bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous baroreflex sensitivity and its association with age, sex, obesity indices and hypertension: a population study
Authors: Man Tengfei , Tegegne Balewgizie S , van Roon Arie M , Rosmalen Judith G M , Nolte Ilja M , Snieder Harold , Riese Harriëtte
Published: July 2021

BACKGROUND

Low baroreflex sensitivity (BRS) was an established risk factor for cardiovascular disorders. We investigated determinants of BRS in a large sample from general population.

METHODS

In a population-based study (n = 901), data were collected on BRS, arm cuff blood pressure (BP), and obesity indices including body mass index, waist-to-hip ratio, waist circumference, and percentage body fat (%BF). BRS was calculated by spectral analysis software based on continuously recorded spontaneous fluctuations in beat-to-beat finger BP for 10–15 minutes. Correlations and multivariable regression analyses were used to test associations of age, sex, obesity indices, and hypertension with BRS while considering effects of lifestyle factors (smoking, alcohol consumption, and physical activity).

RESULTS

In multivariable analysis, age, sex, %BF, and hypertension were independently associated with BRS. BRS decreased with −0.10 (95% confidence interval: −0.15 to −0.06) ms/mm Hg with each year of increase in age. Women had −1.55 (95% confidence interval: −2.28 to −0.73) ms/mm Hg lower mean BRS than men. The effects of %BF (per 10% increase) and hypertension on BRS were −0.55 (95% confidence interval: −0.97 to −0.13) ms/mm Hg and −1.23 (95% confidence interval: −1.92 to −0.46) ms/mm Hg, respectively. There was no evidence of associations between BRS and lifestyle factors. Age, age2, sex, and their interactions plus %BF and hypertension contributed 16.9% of total variance of BRS.

CONCLUSIONS

In this large general population study, we confirmed prior findings that age and sex were important factors associated with BRS and found %BF was more strongly related to less favorable BRS levels than body mass index.
Intravenous fosfomycin as salvage therapy for osteomyelitis caused by multidrug-resistant Pseudomonas aeruginosa
Authors: Wong Maggie , Wong Davie , Malhotra Sangita
Published: July 2021

Purpose

A case of osteomyelitis caused by multidrug-resistant (MDR) Pseudomonas aeruginosa is reported.

An 84-year-old Caucasian male with an underlying history of type 2 diabetes, peripheral vascular disease, and coronary artery disease had chronic nonhealing wounds on his right foot. Wound care and a course of intravenous (IV) ertapenem with oral ciprofloxacin were ineffective. His initial wound culture grew Staphylococcus aureus, group G streptococcus and P. aeruginosa; the Pseudomonas was susceptible to multiple agents. The patient eventually required midtarsal amputation and angioplasties to his right leg. Twenty days after the operation, 2 openings were discovered at the surgical site, 1 of which was probed to the bone. He was readmitted 5 weeks after the operation. A repeat wound swab grew MDR P. aeruginosa and Finegoldia magna. The Pseudomonas was susceptible to gentamicin and colistin. The patient had revision of the infected amputation site with the goal of salvaging his right lower limb. The patient developed acute renal failure after 26 days of IV gentamicin, IV ceftriaxone, and oral metronidazole. Additional susceptibility testing was performed to identify alternatives. The bacteria were considered susceptible to IV fosfomycin, the last resort, by our microbiology laboratory. This was combined with ceftolozane/tazobactam followed by meropenem to treat the residual infection. After 2 weeks of IV fosfomycin, the patient’s wound improved and further amputation was avoided.

Conclusion

Our case demonstrates that IV fosfomycin may provide an effective salvage therapy when combined with β-lactams for the treatment of severe diabetic foot infection or osteomyelitis caused by MDR P. aeruginosa.
Allele mining in diverse accessions of tropical grasses to improve forage quality and reduce environmental impact
Authors: Hanley Steve J , Pellny Till K , de Vega Jose J , Castiblanco Valheeria , Arango Jacobo , Eastmond Peter J , Heslop-Harrison J S (Pat) , Mitchell Rowan A C
Published: July 2021

Background and Aims

The C4Urochloa species (syn. Brachiaria) and Megathyrsus maximus (syn. Panicum maximum) are used as pasture for cattle across vast areas in tropical agriculture systems in Africa and South America. A key target for variety improvement is forage quality: enhanced digestibility could decrease the amount of land required per unit production, and enhanced lipid content could decrease methane emissions from cattle. For these traits, loss-of-function (LOF) alleles in known gene targets are predicted to improve them, making a reverse genetics approach of allele mining feasible. We therefore set out to look for such alleles in diverse accessions of Urochloa species and Megathyrsus maximus from the genebank collection held at the CIAT.

Methods

We studied allelic diversity of 20 target genes (11 for digestibility, nine for lipid content) in 104 accessions selected to represent genetic diversity and ploidy levels of U. brizantha, U. decumbens, U. humidicola, U. ruziziensis and M. maximum. We used RNA sequencing and then bait capture DNA sequencing to improve gene models in a U. ruziziensis reference genome to assign polymorphisms with high confidence.

Key Results

We found 953 non-synonymous polymorphisms across all genes and accessions; within these, we identified seven putative LOF alleles with high confidence, including those in the non-redundant SDP1 and BAHD01 genes present in diploid and tetraploid accessions. These LOF alleles could respectively confer increased lipid content and digestibility if incorporated into a breeding programme.

Conclusions

We demonstrated a novel, effective approach to allele discovery in diverse accessions using a draft reference genome from a single species. We used this to find gene variants in a collection of tropical grasses that could help reduce the environmental impact of cattle production.
Genetic diversity and population structure of a global invader Mayweed chamomile (Anthemis cotula): management implications
Authors: Adhikari Subodh , Revolinski Samuel R , Eigenbrode Sanford D , Burke Ian C
Published: July 2021

Mayweed chamomile (Anthemis cotula) is a globally invasive, troublesome annual weed but knowledge of its genetic diversity, population structure in invaded regions and invasion patterns remains unstudied. Therefore, germplasm from 19 A. cotula populations (sites) from three geographically distinct invaded regions: the Walla Walla Basin (located in southern Washington) and the Palouse (located in both northern Idaho and eastern Washington), Pacific Northwest, USA and Kashmir Valley, India were grown in the greenhouse for DNA extraction and sequencing. A total of 18 829 single-nucleotide polymorphisms were called and filtered for each of 89 samples. Pairwise FST, Nei’s genetic distance, heterozygosity, Wright’s inbreeding coefficient (F) and self-fertilization rates were estimated for populations within and among the three regions with a total of 19 populations comprised of 89 individuals. Overall measurements of genetic variation were low but significant among regions, populations and individuals. Despite the weak genetic structure, two main genetic clusters were evident, one comprised of populations from Palouse and Kashmir Valley, the other comprised of populations from the Walla Walla Basin. Significant selfing was observed in populations from the Walla Walla Basin and Palouse but not from Kashmir Valley, indicating that Mayweed chamomile in the Pacific Northwest, USA could persist with low pollinator or pollen donor densities. Although FST values between the regions indicate Palouse populations are more closely related to Kashmir Valley than to Walla Walla Basin populations, based on Migrate-n analysis, panmixis was the most likely model, suggesting an unrestricted gene flow among all three regions. Our study indicated that Kashmir Valley populations either originated from or shared the origin with the Palouse populations, suggesting human-mediated migration of A. cotula between regions.
Mendelian randomization under the omnigenic architecture
Authors: Wang Lu , Gao Boran , Fan Yue , Xue Fuzhong , Zhou Xiang
Published: July 2021

Mendelian randomization (MR) is a common analytic tool for exploring the causal relationship among complex traits. Existing MR methods require selecting a small set of single nucleotide polymorphisms (SNPs) to serve as instrument variables. However, selecting a small set of SNPs may not be ideal, as most complex traits have a polygenic or omnigenic architecture and are each influenced by thousands of SNPs. Here, motivated by the recent omnigenic hypothesis, we present an MR method that uses all genome-wide SNPs for causal inference. Our method uses summary statistics from genome-wide association studies as input, accommodates the commonly encountered horizontal pleiotropy effects and relies on a composite likelihood framework for scalable computation. We refer to our method as the omnigenic Mendelian randomization, or OMR. We examine the power and robustness of OMR through extensive simulations including those under various modeling misspecifications. We apply OMR to several real data applications, where we identify multiple complex traits that potentially causally influence coronary artery disease (CAD) and asthma. The identified new associations reveal important roles of blood lipids, blood pressure and immunity underlying CAD as well as important roles of immunity and obesity underlying asthma.
Bumblebees, the proficient mountain pollinators: evidence from Stachys germanica (Lamiaceae) along the altitudinal gradient of Mount Olympus, Greece
Authors: Minachilis Konstantinos , Kantsa Aphrodite , Petanidou Theodora
Published: July 2021

Pollen limitation and its drivers along altitudinal clines form a controversial topic, highlighting the need for more studies and in different biomes. We tested the hypothesis that the populations of a predominantly bee-pollinated plant are pollen-limited along elevations and examined whether this is related to bee visitation rate. For two years, we studied flower visitation, pollen limitation and mating system using five populations of Stachys germanica L. occurring between 327 and 1936 m a.s.l. on Mt. Olympus, Greece. S. germanica showed moderate to high self-compatibility, low spontaneous self-pollination and low pollen limitation across all altitudes and years. Bumblebees were the dominant pollinators; their visitation increased with altitude and was positively correlated with seed set and negatively correlated with pollen limitation. The opposite trend was found for the visitation by other pollinators. Seed mass was independent of visitation. Low pollen limitation is evidently due to high bumblebee visitation along the altitude, whereas seed mass could be linked to resource availability or environmental conditions. Our findings underline the functional role of bumblebees on Mediterranean mountains, and the need to focus on bumblebee conservation on this legendary mountain.
Characterization of different oligomeric forms of CRISP2 in the perinuclear theca versus the fibrous tail structures of boar spermatozoa†
Authors: Zhang M , Bromfield E G , Veenendaal T , Klumperman J , Helms J B , Gadella B M
Published: July 2021

Mammalian sperm carry a variety of highly condensed insoluble protein structures such as the perinuclear theca, the fibrous sheath and the outer dense fibers, which are essential to sperm function. We studied the role of cysteine rich secretory protein 2 (CRISP2); a known inducer of non-pathological protein amyloids, in pig sperm with a variety of techniques. CRISP2, which is synthesized during spermatogenesis, was localized by confocal immunofluorescent imaging in the tail and in the post-acrosomal region of the sperm head. High-resolution localization by immunogold labeling electron microscopy of ultrathin cryosections revealed that CRISP2 was present in the perinuclear theca and neck region of the sperm head, as well as in the outer dense fibers and the fibrous sheath of the sperm tail. Interestingly, we found that under native, non-reducing conditions CRISP2 formed oligomers both in the tail and the head but with different molecular weights and different biochemical properties. The tail oligomers were insensitive to reducing conditions but nearly complete dissociated into monomers under 8 M urea treatment, while the head 250 kDa CRISP2 positive oligomer completely dissociated into CRISP2 monomers under reducing conditions. The head specific dissociation of CRISP2 oligomer is likely a result of the reduction of various sulfhydryl groups in the cysteine rich domain of this protein. The sperm head CRISP2 shared typical solubilization characteristics with other perinuclear theca proteins as was shown with sequential detergent and salt treatments. Thus, CRISP2 is likely to participate in the formation of functional protein complexes in both the sperm tail and sperm head, but with differing oligomeric organization and biochemical properties. Future studies will be devoted to the understand the role of CRISP2 in sperm protein complexes formation and how this contributes to the fertilization processes.
Drug-coated balloon angioplasty for failing haemodialysis access: meta-analysis of randomized clinical trials
Authors: Hu H , Tan Q , Wang J , Liu Y , Yang Y , Zhao J
Published: July 2021

Background

Arteriovenous fistulas, a major treatment for end-stage kidney disease, frequently require endovascular reinterventions to maintain haemodialysis function. Drug-coated angioplasty balloons (DCBs) were developed with the intention of reducing reintervention rates. The aim of this study was to perform a systematic review and meta-analysis of DCBs in the treatment of failing haemodialysis access.

Methods

Electronic databases were searched systematically to identify all relevant RCTs and any follow-up studies from RCTs. Pooled estimates of dichotomous outcomes were calculated using the odds ratio (OR) and 95 per cent confidence interval. Effect data are presented as summary hazard ratio and 95 per cent confidence interval.

Results

Some 19 studies from 18 RCTs and comprising 1898 patients were included in the meta-analysis. Compared with plain balloon angioplasty (PBA), DCB use was associated with higher target-lesion primary patency (HR 0.60, 95 per cent c.i. 0.45 to 0.79), access-circuit primary patency (HR 0.67, 0.56 to 0.80), and less target-lesion revascularization (TLR) within 6 months (OR 0.33, 0.23 to 0.47). No difference was observed between DCB and PBA in 12-month TLR (OR 0.62, 0.28 to 1.37). Mortality after DCB use was similar to that associated with PBA use at 6 months (OR 1.20, 0.65 to 2.21) and 12 months (OR 0.99, 0.66 to 1.49), and was higher at 24 months (23.1 versus 16.6 per cent), although the difference was not statistically significant (OR 1.53, 0.92 to 2.53).

Conclusion

Drug-coated balloon angioplasty of haemodialysis fistulas is associated with higher patency rates and lower rates of reintervention in the short to mid term. Although mortality rates appeared to be higher with drug-coated angioplasty at 24 months, this did not reach statistical significance.
Phylogenetic analysis ofDioscorea(Dioscoreaceae) from Japan and adjacent regions based on plastid and nuclear DNA sequences, with special reference to the taxonomic status of selected taxa
Authors: Noda Hiroshi , Fuse Shizuka , Yamashita Jun , Poopath Manop , Pooma Rachun , Tamura Minoru N
Published: July 2021

To clarify phylogenetic relationships among Japanese Dioscorea taxa and to re-examine taxonomy based on these relationships, we conducted molecular phylogenetic analyses of four plastid regions [trnK (including matK), rbcL, atpB and trnL-F] and two nuclear regions (PHYC and 18S rDNA) for all Dioscorea taxa from Japan and selected taxa from adjacent regions. Although species are often sympatric and variation in leaf shape is relatively wide within species and not clearly demarcated between species, our results suggest that Japanese Dioscorea spp. do not hybridize. Our results also resolve several taxonomic issues surrounding Japanese species. We confirm that D. japonica, D. polystachya, D. pseudojaponica and D. tabatae, which are morphologically similar, are distinct species. Further, plants from the Daito Islands identified as D. luzonensis, which have never been observed to flower to our knowledge, are attributable to D. pseudojaponica. Dioscorea zentaroana, often treated as a synonym of D. asclepiadea, was found to be distinct from the latter. Dioscorea izuensis should be treated as D. collettii var. izuensis. In conclusion, 16 species and three varieties of native Dioscorea should be recognized in Japan.
The Robert Capa Myth: Hegemonic Masculinity in Photojournalism’s Professional Indoctrination
Authors: Assaf Christopher T , Bock Mary Angela
Published: July 2021

This project examines the mythos of famed war photographer Robert Capa and its influence on the photojournalistic canon. Using Barthes’ concept of ideological myth as a foundation, the project examines four sets of discourses about Capa: his own self-promotion, biographies, exhibition reviews, and photojournalistic textbooks. The analysis suggests that the Capa myth is characterized by hegemonic masculinity, emphasizing risk-taking, strength and courage, in ways that may occlude the famed photographer’s humanity. The corpus chosen for this project enabled an ideological analysis and critique of the way the Capa myth permeates the field’s indoctrination. The project finds that the mythic portrait of Capa has had considerable influence on photojournalistic education but may no longer serve the larger field.
Leveraging a Preexisting Global Infectious Disease Network for Local Decision Making During a Pandemic
Authors: Herstein Jocelyn J , Lowe John J , Wolf Timo , Vasoo Shawn , Leo Yee Sin , Chin Bum Sik , Shen Yinzhong , Hewlett Angela L , Lawler James V
Published: July 2021

Emerging infectious disease epidemics require a rapid response from health systems; however, evidence-based consensus guidelines are generally absent early in the course of events. Formed in 2017 by 5 high-level isolation units spanning 3 continents, the experience of the Global Infectious Disease Preparedness Network (GIDPN) early in the course of coronavirus disease 2019 (COVID-19) provides a model for accelerating best practice development and improving decision-making in health emergencies. The network served as a platform for real-time, open and transparent information-sharing during unknowns of an active outbreak by clinicians caring for patients, by researchers conducting clinical trials and transmission and infection prevention studies, and by teams advising local and national policy makers. Shared knowledge led to earlier adoption of some treatment modalities as compared to most peer institutions and to implementation of protocols prior to incorporation into national guidelines. GIDPN and similar networks are integral in enhancing preparedness for and response to future epidemics/pandemics.
Disparities in patient engagement with video telemedicine among high-video-use providers during the COVID-19 pandemic
Authors: Grady Connor B , Claus Elizabeth B , Bunn David A , Pagliaro Jaclyn A , Lichtman Judith H , Bhatt Ami B
Published: July 2021

Aims

Known racial, ethnic, age, and socioeconomic disparities in video telemedicine engagement may widen existing health inequities. We assessed if telemedicine disparities were alleviated among patients of high-video-use providers at a large cardiovascular practice.

Methods and results

All telemedicine visits from 16 March to 31 October 2020 and patient demographics were collected from an administrative database. Providers in the upper quintile of video use were classified as high-video-use providers. Descriptive statistics and a multivariable logistic model were calculated to determine the distribution and predictors of a patient ever having a video visit vs. only phone visits. A total of 24 470 telemedicine visits were conducted among 18 950 patients by 169 providers. Video visits accounted for 48% of visits (52% phone). Among telemedicine visits conducted by high-video-use providers (n = 33), ever video patients were younger (P < 0.001) and included 78% of Black patients vs. 86% of White patients (P < 0.001), 74% of Hispanic patients vs. 86% of non-Hispanic patients (P < 0.001), and 79% of public insurance patients vs. 91% of private insurance patients (P < 0.001). High-video-use provider patients had 9.4 (95% confidence interval 8.4–10.4) times the odds of having video visit compared to low-video-use provider patients.

Conclusion

These results suggest that provider-focused solutions alone, including promoting provider adoption of video visits, may not adequately reduce disparities in telemedicine engagement. Even in the presence of successful clinical infrastructure for telemedicine, individuals of Black race, Hispanic ethnicity, older age, and with public insurance continue to have decreased engagement. To achieve equity in telemedicine, patient-focused design is needed.
Supracommissural replacement of the ascending aorta and the aortic valve via partial versus full sternotomy—a propensity-matched comparison in a high-volume centre
Authors: Haunschild Josephina , van Kampen Antonia , von Aspern Konstantin , Misfeld Martin , Davierwala Piroze , Saeed Diyar , Borger Michael A , Etz Christian D
Published: July 2021

OBJECTIVES

Full sternotomy (FS) is the common surgical access for patients undergoing open aortic valve replacement (AVR) with concomitant supracommissural replacement of the tubular ascending aorta. Since minimally invasive approaches are being used with increasing frequency in cardiac surgery, the aim of this study was to compare outcomes of patients undergoing AVR with supracommissural replacement of the tubular ascending aorta via FS versus partial upper sternotomy (PS).

METHODS

We included all patients who underwent elective AVR with concomitant supracommissural replacement of the tubular ascending aorta at our institution between 2000 and 2015. Exclusion criteria were emergency surgery, other major concomitant procedures and reoperations. After 2:1 propensity score matching, outcomes of patients with PS and FS were compared.

RESULTS

A total of 652 consecutive patients were included, 117 patients operated via PS and 234 patients operated via FS. Cardiopulmonary bypass time and aortic cross-clamp time of the PS and FS groups were 89 vs 92 min (P = 0.2) and 65 vs 70 min (P = 0.3), respectively. Postoperative morbidity was low and there were no significant differences in postoperative outcomes between patient groups. In-hospital mortality was 1.7% in the PS vs 0.4% in the FS group (P = 0.3). Kaplan–Meier analysis revealed no difference in mid-term survival (P = 0.3). Reoperation rates for valve or aortic complications were very low with no significant difference between groups.

CONCLUSIONS

In a high-volume centre with extensive experience in minimally invasive cardiac surgery, AVR with concomitant supracommissural replacement of the tubular ascending aorta via PS results in similar outcomes with regard to safety and longevity when compared to conventional FS.
Ticagrelor monotherapy in patients with chronic kidney disease undergoing percutaneous coronary intervention: TWILIGHT-CKD
Authors: Stefanini Giulio G , Briguori Carlo , Cao Davide , Baber Usman , Sartori Samantha , Zhang Zhongjie , Dangas George , Angiolillo Dominick J , Mehta Shamir , Cohen David J , Collier Timothy , Dudek Dariusz , Escaned Javier , Gibson C Michael , Gil Robert , Huber Kurt , Kaul Upendra , Kornowski Ran , Krucoff Mitchell W , Kunadian Vijay , Moliterno David J , Ohman E Magnus , Oldroyd Keith G , Sardella Gennaro , Sharma Samin K , Shlofmitz Richard , Weisz Giora , Witzenbichler Bernhard , Pocock Stuart , Mehran Roxana
Published: July 2021

Aims

The aim of this study was to assess the impact of chronic kidney disease (CKD) on the safety and efficacy of ticagrelor monotherapy among patients undergoing percutaneous coronary intervention (PCI).

Methods and results

In this prespecified subanalysis of the TWILIGHT trial, we evaluated the treatment effects of ticagrelor with or without aspirin according to renal function. The trial enrolled patients undergoing drug-eluting stent implantation who fulfilled at least one clinical and one angiographic high-risk criterion. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was a clinical study entry criterion. Following a 3-month period of ticagrelor plus aspirin, event-free patients were randomly assigned to aspirin or placebo on top of ticagrelor for an additional 12 months. Of the 6835 patients randomized and with available eGFR at baseline, 1111 (16.3%) had CKD. Ticagrelor plus placebo reduced the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding as compared with ticagrelor plus aspirin in both patients with [4.6% vs. 9.0%; hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31–0.80] and without (4.0% vs. 6.7%; HR 0.59, 95% CI 0.47–0.75; P  interaction = 0.508) CKD, but the absolute risk reduction was greater in the former group. Rates of death, myocardial infarction, or stroke were not significantly different between the two randomized groups irrespective of the presence (7.9% vs. 5.7%; HR 1.40, 95% CI 0.88–2.22) or absence of (3.2% vs. 3.6%; HR 0.90, 95% CI 0.68–1.20; P  interaction = 0.111) CKD.

Conclusion

Among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events as compared with ticagrelor plus aspirin.
Artificial intelligence in the diagnosis and management of arrhythmias
Authors: Nagarajan Venkat D , Lee Su-Lin , Robertus Jan-Lukas , Nienaber Christoph A , Trayanova Natalia A , Ernst Sabine
Published: July 2021

The field of cardiac electrophysiology (EP) had adopted simple artificial intelligence (AI) methodologies for decades. Recent renewed interest in deep learning techniques has opened new frontiers in electrocardiography analysis including signature identification of diseased states. Artificial intelligence advances coupled with simultaneous rapid growth in computational power, sensor technology, and availability of web-based platforms have seen the rapid growth of AI-aided applications and big data research. Changing lifestyles with an expansion of the concept of internet of things and advancements in telecommunication technology have opened doors to population-based detection of atrial fibrillation in ways, which were previously unimaginable. Artificial intelligence-aided advances in 3D cardiac imaging heralded the concept of virtual hearts and the simulation of cardiac arrhythmias. Robotics, completely non-invasive ablation therapy, and the concept of extended realities show promise to revolutionize the future of EP. In this review, we discuss the impact of AI and recent technological advances in all aspects of arrhythmia care.
Anticoagulation, therapy of concomitant conditions, and early rhythm control therapy: a detailed analysis of treatment patterns in the EAST - AFNET 4 trial
Authors: Metzner Andreas , Suling Anna , Brandes Axel , Breithardt , Günter , Camm A John , Crijns Harry J G M , Eckardt , Lars , Elvan , Arif , Goette , Andreas , Haegeli , Laurent M , Heidbuchel , Hein , Kautzner , Josef , Kuck , Karl-Heinz , Mont , Luis , Ng G Andre , Szumowski , Lukasz , Themistoclakis , Sakis , van Gelder , Isabelle C , Vardas , Panos , Wegscheider , Karl , Willems , Stephan , Kirchhof Paulus
Published: July 2021

Aims

Treatment patterns were compared between randomized groups in EAST-AFNET 4 to assess whether differences in anticoagulation, therapy of concomitant diseases, or intensity of care can explain the clinical benefit achieved with early rhythm control in EAST-AFNET 4.

Methods and results

Cardiovascular treatment patterns and number of visits were compared between randomized groups in EAST-AFNET 4. Oral anticoagulation was used in >90% of patients during follow-up without differences between randomized groups. There were no differences in treatment of concomitant conditions between groups. The type of rhythm control varied by country and centre. Over time, antiarrhythmic drugs were given to 1171/1395 (84%) patients in early therapy, and to 202/1394 (14%) in usual care. Atrial fibrillation (AF) ablation was performed in 340/1395 (24%) patients randomized to early therapy, and in 168/1394 (12%) patients randomized to usual care. 97% of rhythm control therapies were within class I and class III recommendations of AF guidelines. Patients randomized to early therapy transmitted 297 166 telemetric electrocardiograms (ECGs) to a core lab. In total, 97 978 abnormal ECGs were sent to study sites. The resulting difference between study visits was low (0.06 visits/patient/year), with slightly more visits in early therapy (usual care 0.39 visits/patient/year; early rhythm control 0.45 visits/patient/year, P < 0.001), mainly due to visits for symptomatic AF recurrences or recurrent AF on telemetric ECGs.

Conclusion

The clinical benefit of early, systematic rhythm control therapy was achieved using variable treatment patterns of antiarrhythmic drugs and AF ablation, applied within guideline recommendations.
Nutrient load acts as a driver of gut microbiota load, community composition and metabolic functionality in the simulator of the human intestinal microbial ecosystem
Authors: Minnebo Yorick , De Paepe Kim , Raes Jeroen , de Wiele Tom Van
Published: July 2021

A recently introduced quantitative framework for gut microbiota analysis indicated that microbial load alterations can be linked to various diseases, making it essential to pinpoint its determinants. We identified nutrient load as a main driver of the quantitative microbial community composition and functionality in vitro by stepwise decreasing standardized feed concentrations from 100% to 33%, 20% and 10% in 5-day intervals. While the proportional composition and metabolic profile were mainly determined by the inter-individual variability (35% and 41%), nutrient load accounted for 58%, 23% and 65% of the observed variation in the microbial load, quantitative composition and net daily metabolite production, respectively. After the 10-fold nutrient reduction, the microbial load decreased by 79.72 ± 9% and 82.96 ± 1.66% in the proximal and distal colon, respectively, while the net total short-chain fatty acid production dropped by 79.42 ± 4.42% and 84.58 ± 2.42%, respectively. The majority of microbial taxa quantitatively decreased, whereas a select group of nutritional specialists, such as Akkermansia muciniphila and Bilophila wadsworthia, and a number of opportunistic pathogens remained unaffected. This shows that nutrient load is an important driver of the human gut microbiome and should be considered in future in vitro and in vivo dietary research.
Leveraging histone modifications to improve genome annotations
Authors: Mendieta John Pablo , Marand Alexandre P , Ricci William A , Zhang Xuan , Schmitz Robert J
Published: July 2021

Accurate genome annotations are essential to modern biology; however, they remain challenging to produce. Variation in gene structure and expression across species, as well as within an organism, make correctly annotating genes arduous; an issue exacerbated by pitfalls in current in silico methods. These issues necessitate complementary approaches to add additional confidence and rectify potential misannotations. Integration of epigenomic data into genome annotation is one such approach. In this study, we utilized sets of histone modification data, which are precisely distributed at either gene bodies or promoters to evaluate the annotation of the Zea mays genome. We leveraged these data genome wide, allowing for identification of annotations discordant with empirical data. In total, 13,159 annotation discrepancies were found in Z. mays upon integrating data across three different tissues, which were corroborated using RNA-based approaches. Upon correction, genes were extended by an average of 2128 base pairs, and we identified 2529 novel genes. Application of this method to five additional plant genomes identified a series of misannotations, as well as identified novel genes, including 13,836 in Asparagus officinalis, 2724 in Setaria viridis, 2446 in Sorghum bicolor, 8631 in Glycine max, and 2585 in Phaseolous vulgaris. This study demonstrates that histone modification data can be leveraged to rapidly improve current genome annotations across diverse plant lineages.
Met is required for oligodendrocyte progenitor cell migration inDanio rerio
Authors: Ali Maria F , Latimer Andrew J , Wang Yinxue , Hogenmiller Leah , Fontenas Laura , Isabella Adam J , Moens Cecilia B , Yu Guoqiang , Kucenas Sarah
Published: July 2021

During vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping domains. While this process of developmental OPC migration is well characterized, the nature of the molecular mediators that govern it remain largely unknown. Here, using zebrafish as a model, we demonstrate that Met signaling is required for initial developmental migration of OPCs, and, using cell-specific knock-down of Met signaling, show that Met acts cell-autonomously in OPCs. Taken together, these findings demonstrate in vivo, the role of Met signaling in OPC migration and provide new insight into how OPC migration is regulated during development.
A Stress Test for German Nationalism: Protective Custody in Alsace-Lorraine during the First World War
Authors: Prott Volker
Published: July 2021

When the First World War broke out, the French government declared the return of Alsace-Lorraine its only public war aim, arguing that the population was ‘French in spirit’. In an age rife with claims of national self-determination, trapped in a protracted war of attrition and facing a nationally ambivalent population, the German state soon came under enormous pressure to ensure the loyalty and patriotism of the inhabitants of its western borderland. This article examines why Imperial Germany failed to meet this ‘stress test’. It focuses on the crucial but hitherto neglected issue of protective custody (Schutzhaft), whereby police and military authorities were able to arrest and detain ‘suspect’ civilians without charge or trial. The article finds that protective custody, an emergency measure under martial law, played a central role in the failure of German policy in Alsace-Lorraine: it undermined the rule of law, shifted the focus onto national dissent and gave rise to an atmosphere of suspicion and fear. The article also demonstrates that the Reichstag successfully put limits on protective custody in the second half of the war. Yet leaving the authoritarian doctrine of enforcing national loyalty in place, the more lenient administrative approach had a disintegrative rather than a stabilizing effect, preparing the ground for widespread disaffection with German rule months before the war ended.
Aging, Empathy, and Prosocial Behaviors During the COVID-19 Pandemic
Authors: Cho Isu , Daley Ryan T , Cunningham Tony J , Kensinger Elizabeth A , Gutchess Angela
Published: July 2021

Objectives

Previous literature suggests age-related increases in prosociality. Does such an age–prosociality relationship occur during the coronavirus disease 2019 (COVID-19) pandemic, or might the pandemic—as a stressor that may differently influence young and older adults—create a boundary condition on the relationship? If so, can empathy, a well-known prosocial disposition, explain the age–prosociality relationship? This study investigated these questions and whether the target (distant others compared to close others) of prosocial behaviors differs by age.

Methods

Participants completed a series of surveys on dispositional empathy and prosocial behaviors for a study assessing their experiences during the COVID-19 pandemic. There were 330 participants (aged 18–89) from the United States who completed all of the surveys included in the present analyses.

Results

Age was positively related to greater prosociality during the pandemic. Although empathy was positively associated with individuals’ prosociality, it did not account for the age–prosociality association. Interestingly, increasing age was associated with greater prosocial behaviors toward close others (i.e., family, friends).

Discussion

Results are discussed in the context of socioemotional goals and substantiate that findings of age differences in prosocial behaviors occur during the period of limited resources and threat associated with the COVID-19 pandemic.
Changes in health worker knowledge and motivation in the context of a quality improvement programme in Ethiopia
Authors: Quaife Matthew , Estafinos Abiy Seifu , Keraga Dorka Woldesenbet , Lohmann Julia , Hill Zelee , Kiflie Abiyou , Marchant Tanya , Borghi Josephine , Schellenberg Joanna
Published: July 2021

A knowledgeable and motivated workforce is critical for health systems to provide high-quality services. Many low- and middle-income countries face shortages in human resources and low health worker motivation but are also home to a burgeoning number of quality improvement (QI) programmes. This study evaluates whether and how motivation and clinical knowledge in three cadres of health workers changed in the context of a QI programme for maternal and newborn health in Ethiopia. This mixed-methods study used a pre–post comparison group design with matched comparison areas. We interviewed 395 health workers at baseline in April 2018 and 404 at endline in June 2019 from seven districts (woredas) with QI and seven comparison woredas. Three cadres were interviewed: health extension workers, facility-based skilled midlevel maternal and newborn care providers, and non-patient-facing staff. A qualitative component sought to triangulate and further elucidate quantitative findings using in-depth interviews with 22 health workers. Motivation was assessed quantitatively, exploratory factor analysis was used to categorize motivation dimensions, and regression-based difference-in-difference analyses were conducted. Knowledge was assessed through a clinical vignette. Qualitative data were analysed in a deductive process based on a framework derived from quantitative results. Although knowledge of the QI programme was high (79%) among participants from QI woreda at endline, participation in QI teams was lower (56%). There was strong evidence that health worker knowledge increased more in areas with QI than comparison areas. Three motivation dimensions emerged from the data: (1) ‘helping others’, (2) ‘pride and satisfaction’ and (3) ‘external recognition and support’. We found strong evidence that motivation across these factors improved in both QI and comparison areas, with weak evidence of greater increases in comparison areas. Qualitative data suggested the QI programme may have improved motivation by allowing staff to provide better care. This study suggests that although QI programmes can increase health worker knowledge, there may be little effect on motivation. Programme evaluations should measure a wide range of outcomes to fully understand their impact.
International stem cell tourism: a critical literature review and evidence-based recommendations
Authors: Lyons Samantha , Salgaonkar Shival , Flaherty Gerard T
Published: July 2021

Stem cell tourism is an emerging area of medical tourism activity. Frustrated by the slow translation of stem cell research into clinical practice, patients with debilitating conditions often seek therapeutic options that are not appropriately regulated. This review summarises recent developments in the field of stem cell tourism and provides clinicians with the information necessary to provide basic pretravel health advice to stem cell tourists. PubMed and Scopus databases were consulted for relevant publications, using combinations of the terms ‘stem cell’, ‘tourism’, ‘regenerative medicine’, ‘international’, ‘travel medicine’ and ‘environmental health’. The leading countries in the international stem cell tourism market are the USA, China, India, Thailand and Mexico. As the majority of clinics offering stem cell therapies are based in low- and-middle-income countries, stem cell tourists place themselves at risk of receiving an unproven treatment, coupled with the risk of travel-related illnesses. These clinics do not generally provide even basic travel health information on their websites. In addition to often being ineffective, stem cell therapies are associated with complications such as infection, rejection and tumorigenesis. Physicians, researchers, regulatory bodies, advocacy groups and medical educators are encouraged to work together to improve patient and physician education and address current legislative deficiencies.
A clinical andin vitroassessment of outpatient parenteral benzylpenicillin and ceftriaxone combination therapy for enterococcal endovascular infections
Authors: Ingram Paul R , Ng Jacinta , Mathieson Claire , Mowlaboccus Shakeel , Coombs Geoffrey , Raby Edward , Dyer John
Published: July 2021

Background

Amoxicillin plus ceftriaxone combination therapy is now standard of care for enterococcal endocarditis. Due to amoxicillin instability in infusion devices, benzylpenicillin plus ceftriaxone may be substituted to facilitate outpatient parenteral antimicrobial therapy (OPAT) delivery, despite lack of guideline endorsement.

Objectives

To assess the clinical efficacy of benzylpenicillin plus ceftriaxone for the management of enterococcal endovascular infections, in addition to assessing this combination’s in vitro synergy.

Patients and methods

Retrospective cohort study assessing unplanned readmissions, relapses and mortality for 20 patients with endovascular Enterococcus faecalis infections treated with benzylpenicillin plus ceftriaxone delivered via OPAT. For a subset of isolates, synergism for both amoxicillin and benzylpenicillin in combination with ceftriaxone was calculated using a chequerboard method.

Results

Patients had endovascular infections of native cardiac valves (n = 11), mechanical or bioprosthetic cardiac valves (n = 7), pacemaker leads (n = 1) or left ventricular assistant devices (n = 1). The median duration of OPAT was 22 days, and the most frequent antimicrobial regimen was benzylpenicillin 14 g/day via continuous infusion and ceftriaxone 4 g once daily via short infusion. Rates of unplanned readmissions were high (30%), although rates of relapsed bacteraemia (5%) and 1 year mortality (15%) were comparable to the published literature. Benzylpenicillin less frequently displayed a synergistic interaction with ceftriaxone when compared with amoxicillin (3 versus 4 out of 6 isolates).

Conclusions

Lower rates of synergistic antimicrobial interaction and a significant proportion of unplanned readmissions suggest clinicians should exercise caution when treating enterococcal endovascular infection utilizing a combination of benzylpenicillin and ceftriaxone via OPAT.
Development and Validation of a Quantitative UHPLC–MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning
Authors: Windahl Ulrika , Lundgren Sandra , Sprycha Margareta , Tegner Cecilia , Dreimanis Kristoffer , Tevell Åberg Annica
Published: July 2021

Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative ultra high performance liquid chromatography--tandem mass spectrometry (UHPLC--MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538–17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats.
Major Burn Injury Successfully Treated With Cultured Epithelial Autografts, a Case Series Presentation: Establishing Standard Clinical Practices
Authors: McGovern Kevin P , Rizzo Julie A
Published: July 2021

Cultured epithelial autografts have been an option for coverage of large surface area burns for over two decades. However, there remains extreme variability in clinical practice in wound bed preparation, application of cultured epithelial autografts, and postoperative wound care and rehabilitation practices, demonstrating the need for a standardized and multidisciplinary approach in the treatment of critically injured patients treated with cultured epithelial autografts. The purpose of this case series was to share the development of a clinical practice guideline and competency checklist in our institution where cultured epithelial autograft case volume is low. In this case series, we examined the medical records of three patients treated with cultured epithelial autografts at a single burn center over a period from 2015 to 2018. Operating room times and fluid resuscitation volumes were examined on days when cultured epithelial autograft grafting was performed. In order to facilitate meticulous postoperative wound care in a facility where only one to two cultured epithelial autograft applications are performed per year, a clinical practice guideline and competency checklist were generated and trialed on a series of nurses and rehabilitation therapists for the three applications of cultured epithelial autografts. Among the patients treated with cultured epithelial autografts, the average TBSA burned was 71.6%. Less intraoperative crystalloid administration and faster operative case times were associated with improved cultured epithelial autograft success. The inclusion of the clinical practice guideline and checklist into our practice led to reported improved confidence in patient care, along with the successful outcomes of these cultured epithelial autograft applications.