bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review and Case Study of 3D Imaging Modalities for Female Amniote Reproductive Anatomy
Authors: Clear Emma , Grant Robyn A , Carroll Michael , Brassey Charlotte A
Published: May 2022

Synopsis

Recent advances in non-invasive imaging methods have revitalized the field of comparative anatomy, and reproductive anatomy has been no exception. The reproductive systems of female amniotes present specific challenges, namely their often internal “hidden” anatomy. Quantifying female reproductive systems is crucial to recognizing reproductive pathologies, monitoring menstrual cycles, and understanding copulatory mechanics. Here, we conduct a review of the application of non-invasive imaging techniques to female amniote reproductive anatomy. We introduce the commonly used imaging modalities of computed tomography (CT) and magnetic resonance imaging (MRI), highlighting their advantages and limitations when applied to female reproductive tissues, and make suggestions for future advances. We also include a case study of micro CT and MRI, along with their associated staining protocols, applied to cadavers of female adult stoats (Mustela erminea). In doing so, we will progress the discussion surrounding the imaging of female reproductive anatomy, whilst also impacting the fields of sexual selection research and comparative anatomy more broadly.
Proteomic Signature of Subclinical Coronary Artery Disease in People With HIV: Analysis of the REPRIEVE Mechanistic Substudy
Authors: Kolossváry Márton , deFilippi Chris , Lu Michael T , Zanni Markella V , Fulda Evelynne S , Foldyna Borek , Ribaudo Heather , Mayrhofer Thomas , Collier Ann C , Bloomfield Gerald S , Fichtenbaum Carl , Overton Edgar T , Aberg Judith A , Currier Judith , Fitch Kathleen V , Douglas Pamela S , Grinspoon Steven K
Published: May 2022

Background

People with HIV (PWH) have subclinical coronary artery disease (CAD) despite low traditional atherosclerotic cardiovascular disease (ASCVD) risk scores. Coronary plaque in PWH presents as a unique phenotype, but little is known about the contributions of specific inflammatory pathways to plaque phenotypes in PWH.

Methods

The REPRIEVE Mechanistic Substudy enrolled PWH on ART without known cardiovascular disease. We used a targeted discovery proteomics approach to evaluate 246 unique proteins representing cardiovascular, inflammatory, and immune pathways. Proteomic signatures were determined for presence of coronary artery calcium (CAC > 0) and presence of coronary plaque.

Results

Data were available for 662 participants (aged 51 [SD 6] years, ASCVD risk score 4.9% [SD 3.1%]). Among 12 proteins associated with both CAC and presence of coronary plaque, independent of ASCVD risk score, the odds ratios were highest for NRP1: 5.1 (95% confidence interval [CI], 2.3–11.4) for CAC and 2.9 (95% CI, 1.4–6.1) for presence of plaque. Proteins uniquely related to presence of plaque were CST3, LTBR, MEPE, PLC, SERPINA5, and TNFSF13B; in contrast, DCN, IL-6RA, OSMR, ST2, and VCAM1 were only related to CAC.

Conclusions

Distinct immune and inflammatory pathways are differentially associated with subclinical CAD phenotypes among PWH. This comprehensive set of targets should be further investigated to reduce atherosclerosis and ASCVD in PWH.

Clinical Trials Registration

NCT02344290.
Smart Eco-Friendly Spectrophotometric Methods Resolving Highly Overlapping Spectra: Application to Veterinary Antibiotic Injections
Authors: Fahmy Nesma M , Abdullatif Hind A , Michael Adel M , Ayad Miriam F , Trabik Yossra A
Published: May 2022

Background

Over the last few years, mathematical manipulation has proved to be a very powerful means of successfully resolving severely overlapped spectra for various multicomponent mixtures.

Objective

Smart and environmentally friendly spectrophotometric determination approaches were used for two binary mixtures of fixed dose veterinary injections containing flunixin meglumine (FLU) combined with either florfenicol (FLR), or oxytetracycline HCl (OXY).

Methods

Regarding the first mixture, both FLU and FLR were determined by three successive resolution techniques, which were; constant multiplication coupled with spectrum subtraction (CM-SS), derivative ratio (DD1), and ratio difference (RD), and two progressive resolution techniques which were absorbance subtraction (AS) and amplitude modulation (AM). Also, graphical representation of concentration of the two drugs through concentration value (CNV) method was also applied. Concerning the second mixture, both FLU and OXY showed severely overlapped spectra and a comparative study was conducted for the determination of each drug by constant center (CC), ratio subtraction via amplitude difference coupled with spectrum subtraction (RS/AD-SS), constant value via amplitude difference (CV-AD), and advanced concentration value (ACV) methods.

Results

Calibration graphs of the first mixture were linear over the range 5–40 µg/mL for FLU, and 3–40 µg/mL for FLR. The proposed methods overcame the problem of the overlapped spectra and the presence of a minor component in the mixture. Regarding the second mixture, calibration graphs were linear over the range 2.5–24 µg/mL for FLU and 4–28 µg/mL for OXY.

Conclusion

The proposed methods were successfully validated as per International Council for Harmonization (ICH) guidelines. The obtained results were statistically compared with the official or reported methods, showing no significant difference concerning accuracy and precision. The methods were evaluated for greenness by three different assessment tools: NEMI, analytical ecoscale, and GAPI.

Highlights

The methods were successfully applied for the simultaneous determination of the two combinations in synthetic mixtures and their marketed antibiotic veterinary injections: Megluflor® and Floxon®.
Effects of yeast-based pre- and probiotics in lactation diets of sows on litter performance and antimicrobial resistance of fecal Escherichia coli of sows
Authors: Chance Jenna A , DeRouchey Joel M , Amachawadi Raghavendra G , Ishengoma Victor , Nagaraja Tiruvoor G , Goodband Robert D , Woodworth Jason C , Tokach Mike D , Kang Qing , Loughmiller Joseph A , Hotze Brian , Gebhardt Jordan T
Published: May 2022

A total of 80 sows (Line 241; DNA, Columbus, NE) across three farrowing groups were used in a study to evaluate the effect of feeding live yeast and yeast extracts to lactating sows on sow and litter performance and antimicrobial resistance (AMR) patterns of sow fecal E. coli. Sows were blocked by farrowing group, BW, and parity on day 110 of gestation and allotted to 1 of 2 dietary treatments. Dietary treatments consisted of a standard lactation diet with or without yeast-based pre- and probiotics (0.10% Actisaf Sc 47 HR+ and 0.025% SafMannan; Phileo by Lesaffre, Milwaukee, WI). Diets were fed from day 110 of gestation until weaning (approximately d 19 post-farrow). A tendency (P = 0.073) was observed for increased feed intake through lactation when sows were fed a diet with yeast additives compared with the control diet. There was no evidence (P > 0.10) that treatment influenced any other sow or litter performance measurements. Fecal samples were collected upon entry into the farrowing house and at weaning from the first farrowing group (27 sows) to determine the resistance patterns of E. coli. E. coli was isolated from fecal samples and species confirmed by PCR detection of uidA and clpB genes. Microbroth dilution method was used to determine the minimal inhibitory concentrations (MIC) of E. coli isolates to 14 antimicrobials. Isolates were categorized as either susceptible, intermediate, or resistant based on Clinical and Laboratory Standards Institute guidelines. An interaction (P = 0.026) of diet × sampling day was observed for cefoxitin where fecal E. coli showed no evidence of treatment differences (P = 0.237) in MIC values at entry, but sows fed the control diet had lower (P = 0.035) MIC values at weaning compared with sows fed yeast additives. There were no diet main effects (P > 0.10) on the resistance of fecal E. coli. There was an increased (P < 0.02) toward resistance for 11 of the 14 antimicrobials over time. Fecal E. coli were resistant to tetracycline and ceftriaxone at weaning. Fecal E. coli were susceptible or intermediate in all sampling days to the remaining antimicrobials. In conclusion, feeding live yeast and yeast extracts tended to increase feed intake during lactation but did not influence either sow or litter performance measurements or the resistance of fecal E. coli during lactation except for cefoxitin, which had a higher MIC at the end of lactation when yeast additives were present in the diet.
Influence of yeast-based pre- and probiotics in lactation and nursery diets on nursery pig performance and antimicrobial resistance of fecal Escherichia coli
Authors: Chance Jenna A , DeRouchey Joel M , Amachawadi Raghavendra G , Ishengoma Victor , Nagaraja Tiruvoor G , Goodband Robert D , Woodworth Jason C , Tokach Mike D , Kang Qing , Loughmiller Joseph A , Hotze Brian , Gebhardt Jordan T
Published: May 2022

Two experiments were conducted to determine the impact of various combinations of yeast-based direct fed microbials (DFM) in diets fed to nursery pigs weaned from sows fed lactation diets with or without yeast additives. In Exp. 1, 340 weaned pigs, initially 5.1 kg ± 0.02, were used to evaluate previous sow treatment (control vs. yeast additives) and nursery diets with or without added yeast-based DFM on growth performance and antimicrobial resistance (AMR) patterns of fecal Escherichia coli. Treatments were arranged in a 2 × 2 factorial with main effects of sow treatment (control vs. yeast-based pre- and probiotic diet; 0.10% ActiSaf Sc 47 HR+ and 0.025% SafMannan, Phileo by Lesaffre, Milwaukee, WI) and nursery treatment (control vs. yeast-based pre- and probiotic diet; 0.10% ActiSaf Sc 47 HR+, 0.05% SafMannan, and 0.05% NucleoSaf from days 0 to 7, then concentrations were decreased by 50% from days 7 to 24) with 5 pigs per pen and 17 replications per treatment. Progeny from sows fed yeast additives had increased (P < 0.05) average daily gain (ADG) from days 0 to 24 and days 0 to 45. However, pigs that were fed yeast additives for the first 24 d in the nursery tended to have decreased days 0 to 45 ADG (P = 0.079). Fecal E. coli isolated from pigs from the sows fed yeast group had increased (P = 0.034) resistance to nalidixic acid and a tendency for increased resistance to ciprofloxacin (P = 0.065) and gentamicin (P = 0.054). Yet, when yeast additives were added in the nursery, there was reduced (P < 0.05) fecal E. coli resistance to azithromycin and chloramphenicol. In Exp. 2, 330 weaned pigs, initially 5.8 kg ± 0.03, were used to evaluate diets with two different combinations of DFM on growth performance. Treatments were arranged in a 2 × 3 factorial with main effects of sow treatment (same as described in Exp. 1) and nursery treatment (control; YCW, 0.05% of SafMannan from days 0 to 38 and NucleoSaf at 0.05% from days 0 to 10 and 0.025% from days 10 to 24; or DFM, 0.10% MicroSaf-S from days 0 to 38 and NucleoSaf at 0.05% from days 0 to 10 and 0.025% from days 10 to 24) with 6 pigs per pen and 8 to 10 replications per treatment. From days 0 to 10 post-weaning, progeny of sows fed yeast additives had increased (P < 0.05) ADG and G:F. In conclusion, feeding sows yeast through lactation improved offspring growth performance in the nursery. Although feeding live yeast and yeast extracts reduced nursery pig performance in Exp. 1, feeding DFM improved growth later in the nursery period in Exp. 2.
The Effects of Fair Trade Certification: Evidence from Coffee Producers in Costa Rica
Authors: Dragusanu Raluca , Montero Eduardo , Nunn Nathan
Published: May 2022

We study the effects of Fair Trade (FT) certification of coffee on producers and households in Costa Rica. Examining the production dynamics of all Costa Rican coffee mills from 1999 to 2014, we find that when global coffee prices are lower and the FT guaranteed minimum price is binding, FT certification is associated with a higher sales price, greater sales, and more revenues. We also find that certification reduces the probability of a mill closing down and exiting the industry. Looking at households, we find that certification is associated with higher incomes for farm owners. Part of this is due to a transfer of income from intermediaries whose incomes decrease due to FT. We find no effect of FT on unskilled workers, who are the more disadvantaged group within the coffee sector.
Whole-cell observation of ZIO-stained Golgi apparatus in rat hepatocytes with serial block-face scanning electron microscope, SBF-SEM
Authors: Johkura Kohei , Usuda Nobuteru , Tanaka Yoshihiro , Fukasawa Motoaki , Murata Kazuyoshi , Noda Toru , Ohno Nobuhiko
Published: May 2022

The Golgi apparatus, which plays a role in various biosynthetic pathways, is usually identified in electron microscopy by the morphological criteria of lamellae. A 3-dimensional analyses with serial block-face scanning electron microscope (SBF-SEM), a volume-SEM proficient in obtaining large volumes of data at the whole-cell level, could be a promising technique for understanding the precise distribution and complex ultrastructure of Golgi apparatus, although optimal methods for such analyses remain unclear since the observation can be hampered with sample charging and low image contrast, and manual segmentation often requires significant manpower. The present study attempted the whole-cell observation and semi-automatic classification and segmentation of the Golgi apparatus in rat hepatocytes for the first time by SBF-SEM via ZIO staining, a classical osmium impregnation. The staining electron-densely visualized individual Golgi lamellae, and their ultrastructure could stably be observed without any noticeable charging. The simple thresholding of the serial images enabled the efficient reconstruction of the labeled Golgi apparatus, which revealed plural Golgi apparatus in one hepatocyte. The combination of the heavy metal-based histochemistry of zinc, iodine and osmium (ZIO) staining and SBF-SEM was useful in the 3-dimensional observation of the Golgi apparatus at the whole-cell level because of two technical advantages: (i) visualization of the Golgi apparatus without any heavy metal staining and efficient acquisition of the block-face images without additional conductive staining or any devices for eliminating charging; (ii) easy identification of the staining and hassle-free, semi-automatic classification and segmentation by simple thresholding of the images. This novel approach could elucidate the topographic characteristics of the Golgi apparatus in hepatocytes.
The joint effects of resource stress and grazing on plant–plant interactions in alpine meadows on the eastern Qinghai-Tibetan Plateau
Authors: Mo Li , Yang Hao , Luo Peng , Mou Cheng-Xiang , Wang Jun
Published: May 2022

The stress gradient hypothesis (SGH) proposes that the frequency of positive interactions among plants is increased with stress. However, in alpine meadow ecosystems, the joint effects of herbivore grazing and resource stress on plant–plant interactions remain poorly understood. By investigating the spatial associations of two dominant, widely distributed species—Carex praeclara (unpalatable) and Carum carvi (palatable)—we explored changes in plant–plant interactions at three desertification levels (light, moderate and severe) under grazed and ungrazed conditions to test the generality of the SGH in the desertified alpine meadows on the eastern Qinghai-Tibetan Plateau. Without grazing disturbance, intraspecific interactions of C. praeclara and C. carvi changed from positive to negative, while their interspecific interactions shifted from negative to positive along the desertification gradient from light to severe level. However, intraspecific interactions of C. carvi under grazing remained neutral at all desertification levels, while the net interspecific interactions between these species changed from competitive to facilitative under moderate stress. But, the positive interactions collapsed under severe stress, which is inconsistent with the SGH prediction. Our results reinforced the evidence that livestock grazing strongly influences the balance of intra- and interspecific interactions along the stress gradients in the alpine ecosystems.
Reconciling the local content laws and policies in Trinidad and Guyana with the CARICOM trade rules: lessons from the European Union
Authors: Pereira Eduardo G , Elias-Roberts Alicia , Muinzer Thomas , Reid Aurelia
Published: May 2022

Several Caribbean countries have local content laws that might go against the Revised Treaty of Chaguaramas and frequently reflect a patriotic mindset. Treaties between countries aiming primarily at the union of numerous independent nations might further complicate an industry already beset by challenges because they frequently necessitate the pooling of money and resources. This article will look at how the CARICOM nations of Trinidad and Tobago and Guyana deal with local content in their separate jurisdictions, and how it affects their CARICOM treaty obligations
Paradigms Lost, Paradigms Found
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

This book draws on more than 25 years of experience developing and evaluating anti-stigma programs to reduce negative and unfair treatment experienced by people with a mental or substance use disorder. It builds on a previous edition, Paradigms Lost: Fighting Stigma and the Lessons Learned, that identified new approaches to stigma reduction. This volume examines the newest approaches to stigma reduction with respect to structural stigma, public stigma, and internalized stigma. The goals of anti-stigma work must be to eliminate the social inequities that people with mental and substance use disorders and their families face to promote their full and effective social participation. Awareness raising and mental health literacy are important, but they do little to change the accumulated practices of social groups and social structures that systematically disadvantage those with mental and substance use problems. The book is written with one eye to the past (what we have done well) and one to the future (what we must still do). It goes into depth in targeted areas such as healthcare, workplaces, schools, and the media. We expect that this edition will be a useful sequel to Paradigms Lost, chronicling what we have learned as a global community regarding stigma related to mental illness and substance use and stigma-reduction approaches.
Mental Illness–Related Stigma
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

In the history of medicine, few conditions other than mental illnesses have cast such a pall on an individual, their family, health providers, health systems, and health research. In addition to having serious consequences for one’s social identity, having a mental illness or substance use disorder results in structural inequities that impinge on one’s health, longevity, quality of life, social welfare, civic participation, and access to resources. Stigma also casts a long shadow, affecting all of the supports and structures that people with mental illnesses need in order to recover and embrace socially meaningful roles and relationships. This chapter provides an overview of the nature and nurture of stigma from the era of the asylum to our current recovery paradigm.
Paradigms Found in Fighting Stigma
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

This chapter summarizes the key points and guiding principles for anti-stigma programming. It provides a high-level summary of the important points to keep in mind when developing anti-stigma programming and outlines our model of “enlightened opportunism,” which allows programs to seize opportunities that appear for targeted anti-stigma intervention. It covers topics such as the importance of building networks, targeting programs to specific groups based on their needs, making sure that people with lived experience of mental or substance use disorders are in leadership positions and involved in all aspects of the program, listening to the evidence, building theories of change that explain program effects, realizing the inability of literacy or awareness programs to improve social inclusion or remove structural barriers, aiming for behavioral and structural change, planning for sustainability, thinking big but starting small, and building better practices through evaluation.
Eleven Steps to Build an Anti-stigma Program
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

This chapter provides a non-technical summary of how to build an anti-stigma program. It is intended to help local groups through the process of setting up an anti-stigma program. It draws on the authors’ experiences working with international, national, and local anti-stigma groups and is intended to broadly serve as a “how-to” resource. The advice is pragmatic and expresses the view that everyone can take part in anti-stigma programming, at some level—modest efforts are possible for anyone to achieve. What is important to remember is that anti-stigma programs can be implemented even if there is not specific funding that has been made available, using volunteer resources. The following text offers suggestions for how this can be done. It is offered as a narrative overview, but it could be converted into a manual for action.
Fighting the Good Fight
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

Since World War II there has been a long history of activities designed to protect the human rights of people with mental and substance use disorders. This chapter examines initiatives to reduce stigma and promote social equity for people with mental and substance use disorders. It begins with a broad view of human rights legislation from organizations such as the United Nations, international societies, and national anti-stigma programs. It details selected activities of these groups to implement programs and toolkits and closes with a review of national, regional, and targeted anti-stigma efforts. Initiatives illustrate stigma-reduction activities at the three levels of structural, public, and self-stigma.
Media
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

The news and entertainment media have produced some of the most sensitive, educational, and award-winning material on mental illnesses and the mentally ill. They also have created a vast store of negative imagery with some of the most malignant depictions of madness and horrifying descriptions of psychiatrists and psychiatric treatments. The fact that the latter greatly outweighs the former, and is more memorable, is of immense concern to people with mental health problems, family members, and mental health professionals. This chapter examines the ways in which stigma plays out in the news, entertainment, and social media. It outlines resources that have been developed to help reduce sensationalized views and promote first-person perspectives of people with lived experience. The role of the media as allies in anti-stigma activities is also discussed in order to promote a greater awareness of the importance of advocacy in this field.
Health Systems
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

Healthcare systems, including healthcare providers, have been consistently identified as major contributors to mental illness–related stigma at both interpersonal and system levels. Stigma occurring within health systems is particularly impactful to people who have a mental illness and their family members because it occurs at a time when they are at their most vulnerable. It not only undermines access to and quality of care, but it can also create and reinforce self-stigma and result in negative health outcomes, including increased morbidity and premature mortality. This chapter examines key ways in which health system stigma occurs and reviews examples of novel interventions that could be used to create a non-stigmatizing, person-centered care experience.
Educational Systems
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

Despite the importance of school settings for anti-stigma education, school officials and teachers are often reluctant to offer mental illness–related programs to students for fear of reprisals from parents or unexpected negative emotional reactions from students who, they fear, may be triggered by the content. In addition to worrying about how mental health content may be received, educators may also lack the confidence to deliver mental health–related programing. This is particularly true when programs target the youngest age groups. This chapter will review opportunities for anti-stigma programming from preschool to professional education, drawing on evidence-informed practices when available.
Employment Inequity and Workplace Stigma
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

Despite human rights and employment equity legislation, people with mental illnesses face a number of barriers to employment. Because of stigma, not only is it difficult to get a job, but it is also difficult to keep a job. Yet, employment is a key factor promoting social inclusion and recovery for people with mental illnesses. Employers’ knowledge of workplace adjustments (termed accommodations) that could support people with mental illnesses is often limited, and they may be reluctant to adjust the workplace or workflow to allow someone with an impairment to perform their job. This chapter examines workplace programs that target employers and employees, as well as vocational programs that are designed to help people with mental illnesses gain competitive employment.
Using Technology to Fight Stigma
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

Anti-stigma advocates have made good use of “older” technologies such as television, movies, radio, theater, and printed materials, to name a few. Newer digital technologies are increasingly viewed as a panacea for mental health promotion and stigma reduction. Not only can they reach vast audiences, but they are also cost-effective, relatively easy to produce, and feasible to implement in today’s technological age. Interventions specifically focusing on stigma reduction are relatively new and largely untested. Theories of change explaining why certain interventions might reduce stigma are lacking and the extant literature is relatively silent on evidence-informed approaches. Because the field is so new, with few intervention studies, technology should be viewed as an emerging practice that still requires evidence. This chapter reviews some examples of the approaches that are experimenting with technologies to reduce stigma and promote prosocial behaviors.
Research
Authors: Stuart Heather , Sartorius Norman
Published: May 2022

Since the early 1970s, epidemiological studies have consistently documented a high prevalence of mental illnesses in the population. But it was not until researchers developed the disability-adjusted life-year and applied this internationally that the full public health burden of mental illnesses became known. Stigma is a key driver of inequities in mental health programs, and this chapter shows how stigma is also a key driver of inequities in research and research funding. Approaches to the measurement of stigma are discussed and important and innovative measurement tools that focus on high-priority evaluation outcomes such as behavioral change or self-stigma are highlighted.
‘The happy curing of cephalick diseases’
Authors: Compston Alastair
Published: May 2022

Chapter 10, ‘The happy curing of cephalick diseases: Pharmaceutice rationalis (1674–1679)’, provides a detailed bibliography, using the system described in chapter 4, of seven copies of the Willis’s sixth published book in which is included one treatise: 12. Pharmaceutice rationalis (part 1); four copies of the second part containing one treatise: 13. Pharmaceutice rationalis (part 2); and the single copy of the edition containing both parts. These descriptions are preceded by a narrative highlighting the main bibliographic issues that characterize the various editions, states, and issues of these copies. Of these, some are already known but others newly identified. {98 words}
History and classification of trigeminal neuralgia and other cranial neuralgias
Authors: Zakrzewska Joanna M.
Published: May 2022

Trigeminal neuralgia has been known for centuries but the first descriptions that remain valid today are those by John Fothergill in 1783. The chance naming of the condition as a form of epilepsy led to the use of a wide range of antiepileptic drugs which are still being utilized. Since 1730, surgical techniques have been evolving. Peripheral treatments were first used before surgeons began to devise techniques to reach the Gasserian ganglion, which were facilitated by X-rays. With the advent of the operating microscope, it became possible to carry out effective posterior fossa surgery which carried the best chance of success. In order for patients, clinicians, and researchers to be able to communicate about conditions, internationally agreed classification system have been devised both by the pain community in general and by headache specialists. There are now several in use and there is reasonably good agreement between them.
Review of anatomy and physiology of the face in view of pain-generating and pain-mediating mechanisms
Authors: Obermann Mark , Seltzer Ze’ev , Diehl Scott R.
Published: May 2022

This chapter describes the sensory innervation of the face and head, focusing on anatomical substrates of clinical features that characterize cranial neuralgias. It draws attention to the key role of the caudal part of the trigeminal spinal nucleus and additional roles of the hypothalamus, descending modulation, and the parasympathetic system. The chapter provides an overview of neural excitability together with reasoning of how it can lead to various manifestations of cranial neuralgias. High-throughput ‘whole-genome sequencing’ studies demonstrate that rare mutations in genes involved in a wide range of neuronal functions underlie the risk for developing trigeminal neuralgia. Although still at an early stage, this research strongly suggests that most patients have inherited protein-changing mutations in several genes and that functionally different groups of genes are associated with different clinical subtypes distinguished by sex, age of onset, and presence of neurovascular compression.
Epidemiology of trigeminal neuralgia and its variants
Authors: Aggarwal Vishal R. , Zakrzewska Joanna M.
Published: May 2022

This chapter explores the prevalence and aetiology of trigeminal neuralgia and its variants. A summary review of prevalence studies, both population-based and hospital studies, is included. Studies showed that the prevalence of trigeminal neuralgia ranges between 0.1% and 0.7%. A lack of consistency in disease definition caused some studies to report higher prevalence which reverted to the ‘normal’ range (0.1–0.7%) when the correct disease definitions were applied. Aetiology was poorly understood although multiple sclerosis and hypertension were identified as risk factors. The burden of disease was substantial with a positive diagnosis impacting on quality of life and resulting in increased depression, anxiety, and sleep disorders. Trigeminal neuralgia and its variants are rare. The aetiology is poorly understood. Future high-quality, prospective, population-based studies are needed to identify risk factors and burden of disease. These can then be targeted to improve outcomes for patients suffering from this debilitating condition.
General approach to diagnosis and assessment of the facial pain patient
Authors: Zakrzewska Joanna M. , Nurmikko Turo , Hodaie Mojgan , Davis Karen D. , De Stefano Gianfranco , Truini Andrea
Published: May 2022

The diagnosis of a cranial neuralgia or neuropathy is clinical and rests on a detailed oral history. A working diagnosis can be obtained using eight yes-or-no questions. Clinical examination apart from sensory testing serves to rule out other facial pain conditions. Magnetic resonance imaging is essential as an aetiological investigation but requires use of specific imaging paradigms that allow visualization of the affected cranial nerve, surrounding blood vessels, and respective root entry zones to detect neurovascular compression. Only magnetic resonance imaging is capable of showing strategically placed brain lesions, such as multiple sclerosis plaques or solitary pontine lesions. Neurophysiological testing employing trigeminal reflexes reveals response abnormalities in practically all cases of secondary trigeminal neuralgia. As important as searching for a clinical diagnosis is assessment of the impact of the pain on the patient’s mood, functionality, and quality of life requires dedicated attention. Use of validated psychometric questionnaires will greatly facilitate this.
Trigeminal neuralgia: Diagnosis and classification
Authors: Nurmikko Turo , Zakrzewska Joanna M.
Published: May 2022

International classification systems define trigeminal neuralgia (TN) as a disorder characterized by recurrent, unilateral, brief electric shock-like pains, abrupt in onset and termination, limited to the trigeminal nerve territory, and triggered by innocuous stimuli. The clinical diagnosis is based on history. TN may manifest as purely paroxysmal pain, or be associated with concomitant continuous or near-continuous interparoxysmal pain. On the basis of aetiology, TN is divided into three categories: (1) classical (with magnetic resonance imaging evidence of significant neurovascular compression), (2) secondary (caused by a known disease, such as tumour or multiple sclerosis), and (3) idiopathic (no cause found). Key differential diagnoses include short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), trigeminal neuropathy, persistent idiopathic facial pain, and temporomandibular disorders.
Classical and idiopathic trigeminal neuralgia
Authors: Zakrzewska Joanna M. , Maarbjerg Stine
Published: May 2022

The term primary trigeminal neuralgia is used for classical and idiopathic trigeminal neuralgia as no cause other than compression of the trigeminal nerve is noted on magnetic resonance imaging in the classical cases. The shooting electrical pain is unilateral, evoked by light touch, and occurs as single or multiple episodes of pain lasting seconds to minutes. A more constant dull ache can be reported. Carbamazepine, oxcarbazepine, and other antiseizure medication used as monotherapy or polytherapy are effective. Tolerability of medications and poor quality of life leads patients to surgery. Microvascular decompression offers the longest period of freedom from pain but is associated with an 0.3% risk of mortality or other cerebral complications (0.6%). Ablative procedures typically offer periods of 2–4 years of pain relief, but all carry a high risk of sensory changes which can have a significant impact on quality of life. Multidisciplinary clinics and patient support groups are important sources of support.
Secondary trigeminal neuralgia
Authors: Truini Andrea , Nurmikko Turo
Published: May 2022

Secondary trigeminal neuralgia (TN), caused by a tumour or multiple sclerosis (MS), is symptomatically indistinguishable from classical or idiopathic TN, although patients tend to be younger and show more sensory deficits. Bilateral TN is more frequent in MS. Most tumours and arteriovenous malformations are located in posterior fossa and directly or indirectly cause compression of the trigeminal root. Magnetic resonance imaging is the investigation of choice. Complete resection of a tumour or arteriovenous malformation yields excellent short- and long-term results. Partial resections are accompanied by microvascular decompression, stereotactic radiosurgery, or endovascular embolization as required. Pharmacological management follows the same principles as for classical and idiopathic TN. Because of poor tolerance of centrally acting drugs, MS patients should be considered early for a neuroablative procedure. The role of magnetic resonance imaging-confirmed neurovascular compression as a concause of TN in a patient with MS remains unclear and routine microvascular decompression is not recommended.
Treatment of trigeminal neuralgia: Pharmacological
Authors: Di Stefano Giulia , Nurmikko Turo , Zakrzewska Joanna M.
Published: May 2022

By general consensus, the first-line treatment for trigeminal neuralgia is pharmacological. The two first drugs of choice are carbamazepine and oxcarbazepine, both voltage-gated sodium channel blockers that stabilize the hyperexcited neural membrane and inhibit repetitive firing. Although highly effective in controlling trigeminal neuralgia paroxysms, they are frequently discontinued because of sedative and cognitive side effects. Vixotrigine, a new sodium channel blocker that is selective for the Nav1.7 receptor, has shown promising efficacy without inducing side effects in a phase II trial and is awaiting pivotal clinical trials. If the first-line drugs fail to provide sufficient pain relief or are poorly tolerated, lamotrigine, baclofen, gabapentin, pregabalin, and botulinum toxin type A may be considered either alone or as add-on therapy. During acute exacerbations, in-hospital treatment may be necessary for rehydration, titration of drugs, and, in selected cases, lidocaine or fosphenytoin intravenous infusion, under cardiac monitoring.
Treatment of trigeminal neuralgia: Surgical
Authors: Zakrzewska Joanna M. , Burchiel Kim J. , Sekula Raymond F. , Sindou Marc , Régis Jean , Tuleasca Constantin , Noorani Imran , Sparrow Owen , Burchiel Kim J.
Published: May 2022

When patients with trigeminal neuralgia can no longer achieve adequate pain relief and quality of life becomes poor, surgical procedures need to be considered. There is a lack of high-quality evidence to support surgical treatments so all the recommendations are based on low-grade evidence of prospective or retrospective series. Microvascular decompression, a neurosurgical operation, is the procedure of choice in patients with primary trigeminal neuralgia who have evidence of neurovascular compression of the trigeminal nerve on magnetic resonance imaging. Long-term pain relief of 10 years can be achieved with minimal long-term complications. All the other procedures, including stereotactic radiosurgery, balloon compression, glycerol rhizolysis, and radiofrequency thermocoagulation, are destructive and are suitable for patients who are poor candidates for microvascular decompression including those with significant medical comorbidities. They will result in varying sensory loss and pain relief on average for 4 years. Patients should be made aware of the range of options open to them and the pros and cons of each procedure.
Painful trigeminal neuropathy
Authors: Jääskeläinen Satu K. , Nurmikko Turo
Published: May 2022

Painful trigeminal neuropathy (PTN) or trigeminal neuropathic pain can be caused by an external traumatic event (painful post-traumatic trigeminal neuropathy, previous name: anaesthesia dolorosa), other factors known to be able to cause trigeminal neuropathy (PTN attributed to other disorder), or without known aetiology (idiopathic PTN). The International Classification of Headache Disorders, third edition (ICHD-3) demands plausible neuroanatomical evidence for trigeminal neuropathy, and clinical signs of loss or gain of function for PTN. The first edition of the International Classification of Orofacial Pain (ICOP-I) includes confirmatory test evidence for PTN diagnosis, in addition to clinical signs; without confirmatory test results PTN remains probable. Confirmatory diagnostic tests include psychophysical and neurophysiological recordings, structural imaging, and skin biopsy. They are invaluable in PTN diagnostics, especially at the chronic stage when symptoms and signs may spread outside the original distribution, and clinical sensory examination may remain inconclusive because of its poor diagnostic value. Treatment for PTN consists of standard neuropathic pain medications and therapeutic neuromodulation techniques.
Glossopharyngeal neuralgia and neuropathy and nervus intermedius neuralgia and neuropathy
Authors: Sommer Claudia , Nurmikko Turo , Sekula Raymond F.
Published: May 2022

Glossopharyngeal neuralgia and nervus intermedius neuralgia are rare conditions characterized by paroxysmal pain similar in quality to that of trigeminal neuralgia but located and provoked by mechanical stimuli outside the trigeminal territory. Based on pain location, both pharyngeal and otalgic forms of glossopharyngeal neuralgia exist, while in intermedius neuralgia paroxysmal pain is described deep in the auditory canal. In both conditions, the diagnosis is strictly clinical. High-resolution three-dimensional magnetic resonance imaging is used to identify any neurovascular compression and rule out secondary forms. Pharmacological treatment is identical to that in trigeminal neuralgia. Neurosurgical interventions are advocated in pharmacoresistant cases, and while microvascular decompression with or without nerve resection remains popular, data for their long-term effectiveness remains limited. Peripheral nerve interventions may be useful in exceptional cases. A predominantly continuous and non-paroxysmal pain in the same locations is diagnosed as glossopharyngeal or nervus intermedius neuropathy, respectively.
Other common non-neuropathic facial pain conditions
Authors: Taneja Pankaj , Baad-Hansen Lene
Published: May 2022

The most common reason for pain in the orofacial region originates from the dentoalveolar and associated structures. However, when pain does not fit into this category it is important to evaluate the associated structures of the head and neck. This can mean that referral to the relevant discipline is required, when outside the remit of the investigating clinician. This chapter demonstrates the need for close collaboration between the medical and dental disciplines. Furthermore, depending upon the duration, that is, acute or chronic, the treatment strategy and prognosis may be altered. It is important to remember that more than one condition may be present at any one time. As dentoalveolar pain is very common clinicians may need to obtain a dental opinion especially in patients with heavily restored dentitions.
Role of psychological factors in the experience of trigeminal neuralgia
Authors: Daniel H. Clare
Published: May 2022

Trigeminal neuralgia is an unpredictable and distressing pain that often has psychological, behavioural, and social consequences on people and their lives. Using a purely medical model when assessing someone with trigeminal neuralgia increases the likelihood of the clinician overlooking some aspects of the person’s presentation and reduces the probability of them feeling heard and understood. While cognitive behavioural interventions are conducted by psychological professionals trained in this model, cognitive behavioural principles can be used by all clinicians when working with someone with trigeminal neuralgia. Taking this holistic approach not only reflects what we know about pain processing and perception, it also helps in our interactions with patients and with their engagement in physical and psychological interventions. This chapter is a guide to help all clinicians understand the importance of this approach and provides clinical tips that can be used when working with people with trigeminal neuralgia.
Patient support groups
Authors: Abbott Jillie , Patterson Claire , Semino Elena
Published: May 2022

The Trigeminal Neuralgia Association (now the Facial Pain Association) was formed in 1990 in the USA. A network of similar support groups exists around the world to educate both professionals and patients, raise awareness, and allow patients with trigeminal neuralgia to meet and provide mutual support and share information. These groups provide telephone and email helplines, giving 24-hour assistance. As technology has evolved, these groups now hold online meetings and provide moderated forums for discussion, but face-to-face contact is still vital, as demonstrated by feedback from local meetings and national and international conferences. Analysis of material posted on a UK members online forum shows how patients feel their experiences are validated and that the personal support they receive reduces their isolation and fear. Printed resources and websites can be shared with others for mutual understanding of this complex disorder, and to educate employers. The education gained from networking with others gives patients empowerment and enables them to work in closer partnership with their healthcare professionals.
Face2face: Visual journeys through trigeminal neuralgia
Authors: Eastman Ann , Glenn Alison , Padfield Deborah
Published: May 2022

Face2face was a project where patients with facial pain collaborated with a visual artist to create photographic images that would expand the language around pain. These images have now been made into a pack of 54 pain cards which can be used with other patients to improve consultations between healthcare professionals and patients. Two patients who participated in this project describe their experiences, which began with the difficulty of getting a diagnosis and unnecessary, irreversible dental treatment. The only medications available eventually became ineffective and resulted in significant side effects. They lived in fear, isolation, and low mood. Neurosurgery proved to be the successful treatment, resulting in freedom from pain. This chapter includes ten images they co-created over a period of time with artist Deborah Padfield.
Energy conserving and well-balanced discontinuous Galerkin methods for the Euler–Poisson equations in spherical symmetry
Authors: Zhang Weijie , Xing Yulong , Endeve Eirik
Published: May 2022

This paper presents high-order Runge–Kutta (RK) discontinuous Galerkin methods for the Euler–Poisson equations in spherical symmetry. The scheme can preserve a general polytropic equilibrium state and achieve total energy conservation up to machine precision with carefully designed spatial and temporal discretizations. To achieve the well-balanced property, the numerical solutions are decomposed into equilibrium and fluctuation components that are treated differently in the source term approximation. One non-trivial challenge encountered in the procedure is the complexity of the equilibrium state, which is governed by the Lane–Emden equation. For total energy conservation, we present second- and third-order RK time discretization, where different source term approximations are introduced in each stage of the RK method to ensure the conservation of total energy. A carefully designed slope limiter for spherical symmetry is also introduced to eliminate oscillations near discontinuities while maintaining the well-balanced and total-energy-conserving properties. Extensive numerical examples – including a toy model of stellar core collapse with a phenomenological equation of state that results in core bounce and shock formation – are provided to demonstrate the desired properties of the proposed methods, including the well-balanced property, high-order accuracy, shock-capturing capability, and total energy conservation.