bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of IP3R1 disrupts tubulobulbar complex-ectoplasmic reticulum contact sites and the morphology of apical processes encapsulating late spermatids†
Authors: Adams Arlo , Vogl Wayne
Published: May 2020

Tubulobulbar complexes (TBCs) internalize intercellular junctions during sperm release. One of the characteristic features of TBCs is that they form “bulbs” or swollen regions that have well-defined membrane contact sites (MCS) with adjacent cisternae of endoplasmic reticulum. Previously, we have localized the IP3R calcium channel to the TBC bulb-ER contacts and have hypothesized that fluctuations in local calcium levels may facilitate the maturation of TBC bulbs into putative endosomes, or alter local actin networks that cuff adjacent tubular regions of the TBCs. To test this, we injected the testes of Sprague Dawley rats with small interfering RNAs (siRNAs) against IP3R1 and processed the tissues for either western blot, immunofluorescence, or electron microscopy. When compared to control testes injected with nontargeting siRNAs, Sertoli cells in knocked-down testes showed significant morphological alterations to the actin networks including a loss of TBC actin and the appearance of ectopic para-crystalline actin bundles in Sertoli cell stalks. There also was a change in the abundance and distribution of TBC-ER contact sites and large internalized endosomes. This disruption of TBCs resulted in delay of the withdrawal of apical processes away from spermatids and in spermiation. Together, these findings are consistent with the hypothesis that calcium exchange at TBC-ER contacts is involved both in regulating actin dynamics at TBCs and in the maturing of TBC bulbs into endosomes. The results are also consistent with the hypothesis that TBCs are part of the sperm release mechanism.
Mechanism of semen liquefaction and its potential for a novel non-hormonal contraception†
Authors: Anamthathmakula Prashanth , Winuthayanon Wipawee
Published: May 2020

Semen liquefaction is a proteolytic process where a gel-like ejaculated semen becomes watery due to the enzymatic activity of prostate-derived serine proteases in the female reproductive tract. The liquefaction process is crucial for the sperm to gain their motility and successful transport to the fertilization site in Fallopian tubes (or oviducts in animals). Hyperviscous semen or failure in liquefaction is one of the causes of male infertility. Therefore, the biochemical inhibition of serine proteases in the female reproductive tract after ejaculation is a prime target for novel contraceptive development. Herein, we will discuss protein components in the ejaculates responsible for semen liquefaction and any developments of contraceptive methods in the past that involve the liquefaction process.
Shared Insights across the Ecology of Coral Reefs and African Savannas: Are Parrotfish Wet Wildebeest?
Authors: Burkepile Deron E , Schmitt Melissa H , Stears Keenan , Donovan Mary K , Thompson Dave I
Published: May 2020

Comparison across terrestrial and aquatic ecosystems facilitates a broader understanding of ecological patterns. Although meta-analyses are important for quantitative synthesis across ecosystems, detailed comparisons of natural history and species interactions also illuminate convergence among systems. We compare the ecology of superficially dissimilar African savannas and coral reefs via shared characteristics including: (1) hyperdiverse guilds of large vertebrate herbivores and predators, (2) similar mechanisms driving positive feedback loops between herbivory and primary production, (3) similar roles of disturbance and herbivory in mediating ecosystem state, and (4) numerous smaller vertebrate and invertebrate species that underpin diversity and ecosystem processes. Our goal in comparing the natural history and ecology of these ecosystems is to facilitate others in finding their own comparative systems. We encourage scientists, especially early-career scientists, to explore ecosystems other than their primary focus. Whatever your ecosystem of study, examining the ecology of its analog in another environment may enliven your career.
Methodological considerations for investigating oral anticoagulation persistence in atrial fibrillation
Authors: Paquette Miney , Mbuagbaw Lawrence , Iorio Alfonso , Nieuwlaat Robby
Published: May 2020

Aims 

Reports of long-term oral anticoagulant (OAC) therapy for atrial fibrillation (AF) reveal highly variable, and generally suboptimal estimates of medication persistence. The objective of this review is to summarize current literature and highlight important methodological considerations for interpreting persistence research and designing studies of persistence on OAC treatment.

Methods and results 

We summarize differences in study methodology, setting, timing, treatment, and other factors associated with reports of better or worse persistence. For example, prospective compared with retrospective study designs are associated with higher reported persistence. Similarly, patient factors such as permanent AF or high stroke risk, and treatment with non-vitamin K oral antagonists relative to vitamin K antagonists are associated with higher persistence. Persistence has also been reported to be higher in Europe compared with North America and higher when the treating physician is a general practitioner compared with a specialist. We propose a framework for assessing and designing persistence studies. This framework includes aspects of patient selection, reliability and validity of measures, persistence definitions, clinical utility of measurements, follow-up periods, and analytic approaches.

Conclusions 

Differences in study design, patient selection, treatments, and factors such as the countries/regions where studies are conducted or the type of treating physician may help explain the variability in OAC persistence estimates. A framework is proposed to assess persistence studies. This may have utility to compare and interpret published studies as well as for planning of future studies.
Effects of tobacco cigarettes, e-cigarettes, and waterpipe smoking on endothelial function and clinical outcomes
Authors: Münzel Thomas , Hahad Omar , Kuntic Marin , Keaney John F , Deanfield John E , Daiber Andreas
Published: May 2020

Tobacco smoking is a leading cause of non-communicable disease globally and is a major risk factor for cardiovascular disease (CVD) and lung disease. Importantly, recent data by the World Health Organizations (WHO) indicate that in the last two decades global tobacco use has significantly dropped, which was largely driven by decreased numbers of female smokers. Despite such advances, the use of e-cigarettes and waterpipes (shisha, hookah, narghile) is an emerging trend, especially among younger generations. There is growing body of evidence that e-cigarettes are not a harm-free alternative to tobacco cigarettes and there is considerable debate as to whether e-cigarettes are saving smokers or generating new addicts. Here, we provide an updated overview of the impact of tobacco/waterpipe (shisha) smoking and e-cigarette vaping on endothelial function, a biomarker for early, subclinical, atherosclerosis from human and animal studies. Also their emerging adverse effects on the proteome, transcriptome, epigenome, microbiome, and the circadian clock are summarized. We briefly discuss heat-not-burn tobacco products and their cardiovascular health effects. We discuss the impact of the toxic constituents of these products on endothelial function and subsequent CVD and we also provide an update on current recommendations, regulation and advertising with focus on the USA and Europe. As outlined by the WHO, tobacco cigarette, waterpipe, and e-cigarette smoking/vaping may contribute to an increased burden of symptoms due to coronavirus disease 2019 (COVID-19) and to severe health consequences.
Ewastools: Infinium Human Methylation BeadChip pipeline for population epigenetics integrated into Galaxy
Authors: Murat Katarzyna , Grüning Björn , Poterlowicz Paulina Wiktoria , Westgate Gillian , Tobin Desmond J , Poterlowicz Krzysztof
Published: May 2020

Background

Infinium Human Methylation BeadChip is an array platform for complex evaluation of DNA methylation at an individual CpG locus in the human genome based on Illumina's bead technology and is one of the most common techniques used in epigenome-wide association studies. Finding associations between epigenetic variation and phenotype is a significant challenge in biomedical research. The newest version, HumanMethylationEPIC, quantifies the DNA methylation level of 850,000 CpG sites, while the previous versions, HumanMethylation450 and HumanMethylation27, measured >450,000 and 27,000 loci, respectively. Although a number of bioinformatics tools have been developed to analyse this assay, they require some programming skills and experience in order to be usable.

Results

We have developed a pipeline for the Galaxy platform for those without experience aimed at DNA methylation analysis using the Infinium Human Methylation BeadChip. Our tool is integrated into Galaxy (http://galaxyproject.org), a web-based platform. This allows users to analyse data from the Infinium Human Methylation BeadChip in the easiest possible way.

Conclusions

The pipeline provides a group of integrated analytical methods wrapped into an easy-to-use interface. Our tool is available from the Galaxy ToolShed, GitHub repository, and also as a Docker image. The aim of this project is to make Infinium Human Methylation BeadChip analysis more flexible and accessible to everyone.
Left bundle branch block revealing a primary small bowel carcinoid metastasizing to the interventricular septum
Authors: Said Sameh M , Nijjar Prabhjot , Klein Molly , John Ranjit
Published: May 2020

Carcinoid tumours of the heart occur most commonly as a result of metastatic disease and usually affect the right side of the heart. We report a case of a solitary carcinoid metastasis to the interventricular septum without hepatic involvement in a 74-year-old man.
Heat wave characteristics, mortality and effect modification by temperature zones: a time-series study in 130 counties of China
Authors: Sun Zhiying , Chen Chen , Yan Meilin , Shi Wanying , Wang Jiaonan , Ban Jie , Sun Qinghua , He Mike Z , Li Tiantian
Published: May 2020

Background

The substantial disease burden attributed to heat waves, and their increasing frequency and intensity due to climate change, highlight the importance of understanding the health consequences of heat waves. We explore the mortality risk due to heat wave characteristics, including the timing in the seasons, the day of the heat wave, the intensity and the duration, and the modifying effect of temperature zones.

Methods

Heat waves were defined as ≥ 2 days with a temperature ≥99th percentile for the county from 1 May through 30 September. Heat waves were characterized by their intensity, duration, timing in the season, and day of the heat wave. Within each county, we estimated the total non-accidental death and cardiovascular disease mortality during each heat wave compared with non-heat wave days by controlling for potential confounders in summer. We combined individual heat wave effect estimates using a random-effects model to calculate overall effects at the temperature zone and national levels.

Results

The average daily total number of non-accidental deaths was nine in the warm season (across all the counties). Approximately half of the daily total number of non-accidental deaths were cardiovascular-related deaths (approximately four persons per day). The average and maximum temperatures across the study area were 23.1 °C (range: -1.2–35.9 °C) and 28.3 °C (range: 5.4–42.8 °C), respectively. The average relative humidity during the study was 68.9% (range: 8.0–100.0%). Heat waves increase the risk of total non-accidental death by 15.7% [95% confidence interval (CI): 12.5, 18.9] compared with non-heat wave periods, and the risk of cardiovascular-related death increases by 22.0% (95% CI: 16.9, 27.4). The risk of non-accidental death during the first heat wave of the season increases by 16.3% (95% CI: 12.6, 20.2), the risk during the second heat wave increases by 6.3% (95% CI: 2.8, 9.9) and during subsequent heat waves increases by -2.1% (95% CI: -4.6, 0.4). The first day and the second to third days of heat waves increase the risk of total non-accidental death by 11.7% (95% CI: 7.6, 15.9) and 17.0% (95% CI: 13.1, 21.0), respectively. Effects of heat waves on mortality lasted more than 4 days (6.3%, 95% CI: 2.4, 10.5) and are non-significantly different from the first day of heat waves. We found non-significant differences of the heat wave-associated mortality risks across mid-, warm and subtropical temperature zones.

Conclusions

In China, the effect of heat waves on mortality is acute, and varies by certain characteristics of heat waves. Given these results, national heat wave early warning systems should be developed, as well as precautions and protection warranted according to characteristics of heat waves.
Development and validation of a dosing nomogram for amoxicillin in infective endocarditis
Authors: Rambaud Antoine , Gaborit Benjamin Jean , Deschanvres Colin , Le Turnier Paul , Lecomte Raphaël , Asseray-Madani Nathalie , Leroy Anne-Gaëlle , Deslandes Guillaume , Dailly Éric , Jolliet Pascale , Boutoille David , Bellouard Ronan , Gregoire Matthieu ,   the Nantes Anti-Microbial Agents PK/PD (NAMAP) study group, Raffi Francois , Boutoille David , Biron Charlotte , Lefebvre Maeva , Gaborit Benjamin Jean , Turnier Paul L E , Deschanvres Colin , Lecomte Raphael , Chauveau Marie , Asseray Nathalie , Gregoire Matthieu , Bellouard Ronan , Deslandes Guillaume , Dailly Eric , Leroy Anne-Gaëlle , Corvec Stéphane , Bemer Pascale , Caillon Jocelyne , Guillouzouic Aurélie , Huon Jean-François , Navas Dominique , Raffi Francois , Boutoille David , Biron Charlotte , Lefebvre Maeva , Gaborit Benjamin Jean , Turnier Paul L E , Deschanvres Colin , Lecomte Raphael , Chauveau Marie , Asseray Nathalie , Gregoire Matthieu , Bellouard Ronan , Deslandes Guillaume , Dailly Eric , Leroy Anne-Gaëlle , Corvec Stéphane , Bemer Pascale , Caillon Jocelyne , Guillouzouic Aurélie , Huon Jean-François , Navas Dominique
Published: May 2020

Background

Amoxicillin is the first-line treatment for streptococcal or enterococcal infective endocarditis (IE) with a dose regimen adapted to weight.

Objectives

Covariates influencing pharmacokinetics (PK) of amoxicillin were identified in order to develop a dosing nomogram based on identified covariates for individual adaptation.

Patients and methods

Patients treated with amoxicillin administered by continuous infusion for IE were included retrospectively. The population PK analysis was performed using the Pmetrics package for R (NPAG algorithm). Influence of weight, ideal weight, height, BMI, body surface area, glomerular filtration rate adapted to the body surface area and calculated by the CKD-EPI method (mL/min), additional ceftriaxone treatment and serum protein level on amoxicillin PK was tested. A nomogram was then developed to determine the daily dose needed to achieve a steady-state free plasma concentration above 4× MIC, 100% of the time, without exceeding a total plasma concentration of 80 mg/L.

Results

A total of 160 patients were included. Population PK analysis was performed on 540 amoxicillin plasma concentrations. A two-compartment model best described amoxicillin PK and the glomerular filtration rate covariate significantly improved the model when included in the calculation of the elimination constant Ke.

Conclusions

This work allowed the development of a dosing nomogram that can help to increase achievement of the PK/pharmacodynamic targets in IE treated with amoxicillin.
A review of auditing techniques for the Unified Medical Language System
Authors: Zheng Ling , He Zhe , Wei Duo , Keloth Vipina , Fan Jung-Wei , Lindemann Luke , Zhu Xinxin , Cimino James J , Perl Yehoshua
Published: May 2020

Objective

The study sought to describe the literature related to the development of methods for auditing the Unified Medical Language System (UMLS), with particular attention to identifying errors and inconsistencies of attributes of the concepts in the UMLS Metathesaurus.

Materials and Methods

We applied the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach by searching the MEDLINE database and Google Scholar for studies referencing the UMLS and any of several terms related to auditing, error detection, and quality assurance. A qualitative analysis and summarization of articles that met inclusion criteria were performed.

Results

Eighty-three studies were reviewed in detail. We first categorized techniques based on various aspects including concepts, concept names, and synonymy (n = 37), semantic type assignments (n = 36), hierarchical relationships (n = 24), lateral relationships (n = 12), ontology enrichment (n = 8), and ontology alignment (n = 18). We also categorized the methods according to their level of automation (ie, automated systematic, automated heuristic, or manual) and the type of knowledge used (ie, intrinsic or extrinsic knowledge).

Conclusions

This study is a comprehensive review of the published methods for auditing the various conceptual aspects of the UMLS. Categorizing the auditing techniques according to the various aspects will enable the curators of the UMLS as well as researchers comprehensive easy access to this wealth of knowledge (eg, for auditing lateral relationships in the UMLS). We also reviewed ontology enrichment and alignment techniques due to their critical use of and impact on the UMLS.
AFI Corp. PixeeMo™ for Enumeration of Aerobic Bacteria in Drinking Water: AOAC Performance Tested MethodSM 012002
Authors: Wakizaka Yoshikazu , Itoi Takayuki , Takano Masayo , Kato Eiko , Sato Yusei , Morita Satoshi , Enjoji Takaharu
Published: May 2020

Background

PixeeMo™ is a compact instrument that enables bacterial cell counting using microfluidic chips instead of counting of colonies on culture media. Chips containing electrodes, based on fluid, electric filtering and sorting technology (FES), allow the selection of bacterial cells from other components in the sample. In the United States (US), surface water or ground water affected by surface water must be treated to reduce the total microbial load to less than 500 CFU/mL. In Japan, drinking water regulations limit the total bacterial load to 100 CFU/mL.

Objective

To validate the PixeeMoTM aerobic bacteria method based on the Japanese regulation in the range of 30–300 CFU/mL in drinking water.

Method

PixeeMoTM aerobic bacteria method was compared to the Standard Method for the Examination of Water and Wastewater (SMEWW) 9215B (2017) using naturally contaminated drinking water.

Results

The maximum repeatability standard deviation of the PixeeMoTM method was 14.8%. The difference of mean log10 values between the PixeeMoTM and SMEWW 9215B methods ranged from −0.015 to 0.258. Similar results were obtained in the independent laboratory study.

Conclusions

The PixeeMoTM method is equivalent to that of the SMEWW 9215B methods. The product consistency and stability study demonstrated no significant difference within the expiration date. The robustness study confirmed that there was no effect within the expected range. The instrument variation study also demonstrated no significant difference among the data of three PixeeMoTM instruments.

Highlights

Total counts of bacteria in drinking water can be determined accurately within 1 h with PixeeMoTM.
Differences in enzymatic activity in wild long-arm river prawns, Macrobrachium tenellum (Smith, 1871) (Decapoda: Caridea: Palaemonidae), from different habitats
Authors: de los Santos-Romero Rodolfo , Peña Emyr , Álvarez-González Carlos Alfonso , Cruz-Ramírez Fernanda , López-Vásquez Joshua , García-Guerrero Marcelo U
Published: May 2020

Studies on the nutrition of wild populations of freshwater prawns, valuable in the determination of feeding habits and requirements, are scarce or inadequate. We analyzed the digestive tract of individuals of Macrobrachium tenellum (Smith, 1871) (Palaemonidae) sampled from three different coastal habitats (an estuary, a lagoon, and a river) in the southeastern Mexico Pacific coast to determine if individuals show any variations in their enzymatic activities. Prawns of different size (adult or juvenile) showed the most significant differences among them in the kind and amount of enzyme activity, whereas location and sex differences resulted in less significant differences. Results suggest that feeding habits and not habitat, are the main cause of differences between age classes.
Disgusted and Afraid: Consumer Choices under the Threat of Contagious Disease
Authors: Galoni Chelsea , Carpenter Gregory S , Rao Hayagreeva
Published: May 2020

Consumers regularly encounter cues of contagious disease in daily life—a commuter sneezes on the train, a colleague blows their nose in a meeting, or they read recent headlines about the dangerous spread of a disease. Research has overwhelmingly argued that the dominant response to these cues is disgust—an emotion that leads to a desire to reject and avoid potential contamination. We argue, however, that contagious disease cues can also elicit fear. Across four experiments and two large empirical data analyses of the presence of contagious disease on actual consumption behavior, we find that cues of contagious disease increase both fear and disgust, and these emotions together form a unique behavioral tendency with respect to consumer behavior. Relative to either emotion alone, disgust and fear increase preference for more-familiar products asymmetrically over less-familiar ones. These results contribute theoretically to research on complex emotional states and the behavioral tendencies of emotions, document a systematic and consequential impact of contagious disease cues on real consumption behavior, and have significant practical implications for marketers.
COVID-19 and reproductive justice in Great Britain and the United States: ensuring access to abortion care during a global pandemic
Authors: Romanis Elizabeth Chloe , Parsons Jordan A , Hodson Nathan
Published: May 2020

In this paper we consider the impact that the COVID-19 pandemic is having on access to abortion care in Great Britain (GB) (England, Wales, and Scotland) and the United States (US). The pandemic has exacerbated problems in access to abortion services because social distancing or lockdown measures, increasing caring responsibilities, and the need to self-isolate are making clinics much more difficult to access, and this is when clinics are able to stay open which many are not. In response we argue there is a need to facilitate telemedical early medical abortion in order to ensure access to essential healthcare for people in need of terminations. There are substantial legal barriers to the establishment of telemedical abortion services in parts of GB and parts of the US. We argue that during a pandemic any restriction on telemedicine for basic healthcare is an unjustifiable human rights violation and, in the US, is unconstitutional.
Risk factors for severe gastrointestinal toxicity in patients receiving palliative radiotherapy for metastatic bone tumors: association with the use of molecular-targeted agents
Authors: Murakami Yuji , Kenjo Masahiro , Ishikawa Kazuki , Sakayauchi Toru , Itasaka Satoshi , Negoro Yoshiharu , Jingu Keiichi , Nishimura Yasumasa , Nagata Yasushi , Ogawa Kazuhiko
Published: May 2020

This study aimed to investigate whether the use of molecular-targeted agents could affect gastrointestinal (GI) toxicity in palliative radiotherapy (RT) for metastatic bone tumors in the abdominopelvic region. We collected data of patients who received palliative RT for bone metastases in the abdominopelvic region between 2013 and 2014 from six institutions. Data of 395 patients were collected and184 patients received molecularly targeted therapy, of whom 80 received vascular endothelial growth factor (VEGF)-targeted agents. For 556 lesions, 410 sessions of irradiation were undergone. GI toxicity of ≥G3 was observed in 3.8% of patients. The incidence rates of ≥G3 GI toxicity in patients without targeted agents use, in those using VEGF-targeted agents and in those using non-VEGF-targeted agents were 3.8, 7.5 and 1.0%, respectively. Regarding risk factors of the occurrence of ≥G3 GI toxicity, univariate analysis in all patients showed that a history of abdominopelvic surgery was a significant risk factor (P = 0.01), and the use of VEGF-targeted agents showed a trend of high incidence (P = 0.06). In patients using VEGF-targeted agents, both univariate and multivariate analysis showed that combined anticoagulant use (P = 0.03 and 0.01) and agent use between 1 week before and after RT (P = 0.046 and 0.03) were significant risk factors. In conclusion, the history of abdominopelvic surgery was associated with ≥G3 GI toxicity and the use of VEGF-targeted agents showed a trend for high incidence. When using VEGF-targeted agents, caution should be exercised in the combined use of anticoagulants and in the agent use between 1 week before and after RT.
Laparoscopic repair of Morgagni’s hernia in an elderly female patient
Authors: Leite Cláudia , Aveiro Débora , Simão Rosa , Coelho Sandra , Casimiro Carlos
Published: May 2020

Morgagni’s hernia is a very uncommon congenital diaphragmatic hernia. A few patients may remain asymptomatic until adulthood. Clinical presentation may include bowel obstruction, chest pain or dyspnoea. The authors report the case of a 71-year-old female patient, admitted to the emergency department due to respiratory symptoms, whose thoracic computed tomography revealed a large Morgagni’s hernia, containing colon. She underwent an elective laparoscopic repair with mesh. Thoracic computed tomography is the best imaging study for its diagnosis. Laparoscopic repair is safe and allows symptomatic relief and incarceration risk reduction.
The physiology of drought stress in grapevine: towards an integrative definition of drought tolerance
Authors: Gambetta Gregory A , Herrera Jose Carlos , Dayer Silvina , Feng Quishuo , Hochberg Uri , Castellarin Simone D
Published: May 2020

Water availability is arguably the most important environmental factor limiting crop growth and productivity. Erratic precipitation patterns and increased temperatures resulting from climate change will likely make drought events more frequent in many regions, increasing the demand on freshwater resources and creating major challenges for agriculture. Addressing these challenges through increased irrigation is not always a sustainable solution so there is a growing need to identify and/or breed drought-tolerant crop varieties in order to maintain sustainability in the context of climate change. Grapevine (Vitis vinifera), a major fruit crop of economic importance, has emerged as a model perennial fruit crop for the study of drought tolerance. This review synthesizes the most recent results on grapevine drought responses, the impact of water deficit on fruit yield and composition, and the identification of drought-tolerant varieties. Given the existing gaps in our knowledge of the mechanisms underlying grapevine drought responses, we aim to answer the following question: how can we move towards a more integrative definition of grapevine drought tolerance?
On the Edge of Death—To Intervene or Not
Authors: Zoretich Alexander , Venkat Arvind
Published: May 2020

Advance directives and actionable medical orders are documents that convey a patient’s wishes regarding medical treatment. Common advance directives are living will and health care power-of-attorney documents. Living wills state what a patient wants if not able to communicate for themselves and having an end-stage medical condition or permanent unconsciousness. Health care powers of attorney state whom a patient would want to make medical decisions on their behalf if not able to communicate for themselves. Both of these documents have minimal application in the emergency department given the time constraints of care in this setting. Actionable medical orders, such as Physician Orders for Life-Sustaining Treatment (POLSTs), have immediate application in the emergency department but carry their own challenges in interpretation by emergency physicians. This chapter reviews the nature of advance directives and actionable medical orders and the legal and ethical challenges posed by their application in the emergency department.
Saving Grandpa?
Authors: Shaikh Ahmed , Simon Jeremy R.
Published: May 2020

This chapter discusses the appropriate response of emergency physicians to requests by patients or family to provide treatment that the physician considers futile. The term’s meaning and its scope of application in the emergency department are discussed as well.
Failed Suicide Attempt in the Terminally Ill
Authors: Iserson Kenneth V. , Baker Eileen F.
Published: May 2020

Emergency physicians may be faced with patients at the end of life who present with failed suicide attempts. This presents an ethical dilemma for both those in states where physician-assisted suicide is legal and those in states without such statutes. All 50 states have provisions for upholding the autonomy of competent patients to make decisions about end-of-life care. Three options are available to the emergency physician caring for a terminally ill patient with a failed suicide attempt: to assist a patient in completing an intended suicide (active euthanasia), to offer palliative care (passive euthanasia), or to override the patient’s wishes and provide life-saving treatment (standard treatment). When the patient’s wishes are clear, offering palliative treatment provides care in keeping with the patient’s desire to avoid pain and suffering. In situations in which questions exist regarding the patient’s wishes, a more conservative approach, aimed at stabilizing the patient, should be sought. Ethical and legal consultations are advised.
Managing Bias and Belligerence
Authors: Markus Shannon , Wolfe Carmen
Published: May 2020

The emergency department sees patients from all walks of life, each coming with their own biases and preconceptions. How do we address discriminatory comments or requests for physician reassignment based on race or gender? A difficult balance exists when this occurs in an emergency setting, placing our duty to treat in conflict with a patient’s autonomy and right to refuse care. By exploring the emergent nature of patients’ conditions, their decision-making capacity, specific reasons for their request, and options for response, we can make informed decisions about options to negotiate with the patient or possibly even accommodate a patient if a middle ground cannot be found.
“12/10” Abdominal Pain
Authors: Kraus Chadd K.
Published: May 2020

Pain is the most common reason for presentation to the emergency department (ED). Treating pain and eliciting the etiology of pain are fundamental responsibilities of emergency physicians. Frequently termed drug-seeking behavior, presentations of pain in patients with a history of drug misuse or drug addiction and dependence that are unrelated to an acute injury or illness can pose an ethical dilemma for emergency physicians. Emergent etiologies for the patient’s pain must be excluded and might require diagnostic testing, such as laboratory or imaging studies. The emergency physician should not assume that the patient has no injury or illness and is simply drug seeking. Nonnarcotic, nonpharmacologic, or opioids or other analgesics might be the appropriate treatment for a patient with a history of drug-seeking behavior, addiction, or dependence depending on the clinical situation.
Fear and Loathing in the ED: When Staff Are Afraid to Provide Compassionate Care
Authors: Robey Thomas E. , Brenner Jay M.
Published: May 2020

Opiate use disorder has a wide range of physical and social complications that often present first in the emergency department. Physiological dependence may interfere with a patient’s own attempts to detox from opiate drug use. As a result, emergency providers are faced with difficulty discerning an opiate-dependent patient’s genuine intent, especially when he or she is experiencing withdrawal. Seemingly paternalistic actions may be justified when the patient’s stated goals of “getting clean” conflict with his or her more urgent demands for opiates to end debilitating withdrawal symptoms. Individual capacity may be compromised by drug dependence. Novel approaches adapted to the emergency setting, such as medication-assisted therapy (MAT) with buprenorphine induction can help patients suffering from opiate withdrawal and mitigate conflict that may occur when patients feel undertreated by typical pharmacological approaches to withdrawal. Clinical, mental health, and legal options exist to help treat opiate withdrawal, but their applications are not without ethical dilemmas.
“I Want a Baby, But Not With Him”
Authors: Li-Sauerwine Simiao , Gorgas Diane L.
Published: May 2020

This chapter addresses the ethical issues surrounding provision of emergency contraception in the emergency department. The highlighted case illustrates a case in which a nulliparous woman presents to the emergency department after consensual intercourse and requests emergency contraception. We review recommendations by national organizations regarding emergency contraception, including for which patients and in what situations emergency contraception should be offered. We discuss the disparity between providers in offering emergency contraception and drivers of this disparity, including patient characteristics and provider personal beliefs and education about emergency contraception. Finally, we discuss the validity of conscientious objection in providing emergency contraception in the framework of the principles of medical ethics: autonomy, beneficence, and nonmaleficence.
Making a Diagnosis
Authors: Post Robert M.
Published: May 2020

Bipolar disorder often has long delays to first diagnosis and treatment. Both early onset and treatment delay are risk factors for a poor outcome in adulthood. Poor recognition and treatment of the illness can lead to an accumulation of episodes with their attendant risks for cycle acceleration, neurobiological abnormalities, treatment resistance, cognitive dysfunction, and premature loss of many years of life expectancy. Complicating the appropriate diagnosis is the highly variable presentation of the illness and its multiple imitators and comorbidities, including anxiety disorders, attention-deficit/hyperactivity disorder, oppositional defiant disorder, depression, and substance abuse. One of the most critical keys to correct diagnosis is the longitudinal perspective, both retrospectively assessed in detail and systematically continued prospectively. Awareness of the high incidence of childhood-onset bipolar disorder in the United States compared with Canada and most European countries will hopefully lead to correction of one of the remedial risk factors for a poor outcome—the duration of delay to first treatment. With early and sustained treatment of a first episode of mania, episode recurrence and its attendant cognitive dysfunction may be prevented. Episodes, stressors, and bouts of substance abuse can accumulate and sensitize to further and more severe occurrences, likely on an epigenetic basis. Early diagnosis and treatment are imperative to stopping these mechanisms of illness progression in bipolar disorder.
Assessment Tools
Authors: Youngstrom Eric A. , Janos Jessica A. , Langfus Joshua A.
Published: May 2020

Bipolar disorders are difficult to diagnose and treat, despite their global prevalence and pervasiveness. With the proper tools, however, clinicians and researchers alike are able to detect bipolar disorders in their patients and establish the proper treatment plans. Knowing the prevalence of bipolar disorders and other common diagnoses in a specific setting, gathering predictive information before the first visit, and screening patients with efficient, low-cost assessment options are a few of the ways that clinicians can be better prepared to detect bipolar disorders in their patients. Further, assessment should not halt once a diagnosis is established; brief, recurring measures to collect data about a patient’s current state throughout treatment offer important information about symptoms, progress, and how a treatment plan can be tailored to meet a client’s ongoing needs. This chapter equips clinicians and researchers with the tools to confidently diagnose their patients with bipolar disorders, suggesting tips to establish diagnostic hypotheses as well as specific assessments for both adults and youths for whom the diagnosis seems likely. Technology in particular offers the opportunity to access low-cost assessment options and administer ongoing measures to ensure that clinicians continue to meet their patients’ needs throughout the treatment process.
The influence of age on neurorehabilitation
Authors: Wirz Markus , Rutz-LaPitz Louise
Published: May 2020

This chapter addresses issues related to neurorehabilitation of elderly patients. As society is growing older, the age of patients referred to rehabilitation is also increasing. This is evident in patients with spinal cord injury, which was classically a condition affecting young individuals. The stroke population is typically older. However, the age at the occurrence of stroke is also increasing. There is no clear criterion when a patient is considered old. Defining age exclusively by means of years of one’s life is insufficient. Nowadays, seniors can be healthy, active, and fit. In principle, there is no specific rehabilitation strategy for the aged. However, there are a number of age-related conditions that have to be accounted for during rehabilitation. It is the challenge of the rehabilitation team to uncover and reinforce resources while considering age-related impairments and limitations to return the person to their home, possibly for further rehabilitation, as soon as possible.
Autonomous nervous system dysfunction
Authors: Nightingale Tom E. , Mehnert Ulrich , Kessler Thomas M. , Krassioukov Andrei V.
Published: May 2020

This chapter provides a brief description of the structure and function of the autonomic nervous system (ANS), which is responsible for the involuntary control of visceral organs throughout the human body. The ANS has three main divisions: sympathetic, parasympathetic, and enteric. These continuously monitor and control cardiovascular, bronchopulmonary, sexual, thermoregulatory, lower urinary, and gastrointestinal tract functions. Normally the response of these systems to exercise, environmental challenges, and emotional stress are intricately regulated. ANS dysfunction is commonly prevalent in patients with various neurodegenerative disorders. These can present due to either central or peripheral nervous system aetiologies. In order to determine a correct prognosis for these patients, accurate assessment techniques, described herein, are necessary. The underlying causes of specific autonomic system disorders are also discussed, along with descriptions of various treatment strategies. Medical advances in the field of neurorehabilitation now also provide promising alternative options to address autonomic dysfunctions.
Animal models of damage, repair, and plasticity in the spinal cord
Authors: Freund Patrick , Edgerton V. Reggie , Roy Roland R. , Lu Daniel C. , Gerasimenko Yury
Published: May 2020

Sensorimotor function can improve for years, even after a spinal cord injury (SCI). We also know that an effective intervention that can improve motor function is re-engagement of the spinal neural networks through supraspinal control and that this regularity in re-engagement is fundamental to learning within the activated sensorimotor circuits. Several interventions, ranging from monoclonal antibodies against neurit outgrowth inhibitors to epidural electrical stimulation, have been developed allowing individuals with a SCI to re-engage sensorimotor circuits. These interventions enable spinal neural circuits to neuromodulate the level of excitability closer to a near motor threshold state. This is because of the built-in level of automaticity within the spinal circuits that then is translated into motor commands specified by the sensory input. Another increasingly apparent feature of the spinal circuitry is the highly integrated nature of multiple physiological systems linked to load bearing sensory input. Thus, it is clear that multiple physiological systems are highly responsive to activity-dependent interventions after a severe SCI and that this responsiveness can persist for years post-injury and be therapeutically modulated.
The role of neuroimaging in understanding the impact of neuroplasticity after CNS damage
Authors: Ward Nick S.
Published: May 2020

After stroke, there is little restitution of neural tissue, but reorganization of surviving neural networks appears to be important for recovery of function. Non-invasive techniques such as functional magnetic resonance imaging and magnetoencephalography allow some aspects of this brain reorganization to be studied in humans. For example, early after stroke there appears to be an upregulation in task-related activity which diminishes with time, but more particularly with recovery. Those with the most complete recovery tend to have the most ‘normal’ activation patter, and those with less complete recovery tend to rely on additional brain regions. Disruption of activity in these additional regions can impair performance in stroke patients suggesting that these new patterns of brain activity can support what recovered function there is. In other words, this reorganization is functionally relevant. Advances in functional neuroimaging now allow the study of alterations in connections between brain regions. Understanding how brain organization is related to anatomical damage, as well as impairment and recovery that can take place over weeks and months following stroke opens the way for functional brain imaging to become a clinically useful tool in rehabilitation, particularly in our ability to predict outcomes and response to novel therapies. Understanding the dynamic process of systems level reorganization will allow greater understanding of the mechanisms of recovery and potentially improve our ability to deliver effective restorative therapy.
Rehabilitation of gait and balance after CNS damage
Authors: Duysens Jacques , Verheyden Geert , Massaad Firas , Meyns Pieter , Smits-Engelsman Bouwien , Jonkers Ilse
Published: May 2020

This chapter discusses the importance of basic and clinical science for the rehabilitation of patients with stroke or SCI (spinal cord injury). Examples are given from novel approaches in rehabilitation. Insights can be obtained by investigating normal locomotor or postural activity but it is argued that the use of more challenging locomotor tasks can provide much needed additional information. To update rehabilitation tools it is also essential to keep track of new technological developments and new assessment tools. Careful assessments, based on advanced 3D recordings of posture and gait, can assist in making proper decisions about planned interventions, aimed at alleviating some clinical symptoms such as spasticity. With respect to training, the focus here is on general principles of sensorimotor rehabilitation of gait and posture. Learning is context dependent. The consequence is that current rehabilitation approaches need to emphasize that training should be ‘task-oriented training’, and should involve the whole body.
Treatment of arm and hand dysfunction after CNS damage
Authors: Ward Nick S.
Published: May 2020

Residual upper limb dysfunction after injury to the central nervous system is a major clinical, socioeconomic, and societal problem. Upper limb dysfunction can occur in many disorders of the central nervous system including cervical spinal cord injury and multiple sclerosis, but therapeutic approaches for upper limb dysfunction after stroke are the most thoroughly investigated. General approaches to treatment require (i) avoidance of complications such as spasticity, pain, and loss of range, (ii) early high dose engaging functional motor training, (iii) consideration of how neuroplastic processes might be engaged to enhance the effects of training. The evidence to deliver optimal personalized treatment strategies for all patients is lacking but there is evidence that higher doses and intensity of upper limb therapy will be beneficial to most patients. Recent work has focused on how technological innovation might be used to promote recovery of upper limb function.
Acquired disorders of language and their treatment
Authors: Leff Alex , Crinion Jenny
Published: May 2020

This chapter covers the classification of acquired aphasic syndromes. It illustrates some of the speech errors aphasic stroke patients make with videos of a patient describing a picture and attempting to repeat words. The main part of the chapter assesses the evidence base for speech and language therapy (SALT) and answers the following questions: Does SALT work? What is the correct dose and intensity? And is it ever too late for SALT intervention? We then discuss two main adjuvants to SALT: one old—drug therapy; one new—non-invasive brain stimulation. Finally, we examine the role for e-rehabilitation and augmentative aids before asking what the future might hold for aphasia therapy, and wondering if it might already be here.
Management of lower urinary tract, bowel, and sexual dysfunction
Authors: Mehnert Ulrich , Kessler Thomas M.
Published: May 2020

Lower urinary tract, bowel, and sexual dysfunctions are frequent sequelae of neurotrauma and neurodegenerative diseases that require adequate management. All three pelvic organ dysfunction severely compromise quality of life and can jeopardize health. Thus, treatment is mandatory and therapy options range from simple conservative measures to major surgery. The main therapeutic principles that should be considered in regard to treatment of pelvic organ dysfunction include protection of kidney function, reduction of urinary and/or faecal incontinence, independent management of lower urinary tract and bowel function, ability to sustain a satisfactory sexual relationship, fertility support, and improvement of quality of life. To comply with such principles and to select, initiate, maintain, and eventually adapt the ‘optimal’ treatment regimen for each patient requires a specialized multidisciplinary team not only during inpatient rehabilitation but also during outpatient follow-up.

This chapter provides an overview on the management of lower urinary tract, bowel, and sexual dysfunction and aims to sensitize healthcare professionals for this essential part/aspect of neurorehabilitation.
The assessment and treatment of pain syndromes in neurorehabilitation
Authors: Widerström-Noga Eva
Published: May 2020

Persistent pains associated with injuries or disease involving the central nervous system (CNS), are common. In order to optimally manage persistent pain, the primary underlying mechanisms need to be determined and the treatment targeted to these. A comprehensive pain evaluation including symptoms, sensory function/dysfunction, and psychosocial factors is critical to the translation of research into the clinical pain management, to increasing the understanding of the contributory mechanisms and factors, and to the development of effective pain management. This chapter focuses on the assessment of pain and sensory status, associated psychosocial factors, and pharmacological and non-pharmacological pain management after CNS injury and disease. Principles and utility of the various types of pain-related assessments and examinations including pain report, pain classification, quantitative sensory testing, and psychological factors are discussed. Finally, both pharmacological and non-pharmacological treatment options for these persistent pain conditions are reviewed and discussed in the context of putative mechanisms.