bluuebunny/crossref_metadata_2025 huggingface dataset:
LipidSuite: interactive web server for lipidomics differential and enrichment analysis
Authors: Mohamed Ahmed , Hill Michelle M
Published: April 2021

Advances in mass spectrometry enabled high throughput profiling of lipids but differential analysis and biological interpretation of lipidomics datasets remains challenging. To overcome this barrier, we present LipidSuite, an end-to-end differential lipidomics data analysis server. LipidSuite offers a step-by-step workflow for preprocessing, exploration, differential analysis and enrichment analysis of untargeted and targeted lipidomics. Three lipidomics data formats are accepted for upload: mwTab file from Metabolomics Workbench, Skyline CSV Export, and a numerical matrix. Experimental variables to be used in analysis are uploaded in a separate file. Conventional lipid names are automatically parsed to enable lipid class and chain length analyses. Users can interactively explore data, choose subsets based on sample types or lipid classes or characteristics, and conduct univariate, multivariate and unsupervised analyses. For complex experimental designs and clinical cohorts, LipidSuite offers confounding variables adjustment. Finally, data tables and plots can be both interactively viewed or downloaded for publication or reports. Overall, we anticipate this free, user-friendly webserver to facilitate differential lipidomics data analysis and re-analysis, and fully harness biological interpretation from lipidomics datasets. LipidSuite is freely available at http://suite.lipidr.org.
OpenAnnotate: a web server to annotate the chromatin accessibility of genomic regions
Authors: Chen Shengquan , Liu Qiao , Cui Xuejian , Feng Zhanying , Li Chunquan , Wang Xiaowo , Zhang Xuegong , Wang Yong , Jiang Rui
Published: April 2021

Chromatin accessibility, as a powerful marker of active DNA regulatory elements, provides valuable information for understanding regulatory mechanisms. The revolution in high-throughput methods has accumulated massive chromatin accessibility profiles in public repositories. Nevertheless, utilization of these data is hampered by cumbersome collection, time-consuming processing, and manual chromatin accessibility (openness) annotation of genomic regions. To fill this gap, we developed OpenAnnotate (http://health.tsinghua.edu.cn/openannotate/) as the first web server for efficiently annotating openness of massive genomic regions across various biosample types, tissues, and biological systems. In addition to the annotation resource from 2729 comprehensive profiles of 614 biosample types of human and mouse, OpenAnnotate provides user-friendly functionalities, ultra-efficient calculation, real-time browsing, intuitive visualization, and elaborate application notebooks. We show its unique advantages compared to existing databases and toolkits by effectively revealing cell type-specificity, identifying regulatory elements and 3D chromatin contacts, deciphering gene functional relationships, inferring functions of transcription factors, and unprecedentedly promoting single-cell data analyses. We anticipate OpenAnnotate will provide a promising avenue for researchers to construct a more holistic perspective to understand regulatory mechanisms.
A termination-independent role of Rat1 in cotranscriptional splicing
Authors: Dhoondia Zuzer , Elewa Hesham , Malik Marva , Arif Zahidur , Pique-Regi Roger , Ansari Athar
Published: April 2021

Rat1 is a 5′→3′ exoribonuclease in budding yeast. It is a highly conserved protein with homologs being present in fission yeast, flies, worms, mice and humans. Rat1 and its human homolog Xrn2 have been implicated in multiple nuclear processes. Here we report a novel role of Rat1 in mRNA splicing. We observed an increase in the level of unspliced transcripts in mutants of Rat1. Accumulation of unspliced transcripts was not due to the surveillance role of Rat1 in degrading unspliced mRNA, or an indirect effect of Rat1 function in termination of transcription or on the level of splicing factors in the cell, or due to an increased elongation rate in Rat1 mutants. ChIP-Seq analysis revealed Rat1 crosslinking to the introns of a subset of yeast genes. Mass spectrometry and coimmunoprecipitation revealed an interaction of Rat1 with the Clf1, Isy1, Yju2, Prp43 and Sub2 splicing factors. Furthermore, recruitment of splicing factors on the intron was compromised in the Rat1 mutant. Based on these findings we propose that Rat1 has a novel role in splicing of mRNA in budding yeast. Rat1, however, is not a general splicing factor as it crosslinks to only long introns with an average length of 400 nucleotides.
The N
6-methyladenosine RNA-binding protein YTHDF1 modulates the translation of TRAF6 to mediate the intestinal immune response
Authors: Zong Xin , Xiao Xiao , Shen Bin , Jiang Qin , Wang Hong , Lu Zeqing , Wang Fengqin , Jin Mingliang , Min Junxia , Wang Fudi , Wang Yizhen
Published: April 2021

The intestinal invasion of pathogenic microorganisms can have serious health consequences. Recent evidence has shown that the N6-methyladenosine (m6A) mRNA modification is closely associated with innate immunity; however, the underlying mechanism is poorly understood. Here, we examined the function and mechanism of m6A mRNA modification and the YTH domain-containing protein YTHDF1 (YTH N6-methyladenosine RNA-binding protein 1) in the innate immune response against bacterial pathogens in the intestine. Ribo-seq and m6A-seq analyses revealed that YTHDF1 directs the translation of Traf6 mRNA, which encodes tumor necrosis factor receptor-associated factor 6, thereby regulating the immune response via the m6A modification near the transcript's stop codon. Furthermore, we identified a unique mechanism by which the P/Q/N-rich domain in YTHDF1 interacts with the DEAD domain in the host factor DDX60, thereby regulating the intestinal immune response to bacterial infection by recognizing the target Traf6 transcript. These results provide novel insights into the mechanism by which YTHDF1 recognizes its target and reveal YTHDF1 as an important driver of the intestinal immune response, opening new avenues for developing therapeutic strategies designed to modulate the intestinal immune response to bacterial infection.
Future climate change will impact the size and location of breeding and wintering areas of migratory thrushes in South America
Authors: Da Silveira Natália Stefanini , Vancine Maurício Humberto , Jahn Alex E , Pizo Marco Aurélio , Sobral-Souza Thadeu
Published: April 2021

Bird migration patterns are changing worldwide due to current global climate changes. Addressing the effects of such changes on the migration of birds in South America is particularly challenging because the details about how birds migrate within the Neotropics are generally not well understood. Here, we aim to infer the potential effects of future climate change on breeding and wintering areas of birds that migrate within South America by estimating the size and elevations of their future breeding and wintering areas. We used occurrence data from species distribution databases (VertNet and GBIF), published studies, and eBird for 3 thrush species (Turdidae; Turdus nigriceps, T. subalaris, and T. flavipes) that breed and winter in different regions of South America and built ecological niche models using ensemble forecasting approaches to infer current and future potential distributions throughout the breeding and wintering periods of each species. Our findings point to future shifts in wintering and breeding areas, mainly through elevational and longitudinal changes. Future breeding areas for T. nigriceps, which migrates along the Andes Mountains, will be displaced to the west, while breeding displacements to the east are expected for the other 2 species. An overall loss in the size of future wintering areas was also supported for 2 of the species, especially for T. subalaris, but an increase is anticipated for T. flavipes. Our results suggest that future climate change in South America will require that species shift their breeding and wintering areas to higher elevations in addition to changes in their latitudes and longitude. Our findings are the first to show how future climate change may affect migratory birds in South America throughout the year and suggest that even closely related migratory birds in South America will be affected in different ways, depending on the regions where they breed and overwinter.
Vaccine responses in ageing and chronic viral infection
Authors: Rees-Spear Chloe , McCoy Laura E
Published: April 2021

Over the last few decades, changing population demographics have shown that there are a growing number of individuals living past the age of 60. With this expanding older population comes an increase in individuals that are more susceptible to chronic illness and disease. An important part of maintaining health in this population is through prophylactic vaccination, however, there is growing evidence that vaccines may be less effective in the elderly. Furthermore, with the success of anti-viral therapies, chronic infections such as HIV are becoming increasingly prevalent in older populations and present a relatively unstudied population with respect to the efficacy of vaccination. Here we will examine the evidence for age-associated reduction in antibody and cellular responsiveness to a variety of common vaccines and investigate the underlying causes attributed to this phenomenon, such as inflammation and senescence. We will also discuss the impact of chronic viral infections on immune responses in both young and elderly patients, particularly those living with HIV, and how this affects vaccinations in these populations.
Evaluation of the Phytotoxicity of 2,4-Diacetylphloroglucinol and Pseudomonas brassicacearum Q8r1-96 on Different Wheat Cultivars
Authors: Yang Mingming , Thomashow Linda S. , Weller David M.
Published: April 2021

Pseudomonas brassicacearum Q8r1-96 and other 2,4-diacetylphloroglucinol (DAPG)-producing pseudomonads of the P. fluorescens complex possess both biocontrol and growth-promoting properties and play an important role in suppression of take-all of wheat in the Pacific Northwest (PNW) of the United States. However, P. brassicacearum can also reduce seed germination and cause root necrosis on some wheat cultivars. We evaluated the effect of Q8r1-96 and DAPG on the germination of 69 wheat cultivars that have been or currently are grown in the PNW. Cultivars varied widely in their ability to tolerate P. brassicacearum or DAPG. The frequency of germination of the cultivars ranged from 0 to 0.87 and 0.47 to 0.90 when treated with Q8r1-96 and DAPG, respectively. There was a significant positive correlation between the frequency of germination of cultivars treated with Q8r1-96 in assays conducted in vitro and in the greenhouse. The correlation was greater for spring than for winter cultivars. In contrast, the effect of Q8r1-96 on seed germination was not correlated with that of DAPG alone, suggesting that DAPG is not the only factor responsible for the phytotoxicity of Q8r1-96. Three wheat cultivars with the greatest tolerance and three cultivars with the least tolerance to Q8r1-96 were tested for their ability to support root colonization by strain Q8r1-96. Cultivars with the greatest tolerance supported significantly greater populations of strain Q8r1-96 than those with the least tolerance to the bacteria. Our results show that wheat cultivars differ widely in their interaction with P. brassicacearum and the biocontrol antibiotic DAPG.
Association Between Skin Injuries in Medical Staff and Protective Masks Combined with Goggles During the COVID-19 Pandemic
Authors: Jiang Qixia , Liu Yuxiu , Song Siping , Wei Wei , Bai Yuxuan
Published: April 2021

OBJECTIVE

To explore the relationship between wearing protective masks and goggles and skin injuries in medical staff during the COVID-19 pandemic.

METHODS

Researchers conducted a cross-sectional, multicenter online survey. Respondents voluntarily completed the questionnaire on their smartphones. Ordinal and multinomial logistic regressions were used to identify factors related to skin injuries.

RESULTS

In total, 1,611 respondents wore protective masks combined with goggles in 145 hospitals in China; 1,281 skin injuries were reported (overall prevalence, 79.5%). Multiple concomitant skin injuries (68.5%) and injuries in four anatomic locations (24.0%) were the most common, followed by injuries in three (22.8%), two (21.7%), and one location (11.0%). Multinomial logistic regression indicated that sweating increased the risk of injuries in one to four anatomic locations (95% confidence interval for odds ratio 16.23-60.02 for one location and 38.22-239.04 for four locations), and wearing an N95 mask combined with goggles and a daily use longer than 4 hours increased the risk of injuries in four locations (95% confidence interval for odds ratio 1.18–5.31 and 1.14–3.93, respectively).

CONCLUSIONS

The prevalence of skin injuries among medical staff wearing protective masks combined with goggles was very high. These were mainly device-related pressure injuries, moisture-associated skin damage, and skin tears. The combination of various factors resulted in skin injuries at multiple sites. Preventing and managing sweating should be a focus for medical staff who wear protective masks combined with goggles for more than 4 hours.
Concerns About Fluoroquinolones and Aortic Aneurysm
Authors: Aschenbrenner Diane S.
Published: April 2021

Recent research indicates that all adults may be at risk for aortic aneurysm after fluoroquinolone use, not only those with aortic aneurysm risk factors.
First Extended-Release Injectable Drug Therapy for HIV
Authors: Aschenbrenner Diane S.
Published: April 2021

Cabenuva—an injectable formulation of cabotegravir and rilpivirine and the first injectable complete therapy for adults with HIV-1—is now approved.

It is administered once a month as two intramuscular injections following a month of treatment with the oral forms of these drugs.
Labeling Changes for Vinca Alkaloid Chemotherapies
Authors: Aschenbrenner Diane S.
Published: April 2021

The labeling for vinca alkaloid chemotherapy drugs is being revised to remove instructions for their administration with use of a syringe. This revision is in response to inadvertent intrathecal administration of vinca alkaloids, which is normally fatal.
Addressing Hospital-Acquired Hypoglycemia
Authors: Hughes Lucille , Caragher Maura
Published: April 2021

Background:

Hospitalized patients who have diabetes often experience hospital-acquired hypoglycemia, a potentially serious adverse event; as a result, management of this condition has become an important quality of care indicator in the inpatient environment. A growing body of research and evidence-based clinical guidelines support proper timing of point of care (POC) blood glucose (BG) measurements, mealtime insulin administration, and meal delivery to reduce the incidence of both hypoglycemic and hyperglycemic events. Monitoring and improving the timing of these three patient care interventions are recognized as a crucial step in the safe and effective care of patients with diabetes.

Purpose:

The objective of the QI project was to improve the timing of mealtime insulin administration related to bedside BG monitoring and meal delivery for patients with diabetes who receive mealtime insulin; a secondary goal was to decrease the number of episodes of recurrent hypoglycemia. The overall strategy was to change staff members' approach to mealtime insulin management from a series of individual tasks to a process-oriented collaborative approach.

Methods:

Nurses on the medical–surgical unit at one hospital within a large health system formed a QI team with staff members in information technology and food and nutrition services. The team implemented an eight-week QI pilot project (July 3 to August 26, 2017) using a multidisciplinary approach to coordinate between POC BG measurement, mealtime insulin administration, and meal delivery.

Results:

More than two years after the hospital-wide rollout of the practice change, follow-up analysis has shown that, on both noncritical and critical care units, recurrent hypoglycemia has decreased. For example, comparing data obtained in a six-month period before the pilot project (November 2016 through April 2017) with the same six-month period in 2018 and 2019, more than a year after the pilot project, the percentage of patient stays (admissions) on noncritical care units in which there was a recurrence of hypoglycemia fell from 41.8% (of 1,162 total hospital admissions) to 35.1% (of 792 total hospital admissions); similarly, the percentage of patient stays on critical care units in which recurrent hypoglycemia occurred decreased from 36.8% to 22.8%.

Conclusions:

Findings suggest that ensuring a consistent 30-minute window between POC BG measurement and meal delivery enabled nursing staff to perform timely POC BG measurements and administer a more optimal mealtime insulin dose. Increasing interdisciplinary communication, collaboration, and awareness of best practice guidelines relating to proper mealtime insulin administration resulted in a sustained improvement in timing between POC BG measurements and mealtime insulin administration and between mealtime insulin administration and meal delivery.
PPI Use Linked to Increased Asthma Risk in Children
Authors: Rosenberg Karen
Published: April 2021

According to this study:

Use of proton pump inhibitors compared with nonuse was associated with an increased risk of asthma in children.
Pediatric Acute Alcohol Intoxication Admitted to the ICU: A Review of 102 Cases in France
Authors: Ruetsch Valerie , Zarka Jonathan , Vanel Blandine , Tissieres Pierre , Megarbane Bruno , Renolleau Sylvain , Dauger Stéphane , Guilbert Anne-Sophie , Leteurtre Sylvain , Charpentier Julien , Vaugier Isabelle , Bergounioux Jean
Published: April 2021

OBJECTIVES:

To describe the profile and clinical outcomes of children (<18 yr) admitted to intensive care for acute alcohol intoxication, with special attention to complications and to the subgroup that required intubation.

DESIGN:

Retrospective observational study.

SETTING:

Seven pediatric and three adult ICUs in France.

PATIENTS:

Children 1–17 yr admitted to intensive care for acute alcohol intoxication between January 1, 2010, and December 30, 2017.

INTERVENTIONS:

The study was observational and patients received standard care.

MEASUREMENTS AND MAIN RESULTS:

We included 102 patients, with 71 males (69.6%) and 31 females (30.4%). Mean age was not different between males and females (14.0 ± 3.0 yr [range, 2–17 yr] and 14.2 ± 1.3 yr [range, 11–17 yr]; p = 0.67); six children were younger than 10 years. Mean blood alcohol concentration was not significantly different in males and females (2.42 ± 0.86 and 2.20 ± 0.54 g/L, respectively; p = 0.51). Of the 102 patients, 58 (57%) required intubation. Factors significantly associated with requiring intubation were lower Glasgow Coma Scale score (p = 0.002), lower body temperature (p = 0.045), and higher blood alcohol concentration (p = 0.012); vascular filling, and electrolyte disturbances were not associated with needing intubation. Mean intubation time was 9.7 ± 5.2 hours. Among the 59 patients with Glasgow Coma Scale score less than 8, 12 did not require intubation. The most common metabolic disturbance was a high lactate level (48%), followed by hypokalemia (27.4%); 59 (58.2%) patients had hyperglycemia and three had hypoglycemia.

CONCLUSIONS:

Male adolescents make up the majority of pediatric patients admitted to intensive care for acute alcohol intoxication. A need for intubation was associated with a worse Glasgow Coma Scale, lower body temperature, and higher blood alcohol concentration. Intubation was usually required for less than 12 hours. Other acute medical complications reported in adults with acute alcohol intoxication, such as electrolyte disturbances and aspiration pneumonia, were rare in our pediatric patients.
Comparison of Bivalirudin Versus Heparin for Maintenance Systemic Anticoagulation During Adult and Pediatric Extracorporeal Membrane Oxygenation
Authors: Seelhammer Troy G. , Bohman John K. , Schulte Phillip J. , Hanson Andrew C. , Aganga Devon O.
Published: April 2021

OBJECTIVES:

To provide a comparative analysis of conventional heparin-versus bivalirudin-based systemic anticoagulation in adult and pediatric patients supported on extracorporeal membrane oxygenation.

DESIGN:

Retrospective chart review study of adult and pediatric patients receiving extracorporeal membrane oxygenation from January 1, 2014, to October 1, 2019.

SETTING:

A large, high-volume tertiary referral adult and pediatric extracorporeal membrane oxygenation center.

PATIENTS:

Four hundred twenty-four individuals requiring extracorporeal membrane oxygenation support and systemically anticoagulated with either unfractionated heparin (223 adult and 65 pediatric patients) or bivalirudin (110 adult and 24 pediatric patients) were included.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Digital data abstraction was used to retrospectively collect patient details. The majority of both groups were cannulated centrally (67%), and the extracorporeal membrane oxygenation type was predominantly venoarterial (84%). The adult bivalirudin group had a greater occurrence of heparin-induced thrombocytopenia (12% vs 1%; p < 0.01) and was more likely to require postcardiotomy extracorporeal membrane oxygenation (36% vs 55%; p < 0.01). There were no statistical differences between the groups in regards to age, sex, and extracorporeal membrane oxygenation initiation location. The main finding was a reduced mortality in the adult bivalirudin group (odds ratio, 0.39; p < 0.01), whereas no difference was noted in the pediatric group. A significant reduction in the composite transfusion requirement in the first 24 hours was noted in the pediatric bivaluridin group with an odds ratio of 0.28 (p = 0.02). Groups did not differ in regard to laboratories per day, anticoagulant dose adjustments, or ischemic complications.

CONCLUSIONS:

When compared with heparin-based systemic anticoagulation, bivalirudin demonstrated feasibility and safety as established by the absence of increases in identifiable adverse outcomes while manifesting substantial improvements in hospital mortality in adult patients. Further studies are necessary to corroborate these findings and further elucidate the role of bivalirudin during extracorporeal membrane oxygenation support.
Utilization of ICU Rehabilitation Services in Pediatric Patients With a Prolonged ICU Stay*
Authors: Betters Kristina A. , Le Truc M. , Gong Wu , Lindsell Chris J. , Smith Heidi AB , Smith Andrew H.
Published: April 2021

OBJECTIVES:

To describe rehabilitation practice patterns among critically ill children with prolonged ICU stays and explore the association between institution-level utilization of rehabilitative services and patient outcomes.

DESIGN:

Retrospective cohort study using an administrative database of inpatient clinical and resource utilization data from participating pediatric hospitals in the United States. Center-level utilization of physical therapy and occupational therapy among critically ill patients was used to divide hospitals by quartile into high utilization centers or standard utilization centers.

SETTING:

Fifty-one pediatric hospitals in the United States.

PATIENTS:

Critically ill pediatric patients with prolonged critical illness (defined as an ICU length of stay of at least 7 d) discharged from July 2016 to June 2017.

INTERVENTIONS:

Not applicable.

MEASUREMENTS AND MAIN RESULTS:

Seventeen thousand four hundred seventy encounters met criteria for study inclusion. Of those, 6,040 (35%) were not charged for either physical therapy or occupational therapy services. There was wide variability in center-level utilization of rehabilitative services while in the ICU, ranging from 81% utilization of physical therapy or occupational therapy services among high utilization centers to 46% utilization among centers within the lowest quartile. In univariate analyses, children cared for at an high utilization center were less likely to require discharge to an inpatient rehabilitation facility (1.7% vs 3.5%; p < 0.001) and less likely to incur a new pressure injury (2.2% vs 3.1%; p = 0.001). In multivariable analyses, the direction and magnitude of effects remained similar, although the effect was no longer statistically significant (discharge to inpatient rehabilitation facility: odds ratio, 0.64; 95% CI, 0.18–2.26; pressure injury: odds ratio, 0.77; 95% CI, 0.48–1.24).

CONCLUSIONS:

Institutional use of rehabilitative services for children with prolonged critical illness varies greatly in the United States. Further research is needed into the potential benefits for patients cared for at centers with high usage of rehabilitation services in the ICU during prolonged critical illness.
Mechanism of a Flexible ICU Visiting Policy for Anxiety Symptoms Among Family Members in Brazil: A Path Mediation Analysis in a Cluster-Randomized Clinical Trial
Authors: Rosa Regis Goulart , Pellegrini José Augusto Santos , Moraes Rafael Barberena , Prieb Rita Gigliola Gomes , Sganzerla Daniel , Schneider Daniel , Robinson Caroline Cabral , Kochhann Renata , da Silva Daiana Barbosa , Amaral Alexandre , Prestes Rejane Martins , Medeiros Gregory Saraiva , Falavigna Maicon , Teixeira Cassiano
Published: April 2021

OBJECTIVES:

To investigate whether the effect of a flexible ICU visiting policy that includes flexible visitation plus visitor education on anxiety symptoms of family members is mediated by satisfaction and involvement in patient care.

DESIGN:

We embedded a multivariable path mediation analysis within a cluster-randomized crossover trial as a secondary analysis of The ICU Visits Study (ClinicalTrials.gov number: NCT02932358).

SETTING:

Thirty-six medical-surgical ICUs in Brazil.

PATIENTS:

Closest relatives of adult ICU patients.

INTERVENTIONS:

Flexible visitation (12 hr/d) supported by family education or usual restricted visitation (median, 1.5 hr/d).

MEASUREMENTS AND MAIN RESULTS:

Overall, 863 family members were assessed (mean age, 44.7 yr; women, 70.1%). Compared with the restricted visitation (n = 436), flexible visitation (n = 427) resulted in better mean anxiety scores (6.1 vs 7.8; mean difference, –1.78 [95% CI, –2.31 to –1.22]), as well as higher standardized scores of satisfaction (67% [95% CI, 55–79]) and involvement in patient care (77% [95% CI, 64–89]). The mediated effect of flexible visitation on mean anxiety scores through each incremental sd of satisfaction and involvement in patient care were –0.47 (95% CI, –0.68 to –0.24) and 0.29 (95% CI, 0.04–0.54), respectively. Upon exploratory analyses, emotional support, helping the ICU staff to understand patient needs, helping the patient to interpret ICU staff instructions, and patient reorientation were the domains of involvement in patient care associated with increased anxiety.

CONCLUSIONS:

A flexible ICU visiting policy reduces anxiety symptoms among family members and appears to work by increasing satisfaction. However, increased participation in some activities of patient care as a result of flexible visitation was associated with higher severity of anxiety symptoms.
Oxygen Therapy Lowers Right Ventricular Afterload in Experimental Acute Pulmonary Embolism
Authors: Lyhne Mads Dam , Hansen Jacob Valentin , Dragsbæk Simone Juel , Mortensen Christian Schmidt , Nielsen-Kudsk Jens Erik , Andersen Asger
Published: April 2021

OBJECTIVES:

To investigate if oxygen could unload the right ventricle and improve right ventricle function in a porcine model mimicking intermediate-high risk acute pulmonary embolism.

DESIGN:

Controlled, blinded, animal study.

SETTING:

Tertiary university hospital, animal research laboratory.

SUBJECTS:

Female, Danish pigs (n = 16, approximately 60 kg).

INTERVENTIONS:

Acute autologous pulmonary embolism was induced until doubling of baseline mean pulmonary arterial pressure. Group 1 animals (n = 8) received increasing Fio
2 (40%, 60%, and 100%) for time intervals of 15 minutes returning to atmospheric air between each level of Fio
2. In group 2 (n = 8), the effects of Fio
2 40% maintained over 75 minutes were studied. In both groups, pulmonary vasodilatation from inhaled nitric oxide (40 parts per million) was used as a positive control.

MEASUREMENTS AND MAIN RESULTS:

Effects were evaluated by biventricular pressure-volume loop recordings, right heart catheterization, and arterial and mixed venous blood gasses. Pulmonary embolism increased mean pulmonary arterial pressure from 15 ± 4 to 33 ± 6 mm Hg (p = 0.0002) and caused right ventricle dysfunction (p < 0.05) with troponin release (p < 0.0001). In group 1, increasing Fio
2 lowered mean pulmonary arterial pressure (p < 0.0001) and pulmonary vascular resistance (p = 0.0056) and decreased right ventricle volumes (p = 0.0018) and right ventricle mechanical work (p = 0.034). Oxygenation was improved and pulmonary shunt was lowered (p < 0.0001). Maximal hemodynamic effects were seen at Fio
2 40% with no additional benefit from higher fractions of oxygen. In group 2, the effects of Fio
2 40% were persistent over 75 minutes. Supplemental oxygen showed the same pulmonary vasodilator efficacy as inhaled nitric oxide (40 parts per million). No adverse effects were observed.

CONCLUSIONS:

In a porcine model mimicking intermediate-high risk pulmonary embolism, oxygen therapy reduced right ventricle afterload and lowered right ventricle mechanical work. The effects were immediately present and persistent and were similar to inhaled nitric oxide. The intervention is easy and safe. The study motivates extended clinical evaluation of supplemental oxygen in acute pulmonary embolism.
Clear Cell Differentiation in Eccrine Porocarcinoma as a High-Risk Feature: Epidemiologic and Pathologic Features of Eccrine Porocarcinoma in a Single-Center Case Series
Authors: Koh Michelle , Telang Gladys , Fonseca Allene , Ghanian Soha , Walker Joanna
Published: April 2021

Eccrine porocarcinoma (EPC) is a rare sweat gland malignancy. Recognition of histologic features is challenging, and specific pathologic features correlate with risk of poor outcome. This single-center retrospective review and case series of 58 EPC cases from 2000 to 2016 elucidates epidemiologic and pathologic characteristics of EPC. Pathology slides from 52 cases were analyzed by a dermatopathologist for standardized variable characteristics, including previously determined high-risk features (HRF) associated with poor prognosis. The incidence of EPC increased over the study period with 3 times more cases diagnosed in the last 4 years than in the first 4 years. Most cases were in the elderly males (mean age 75 years), and 50% were located in the head and neck region. Although 38% of tumors exhibited one histologic HRF, only 10% exhibited more than one. Of the HRF, a greater tumor depth was associated with both increased age (P = 0.04) and clear cell differentiation (P = 0.02). This study elucidates epidemiologic and pathologic features of EPC and highlights how age and clear cell differentiation can be associated with greater tumor depth, although further research is needed to determine whether clear cell differentiation is associated with poor clinical outcome.
New aspects in the management of hypertension in the digital era
Authors: Milani Richard V. , Lavie Carl J. , Ventura Hector O.
Published: April 2021

Purpose of review

Hypertension (HTN) is the most common chronic disease impacting over half the US adult population. Our current office-based model of care is failing in its ability to control blood pressure (BP) as only 44% of adult US hypertensives are achieving minimal levels of BP control (< 140/90 mmHg), leading to high rates of preventable cardiovascular events and death.

Recent findings

Reengineering care delivery using a fully digital platform combined with a dedicated team-based approach to HTN management has demonstrated superior BP control rates, very high levels patient acceptance, and the ability to better diagnose and treat masked and white coat HTN.

A digital medicine program in the clinical care setting can be an effective and convenient mechanism of delivering HTN management, outperforming traditional office-based care, and is well accepted by patients.
Epidemiology of Culture-confirmed Candidemia Among Hospitalized Children in South Africa, 2012–2017
Authors: Shuping Liliwe , Mpembe Ruth , Mhlanga Mabatho , Naicker Serisha D. , Maphanga Tsidiso G. , Tsotetsi Ernest , Wadula Jeannette , Velaphi Sithembiso , Nakwa Firdose , Chibabhai Vindana , Mahabeer Prasha , Moncho Masego , Prentice Elizabeth , Bamford Colleen , Reddy Kessendri , Maluleka Caroline , Mawela Dini , Modise Motshabi , Govender Nelesh P. ,   for GERMS-SA
Published: April 2021

Background:

We aimed to describe the epidemiology of candidemia among children in South Africa.

Methods:

We conducted laboratory-based surveillance among neonates (≤28 days), infants (29 days to <1 year), children (1–11 years) and adolescents (12–17 years) with Candida species cultured from blood during 2012–2017. Identification and antifungal susceptibility of viable isolates were performed at a reference laboratory. We used multivariable logistic regression to determine the association between Candida parapsilosis candidemia and 30-day mortality among neonates.

Results:

Of 2996 cases, neonates accounted for 49% (n = 1478), infants for 27% (n = 806), children for 20% (n = 589) and adolescents for 4% (n = 123). The incidence risk at tertiary public sector hospitals was 5.3 cases per 1000 pediatric admissions (range 0.39–119.1). Among 2943 cases with single-species infections, C. parapsilosis (42%) and Candida albicans (36%) were most common. Candida auris was among the 5 common species with an overall prevalence of 3% (n = 47). Fluconazole resistance was more common among C. parapsilosis (55% [724/1324]) versus other species (19% [334/1737]) (P < 0.001). Of those with known treatment (n = 1666), 35% received amphotericin B deoxycholate alone, 32% fluconazole alone and 30% amphotericin B deoxycholate with fluconazole. The overall 30-day in-hospital mortality was 38% (n = 586) and was highest among neonates (43% [323/752]) and adolescents (43% [28/65]). Compared with infection with other species, C. parapsilosis infection was associated with a reduced mortality among neonates (adjusted odds ratio 0.41, 95% confidence interval: 0.22–0.75, P = 0.004).

Conclusions:

Candidemia in this setting mainly affected neonates and infants and was characterized by fluconazole-resistant C. parapsilosis with no increased risk of death.
Alternative indications for corneal crosslinking
Authors: Van Tigchelt Laurens , Van Eijgen Jan , Delbeke Heleen
Published: April 2021

Corneal crosslinking (CXL) is the current mainstay treatment for progressive keratoconus. In the past 15 years, a variety of other indications have been tested. A systematic review was conducted to examine these alternative indications for CXL. In total, 143 papers on crosslinking as a treatment for infectious keratitis, bullous keratopathy, pellucid marginal degeneration, and postlaser in situ keratomileusis (LASIK) ectasia and as a way to improve vision either on its own or in combination with other interventions were included. Post-LASIK ectasia is a definite indication for crosslinking. Surprisingly, only limited research has been performed on pellucid marginal degeneration, with no randomized trials available to date. Other interesting applications are the combined use of refractive lasers and crosslinking for suspicious or ectatic corneas and crosslinking as a standalone intervention for minor refractive errors. CXL might offer a solution for refractory bacterial keratitis. In bullous keratopathy, it seems to offer only a transient benefit.
Efficacy and complications of cataract surgery in high myopia
Authors: Yao Yunqian , Lu Qiang , Wei Ling , Cheng Kaiwen , Lu Yi , Zhu Xiangjia
Published: April 2021

To evaluate the efficacy and complications of cataract surgery in high myopia, a comprehensive search query was conducted from January 2000 to August 2020. A total of 19 586 highly myopic eyes from 28 studies were included. Modern cataract surgery turns out efficacious in highly myopic eyes with significant improvement of visual acuity. However, phacoemulsification-related complications such as posterior capsular rupture (3.91%, 95% CI, 1.98%-6.37%), retinal detachment (1.74%, 95% CI, 1.36%-2.15%), progressed myopic traction maculopathy (5.07%, 95% CI, 1.80%-9.37%), capsular contraction syndrome (2.1%), intraocular lens dislocation (0.58%), and transient intraocular pressure elevation (28.15%, 95% CI, 20.29%-36.70%) occurred more frequently in the highly myopic population. Separate analyses were also conducted based on follow-up period. In conclusion, modern cataract surgery was effective for highly myopic cataract patients, whereas careful precautions and sufficient follow-ups were of great value because of higher incidences of intraoperative and postoperative complications.
Real-time dynamic changes in intraocular pressure after occlusion break: comparing 2 phacoemulsification systems
Authors: Vasavada Vaishali , Vasavada Abhay R. , Vasavada Viraj A. , Vasavada Shail A. , Bhojwani Deepak
Published: April 2021

Purpose:

To compare real-time intraocular pressure (IOP) response to occlusion break event in 2 phacoemulsification systems.

Setting:

Iladevi Cataract and IOL Research Center, India.

Design:

Randomized, experimental study.

Methods:

Rabbits were randomized to:Group I (n = 10 eyes), Centurion Vision system with active fluidics, or, Group II (n = 10 eyes), Centurion with Active Sentry. Within each group, parameter set 1 (IOP 30 mm Hg, aspiration flow rate [AFR] 20 mL/min, and vacuum 600 mm Hg) and parameter set 2 (IOP 50 mm Hg, AFR 25 mL/min, and vacuum 600 mm Hg) were tested. Real-time rate of drop and rise of IOP after occlusion break event (mm Hg per second) and percentage reduction of IOP from maximum during nuclear fragment removal were compared.

Results:

10 rabbits (20 eyes) were included. Rate of drop of IOP after occlusion break was not significantly different between groups. Rate of rise of IOP was statistically significantly higher in Group II with both parameter sets (199.09 ± 69.28 vs 94.33 ± 45.66 in parameter set 1, P = .006; and 256 ± 45.05 vs 165.25 ± 51.80 in parameter set 2, P = .005), suggesting faster recovery to baseline IOP after occlusion break. The mean percentage reduction of IOP from maximum was significantly higher in Group I (P = .003).

Conclusions:

Rise of IOP to baseline after occlusion break event was faster and mean percentage reduction of IOP from maximum during nuclear fragment removal was lower when using the Centurion Vision system with the Active Sentry upgrade compared with the traditional handpiece. The ability to sense IOP at the level of the handpiece with the Active Sentry upgrade allows faster mitigation of surge response.
Membrane potential instabilities in sensory neurons: mechanisms and pathophysiological relevance
Authors: Velasco Enrique , Alvarez Julio L. , Meseguer Victor M. , Gallar Juana , Talavera Karel
Published: April 2021

Peripheral sensory neurons transduce physicochemical stimuli affecting somatic tissues into the firing of action potentials that are conveyed to the central nervous system. This results in conscious perception, adaptation, and survival, but alterations of the firing patterns can result in pain and hypersensitivity conditions. Thus, understanding the molecular mechanisms underlying action potential firing in peripheral sensory neurons is essential in sensory biology and pathophysiology. Over the past 30 years, it has been consistently reported that these cells can display membrane potential instabilities (MPIs), in the form of subthreshold membrane potential oscillations or depolarizing spontaneous fluctuations. However, research on this subject remains sparse, without a clear conductive thread to be followed. To address this, we here provide a synthesis of the description, molecular bases, mathematical models, physiological roles, and pathophysiological implications of MPIs in peripheral sensory neurons. Membrane potential instabilities have been reported in trigeminal, dorsal root, and Mes-V ganglia, where they are believed to support repetitive firing. They are proposed to have roles also in intercellular communication, ectopic firing, and responses to tonic and slow natural stimuli. We highlight how MPIs are of great interest for the study of sensory transduction physiology and how they may represent therapeutic targets for many pathological conditions, such as acute and chronic pain, itch, and altered sensory perceptions. We identify future research directions, including the elucidation of the underlying molecular determinants and modulation mechanisms, their relation to the encoding of natural stimuli and their implication in pain and hypersensitivity conditions.
Prevalence of chronic pain among adults in the United States
Authors: Yong R. Jason , Mullins Peter M. , Bhattacharyya Neil
Published: April 2021

Chronic pain is associated with reduced quality of life, increased medical expenditures, and significant economic costs. Chronic pain is among the most common chronic conditions in the United States, although estimates vary widely regarding its precise prevalence. Understanding the scope of the problem using the most contemporaneous data is therefore an important goal. This study sought to determine the prevalence of chronic pain and its impacts among adults in the United States using the National Health Interview Survey, a household-based annual survey of self-reported health status of U.S. adults that can be used to generate national-level estimates. Using a chronic pain module introduced in the 2019 edition of National Health Interview Survey, we found that 50.2 million adults (20.5%) reported pain on most days or every day. The most common pain locations were back pain and hip, knee, or foot pain. The most commonly used management strategies for chronic pain were physical therapy and massage. Respondents with chronic pain reported limitations in daily functioning, including social activities and activities of daily living. Respondents with chronic pain reported significantly more workdays missed compared with those without chronic pain (10.3 vs 2.8, P < 0.001). Overall, these findings indicate that more than 1 in 5 adults in America experiences chronic pain; additional attention to managing the burden of this disease is warranted.
Reciprocal interaction between depression and pain: results from a comprehensive bidirectional Mendelian randomization study and functional annotation analysis
Authors: Tang Bowen , Meng Weihua , Hägg Sara , Burgess Stephen , Jiang Xia
Published: April 2021

To understand a putative causal link for depression and pain, we retrieved summary statistics from genome-wide association studies conducted for pain at 7 different body sites (N = 151,922-226,683) and major depression disorder (MDD, Ncase/control = 246,363/561,190). We conducted a bidirectional Mendelian randomization analysis using distinct genome-wide association studies-identified single nucleotide polymorphisms for each trait as instrumental variables and performed several sensitivity analyses to verify Mendelian randomization assumptions. We also conducted functional annotation analysis using 396 tissue-specific annotations from the roadmap project. Across 7 different body sites, genetic predisposition to depression was associated with pain at the neck/shoulder (odds ratio [OR] = 1.08 per one log-unit increase in depression risk, 95% confidence interval [CI]: 1.06-1.10), back (OR = 1.05, 95% CI: 1.04-1.07), abdominal/stomach (OR = 1.03, 95% CI: 1.02-1.04), as well as headache (OR = 1.10, 95% CI: 1.07-1.12), but not with pain on the face, hip, and knee. In the reverse direction, genetically instrumented multisite chronic pain (OR = 1.78 per one increment in the number of pain site, 95% CI: 1.51-2.11) and headache (OR = 1.55 per one log-unit increase in headache risk, 95% CI = 1.13-2.10) were associated with MDD. Functional annotation analysis showed differential clustering patterns where depression clustered closely with headache and neck/shoulder pain, exhibiting substantial brain tissue enrichment. Our study indicates that depression is a causal risk factor for headache and pain localized at neck/shoulder, back, and abdominal/stomach, rather than pain at face, hip, and knee, and suggests common neurological pathologies underlying the development of depression, headache, and neck/shoulder pain.
Pain response to cannabidiol in induced acute nociceptive pain, allodynia, and hyperalgesia by using a model mimicking acute pain in healthy adults in a randomized trial (CANAB I)
Authors: Schneider Tobias , Zurbriggen Laura , Dieterle Markus , Mauermann Eckhard , Frei Priska , Mercer-Chalmers-Bender Katja , Ruppen Wilhelm
Published: April 2021

Preclinical studies have demonstrated the analgesic potential of cannabidiol (CBD). Those suggesting an effect on pain-processing receptors have brought CBD back into focus. This study assessed the effect of CBD on acute pain, hyperalgesia, and allodynia compared with placebo. Twenty healthy volunteers were included in this randomized, placebo-controlled, double-blinded, crossover study assessing pain intensities (using numeric rating scale), secondary hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a well-established acute pain model with intradermal electrical stimulation. The authors compared the effect of 800-mg orally administered CBD on pain compared with placebo. They further examined the effect on hyperalgesia and allodynia. Cannabidiol whole blood levels were also measured. Pain ratings (mean ± SD) did not differ significantly after CBD application compared with placebo (5.2 ± 0.7 vs 5.3 ± 0.7, P-value 0.928), neither did the areas of hyperalgesia and allodynia differ significantly after CBD application compared with placebo (hyperalgesia 23.9 ± 19.2 cm2 vs 27.4 ± 17.0 cm2, P-value 0.597; allodynia 16.6 ± 13.1 cm2 vs 17.3 ± 14.1 cm2, P-value 0.884). The CBD whole blood level (median, first to third quartile) was 2.0 µg/L (1.5-5.1) 60 minutes and 5.0 µg/L (4.0-10.4) 130 minutes after CBD application. Although the oral application of 800-mg CBD failed to show a significant effect, it is important to focus future research on different dosing, routes of administration, and CBD as a part of multimodal treatment strategies before negating its effects on acute pain.
Heart Health in Teachers—Do We Need to Know More?
Authors: Barron Keri A. , Ford Cassandra D. , Wang Hui
Published: April 2021

Objectives:

To evaluate the relationship between the prevalence and risk factors for cardiovascular disease and hypertension, physical activity, and mental health in teachers.

Methods:

Data were drawn from the 2011–2012 National Health and Nutrition Examination Survey. A series of analyses were conducted utilizing exploratory data analysis, nominal logistic regression, and multivariate regression analysis.

Results:

The study sample included 148 participants. The results showed that an increase in age and BMI contributed to an increase in high blood pressure. Significance was not seen between physical activity, anxiety, and mental well-being as they related to cardiovascular disease and teaching.

Conclusions:

Our results showed that the prevalence of cardiovascular disease and hypertension could be related to the occupation of teaching; however, additional research should be done to assess the relationship between the occupation of teaching and cardiovascular disease.