bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of an Experimentally Designed Molecular Imprinted Polyurethane Foam Performance for Extraction of Alprazolam
Authors: Tavakoli Zeynab , Soleimani Majid , Nikje Mir Mohammad Alavi
Published: April 2019

Industrial polyurethane rigid foam (PUF) was selected as a substrate for selective solid phase extraction of Alprazolam. Effective parameters for raising selectivity of the PUF were evaluated. Synthetic molecularly imprinted polyurethane foam (MIPUF) was tracked as selective adsorbent and its characteristic was pondered by analytical methods. Optimization was done by central composite design (CCD) to have high efficiency of the polymer adsorption. Two different extraction methods were compared in the selective adsorption processes using MIPUF and NIPUF, batch system and continuous (cartridge) system. Results of the adsorption of alprazolam on the MIPUF had 39% more recovery than NIPUF (reference polymer). Then, the proposed method suggests a selective extraction of mentioned analyte from urine and tablets as complex matrixes.
Atrial fibrillation screening with photo-plethysmography through a smartphone camera
Authors: Verbrugge Frederik H , Proesmans Tine , Vijgen Johan , Mullens Wilfried , Rivero-Ayerza Maximo , Van Herendael Hugo , Vandervoort Pieter , Nuyens Dieter
Published: April 2019

Aims

This cross-sectional study was set up to assess the feasibility of mass screening for atrial fibrillation (AF) with only the use of a smartphone.

Methods and results

A local newspaper published an article, allowing to subscribe for a 7-day screening period to detect AF. Screening was performed through an application that uses photo-plethysmography (PPG) technology by exploiting a smartphone camera. Participants received instructions on how to perform correct measurements twice daily, with notifications pushed through the application’s software. In case of heart rhythm irregularities, raw PPG signals underwent secondary offline analysis to confirm a final diagnosis. From 12 328 readers who voluntarily signed up for screening (49 ± 14 years; 58% men), 120 446 unique PPG traces were obtained. Photo-plethysmography signal quality was adequate for analysis in 92% of cases. Possible AF was detected in 136 individuals (1.1%). They were older (P < 0.001), more frequently men (P < 0.001), and had higher body mass index (P = 0.004). In addition, participants who strictly adhered to the recommended screening frequency (i.e. twice daily) were more often diagnosed with possible AF (1.9% vs. 1.0% in individuals who did not adhere; P = 0.008). Symptoms of palpitations, confusion, and shortness of breath were more frequent in case of AF (P < 0.001). The cumulative diagnostic yield for possible AF increased from 0.4% with a single heart rhythm assessment to 1.4% with screening during the entire 7-day screening period.

Conclusion

Mass screening for AF using only a smartphone with dedicated application based on PPG technology is feasible and attractive because of its low cost and logistic requirements.
Novel, Film and the Art of Translational Storytelling: Dai Sijie's Balzac et la petite tailleuse chinoise
Authors: Li Shuangyi
Published: April 2019

This article examines the novel and film Balzac et la Petite Tailleuse chinoise, by the Franco-Chinese writer and filmmaker Dai Sijie, the story of which takes place against the background of the Cultural Revolution. The first part of my analysis will make clear how the film illuminates and dramatizes the special texture, aesthetic and structure of the novel, highlighting the cinematic sensibility of Dai’s literary aesthetic. I then move on to investigate the linguistic aspects of the various translations between the novel and the film in French, Mandarin Chinese and Sichuanese. The aesthetic effects of dubbing, in particular, will allow me to investigate new possibilities of reading exophone literature. Finally, this paper highlights the central role of oral storytelling in the Chinese tradition in/through various forms of translation: interlingual as well as intermedial. In so doing, this article aims to add nuance to and enrich current debates on issues such as intercultural misreading and exoticism in Dai’s works.
Identifying Characteristics of Frailty in Female Mice Using a Phenotype Assessment Tool
Authors: Kwak Dongmin , Baumann Cory W , Thompson LaDora V
Published: April 2019

Preclinical studies are important in identifying the underlying mechanisms contributing to frailty. Frailty studies have mainly focused on male rodents with little directed at female rodents. Therefore, the purposes of this study were to identify the onset and prevalence of frailty across the life span in female mice, and to determine if frailty predicts mortality. Female C57BL/6 (n = 27) mice starting at 17 months of age were assessed across the life span using a frailty phenotype, which included body weight, walking speed, strength, endurance, and physical activity. The onset of frailty occurred at approximately 17 months (1/27 mice), with the prevalence of frailty increasing thereafter. At 17 months, 11.1% of the mice were pre-frail and by 26 months peaked at 36.9%. The percentage of frail mice progressively increased up to 66.7% at 32 months. Non-frail mice lived to 29 months whereas frail/pre-frail mice lived only to 26 months (p = .04). In closing, using a mouse frailty phenotype, we are able to identify that the prevalence of frailty in female mice increases across the life span and accurately predicts mortality. Together, this frailty phenotype has the potential to yield information about the underlying mechanisms contributing to frailty.
The first large-scale assessment of three-spined stickleback (Gasterosteus aculeatus) biomass and spatial distribution in the Baltic Sea
Authors: Olsson Jens , Jakubavičiūtė Eglė , Kaljuste Olavi , Larsson Niklas , Bergström Ulf , Casini Michele , Cardinale Massimiliano , Hjelm Joakim , Byström Pär
Published: April 2019

Declines in predatory fish in combination with the impact of climate change and eutrophication have caused planktivores, including three-spined stickleback (Gasterosteus aculeatus), to increase dramatically in parts of the Baltic Sea. Resulting impacts of stickleback on coastal and offshore foodwebs have been observed, highlighting the need for increased knowledge on its population characteristics. In this article, we quantify abundance, biomass, size structure, and spatial distribution of stickleback using data from the Swedish and Finnish parts of the Baltic International Acoustic Survey (BIAS) during 2001–2014. Two alternative methods for biomass estimation suggest an increase in biomass of stickleback in the Baltic Proper, stable or increasing mean size over time, and larger individuals toward the north. The highest abundance was found in the central parts of the Baltic Proper and Bothnian Sea. The proportion of stickleback biomass in the total planktivore biomass increased from 4 to 10% in the Baltic Proper and averaged 6% of the total planktivore biomass in the Bothnian Sea. In some years, however, stickleback biomass has ranged from half to almost twice that of sprat (Sprattus sprattus) in both basins. Given the recent population expansion of stickleback and its potential role in the ecosystem, we recommend that stickleback should be considered in future monitoring programmes and in fisheries and environmental management of the Baltic Sea.
Hedging in South Asia: balancing economic and security interests amid Sino-Indian competition
Authors: Lim Darren J , Mukherjee Rohan
Published: April 2019

The literature on hedging as a secondary state strategy – built largely on evidence from United States-China competition in East and Southeast Asia – focuses on conditions where a major power presents both an economic opportunity and a security threat. In South Asia, in contrast, secondary states facing strategic competition between India and China have pursued hedging strategies in the absence of a security threat. We develop a theoretical reconciliation of these two phenomena. Hedging at its core involves a trade-off between the material benefits and autonomy costs of cooperating with a major power in a competitive environment. States are likely to hedge when these benefits and costs are simultaneously rising. We test the plausibility of this theory in the cases of the Maldives and Sri Lanka. The autonomy trade-off operates both in the absence and in the presence of a security threat, thus offering a theoretical advancement with greater empirical scope.
Prevalence and molecular epidemiology of ESBLs, plasmid-determined AmpC-type β-lactamases and carbapenemases among diarrhoeagenic Escherichia coli isolates from children in Gwangju, Korea: 2007–16
Authors: Kim Kwang gon , Jeong Jin , Kim Min ji , Park Duck woong , Shin Ji hyun , Park Hye jung , Chung Jae keun , Kee Hye young
Published: April 2019

Objectives

Young children could act as important carriers of cefotaxime-resistant Enterobacteriaceae. However, most studies on these bacteria have focused on hospitalized adults. Therefore, we determined the prevalence and characteristics of ESBL-, plasmid-determined AmpC-type β-lactamase (PABL)- and carbapenemase-producing diarrhoeagenic Escherichia coli isolates mainly from infants and children in the south-west region of Korea over a 10 year period.

Methods

Non-duplicate E. coli clinical isolates were recovered from diarrhoeagenic patient specimens at 12 hospitals in Gwangju, Korea, between January 2007 and December 2016. Antimicrobial susceptibilities and molecular features of ESBL- and carbapenemase-producing isolates were determined.

Results

A total of 1047 pathogenic E. coli isolates were collected and 58 cefotaxime-resistant E. coli isolates (5.5%) were identified. The prevalence and types of β-lactamase genes increased steadily from 5.7% in 2007 to 11.6% in 2016 with some fluctuations. CTX-M-14 (53.4%) was the predominant CTX-M genotype. PFGE revealed high genetic heterogeneities among diarrhoeagenic E. coli isolates, suggesting horizontal transfer of antibiotic resistance genes, which was also proved by conjugation assay.

Conclusions

Progressive increases in carriage rates and the number of β-lactamase types, and the possibility of community outbreaks of these food-borne bacteria in young children, may pose tangible public health threats.
Estimation of Genetic Variance in Fitness, and Inference of Adaptation, When Fitness Follows a Log-Normal Distribution
Authors: Bonnet Timothée , Morrissey Michael B , Kruuk Loeske E B
Published: April 2019

Additive genetic variance in relative fitness (σA2(w)) is arguably the most important evolutionary parameter in a population because, by Fisher’s fundamental theorem of natural selection (FTNS; Fisher RA. 1930. The genetical theory of natural selection. 1st ed. Oxford: Clarendon Press), it represents the rate of adaptive evolution. However, to date, there are few estimates of σA2(w) in natural populations. Moreover, most of the available estimates rely on Gaussian assumptions inappropriate for fitness data, with unclear consequences. “Generalized linear animal models” (GLAMs) tend to be more appropriate for fitness data, but they estimate parameters on a transformed (“latent”) scale that is not directly interpretable for inferences on the data scale. Here we exploit the latest theoretical developments to clarify how best to estimate quantitative genetic parameters for fitness. Specifically, we use computer simulations to confirm a recently developed analog of the FTNS in the case when expected fitness follows a log-normal distribution. In this situation, the additive genetic variance in absolute fitness on the latent log-scale (σA2(l)) equals (σA2(w)) on the data scale, which is the rate of adaptation within a generation. However, due to inheritance distortion, the change in mean relative fitness between generations exceeds σA2(l) and equals (exp⁡(σA2(l))−1). We illustrate why the heritability of fitness is generally low and is not a good measure of the rate of adaptation. Finally, we explore how well the relevant parameters can be estimated by animal models, comparing Gaussian models with Poisson GLAMs. Our results illustrate 1) the correspondence between quantitative genetics and population dynamics encapsulated in the FTNS and its log-normal-analog and 2) the appropriate interpretation of GLAM parameter estimates.
Time to rethink the law on part-human chimeras
Authors: Koplin Julian J , Savulescu Julian
Published: April 2019

It may soon be possible to generate human tissues and organs inside of part-human chimeras via a technique known as interspecies blastocyst complementation. Using Australian legislation as a case study, we show why this technique of creating part-human chimeras falls within the gaps of existing legislation. We give an overview of the key ethical issues raised by part-human chimera research, and we describe how well these issues are met by a range of possible regulatory approaches. We ultimately argue that regulation of part-human chimera research should be (re)designed to balance two key aims: to facilitate ethical research involving part-human chimeras and to prevent unethical experimentation with chimeras that have an uncertain—and potentially substantial—degree of moral status.
Nitric oxide signaling, metabolism and toxicity in nitrogen-fixing symbiosis
Authors: Berger Antoine , Boscari Alexandre , Frendo Pierre , Brouquisse Renaud
Published: April 2019

Interactions between legumes and rhizobia lead to the establishment of a symbiotic relationship characterized by the formation of a new organ, the nodule, which facilitates the fixation of atmospheric nitrogen (N2) by nitrogenase through the creation of a hypoxic environment. Significant amounts of nitric oxide (NO) accumulate at different stages of nodule development, suggesting that NO performs specific signaling and/or metabolic functions during symbiosis. NO, which regulates nodule gene expression, accumulates to high levels in hypoxic nodules. NO accumulation is considered to assist energy metabolism within the hypoxic environment of the nodule via a phytoglobin–NO-mediated respiration process. NO is a potent inhibitor of the activity of nitrogenase and other plant and bacterial enzymes, acting as a developmental signal in the induction of nodule senescence. Hence, key questions concern the relative importance of the signaling and metabolic functions of NO versus its toxic action and how NO levels are regulated to be compatible with nitrogen fixation functions. This review analyses these paradoxical roles of NO at various stages of symbiosis, and highlights the role of plant phytoglobins and bacterial hemoproteins in the control of NO accumulation.
Nitrite and nitric oxide are important in the adjustment of primary metabolism during the hypersensitive response in tobacco
Authors: Mur Luis A J , Kumari Aprajita , Brotman Yariv , Zeier Jurgen , Mandon Julien , Cristescu Simona M , Harren Frans , Kaiser Werner M , Fernie Alisdair R , Gupta Kapuganti Jagadis
Published: April 2019

Nitrate and ammonia deferentially modulate primary metabolism during the hypersensitive response in tobacco. In this study, tobacco RNAi lines with low nitrite reductase (NiRr) levels were used to investigate the roles of nitrite and nitric oxide (NO) in this process. The lines accumulate NO2–, with increased NO generation, but allow sufficient reduction to NH4+ to maintain plant viability. For wild-type (WT) and NiRr plants grown with NO3–, inoculation with the non-host biotrophic pathogen Pseudomonas syringae pv. phaseolicola induced an accumulation of nitrite and NO, together with a hypersensitive response (HR) that resulted in decreased bacterial growth, increased electrolyte leakage, and enhanced pathogen resistance gene expression. These responses were greater with increases in NO or NO2– levels in NiRr plants than in the WT under NO3– nutrition. In contrast, WT and NiRr plants grown with NH4+ exhibited compromised resistance. A metabolomic analysis detected 141 metabolites whose abundance was differentially changed as a result of exposure to the pathogen and in response to accumulation of NO or NO2–. Of these, 13 were involved in primary metabolism and most were linked to amino acid and energy metabolism. HR-associated changes in metabolism that are often linked with primary nitrate assimilation may therefore be influenced by nitrite and NO production.
Root stem cell niche maintenance and apical meristem activity critically depend on THREONINE SYNTHASE1
Authors: Reyes-Hernández Blanca Jazmín , Shishkova Svetlana , Amir Rachel , Quintana-Armas Aranza Xhaly , Napsucialy-Mendivil Selene , Cervantes-Gamez Rocio Guadalupe , Torres-Martínez Héctor Hugo , Montiel Jesús , Wood Christopher D , Dubrovsky Joseph G
Published: April 2019

Indeterminate root growth depends on the stem cell niche (SCN) and root apical meristem (RAM) maintenance whose regulation permits plasticity in root system formation. Using a forward genetics approach, we isolated the moots koom1 (‘short root’ in Mayan) mutant that shows complete primary RAM exhaustion and abolished SCN activity. We identified that this phenotype is caused by a point mutation in the METHIONINE OVERACCUMULATOR2 (MTO2) gene that encodes THREONINE SYNTHASE1 and renamed the mutant as mto2-2. The amino acid profile showed drastic changes, most notorious of which was accumulation of methionine. In non-allelic mto1-1 (Arabidopsis thaliana cystathionine gamma-synthetase1) and mto3-1 (S-adenosylmethionine synthetase) mutants, both with an increased methionine level, the RAM size was similar to that of the wild type, suggesting that methionine overaccumulation itself did not cause RAM exhaustion in mto2 mutants. When mto2-2 RAM is not yet completely exhausted, exogenous threonine induced de novo SCN establishment and root growth recovery. The threonine-dependent RAM re-establishment in mto2-2 suggests that threonine is a limiting factor for RAM maintenance. In the root, MTO2 was predominantly expressed in the RAM. The essential role of threonine in mouse embryonic stem cells and in RAM maintenance suggests that common regulatory mechanisms may operate in plant and animal SCN maintenance.
Interaction of bZIP transcription factor TGA6 with salicylic acid signaling modulates artemisinin biosynthesis in Artemisia annua
Authors: Lv Zongyou , Guo Zhiying , Zhang Lida , Zhang Fangyuan , Jiang Weimin , Shen Qian , Fu Xueqing , Yan Tingxiang , Shi Pu , Hao Xiaolong , Ma Yanan , Chen Minghui , Li Ling , Zhang Lei , Chen Wansheng , Tang Kexuan
Published: April 2019

Artemisinin is a sesquiterpene lactone produced by the Chinese traditional herb Artemisia annua and is used for the treatment of malaria. It is known that salicylic acid (SA) can enhance artemisinin content but the mechanism by which it does so is not known. In this study, we systematically investigated a basic leucine zipper family transcription factor, AaTGA6, involved in SA signaling to regulate artemisinin biosynthesis. We found specific in vivo and in vitro binding of the AaTGA6 protein to a ‘TGACG’ element in the AaERF1 promoter. Moreover, we demonstrated that AaNPR1 can interact with AaTGA6 and enhance its DNA-binding activity to its cognate promoter element ‘TGACG’ in the promoter of AaERF1, thus enhancing artemisinin biosynthesis. The artemisinin contents in AaTGA6-overexpressing and RNAi transgenic plants were increased by 90–120% and decreased by 20–60%, respectively, indicating that AaTGA6 plays a positive role in artemisinin biosynthesis. Importantly, heterodimerization with AaTGA3 significantly inhibits the DNA-binding activity of AaTGA6 and plays a negative role in target gene activation. In conclusion, we demonstrate that binding of AaTGA6 to the promoter of the artemisinin-regulatory gene AaERF1 is enhanced by AaNPR1 and inhibited by AaTGA3. Based on these findings, AaTGA6 has potential value in the genetic engineering of artemisinin production.
NF-YC12 is a key multi-functional regulator of accumulation of seed storage substances in rice
Authors: Xiong Yufei , Ren Ye , Li Wang , Wu Fengsheng , Yang Wenjie , Huang Xiaolong , Yao Jialing
Published: April 2019

Starch and storage proteins, the primary storage substances of cereal endosperm, are a major source of food for humans. However, the transcriptional regulatory networks of the synthesis and accumulation of storage substances remain largely unknown. Here, we identified a rice endosperm-specific gene, NF-YC12, that encodes a putative nuclear factor-Y transcription factor subunit C. NF-YC12 is expressed in the aleurone layer and starchy endosperm during grain development. Knockout of NF-YC12 significantly decreased grain weight as well as altering starch and protein accumulation and starch granule formation. RNA-sequencing analysis revealed that in the nf-yc12 mutant genes related to starch biosynthesis and the metabolism of energy reserves were enriched in the down-regulated category. In addition, starch and protein contents in seeds differed between NF-YC12-overexpression lines and the wild-type. NF-YC12 was found to interact with NF-YB1. ChIP-qPCR and yeast one-hybrid assays showed that NF-YC12 regulated the rice sucrose transporter OsSUT1 in coordination with NF-YB1 in the aleurone layer. In addition, NF-YC12 was directly bound to the promoters of FLO6 (FLOURY ENDOSPERM6) and OsGS1;3 (glutamine synthetase1) in developing endosperm. This study demonstrates a transcriptional regulatory network involving NF-YC12, which coordinates multiple pathways to regulate endosperm development and the accumulation of storage substances in rice seeds.
Nucleocytosolic mRNA transport in plants: export factors and their influence on growth and development
Authors: Ehrnsberger Hans F , Grasser Marion , Grasser Klaus D
Published: April 2019

In eukaryotes, the regulated transport of mRNAs from the cell nucleus to the cytosol is a critical step in the expression of protein-coding genes, as it links nuclear mRNA synthesis with cytosolic translation. The pre-mRNAs that are synthesised by RNA polymerase II are processed by 5´-capping, splicing, and 3´-polyadenylation. The multi-subunit THO/TREX complex integrates mRNA biogenesis with their nucleocytosolic transport. Various export factors are recruited to the mRNAs during their maturation, which occurs essentially co-transcriptionally. These RNA-bound export factors ensure efficient transport of the export-competent mRNAs through nuclear pore complexes. In recent years, several factors involved in plant mRNA export have been functionally characterised. Analysis of mutant plants has demonstrated that impaired mRNA export causes defects in growth and development. Moreover, there is accumulating evidence that mRNA export can influence processes such as plant immunity, circadian regulation, and stress responses. Therefore, it is important to learn more details about the mechanism of nucleocytosolic mRNA transport in plants and its physiological significance.
Minority Stress Theory and Internalized Prejudice
Authors: Crawford Christine , Sangermano Lisa , Trinh Nhi-Ha T.
Published: April 2019

Minority groups within the United States continuously endure stress placed upon them by the dominant culture. The ongoing stresses of racism, prejudice, and discrimination have lasting and deleterious effects on minorities’ physical and emotional well-being. In this chapter, we provide an overview of the concept of minority stress theory and describe the various sociological and psychological constructs contributing to its development. We then examine the various elements of internalized prejudice, review validated measurement scales used to quantify internalized prejudice in minority populations, and present evidence on the role of internalized prejudice in a number of psychiatric conditions. We discuss the concept of intersectionality and its implications for mental health. At the end of this chapter, we provide clinical recommendations to address the complexities of minority stress theory and internalized prejudice in psychiatric illness.
Implicit Bias in Mental Health Care
Authors: Heberlein Andrea S. , Chen Justin A. , Trinh Nhi-Ha T.
Published: April 2019

Explicit attitudes are obviously predictive of behavior. However, two decades of research has shown that implicit attitudes have greater predictive validity than explicit attitudes in a particular set of situations. This chapter defines implicit and explicit attitudes and associations and reviews the scientific literature regarding implicit bias in the medical, psychology, and psychiatry literature. The authors pay specific attention to documented effects of implicit bias related to race and ethnicity, as well as to mental health diagnoses and body weight. The authors also outline interventions to decrease implicit bias in clinical care, as well as pitfalls to avoid when attempting to decrease implicit bias.
Responding to Patients’ Provider Preferences
Authors: Reynolds Kimberly L. , Knight Rodriguez Kira , Rupert Loucresie , Owusu Michaela
Published: April 2019

In today’s increasingly diverse world, patients will inevitably interact with physicians who are of very different racial, ethnic, religious, and/or geographical backgrounds from themselves. When a patient requests a physician of another race, religion, or gender, or one who speaks another language, the physician must take many factors into consideration when determining whether to accede to the request. These considerations include historical factors (e.g., bigotry vs. the potential benefits of race concordance), ethical considerations (e.g., autonomy, justice), patient factors (e.g., the patient’s decision-making capacity), and organizational factors (e.g., policies and procedures to respect both patients and providers). This chapter presents a general framework to help psychiatrists to make these sometimes difficult decisions. Case vignettes are provided and analyzed throughout the chapter.
Functional Neuroanatomy of Autonomic Nervous System
Authors: Novak Peter
Published: April 2019

A basic understanding of the functional and physiological structure of the autonomic nervous system (ANS) is essential in interpreting test results. This chapter summarizes the functional anatomy of the ANS. The ANS has been divided into the central autonomic system (CAN), also called preganglionic system, and the peripheral (or postganglionic system), which includes the parasympathetic system, sympathetic system, and enteric system. The anatomy and functions of the ANS and its various divisions are explained. Also described is the anatomy and functions of the baroreceptor reflex (BR), which is important in controlling the heart rate and blood pressure.
Laboratory Equipment
Authors: Novak Peter
Published: April 2019

This chapter describes the main characteristics of laboratory equipment used in autonomic testing.
Case 6: Syncope, Neurally Mediated with Prolonged Asystole
Authors: Novak Peter
Published: April 2019

This chapter describes a characteristic pattern of neurally mediated mixed syncope on the tilt test with prolonged asystole.
Case 23: Orthostatic Cerebral Hypoperfusion Syndrome, Severe
Authors: Novak Peter
Published: April 2019

The tilt test showed severe orthostatic cerebral hypoperfusion syndrome (OCHOS) with reduced cerebral blood flow velocity. OCHOS is associated with reduced orthostatic cerebral blood flow velocity without orthostatic hypotension or arrhythmia.
Case 36: Orthostatic Hypertension
Authors: Novak Peter
Published: April 2019

Orthostatic hypertension is a syndrome associated with a rise in orthostatic blood pressure, for example in essential hypertension, diabetes, and dysautonomia. Therapy with calcium channel blockers may reduce hypertension and also may improve cerebral perfusion since calcium channel blockers dilate cerebral vessels.
Case 53: Small Fiber Neuropathy with Striational Antibodies
Authors: Novak Peter
Published: April 2019

This case describes neuropathic postural tachycardia syndrome (POTS) with striational antibodies that can be associated with small fiber neuropathy and respond to IVIG.
Case 54: Polyneuropathy Affecting Large and Small Fibers in Multiple Autoimmune Disorders
Authors: Novak Peter
Published: April 2019

This patient had diagnoses of multiple autoimmune disorders including Sjögren syndrome, rheumatoid arthritis, and systemic lupus erythematosus. Sjögren syndrome can be accompanied by severe painful neuropathy and dysautonomia. Orthostatic intolerance was due to cerebral autoregulatory failure.
Case 57: Small Fiber Neuropathy and Hypocapnic Cerebral Hypoperfusion with Elevated Antibodies to N-type Calcium Channel
Authors: Novak Peter
Published: April 2019

Autonomic testing revealed severe small fiber neuropathy and severe hypocapnic cerebral hypoperfusion (HYCH). Both findings are relevant to patient symptoms. The dysautonomia was mild and of questionable clinical significance.
Case 86: Paroxysmal Dysautonomia
Authors: Novak Peter
Published: April 2019

Paroxysmal dysautonomia, hyperventilation, and hypocapnic cerebral hypoperfusion can underlie spells of altered consciousness and dizziness.
Drug Information
Authors: Bartlett John G. , Redfield Robert R. , Pham Paul A.
Published: April 2019

Abstract: This chapter is about pharmacology, side effects, and drug interactions of various drugs, including abacavir (ABC), acyclovir, Amphotericin B, atazanavir (ATV), atorvastatin, atovaquone, azithromycin, azoles, bedaquiline, bictegravir (BIC), bupropion, buspirone, caspofungin, cidofovir, ciprofloxacin, clarithromycin, clindamycin, clotrimazole, cobicistat (COBI), dapsone, darunavir (DRV), daunorubicin citrate liposome, didanosine (ddI), dolutegravir (DTG), doxycycline, efavirenz (EFV), emtricitabine (FTC), elvitegravir (EVG), enfuvirtide (T-20), entecavir, erythropoietin, ethambutol, etravirine (ETR), fentanyl, fluconazole, flucytosine, fluoxetine, fosamprenavir (FPV), ibalizumab-uiyk (Trogarzo), indinavir (IDV), itraconazole, lamivudine (3TC), leucovorin, lopinavir/ritonavir (LPV/r), maraviroc (MVC), methadone, nelfinavir (NFP), nevirapine (NVP), oxandrolone, paromomycin, pegylated interferon, pentamidine, pravastatin, pyrazinamide, pyrimethamine, raltegravir (RAL), ribavirin, rifabutin, rifampin, rilpivirine (RPV), ritonavir (RTV), saquinavir (SQV), stavudine (d4T), sulfadiazine, tenofovir (TDF and TAF), testosterone, thalidomide, tipranavir (TPV), trazodone, trimethoprim, trimethoprim-sulfamethoxazole, voriconazole,zidovudine, and Hep C antiviral agents.
Lateralized Overgrowth
Authors: Kalish Jennifer M. , Ferrero Giovanni Battista , Mussa Alessandro
Published: April 2019

The chapter discusses body asymmetry occurring as an isolated clinical feature or as part of well-characterized syndromes. The term “lateralized overgrowth” has been recently introduced to describe conditions characterized by disproportionate growth of one side of the body that might be caused by hemihyperplasia and/or hemihypertrophy. The chapter also provides a brief clinical overview of the major syndromes associated with lateralized overgrowth and discusses the molecular anomalies causing this disorder. Prognosis of conditions characterized by lateralized overgrowth varies according to the underlying cause. Treatment and management of conditions characterized by lateralized overgrowth mainly focus on tumor surveillance and management of eventual difference of limb length. Leg-length discrepancy can be associated with significant morbidity and can negatively influence the quality of life.
PIK3CA-Related Overgrowth Spectrum
Authors: Keppler-Noreuil Kim M.
Published: April 2019

Postzygotic mutations of the PIK3CA gene are associated with a series of clinical phenotypes characterized by segmental overgrowth and recently grouped under the term PIK3CA-related overgrowth spectrum (PROS). This chapter provides an overview of the clinical features shared by the phenotypes in PROS, including both the conditions with isolated features and the ones with syndromal presentation. The somatic overgrowth in cases with PROS is asymmetric, progressive, and “ballooning” in appearance and tends to involve predominantly the limbs, including fingers and toes, although the trunk and face are often affected as well. The tissues affected in the overgrowth can include all or some of these types: fibrous, adipose, vascular, nervous, and skeletal. Somatic gain-of-function mutations of PIK3CA cause activation of the PI3K-AKT pathway, leading to excessive cell growth and proliferation. Timing of PIK3CA mutations, tissue specificity, and type of mutation may play a role in the phenotypic variability of PROS.
Transthoracic echocardiography, sonoanatomy, and standard views
Authors: Russell Conn
Published: April 2019

This chapter will describe all the standard focused cardiac ultrasound (FoCUS) views, including the anatomical structures one should expect to see and, importantly, how to obtain and optimize these images to extract the best diagnostic information. It will discuss the cardiac axis, probe handling, and pitfalls in image acquisition. The advanced section will introduce additional views, which are used in comprehensive echocardiography, because some are obtained inadvertently during FoCUS scanning and can be used to guide the operator back to standard views.
Left ventricular assessment
Authors: Peck Marcus
Published: April 2019

This chapter will outline the relevant structure and function of the left ventricle and its common pathophysiology such as left ventricular hypertrophy, regional wall motion abnormalities, systolic and diastolic heart failure, and Takotsubo cardiomyopathy. It will describe how focused cardiac ultrasound can be used to assess left ventricular size, shape, wall thickness, and systolic function, including linear, area, and volumetric methods, and how loading conditions impact on these. It will demonstrate how to recognize common left ventricular pathophysiology, and the advanced section will introduce how tissue Doppler can be used to assess systolic and diastolic function.
Intravascular volume and cardiac output assessment
Authors: Parulekar Prashant , Harris Tim
Published: April 2019

This chapter will focus on two-dimensional echo techniques that can detect potential hypovolaemia and hypervolaemia. It will discuss both dynamic and static parameters and how these may help to predict fluid responsiveness and fluid tolerance, respectively. The advanced section will then introduce established Doppler-based echo techniques that can be used to estimate stroke volume and guide volume resuscitation, as well as novel approaches currently under investigation.
Vascular access
Authors: Labib Ahmed , Bodenham Andrew R
Published: April 2019

Ultrasound guidance has become a standard of care when undertaking vascular access for central venous cannulation and is increasingly used for peripheral procedures in challenging patients. This chapter describes how to use ultrasound to guide central venous, peripheral venous, and arterial cannulation, using both in-plane and out-of-plane techniques. The sonoanatomy of common areas for vascular access are described and any pitfalls highlighted.
Pleural drainage
Authors: Stephens Jennie
Published: April 2019

Ultrasound guidance is recommended by the British Thoracic Society when undertaking any procedure on a pleural effusion in order to reduce complications. This chapter outlines the indications for draining a pleural effusion and describes the technique for using ultrasound to identify a safe site for drainage. A detailed description of how to undertake an ultrasound-guided pleural aspiration, thoracocentesis, and insertion of chest drain follows.
Governance in point-of-care ultrasound
Authors: Macnaughton Peter , Peck Marcus
Published: April 2019

The performance and interpretation of ultrasound examination are very user-dependent that require significant training and experience. This chapter details the processes that should be adopted within an intensive care unit using point-of-care ultrasound to ensure that practitioners are appropriately trained and are able to maintain and develop their skills. The chapter also outlines recommendations regarding good practice in reporting and image storage, together with guidance regarding equipment management, to ensure patient safety.
Overlap ECG patterns in the athlete’s heart and cardiomyopathies
Authors: Dhutia Harshil , Papadakis Michael
Published: April 2019

Physiological adaptation to exercise manifests on the surface ECG with phenotypes that occasionally overlap with those present in patients with cardiomyopathy, one of the leading causes of exercise-related cardiac death in young athletes. In the era of pre-participation screening, differentiation of physiology from pathology is crucial given the potential consequences of an erroneous diagnosis or false reassurance. This chapter provides a comprehensive overview of the ECG anomalies that may cause diagnostic dilemmas in clinical practice, delineates the size of the ‘ECG grey zones’, and provides practical algorithms for ascertaining which ECG phenotypes require further evaluation.
Drug prescribing
Authors: Rees Lesley , Webb Nicholas J.A , Bockenhauer Detlef , Punaro Marilynn G.
Published: April 2019

Great care should be exercised when prescribing for children with kidney disease. Many drugs are renally excreted and require dose adjustment in the presence of chronic kidney disease. Children with kidney disease, particularly those who have undergone kidney transplantation, frequently receive a large number of drugs and there is significant potential for drug–drug interaction. Information is available in the British National Formulary for Children and other texts; however, advice from an experienced paediatric nephrologist or specialist renal pharmacist should be sought where there is uncertainty.
Primary prevention and health promotion in childhood
Authors: Adams Cheryll , Cowley Sarah
Published: April 2019

This chapter begins by offering some definitions and an explanation of why prevention needs to start with early child development. Then, it considers some of the practicalities of providing primary prevention services, using examples to show the processes of assessing needs and delivering services. Next, key principles and practice approaches that have been found helpful to the preventive effort are explained. Finally, there is a discussion of some effective approaches to health promotion for families and promoting effective parenting.
Growth monitoring
Authors: Wright Charlotte M.
Published: April 2019

The subject of how growth should be monitored and recorded was addressed by the Royal College of Paediatrics and Child Health Growth Chart working group in the process of developing and implementing the UK-World Health Organization growth charts between 2008 and 2012. The group developed chart instructions and supporting educational material, drawing on the collective views of focus groups, stakeholder meetings, and the considered views of the working group. These have been expanded or modified where there is newer relevant evidence and the section is also informed by the 2008 National Institute for Health and Care Excellence guideline on maternal and child nutrition and the new guideline on faltering growth.
Physical examination
Authors: Emond Alan
Published: April 2019

The NHS newborn and infant physical examination screening programme recommends screening of newborn babies and then once again between 6 to 8 weeks, for conditions relating to their heart, hips, eyes, and testes. The evidence supporting this recommendation is reviewed, and good practice in identifying other common physical abnormalities is described. Congenital heart disease, developmental dysplasia of the hip, congenital cataract, undescended testes, cleft lip, tongue tie, and jaundice are discussed in more detail
Health workers and health systems
Authors: Mandeville Kate , Wolfe Ingrid
Published: April 2019

This chapter describes the critical role that health workers and strong health systems play in improving maternal and child health. A strong health system should deliver improved health, financial protection, equity of access, and a responsive service. Delivering these goals relies on strengthening all parts of the health system, in the context of social, political, and historical factors. There are many lessons to be learned from country experiences, including the importance of universal health coverage and investment in health workers. Universal health coverage is vital for ensuring good health for all; however, both establishing and expanding such coverage is fraught with challenges. Health workforces need to be aligned to a country’s population and disease burden, with retention of health workers given as much priority as increased production. Strengthening health systems is an essential part of the global effort to safeguard health for mothers and children, now and in the future.
Introduction to adolescent health
Authors: Sawyer Susan M , Abdul-Razak Suraya , Patton George C
Published: April 2019

This chapter describes adolescence as a highly dynamic developmental period where health risks and outcomes are shaped by biological development and social influences. Previously neglected, the world’s 1.8 billion adolescents constitute a quarter of the population and are supported by the new Global Strategy on Women’s Children’s and Adolescents’ Health. Investing in building adolescent capabilities and assets yields a ‘triple dividend’ by improving the health of adolescents, reducing the burden of disease in adults, and improving the health and development of the next generation. Adolescent health profiles differ greatly between and within countries, reflecting different social, educational, economic, cultural, and technological opportunities and risks; the focus of required investments must therefore match different needs. Investments extend from actions directed towards conspicuous health problems (e.g. HIV, asthma, anxiety) to emergent health risks (e.g. tobacco smoking), to broader social determinants (e.g. quality schooling, avoidance of child marriage).
Adolescent mental health
Authors: Clarke Kelly , Yasuda Sílvia Shikanai , Rahman Atif
Published: April 2019

Adolescent mental health disorders have serious health and socioeconomic consequences and may persist into adulthood and affect future generations. They account for four of the top ten causes of DALYs among young people, with suicide as the main cause of adolescent mortality. New threats are constantly emerging and changing with urbanisation, social media, and armed conflicts. As a neglected area of public health, resources are needed to improve awareness and develop global research, policies and training. Stakeholder involvement and government commitment are also essential to address the gap between burden and resource allocation. Promotion and prevention at a community level, coordinated between different sectors, could help to foster youth resilience. Non-specialist mental healthcare provision is a promising approach in low-resource settings but must be adapted to local needs.
Strategies to improve adolescent health
Authors: Sadoo Samantha , Ross David A
Published: April 2019

Adolescents have previously been neglected on the global health agenda, but recent progress has been made with the inclusion of adolescents in the UN Global Strategy for Women’s, Children’s, and Adolescents’ Health (2016-2030), and the landmark 2017 document the from WHO and other agencies, AA-HA! Guidance, designed to support in-country implementation of strategies for adolescent health. Investing in adolescent programmes yields a triple return; improving the health of the adolescent, of their future selves as adults, and then of their children. As the main determinants of adolescent health are outside the specific remit of the health sector, interventions must be delivered by multiple sectors, including education, social protection, roads and infrastructure, and employment, and be targeted more widely at various levels of influence; the individual and family, community, school, media and technology, environment, and legal frameworks. Adolescent participation and engagement in programmes is key to their success.
Introduction to maternal and reproductive health
Authors: Kamanga Martha , Hall Jennifer , Malata Address
Published: April 2019

Pregnancy and childbirth have a huge impact on the physical, mental, emotional, and socioeconomic health of women and their families. Poor maternal health remains a significant problem both in developed and developing countries. While motherhood offers a rewarding experience, for too many women it is associated with suffering, ill health, and even death. Many women, including adolescents, die from preventable causes related to pregnancy and childbirth. Maternal deaths are classified as direct or indirect. Direct causes are those related to obstetric complications of pregnancy, labour, delivery, and the postnatal period, while indirect causes are those relating to pre-existing medical conditions that may be aggravated by the physiological demands of pregnancy. Opportunities to prevent and control diseases occur at multiple stages of life. Identifying which groups of women experience poorer physical and mental health, and understanding risk factors, will enable midwives and other health professionals to better support women before, during, and after pregnancy and childbirth.
Direct maternal deaths
Authors: Merriel Abi , Kanthiti Raymond , Lissauer David
Published: April 2019

This chapter discusses direct causes of maternal death, which account for nearly three quarters of maternal deaths worldwide. These deaths occur disproportionately in low-resource settings and are largely due to obstetric complications. It is therefore possible to significantly reduce these deaths. We discuss the five most important causes: postpartum haemorrhage, abortion-related deaths, hypertensive disorders, sepsis, and obstructed labour. The three delays in deciding, reaching, and receiving adequate care are then used to consider the broad areas to address to reduce direct maternal deaths. Possible strategies which could be implemented to reduce preventable direct maternal deaths such as implementing women’s groups and skills training are discussed. Finally, we highlight some of the challenges surrounding reducing direct deaths, including difficulties in measurement and increasing skilled attendance at birth. To overcome these challenges and prevent direct maternal deaths, comprehensive strategies addressing both community and health systems issues need to be employed.
Maternal morbidity
Authors: McCauley Mary , van den Broek Nynke
Published: April 2019

Maternal morbidity describes complications that have a significant effect on women during and after pregnancy, and are a leading cause of ill-health among women of reproductive age, especially in low- and middle-income countries. With the introduction of the new Sustainable Development Goals, the scope of global maternal health targets has been expanded, moving from a focus on preventing maternal mortality to formulating targets and emphasising the importance of maternal health and wellbeing. This chapter introduces the new concept of maternal morbidity, suggests how this relates to maternal mortality, and summarises what is known about the burden of maternal morbidity globally and what interventions and research are needed to improve maternal health during and after pregnancy, with an emphasis on the context of low- and middle-income countries.
Neonatal infection
Authors: Seale Anna , Brotherton Helen
Published: April 2019

This chapter describes neonatal infection, which accounts for around a quarter of all neonatal deaths, most of which are in resource-limited settings. Whilst a range of pathogens can cause neonatal infection, diagnosis and treatment of possible serious bacterial infection (including sepsis, meningitis, and pneumonia) is most critical, to reduce the high mortality associated with these serious infections. However, empiric antibiotic treatment strategies are threatened by the worldwide increase in drug resistant infections, and understanding aetiologies of disease, to target treatments and direct empiric treatment guidelines, remains critical. Prevention of neonatal infection is important, and ensuring appropriate antisepsis measures will reduce disease as well as ensuring high maternal vaccine coverage for existing vaccines (e.g. for tetanus) whilst new maternal vaccines are in development.