bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound subclinical synovitis in anti-CCP-positive at-risk individuals with musculoskeletal symptoms: an important and predictable stage in the rheumatoid arthritis continuum
Authors: Di Matteo Andrea , Duquenne Laurence , Cipolletta Edoardo , Nam Jacqueline L , Garcia-Montoya Leticia , Wakefield Richard J , Mahler Michael , Mankia Kulveer , Emery Paul
Published: November 2021

Objectives

To investigate whether anti-CCP2-positive at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis (CCP2+ at-risk) develop US subclinical synovitis before inflammatory arthritis and if US subclinical synovitis can be predicted.

Methods

First, US scans of CCP2+ at-risk individuals who developed inflammatory arthritis (‘progressors’) were reviewed for subclinical synovitis prior to inflammatory arthritis development. Patients in whom the pre-progression US scan was negative but the scan was conducted >6 months before progression were excluded. Subsequently, regression analyses were performed to identify predictors of US synovitis in CCP2+ at-risk individuals without baseline US abnormalities who had one or more longitudinal US scan and a complete dataset.

Results

US subclinical synovitis was detected in one or more scan in 75 of 97 progressors (77.3%) {median time to inflammatory arthritis development from first evidence of US synovitis 26.5 weeks [interquartile range (IQR) 7–60]}, in whom one or more scan was available, excluding those with a negative scan >6 months from inflammatory arthritis development (n = 38). In 220 CCP2+ at-risk individuals with normal baseline US scans, who had one or more longitudinal US scan and a complete dataset, US synovitis was detected in 69/220 (31.4%) [median time to first developing US synovitis 56.4 weeks (IQR 33.0–112.0)]. In the multivariable analysis, only anti-CCP3 antibodies were predictive for the development of US synovitis [odds ratio 4.75 (95% CI 1.97, 11.46); P < 0.01].

Conclusions

In anti-CCP2+ at-risk individuals, a stage of subclinical synovitis usually precedes the development of inflammatory arthritis. Anti-CCP2+/CCP3+ individuals without clinical or US subclinical synovitis may represent the optimal window of opportunity for intervention to prevent joint disease.
Association between insomnia patients’ pre-treatment characteristics and their responses to distinctive treatment sequences
Authors: Edinger Jack D , Beaulieu-Bonneau Simon , Ivers Hans , Guay Bernard , Bélanger Lynda , Simmons Bryan , Morin Charles M
Published: November 2021

Study Objectives

It is common to provide insomnia patients a second treatment when the initial treatment fails, but little is known about optimal treatment sequences for different patient types. This study examined whether pre-treatment characteristics/traits predict optimal treatment sequences for insomnia patients.

Methods

A community sample of 211 adults (132 women; Mage = 45.6 ± 14.9 years) with insomnia were recruited. Patients were first treated with behavioral therapy (BT) or zolpidem (Zol). Non-remitting BT recipients were randomized to a second treatment with either Zol or cognitive therapy; non-remitting Zol recipients underwent BT or Trazodone as a second treatment. Remission rates were assessed at the end of the first and second 6-week treatments. We then compared the remission rates of dichotomous groups formed on the basis of gender, age, pretreatment scores on SF36 and Multidimensional Fatigue Scale, the presence/absence of psychiatric/medical comorbidities or pain disorders, and mean subjective sleep duration and efficiency within and across treatment sequences.

Results

Lower remission rates were noted for those: with a pain disorder, poor mental health perceptions, high MFI fatigue scores, and lower sleep times and efficiencies. Patients with a pain disorder responded best to the BT-to-Zol sequence, whereas patients with more mental impairment, severe fatigue, short sleep, and low sleep efficiency responded poorly to treatment starting with BT.

Conclusions

Pain, fatigue, poor mental health status, and subjective sleep duration and efficiency all affect response to different insomnia treatment sequences. Findings may guide clinicians in matching insomnia treatments to their patients.

Clinical Trial Registration

ClinicalTrials.gov Identifier: NCT01651442, Protocol version 4, April 20, 2011, registered June 26, 2012, https://clinicaltrials.gov/ct2/show/NCT01651442?rslt=With&type=Intr&cond=Insomnia&cntry=US&state=US%3ACO&city=Denver&age=12&draw=2&rank=1.
Obstructive sleep apnea is an independent risk factor for severe COVID-19: a population-based study
Authors: Rögnvaldsson Kristján Godsk , Eyþórsson Elías Sæbjörn , Emilsson Össur Ingi , Eysteinsdóttir Björg , Pálsson Runólfur , Gottfreðsson Magnús , Guðmundsson Gunnar , Steingrímsson Vilhjálmur
Published: November 2021

Study Objectives

Obstructive sleep apnea (OSA) has been proposed as a risk factor for severe COVID-19. Confounding is an important consideration as OSA is associated with several known risk factors for severe COVID-19. Our aim was to assess the association of OSA with hospitalization due to COVID-19 using a population-based cohort with detailed information on OSA and comorbidities.

Methods

Included were all community-dwelling Icelandic citizens 18 years of age and older diagnosed with SARS-CoV-2 infection in 2020. Data on demographics, comorbidities, and outcomes of COVID-19 was obtained from centralized national registries. Diagnosis of OSA was retrieved from the centralized Sleep Department Registry at Landspitali – The National University Hospital. Severe COVID-19 was defined as the composite outcome of hospitalization and death. The associations between OSA and the outcome were expressed as odds ratios (OR) with 95% confidence intervals (95% CI), calculated using logistic regression models and inverse probability weighting.

Results

A total of 4,756 individuals diagnosed with SARS-CoV-2 infection in Iceland were included in the study (1.3% of the Icelandic population), of whom 185 had a diagnosis of OSA. In total, 238 were hospitalized or died, 38 of whom had OSA. Adjusted for age, sex, and BMI, OSA was associated with poor outcome (OR 2.2, 95% CI 1.4–3.5). This association was slightly attenuated (OR 2.0, 95% CI 2.0, 1.2–3.2) when adjusted for demographic characteristics and various comorbidities.

Conclusions

OSA was associated with twofold increase in risk of severe COVID-19, and the association was not explained by obesity or other comorbidities.
The case for prioritizing implementation strategy fidelity measurement: benefits and challenges
Authors: Akiba Christopher F , Powell Byron J , Pence Brian W , Nguyen Minh X B , Golin Carol , Go Vivian
Published: November 2021

Implementation strategies are systematic approaches to improve the uptake and sustainability of evidence-based interventions. They frequently focus on changing provider behavior through the provision of interventions such as training, coaching, and audit-and-feedback. Implementation strategies often impact intermediate behavioral outcomes like provider guideline adherence, in turn improving patient outcomes. Fidelity of implementation strategy delivery is defined as the extent to which an implementation strategy is carried out as it was designed. Implementation strategy fidelity measurement is under-developed and under-reported, with the quality of reporting decreasing over time. Benefits of fidelity measurement include the exploration of the extent to which observed effects are moderated by fidelity, and critical information about Type-III research errors, or the likelihood that null findings result from implementation strategy fidelity failure. Reviews of implementation strategy efficacy often report wide variation across studies, commonly calling for increased implementation strategy fidelity measurement to help explain variations. Despite the methodological benefits of rigorous fidelity measurement, implementation researchers face multi-level challenges and complexities. Challenges include the measurement of a complex variable, multiple data collection modalities with varying precision and costs, and the need for fidelity measurement to change in-step with adaptations. In this position paper, we weigh these costs and benefits and ultimately contend that implementation strategy fidelity measurement and reporting should be improved in trials of implementation strategies. We offer pragmatic solutions for researchers to make immediate improvements like the use of mixed methods or innovative data collection and analysis techniques, the inclusion of implementation strategy fidelity assessment in reporting guidelines, and the staged development of fidelity tools across the evolution of an implementation strategy. We also call for additional research into the barriers and facilitators of implementation strategy fidelity measurement to further clarify the best path forward.
Care Coordination: A Concept Analysis
Authors: Anderson Amanda , Hewner Sharon
Published: November 2021

Care coordination is both a well-known concept discussed in a wide range of multidisciplinary health care literature and a familiar nursing role in clinical practice; however, the definition of care coordination lacks role clarity across disciplines and within the nursing profession. Despite variations, defining factors of care coordination practice exist; however, role ambiguity limits the effective implementation of evidence-based care coordination in practice and policy. Following Walker and Avant's eight-step concept analysis method, we aim to further clarify care coordination as a concept and practice role and examine the value that nursing brings to its implementation.
Guiding Preclinical Medical Students in Finding, Synthesizing, and Communicating Translational Basic Research Literature: Roles for Basic Science Research Mentors
Authors: Maxwell Steve A. , Fuchs-Young Robin , Wells Gregg B. , Kapler Geoffrey M. , Conover Gloria M. , Green Sheila , Pepper Catherine , Gastel Barbara , Huston David P.
Published: November 2021

Problem

Understanding and communicating medical advances driven by basic research, and acquiring foundational skills in critically appraising and communicating translational basic research literature that affects patient care, are challenging for medical students to develop.

Approach

The authors developed a mandatory course from 2012 to 2018 at Texas A&M University College of Medicine to address this problem. Medical Student Grand Rounds (MSGR) trains first-year students to find, critically assess, and present primary research literature about self-selected medically relevant topics. With basic science faculty mentoring, students completed milestones culminating in oral presentations. Students learned to search literature databases and then choose a clinical subject using these skills. They outlined the clinical subject area background and a mechanistic research topic into a clinical problem based on deeper evaluation of primary research literature. “Mechanistic” was defined in this context as providing experimental evidence that explained the “how” and “why” underlying clinical manifestations of a disease. Students received evaluations and feedback from mentors about discerning the quality of information and synthesizing information on their topics. Finally, students prepared and gave oral presentations, emphasizing the primary literature on their topics.

Outcomes

In the early stages of the course development, students had difficulty critically assessing and evaluating research literature. Mentored training by research-oriented faculty, however, dramatically improved student perceptions of the MSGR experience. Mentoring helped students develop skills to synthesize ideas from basic research literature. According to grades and self-evaluations, students increased proficiency in finding and interpreting research articles, preparing and delivering presentations, and understanding links among basic and translational research and clinical applications.

Next Steps

The authors plan to survey fourth-year students who have completed MSGR about their perceptions of the course in the context of clinical experiences in medical school to guide future refinements.
The State of Point-of-Care Ultrasound Training in Undergraduate Medical Education: Findings From a National Survey
Authors: Russell Frances M. , Zakeri Bita , Herbert Audrey , Ferre Robinson M. , Leiser Abraham , Wallach Paul M.
Published: November 2021

Purpose

The primary aim of this study was to evaluate the current state of point-of-care ultrasound (POCUS) integration in undergraduate medical education (UME) at MD-granting medical schools in the United States.

Method

In 2020, 154 clinical ultrasound directors and curricular deans at MD-granting medical schools were surveyed. The 25-question survey collected data about school characteristics, barriers to POCUS training implementation, and POCUS curriculum details. Descriptive analysis was conducted using frequency and percentage distributions.

Results

One hundred twenty-two (79%) of 154 schools responded to the survey, of which 36 were multicampus. Sixty-nine (57%) schools had an approved POCUS curriculum, with 10 (8%) offering a longitudinal 4-year curriculum. For a majority of schools, POCUS instruction was required during the first year (86%) and second year (68%). Forty-two (61%) schools were teaching fundamentals, diagnostic, and procedural ultrasound. One hundred fifteen (94%) schools identified barriers to implementing POCUS training in UME, which included lack of trained faculty (63%), lack of time in current curricula (54%), and lack of equipment (44%). Seven (6%) schools identified no barriers.

Conclusions

Over half of the responding medical schools in the United States had integrated POCUS instruction into their UME curricula. Despite this, a very small portion had a longitudinal curriculum and multiple barriers existed for implementation, with the most common being lack of trained faculty. The data from this study can be used by schools planning to add or expand POCUS instruction within their current curricula.
Transfer of Clinical Decision-Making–Related Learning Outcomes Following Simulation-Based Education in Nursing and Medicine: A Scoping Review
Authors: Lavoie Patrick , Lapierre Alexandra , Maheu-Cadotte Marc-André , Fontaine Guillaume , Khetir Imène , Bélisle Marilou
Published: November 2021

Purpose

Simulation is often depicted as an effective tool for clinical decision-making education. Yet, there is a paucity of data regarding transfer of learning related to clinical decision-making following simulation-based education. The authors conducted a scoping review to map the literature regarding transfer of clinical decision-making learning outcomes following simulation-based education in nursing or medicine.

Method

Based on the Joanna Briggs Institute methodology, the authors searched 5 databases (CINAHL, ERIC, MEDLINE, PsycINFO, and Web of Science) in May 2020 for quantitative studies in which the clinical decision-making performance of nursing and medical students or professionals was assessed following simulation-based education. Data items were extracted and coded. Codes were organized and hierarchized into patterns to describe conceptualizations and conditions of transfer, as well as learning outcomes related to clinical decision-making and assessment methods.

Results

From 5,969 unique records, 61 articles were included. Only 7 studies (11%) assessed transfer to clinical practice. In the remaining 54 studies (89%), transfer was exclusively assessed in simulations that often included one or more variations in simulation features (e.g., scenarios, modalities, duration, and learner roles; 50, 82%). Learners’ clinical decision-making, including data gathering, cue recognition, diagnoses, and/or management of clinical issues, was assessed using checklists, rubrics, and/or nontechnical skills ratings.

Conclusions

Research on simulation-based education has focused disproportionately on the transfer of learning from one simulation to another, and little evidence exists regarding transfer to clinical practice. The heterogeneity in conditions of transfer observed represents a substantial challenge in evaluating the effect of simulation-based education. The findings suggest that 3 dimensions of clinical decision-making performance are amenable to assessment—execution, accuracy, and speed—and that simulation-based learning related to clinical decision-making is predominantly understood as a gain in generalizable skills that can be easily applied from one context to another.
Impact of COVID-19 on Medical Education: Perspectives From Students
Authors: Walters Marie , Alonge Taiwo , Zeller Matthew
Published: November 2021

This article provides an overview of issues facing medical students in such key areas as communication, preclinical and clinical education, increased isolation, disruption to time-based curricula, inequities in virtual learning, racial trauma, medical student activism, increased conversations surrounding race and racism, LGBTQIA+ students, dual-degree students, and the virtual residency cycle. This article described challenges navigated by medical students during the COVID-19 pandemic, as well as triumphs resulting from the disruption and actionable recommendations in key areas. While the pandemic presented new challenges for medical students, it also uncovered or exacerbated long-standing problems. The intent is for medical schools and institutions to use these recommendations to create learning environments that do not depend on medical student resilience. The main takeaways for medical schools are to: (1) maintain an individualized and learner-centered ethos while remaining dynamic, flexible, and ready to embrace both immediate and incremental changes; (2) maintain open lines of communication; (3) implement policies and practices that support students’ academic, physical, and mental well-being; (4) engage and support students who bear historically disadvantaged identities on the basis of race, ethnicity, sexual orientation, gender, or disability; and (5) support creative and collaborative partnerships between medical institutions and students to ensure the ongoing evolution of medical education to meet the needs of learners and patients.
Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury
Authors: Adegboye Janet , Sapatnekar Suneeti , Mascha Edward J. , Shah Karan , Lioudis Michael , Essber Hani , Cohen Barak , Rivas Eva , Heddle Nancy M. , Eikelboom John W. , Ellis Martin H. , Sharon Yehudit , Sinha Romi , Kurz Andrea , Sessler Daniel I.
Published: November 2021

Background

Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury.

Methods

The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria.

Results

The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units.

Conclusions

In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
The Effect of a Single Dose of Thiamine on Oxygen Consumption in Patients Requiring Mechanical Ventilation for Acute Illness: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Berg Katherine M. , Grossestreuer Anne V. , Andersen Lars W. , Liu Xiaowen , Donnino Michael W.
Published: November 2021

IMPORTANCE:

Lower oxygen consumption is associated with worse survival in septic shock and in other forms of critical illness. No treatment that increases oxygen extraction, a key determinant of oxygen consumption, has been found. Thiamine is required for aerobic metabolism, and deficiency is common in the critically ill.

OBJECTIVES:

We evaluated the effect of thiamine on oxygen consumption in patients requiring mechanical ventilation for an acute illness.

DESIGN:

Phase II, randomized, double-blind, and placebo-controlled trial.

SETTING AND PARTICIPANTS:

ICUs in a tertiary care hospital in the United States. Patients admitted to the ICU and requiring mechanical ventilation were screened for enrollment.

INTERVENTIONS:

After enrollment, baseline measurement of oxygen consumption and baseline laboratories including lactate, central venous oxygen saturation, and pyruvate dehydrogenase, a single dose of 200 mg IV thiamine or placebo was administered. Oxygen consumption was then monitored for 6 additional hours and repeat laboratories were drawn at the end of the protocol.

MAIN OUTCOMES AND MEASURES:

The primary outcome was the change in oxygen consumption. Analysis was done using linear regression with a first-order autoregressive variance-covariance structure to account for repeated measures within subjects. Secondary outcomes included change in lactate, central venous oxygen saturation, and pyruvate dehydrogenase quantity and activity.

RESULTS:

Sixty-seven patients were enrolled. After excluding 11 patients due to inadequate quantity or quality of oxygen consumption data, 56 patients were included. There was no difference in change in oxygen consumption in the 6 hours after study drug. Results for secondary outcomes were similarly negative. In the prespecified subgroup of 18 thiamine deficient patients, there was a difference in the two oxygen consumption curves (p = 0.006), although no difference in median oxygen consumption or area under the curve.

CONCLUSIONS AND RELEVANCE:

A single dose of IV thiamine did not alter oxygen consumption in patients requiring mechanical ventilation for acute illness.
WAS IT LEUCONOSTOC SPECIES? A CASE OF DELAYED-ONSET ENDOPHTHALMITIS PRESENTING 14 YEARS AFTER CATARACT SURGERY
Authors: Foster Lucas D. , McDonald Heather M. , Sheidow Tom G.
Published: November 2021

Purpose:

To report a case of delayed-onset endophthalmitis presenting 14 years after an uncomplicated cataract surgery.

Methods:

Case report.

Results:

An 89-year-old pseudophakic man complained of redness and reduced visual acuity in his right eye. He had no history of trauma or systemic infection, and his only surgery on the right eye was an uncomplicated cataract surgery 14 years before. On physical examination, he was found to have keratic precipitates and a white posterior capsular plaque in the right eye. He was treated with a right pars plana vitrectomy and intraocular lens removal. Microbiological classification of the samples revealed the presence of a Leuconostoc species within the vitreous humor and coagulase-negative staphylococci on the lens. Two months after placement of the intraocular lens, he achieved a best-corrected visual acuity of 20/200 in his right eye.

Conclusion:

To the best of our knowledge, this is the first reported case of delayed-onset endophthalmitis occurring more than 10 years after an uncomplicated cataract surgery. This case highlights a highly unusual presentation of delayed-onset endophthalmitis and reports a potential novel microbiological cause of plaque formation.
Sensorineural Hearing Loss After Teprotumumab Therapy for Thyroid Eye Disease: A Case Report
Authors: Ding Andy S. , Mahoney Nicholas R. , Campbell Ashley A. , Creighton Francis X.
Published: November 2021

Background and Objective:

Teprotumumab is a fully human IgG1 monoclonal antibody against insulin-like growth factor-1 receptor (IGF-1R). It has been approved by the FDA to treat thyroid eye disease (TED) by reducing extraocular muscle and orbital fat volume. In clinical trials, hearing loss was noted as a side effect in 7 to 12% of patients, but no formal audiometric investigations of these patients were reported. Furthermore, the FDA and manufacturer offer no formal guidelines for audiometric monitoring. This case report is the first to describe sensorineural hearing loss (SNHL) in a patient undergoing treatment with teprotumumab.

Patient:

A 77-year-old woman presenting with bilateral SNHL after treatment with teprotumumab therapy for TED.

Intervention:

Audiometric testing was performed due to worsening and prolonged SNHL after subsequent teprotumumab infusions.

Main Outcome Measures:

Word recognition scores, pure tone average.

Results:

Audiometry after discontinuation of therapy showed moderate to moderate-severe SNHL with word recognition scores of 64% in the right ear and 68% in the left ear.

Conclusions:

There are currently no formal guidelines for routine audiograms before, during, and after infusion of teprotumumab. Given that such guidelines exist for ototoxic medications such as gentamicin and cisplatin, we strongly encourage audiometric monitoring for patients undergoing treatment with teprotumumab.
Automated Calculation of Cochlear Implant Electrode Insertion Parameters in Clinical Cone-Beam CT
Authors: Andersen Steven Arild Wuyts , Keith Jason P. , Hittle Brad , Riggs William J. , Adunka Oliver , Wiet Gregory J. , Powell Kimerly A.
Published: November 2021

Hypothesis:

Automated processing of postoperative clinical cone-beam CT (CBCT) of cochlear implant (CI) patients can be used to accurately determine electrode contacts and integrated with an atlas-based mapping of cochlear microstructures to calculate modiolar distance, angular insertion distance, and scalar location of electrode contacts.

Background:

Hearing outcomes after CI surgery are dependent on electrode placement. CBCT is increasingly used for in-office temporal bone imaging and might be routinely used for pre- and post-surgical evaluation.

Methods:

Thirty-six matched pairs of pre- and postimplant CBCT scans were obtained. These were registered with an atlas to model cochlear microstructures in each dataset. Electrode contact center points were automatically determined using thresholding and electrode insertion parameters were calculated. Automated localization and calculation were compared with manual segmentation of contact center points as well as manufacturer specifications.

Results:

Automated electrode contact detection aligned with manufacturer specifications of spacing and our algorithms worked for both distantly- and closely spaced arrays. The average difference between the manual and the automated selection was 0.15 mm, corresponding to a 1.875 voxel difference in each plane at the scan resolution. For each case, we determined modiolar distance, angular insertion depth, and scalar location. These calculations also resulted in similar insertion values using manual and automated contact points as well as aligning with electrode properties.

Conclusion:

Automated processing of implanted high-resolution CBCT images can provide the clinician with key information on electrode placement. This is one step toward routine use of clinical CBCT after CI surgery to inform and guide postoperative treatment.
Angiopoietin-like proteins and postprandial partitioning of fatty acids
Authors: DiDonna Nicole M. , Chen Yan Q. , Konrad Robert J.
Published: November 2021

Purpose of review

Over the last two decades, evolving discoveries around angiopoietin-like (ANGPTL) proteins, particularly ANGPTL3, ANGPTL4, and ANGPTL8, have generated significant interest in understanding their roles in fatty acid (FA) metabolism. Until recently, exactly how this protein family regulates lipoprotein lipase (LPL) in a tissue-specific manner to control FA partitioning has remained elusive. This review summarizes the latest insights into mechanisms by which ANGPTL3/4/8 proteins regulate postprandial FA partitioning.

Recent findings

Accumulating evidence suggests that ANGPTL8 is an insulin-responsive protein that regulates ANGPTL3 and ANGPTL4 by forming complexes with them to increase or decrease markedly their respective LPL-inhibitory activities. After feeding, when insulin levels are high, ANGPTL3/8 secreted by hepatocytes acts in an endocrine manner to inhibit LPL in skeletal muscle, whereas ANGPTL4/8 secreted by adipocytes acts locally to preserve adipose tissue LPL activity, thus shifting FA toward the fat for storage. Insulin also decreases hepatic secretion of the endogenous ANGPTL3/8 inhibitor, apolipoprotein A5 (ApoA5), to accentuate ANGPTL3/8-mediated LPL inhibition in skeletal muscle.

The ANGPTL3/4/8 protein family and ApoA5 play critical roles in directing FA toward adipose tissue postprandially. Selective targeting of these proteins holds significant promise for the treatment of dyslipidemias, metabolic syndrome, and their related comorbidities.
Abdominal Symptoms Assessed With the CFAbd‐Score are Associated With Intestinal Inflammation in Patients With Cystic Fibrosis
Authors: Jaudszus Anke , Pfeifer Elena , Lorenz Michael , Beiersdorf Nathalie , Hipler Uta Christina , Zagoya Carlos , Mainz Jochen G.
Published: November 2021

Objectives:

This prospective study evaluated the relationship between fecal markers of intestinal inflammation and cystic fibrosis (CF)‐associated abdominal symptoms. These were assessed using the CFAbd‐Score, a CF‐specific patient‐related outcome measure developed and validated, following FDA guidelines.

Methods:

In feces from patients with CF (n = 41) and healthy volunteers (n = 27), concentrations of fecal calprotectin (FC), M2‐pyruvate kinase (M2‐PK), interleukins IL‐1β, IL‐6, IL‐8, and neutrophilic elastase (NE) were measured. Abdominal symptoms during the 2 preceding weeks were recorded using the CFAbd‐Score. This patient‐reported outcome measure (PROM) for assessment of the multi‐organic abdominal involvement in CF includes 28 items in five domains.

Results:

Inflammatory parameters FC, IL‐1β, M2‐PK, and NE in feces, as well as CFAbd‐Scores resulted significantly higher in CF patients than in healthy controls (all P < 0.01). Furthermore, significant differences between both groups were found for pain‐symptoms, disorders of bowel movement, impaired quality of life, as well as disorders of eating and appetite. With 83% sensitivity and 74% specificity, FC was the most reliable measure for CF‐related intestinal inflammation, which, in the CFAbd‐Score, was associated to significantly higher rates of abdominal pain, as well as to general quality of life items such as gastrointestinal‐related impaired sleep and frustration.

Conclusion:

Using the CFAbd‐Score as a CF‐specific PROM for identification and quantification of abdominal symptoms revealed that abdominal pain and impaired quality of life are associated with intestinal inflammation in CF.
Issues faced by people with amputation(s) during lower limb prosthetic rehabilitation: A thematic analysis
Authors: Turner Shruti , Belsi Athina , McGregor Alison H.
Published: November 2021

Background:

Successful rehabilitation is essential to improve the physical and mental outcomes of people with lower limb amputation(s). Individuals have different goals and expectations of successful rehabilitation and experience issues that affect their quality of life.

Objectives:

To determine factors affecting lower limb prosthetic rehabilitation from people with amputation(s), important for studies focusing on prosthetic and socket design and fitting because they provide context of need and user issues.

Study design:

Thematic analysis of semistructured interviews.

Methods:

Ten people with amputation(s) were self-selected from a survey identifying factors affecting lower limb prosthetic rehabilitation. The telephone interviews were semistructured exploring the biggest impactors on and frustrations with rehabilitation and the socket. A thematic analysis was completed by following the undermentioned steps: familiarization, coding, generating themes, reviewing themes, defining and naming themes, and reporting.

Results:

Five distinct but interrelated themes were identified: External to Prosthesis, Body Impactors, Consequences of Ill-Fit, Prosthesis Irritants, and Work and Social Impact. Those living with amputation(s) mentioned prosthetic-related issues affecting their work and social life, including difficulties wearing their prosthesis all day, the socket's rigidity, and the ability to participate in hobbies.

Conclusions:

The study provides new insights into the issues experienced during prosthetic rehabilitation, highlighting impacts beyond just physical health consequences. The study provides an evidence base for areas of the rehabilitation journey which could be improved to improve the quality of life of people with amputation(s).
Causes of death following discharge after trauma in North Carolina
Authors: Bryant Mary K. , Aubry Staci , Schiro Sharon , Raff Lauren , Perez Arielle J. , Reid Trista , Maine Rebecca G.
Published: November 2021

BACKGROUND

While a “fourth peak” of delayed trauma mortality has been described, limited data describe the causes of death (CODs) for patients in the years following an injury. This study investigates the difference in COD statewide for patients with and without a recent trauma admission.

METHODS

This retrospective cohort study compared COD for trauma and nontrauma patients in North Carolina. Death certificates in NC's death registry were matched with the NC trauma registry between January 2013 and December 2018 using matching on name and date of birth. Patients who died during the index trauma admission were excluded. Underlying COD recorded on the death certificate were used for the primary analysis.

RESULTS

Of 481,415 death records, 19,083 (4.0%) were linked to an alive discharge within the trauma registry during the study period. Prior trauma patients (PTPs) had a higher incidence of mental illness (9.2 vs. 6.1%), Alzheimer's (6.1% vs. 4.2%), and opioid-related (1.8% vs. 1.6%) COD compared to nontrauma patients, p < 0.05. Overall, suicide was higher in the nontrauma cohort (1.5% vs. 1.1%); however, PTP had higher incidences of death by motor vehicle collision and other injury (6.0% vs. 3.8%) and homicide (0.9% vs. 0.6%), p < 0.001. Prior trauma patients had 1.16 increased odds of an opioid-related death (p = 0.009; 95% confidence interval, 1.04–1.29) compared with those without prior trauma. Younger PTP had a much higher rate of death from suicide (12.0%) compared with those 41 to 65 years (2.8%) and older than 65 years (0.2%; p < 0.001). Discharge to skilled nursing facility (odds ratio, 1.87; p < 0.05) and severe injury (odds ratio, 1.93; p < 0.05) were associated with early death after discharge (≤90 days).

CONCLUSION

After hospital discharge, PTPs remain at risk of dying from future trauma and opioid-related conditions. Prevention strategies for PTP should address the increased risk of death from a subsequent traumatic injury and the at-risk populations for early death after discharge.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic, Level IV.
Resuscitative endovascular balloon occlusion of the aorta management guided by a novel handheld pressure transducer
Authors: Holtestaul Torbjorg , Jones Ian , Conner Jeffrey , Lammers Daniel , Weiss Jessica , Bingham Jason , Martin Matthew J. , Eckert Matthew
Published: November 2021

BACKGROUND

Management of noncompressible truncal hemorrhage using resuscitative endovascular balloon occlusion of the aorta (REBOA) requires arterial pressure monitoring that can be logistically challenging in austere or emergency settings. Novel pressure transducer devices such as the Centurion Compass device (CD) (Medline, Northfield, IL) offer an alternative to traditional monitoring systems. We sought to assess the feasibility of maintaining permissive hypotension during intermittent REBOA in a porcine model guided by CD monitoring.

METHODS

Eight Yorkshire swine underwent 20% hemorrhage with an uncontrolled iliofemoral vascular injury. Time-based intermittent zone 1 REBOA was performed with volume-based resuscitation to maintain permissive hypotension. Proximal mean arterial pressures (MAPs) from a carotid arterial line (AL) were obtained and compared with CD readings from the proximal REBOA port. The operator was blinded to AL MAP, and the REBOA was managed with exclusively the CD.

RESULTS

Mean survival time was 100 minutes (range, 41–120 minutes) from injury. Arterial line and CD measurements were closely correlated (r = 0.94, p < 0.001). Bland-Altman analysis for comparison of clinical measurements demonstrated a mean difference of 6 mm Hg (95% confidence interval, −22 to 34 mm Hg) for all MAPs, with a mean difference of 3 mm Hg (95% confidence interval, −6 to 12 mm Hg) in a clinically relevant MAP of <65 mm Hg subset.

CONCLUSION

The CD represents a miniaturized and portable arterial pressure monitor that provides an accurate alternative to logistically burdensome AL monitoring to guide REBOA use. The device is highly accurate even at hypotensive pressures and can be used to guide intermittent REBOA strategies.
We go farther together: practical steps towards conducting a collaborative autoethnographic study
Authors: Ratnapalan Savithiri , Haldane Victoria
Published: November 2021

Autoethnography is an underused qualitative research method in implementation science. Autoethnography can be used to reflect on and archive personal experiences, which can yield useful information to advance our knowledge. In particular, collaborative autoethnography is an important method towards providing greater insights on the experiences of multidisciplinary teams conducting research amidst complexity and intersectionality. In conducting a collaborative autoethnography, all authors are participants who narrate, analyze and theorize about their individual and or collective experiences. This article provides an overview of collaborative autoethnography for health research teams and implementation scientists embarking on autoethnographic studies.
Cryobanking of human distal lung epithelial cells for preservation of their phenotypic and functional characteristics
Authors: Konda Bindu , Mulay Apoorva , Yao Changfu , Israely Edo , Beil Stephen , Huynh Carissa A. , Tourtellotte Warren G. , Rampolla Reinaldo , Chen Peter , Carraro Gianni , Stripp Barry R.
Published: November 2021

The epithelium lining airspaces of the human lung is maintained by regional stem cells including basal cells of pseudostratified airways and alveolar type 2 pneumocytes (AT2) of the alveolar gas-exchange region. Despite effective methods for long-term preservation of airway basal cells, methods for efficient preservation of functional epithelial cell types of the distal gas-exchange region are lacking. Here we detail a method for cryobanking of epithelial cells from either mouse or human lung tissue for preservation of their phenotypic and functional characteristics. Flow cytometric profiling, epithelial organoid-forming efficiency, and single cell transcriptomic analysis, were used to compare cells recovered from cryopreserved tissue with those of freshly dissociated tissue. Alveolar type 2 cells within single cell suspensions of enzymatically digested cryobanked distal lung tissue retained expression of the pan-epithelial marker CD326 and the AT2 cell surface antigen recognized by monoclonal antibody HTII-280, allowing antibody-mediated enrichment and downstream analysis. Isolated AT2 cells from cryobanked tissue were comparable with those of freshly dissociated tissue both in their single cell transcriptome and their capacity for in vitro organoid formation in 3D cultures. We conclude that the cryobanking method described herein allows long-term preservation of distal human lung tissue for downstream analysis of lung cell function and molecular phenotype, and is ideally suited for creation of an easily accessible tissue resource for the research community.
Zika virus-induced TNF-α signaling dysregulates expression of neurologic genes associated with psychiatric disorders
Authors: Kung Po-Lun , Chou Tsui-Wen , Lindman Marissa , Chang Nydia P. , Buckley Benjamin D. , Atkins Colm , Daniels Brian P.
Published: November 2021

Zika virus (ZIKV) is an emerging flavivirus of global concern. ZIKV infection of the central nervous system has been linked to a variety of clinical syndromes, including microcephaly in fetuses and rare but serious neurologic disease in adults. However, the potential for ZIKV to influence brain physiology and host behavior following recovery from apparently mild or subclinical infection is less well understood. Furthermore, though deficits in cognitive function are well-documented following recovery from neuroinvasive viral infection, the potential impact of ZIKV on other host behavioral domains has not been thoroughly explored. In our study, we performed transcriptomic profiling of primary neuron cultures following ZIKV infection, which revealed altered expression of key genes associated with major psychiatric disorders, such as bipolar disorder and schizophrenia. Gene ontology enrichment analysis also revealed significant changes in gene expression associated with fundamental neurobiological processes, including neuronal development, neurotransmission, and others. These alterations to neurologic gene expression were also observed in the brainin vivousing an immunocompetent mouse model of ZIKV infection. Mechanistic studies identified TNF-α signaling via TNFR1 as a major regulatory mechanism controlling ZIKV-induced changes to neurologic gene expression. Our studies reveal that cell-intrinsic innate immune responses to ZIKV infection profoundly shape neuronal transcriptional profiles, highlighting the need to further explore associations between ZIKV infection and disordered host behavioral states.
The physics of liquid-to-solid transitions in multi-domain protein condensates
Authors: Ranganathan Srivastav , Shakhnovich Eugene
Published: November 2021

Many RNA-binding proteins (RBPs) that assemble into membraneless organelles, have a common architecture including disordered prion-like domain (PLD) and folded RNA-binding domain (RBD). An enrichment of PLD within the condensed phase gives rise to formation, on longer time scales, amyloid-like fibrils (aging). In this study, we employ coarse-grained Langevin dynamics simulations to explore the physical basis for the structural diversity in condensed phases of multi-domain RBPs. We discovered a highly cooperative first order transition between disordered structures and an ordered phase whereby chains of PLD organize in fibrils with high nematic orientational order. An interplay between homo-domain (PLD-PLD) and hetero-domain (PLD-RBD) interactions results in variety of structures with distinct spatial architectures. Interestingly, the different structural phases also exhibit vastly different intra-cluster dynamics of proteins, with diffusion coefficients 5 (disordered structures) to 50 times (ordered structures) lower than that of the dilute phase. Cooperativity of this liquid-solid transition makes fibril formation highly malleable to mutations or post-translational modifications. Our results provide a mechanistic understanding of how multi-domain RBPs could form assemblies with distinct structural and material properties.

Significance Statement

Assembly of proteins and nucleic acids into dense, liquid-like pockets is associated with several key functions including stress response, gene-regulation, DNA-repair and RNA processing. Several RNA binding proteins such as FUS are known to form liquid-like condensates that progressively harden into more dynamically, solid-like structures, a phenomenon that gets accelerated by disease mutations. In this study, we discover the mechanistic origins of this transition and show that small mutational or posttranslational modifications could result in sharp disorder-order transitions that could characterize accelerated liquid-solid transition in disease mutants.
Reconstitution of minimal motility system based on Spiroplasma swimming by expressing two bacterial actins in synthetic minimal bacterium
Authors: Kiyama Hana , Kakizawa Shigeyuki , Sasajima Yuya , Tahara Yuhei O , Miyata Makoto
Published: November 2021

Motility is one of the most important features of life, but its evolutionary origin remains unknown. In this study, we focused on Spiroplasma, commensal, or parasitic bacteria. They swim by switching the helicity of a ribbon-like cytoskeleton that comprises six proteins, each of which evolved from a nucleosidase and bacterial actin called MreB. We expressed these proteins in a synthetic, non-motile minimal bacterium, JCVI-syn3.0B, whose reduced genome was computer-designed and chemically synthesized. The synthetic bacterium exhibited swimming motility with features characteristic of Spiroplasma swimming. Moreover, some combinations of the two proteins produced a helical cell shape and swimming, suggesting that the swimming originated from the differentiation and coupling of bacterial actins, and we also obtained a minimal system for motility of the synthetic bacterium.

One-Sentence Summary

The minimal system comprised two bacterial actins that provided cell helicity and swimming to the synthetic minimal bacterium.
Chromatin fiber breaks into clutches under tension and crowding
Authors: Liu Shuming , Lin Xingcheng , Zhang Bin
Published: November 2021

The arrangement of nucleosomes inside chromatin is of extensive interest. While in vitro experiments have revealed the formation of 30 nm fibers, most in vivo studies have failed to confirm their presence in cell nuclei. To reconcile the diverging experimental findings, we characterized chromatin organization using a near atomistic model. The computed force-extension curve matches well with measurements from single-molecule experiments. Notably, we found that a dodeca-nucleosome in the two-helix zigzag conformation breaks into structures with nucleosome clutches and a mix of trimers and tetramers under tension. Such unfolded configurations can also be stabilized through trans interactions with other chromatin chains. Our study supports a hypothesis that disordered, in vivo chromatin configurations arise as folding intermediates from regular fibril structures. We further revealed that chromatin segments with fibril or clutch structures engaged in distinct binding modes and discussed the implications of these inter-chain interactions for a potential sol-gel phase transition.