bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation-Based Training Improves Fellows’ Competence in Brain Death Discussion and Declaration
Authors: Chen Patrick M. , Trando Aaron , LaBuzetta Jamie Nicole
Published: November 2021

Background:

Despite well-defined American Academy of Neurology guidelines for death by whole brain criteria (brain death), there is marked variability in national practice, which some have attributed to lack of formal education. Further, communication with surrogates and families about brain death is integral to brain death declaration. As such, we developed a targeted brain death curriculum combining didactics and simulation-based education to improve examination and subsequent communication skills with families.

Methods:

Multidisciplinary critical care fellows participated in (1) didactic and case-based curriculum, (2) brain death simulated examination (SimMan3G mannequin), and (3) a standardized family scenario with delivery of a brain death diagnosis to a surrogate “family member”. Fellows completed a precurriculum and postcurriculum multiple choice knowledge test and survey (Likert 1 to 10 scale) evaluating measures regarding diagnosis and communication of brain death. t Test and 2-tailed Wilcoxon signed rank test were used for statistical analysis (P<0.05).

Results:

Thirteen critical care fellows participated in the curriculum. Most fellows [80% (N=12)] had only participated in 0 to 5 brain death declarations before this intervention. There was significant improvement across all measures: self-rated knowledge (P=0.004), perceived knowledge relative to peers (P=0.002), confidence (P=0.001), and comfort (P=0.001) with performing a brain death exam, and comfort with family discussion (P=0.01). Objective test scores improved from 56 to 73% after simulation (P=0.004). All fellows found the curriculum beneficial.

Conclusion:

Trainees may lack sufficient exposure to brain death education. Didactics with simulation-based education can improve objective knowledge and subjective measures of comfort with brain death declaration and surrogate communication.
Marfan Syndrome Presenting as Spontaneous Coronary Artery Dissection and Arteriopathy
Authors: Blech Benzion , Dhamija Radhika , Ingall Timothy
Published: November 2021

Introduction:

Spontaneous coronary artery dissection (SCAD) is a term used to define a spontaneous separation of the coronary artery wall not related to underlying risk factors, such as trauma or underlying atherosclerotic disease. While SCAD has a range of different etiologies, with fibromuscular dysplasia being the most common, most cases of SCAD have no concomitant arteriopathy.

Case Report:

Here we describe a case of a patient who presented to our institution with SCAD and evidence of an asymptomatic arteriopathy involving extracranial segments of the carotid and vertebral arteries, later found to have a pathogenic variant in the FBN1 gene and ultimately diagnosed with Marfan syndrome. This has only been rarely described in the literature as an etiology for SCAD.

Conclusion:

Although rare, it is important to consider underlying connective tissue disorders in patients presenting with spontaneous coronary artery dissection and arteriopathy without underlying cardiovascular risk factors.
Internet+Continuing Nursing (ICN) Program Promotes Motor Function Rehabilitation of Patients With Ischemic Stroke
Authors: Chen Shuangqin , Huang Jianghua , Yao Lan , Zeng Yahua , Quan Huijun , Kang Huiling , Ou Yulan , Chen Shuangxi
Published: November 2021

Background and Purpose:

Ischemic stroke is a severe disorder with high rates of death and recurrence that causes disability in patients and for which there is currently no effective treatment. Internet-based rehabilitation helps patients with disability recover at home with the help of their household or family members in a nonclinical setting. However, the effects of the internet+continuing nursing (ICN) program on the recovery of patients after ischemic stroke remains unknown.

Methods:

In the present study, patients were treated with an ICN-based rehabilitation training program; subsequently, the Self-efficacy Scale for Chronic Disease, Questionnaire of Exercise Adherence, Motor Assessment Scale, Activities of Daily Living, and Stroke-specific Quality of Life were performed to evaluate the effects of the ICN program on patient self-confidence to persist with rehabilitation, functional exercise compliance, motor function, ability to live independently and quality of life following ischemic stroke.

Results:

We observed that, after the ICN intervention for 6 weeks and 3 months, the scores of Self-efficacy Scale for Chronic Disease, Questionnaire of Exercise Adherence, Motor Assessment Scale, Activities of Daily Living, and Stroke-specific Quality of Life in the ICN-treated group were significantly higher compared with those in the control group.

Conclusion:

These results suggested that the ICN program may promote the recovery of patients after ischemic stroke.
Bilateral Vestibular Failure May Improve With Treatment of the Underlying Condition
Authors: Smyth Duncan , Mossman Stuart
Published: November 2021

Introduction:

Bilateral vestibular failure (BVF) is an uncommon condition with numerous etiologies. It causes chronic oscillopsia and imbalance and is usually irreversible. We report 2 cases of BVF due to unusual causes, both of which improved with treatment of the underlying condition.

Case Reports:

The first patient was a 39-year-old female who developed profound BVF due to neurosarcoidosis. She was started on steroids and azathioprine and her vestibular function gradually improved, with essentially normal function 4.5 years after starting treatment. The second patient was a 54-year-old female who developed BVF in the context of glucagonoma. After treatment with octreotide, her vestibular function improved to almost normal, and she thus met the criteria for a probable paraneoplastic syndrome.

Conclusions:

While BVF is usually permanent, this report demonstrates that some cases are likely to be reversible with treatment of the underlying cause. It is therefore imperative for clinicians to ensure that patients with BVF are thoroughly investigated.
Artery of Percheron Occlusion in China
Authors: Cai Lina , Wang Qi , Cui Bin , Wang Peifu
Published: November 2021

Introduction:

The artery of Percheron (AOP) is a rare anatomical variant in which bilateral paramedian thalami are supplied by a single vascular branch arising from the P1 segment of the posterior cerebral artery. We present a case of AOP occlusion presenting as loss of consciousness and summarize the literature in Chinese to find the clinical characteristics.

Case Report:

An 83-year-old woman was found unconscious for 1 day at home and was sent to the hospital the next day. Cerebral magnetic resonance imaging on day 1 of the patient showed a recent bilateral paramedian thalamic infarction. Simultaneously, magnetic resonance angiography found evident artery stenosis of the right P1 segment of the posterior cerebral artery, suggesting that the patient was diagnosed with AOP occlusion. Since the patient has missed the best time for thrombolytic therapy, anticoagulant therapy was given immediately; as the patient was then found to have pulmonary infections, antibiotic therapy was also initiated. The neurological status of this patient improved very slow. In about 2 weeks, the patient becomes more conscious but still could not speak or move.

Conclusion:

Our report suggests that unusual mood disorder and language disorder of aged patients might indicate the AOP occlusion, and cerebral imaging of magnetic resonance imaging (better with magnetic resonance angiography) should be performed to establish the diagnosis of AOP occlusion. The fast and accurate diagnosis of stroke because of AOP occlusion could best benefit the patients.
Balloon-Assisted Angioplasty for the Treatment of In-Stent Restenosis After Vertebral Artery Ostium Stenting
Authors: Cai Xueli , Chen Xueping , Xiang Yian , Chen Liujing , Sun Jingping
Published: November 2021

Background:

Stenting appears to be a safe means of treatment for vertebral artery ostium stenosis with low complication rates and positive long-term effects, but the incidence of in-stent restenosis (ISR) after stenting is high. Different treatment strategies are applied for the revascularization of ISR; however, currently the optional approach is not recommended. The study was designed to investigate the feasibility, safety, and effectiveness of balloon-assisted angioplasty for the treatment of ISR after vertebral artery ostium stenosis.

Methods:

In this study, we included patients from the Department of Neurology, Lishui Hospital of Zhejiang University, who were treated with balloon-assisted angioplasty as a result of suffering from ISR after previously undergoing vertebral artery ostium stenting. We retrospectively analyzed the clinical and functional outcomes of the patients.

Results:

From January 2015 to December 2019, 11 patients were included in the study. The technical success rate reached 100% and the average operation time was 73 minutes. The Thrombolysis in Cerebral Infarction Score 2b-3 was acquired in all patients except 1 patient, who was presented with symptoms of hypoperfusion syndrome. The remaining 10 patients did not experience any intraoperative or postoperative complications. No restenosis, new cerebral infarction or transient ischemic attack were reported within 6 months of follow-up.

Conclusion:

Balloon-assisted angioplasty could be feasible for the treatment of ISR after vertebral artery ostium stenting, however, more research is needed to confirm this.
Evaluating the Jaccard Similarity Index as a Persistence Measure of Multiple Anal Human Papillomavirus Among Nigerian Men Who Have Sex With Men
Authors: Nowak Rebecca G. , Bentzen Søren M. , Schumaker Lisa M. , Ambulos Nicholas P. , Ndembi Nicaise , Dauda Wuese , Mitchell Andrew , Mathias Trevor J. , Crowell Trevor A. , Baral Stefan D. , Blattner William A. , Charurat Manhattan E. , Palefsky Joel M. , Cullen Kevin J. ,   on behalf of the TRUST/RV368 Study Group
Published: November 2021

Background

Multiple anal human papillomavirus (HPVs) may increase the risk of anal cancer among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). The Jaccard Similarity Index (JSI) was explored as a measure of multiple HPV persistence.

Methods

The TRUST/RV368 cohort enrolled MSM living with and without HIV in Abuja and Lagos, Nigeria. Participants with anal swabs at baseline, 3- and 12-month visits were tested for high- and low-risk HPVs using a next-generation sequencing assay. Persistence of the same HPV genotypes over time was calculated using the JSI and categorized into high, medium, and low similarity tertiles. Factors associated with higher versus lower similarity were estimated with multivariable ordinal logistic regression and reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

Results

Of the 225 participants, median age was 25 years (interquartile range, 22–29 years), 62% were living with HIV, median HPVs was 3 (interquartile range, 2–5), and HPV6 (28%), HPV16 (26%), HPV11 (23%), and HPV45 (20%) were most prevalent. Fifty-three percent of participants had highly similar HPVs at 3 months, and the similarity was associated with HIV (aOR, 3.11; 95% CI, 1.6–5.9) and recent receptive sex (aOR, 1.9; 95% CI, 1.0–3.5). By 12 months, 20% had highly similar HPVs, and it was associated with 12 years or longer since anal coital debut (aOR, 6.8; 95% CI, 3.1–5.2), self-reported genital warts (aOR, 3.1; 95% CI, 1.5–6.6), and 200 or less CD4 cells/mm3 (aOR, 13.3; 95% CI, 2.7–65.2) for those living with HIV.

Conclusions

Studies evaluating the JSI as a predictor of high-grade intraepithelial lesions would further confirm its applicability as a quantitative measure of multiple HPV persistence.
Pediatric Web-based Video Capsule Endoscopy Curriculum: A Pilot Study to Determine the Ability to Implement a Standardized Educational Curriculum
Authors: Phatak Uma Padhye , Scherer Corey , Du Nan , Friedlander Joel A.
Published: November 2021

Objectives:

Video capsule endoscopy (VCE) is a noninvasive modality to broadly image the gastrointestinal tract. Previously, the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and its endoscopy committee noted a lack of standardized pediatric VCE training. It was hypothesized that a web-based curriculum could be broadly implemented and help to enhance comfort and develop VCE skills.

Methods:

A pilot web-based VCE curriculum was created using REDCap database. An email invitation asking for participation was sent to a pediatric gastroenterology Listserv. Baseline comfort and knowledge regarding VCE skills were measured. Educational links and materials were provided following which participants completed VCE cases with immediate feedback. Finally, participants completed a posttest and a survey to complete the curriculum.

Results:

Fifty-two participants began the curriculum of which 37 (71%) partially completed, 12 (23%) completed, and 3 (6%) withdrew. Significant improvement was noted regarding self-reported mean comfort level in explaining indications (P = 0.0097), contraindications (P = 0.0036), managing complications (P = 0.0048), using VCE software (P = 0.00035), and interpreting VCE findings (P = 0.00015). Participants showed significant improvement in knowledge (P = 0.041) and photo recognition posttests (P = 0.015). All participants who completed the curriculum found it helpful and reported that they would recommend it to their colleagues.

Conclusions:

This pilot curriculum demonstrated an improvement in participant self-reported comfort and an increase in VCE knowledge. Further resources would make a web-based curriculum easier to navigate and complete. Providing Continuation of Medical Education and Maintenance of Certification credits for future curricular iterations would provide an opportunity for training with recognition for pediatric gastroenterologists.
Severe Combined Immunodeficiency with De Novo Duchenne Muscular Dystrophy Mutation
Authors: Shah Kevin P. , Ramachandran Vignesh , Nicholas Sarah K. , Hanson Imelda C. , Lotze Timothy E. , Martinez Caridad A. , Fishman Douglas S.
Published: November 2021

Both severe combined immunodeficiency (SCID) syndrome and Duchenne muscular dystrophy (DMD) are rare conditions. Patients with X-linked SCID have pathogenic variants of the IL2RG gene, resulting in defective cellular and humoral immunity. DMD is also an X-linked condition caused by a dystrophin gene mutation, causing progressive proximal muscle weakness. We present a patient diagnosed with SCID at birth who underwent matched unrelated donor bone marrow transplant (BMT). Several months after, he was noted to have persistently elevated aminotransferases. Despite a lack of clinical signs of graft versus host disease (GvHD), a liver biopsy revealed mild GvHD. Creatine kinase (CK) levels of >19,000 U/L prompted evaluation for muscular dystrophies. Given BMT, genetic analysis was not an option. Muscle biopsy confirmed DMD. This case highlights the complexity of diagnosing and managing uncommon genetic conditions through a multidisciplinary team-based approach. This case is only the second reported case of SCID and DMD together.
CFTR:F508d/A613T Mutation Is Associated With Recurrent Episodes of Pancreatitis
Authors: Lin Cindy , Woolfson Jessica P.
Published: November 2021

Pancreatic insufficiency (PI) is found in 85% of individuals with cystic fibrosis (CF). Of the remaining who are pancreatic sufficient (PS), there is potential for developing pancreatitis, and is described in ~20% of PS individuals. We report a case of a 17.5-year-old female presenting with acute recurrent pancreatitis (ARP) and PS, later diagnosed with CF. This is the first reported case of ARP in an individual with a F508d/A613T genotype. To date, there are only 6 other individuals with this genotype, and the mechanisms of it causing ARP and no overt respiratory symptoms of CF are unclear. Her diagnosis occurred 10 years after her initial presentation of pancreatitis, highlighting the importance of screening for CFTR mutations in the workup for ARP with no clear etiology.
The Interoceptive Sensitivity and Attention Questionnaire: Evaluating Aspects of Self-Reported Interoception in Patients With Persistent Somatic Symptoms, Stress-Related Syndromes, and Healthy Controls
Authors: Bogaerts Katleen , Walentynowicz Marta , Van Den Houte Maaike , Constantinou Elena , Van den Bergh Omer
Published: November 2021

Objective

This study aimed to validate the Interoceptive Sensitivity and Attention Questionnaire (ISAQ), a 17-item self-report measure assessing sensitivity and attention to interoceptive signals.

Methods

In study 1, exploratory and confirmatory factor analysis was performed in a student convenience sample (n = 1868). In study 2, ISAQ data of a healthy sample (n = 144) and various patient groups experiencing stress-related syndromes (overstrain, n = 63; burnout, n = 37; panic disorder [PD]. n = 60) and/or persistent somatic symptoms in daily life (irritable bowel syndrome, n = 38; fibromyalgia and/or chronic fatigue syndrome, n = 151; medically unexplained dyspnea [MUD], n = 29) were compared.

Results

Three subscales were revealed: (F1) sensitivity to neutral bodily sensations, (F2) attention to unpleasant bodily sensations, and (F3) difficulty disengaging from unpleasant bodily sensations. Overall, patients with fibromyalgia and/or chronic fatigue syndrome and patients with MUD scored significantly higher on F1 (p = .009 and p = .027, respectively) and F2 (p = .002 and p < .001, respectively) than healthy controls. Patients with PD had higher scores on subscales F2 (p < .001) and F3 (p < .001) compared with healthy controls, as well as higher scores on F2 compared with all other patient groups (p
PD versus MUD = .008; all other p values < .001).

Conclusions

Interoceptive sensibility—the self-reported aspect of interoception—is not a homogeneous or unitary construct. The subscales of the ISAQ differentiate healthy controls from patients with persistent somatic and/or stress-related complaints in daily life and distinguish different patient groups. The ISAQ can be used as a concise, reliable, and clinically relevant research tool to further disentangle adaptive and maladaptive aspects of interoceptive ability.
The Influence of Cognitive Behavioral Intervention for Anger Management on Endothelial Function in Patients With Recent Myocardial Infarction: A Randomized Clinical Trial
Authors: Schmidt Karine Elisa Schwarzer , de Quadros Alexandre Schaan , Eibel Bruna , Aires Aline Marques , Gottschall Carlos Antônio Mascia , Moura Mauro Regis Silva , Schmidt Márcia Moura
Published: November 2021

Objective

Anger may cause adverse cardiovascular responses, but the effects of anger management on clinical cardiovascular outcomes are insufficiently understood. We sought to assess the influence of anger management through a cognitive behavioral intervention on endothelial function in patients with a recent myocardial infarction (MI).

Methods

Patients with ST-elevation MI and a low anger control score were enrolled during hospitalization in a randomized, parallel, controlled clinical trial. Intervention was anger management with cognitive behavioral techniques implemented by a psychologist in two individual monthly sessions. The primary end point was the between-group difference in the variation of flow-mediated dilation (FMD) in the brachial artery from baseline to the 3-month follow-up. The second end point comprised major cardiovascular events at 24-month follow-up.

Results

A total of 43 patients (age = 56 [9] years; 23.3% women) were randomized to the intervention group and 47 patients (age = 58 [10] years; 19.1% women) to the control group. Baseline clinical characteristics were not statistically different between groups. Both groups showed a significant improvement in anger control from baseline to end point; however, the difference in intergroup variation was not statistically significant. The difference in FMD variation from baseline to the 3-month follow-up was significantly higher in the intervention group. The partial η
2 was 0.057 (p = .024), indicating a medium effect size. There was no difference between groups regarding major cardiovascular events.

Conclusions

Anger management by cognitive behavioral techniques may improve endothelial function in post-MI patients with low anger control, but it remains unclear via which mechanism these effects occurred. Further studies with larger numbers of patients, assessments of changes in anger, improved comparability of preintervention FMD, and longer follow-up are warranted.

Trial Registration:
ClinicalTrials.gov identifier: NCT02868216.
Comparisons of Fall Prevention Activities Using Electronic Nursing Records: A Case-Control Study
Authors: Jung Hyesil , Park Hyeoun-Ae , Lee Ho-Young
Published: November 2021

Objective

The aim of this study was to compare the current fall prevention nursing practices with the evidence-based practices recommended in clinical practice guidelines according to the risk of falling and specific risk factors.

Methods

The standardized nursing statements of 12,277 patients were extracted from electronic nursing records and classified into groups according to the risk of falling and individual patients’ specific risk factors. The mean frequencies of the fall prevention practices in 10 categories derived from clinical practice guidelines were compared among the groups. We additionally analyzed the differences in the mean frequencies of tailored fall prevention practices according to individual patients’ specific risk factors.

Results

The nurses documented more fall prevention practices for patients at a high risk of falling and nonfallers than for patients at a low risk of falling and fallers. Specifically, the difference in nursing practices related to environmental modifications was largest between patients at a high risk of falling and those at a low risk of falling. There were also large differences in the nursing practices related to mental status, dizziness/vertigo, and mobility limitations between fallers and nonfallers. There was more documentation of tailored fall prevention practices related to mobility limitations for patient with mild lower limb weakness than for those with good power and balance. In contrast, patients with severe lower limb weakness had received fewer fall prevention practices related to mobility limitations.

Conclusions

The present findings emphasize that individual risk-specific nursing interventions in addition to universal precautions are crucial for preventing falls among patients.
Impact of Variation in Pill/Package Appearance of Drugs on Patients’ Behavior: A Systematic Review
Authors: Lumbreras Blanca , Sanz-Valero Javier , López-Pintor Elsa
Published: November 2021

Objective

This systematic review aims to identify and critically evaluate the available evidence on the impact of switches in pill appearance/packaging on patient’s behavior.

Methods

Studies from inception to March 2021 were searched across MEDLINE through PubMed, the Cochrane Library, Embase, and Scopus. Included studies carried out an original evaluation in English or Spanish language that evaluated the impact of switches in pill appearance/packaging on patient’s behavior. Two authors independently extracted study data and evaluated studies for methodological quality according to the STROBE guidelines.

Results

Ten studies were included, and the mean (SD) number of STROBE criteria satisfied was 17.2 (3.9). Three of 5 studies found a significant association between change in pill appearance and persistence to treatment; the 3 studies that evaluated the impact of a change on adherence to treatment found a significant association; 1 of the 2 studies that evaluated the relationship between a change a clinical outcome found a significant association with the prevalence of uncontrolled blood pressure; and 1 study showed lower rates of switchbacks to the branded product compared with patients who switched to generic drug products, with different appearance.

Conclusions

This systematic review showed an impact of the change in pill/package appearance on patients’ behavior in 7 of the 10 studies included. Generic switching may lead to unintended consequences on patients’ behavior, mainly regarding adherence to treatment.
Evaluation of the Culture of Safety and Quality in Pediatric Primary Care Practices
Authors: Oyegoke Sarah , Gigli Kristin Hittle
Published: November 2021

Objectives

The purposes of this article were to describe the perceptions of the culture of safety in pediatric primary care and evaluate whether organizational factors and staff roles are associated with perceptions of the culture of safety.

Methods

We conducted a secondary data analysis using 2020 Agency for Healthcare Research and Quality Medical Office Survey on Patient Safety Culture to examine the culture of safety and quality in pediatric primary care practices. We used descriptive statistics and calculated differences in perceptions of patient safety and quality based on practice size, ownership, and staff roles using bivariate and logistic regressions.

Results

The sample included 99 pediatric primary care practices and 1228 staff (physicians n = 169, advanced practice providers n = 70, nurses n = 338, and administration/management n = 651). The “teamwork” domain had the highest positive ratings (≥81.6% positive responses), whereas the “work pressure and pace” domain had the lowest positive ratings (≤28.6% positive response). There were no differences in perceptions of safety or quality based on practice size or ownership. However, there were differences based on staff roles, specifically between administration/management and direct care staff.

Conclusions

Overall, perceptions of the culture of safety and quality in pediatric primary care practices were positive. Differences in perceptions existed based on staff role. Future studies are needed to determine whether differences are clinically meaningful and how to narrow differences in perceptions among staff and improve of the culture of safety as a mechanism to improve the safety and quality of pediatric primary care.
Implementation of a Preoperative Huddle at a Level 1 Trauma Center
Authors: Scofield Harrison , Teigen Kari , Blair Somer , Rechter Griffin R. , Webb Brian
Published: November 2021

Objective

Medical errors resulting in patient harm still occur at an alarmingly high rate. Surgery is a high-risk area that can frequently result in patient harm if errors occur. There is a need for standardization of communication and processes to decrease errors. We sought to determine whether the implementation of a preoperative huddle at our hospital could standardize communication and decrease medical errors.

Methods

A unique preoperative huddle was developed and implemented at a level 1 trauma center. We reviewed data before and after the implementation of the preoperative huddle including patient surveys and comments, the percentage of on-time operating room (OR) starts, OR turnover times, and the number of sentinel events.

Results

After huddle implementation, we observed a trend of improvement in our patient survey results on patient’s perception that the doctors/nurses explained the procedure understandably after huddle implementation. There was a statistically yet limited clinically significant increase in OR turnover time from 37 to 40 minutes (P < 0.001). There was also an increase in on-time OR starts from 37% to 45% (P < 0.001). We observed a decrease in the number of sentinel events, with only 1 occurring each year since implementation.

Conclusions

A preoperative huddle was successfully implemented at a level 1 trauma hospital and helped standardize communication without significantly disrupting workflow. To our knowledge, this method of preoperative huddling has not been previously described in the literature.
Precision medicine in secondary prevention of ischemic stroke: how may blood-based biomarkers help in clinical routine? An expert opinion
Authors: Bicciato Giulio , Arnold Markus , Gebhardt Aidan , Katan Mira
Published: November 2021

Purpose of review

One in eight patients unfortunately suffers a new stroke within 5 years of their first stroke, even today. Research in precision medicine could lead to a more individualized treatment allocation, possibly achieving lower recurrence rates of ischemic stroke. In this narrative review, we aim to discuss potential clinical implementation of several promising candidate blood biomarkers.

Recent findings

We discuss specifically some promising blood-based biomarkers, which may improve the identification of underlying causes as well as risk stratification of patients according to their specific cerebrovascular risk factor pattern.

Multimodal profiling of ischemic stroke patients by means of blood biomarkers, in addition to established clinical and neuroradiological data, may allow in the future a refinement of decision algorithms for treatment allocation in secondary ischemic stroke prevention.
Vestibular-autonomic interactions: beyond orthostatic dizziness
Authors: Bogle Jamie M. , Benarroch Eduardo , Sandroni Paola
Published: November 2021

Purpose of review

This review aims to summarize the current literature describing vestibular-autonomic interactions and to describe their putative role in various disorders’ clinical presentations, including orthostatic dizziness and motion sensitivity.

Recent findings

The vestibular-autonomic reflexes have long been described as they relate to cardiovascular and respiratory function. Although orthostatic dizziness may be in part related to impaired vestibulo-sympathetic reflex (orthostatic hypotension), there are various conditions that may present similarly. A recent clinical classification aims to improve identification of individuals with hemodynamic orthostatic dizziness so that appropriate recommendations and management can be efficiently addressed. Researchers continue to improve understanding of the underlying vestibular-autonomic reflexes with recent studies noting the insular cortex as a cortical site for vestibular sensation and autonomic integration and modulation. Work has further expanded our understanding of the clinical presentation of abnormal vestibular-autonomic interactions that may occur in various conditions, such as aging, peripheral vestibular hypofunction, traumatic brain injury, and motion sensitivity.

The vestibular-autonomic reflexes affect various sympathetic and parasympathetic functions. Understanding these relationships will provide improved identification of underlying etiology and drive improved patient management.
COVID-19 trends and severity among symptomatic children aged 0-17 years in ten EU countries, 3 August 2020 – 3 October 2021
Authors: Bundle Nick , Dave Nishi , Pharris Anastasia , Spiteri Gianfranco , Deogan Charlotte , Suk Jonathan E. ,   study group members
Published: November 2021

To guide evidence-based prevention of COVID-19 in children, we estimated risks of severe outcomes in 820,404 symptomatic paediatric cases reported by 10 EU Member States between August 2020 and October 2021. Case and hospitalisation rates rose as overall transmission increased but severe outcomes were rare: 9,611 (1.2%) were hospitalised, 640 (0.08%) required intensive care and 84 (0.01%) died. Despite increased individual risk (aOR; 95% CI for hospitalisation: 7.3; 3.3 - 16.2, ICU: 8.7; 6.2 - 12.3) in cases with comorbidities such as cancer, diabetes, cardiac or lung disease, most (83.7%) hospitalised children had no reported comorbidity.
The reproduction process of Gram-positive protocells
Authors: Kanaparthi Dheeraj , Lampe Marko , Krohn Jan-Hagen , Zhu Baoli , Hildebrand Falk , Boesen Thomas , Klingl Andreas , Phapale Prasad , Lueders Tillmann
Published: November 2021

Prokaryotes are hypothesized to have evolved from more primitive protocells. Unlike present-day cells, protocells are thought to have been devoid of complex molecular biological processes. They are believed to have mediated reproduction entirely by biophysical forces under favorable environmental conditions. Despite this proposition, little is known about the actual mechanism of their reproduction. To understand the reproduction process of protocells in their native habitat, here we used a top-down approach to transform bacterial cells into a primitive lipid vesicle-like state. Given that environmental conditions are thought to have played an essential role in mediating protocell reproduction, we then studied these cells under the presumed environmental conditions of Archaean Eon Earth. Even in the absence of functioning biological processes, cells in our study reproduced in a defined sequence of steps, always leading to the formation of viable daughter cells. Their reproduction mechanism can be explained by the interaction between intracellular metabolism, physicochemical properties of cell constituents, and, most importantly, environmental conditions. Given the simplicity of this reproduction mechanism and its suitability to environmental conditions of early Earth, we propose that protocells reproduced by this process. Moreover, this method of reproduction is also in tune with the earlier theoretical propositions on protocells, the results of the top- down approach of building a minimal cell, and the paleontological record of the Achaean Eon. Our study is the first to bridge the gap between non-living systems like lipid vesicles, living cells, and the paleontology of the Archaean Eon.
US women screen at lower rates for both cervical and colorectal cancers than a single cancer
Authors: Harper Diane M , Plegue Melissa , Jimbo Masahito , Sen Ananda , Gorin Sherri Sheinfeld
Published: November 2021

Introduction

Using screen counts, women 50-64 yo have lower cancer screening rates for cervical and colorectal cancers compared to all other age ranges. The primary aim of this paper is to present cervical cancer and CRC screenings per woman and determine the predictors of being up-to-date for both.

Methods

We used the Behavioral Risk Factor Surveillance System (BRFSS), an annual survey to guide health policy in the US, to explore the up-to-date status of dual cervical and colorectal cancer screening for women 50-64 yo. We categorized women into four mutually exclusive categories: up-to-date for dual screening, each single-screen, or neither screen. Multinomial multivariate regression modeling was used to evaluate the predictors of each category.

Results

Among women ages 50-64 yo, dual screening was reported for 58.7% (57.6-59.9), cervical cancer screening alone (27.0% (25.9-28.1), CRC screening alone (5.3% (4.8-5.8), and neither screen (9% (8.4-9.6). Age, race, education, income, and chronic health conditions were significantly associated with dual screening compared to neither screen. Hispanic women compared to non-Hispanic White women were more likely to be up-to-date with cervical cancer screening than dual screening (aOR 1.38 (1.08, 1.77). By comparison to younger women, those 60-64 years are significantly more likely to be up-to-date with CRC screening than dual screening (aOR 1.75 (1.30, 2.34)).

Conclusions

Screening received by each woman shows a much lower rate of dual screening than prior single cancer screening rates. Addressing dual screening strategies rather than single cancer screening programs for women 50-64 years may increase both cancer screening rates.

Graphical Abstract

Screening rates differ by calculation approach. A better population metric for cancer prevention is to consider the screens each woman has received. Our data show much lower cervical cancer and CRC screening rates than a single screen calculation.

Tweet

Women 50-64 years old lack dual cervical and colorectal cancer screening. Women who screen for only one cancer of the two, screen for cervical cancer almost five times more often than colorectal cancer.

Lay Summary

Routine cervical and colorectal cancer (CRC) screenings can detect early, treatable, curable cancers. Using the responses to the 2018 Behavioral Risk Factor Surveillance Survey (BRFSS) we approached prevention by what the woman has received rather than by how many screens were done. We showed that women 50-64 years old were only up-to-date for both cervical and CRC screening 59% of the time, whereas, by traditional screening calculations, our data showed 86% of women were up-to-date for cervical cancer screening and 64% were up to date with CRC screening, irrespective of any other cancer screenings.
Likelihood of infecting or getting infected with COVID-19 as a function of vaccination status, as investigated with a stochastic model for New Zealand (Aotearoa) for Delta and Omicron variants
Authors: Watson Leighton M.
Published: November 2021

Aim

The New Zealand government has transitioned from the Alert Level framework, which relied on government action and population level controls, to the COVID-19 Protection Framework, which relies on vaccination rates and allows for greater freedoms (for the vaccinated). Under the COVID-19 Protection Framework and current widespread community transmission of Omicron, there is significant interest in understanding the relative risk of spreading COVID-19 posed by unvaccinated, vaccinated, and boosted individuals.

Methods

A stochastic branching process model is used to simulate the spread of COVID-19 for outbreaks seeded by unvaccinated, vaccinated, or boosted individuals. The likelihood of infecting or getting infected with COVID-19 is calculated based on vaccination status. The model is applied to both the Delta and Omicron variants.

Results

For the Delta variant a vaccinated traveler infected with COVID-19 is 9x less likely to seed an outbreak than an unvaccinated traveler infected with COVID-19, however, for the Omicron variant there is little difference between outbreaks seeded by unvaccinated and vaccinated individuals (boosted individuals are slightly less likely to seed large outbreaks). For the Delta variant unvaccinated individuals are responsible for 87% of all infections whereas only 3% of infections are from vaccinated to vaccinated when normalized by population. Therefore, a vaccinated individual is 6.8x more likely to be infected by an unvaccinated individual than by a vaccinated individual. For the Omicron variant unvaccinated individuals are responsible for 45% of all infections compared to 39% for vaccinated (two-doses) and 15% for boosted (three-doses) individuals when normalized by population. Despite the vaccine being less effective at preventing breakthrough transmission for Omicron, only 3% of all infections are from boosted to boosted individuals when normalized by population indicating that three doses of the vaccine provide good protection from infection and breakthrough transmission.

Conclusions

This work demonstrates that most new infections are caused by unvaccinated individuals, especially for the Delta variant. These simulations illustrate the importance of vaccination in stopping individuals from becoming infected with COVID-19 and in preventing onward transmission. For Omicron, individuals vaccinated with two doses are only slightly less likely to spread COVID-19 than those who are unvaccinated. This work suggests that for the current Omicron outbreak the COVID-19 Protection Framework should potentially be updated to distinguish between those who have received two primary doses of the Pfizer-BioNTech vaccine (vaccinated individuals) and those who have received three doses (boosted individuals).
The phenotypic landscape of essential human genes
Authors: Funk Luke , Su Kuan-Chung , Feldman David , Singh Avtar , Moodie Brittania , Blainey Paul C. , Cheeseman Iain M.
Published: November 2021

Understanding the basis for cellular growth, proliferation, and function requires determining the contributions of essential genes to diverse cellular processes. Here, we combined pooled CRISPR/Cas9-based functional screening of 5,072 fitness-conferring genes in human cells with microscopy-based visualization of DNA, DNA damage, actin, and microtubules. Analysis of >31 million individual cells revealed measurable phenotypes for >90% of genes. Using multi-dimensional clustering based on hundreds of quantitative phenotypic parameters, we identified co-functional genes across diverse cellular activities, revealing novel gene functions and associations. Pooled live-cell screening of ∼450,000 cell division events for 239 genes further identified functional contributions to chromosome segregation. Our work creates a resource for the phenotypic analysis of core cellular processes and defines the functional landscape of essential human genes.
Multi-omics Analyses Provide Insight into the Biosynthesis Pathways of Fucoxanthin in Isochrysis galbana
Authors: Chen Duo , Yuan Xue , Zheng XueHai , Fang Jingping , Lin Gang , Li Rongmao , Chen Jiannan , He Wenjin , Huang Zhen , Fan Wenfang , Liang Limin , Lin Chentao , Zhu Jinmao , Chen Youqiang , Xue Ting
Published: November 2021

Isochrysis galbana is considered an ideal bait for functional foods and nutraceuticals in humans because of its high fucoxanthin (Fx) content. However, multi-omics analysis of the regulation networks for Fx biosynthesis in I. galbana has not been reported. In this study, we report a high-quality genome sequence of I. galbana LG007, which has a 92.73 Mb genome size, with a contig N50 of 6.99 Mb and 14,900 protein-coding genes. Phylogenomic inferences confirmed the monophyly of Haptophyta, with I. galbana sister to Emiliania huxleyi and Chrysochromulina tobinii. Evolutionary analysis revealed an estimated divergence time between I. galbana and E. huxleyi of ~ 133 million years ago (Mya). Gene family analysis indicated that lipid metabolism-related genes exhibited significant expansion, including IgPLMT, IgOAR1 and Δ-4 desaturase. Metabolome analysis showed that the content of carotenoid in I. galbana cultured under green light for 7 days was higher than that of white light, and β-carotene was the main carotenoids, accounting for 79.09% of the total carotenoids. Comprehensive analysis of multi-omics analysis revealed that β-carotene, antheraxanthin, zeaxanthin, and Fx content was increased by green light induction, which was significantly correlated with the expression of IgMYB98, IgZDS, IgPDS, IgLHCX2, IgZEP, IgLCYb, and IgNSY. These findings contribute to understanding Fx biosynthesis and its regulation, providing a valuable reference for food and pharmaceutical applications.
Global analysis of human-to-mouse contact-dependent intercellular mRNA and lncRNA transfer in cell culture
Authors: Dasgupta Sandipan , Dayagi Daniella Y. , Haimovich Gal , Wyler Emanuel , Olender Tsviya , Singer Robert H. , Landthaler Markus , Gerst Jeffrey E.
Published: November 2021

Full-length mRNAs can transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (thetransferome) is unknown. Here, we analyzed whole transcriptome mRNA and lncRNA transfer between heterogeneous human-mouse cell populations inin vitroco-culture using RNA-sequencing. Our data indicate that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells (MCF7). These results were validated by both quantitative RT-PCR andin situhybridization, and analysis shows that typically <1% of endogenous mRNAs and lncRNAs undergo transfer. Non-selective expression-dependent RNA transfer was further validated using synthetic RNA reporters. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions.
Rethinking protein drug design with highly accurate structure prediction of anti-CRISPR proteins
Authors: Park Ho-min , Park Yunseol , Vankerschaver Joris , Van Messem Arnout , De Neve Wesley , Shim Hyunjin
Published: November 2021

Protein therapeutics play an important role in controlling the functions and activities of disease-causing proteins in modern medicine. Despite protein therapeutics having several advantages over traditional small-molecule therapeutics, further development has been hindered by drug complexity and delivery issues. However, recent progress in deep learning-based protein structure prediction approaches such as AlphaFold opens new opportunities to exploit the complexity of these macro-biomolecules for highly-specialised design to inhibit, regulate or even manipulate specific disease-causing proteins. Anti-CRISPR proteins are small proteins from bacteriophages that counter-defend against the prokaryotic adaptive immunity of CRISPR-Cas systems. They are unique examples of natural protein therapeutics that have been optimized by the host-parasite evolutionary arms race to inhibit a wide variety of host proteins. Here, we show that these Anti-CRISPR proteins display diverse inhibition mechanisms through accurate structural prediction and functional analysis. We find that these phage-derived proteins are extremely distinct in structure, some of which have no homologues in the current protein structure domain. Furthermore, we find a novel family of Anti-CRISPR proteins which are structurally homologous to the recently-discovered mechanism of manipulating host proteins through enzymatic activity, rather than through direct inference. Using highly accurate structure prediction, we present a wide variety of protein-manipulating strategies of anti-CRISPR proteins for future protein drug design.
Functionalizing lipid sponge droplets with DNA
Authors: Cho Christy , Niederholtmeyer Henrike , Seo Hyeonglim , Bhattacharya Ahanjit , Devaraj Neal K.
Published: November 2021

Nucleic acids are among the most versatile molecules for the construction of biomimetic systems because they can serve as information carriers and programmable construction materials. How nucleic acids interact with membranous coacervate compartments such as lipid sponge droplets is not known. Here we systematically characterize the potential of DNA to functionalize lipid sponge droplets and demonstrate a strong size dependence for sequestration into the sponge phase. Double stranded DNA molecules of more than 300 bp are excluded and form a corona on the surface of droplets they are targeted to. Shorter DNA molecules partition efficiently into the lipid sponge phase and can direct DNA-templated reactions to droplets. We demonstrate repeated capture and release of labeled DNA strands by dynamic hybridization and strand displacement reactions that occur inside droplets. Our system opens new opportunities for DNA-encoded functions in lipid sponge droplets such as cargo control and signaling.