, investigating these models may address the long-standing debate regarding whether accelerated evolution through conflicts can be adaptive. To distinguish between the adaptive and neutral models, we conducted single nucleotide polymorphism (SNP) analyses on wild strains of bacteria, from divergent phyla. To test the adaptive hypothesis, we analyzed convergent mutation patterns. As a simple test of the neutral hypothesis, we performedin silicomodeling. Our results show that convergent mutations are enriched in lagging strand genes and that these mutations are unlikely to have arisen by chance. Additionally, we observe that convergent mutation frequency has a stronger positive correlation with gene-length in lagging strand genes. This effect strongly suggests that head-on conflicts between the DNA replication and transcription machineries are a key mechanism driving the formation of convergent mutations. Together, our data indicate that head-on replication-transcription conflicts can promote adaptive evolution in a variety of bacterial species, and potentially other organisms.
In silicoidentification of conservedcis-acting RNA elements in the SARS-CoV-2 genome
Authors: Alhatlani Bader Y.
Published: June 2020

Aim

The aim of this study was to computationally predict conserved RNA sequences and structures known ascis-acting RNA elements (CREs) located within the SARS-CoV-2 genome.

Materials & methods

Bioinformatics tools were used to analyse and predictcis-acting regulatory elements by obtaining viral sequences from available databases.

Results

Computational analysis prediction revealed the presence of RNA stem-loop structures within the 3’ end of the ORF1ab region that are analogous to the previously identified SARS-CoV genomic packaging signals. Alignment-based RNA secondary structures prediction of the 5’ end of the SARS-CoV-2 genome identified also conserved CREs.

Conclusion

These CREs could be used as potential targets for a vaccine and/or antiviral therapeutics developments; however, further studies would be required to confirm their roles in the SARS-CoV-2 life cycle.
Daptomycin resistance inEnterococcus faeciumcan be delayed by disruption of the LiaFSR stress response pathway
Authors: Prater Amy G. , Mehta Heer H. , Beabout Kathryn , Supandy Adeline , Miller William R. , Tran Truc T. , Arias Cesar A. , Shamoo Yousif
Published: June 2020

The LiaFSR signaling pathway plays a major role in mediating daptomycin (DAP) resistance for bothEnterococcus faecalisandEnterococcus faecium. LiaFSR inhibition induces DAP hypersusceptibility but could also potentially delay the acquisition of DAP resistance in a combinatorial therapy of DAP with a LiaFSR inhibitor. To evaluate the potential efficacy of this approach, the adaptation to DAP by bothE. faecalisandE. faeciumlacking a functional LiaFSR were examined. Here, clinical isolates ofE. faeciumwithliaRdeletions were evolved to DAP resistance usingin vitroexperimental evolution. Genomic analysis of resistant populations was used to identify both the alleles and their relative frequencies in driving DAP resistance. Microscopic and biochemical analyses were then employed to investigate how those adaptive alleles contributed to DAP resistance. We found that deletion ofliaRfrom theE. faeciumgenome significantly delayed the onset of DAP resistance. Unsurprisingly, resistance strategies emerged eventually. These alternative strategies were influenced by both environment and ancestral genome. The delay in the acquisition of DAP resistance whenliaRwas deleted supports the concept of developing a LiaFSR pathway inhibitor to prolong DAP efficacy against enterococci. The loss of a functional LiaFSR pathway reset the adaptive landscape and forced adaptation to progress in new ways that were slower in providing DAP tolerance. The observed adaptive trajectories were strongly influenced by both the environment and ancestral genome.
Stroke increases the expression of ACE2, the SARS-CoV-2 binding receptor, in murine lungs
Authors: Singh Vikramjeet , Beer Alexander , Kraus Andreas , Zhang Xiaoni , Xue Jinhua , Hermann Dirk M , Gunzer Matthias
Published: June 2020

Background

The newly emerged severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a worldwide pandemic of human respiratory disease. Angiotensin-converting enzyme (ACE) 2 is the key receptor on lung epithelial cells to facilitate initial binding and infection of SARS-CoV-2. The binding to ACE2 is mediated via the spike glycoprotein present on the virus surface. Recent clinical data have demonstrated that patients suffering from stroke are particularly susceptible to severe courses of SARS-CoV-2 infection, thus forming a defined risk group. However, a mechanistic explanation for this finding is lacking. Sterile tissue injuries including stroke induce lymphocytopenia and systemic inflammation that might modulate the expression levels of surface proteins in distant organs. Whether systemic inflammation following stroke can specifically modulate ACE2 expression in the lung has not been investigated.

Methods

Mice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min and sacrificed after 24 h and 72 h for analysis of brain and lung tissues. Gene expression and protein levels of ACE2, ACE, IL-6 and IL1β were measured by quantitative PCR and Western blot, respectively. Immune cell populations in lymphoid organs were analyzed by flow cytometry.

Results

Strikingly, 24 h after stroke, we observed a substantial increase in the expression of ACE2 both on the transcriptional and protein levels in the lungs of MCAO mice compared to sham-operated mice. This increased expression persisted until day 3 after stroke. In addition, MCAO increased the expression of inflammatory cytokines IL-6 and IL-1β in the lungs. Higher gene expression of cytokines IL-6 and IL-1β was found in ischemic brain hemispheres and a reduced number of T-lymphocytes were present in the blood and spleen as an indicator of sterile tissue injury-induced immunosuppression.

Conclusions

We demonstrate significantly augmented ACE2 levels and inflammation in murine lungs after experimental stroke. These pre-clinical findings might explain the clinical observation that patients with pre-existing stroke represent a high-risk group for the development of severe SARS-CoV-2 infections. Our studies call for further investigations into the underlying signaling mechanisms and possible therapeutic interventions.

Highlights

Brain tissue injury increases ACE2 levels in the lungs

Brain injury induces pro-inflammatory cytokine expression in the lungs

Brain injury causes parenchymal inflammation and systemic lymphopenia
SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids
Authors: Giobbe Giovanni Giuseppe , Bonfante Francesco , Zambaiti Elisa , Gagliano Onelia , Jones Brendan C. , Luni Camilla , Laterza Cecilia , Perin Silvia , Stuart Hannah T. , Pagliari Matteo , Bortolami Alessio , Mazzetto Eva , Manfredi Anna , Colantuono Chiara , Di Filippo Lucio , Pellegata Alessandro , Li Vivian Sze Wing , Eaton Simon , Thapar Nikhil , Cacchiarelli Davide , Elvassore Nicola , De Coppi Paolo
Published: June 2020

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as anin vitromodel for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2.
Strengthening The Organization and Reporting of Microbiome Studies (STORMS): A Reporting Checklist for Human Microbiome Research
Authors: Mirzayi Chloe , Renson Audrey , Zohra Fatima , Elsafoury Shaimaa , Geistlinger Ludwig , Kasselman Lora , Eckenrode Kelly , van de Wijgert Janneke , Loughman Amy , Marques Francine Z. ,   STORMS Consortium,   Genomic Standards Consortium,   Massive Analysis and Quality Control Society, Segata Nicola , Huttenhower Curtis , Dowd Jennifer B. , Jones Heidi E. , Waldron Levi
Published: June 2020

Background

Human microbiome research is a growing field with the potential for improving our understanding and treatment of diseases and other conditions. The field is interdisciplinary, making concise organization and reporting of results across different styles of epidemiology, biology, bioinformatics, translational medicine, and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies.

Methods

A multidisciplinary group of microbiome epidemiology researchers reviewed elements of available reporting guidelines for observational and genetic studies and adapted these for application to culture-independent human microbiome studies. New reporting elements were developed for laboratory, bioinformatic, and statistical analyses tailored to microbiome studies, and other parts of these checklists were streamlined to keep reporting manageable.

Results

STORMS is a 17-item checklist for reporting on human microbiome studies, organized into six sections covering typical sections of a scientific publication, presented as a table with space for author-provided details and intended for inclusion in supplementary materials.

Conclusions

STORMS provides guidance for authors and standardization for interdisciplinary microbiome studies, facilitating complete and concise reporting and augments information extraction for downstream applications.

Availability

The STORMS checklist is available as a versioned spreadsheet fromhttps://www.stormsmicrobiome.org/.