bluuebunny/crossref_metadata_2025 huggingface dataset:
Less in-toeing after femoral derotation osteotomy in adult patients with increased femoral version and posterior hip impingement compared to patients with femoral retroversion
Authors: Lerch Till D , Boschung Adam , Leibold Christiane , Kalla Roger , Kerkeni Hassen , Baur Heiner , Eichelberger Patric , Siebenrock Klaus A , Tannast Moritz , Steppacher Simon D , Liechti Emanuel F
Published: April 2022

In-toeing of the foot was associated with high femoral version (FV), while Out-toeing was associated with femoral-retroversion. Therefore, we report on (i) foot-progression-angle (FPA), (ii) prevalence of In-toeing and Out-toeing, and (iii) clinical outcome of patients treated with femoral-derotation-osteotomy (FDO). We performed a retrospective analysis involving 20 patients (20 hips) treated with unilateral FDO (2017–18). Of them, 14 patients had increased FV, 6 patients had femoral-retroversion. Follow-up time was mean 1 ± 1 years. All patients had minimal 1-year follow-up and the mean age was 29 ± 8 years. Patients with increased FV (FV > 35°) presented with positive posterior-impingement-test and mean FV was 49 ± 11° (Murphy method). Six patients with femoral-retroversion (FV < 10°) had positive anterior impingement test and mean FV of 5 ± 4°. Instrumented gait analysis was performed preoperatively and at follow-up using the Gaitrite system to measure FPA and was compared to a control group of 18 healthy asymptomatic volunteers (36 feet, mean age 29 ± 6 years). (i) Mean FPA increased significantly (P = 0.006) from preoperative 1.3 ± 7° to 4.5 ± 6° at follow-up for patients with increased FV and was not significantly different compared to the control group (4.0 ± 4.5°). (ii) In-toeing decreased from preoperatively (five patients) to follow-up (two patients) for patients with increased FV. Out-toeing decreased from preoperatively (two patients) to follow-up (no patient) for patients with femoral-retroversion. (iii) Subjective-hip-value of all patients increased significantly (P < 0.001) from preoperative 21 to 78 points at follow-up. WOMAC was 12 ± 8 points at follow-up. Patients with increased FV that underwent FDO walked with less In-toeing. FDO has the potential to reduce In-toeing and Out-toeing and to improve subjective satisfaction at follow-up.
Plug disintegration in gamma-ray burst jet eruption
Authors: Yalinewich Almog , Beniamini Paz
Published: April 2022

In this work, we consider the eruption of a tenuous relativistic hydrodynamic jet from a dense baryonic envelope. As the jet moves out and away, it carries along and continues to accelerate a layer of baryonic material, which we refer to as the plug. We solve the relativistic equations of motion for the trajectory of the plug, and verify it using a relativistic hydrodynamic simulation. We show that under these conditions, the plug breaks up at a radius larger by a factor of a few from the radius of the envelope, due to the onset of the Rayleigh–Taylor instability. After breakup, the jet continues to accelerate to higher Lorentz factors, while the plug fragments maintain a moderate Lorentz factor. The presence of slower moving ejecta can explain late time features of gamma-ray bursts such as X-ray flares without recourse to a long-lived engine.
Detection of strong scattering close to the eclipse region of PSR B1957+20
Authors: Bai J T , Dai S , Zhi Q J , Coles W A , Li D , Zhu W W , Hobbs G , Qiao G J , Wang N , Yuan J P , Filipović M D , Wang J B , Pan Z C , Shang L H , Dang S J , Wang S Q , Miao C C
Published: April 2022

We present the first measurement of pulse scattering close to the eclipse region of PSR B1957+20, which is in a compact binary system with a low-mass star. We measured pulse scattering time-scales up to 0.2 ms close to the eclipse and showed that it scales with the dispersion measure (DM) excess roughly as τ ∝ ΔDM2. Our observations provide the first evidence of strong scattering due to multipath propagation effects in the eclipsing material. We show that Kolmogorov turbulence in the eclipsing material with an inner scale of ∼100 m and an outer scale of the size of the eclipse region can naturally explain the observation. Our results show that the eclipsing material in such systems can be highly turbulent and suggest that scattering is one of the main eclipsing mechanisms at around 1.4 GHz.
The formation of globular clusters as a case of overcooling
Authors: Renzini Alvio , Marino Anna F , Milone Antonino P
Published: April 2022

Driven by recent observational findings, we select massive interactive binaries as the most suitable among the existing candidates for producing the chemical patterns typical of multiple populations of Galactic globular clusters. Still, to avoid supernova contamination, we are further driven to endorse the notion that above a critical mass stars fail to produce supernova events, but rather eventually sink into black holes without ejecting much energy and heavy metals. This assumption has the attractive implication of suppressing star formation feedback for some 5–10 million yr, in practice leading to runaway star formation, analog to overcooling that in absence of feedback would have turned most baryons into stars in the early Universe. Under such conditions, multiple episodes of star formation, incorporating binary star ejecta from previous episodes, appear to be unavoidable, thus accounting for the ubiquity of the multiple population phenomenon in globular clusters.
Toward resilience
Authors: Colombo Karen
Published: April 2022

Practicing self-care during the COVID-19 pandemic is crucial for nursing students to balance their academic lives and for their future success in the nursing profession.
Safety Does Not Happen by Accident: Preventing Human Error Through High-Reliability Practices
Authors: Vitale Michael G. , Raman Divya L.
Published: April 2022

Systems-level solutions are needed to combat human fallibility in health care delivery. We propose 3 key strategies to promoting patient safety: incorporating work-aids into clinical workflows, promoting interdisciplinary collaboration and teamwork, and investing in a culture of psychological safety.
Nonaccidental Trauma in Pediatric Elbow Fractures: When You Should Be Worried
Authors: Tadepalli Vaibhav , Schultz Jacob D. , Rees Andrew B. , Wollenman Lucas C. , Louer Craig R. , Lempert Nathaniel L. , Moore-Lotridge Stephanie N. , Schoenecker Jonathan G.
Published: April 2022

Background:

Nonaccidental trauma (NAT) is a rising source of morbidity and mortality in the pediatric population. Fractures are often the first cause for presentation to health care providers in the case of NAT but can be misidentified as accidental. Given that elbow fractures are the most common accidental injuries among pediatric patients, they are not traditionally associated with NAT. This study aims to determine the prevalence of NAT among elbow fractures and identify common features in nonaccidental elbow fractures.

Methods:

Current Procedural Terminology (CPT) codes were used to retrospectively identify all pediatric (0 to 17) elbow fractures at a single, tertiary children’s hospital between 2007 and 2017. Among these, all fractures for which an institutional child abuse evaluation team was consulted were identified. The medical record was then used to determine which of these fractures were due to NAT. Standard injury radiographs of all victims of NAT as well as all patients under 1 year of age were blinded and radiographically evaluated for fracture type by a pediatric orthopaedic surgeon.

Results:

The prevalence of nonaccidental elbow fractures across the 10-year study period was 0.4% (N=18). However, the prevalence of nonaccidental elbow fractures in those patients below 1 year of age was markedly higher at 30.3% (10/33). Among all elbow fractures in patients below 1 year of age, supracondylar humerus fractures were the most common fracture type (19/33, 57.6%), yet transphyseal fractures (6/33, 18.1%) were most commonly the result of NAT (5/6, 83.3%). In children over 1 year of age, fracture type was not an indicator of NAT.

Conclusions:

The vast majority of pediatric elbow fractures (99.6%) are accidental. However, certain factors, namely age below 1 year and transphyseal fractures increase the likelihood that these fractures may be a result of NAT.

Level of Evidence:

Level IV: retrospective case series.
Cutaneous Invasive Fungal Infections with Saksenaea Species in Immunocompetent Patients in Europe: A Systematic Review and Case Report
Authors: Planegger Andrea , Uyulmaz Semra , Poskevicius Audrius , Zbinden Andrea , Müller Nicolas J. , Calcagni Maurizio
Published: April 2022

Background:

Invasive fungal infections from Saksenaea, a fungus belonging to the Mucorales, have been rarely reported in central European climate zones. This study aims to raise awareness of invasive cutaneous infections with Saksenaea species. The first case of a cutaneous infection was diagnosed in Switzerland in an immunocompetent 79-year-old patient. A minor skin trauma of her left lower leg led to a fulminant infection causing necrosis and extensive loss of tissue. The combination of surgical debridement and administration of antifungal agents averted a prolonged course with a possible worse outcome. A pedicled hemisoleus muscle flap was used to reconstruct the defect and treatment was continued for 63 days.

Methods:

A systematic review in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis guidelines was conducted to identify all European cases of infection with Saksenaea species in immunocompetent hosts. The epidemiology, clinical presentation, microbiological diagnosis, and management of cases reported in Europe were summarized and analyzed.

Conclusions:

The prognosis of soft tissue infections with Saksenaea species. depends on early diagnosis and appropriate antifungal and surgical treatment. Reconstruction can be successful under ongoing antifungal treatment.
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in the Setting of Daptomycin Administration
Authors: Repetsky Christopher D. , Morehart Candice Rae , Henning Ania K.
Published: April 2022

We present a case of Stevens-Johnson syndrome/toxic epidermal necrolysis in a 71-year-old male patient who was treated with daptomycin for infection of a prosthetic shoulder joint. After total shoulder arthroplasty, he had developed symptoms concerning for infection and had a PICC line placed for antibiotic therapy. He developed fever, tachycardia, hypoxia, and a diffuse bodily rash involving the skin and mucous membranes. He was admitted to the hospital. Daptomycin was stopped and was treated symptomatically. He ultimately required transfer to the local burn unit–equipped facility and was able to be discharged after short convalescence.
The Smartphone Hanger
Authors: Young Peter A. , Bae Gordon H.
Published: April 2022

As the COVID-19 pandemic smolders on, learners in medicine continue to face significant barriers to accruing essential clinical exposure because of social distancing, preceptor availability, and fluctuating patient volumes. The smartphone hanger represents a free and easily accessible means of rapidly disseminating high-quality, The Health Insurance Portability and Accountability Act of 1996-compliant skills tutorials during a time when learner access to in-person hands-on dermatology mentorship is unpredictable and less available.
Outpatient Pain Management in Children With Chronic Pancreatitis
Authors: Perito Emily R. , Pohl John F. , Bakker Caitlin , Armfield Matthew A. , Barth Bradley , Cuneo Addison , Mascarenhas Maria , Mehta Megha , Schwarzenberg Sarah Jane
Published: April 2022

Objectives

Although pain management is central to pediatric chronic pancreatitis (CP) care, no evidence-based guidelines exist. In this scoping systematic review, we sought promising strategies for CP pain treatment in children.

Methods

We systematically reviewed literature on pain management in children and adults with CP, and 2 conditions with similar pain courses: juvenile idiopathic arthritis and sickle cell disease.

Results

Of 8997 studies identified, 287 met inclusion criteria. There are no published studies of analgesic medications, antioxidants, dietary modification, integrative medicine, or regional nerve blocks in children with CP. In adults with CP, studies of nonopioid analgesics, pancreatic enzymes, and dietary interventions have mixed results. Retrospective studies suggest that endoscopic retrograde cholangiopancreatography and surgical procedures, most durably total pancreatectomy with islet autotransplant, improve pain for children with CP. Follow-up was short relative to a child's life. Large studies in adults also suggest benefit from endoscopic therapy and surgery, but lack conclusive evidence about optimal procedure or timing. Studies on other painful pediatric chronic illnesses revealed little generalizable to children with CP.

Conclusions

No therapy had sufficient high-quality studies to warrant untempered, evidence-based support for use in children with CP. Multicenter studies are needed to identify pain management “best practices.”
Barriers and Motives for Complying With “Sexual Distancing” Among Men Who Have Sex With Men During the First COVID-19 Pandemic Lockdown in Amsterdam: A Qualitative Study
Authors: de Vries Dominique C. , Zimmermann Hanne M.L. , Drückler Susanne , Davidovich Udi , Hoornenborg Elske , de Vries Henry John C.
Published: April 2022

Background

Between March 15 and May 31, 2020, the Dutch government imposed lockdown and health measures to curb the coronavirus disease 2019 (COVID-19) pandemic. As part of social distancing, sexual distancing was one of these measures. Sexual distancing implied refraining from sex with partners outside of one's household. We aimed to elucidate barriers and motives for complying with sexual distancing and related factors that could have led to (non)compliance among men who have sex with men.

Methods

In this exploratory qualitative study, we interviewed men who have sex with men who visited the center for sexual health in Amsterdam during the first COVID-19 lockdown using a semistructured interview guide from March to May 2020. We interviewed both men who complied and did not comply with sexual distancing. The interviews were transcribed verbatim and analyzed using an open-coding process in MAXQDA.

Results

We included 18 noncompliers and 4 compliers to COVID-19 sexual distancing. Barriers to compliance were the following: lack of information on, or understanding of, the need for sexual distancing; being single; having had an active sex life before COVID-19; a high perceived importance of the social aspect of sex; a strong urge for sex; using sex to cope with the negative impact of the pandemic; being under the influence of alcohol or drugs; and not perceiving COVID-19 as a serious health threat. Motives for compliance were the following: perceiving COVID-19 as a serious health threat, direct confrontation with critically ill COVID-19 patients, protecting someone dear from COVID-19, and being convinced of the importance of social and/or sexual distancing measures.

Conclusions

Information on sexual distancing needs to be made more explicit, accessible, understandable, inclusive, customized to individual barriers, and relatable to the key populations. This may improve the effectiveness of measures and health recommendations in both the current COVID-19 pandemic and future respiratory outbreaks.
Association Between Digoxin Use and Cardiac Function in Infants With Single-Ventricle Congenital Heart Disease During the Interstage Period
Authors: Kumar Karan R. , Flair Antonina , Thompson Elizabeth J. , Zimmerman Kanecia O. , Andersen Nicholas D. , Hill Kevin D. , Hornik Christoph P.
Published: April 2022

OBJECTIVES:

To examine the association between digoxin use and cardiac function assessed by echocardiographic indices in infants with single-ventricle (SV) congenital heart disease (CHD) during the interstage period.

DESIGN

Retrospective cohort study.

SETTING:

Fifteen North American hospitals.

PATIENTS:

Infants discharged home following stage 1 palliation (S1P) and prior to stage 2 palliation (S2P). Infants with no post-S1P and pre-S2P echocardiograms were excluded.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Of 373 eligible infants who met inclusion criteria, 140 (37.5%) were discharged home on digoxin. In multivariable linear and logistic regressions, we found that compared with infants discharged home without digoxin, those discharged with digoxin had a smaller increase in end-systolic volume (β = –8.17 [95% CI, –15.59 to –0.74]; p = 0.03) and area (β = –1.27 [–2.45 to –0.09]; p = 0.04), as well as a smaller decrease in ejection fraction (β = 3.38 [0.47–6.29]; p = 0.02) and fractional area change (β = 2.27 [0.14–4.41]; p = 0.04) during the interstage period.

CONCLUSIONS:

Digoxin may partially mitigate the expected decrease in cardiac function during the interstage period through its positive inotropic effects. Prospective clinical trials are needed to establish the pharmacokinetics, safety, and efficacy of digoxin use in SV CHD.
Impact of Blood Sampling on Anemia in the PICU: A Prospective Cohort Study
Authors: François Tine , Sauthier Michaël , Charlier Julien , Dessureault Jessica , Tucci Marisa , Harrington Karen , Ducharme-Crevier Laurence , Al Omar Sally , Lacroix Jacques , Du Pont-Thibodeau Geneviève
Published: April 2022

OBJECTIVES:

Fifty percent of children are anemic after a critical illness. Iatrogenic blood testing may be a contributor to this problem. The objectives of this study were to describe blood sampling practice in a PICU, determine patient factors associated with increased sampling, and examine the association among blood sampling volume, anemia at PICU discharge, and change in hemoglobin from PICU entry to PICU discharge.

DESIGN

Prospective observational cohort study.

SETTING:

PICU of Sainte-Justine University Hospital.

PATIENTS:

All children consecutively admitted during a 4-month period.

MEASUREMENTS AND MAIN RESULTS:

Four hundred twenty-three children were enrolled. Mean blood volume sampled was 3.9 (±19) mL/kg/stay, of which 26% was discarded volume. Children with central venous or arterial access were sampled more than those without access (p < 0.05). Children with sepsis, shock, or cardiac surgery were most sampled, those with a primary respiratory diagnosis; the least (p < 0.001). We detected a strong association between blood sample volume and mechanical ventilation (H, 81.35; p < 0.0001), but no association with severity of illness (Worst Pediatric Logistic Organ Dysfunction score) (R, –0.044; p = 0.43). Multivariate analysis (n = 314) showed a significant association between the volume of blood sampled (as continuous variable) and anemia at discharge (adjusted OR, 1.63; 95% CI, 1.18–2.45; p = 0.003). We lacked power to detect an association between blood sampling and change in hemoglobin from PICU admission to PICU discharge.

CONCLUSIONS:

Diagnostic blood sampling in PICU is associated with anemia at discharge. Twenty-five percent of blood losses from sampling is wasted. Volumes are highest for patients with sepsis, shock, or cardiac surgery, and in patients with vascular access or ventilatory support.
Trainee-led Engagement of the Care Team Improves Application of an Institutional Blood Culture Clinical Decision Algorithm to Pediatric Oncology Inpatients: A Single-institution Quality Improvement Project
Authors: Lemberg Kathryn M. , Koontz Danielle W. , Young David J. , DiDomizio P. Galen , King Anne , Chen Allen R. , Gamper Christopher J. , Colantuoni Elizabeth , Milstone Aaron M. , Cooper Stacy L.
Published: April 2022

Introduction:

Meaningful engagement in quality improvement (QI) projects by trainees is often challenging. A fellow-led QI project aimed to improve adherence to a blood culture clinical decision algorithm and reduce unnecessary cultures in pediatric oncology inpatients.

Methods:

We visualized preintervention rates of blood cultures drawn on pediatric oncology inpatients using a control chart. Following the introduction of the algorithm to our division, an Ishikawa fishbone diagram of cause-and-effect identified two areas for improvement: prescriber education on the algorithm and targeted feedback on its use. We developed two interventions to support algorithm awareness and use: (1) bundled educational interventions and (2) targeted chart review and feedback. Fellows reviewed >750 blood culture episodes and adjudicated each as “adherent” or “nonadherent” to the algorithm. In addition, fellows provided direct feedback to prescribers regarding nonadherent episodes and discussed strategies for algorithm adherence.

Results:

Blood culture rates in preintervention, intervention, and follow-up periods were 33.35, 25.24, and 22.67 cultures/100 patient-days, respectively. The proportion of nonadherent culture episodes decreased from 47.14% to 11.11%. The use of the algorithm did not prolong the time to cultures drawn on patients with new fever. Seventy-five percent of fellows provided feedback to inpatient teams on algorithm use. Following this project, trainees reported feeling more qualified to apply QI principles to patient care.

Conclusions:

Implementation of a clinical decision algorithm reduced the rate of cultures drawn on pediatric oncology inpatients. Fellow-led education of the care team decreased the proportion of nonadherent culture episodes and provided active engagement in QI.
Disease Course of Primary Dupuytren Disease: 5-Year Results of a Prospective Cohort Study
Authors: Broekstra Dieuwke C. , Lanting Rosanne , Werker Paul M. N. , van den Heuvel Edwin R.
Published: April 2022

Background:

Predicting progression of Dupuytren disease becomes relevant in an upcoming era with progression-preventing treatment. This study aimed to determine the course of Dupuytren disease and identify factors associated with progression.

Methods:

Two hundred fifty-eight patients with Dupuytren disease participated in this prospective cohort study, obtaining 17,645 observations in 5 years. Outcomes were disease extent (surface area) and contracture severity (total passive extension deficit). Demographics, lifestyle, health status, exposure to manual work, and genetic risk scores were gathered as potential predictors. Subject-specific, mixed-effects models were used to estimate disease course, and logistic regression with least absolute shrinkage and selection operator was used to evaluate factors associated with the presence of progression.

Results:

On average, Dupuytren disease was progressive in all finger rays with regard to area [yearly increase, 0.07 cm2 (95% CI, 0.02 to 0.13 cm2) to 0.25 cm2 (95% CI, 0.11 to 0.39 cm2)]. Progression in total passive extension deficit was only present on the small finger side [yearly increase, 1.75 degrees (95% CI, 0.30 to 3.20 degrees) to 6.25 degrees (95% CI, 2.81 to 9.69 degrees)]. Stability or regression in area and total passive extension deficit was observed in 11 and 13 percent and 16 and 15 percent (dominant and nondominant hands), respectively. Smoking, cancer, genetic risk score, and hand injury were univariate associated with progression in area, but after multivariate variable selection, none of these associations remained. No predictors for progression in total passive extension deficit were found.

Conclusions:

Dupuytren disease is progressive, especially with respect to disease extent. Progression in contracture severity is mainly present on the small finger side of the hand. None of the traditional risk and diathesis factors were associated with progression, indicating that new hypotheses about Dupuytren disease progression might be needed.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Can Posttransarterial Chemoembolization Volumetric Oil Deposition on Computed Tomography Predict Treatment Response on Magnetic Resonance Imaging in Leiomyosarcoma Metastases to the Liver?
Authors: Hazhirkarzar Bita , Shaghaghi Mohammadreza , Baghdadi Azarakhsh , Ghadimi Maryam , Ghasabeh Mounes Aliyari , Wu Qingxia , Tang Hao , Khoshpouri Pegah , Ameli Sanaz , Habibabadi Roya R. , Motaghi Mina , Meyer Christian F. , Kamel Ihab R.
Published: April 2022

Objective

To predict early tumor response to transarterial chemoembolization (TACE) based on volumetric oil deposition on posttreatment computed tomography (CT) in patients with leiomyosarcoma liver metastases.

Methods

This retrospective lesion-by-lesion based study included 32 lesions. The volumetric percent enhancing tumor on pre-TACE and 1-month post-TACE venous phase magnetic resonance imaging (MRI), and the percent oil deposition on CT 1 day after TACE were calculated. The predicted post-TACE enhanced percentage was computed by subtracting percent oil deposition from baseline percent enhanced.

Results

Mean percentage of viable tumor on pre-TACE MRI was 90.6% ± 9.3%. Mean oil deposition was calculated as 51.4% ± 26.2%. Mean percentage of measured residual tumor enhancement 1 month after TACE was 58.3% ± 27%, which correlates with predicted enhancement percentage of 43.9% ± 25.1% (r = 0.72, P < 0.001). A threshold of 35.5% for enhancement reduction was determined to predict tumor response with an accuracy of 78.1%.

Conclusion

Volumetric oil deposition on CT can predict residual enhancement on post-TACE MRI.
A Modified Bowel Displacement Technique for Magnetic Resonance Imaging–Guided Focused Ultrasound Surgery in the Treatment of Uterine Fibroids and Adenomyosis
Authors: Lai Mao , Chen Ye , Li Haoxiong , Li Yajie , Wu Shiman , Li Zhanfeng , Zhang Qi
Published: April 2022

Objective

The clinical application of magnetic resonance imaging–guided focused ultrasound (MRgFUS) surgery for treatment of symptomatic uterine fibroids is often limited because of the bowel between the abdominal wall and uterus. If bowels are in the pathway of sonication path, firstly filling the bladder, then filling the rectum, and emptying the bladder subsequently can be used to avoid them in recent research. The purpose of this study was to evaluate whether the modified bowel displacement technique (rectal filling first and then bladder filling, with or without subsequent bladder emptying) was feasible to create secure acoustic window.

Methods

A total of 78 patients who had undergone MRgFUS treatment for uterine fibroids and adenomyosis from January 2020 to November 2020 were included in this retrospective study. Of the 78 patients, 19 patients were treated using a modified bowel displacement technique, whereas the rest of the patients did not require intestinal displacement. High-intensity focused ultrasound was performed using GE Sightec HDXT 1.5 Tesla MR and ExAblate high-intensity focused ultrasound system.

Results

Of the 19 patients requiring bowel displacement techniques, 17 patients successfully completed MRgFUS surgery. Magnetic resonance imaging–guided focused ultrasound surgery was feasible in 4 patients after rectal filling, bladder filling, and subsequent bladder emptying. The others received ablation through the extended bladder because of bowel descending after emptying the bladder. The surgery caused no intestinal or uterine complications and no serious discomfort to the patient.

Conclusions

The modified bowel displacement technique was effective in displacing interposed bowels during MRgFUS treatment to create safe acoustic pathway for ablating uterine fibroids and adenomyosis.
Intensive Care Unit Critical Incident Analysis as an Objective Tool to Select Content for a Simulation Curriculum
Authors: Yartsev Alex , Yang Feibi
Published: April 2022

Introduction

The intensive care unit (ICU) offers a unique environment where emergency events are frequent, high-stakes, and carefully documented, which makes it an ideal setting to research the specific technical skills, which are deployed during such events. This study aimed to describe a method of objectively identifying skills and scenarios, which should be prioritized for inclusion in a simulation curriculum.

Method

A retrospective audit of all available critical incident data (11 months) from a 36-bed tertiary ICU was performed. Code blue events were analyzed. Data were coded according to a rubric based on Le Guen and Costa-Pinto (Intern Med J. 2020;51(8):1298–1303) tallying the occurrence of common ICU scenarios and skills.

Documentation of each event was analyzed. The frequency with which a skill or scenario appeared in these events was considered as “high frequency” if it occurred in more than 20% of the events.

The trainees' confidence in a particular skill was assessed by means of a self-assessment survey questionnaire (based on an anchored 6-item rating scale).

Results

One hundred twenty-one incidents were analyzed. Sixteen were eliminated because of insufficient documentation. The most common skills during these emergency events were familiarity with the advanced life support trolley (34% of events), electrocardiogram (ECG) rhythm strip interpretation (32.4%), and the operation of an external defibrillator (29.5%).

Most trainees surveyed are preparing to undergo training in anesthesia (58%) or intensive care (28%). Specialized areas of expertise (troubleshooting an extra-corporeal membrane oxygenation (ECMO) circuit or intra-aortic balloon pump) had the lowest confidence scores (average scores of 0.81 and 0.72).

Conclusions

We highlighted a novel, reproducible, and objective methodology by which critical incident data can be integrated with trainee self-assessment to generate a targeted simulation curriculum.
Social Support during pregnancy: A phenomenological exploration of young women’s experiences of support networks on pregnancy care and wellbeing in Soweto, South Africa
Authors: Mabetha Khuthala , Soepnel Larske , Klingberg Sonja , Mabena Gugulethu , Motlhatlhedi Molebogeng , Norris Shane A , Draper Catherine E
Published: April 2022

Social support is deemed to have a crucial influence on maternal health and wellbeing during pregnancy. The objective of the study was to explore the experiences of pregnant young females and their receipt of social support in Soweto, South Africa. An interpretive phenomenological approach was employed to understand and interpret pregnant young women’s lived experiences of support networks on their pregnancy care and wellbeing. Data was collected conducting 18 indepth interviews with young pregnant women. Analysis of the data resulted in the development of two superordinate themes: (1) relationships during pregnancy and (2) network involvement. Each superordinate theme was linked to subthemes that helped explain whether young women had positive or negative experiences of social support during their pregnancy care, and their wellbeing. The sub-themes emanating from the superordinate theme ‘relationships during pregnancy’ were (a) behavioural response of partner following disclosure of pregnancy, (b) behavioural response of family following disclosure of pregnancy, and (c) sense of emotional security. Accompanying subthemes of the superordinate theme ‘network involvement’ were (a) emotional and instrumental support, and (b) information support. An interpretation of the young women’s experiences has revealed that young women’s satisfaction with existing support networks and involvement of the various social networks contributed greatly to the participants having a greater sense of potential parental efficacy and increased acceptance of their pregnancies. Pregnant women who receive sufficient social support from immediate networks have increased potential to embrace and give attention to pregnancy-related changes. This could, in turn, foster positive behavioural outcomes that encourage engaging in good pregnancy care practices and acceptance of motherhood.

Focusing on previously unexamined factors that could improve maternal health, such as social support, could improve maternal mortality rates and help achieve reproductive health accessibility universally.
Functional response to a microbial synbiotic in the gastrointestinal system of constipated children
Authors: Tierney Braden T. , Versalovic James , Fasano Alessio , Petrosino Joseph F , Chumpitazi Bruno , Mayer Emeran A. , Boetes Jared , Smits Gerard , Parkar Shanthi G. , Voreades Noah , Kartal Ece , Bron Peter A. , Reid Gregor , Dhir Raja , Mason Christopher E.
Published: April 2022

Background

Oral microbial therapy has been studied as an intervention for a range of gastrointestinal and immunological disorders. Though emerging research suggests microbial exposure may intimately affect the gastrointestinal system, motility, and host immunity in a pediatric population, data has been inconsistent and variable, with the majority of prior studies conducted in neither a randomized nor placebo-controlled setting. The aim of this placebo-controlled study was to evaluate efficacy of a synbiotic (a prebiotic and rationally-defined microbial consortia) on increasing weekly bowel movement frequency in constipated children.

Methods

Sixty-four children (3-17 years of age) were randomized to receive a synbiotic composition (n=33) comprised of mixed-chain length, prebiotic oligosaccharides and nine microbial strains or placebo (n=31) for 84 days. Stool microbiota was analyzed using shotgun metagenomic sequencing on samples collected at baseline (T1) and completion (T2). The primary outcome was change from baseline of Weekly Bowel Movements (WBMs) in children compared to placebo.

Results

Treatment with a multi-strain synbiotic significantly (p < 0.05) increased the number of WBMs in children with low bowel movement frequency (< 4 WBMs and < 5 WBMs), irrespective of broadly distinctive microbiome signatures at baseline. Metagenomic shotgun sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p = 0.00074).

Conclusions

These findings suggest the potential for (i) multi-species synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children.

Impact

Synbiotic microbial treatment exerted functional improvements in the number of spontaneous Weekly Bowel Movements in children compared to placebo

Intervention induced a significant bifidogenic effect in children compared to placebo

All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo

Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention
Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV
Authors: Bessen Clara , Plaza-Sirvent Carlos , Bhat Jaydeep , Marheinecke Corinna , Urlaub Doris , Bonowitz Petra , Busse Sandra , Schumann Sabrina , Vidal Blanco Elena , Skaletz-Rorowski Adriane , Brockmeyer Norbert H , Overheu Oliver , Reinacher-Schick Anke , Faissner Simon , Watzl Carsten , Pfaender Stephanie , Potthoff Anja , Schmitz Ingo
Published: April 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and an ongoing global pandemic. Despite the development of vaccines, which protect healthy people from severe and life-threatening COVID-19, the immunological responses of people with secondary immunodeficiencies to SARS-CoV-2 mRNA vaccines are currently not well understood. Human Immunodeficiency Virus (HIV), causing acquired immunodeficiency syndrome (AIDS), targets CD4+ T helper (Th) cells that orchestrate the immune response. Anti-retroviral therapy suppresses HIV burden and restores Th cell numbers. Here, we investigated the humoral and cellular immune responses elicited by the BTN162b2 vaccine in a cohort of people living with HIV (PLWH), who receive anti-retroviral therapy. While antibody responses in PLWH increased progressively after the first and second vaccination compared to baseline, they were reduced compared to HIV negative study participants (controls). CD8+ T cells exhibited a general activated phenotype and increased effector and effector memory compartments. In contrast, CD4+ Th cell responses exhibited a vaccination-dependent increase and were comparable between PLWH and controls. In line with their reduced humoral response, the correlation between neutralizing antibodies and the CD4+ T cell response was decreased in PLWH compared to healthy controls. Interestingly, CD4+ T cell activation negatively correlated with the CD4 to CD8 ratio, indicating that low CD4 T cell numbers do not necessarily interfere with cellular immune responses. Taken together, our data demonstrate that COVID-19 mRNA vaccination in PLWH results in potent cellular immune responses, but the reduced antibody responses suggest that booster vaccination might be required for preventing disease.
Autophagic state prospectively identifies facultative stem cells in the intestinal epithelium
Authors: Johnson NM , Parham LR , Na J , Monaghan KE , Kolev HM , Klochkova A , Kim MS , Danan CH , Cramer Z , Simon LA , Naughton KE , Adams-Tzivelekidis S , Tian Y , Williams PA , Leu NA , Sidoli S , Whelan KA , Li N , Lengner CJ , Hamilton KE
Published: April 2022

The intestinal epithelium exhibits a rapid and efficient regenerative response to injury. Emerging evidence supports a model where plasticity of differentiated cells, particularly those in the secretory lineages, contributes to epithelial regeneration upon ablation of injury-sensitive stem cells. However, such facultative stem cell activity is rare within secretory populations. Here we ask whether specific functional properties predict facultative stem cell activity. We utilize in vivo labeling combined with ex vivo organoid formation assays to evaluate how cell age and autophagic state contribute to facultative stem cell activity within secretory lineages. Strikingly, we find that cell age (time elapsed since cell cycle exit) does not correlate with secretory cell plasticity. Instead, high autophagic activity predicts plasticity and resistance to DNA damaging injury independently of cell lineage. Our findings indicate that autophagic status prior to injury serves as a lineageagnostic marker for the prospective identification of facultative stem cells.
Multiple distinct evolutionary mechanisms govern the dynamics of selfish mitochondrial genomes
Authors: Gitschlag Bryan L. , Pereira Claudia V. , Held James P. , McCandlish David M. , Patel Maulik R.
Published: April 2022

Cells possess multiple mitochondrial DNA (mtDNA) copies, which undergo semi-autonomous replication and stochastic inheritance. This enables mutant mtDNA variants to arise and selfishly compete with cooperative (wildtype) mtDNA. Selfish mitochondrial genomes are subject to selection at different levels: they compete against wildtype mtDNA directly within hosts and indirectly through organismal selection. However, determining the relative contributions of selection at different levels has proven challenging. We overcome this challenge by combining mathematical modeling with experiments designed to isolate the levels of selection. Applying this approach to many selfish mitochondrial genotypes inCaenorhabditis elegansrevealed an unexpected diversity of evolutionary mechanisms. Some mutant genomes persist at high frequency for many generations, despite a host fitness cost, by aggressively outcompeting cooperative genomes within hosts. Conversely, some mutant genomes persist by evading organismal selection. Strikingly, the mutant genomes vary dramatically in their susceptibility to neutral drift. Although different mechanisms can cause high frequency of selfish mtDNA, we show how they give rise to characteristically different distributions of mutant frequency among individuals. Given that heteroplasmic frequency represents a key determinant of phenotypic severity, this work outlines an evolutionary theoretic framework for predicting the distribution of phenotypic consequences among individuals carrying a selfish mitochondrial genome.
Diversity and evolution of telomere and subtelomere DNA sequences in insects
Authors: Lukhtanov Vladimir A.
Published: April 2022

In insects, two types of telomere length maintenance are known: telomerase-dependent, resulting in chromosome ends consisting of short nucleotide repeats (typically TTAGG), and telomerase-independent, resulting in chromosome ends consisting of long nucleotide repeats or transposon-like elements. However, only a few species have been previously studied with regard to their telomere DNA sequences. Here, based on analysis of chromosome-level genome assemblies, I present the data on telomere and subtelomere organization for 180 species from 148 genera, 53 families and 8 orders of insects.

Analysis of these taxa reveals that in fact chromosome ends of most insect species have an intermediate structure and consist of numerous arrays of short telomeric repeats interspersed with telomere-specific non-LTR retrotransposons. An unexpectedly high level of diversity of short telomeric motifs (22 variants ranging in length from 1 to 17 nucleotides) is documented. Telomeres consisting of long repeats (from 173 to 374 bp) are confirmed for flies (the order Diptera) and also found in the orders Odonata and Hymenoptera. The most unusual telomere structure is found in the bee Lasioglossum lativentre, in which the chromosomes possess the short telomeric repeat TTAGGTCTGGG at only one end, whereas opposing ends terminate with medium and long repeats.

I conclude that different types of telomere organization and numerous variants of long and short T-containing motifs, including the (T)n mononucleotide sequence, are compatible with the performance of telomere functions. I argue that both telomerase-dependent and telomerase-independent mechanisms for maintaining telomere length operate simultaneously in many insects. The balance between them and the exchange of sequences between telomeres and subtelomeres are most likely the key factors that determine the structure and evolution of telomeres.

Significance

Multilayer telomeres, resulted from numerous, site-specific insertions of retrotransposons into the region of short telomeric repeats, are not an aberrant type of organization, as previously thought. They are widely distributed among insects and can represent up to 30-40 % of eukaryotic species diversity. Accordingly, the telomere maintenance mechanism based on the joint work of telomerase-dependent and telomerase-independent mechanisms can also be extremely widespread in nature.
Unexpected proteinopathies in hippocampal PDE11A4 promote age-related cognitive decline of social associative memories
Authors: Pilarzyk K , Porcher L , Capell WR , Burbano SD , Davis J , Fisher JL , Gorny N , Petrolle S , Kelly MP
Published: April 2022

In humans, associative memories are more susceptible to age-related cognitive decline (ARCD) than are recognition memories. Reduced cAMP/cGMP signaling in the hippocampus may contribute to ARCD. Here, we found that both aging and traumatic brain injury-associated dementia increased expression of the cAMP/cGMP-degrading enzyme phosphodiesterase 11A (PDE11A) in the human hippocampus. Further, age-related increases in hippocampal PDE11A4 mRNA and protein were conserved in mice, as was the increased vulnerability of associative versus recognition memories to ARCD. Interestingly, mouse PDE11A4 protein in the aged ventral hippocampus (VHIPP) ectopically accumulated in the membrane fraction and filamentous structures we term “ghost axons”. These age-related increases in expression were driven by reduced exoribonuclease-mediated degradation of PDE11A mRNA and increased PDE11A4-pS117/pS124, the latter of which also drove the punctate accumulation of PDE11A4. In contrast, PDE11A4-pS162 caused dispersal. Importantly, preventing age-related increases in PDE11 expression via genetic deletion protected mice from ARCD of short-term and remote long-term associative memory (aLTM) in the social transmission of food preference assay, albeit at the expense of recent aLTM. Further, mimicking age-related overexpression of PDE11A4 in CA1 of old KO mice caused aging-like impairments in CREB function and remote social—but not non-social—LTMs. RNA sequencing and phosphoproteomic analyses of VHIPP identified cGMP-PKG—as opposed to cAMP-PKA—as well as circadian entrainment, glutamatergic/cholinergic synapses, calcium signaling, oxytocin, and retrograde endocannabinoid signaling as mechanisms by which PDE11A deletion protects against ARCD. Together, these data suggest that PDE11A4 proteinopathies acutely impair signaling in the aged brain and contribute to ARCD of social memories.
Evolutionary history mediates population response to rapid environmental change through within-generational and transgenerational plasticity
Authors: Clement Dale , Neylan Isabelle P. , Roberts Nicholas J. , Schreiber Sebastian , Trimmer Pete C. , Sih Andrew
Published: April 2022

Rapid environmental change is affecting many organisms; some are coping well but many species are in decline. A key mechanism for facilitating success following environmental change is phenotypic plasticity. Organisms use cues to respond phenotypically to environmental conditions; many incorporate recent information (within-generation plasticity) and information from previous generations (transgenerational plasticity). We extend an existing evolutionary model where organisms utilize within-generational plasticity, transgenerational plasticity, rapid evolution, and bet-hedging. We show how, when rapid evolution of plasticity is not possible, the effect of environmental change (altering the environment mean, variance, or autocorrelation, or cue reliability) on population growth rate depends on selection for within-generation plasticity and transgenerational plasticity under historical environmental conditions. We then evaluate the predictions that populations adapted to highly variable environments, or with greater within-generational plasticity, are more likely to successfully respond to environmental change. We identify when these predictions fail, and show environmental change is most detrimental when previously reliable cues become unreliable. When multiple cues become unreliable, environmental change can cause deleterious effects regardless of the population’s evolutionary history. Overall, this work provides a general framework for understanding the role of plasticity in population responses to rapid environmental change.
THEMIS: A Framework for Cost-Benefit Analysis of COVID-19 Non-Pharmaceutical Interventions
Authors: Bertsimas Dimitris , Li Michael Lingzhi , Soni Saksham
Published: April 2022

Since December 2019, the world has been ravaged by the COVID-19 pandemic, with over 150 million confirmed cases and 3 million confirmed deaths worldwide. To combat the spread of COVID-19, governments have issued unprecedented non-pharmaceutical interventions (NPIs), ranging from mass gathering restrictions to complete lockdowns. Despite their proven effectiveness in reducing virus transmission, the policies often carry significant economic and humanitarian cost, ranging from unemployment to depression, PTSD, and anxiety. In this paper, we create a data-driven system dynamics framework, THEMIS, that allows us to compare the costs and benefits of a large class of NPIs in any geographical region across different cost dimensions. As a demonstration, we analyzed thousands of alternative policies across 5 countries (United States, Germany, Brazil, Singapore, Spain) and compared with the actual implemented policy.

Our results show that moderate NPIs (such as restrictions on mass gatherings) usually produce the worst results, incurring significant cost while unable to sufficiently slow down the pandemic to prevent the virus from becoming endemic. Short but severe restrictions (complete lockdown for 4-5 weeks) generally produced the best results for developed countries, but only if the speed of reopening is slow enough to prevent a resurgence. Developing countries exhibited very different trade-off profiles from developed countries, and suggests that severe NPIs such as lockdowns might not be as suitable for developing countries in general.