bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of potential drug interactions with sodium zirconium cyclosilicate: a single-center, open-label, one sequence crossover study in healthy adults
Authors: Någård Mats , Kramer William G , Boulton David W
Published: October 2020

Background

Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is an oral potassium binder for the treatment of hyperkalemia in adults. SZC acts in the gastrointestinal tract and additionally binds hydrogen ions in acidic environments like the stomach, potentially transiently increasing gastric pH and leading to drug interactions with pH-sensitive drugs. This study assessed potential pharmacokinetic (PK) interactions between SZC and nine pH-sensitive drugs.

Methods

In this single-dose, open-label, single-sequence cross-over study in healthy adults, amlodipine, atorvastatin, clopidogrel, dabigatran, furosemide, glipizide, levothyroxine, losartan or warfarin were each administered alone and, following a washout interval, with SZC 10 g. Maximum plasma concentration (Cmax), area under the plasma concentration–time curve from 0 to the last time point (AUC0–t) and AUC extrapolated to infinity (AUCinf) were evaluated. No interaction was concluded if the 90% confidence interval for the geometric mean ratio (SZC coadministration versus alone) of the PK parameters was within 80–125%.

Results

During SZC coadministration, all PK parameters for amlodipine, glipizide, levothyroxine and losartan showed no interaction, while reductions in clopidogrel and dabigatran Cmax, AUC0–t and AUCinf (basic drugs) were <50% and increases in atorvastatin, furosemide and warfarin Cmax (acidic drugs) exceeded the no-interaction range by ˂2-fold.

Conclusions

SZC coadministration was associated with small changes in plasma concentration and exposure of five of the nine drugs evaluated in this study. These PK drug interactions are consistent with transient increases in gastric pH with SZC and are unlikely to be clinically meaningful.
Health care for undocumented immigrants during the early phase of the Covid-19 pandemic in Lombardy, Italy
Authors: Devillanova Carlo , Colombo Cinzia , Garofolo Primo , Spada Anna
Published: October 2020

Despite concern on the impact of coronavirus disease 2019 (COVID-19) pandemic on undocumented immigrants, quantitative evidence on the issue is scant. We analyze socioeconomic and health conditions of 1590 undocumented immigrants in Milan, Lombardy, one of the regions with the highest COVID-19 clinical burden in the world that does not guarantee access to primary care for these individuals. We document a sharp reduction in visit number after lockdown, with 16% frequency of acute respiratory infections, compatible with COVID-19. Moreover, housing conditions make it difficult to implement public health measures. Results suggest the need to foster primary care by undocumented immigrants to face COVID-19 emergency.
Beyond the truce: how conflict affects teams’ decisions whether to enact routines or creative projects
Authors: Oehler Patrick J , Stumpf-Wollersheim Jutta , Welpe Isabell M , Obstfeld David
Published: October 2020

This study explores the causal relationship between conflict and actions taken by teams to accomplish their tasks. We differentiated between two forms of action trajectories, routines, and creative projects and used a laboratory experiment with a 2 (task conflict: yes vs. no) × 2 (interpersonal conflict: yes vs. no) factorial design to test how task and interpersonal conflicts affect teams’ decisions to enact routines or less routine creative projects. Teams subjected to task, interpersonal, or a combination of task and interpersonal conflict solved recurring challenges in the computer game Minecraft. We find that both task and interpersonal conflict independently increase teams’ tendency to pursue change by enacting creative projects. We conclude that task and interpersonal conflict lead teams to avoid developing routines and to attempt creative projects.
Fundamental resource trade-offs for encoded distributed optimization
Authors: Avestimehr A Salman , Mohammadreza Mousavi Kalan Seyed , Soltanolkotabi Mahdi
Published: October 2020

Dealing with the shear size and complexity of today’s massive data sets requires computational platforms that can analyze data in a parallelized and distributed fashion. A major bottleneck that arises in such modern distributed computing environments is that some of the worker nodes may run slow. These nodes a.k.a. stragglers can significantly slow down computation as the slowest node may dictate the overall computational time. A recent computational framework, called encoded optimization, creates redundancy in the data to mitigate the effect of stragglers. In this paper, we develop novel mathematical understanding for this framework demonstrating its effectiveness in much broader settings than was previously understood. We also analyze the convergence behavior of iterative encoded optimization algorithms, allowing us to characterize fundamental trade-offs between convergence rate, size of data set, accuracy, computational load (or data redundancy) and straggler toleration in this framework.
Impact of Immune Priming, Vaccination, and Infection on Influenza A(H3N2) Antibody Landscapes in Children
Authors: Hinojosa Michael , Shepard Samuel S , Chung Jessie R , King Jennifer P , McLean Huong Q , Flannery Brendan , Belongia Edward A , Levine Min Z
Published: October 2020

Background

Preexisting antibodies to influenza, shaped by early infection and subsequent exposures, may impact responses to influenza vaccination.

Methods

We enrolled 72 children (aged 7–17 years) in 2015–2016; all received inactivated influenza vaccines. Forty-one were also vaccinated in 2014–2015, with 12 becoming infected with A(H3N2) in 2014–2015. Thirty-one children did not have documented influenza exposures in the prior 5 seasons. Sera were collected pre- and postvaccination in both seasons. We constructed antibody landscapes using hemagglutination inhibition antibody titers against 16 A(H3N2) viruses representative of major antigenic clusters that circulated between 1968 and 2015.

Results

The breadth of the antibody landscapes increased with age. Vaccine-induced antibody responses correlated with boosting of titers to previously encountered antigens. Postvaccination titers were the highest against vaccine antigens rather than the historic A(H3N2) viruses previously encountered. Prevaccination titers to the vaccine were the strongest predictors of postvaccination titers. Responses to vaccine antigens did not differ by likely priming virus. Influenza A(H3N2)-infected children in 2014–2015 had narrower antibody landscapes than those uninfected, but prior season infection status had little effect on antibody landscapes following 2015–2016 vaccination.

Conclusions

A(H3N2) antibody landscapes in children were largely determined by age-related immune priming, rather than recent vaccination or infection.
A low-density SNP genotyping panel for the accurate prediction of cattle breeds
Authors: Reverter Antonio , Hudson Nicholas J , McWilliam Sean , Alexandre Pamela A , Li Yutao , Barlow Robert , Welti Nina , Daetwyler Hans , Porto-Neto Laercio R , Dominik Sonja
Published: October 2020

Genomic tools to better define breed composition in agriculturally important species have sparked scientific and commercial industry interest. Knowledge of breed composition can inform multiple scientifically important decisions of industry application including DNA marker-assisted selection, identification of signatures of selection, and inference of product provenance to improve supply chain integrity. Genomic tools are expensive but can be economized by deploying a relatively small number of highly informative single-nucleotide polymorphisms (SNP) scattered evenly across the genome. Using resources from the 1000 Bull Genomes Project we established calibration (more stringent quality criteria; N = 1,243 cattle) and validation (less stringent; N = 864) data sets representing 17 breeds derived from both taurine and indicine bovine subspecies. Fifteen successively smaller panels (from 500,000 to 50 SNP) were built from those SNP in the calibration data that increasingly satisfied 2 criteria, high differential allele frequencies across the breeds as measured by average Euclidean distance (AED) and high uniformity (even spacing) across the physical genome. Those SNP awarded the highest AED were in or near genes previously identified as important signatures of selection in cattle such as LCORL, NCAPG, KITLG, and PLAG1. For each panel, the genomic breed composition (GBC) of each animal in the validation dataset was estimated using a linear regression model. A systematic exploration of the predictive accuracy of the various sized panels was then undertaken on the validation population using 3 benchmarking approaches: (1) % error (expressed relative to the estimated GBC made from over 1 million SNP), (2) % breed misassignment (expressed relative to each individual’s breed recorded), and (3) Shannon’s entropy of estimated GBC across the 17 target breeds. Our analyses suggest that a panel of just 250 SNP represents an adequate balance between accuracy and cost—only modest gains in accuracy are made as one increases panel density beyond this point.
A unique presentation of perforated duodenal ulcer in a postpartum woman: a case report
Authors: Jain Ashali , Azzolini Anthony , Kipnis Seth
Published: October 2020

Gallbladder disease and peptic ulcer disease (PUD) can present very similarly, and misdiagnosis can often result because of conflicting symptoms. PUD in pregnancy is relatively rare, in part due to the changes in estrogen and progesterone levels. We present a case of a postpartum female, post operation Day 5, with signs/symptoms, physical exam and laboratory work consistent with acute cholecystitis that was found to have a perforated duodenal ulcer intraoperatively. The authors suggest that a fistula would have resulted with ongoing disease. Bilio-enteric fistulas can often form due to ongoing cholelithiasis disease. Cholecystoduodenal fistulas (CDFs) are the most common fistulas to present. It is possible that the incidence of CDF formation secondary to perforated duodenal ulcers is underestimated due to signs and symptoms not presenting until gallstone ileus is diagnosed.
A seismic shift in US travel health nursing: the achievement of specialty recognition and its implications
Authors: Richards Julie A , Rosselot Gail A
Published: October 2020

Identifying an important need, The American Travel Health Nurses Association (ATHNA), working on behalf of U.S. nurses, set out to develop a scope of practice and performance standards for travel health nursing1. Based on these efforts, the American Nurses Association (ANA) voted to recognize travel health nursing as a distinct specialty. We discuss the process that led to this achievement and its implications for travel health providers and practice.
On the significance of relativistically hot pairs in the jets of FR II radio galaxies
Authors: Sikora Marek , Nalewajko Krzysztof , Madejski Greg M
Published: October 2020

The energetic composition of radio lobes in the FR II galaxies – estimated by comparing their radio luminosities with the powers required to inflate cavities in the external medium – seems to exclude the possibility of their energetic domination by protons. Furthermore, if the jets were dominated by the kinetic energy of cold protons, it would be difficult to efficiently accelerate leptons in the jets’ terminal shocks. Assuming that the relative energy contents of leptons, protons, and magnetic fields are preserved across the shocks, the above implies that the large-scale jets should also be energetically dominated by leptons: Pe,j ≳ Pp,j. On the other hand, previous studies of small-scale jets in blazars and radio cores suggest a pair content (number of electrons and positrons per proton) of the order of ne/np ∼ 20. Assuming further that the particle composition of jets does not evolve beyond the blazar scales, we show that this implies an average random Lorentz factor of leptons in large-scale jets of $\bar{\gamma }_{\rm e,j} \gtrsim 70(1+\chi _{\rm p})(20n_{\rm p}/n_{\rm e})$, and that the protons should be mildly relativistic with χp ≡ (ϵp + pp)/ρpc2 ≲ 2, pp the pressure of protons, ϵp the internal energy density of protons, and ρpc2 the rest-mass energy density of protons. We derive the necessary conditions for loading the inner jets by electron–positron pairs and proton–electron plasma, and provide arguments that heating of leptons in jets is dominated by magnetic reconnection.
Soft gamma-ray selected giant radio galaxies: an update
Authors: Bassani L , Ursini F , Malizia A , Bruni G , Panessa F , Masetti N , Saviane I , Monaco L , Venturi T , Dallacasa D , Bazzano A , Ubertini P
Published: October 2020

We present an update on the sample of soft gamma-ray selected giant radio galaxies (GRGs) extracted from INTEGRAL/IBIS and Swift/BAT surveys; it includes eight new sources and one candidate object. In the new sample, all but one source display FR II radio morphologies; the only exception is B21144+35B, which is an FR I. The objects belong to both type 1 and type 2 active galactic nucleus (AGN) optical classes and have redshifts in the range 0.06–0.35, while the radio sizes span from 0.7 to 1 Mpc. In this study, we present for the first time two objects that were never discussed as GRGs before and propose a new candidate GRG. We confirm the correlation between the X-ray luminosity and the radio core luminosity found for other soft gamma-ray selected GRGs and expected for AGNs powered by efficient accretion. We also corroborate previous results that indicate that the luminosity of the radio lobes is relatively low compared with the nuclear X-ray emission. This supports the idea that the nucleus of these GRGs is now more powerful than in the past, consistent with a restarting activity scenario.
INDEL detection, the ‘Achilles heel’ of precise genome editing: a survey of methods for accurate profiling of gene editing induced indels
Authors: Bennett Eric Paul , Petersen Bent Larsen , Johansen Ida Elisabeth , Niu Yiyuan , Yang Zhang , Chamberlain Christopher Aled , Met Özcan , Wandall Hans H , Frödin Morten
Published: October 2020

Advances in genome editing technologies have enabled manipulation of genomes at the single base level. These technologies are based on programmable nucleases (PNs) that include meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) nucleases and have given researchers the ability to delete, insert or replace genomic DNA in cells, tissues and whole organisms. The great flexibility in re-designing the genomic target specificity of PNs has vastly expanded the scope of gene editing applications in life science, and shows great promise for development of the next generation gene therapies. PN technologies share the principle of inducing a DNA double-strand break (DSB) at a user-specified site in the genome, followed by cellular repair of the induced DSB. PN-elicited DSBs are mainly repaired by the non-homologous end joining (NHEJ) and the microhomology-mediated end joining (MMEJ) pathways, which can elicit a variety of small insertion or deletion (indel) mutations. If indels are elicited in a protein coding sequence and shift the reading frame, targeted gene knock out (KO) can readily be achieved using either of the available PNs. Despite the ease by which gene inactivation in principle can be achieved, in practice, successful KO is not only determined by the efficiency of NHEJ and MMEJ repair; it also depends on the design and properties of the PN utilized, delivery format chosen, the preferred indel repair outcomes at the targeted site, the chromatin state of the target site and the relative activities of the repair pathways in the edited cells. These variables preclude accurate prediction of the nature and frequency of PN induced indels. A key step of any gene KO experiment therefore becomes the detection, characterization and quantification of the indel(s) induced at the targeted genomic site in cells, tissues or whole organisms. In this survey, we briefly review naturally occurring indels and their detection. Next, we review the methods that have been developed for detection of PN-induced indels. We briefly outline the experimental steps and describe the pros and cons of the various methods to help users decide a suitable method for their editing application. We highlight recent advances that enable accurate and sensitive quantification of indel events in cells regardless of their genome complexity, turning a complex pool of different indel events into informative indel profiles. Finally, we review what has been learned about PN-elicited indel formation through the use of the new methods and how this insight is helping to further advance the genome editing field.
Association of lactate dehydrogenase with mortality in incident hemodialysis patients
Authors: Ryu Soh Young , Kleine Carola-Ellen , Hsiung Jui-Ting , Park Christina , Rhee Connie M , Moradi Hamid , Hanna Ramy , Kalantar-Zadeh Kamyar , Streja Elani
Published: October 2020

Background

Lactate dehydrogenase (LDH) plays a role in the glucose metabolism of the human body. Higher LDH levels have been linked to mortality in various cancer types; however, the relationship between LDH and survival in incident hemodialysis (HD) patients has not yet been examined. We hypothesized that higher LDH level is associated with higher death risk in these patients.

Methods

We examined the association of baseline and time-varying serum LDH with all-cause, cardiovascular and infection-related mortality among 109 632 adult incident HD patients receiving care from a large dialysis organization in the USA during January 2007 to December 2011. Baseline and time-varying survival models were adjusted for demographic variables and available clinical and laboratory surrogates of malnutrition–inflammation complex syndrome.

Results

There was a linear association between baseline serum LDH levels and all-cause, cardiovascular and infection-related mortality in both baseline and time-varying models, except for time-varying infection-related mortality. Adjustment for markers of inflammation and malnutrition attenuated the association in all models. In fully adjusted models, baseline LDH levels ≥360 U/L were associated with the highest risk of all-cause mortality (hazard ratios = 1.19, 95% confidence interval 1.14–1.25). In time-varying models, LDH >280 U/L was associated with higher death risk in all three hierarchical models for all-cause and cardiovascular mortality.

Conclusions

Higher LDH level >280 U/L was incrementally associated with higher all-cause and cardiovascular mortality in incident dialysis patients, whereas LDH <240 U/L was associated with better survival. These findings suggest that the assessment of metabolic functions and monitoring for comorbidities may confer survival benefit to dialysis patients.
Heart failure in chronic kidney disease: the emerging role of myocardial fibrosis
Authors: Romero-González Gregorio , González Arantxa , López Begoña , Ravassa Susana , Díez Javier
Published: October 2020

Heart failure (HF) is one of the main causes of morbidity and mortality in patients with chronic kidney disease (CKD). Decreased glomerular filtration rate is associated with diffuse deposition of fibrotic tissue in the myocardial interstitium [i.e. myocardial interstitial fibrosis (MIF)] and loss of cardiac function. MIF results from cardiac fibroblast-mediated alterations in the turnover of fibrillary collagen that lead to the excessive synthesis and deposition of collagen fibres. The accumulation of stiff fibrotic tissue alters the mechanical properties of the myocardium, thus contributing to the development of HF. Accumulating evidence suggests that several mechanisms are operative along the different stages of CKD that may converge to alter fibroblasts and collagen turnover in the heart. Therefore, focusing on MIF might enable the identification of fibrosis-related biomarkers and targets that could potentially lead to a new strategy for the prevention and treatment of HF in patients with CKD. This article summarizes current knowledge on the mechanisms and detrimental consequences of MIF in CKD and discusses the validity and usefulness of available biomarkers to recognize the clinical–pathological variability of MIF and track its clinical evolution in CKD patients. Finally, the currently available and potential future therapeutic strategies aimed at personalizing prevention and reversal of MIF in CKD patients, especially those with HF, will be also discussed.
Can the assessment of ultrasound lung water in haemodialysis patients be simplified?
Authors: Torino Claudia , Tripepi Rocco , Loutradis Charalampos , Sarafidis Pantelis , Tripepi Giovanni , Mallamaci Francesca , Zoccali Carmine
Published: October 2020

Background

Lung ultrasound (US) reliably estimates lung water and it is increasingly applied in clinical practice in dialysis patients. A semi-quantitative US score summing up the US-B lines (an equivalent of B lines in the standard chest X-ray) at 28 sites in the intercostal spaces (Jambrik et al. Usefulness of ultrasound lung comets as a non-radiologic sign of extravascular lung water. Am J Cardiol 2004; 93: 1265–1270) is the most used score.

Methods

We compared the prognostic performance for death, and cardiovascular (CV) events of the 28-sites US score with a score restricted to eight sites in a cohort of 303 haemodialysis (HD) patients.

Results

The 8- and the 28-sites scores were highly inter-related (Spearman’s ρ = 0.93, P < 0.001), and their concordance index was fairly good (k = 0.79, 95% confidence interval 0.74–0.84). During a mean follow-up of 3 years, 112 patients died, and 129 experienced a CV event. At univariate and multivariate analysis, both scores were associated with mortality (P ≤ 0.01) and CV events (P ≤ 0.05). The explained variances (R2) for death and CV events of the 28-sites score in multivariate models including major risk factors for these outcomes in the end-stage kidney disease (ESKD) population were 3.9 and 2.2%, and those of the 8-sites score were 3.1 and 2.4%, respectively. The median time needed to perform the examination was 3.05 min [interquartile range (IQR) 2.22–5.00 min] for the 28-sites score and 1.35 min (IQR 1.16–2.00 min) for the 8-sites score.

Conclusion

The 8-sites score is tightly related to the classical Jambrik 28-sites score and this score holds an almost identical predictive power to the reference score. Even though the 28-sites score can be completed just in ∼3 min, the 8-sites score requires only ∼1.30 min, and it is, therefore, better suited for application in everyday clinical practice in HD units.
Combination MEK and mTOR inhibitor therapy is active in models of glioblastoma
Authors: Schreck Karisa C , Allen Amy N , Wang Jiawan , Pratilas Christine A
Published: October 2020

Background

RAS effector signaling pathways such as PI3K/mTOR and ERK are frequently dysregulated in glioblastoma. While small molecule targeted therapies against these pathways have appeared promising in preclinical studies, they have been disappointing in clinical trials due to toxicity and de novo and adaptive resistance. To identify predictors of glioblastoma sensitivity to dual pathway inhibition with mTORC1/2 and MEK inhibitors, we tested these agents, alone and in combination, in a cohort of genomically characterized glioblastoma cell lines.

Methods

Seven genomically characterized, patient-derived glioblastoma neurosphere cell lines were evaluated for their sensitivity to the dual mTORC1/2 kinase inhibitor sapanisertib (MLN0128, TAK-228) alone or in combination with the MEK1/2 inhibitor trametinib (GSK1120212), using assessment of proliferation and evaluation of the downstream signaling consequences of these inhibitors.

Results

Sapanisertib inhibited cell growth in neurosphere lines, but induced apoptosis only in a subset of lines, and did not completely inhibit downstream mTOR signaling via ribosomal protein S6 (RPS6). Growth sensitivity to MEK inhibitor monotherapy was observed in a subset of lines defined by loss of NF1, was predicted by an ERK-dependent expression signature, and was associated with effective phospho-RPS6 inhibition. In these lines, combined MEK/mTOR treatment further inhibited growth and induced apoptosis. Combined MEK and mTOR inhibition also led to modest antiproliferative effects in lines with intact NF1 and insensitivity to MEK inhibitor monotherapy.

Conclusions

These data demonstrate that combined MEK/mTOR inhibition is synergistic in glioblastoma cell lines and may be more potent in NF1-deficient glioblastoma.
A House but Not a Home: How Surveillance in Subsidized Housing Exacerbates Poverty and Reinforces Marginalization
Authors: Hughes Cayce C
Published: October 2020

A robust literature has shown that surveillance disproportionately targets poor people of color through the criminal justice and welfare systems. However, little empirical research traces the mechanisms through which surveillance reproduces inequality in other domains, such as subsidized housing, where private actors including property owners and landlords do the work of surveilling tenants. In this article, I apply the theoretical lens of surveillance to the case of subsidized housing to explore the symbolic and material consequences of being monitored at home. Drawing on in-depth interviews with 67 low-income Black mothers in the Sunnyside neighborhood in Houston, Texas, I argue that the scrutiny mothers face in and around their homes reproduces inequality through two key mechanisms. First, surveillance creates a home environment devoid of privacy, that mothers liken to being in prison. Mothers interpret this scrutiny as an effort to control and contain them because of their race, reinforcing racialized notions of presumptive Black criminality. Second, surveillance heightens the material risk for mothers of being caught breaking rules, which paves the way for eventual eviction and exacerbates poverty. Although mothers develop strategies to counter and at times resist disciplinary monitoring, these efforts come with drawbacks that can make surviving poverty harder. Taken together, these findings suggest that being surveilled at home not only diminishes low-income Black mothers’ status in society, but also pushes them into deeper economic precarity. This research extends our understanding of the reach of surveillance into the lives of the poor even in spaces considered to be private.
Beneficial effects of polyherbal formulation (Bronco-T) on formaldehyde-induced lung toxicity in male Wistar rats
Authors: Sholapuri Payani , Chintha Venkataramaiah , Matcha Bhaskar , Pradeepkiran JangampalliAdi
Published: October 2020

Abstarct

Polyherbal compound (Bronco-T) has been extensively used as a traditional medicine for various therapies. However, very few report studies on anti-inflammatory and lung regeneration properties are evidenced. In the present study, we evaluated the beneficial actions and anti-inflammatory properties of polyherbal medicine, Bronco-T, exhibited by treating the lungs of rats exposed to formaldehyde to evaluate the beneficial properties. For this study, we divided into five groups’: i.e. Group-I served as a control and the other four groups such as II, III, IV, and V are experimental. All animals maintained by regular feed and water ad libitum during the study. Formaldehyde vapors exposure at a single period of time (1 hour) daily (40%formaldehyde at room temperature) for 21 days period exposed all groups. The Bronco-T extracts about 50 mg/kg BW administered to experimental groups and group IV rats treated with 500μ grams/Kg BW salbutamol. To understand the impact of formaldehyde exposure on the beneficial effects of Bronco-T, we evaluated hematological parameters, bronchoalveolar lavage (BAL), histamine levels, and histological alterations of lung architecture. Formaldehyde-induced adverse effects in lung and increased histamine levels in BAL compared to Bronco-T-treated rats act as a preventive immunological role in blood toxicity and recovery of lung architecture in Bronco-T-treated rats. This study showed the evaluation of antihistamine levels through HPLC analysis. Bronco-T has antioxidant and anti-histamine properties as the widest therapeutic window, and we continue to evaluate the pharmacological evaluations needed in our further studies.
Essential role of Zp54, the human RCK/p54 (DDX6) homologue, in zebrafish neuronal development
Authors: Yeh Chih-Chun , Lee Shyh-Jye , Chu Chia-Ying
Published: October 2020

RCK/p54 (DDX6), a RNA helicase of DEAD box family, plays multiplex roles in RNA metabolism. Previous studies of RCK/p54 homologues in yeast, C. elegans, Drosophila and Xenopus showed that RCK/p54 functions as a translational repressor and modulates RNA stability. RCK/p54 also interacts with Ago2 in the miRNA‐induced silencing complex (miRISC), represses mRNA translation and facilitates the formation of P‐body in human cells. However, the role of RCK/p54 in animal development remains unclear. Here we examine the function of human RCK/p54 homologue, Zp54, in zebrafish embryogenesis. We monitored the mRNA and protein levels of Zp54 in zebrafish embryos. Our results showed that zp54 is highly expressed at early stages and the level is dramatically deceased from one‐cell stage to 72hpf. Knockdown of zp54 by injecting zp54 morpholinos results in a severe delay of embryogenesis, and specifically affect on the neuronal development at later stages. Our data also indicates that Zp54 is functional redundant with human RCK/p54 suggesting that Zp54 is structural and functional conserved in vertebrates and might play important roles during Zebrafish development.
Improving Shoulder Dystocia Outcomes With Teamwork and Deliberate Practice [26S]
Authors: Seif Karl E. , Nies Barbara , Dada Adedayo , Donlan Amy , Marko Emily
Published: October 2020

INTRODUCTION:

The management of shoulder dystocia requires coordinated time-sensitive teamwork. A complication of performing the posterior arm delivery is neonatal humerus fracture. The study objective was to determine the effectiveness of teaching shoulder dystocia management using simulation aimed at teamwork and communication, with a focus on deliberate practice of posterior arm delivery skills.

METHODS:

A prospective pre/post educational study design was used to assess effectiveness of a curriculum designed for labor and delivery personnel using simulation for the coordinated team management of shoulder dystocia. A portable task trainer was used to practice safe delivery of the posterior arm including inserting the provider hand on the side of the fetal chest and splinting of the humerus. Outcomes were measured using performance assessment scores, safety culture surveys and the rate of neonatal humerus fractures in shoulder dystocias over one year. Internal review board exemption was obtained. Paired t-tests and repeated measures were used for data analysis.

RESULTS:

Teamwork drills were held with 166 multi-disciplinary participants in a large obstetrical hospital over one year. Statistically significant improvement occurred in knowledge (pre 64.01%, post 94.22%, p<0.0001), performance (pre 61.83%, post 92.86%, p<0.0001) and safety culture surveys (pre 3.27, post 1.57, p<0.0001, 1=high, 5=low). Compared with the year prior to the study, the rate of neonatal humerus fractures in shoulder dystocias was reduced by 42.86%, (pre 5.51%, post 3.88%, p<0.0001).

CONCLUSION:

Simulation training improved teamwork performance during shoulder dystocia emergencies. Deliberate practice of posterior arm delivery skills significantly reduced the rate of neonatal humerus fractures.
A Quality Improvement Project Comparing Two Treatments for Deep-Tissue Pressure Injuries to Feet and Lower Legs of Long-term Care Residents
Authors: Henson Autumn , Kennedy-Malone Laurie
Published: October 2020

OBJECTIVE

To retrospectively examine clinical outcomes from a feasibility study that compared two treatment options for deep-tissue pressure injuries (DTPIs), including the clinical indicators increasing the risk of deteriorating DTPIs among long-term care residents.

METHODS

A retrospective chart audit of 40 DTPIs from 33 long-term care residents in two long-term care facilities was conducted to compare (1) polymeric membrane dressings (PMDs) with offloading and (2) a skin barrier film with offloading.

RESULTS

Of the 13 DTPIs treated with PMDs, only 23% deteriorated to a stage 3 or 4 pressure injury (PI), whereas of the 27 DTPIs treated with skin barrier film, 41% deteriorated to a stage 3 or 4 PI. The clinical factors found to increase the risk of developing and deteriorating DTPIs included weight loss, hypoalbuminemia, debility, dementia, coronary artery disease, and cerebrovascular disease.

CONCLUSIONS

The PMD group’s DTPIs evolved into fewer open PIs despite having higher percentages of clinical indicators for DTPIs. The project findings support the use of PMD dressings for DTPIs; however, more robust research is warranted.
Informed Application of the Standards on Support Surface Performance for Clinically Meaningful Use
Authors: Sylvia Cynthia , Gruccio Paula , Jordan Rosalyn , Morello Susan Smith , Thurman Kristen
Published: October 2020

BACKGROUND

The Support Surface Standards Initiative (S3I) has evolved with the goal of standardizing language and performance evaluation of support surfaces. There is a consumer need for education about support surface standards to transfer new information with clinical relevance.

OBJECTIVE

To develop a framework for meaningful dialogue through consensus building that drives value-based purchasing, propose a clinically relevant path for understanding how to apply data from the standards into critical interprofessional analysis and support surface selection, and navigate the first tier of a process targeted as an educational initiative within the Standards Committee.

METHODS

The authors purposively sampled the S3I Tissue Integrity Group with a semi-structured qualitative survey to identify the essential components of support surfaces standard performance testing. A two-phase interview and review process was implemented within the larger S3I group to achieve consensus on content for knowledge transfer, with a threshold of 80% agreement within the Standards Committee.

RESULTS

Meaningful consensus was achieved on content associated with knowledge transfer of standards data. These standards will function as reliable benchmarks, enabling consumers to compare individual characteristics of one support surface to another. Product comparison will be based on the single characteristics of support surfaces and how those characteristics are relevant to the specific needs of the individual patient or patient populations, transferred in language that is meaningful to end users of the standards.

CONCLUSIONS

The consensus process facilitated construction of a clinically relevant, interprofessional framework for the product selection process within the Standards Committee. It will enable the next tier of educational dissemination beyond the Standards Committee to a broader base of consumers to engage in value-based purchasing with enhanced understanding of support surface performance characteristics.
Microecology research: a new target for the prevention of asthma
Authors: Shi Hong-Lei , Lan Yu-Hao , Hu Zheng-Chuan , Yan Zi-Ning , Liu Ze-Zhong , Kadier Xiriaili , Ma Li , Yu Jin-Yan , Liu Jing
Published: October 2020

The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of “when and how” to regulate microbiome is still needed.
Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis
Authors: Cai Lin , Zhang Jian-Zhong , Yao Xu , Gu Jun , Liu Quan-Zhong , Zheng Min , Zhang Shi-Fa , Xu Jin-Hua , Li Cheng-Xin , Cheng Hao , Guo Qing , Pan Wei-Li , Li Shen-Qiu , Li Ruo-Yu , Guo Zai-Pei , Song Zhi-Qi , Li Shan-Shan , Dong Xiu-Qin , Wang Linda , Fu Rong , Regnault Pascaline , Charef Pascal , Mazur Rafal , Patekar Manmath
Published: October 2020

Background:

Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.

Methods:

This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12.

Results:

A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.

Conclusion:

Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis.

Trial Registration:

ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Non–Vitamin K Antagonist Oral Anticoagulants and Factors Influencing the Ischemic and Bleeding Risk in Elderly Patients With Atrial Fibrillation: A Review of Current Evidence
Authors: Patti Giuseppe , Haas Sylvia
Published: October 2020

Non–vitamin K antagonist oral anticoagulants (NOACs) are a widely prescribed treatment to prevent stroke in patients with nonvalvular atrial fibrillation, and a therapy and preventative measure to prevent recurrences following venous thromboembolism. Optimal use of NOACs requires a thorough knowledge of the pharmacology of these drugs, as well as an understanding of patient factors affecting their use. The 4 NOACs—dabigatran, apixaban, edoxaban, and rivaroxaban are available in a range of doses suitable for differing indications and with a variety of dose reduction criteria. Identification of the correct dose is one of the key challenges in the individualization of treatment. Elderly patients with atrial fibrillation are at a greater risk of both ischemic and bleeding events than younger patients. Consequently, it is essential to achieve balance in anticoagulation strategies. Medication adherence to NOACs is important for safe and effective treatment, particularly in elderly populations. A growing body of evidence shows that once-daily dosing improves adherence and persistence to therapy, without having an impact on bleeding risk.
Plasma Concentrations and Cardiovascular Effects of Citalopram Enantiomers After Oral Versus Infusion Citalopram Therapy in Dextromethorphan-Mephenytoin-Phenotyped Patients With Major Depression
Authors: Baumann Pierre , Bertschy Gilles , Ramseier Fritz , Nil Rico
Published: October 2020

Background:

Authors compared plasma concentrations of citalopram (CIT) enantiomers and their metabolites in patients with depression administered either intravenously (IV) or as oral racemic CIT. Then, plasma concentrations were related to the metabolism of probes used for phenotyping patients with depression for CYP2C19 and CYP2D6 activity and cardiovascular functions.

Methods:

Dextromethorphan–mephenytoin-phenotyped patients with depression were administered racemic CIT (days 1 and 2: 20 mg/d; days 3–10: 40 mg/d) either orally or as a slow-drop infusion for 10 days and were then orally administered the drug for another 32 days. Blood probes were collected at the time of minimal and maximal concentrations on day 10, immediately before and 2 hours after drug administration, and on days 21 and 42. Plasma CIT and its metabolites were assayed by stereoselective high-performance liquid chromatography.

Results:

The following concentrations (ng/mL) were noted in the group receiving active IV infusion (IV-POS group, n = 27) of racemic CIT on day 10, before drug administration: escitalopram (S-CIT): 24 ± 10.2; R-citalopram (R-CIT): 45 ± 14.5; S-desmethyl-CIT: 13 ± 4.4; and R-desmethyl-CIT: 17 ± 8.2. In patients receiving oral administration (POS-POS group, n = 25), the values were 30 ± 12.7, 51 ± 17.4, 13 ± 4.6, and 17 ± 7.9 ng/mL, respectively. In the IV-POS group, 3 patients were poor dextromethorphan (CYP2D6) metabolizers; in the POS-POS group, one was a poor mephenytoin (CYP2C19) metabolizer. On day 10, before CIT treatment, S/R-CIT and S/R-mephenytoin ratios were significantly correlated, determined at baseline. Overall, CIT reduced the heart rate but did not significantly modify QTc. No relationship was found between any cardiovascular parameters and pharmacokinetic and pharmacogenetic data.

Conclusions:

Owing to CIT's high bioavailability, the plasma concentrations of its enantiomers remained largely independent on the administration route. CYP2C19 preferentially demethylated S-CIT after CIT therapy.
Two-year outcomes from the PARTNER 3 trial: where do we stand?
Authors: Muller Moran Hellmuth R. , Eikelboom Rachel , Lodewyks Carly , Yan Weiang , Zelentsov Ivan , Arora Rakesh C. , Yamashita Michael H.
Published: October 2020

Purpose of review

The PARTNER 3 trial was conducted to compare outcomes after transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve and surgical aortic valve replacement (SAVR) in individuals at low surgical risk with aortic stenosis. Recently reported rates of death, stoke and valve thrombosis in the TAVR arm have raised concerns about the longevity of this intervention in low-risk individuals. It is incumbent on all members of the Heart Team to understand the potential consequences of these findings.

Recent findings

TAVR was initially superior to SAVR at 1 year for a primary composite endpoint of death, stroke and rehospitalization. Results at 2 years now indicate noninferiority. Potential causative factors, comparisons with other transcatheter valves and implications for patients, providers and trainees are explored. Recommendations are additionally provided regarding TAVR and SAVR in individuals with aortic stenosis.

Concerns regarding the longevity of TAVR in low-risk individuals notwithstanding, results from PARTNER 3 indicate that TAVR is at least noninferior to SAVR out to 2 years. Longer follow-up will be required to determine whether these newly founded concerns are justifiable.
Simplified blood pressure measurement approaches and implications for hypertension screening: the Atherosclerosis Risk in Communities study
Authors: Lu Yifei , Tang Olive , Brady Tammy M. , Miller Edgar R. , Heiss Gerardo , Appel Lawrence J. , Matsushita Kunihiro
Published: October 2020

Objectives:

Averaging multiple blood pressure (BP) measurements is recommended for hypertension (HTN) screening but can be impractical, especially in resource-constrained settings. We aimed to explore the implications of fewer BP measurements on BP classification and subsequent cardiovascular disease (CVD) risk.

Methods:

We studied 8905 middle-aged participants without diagnosed HTN and quantified misclassified HTN (≥140/90 mmHg) by simplified BP approaches (e.g. single 1st BP, single 2nd BP, mainly 1st but 2nd BP if 1st was in a certain range) vs. the reference standard of the average of 2nd and 3rd BP. We also assessed CVD risk related to HTN status.

Results:

There were 823 participants classified as HTN by the standard approach. With single 1st BP, 2.8% of non-HTN were overidentified as HTN, and 18.3% of HTN were identified as not having HTN. The corresponding estimates with single 2nd BP were 2.1 and 6.4%. Similar estimates were seen when 2nd BP was used if 1st BP at least 130/80 (1.9 and 8.1%), with only 27.8% requiring 2nd BP. Two thousand, one hundred and seventy-eight CVD cases were documented in this population over 30 years. HTN by either the standard approach or any of the simplified approaches conferred higher CVD risk vs. consistent no HTN by both approaches.

Conclusion:

In those without diagnosed HTN, a simplified BP measurement approach using the 2nd BP only when the 1st BP is at least 130/80 could reduce the total number of BP measurements by more than 50%, identify HTN with limited misclassification (2–8%), and predict CVD risks reasonably well.
Associations of Intussusception With Adenovirus, Rotavirus, and Other Pathogens: A Review of the Literature
Authors: Burnett Eleanor , Parashar Umesh D. , Tate Jacqueline E.
Published: October 2020

Background:

Intussusception is the leading cause of acute intestinal obstruction in infants. Intussusception is mostly idiopathic, but infectious pathogens are sometimes implicated. In addition, live oral rotavirus vaccines have been associated with intussusception.

Methods:

We searched the literature published between January 1, 1990, and March 16, 2020, to describe the association between intussusception among infants and young children and various pathogens, particularly adenovirus and wild rotavirus. We tallied the number of evaluations reporting a statistically significant positive association, no association and a protective association by pathogen, using any statistical method. We also calculated the median reported odds ratios (OR) of intussusception with adenovirus and rotavirus.

Results:

We identified 3793 records on intussusception from the literature; 17 evaluations from 15 countries that evaluated 52 pathogens were included in the analysis. All 14 evaluations of adenovirus reported a statistically significant positive association with intussusception; the median OR from 9 evaluations was 3.7 (interquartile range, 3.3, 8.2). Nine of 12 evaluations assessing rotavirus found no statistically significant association, 1 found a positive association and 2 reported a protective effect; the median OR from 12 evaluations was 0.9 (interquartile range, 0.2, 1.8). No consistent relationship was observed between any other pathogens and intussusception.

Conclusions:

We documented a consistent association of intussusception with adenovirus, but no relationship between wild-type rotavirus and intussusception. Future research should focus on better understanding the mechanisms of intussusception with infectious pathogens, including following a rotavirus vaccination.