bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiome signatures in prostate cancer
Authors: Banerjee Sagarika , Alwine James C , Wei Zhi , Tian Tian , Shih Natalie , Sperling Colin , Guzzo Thomas , Feldman Michael D , Robertson Erle S
Published: February 2019

We have established a microbiome signature for prostate cancer using an array-based metagenomic and capture-sequencing approach. A diverse microbiome signature (viral, bacterial, fungal and parasitic) was observed in the prostate cancer samples compared with benign prostate hyperplasia controls. Hierarchical clustering analysis identified three distinct prostate cancer-specific microbiome signatures. The three signatures correlated with different grades, stages and scores of the cancer. Thus, microbiome signature analysis potentially provides clinical diagnosis and outcome predictions. The array data were validated by PCR and targeted next-generation sequencing (NGS). Specific NGS data suggested that certain viral genomic sequences were inserted into the host somatic chromosomes of the prostate cancer samples. A randomly selected group of these was validated by direct PCR and sequencing. In addition, PCR validation of Helicobacter showed that Helicobacter cagA sequences integrated within specific chromosomes of prostate tumor cells. The viral and Helicobacter integrations are predicted to affect the expression of several cellular genes associated with oncogenic processes.
Factors associated with parathyroid hormone control in haemodialysis patients with secondary hyperparathyroidism treated with cinacalcet in real-world clinical practice: Mimosa study
Authors: Rottembourg Jacques , Ureña-Torres Pablo , Toledano Daniel , Gueutin Victor , Hamani Abdelaziz , Coldefy Olivier , Hebibi Hedia , Guincestre Thomas , Emery Corinne
Published: February 2019

Background

Secondary hyperparathyroidism (SHPT) is frequent in haemodialysis (HD) patients. Oral cinacalcet-hydrochloride (HCl) decreases parathyroid hormone (PTH); however, real-life PTH data, according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, are still lacking. Our goal is to assess the percentage of cinacalcet-HCl-treated HD patients with controlled SHPT (PTH <9× upper limit of the normal range) after 12 months (M12) of treatment.

Methods

This is a retrospective observational study in HD patients with SHPT treated by cinacalcet-HCl between 2005 and 2015 and dialysed in seven French HD centres using the same database (Hemodial™).

Results

The study included 1268 patients with a mean (standard deviation) follow-up of 21 ± 12 months. Their mean dialysis vintage was 4.3 ± 5.6 years. PTH values were available and exploitable at M12 in 50% of them (645 patients). Among these patients, 58.9% had controlled (mean PTH of 304 ± 158 pg/mL) and 41.1% uncontrolled SHPT (mean PTH of 1084 ± 543) at M12. At the baseline, patients with controlled SHPT were older (66 ± 15 versus 61 ± 17 years), and had lower PTH (831 ± 346 versus 1057 ± 480 pg/mL) and calcaemia (2.18 ± 0.2 versus 2.22 ± 0.19 mmol/L) than uncontrolled patients. In multivariate analysis, these three factors still remained significantly associated with controlled SHPT.

Conclusion

In this real-life study, 41.1% of HD patients with SHPT treated with cinacalcet-HCl remained with a PTH above the KDIGO recommended target after 12 months of treatment. Apart from the possibility of non-compliance, the severity of SHPT appears to be a major factor determining the response to cinacalcet-HCl treatment, reinforcing the importance of treating SHPT at earlier stages.
Pulmonary artery pressure telemonitoring by CardioMEMS in a patient pre- and post-left ventricular assist device implantation
Authors: Veenis Jesse F , Birim Ozcan , Brugts Jasper J
Published: February 2019

We present a case to demonstrate the feasibility of pulmonary artery monitoring with the CardioMEMS sensor for the preoperative optimization of patients with end-stage heart failure undergoing LVAD surgery. Additionally, we demonstrate the feasibility of combining two state-of-the-art techniques by integrating haemodynamic feedback from CardioMEMS and static pump settings of an LVAD. CardioMEMS aids in the remote monitoring of LVAD patients with the potential of identifying complications, pump dysfunction or filling status alterations.
KIBRA and APOE Gene Variants Affect Brain Functional Network Connectivity in Healthy Older People
Authors: Wang Dawei , Hu Li , Xu Xinghua , Ma Xiangxing , Li Yi , Liu Yong , Wang Qing , Zhuo Chuanjun
Published: February 2019

Genetic factors play a critical role in the development of Alzheimer’s disease (AD). Kidney and brain expressed protein (KIBRA) and apolipoprotein E (APOE) are involved in episodic memory performance and AD. However, the interactions between KIBRA and APOE on brain functional network connectivity (FNC) remain unknown in healthy older people. Using independent component analysis, we systematically investigated additive and epistatic interactions of KIBRA rs1707045 and APOE on FNC in 170 healthy older Chinese people of Han ethnicity. We found significant additive KIBRA–APOE interactions on brain FNC in the right medial prefrontal cortex, the posterior cingulate cortex in the default-mode network, and the dorsal anterior cingulate cortex in the salience network. We also found significant epistatic KIBRA–APOE interactions on brain FNC in the left superior frontal gyrus and left angular gyrus in default-mode network. No significant KIBRA–APOE interactions were detected in other brain resting-state networks. These findings suggest that healthy older people have additive and epistatic interactions of KIBRA and APOE gene variants, which modulate brain FNC and may partly elucidate their association with episodic memory performance and AD.
A model-based approach to incorporate environmental variability into assessment of a commercial fishery: a case study with the American lobster fishery in the Gulf of Maine and Georges Bank
Authors: Tanaka Kisei R , Cao Jie , Shank Burton V , Truesdell Samuel B , Mazur Mackenzie D , Xu Luoliang , Chen Yong
Published: February 2019

Changes in bottom-up forcing are fundamental drivers of fish population dynamics. Recent literature has highlighted the need to incorporate the role of dynamic environmental conditions in stock assessments as a key step towards adaptive fishery management. Combining a bioclimate envelope model and a population dynamic model, we propose a model-based approach that can incorporate ecosystem products into single-species stock assessments. The framework was applied to a commercially important American lobster (Homarus americanus) stock in the Northwest Atlantic. The bioclimate envelope model was used to hindcast temporal variability in a lobster recruitment habitat suitability index (HSI) using bottom temperature and salinity. The climate-driven HSI was used to inform the lobster recruitment dynamics within the size-structured population dynamics model. The performance of the assessment model with an environment-explicit recruitment function is evaluated by comparing relevant assessment outputs such as recruitment, annual fishing mortality, and magnitude of retrospective biases. The environmentally-informed assessment model estimated (i) higher recruitment and lower fishing mortality and (ii) reduced retrospective patterns. This analysis indicates that climate-driven changes in lobster habitat suitability contributed to increased lobster recruitment and present potential improvement to population assessment. Our approach is extendable to other stocks that are impacted by similar environmental variability.
3D Muscle Architecture of the Pectoral Muscles of European Starling (Sturnus vulgaris)
Authors: Sullivan S P , McGechie F R , Middleton K M , Holliday C M
Published: February 2019

Avian flight is achieved through a number of modifications to the body, including the pectoral girdle, yet little is known about the architecture of the pectoral musculature. Muscle architecture is a critical variable in determining the biomechanical function of the vertebrate musculoskeletal system; however, accurate three-dimensional (3D) understanding of muscle architecture has been historically difficult to acquire. Here, we present a musculoskeletal model of a European starling (Sturnus vulgaris) pectoral girdle generated from iodine contrast-enhanced micro-computed-tomography (CT) data and 3D fiber tracking analysis. We used a template-based fiber-tracking algorithm to reconstruct muscle fibers in 3D based on grayscale differences in CT images, which allowed us to estimate fascicle lengths, pennation angles, muscle volumes, and physiological cross-sectional area. Our modeled muscles were qualitatively accurate; however, quantitative muscle architecture data differed between digital and traditional gross-dissection methods reflecting the complex organization of the tissue and differing natures of data collection. We found that model quality is affected by the resolution of CT image data and the fiber-tracking program’s input parameters. Nonetheless, digital fiber tracking offers numerous advantages over gross-dissection methods, most importantly, the ability to visualize and quantify entire muscles in three-dimensions, yielding a much more accurate estimation of whole muscle architecture.
Invasive Group A Streptococcus Infection in Children in Southern Israel Before and After the Introduction of Varicella Vaccine
Authors: Hasin Ori , Hazan Guy , Rokney Assaf , Dayan Roy , Sagi Orli , Ben-Shimol Shalom , Greenberg David , Danino Dana
Published: February 2019

The annual rates of group A Streptococcus bacteremia per 100 000 children in southern Israel declined after introduction of the varicella vaccine to the national immunization program, from 2.43 (95% confidence interval, 1.73–3.13) in 1995–2002 to 1.30 (95% confidence interval, 0.91–1.72) in 2010–2016 (P = .04). This reduction correlated with the disappearance of varicella rash as a predisposing factor.
Faculties, Knowledge, and Reasons for Doubt in the Cartesian Circle
Authors: Clark Matthew
Published: February 2019

This paper argues for a novel solution to the Cartesian Circle by emphasising the important epistemic role of the Second Meditation and Descartes’ faculty epistemology. I argue that, for Descartes: doubt requires a ‘good reason’ to doubt (§2.1); whether a reason qualifies as a ‘good reason’ depends on which faculty produces that reason (§2.2); and for distinct metaphysical perceptions from the faculty of the intellect, no other faculty can provide ‘good reasons’ to doubt (§2.3). The upshot of §2 is that the doubts raised up to the Third Meditation do not apply to the distinct metaphysical perceptions of the intellect, and in particular do not apply to the premises of the proof of the existence of God. I present the role of God as primarily to secure clear and distinct perceptions beyond the intellect, and knowledge of conclusions when those conclusions are no longer being clearly and distinctly perceived (§3.1). Finally, I give an account of Descartes’ use of ‘cognoscere’, ‘scire’, and ‘scientia’ as three distinct epistemic levels, providing a valuable structure within which one can see the meditator progress (§3.2).
Developing Physician Leadership in Hospital Policy Development: A Case Study of Resident-Driven Policy Initiatives in the Department of Neurosurgery at the University of Alabama at Birmingham
Authors: Shank Christopher D , Kuhn Elizabeth N , Hadley Mark N , Walters Beverly C
Published: February 2019

The bulk of a resident's daily work is patient care related; however, other aspects of residency training are vital both to a resident's education and to the advancement of the field. Basic science and clinical research are the more common academic activities in which residents participate after completion of daily patient care objectives. Less frequently, residents participate in a process vital to the delivery of efficient, cost-effective, and safe patient care: hospital policy development.

Two policies were identified as outdated or absent: (1) the process for the declaration of brain death and (2) a policy for the use of hypertonic saline in the Neurosciences Intensive Care Unit. The policies were rewritten after review of the existing policy (when applicable), other institutions’ examples, national guidelines, and state and federal laws. Once written, proposals were reviewed by department leadership, hospital ethics, legal counsel, ad hoc specialty committees, the Medical Directors Council, and the Medical Executive Committee. After multiple revisions, each proposal was endorsed by the above bodies and ratified as hospital policy.

Residents may make a substantial impact on patient care through active participation in the authorship and implementation of hospital policy. The inclusion of residents in policy development has improved the process for declaring brain death and management of patients with devastating neurological pathology. Resident involvement in hospital policy initiatives can be successful, valuable to the institution, and beneficial to patient care. Resident involvement is predicated on faculty and institutional support of such endeavors.
The proper strategy to compress and protect plasmid DNA in the Pluronic L64-electropulse system for enhanced intramuscular gene delivery
Authors: He Yutong , Liu Yili , Sun Zhe , Han Fei , Tang James Zhenggui , Gao Rong , Wang Gang
Published: February 2019

Intramuscular expression of functional proteins is a promising strategy for therapeutic purposes. Previously, we developed an intramuscular gene delivery method by combining Pluronic L64 and optimized electropulse, which is among the most efficient methods to date. However, plasmid DNAs (pDNAs) in this method were not compressed, making them unstable and inefficient in vivo. We considered that a proper compression of pDNAs by an appropriate material should facilitate gene expression in this L64-electropulse system. Here, we reported our finding of such a material, Epigallocatechin gallate (EGCG), a natural compound in green teas, which could compress and protect pDNAs and significantly increase intramuscular gene expression in the L64-electropulse system. Meanwhile, we found that polyethylenimine (PEI) could also slightly improve exogenous gene expression in the optimal procedure. By analysing the characteristic differences between EGCG and PEI, we concluded that negatively charged materials with strong affinity to nucleic acids and/or other properties suitable for gene delivery, such as EGCG, are better alternatives than cationic materials (like PEI) for muscle-based gene delivery. The results revealed that a critical principle for material/pDNA complex benefitting intramuscular gene delivery/expression is to keep the complex negatively charged. This proof-of-concept study displays the breakthrough in compressing pDNAs and provides a principle and strategy to develop more efficient intramuscular gene delivery systems for therapeutic applications.
Epigenome-wide association study identifies Behçet’s disease-associated methylation loci in Han Chinese
Authors: Yu Hongsong , Du Liping , Yi Shenglan , Wang Qingfeng , Zhu Yunyun , Qiu Yiguo , Jiang Yan , Li Minghui , Wang Detao , Wang Qing , Yuan Gangxiang , Cao Qingfeng , Kijlstra Aize , Yang Peizeng
Published: February 2019

Objective

The aetiology of Behçet’s disease (BD), known as a systemic vasculitis, is not completely understood. Increasing evidence suggests that aberrant DNA methylation may contribute to the pathogenesis of BD. The aim of this epigenome-wide association study was to identify BD-associated methylation loci in Han Chinese.

Methods

Genome-wide DNA methylation profiles were compared between 60 BD patients and 60 healthy controls using the Infinium Human Methylation 450 K Beadchip. BD-associated methylation loci were validated in 100 BD patients and 100 healthy controls by pyrosequencing. Gene expression and cytokine production was quantified by real-time PCR and ELISA.

Results

A total of 4332 differentially methylated CpG sites were associated with BD. Five differentially methylated CpG sites (cg03546163, cg25114611, cg20228731, cg23261343 and cg14290576) revealed a significant hypomethylation status across four different genes (FKBP5, FLJ43663, RUNX2 and NFIL3) and were validated by pyrosequencing. Validation results showed that the most significant locus was located in the 5’UTR of FKBP5 (cg03546163, P = 3.81E-13). Four CpG sites with an aberrant methylation status, including cg03546163, cg25114611, cg23261343 and cg14290576, may serve as a diagnostic marker for BD (area under the receiver operating curve curve = 83.95%, 95% CI 78.20, 89.70%). A significantly inverse correlation was found between the degree of methylation at cg03546163 as well as cg25114611 and FKBP5 mRNA expression. Treatment with a demethylation agent, 5-Aza-2’-deoxycytidine resulted in an increase of FKBP5 mRNA expression and a stimulated IL-1β production.

Conclusion

Our findings suggest that aberrant DNA methylation, independently of previously known genetic variants, plays a vital role in the pathogenesis of BD.

Trial registration

Chinese Clinical Trial Registry, chictr.org.cn, ChiCTR-CCC-12002184.
Prognostic role of disease extent and lymphocyte–monocyte ratio in advanced melanoma
Authors: Iacono Donatella , Basile Debora , Gerratana Lorenzo , Vitale Maria G. , Pelizzari Giacomo , Cinausero Marika , Poletto Elena , Puglisi Fabio , Fasola Gianpiero , Minisini Alessandro M.
Published: February 2019

Advanced melanoma (AM) represents the leading cause of death from skin cancer. To date, the crucial role of the immune system in AM pathogenesis and progression is well known, but the prognostic value of clinicopathological characteristics remains unclear. Lactate dehydrogenase (LDH) is an ascertained prognostic indicator and previous data showed that AM patients treated with BRAF and MEK inhibitors with normal LDH values and fewer than three metastatic sites achieved a better outcome. Moreover, the neutrophil-to-lymphocytes ratio and the lymphocyte-to-monocyte ratio (LMR) have been suggested as other potential prognostic factors. The aim of this study was to evaluate the prognostic value of LMR together with other clinical biomarkers in patients with AM. We retrospectively analyzed 162 consecutive patients with AM treated between January 2010 and March 2016. Outcome was measured in terms of overall survival (OS). In our cohort, the BRAF mutation was present in 74 (46%) patients. Overall, 42 and 26% of the patients received targeted therapy and immunotherapy, respectively. After 48 months of follow-up, 129 (78%) patients died; the median OS was 12.8 months. High LMR was associated with the following clinicopathological characteristics: absence of central nervous system localization (P = 0.011), fewer than three metastatic sites (P = 0.014), and normal LDH (P = 0.006). In multivariate analysis, Eastern Cooperative Oncology Group Performance Status >1 [hazard ratio (HR) 7.87, P = 0.001], high LDH (HR 2.76, P = 0.006), and high LMR (HR 0.76, P = 0.033) were associated significantly with OS. In conclusion, LMR seems to be associated with OS. Further prospective investigations are needed to confirm these data and introduce peripheral blood cell count in daily clinical use.
Adverse Drug Reactions, still masquerading after all these years?
Authors: Gray Laurence A. , Routledge Philip A.
Published: February 2019

In this journal in 1976, Professor Duncan Vere suggested that some adverse drug reactions could behave as “masqueraders”, sometimes evading detection for a considerable time after a medicine was introduced into clinical practice. Using contemporary examples, we illustrate why we believe the five main reasons he cited for adverse drug reactions masquerading in this manner remain just as relevant today. Although newer methods of investigation are increasingly contributing to improved surveillance, individual case reports and spontaneous reporting systems for suspected adverse drug reactions remain a cornerstone of pharmacovigilance and should continue during the whole of the time that medicines continue to be used therapeutically.
10-year Follow-up of Mod Quad and Triangle Tilt Surgeries in Obstetric Brachial Plexus Injury
Authors: Nath Rahul K. , Somasundaram Chandra
Published: February 2019

Aim:

To evaluate whether obstetric brachial plexus injury (OBPI) children who had mod Quad and triangle tilt surgeries maintained their recovered upper extremity functional movements over 10 years.

Background:

The short-term outcomes of surgery in OBPI patients are well documented. However, only a few publications with results over 10-year postoperative follow-up exist. We have previously reported the outcomes of these 2 surgeries in OBPI after 1, 2, and 5 years. Here, we report the successful outcomes in 17 of these patients over 10 years.

Methods:

Seventeen OBPI patients, who had mod Quad, a modified muscle release operation and triangle tilt, a bony surgical procedure with us between 2005 and 2008, had postoperative follow-up of 10 years and met the inclusion criteria. Patients who had multiple surgeries and did not have 10-year follow-up are excluded in this study.

Results:

Fifteen of 17 children maintain their recovered upper extremity functions for extended long period (mean, 10 years; range, 9–13 years). There was statistically significant improvement in total functional Mallet score after 3 years (mean, 18.8 ± 2.1; P ≤ 0.01) from the preoperative mean total Mallet score of 14.5 ± 1.2. This improvement was not only maintained for extended period but also improved (mean total Mallet score, 20.35 ± 2.3; P ≤ 0.01) in some patients.

Conclusions:

Overall, all upper extremity functions improved greatly after mod Quad and triangle tilt surgeries in OBPI children, and they were able to maintain their recovered functional movements over extended period of 10 years.
Determining Reliability of Arthroscopic Classifications for Hip Labral Tears
Authors: Guimarães Barros Antônio Augusto , Vassalo Carlos César , Costa Lincoln Paiva , de Oliveira Paganini Vinícius , de Carvalho Guedes Euler , Percope de Andrade Marco Antônio
Published: February 2019

Objective:

Evaluate interobserver and intraobserver reliability of hip arthroscopic classifications for labral tears.

Design:

Retrospective diagnostic study of nonconsecutive patients.

Setting:

Institutional study.

Patients:

From a database of 278 hip arthroscopy videos for treatment of femoroacetabular impingement, 70 videos were chosen by simple random sampling. Exclusion criteria included presence of radiological arthrosis (Tonnis > 2), previous hip surgery, inadequate lesion palpation, poor image quality, and refusal to participate in the study. The final sample included 60 videos.

Interventions:

Four hip surgeons evaluated the videos twice at 1-month intervals and classified the lesions according to Lage, Seldes, and Beck classifications for hip labral tears.

Main Outcome Measures:

Interobserver and intraobserver reliability with the percent of agreement and weighted Cohen kappa values.

Results:

Patients had a mean age of 33 years (SD, 7; range, 18-47 years), and 32 (53%) were men. Femoroacetabular impingement types included combined (CAM and pincer) in 31 (52%), CAM in 27 (45%), and pincer in 2 (3%). For interobserver reliability, the average weighted kappa values were 0.68, 0.65, and 0.78 for the Lage, Seldes, and Beck classifications, respectively. For intraobserver reliability, the mean weighted kappa values were 0.87, 0.64, and 0.93 for the Lage, Seldes, and Beck classifications, respectively.

Conclusions:

Beck classification had the highest average values for interobserver and intraobserver agreements. Lage, Seldes, and Beck scores for acetabular labrum tears showed substantial interobserver agreement. In the intraobserver evaluation, the Seldes system presented substantial agreement, whereas Lage and Beck classifications were considered excellent agreement.
The Art of Living With Symptoms: A Qualitative Study Among Patients With Primary Brain Tumors Receiving Proton Beam Therapy
Authors: Langegård Ulrica , Ahlberg Karin , Björk-Eriksson Thomas , Fransson Per , Johansson Birgitta , Ohlsson-Nevo Emma , Witt-Nyström Petra , Sjövall Katarina
Published: February 2019

Background

Symptom management in conjunction with proton beam therapy (PBT) from patient's perspective has not been explored. Such knowledge is essential to optimize the care in this relatively new treatment modality.

Objective

The aim of this study was to explore the process of symptom management in patients with brain tumor receiving PBT.

Methods

Participants were 22 patients with primary brain tumor who received PBT, recruited in collaboration with a national center for proton therapy and 2 oncology clinics at 2 university hospitals in Sweden. Interviews using open-ended questions were conducted before, during, and/or after treatment. Verbatim interview transcripts were analyzed using classic Grounded Theory.

Results

“The art of living with symptoms” emerged as the core concept. This encompassed 3 interconnected symptom management concepts: “Adapting to limited ability,” “Learning about oneself,” and “Creating new routines.” These concepts were summarized in a substantive theoretical model of symptom management. Despite the struggle to manage symptoms, participants lived a satisfactory life.

Conclusions

Symptom management in conjunction with PBT comprises a process of action, thoughts, and emotions. The concepts that emerged indicated patients' symptom management strategies were based on their own resources.

Implications for Practice

It is important that PBT facilities develop an approach that facilitates the symptom management process based on patients' experiences of symptoms, as well as their actions and available resources.
Therapeutic Hypothermia After Perinatal Asphyxia in Infants With Severe, Ductal-Dependent Congenital Heart Disease*
Authors: Boos Vinzenz , Tietze Anna , Berger Felix , Bührer Christoph
Published: February 2019

Objectives:

Patients with severe congenital heart disease and cardiac anomalies such as restrictive foramen ovale, intact atrial septum, or narrowing of ductus arteriosus are at risk for perinatal asphyxia, leading to hypoxic-ischemic encephalopathy. We hypothesize that therapeutic hypothermia can be applied to these patients and seek to investigate feasibility and safety of this method.

Design:

A retrospective observational study.

Setting:

The Department of Neonatology of Charité, University Hospital, Berlin, Germany.

Patients:

Newborns with severe congenital heart disease and perinatal asphyxia were retrospectively analyzed over a 6-year period.

Interventions:

Application of therapeutic hypothermia.

Measurements and Main Results:

Ten patients with perinatal asphyxia were enrolled in this study. All patients received low-dose prostaglandin E1 for ductal maintenance. Three patients without evidence for hypoxic-ischemic encephalopathy did not receive therapeutic hypothermia. One patient died at the age of 15 hours, and therapeutic hypothermia was discontinued after 19 hours in another patient with severe arterial hypotension. Adverse effects during hypothermia included respiratory insufficiency (100%), arterial hypotension (71%), the need for inotropic support (71%), and pulmonary hypertension (43%), the latter associated with prolonged postoperative inotropic support. No neurologic complications occurred before or after the surgery. Operative outcome of surviving patients was excellent. Early brain MRI scans were suggestive of good neurodevelopmental prognosis for most patients.

Conclusions:

Therapeutic hypothermia can be applied to patients with severe congenital heart disease and hypoxic-ischemic encephalopathy. Low-dose prostaglandin E1 infusions are safe for ductal maintenance during cooling, but cardiopulmonary adverse effects should be anticipated.
Hypotensive Response to IV Acetaminophen in Pediatric Cardiac Patients*
Authors: Achuff Barbara-Jo , Moffett Brady S. , Acosta Sebastian , Lasa Javier J. , Checchia Paul A. , Rusin Craig G.
Published: February 2019

Objectives:

Acetaminophen is ubiquitously used as antipyretic/analgesic administered IV to patients undergoing surgery and to critically ill patients when enteral routes are not possible. Widely believed to be safe and free of adverse side effects, concerns have developed in adult literature regarding the association of IV acetaminophen and transient hypotension. We hypothesize that there are hemodynamic effects after IV acetaminophen in the PICU and assess the prevalence of such in a large pediatric cardiovascular ICU population using high-fidelity data.

Design:

Observational study analyzing an enormous set of continuous physiologic data including millions of beat to beat blood pressures surrounding medication administration.

Setting:

Quaternary pediatric cardiovascular ICU between January 1, 2013, and November 13, 2017.

Patients:

All patients less than or equal to 18 years old who received IV acetaminophen. Mechanical support devices excluded.

Interventions:

None.

Measurements and Main Results:

Physiologic vital sign data were analyzed in 5-minute intervals starting 60 minutes before through 180 minutes after completion. Hypotension defined as mean arterial pressure –15% from baseline and relative hypotension defined –10%. Only doses where patients received no other medications, including vasopressors, within the previous hour were included. t test and a correlation matrix were used to eliminate correlated factors before a logistic regression analysis was performed. Six-hundred eight patients received 777 IV acetaminophen doses. Median age was 8.8 months (interquartile range, 2–62 mo) with a dose of 12.5 mg/kg (interquartile range, 10–15 mg/kg). Data were normalized for age and reference values. One in 20 doses (5%) were associated with hypotension, and one in five (20%) associated with relative hypotension. Univariate analysis revealed hypotension associated with age, baseline mean arterial pressure, and skin temperature (p = 0.05, 0.01, and 0.09). Logistic regression revealed mean arterial pressure (p = 0.01) and age (p = 0.05) remained predictive for hypotension.

Conclusions:

In isolation of other medication, a hemodynamic response to IV acetaminophen has a higher prevalence in critically ill children with cardiac disease than previously thought and justifies controlled studies in the perioperative and critical care setting. The added impact on individual patient hemodynamics and physiologic instability will require further study.
Psychological Traits, Heart Rate Variability, and Risk of Coronary Heart Disease in Healthy Aging Women—The Women's Health Initiative
Authors: Salmoirago-Blotcher Elena , Hovey Kathleen M. , Andrews Cristopher A. , Allison Matthew , Brunner Robert L. , Denburg Nathalie L. , Eaton Charles , Garcia Lorena , Sealy-Jefferson Shawnita M. , Zaslavsky Oleg , Kang Joseph , López Lenny , Post Stephen G. , Tindle Hilary , Wassertheil-Smoller Sylvia
Published: February 2019

Objective

Psychological traits such as optimism and hostility affect coronary heart disease (CHD) risk, but mechanisms for this association are unclear. We hypothesized that optimism and hostility may affect CHD risk via changes in heart rate variability (HRV).

Methods

We conducted a longitudinal analysis using data from the Women's Health Initiative Myocardial Ischemia and Migraine Study. Participants underwent 24-hour ambulatory electrocardiogram monitoring 3 years after enrollment. Optimism (Life Orientation Test-Revised), cynical hostility (Cook-Medley), demographics, and coronary risk factors were assessed at baseline. HRV measures included standard deviation of average N-N intervals (SDNN); standard deviation of average N-N intervals for 5 minutes (SDANN); and average heart rate (HR). CHD was defined as the first occurrence of myocardial infarction, angina, coronary angioplasty, and bypass grafting. Linear and Cox regression models adjusted for CHD risk factors were used to examine, respectively, associations between optimism, hostility, and HRV and between HRV and CHD risk.

Results

Final analyses included 2655 women. Although optimism was not associated with HRV, hostility was inversely associated with HRV 3 years later (SDANN: adjusted β = −0.54; 95% CI = −0.97 to −0.11; SDNN: −0.49; 95% CI = −0.93 to −0.05). HRV was inversely associated with CHD risk; for each 10-millisecond increase in SDNN or SDANN, there was a decrease in CHD risk of 9% (p = .023) and 12% (p = .006), respectively.

Conclusions

HRV did not play a major role in explaining why more optimistic women seem to be somewhat protected from CHD risk. Although hostility was inversely associated with HRV, its role in explaining the association between hostility and CHD risk remains to be established.
Implanted Nerve Electrical Stimulation allows to Selectively Restore Hand and Forearm Movements in Patients with a Complete Tetraplegia
Authors: Tigra Wafa , Azevedo Christine , Teissier Jacques , Gelis Anthony , Coulet Bertrand , Divoux Jean-Louis , Guiraud David
Published: February 2019

Background

Functional Electrical Stimulation (FES) is used for decades in rehabilitation centers. For patients with a spinal cord injury (SCI), FES can prevent muscular atrophy, reduce spasticity and/or restore limb movements. To this last aim, FES external devices can be used, but elicit imprecise movements. FES implanted devices used neuromuscular stimulation and required implantation of one electrode for each site (muscle) to stimulate, an heavy surgical procedure and 10 times more electrical charges than nerve stimulation. Moreover, complications related to the numerous implanted components could appear over time. The purpose of this work is to evaluate whether a multi-contact nerve cuff electrode can selectively activate forearm and hand muscles and restore functional movements in patient with a complete tetraplegia.

Methods

A 12-contacts cuff electrode was designed to selectively activate, without damage it, multi fascicular peripheral nerve (1). Six subjects rwith at least one extensor or one flexor muscle stimulable by surface electrical stimulation, have been enrolled into the study. During the surgical procedure, radial or median nerve was stimulated through up to 35 different configurations of stimulation at an intensity up to 2.1 mA (25 Hz, pulse width 250 µs, inter-pulse 100 µs). Surface electrodes were positioned upon the forearm to record compound muscle action potentials elicited by nerve electrical stimulation. Recruitments curves and videos were recorded.

Results

The multicontact cuff electrode allowed us to selectively activate group of muscles to produce multiple, independent and functional hand and forearm movements in persons with tetraplegia. A surface electrical stimulation did not allow all those movements.
Prey capturing and feeding apparatus of dragonfly nymph
Authors: Kundanati Lakshminath , Das Prashant , Pugno Nicola M.
Published: February 2019

Aquatic predatory insects, like the nymphs of a dragonfly, use rapid movements to catch their prey. Dragonfly nymphs are voracious predators that feed on smaller aquatic organisms. In this study, we examine dragonfly nymph (Libellulidae: Insecta: Odonata)mouthparts that are used in prey capturing and feeding. In particular, we characterise the morphology of the labium and mechanical properties of the mandibles of the nymph. Additionally, we record and analyse the preying mechanism using high-speed photography. The morphological details suggest that the prey capturing mechanism is a complex grasping mechanism with additional sensory organs that might aid in sensing the surroundings. The times taken for the extension and retraction of labial organ during prey capture was 187±54 ms. The Young’s modulus and hardness of the mandibles samples were 9.1±1.9 GPa and 0.85±0.13 GPa. Gradation in the mechanical properties was also observed in the mandible tip regions with increased properties at the tip end. The overall mechanism with its sensory capabilities provides a unique design to develop bioinspired underwater deployable mechanisms.
Y-Family DNA Polymerases Have Three Structural Elements That Promote Accurate dCTP Insertion And Minimize dATP/dGTP/dTTP Misinsertion Opposite a N2-dG Adduct of Benzo[a]pyrene
Authors: Sholder Gabriel , Tonzi Peter , Chandani Sushil , Loechler Edward L.
Published: February 2019

To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N2-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N2-dG. To investigate structural differences between Y-Family-classes, Dpo4 (a canonical η/V-class-member) is modified to make it more κ/IV-like, as evaluated via primer-extension studies with a BP-N2-dG-containing template. Three protein structural elements are identified that promote fidelity. (1) Watson-Crick-like [dCTP:BP-N2-dG] pairing requires the BP-moiety to be in the minor groove. Thus, as expected, dCTP insertion is facilitated by having large openings in the protein surface that can accommodate BP-bulk in the minor groove. The BP-moiety is also in the minor groove during dATP and dTTP misinsertion, though evidence suggests that each of these three minor groove BP-conformations differ. (2) Plugging an opening on the major groove side of the protein suppresses dGTP misinsertion, implying BP-N2-dG bulk is in the major groove during Hoogsteensyn-adduct-dG:dGTP pairing. (3) Y-Family DNAPs have non-covalent bridges (NCBs) holding their little finger-domain in contact with their catalytic core-domain; dATP/dGTP/dTTP misinsertions are suppressed by the quantity and quality of NCBs, including one near and another distal to the active site on the minor groove side. In conclusion, three protein structural elements enhance dCTP and/or suppress dATP/dGTP/dTTP insertion; four different BP-adduct conformations are responsible for the four different dNTP insertional pathways opposite BP-N2-dG; generalizations about Y-Family structure are also considered.
Real-time, functional intra-operative localization of rat cavernous nerve network using near-infrared cyanine voltage-sensitive dye imaging
Authors: Kang Jeeun , Le Hanh N. D. , Karakus Serkan , Malla Adarsha P. , Harraz Maged M. , Kang Jin U. , Burnett Arthur L. , Boctor Emad M.
Published: February 2019

Despite current progress achieved in the surgical technique of radical prostatectomy, post-operative complications such as erectile dysfunction and urinary incontinence persist at high incidence rates. In this paper, we present a methodology for functional intra-operative localization of the cavernous nerve (CN) network for nerve-sparing radical prostatectomy using near-infrared cyanine voltage-sensitive dye (VSD) imaging, which visualizes membrane potential variations in the CN and its branches (CNB) in real time. As a proof-of-concept experiment, we demonstrate a functioning complex nerve network in response to electrical stimulation of the CN, which was clearly differentiated from surrounding tissues in anin vivorat prostate model. Stimulation of an erection was confirmed by correlative intracavernosal pressure (ICP) monitoring. Within 10 minutes, we performed trans-fascial staining of the CN by direct VSD administration. Our findings suggest the applicability of VSD imaging for real-time, functional imaging guidance during nerve-sparing radical prostatectomy.
Preparation of Mouse Tissue Lysates for Polymerase Chain Reaction
Authors: Perry William
Published: February 2019

A simple cell or tissue lysate can provide a sufficient quality and amount of template DNA for polymerase chain reaction (PCR). This protocol can be used to prepare embryonic tissues or yolk sac samples for PCR analysis, but it is also useful for adult tissues (such as tail) that do not lyse completely by boiling in SDS/NaOH. Nonionic detergents are substituted for SDS because they interfere less with the polymerase reaction.
Tandem Immunoaffinity Purification Using Anti-FLAG and Anti-HA Antibodies
Authors: DeCaprio James , Kohl Thomas O.
Published: February 2019

The immunoaffinity purification of target proteins followed by the identification and characterization of associated proteins by mass spectrometry is a widely used technique. An immunoaffinity purification bears resemblance to a standard immunoprecipitation; however, the end product for mass spectrometric analysis in the femtomole (10−15) to attomole (10−18) range is required to be of exceptional purity. This high degree of sensitivity in detection renders it of extreme importance to eliminate most if not all of the nonspecific background proteins and can be achieved by performing a tandem affinity purification (TAP). In TAP, the cDNA of the target protein is engineered to contain at least two different epitope tags, and the target protein is extracted under nondenaturing conditions upon expression using an appropriate protein expression platform (CHO cells, HEK 293 cells, or yeast). The expressed protein is initially immunoprecipitated using an antibody against one epitope tag and is eluted in the presence of excess peptide by competition for antibody-binding sites, before being reimmunoprecipitated using an antibody that specifically recognizes the second epitope. These sequential immunoprecipitations significantly reduce the presence of associated nonspecific proteins. Numerous combinations of epitope tags have been applied for tandem affinity purification, and this protocol illustrates the use of tandem hemagglutinin (HA) and FLAG epitope tags. The first immunoprecipitation uses an anti-FLAG antibody followed by the elution in the presence of a competing FLAG peptide before the reimmunoprecipitation of the protein using an anti-HA antibody. Numerous high-quality antiepitope tag antibodies are commercially available from different antibody manufacturers.
Senescence and Defense Pathways Contribute to Heterosis
Authors: Gonzalez-Bayon Rebeca , Shen Yifei , Groszmann Michael , Zhu Anyu , Wang Aihua , Allu Annapurna D. , Dennis Elizabeth S. , Peacock W. James , Greaves Ian K.
Published: February 2019

Hybrids are used extensively in agriculture due to their superior performance in seed yield and plant growth, yet the molecular mechanisms underpinning hybrid performance are not well understood. Recent evidence has suggested that a decrease in basal defense response gene expression regulated by reduced levels of salicylic acid (SA) may be important for vigor in certain hybrid combinations. Decreasing levels of SA in the Arabidopsis (Arabidopsis thaliana) accession C24 through the introduction of the SA catabolic enzyme salicylate1 hydroxylase (NahG) increases plant size, phenocopying the large-sized C24/Landsberg erecta (Ler) F1 hybrids. C24♀ × Ler♂ F1 hybrids and C24 NahG lines shared differentially expressed genes and pathways associated with plant defense and leaf senescence including decreased expression of SA biosynthetic genes and SA response genes. The expression of TL1 BINDING TRANSCRIPTION FACTOR1, a key regulator in resource allocation between growth and defense, was decreased in both the F1 hybrid and the C24 NahG lines, which may promote growth. Both C24 NahG lines and the F1 hybrids showed decreased expression of the key senescence-associated transcription factors WRKY53, NAC-CONTAINING PROTEIN29, and ORESARA1 with a delayed onset of senescence compared to C24 plants. The delay in senescence resulted in an extension of the photosynthetic period in the leaves of F1 hybrids compared to the parental lines, potentially allowing each leaf to contribute more resources toward growth.
X-ray characterization of contact holes for block copolymer lithography
Authors: Sunday Daniel F. , Delachat Florian , Gharbi Ahmed , Freychet Guillaume , Liman Christopher D. , Tiron Raluca , Kline R. Joseph
Published: February 2019

The directed self-assembly (DSA) of block copolymers (BCPs) is a promising low-cost approach to patterning structures with critical dimensions (CDs) which are smaller than can be achieved by traditional photolithography. The CD of contact holes can be reduced by assembling a cylindrical BCP inside a patterned template and utilizing the native size of the cylinder to dictate the reduced dimensions of the hole. This is a particularly promising application of the DSA technique, but in order for this technology to be realized there is a need for three-dimensional metrology of the internal structure of the patterned BCP in order to understand how template properties and processing conditions impact BCP assembly. This is a particularly challenging problem for traditional metrologies owing to the three-dimensional nature of the structure and the buried features. By utilizing small-angle X-ray scattering and changing the angle between the incident beam and sample we can reconstruct the three-dimensional shape profile of the empty template and the residual polymer after self-assembly and removal of one of the phases. A two-dimensional square grid pattern of the holes results in scattering in both in-plane directions, which is simplified by converting to a radial geometry. The shape is then determined by simulating the scattering from a model and iterating that model until the simulated and experimental scattering profiles show a satisfactory match. Samples with two different processing conditions are characterized in order to demonstrate the ability of the technique to evaluate critical features such as residual layer thickness and sidewall height. It was found that the samples had residual layer thicknesses of 15.9 ± 3.2 nm and 4.5 ± 2.2 nm, which were clearly distinguished between the two different DSA processes and in good agreement with focused ion beam scanning transmission electron microscopy (FIBSTEM) observations. The advantage of the X-ray measurements is that FIBSTEM characterizes around ten holes, while there are of the order of 800 000 holes illuminated by the X-ray beam.
US and Chinese yield curve responses to RMB exchange rate policy shocks
Authors: Hong Zhiwu , Niu Linlin , Zeng Gengming
Published: February 2019

Purpose

Using a discrete-time version of the arbitrage-free Nelson–Siegel (AFNS) term structure model, the authors examine how yield curves in the US and China react to exchange rate policy shocks as China introduces gradual reforms to make its exchange rate regime more flexible. The paper aims to discuss this issue.

Design/methodology/approach

The authors characterize the specification of the discrete-time AFNS model, prove the uniqueness of the solution for model identification, perform specification analysis on its canonical form and detail the MCMC estimation method with a fast and reliable prior extraction step.

Findings

Model decomposition reveals that in the US yield responses, changes in risk premia for medium- to long-term yields dominate changes in yield expectation for short- to medium-term yields, indicating that the portfolio rebalancing effect due to varying risk perception is stronger than the signaling effect due to policy rate expectation.

Practical implications

The results are helpful in diagnosing market sentiment and exchange rate risk pricing as China further internationalizes its currency.

Originality/value

The methodology can be easily extended to study yield curve responses to other scenarios of policy shocks or regime changes.