bluuebunny/crossref_metadata_2025 huggingface dataset:
Antileishmanial effect of the natural immunomodulator genipin through suppression of host negative regulatory protein UCP2
Authors: Gupta Anand Kumar , Roy Shalini , Das Pijush K
Published: September 2020

Objectives

To evaluate the antileishmanial efficacy of genipin, which specifically inhibits uncoupling protein 2 (UCP2) that is induced in leishmaniasis to neutralize reactive oxygen species (ROS).

Methods

The effect of genipin was assessed against intracellular parasites in cultured macrophages and in suppressing spleen and liver parasite burdens in a BALB/c mouse model of visceral leishmaniasis by microscopic evaluation of intracellular amastigotes stained with Giemsa. ROS and mitochondrial membrane potential were measured by H2DCFDA- and JC-1-based fluorometric analysis. ELISA was performed for various Th1 and Th2 cytokines in both in vitro and in vivo infected conditions to evaluate the type of immunological responses. The role of UCP2 was assessed by lipofectamine-mediated transfection and overexpression in macrophages and short hairpin RNA-mediated knockdown of UCP2 in infected animals.

Results

Genipin reduced the infection-induced UCP2 levels in macrophages, with optimum effect at 100 μM. Genipin reversed parasite-induced ROS suppression and mitochondrial membrane potential disruption. It has no inhibitory effect on promastigote or axenic amastigote forms, but markedly suppressed amastigote multiplication within macrophages, which was reversed by the ROS scavenger N-acetyl cysteine. Genipin administration (30 mg/kg/day) in infected mice showed significant suppression of liver and spleen parasite burdens with an enhanced host-favourable cytokine balance in a ROS–p38 mitogen-activated protein kinase-dependent manner. Co-treatment with genipin plus a sublethal dose of sodium antimony gluconate (SAG50) showed almost a curative reduction in spleen and liver parasite burden.

Conclusions

These results suggest the effectiveness of genipin as a synergistic agent for the front-line antileishmanial drug SAG in circumventing the resistance and toxicity problems associated with its high curative dose.
One Brand, Many Trajectories: Narrative Navigation in Transmedia
Authors: Feiereisen Stephanie , Rasolofoarison Dina , Russell Cristel Antonia , Schau Hope Jensen
Published: September 2020

In an era of unprecedented consumer access to media and the tools to control narrative delivery, speed, and exposure to transmedia content, there is no longer the illusion of a cohesive narrative managed by a recognized singular author or unified authorial voice. Instead, consumers carve their own trajectories through brand narratives. Our multimethod inquiry of television series viewing, based on a combination of interviews, diaries, video recordings followed by member-check interviews and online forum analyses, identifies two key forces that guide narrative navigation: how consumers manage a text’s gravitational pull and its permeability to transmedia content. We find that consumers shape their own trajectories by adopting and/or moving between nine documented narrative positions. This more nuanced understanding of narrative consumption in a transmedia environment offers new insights for the study of narrative brand spaces and brand storytelling.
Enlightenment architectures: the reconstruction of Sir Hans Sloane’s cabinets of ‘Miscellanies’
Authors: Sloan Kim , Nyhan Julianne
Published: September 2020

Focusing on Sir Hans Sloane’s catalogue of ‘Miscellanies’, now in the British Museum, this paper asks firstly how Sloane described objects and secondly whether the original contents of the cabinets can be reconstructed from his catalogue. Drawing on a sustained, digitally augmented analysis – the first of its kind – of Sloane’s catalogues, we respond to these questions and offer an initial analysis of the contents of the cabinets that held the miscellaneous objects at Sloane’s manor house in Chelsea. Knowledge of how and why Sloane catalogued this part of his collection has hitherto remained underdeveloped. We argue that his focus on preservation and documentation in his cataloguing did not preclude a research role, but rather was founded on immersive participation. Our work was undertaken as part of a Leverhulme Trust funded research project, Enlightenment Architectures: Sir Hans Sloane’s Catalogues of his Collections (2016–19), a collaboration between the British Museum and University College London.
Modeling the Sensitivity of Blacklegged Ticks (Ixodes scapularis) to Temperature and Land Cover in the Northeastern United States
Authors: Winter Jonathan M , Partridge Trevor F , Wallace Dorothy , Chipman Jonathan W , Ayres Matthew P , Osterberg Erich C , Dekker Eliza R
Published: September 2020

The prevalence of Lyme disease and other tick-borne diseases is dramatically increasing across the United States. While the rapid rise in Lyme disease is clear, the causes of it are not. Modeling Ixodes scapularis Say (Acari: Ixodidae), the primary Lyme disease vector in the eastern United States, presents an opportunity to disentangle the drivers of increasing Lyme disease, including climate, land cover, and host populations. We improved upon a recently developed compartment model of ordinary differential equations that simulates I. scapularis growth, abundance, and infection with Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) by adding land cover effects on host populations, refining the representation of growth stages, and evaluating output against observed data. We then applied this model to analyze the sensitivity of simulated I. scapularis dynamics across temperature and land cover in the northeastern United States. Specifically, we ran an ensemble of 232 simulations with temperature from Hanover, New Hampshire and Storrs, Connecticut, and land cover from Hanover and Cardigan in New Hampshire, and Windsor and Danielson in Connecticut. Consistent with observations, simulations of I. scapularis abundance are sensitive to temperature, with the warmer Storrs climate significantly increasing the number of questing I. scapularis at all growth stages. While there is some variation in modeled populations of I. scapularis infected with B. burgdorferi among land cover distributions, our analysis of I. scapularis response to land cover is limited by a lack of observations describing host populations, the proportion of hosts competent to serve as B. burgdorferi reservoirs, and I. scapularis abundance.
Ferroptosis in plants: triggers, proposed mechanisms, and the role of iron in modulating cell death
Authors: Distéfano Ayelén Mariana , López Gabriel Alejandro , Setzes Nicolás , Marchetti Fernanda , Cainzos Maximiliano , Cascallares Milagros , Zabaleta Eduardo , Pagnussat Gabriela Carolina
Published: September 2020

Regulated cell death plays key roles during essential processes throughout the plant life cycle. It takes part in specific developmental programs and maintains homeostasis of the organism in response to unfavorable environments. Ferroptosis is a recently discovered iron-dependent cell death pathway characterized by the accumulation of lipid reactive oxygen species. In plants, ferroptosis shares all the main hallmarks described in other systems. Those specific features include biochemical and morphological signatures that seem to be conserved among species. However, plant cells have specific metabolic pathways and a high degree of metabolic compartmentalization. Together with their particular morphology, these features add more complexity to the plant ferroptosis pathway. In this review, we summarize the most recent advances in elucidating the roles of ferroptosis in plants, focusing on specific triggers, the main players, and underlying pathways.
Multi-dimensional Interpretations of Presburger Arithmetic in Itself
Authors: Pakhomov Fedor , Zapryagaev Alexander
Published: September 2020

Presburger arithmetic is the true theory of natural numbers with addition. We study interpretations of Presburger arithmetic in itself. The main result of this paper is that all self-interpretations are definably isomorphic to the trivial one. Here we consider interpretations that might be multi-dimensional. We note that this resolves a conjecture by Visser (1998, An overview of interpretability logic. Advances in Modal Logic, pp. 307–359). In order to prove the result, we show that all linear orderings that are interpretable in $({\mathbb{N}},+)$ are scattered orderings with the finite Hausdorff rank and that the ranks are bounded in the terms of the dimensions of the respective interpretations.
Health Literacy
Authors: Wittenberg Elaine , Goldsmith Joy V. , Ragan Sandra L. , Parnell Terri Ann
Published: September 2020

Caregivers require the skills needed to support complex medical conditions and utilize opportunities to access, understand, and share reliable health information with care recipients to advocate for successful disease management and decisions. This chapter addresses the unique characteristics of caregiver health literacy and the burden of navigating increasingly complex healthcare systems. The connection and consequence between health literacy and social determinants of health upon caregiving, the implications of caregiver health literacy skills, and the influence of culturally and linguistically appropriate standards on enhanced caregiver health literacy, clear communication, and family-centered care are discussed. Health literacy involves not only caregivers’ and patients’ cognitive and functional skills, but also the collaborative efforts among patients, caregivers, healthcare organizations, healthcare providers, and communities. This collaborative view of health literacy underscores the synergy among healthcare recipients, formal and informal healthcare providers, and resources from healthcare systems to reduce health literacy barriers, ease communication burden, and lessen inequities in health.
Caring for the Family Caregiver
Authors: Wittenberg Elaine , Goldsmith Joy V. , Ragan Sandra L. , Parnell Terri Ann
Published: September 2020

There is little evidence for caregiver assessment and interventions based on unique social and contextual factors of caregiving. Current approaches to caring for the family caregiver involve a “one size fits all” approach where caregiver assessment may or may not occur, and there is no link between identification of caregiver needs and recommended resources. When caregiver assessment does occur, it does not involve unique caregiving characteristics that positively impact communication and health literacy. Caring for the Family Caregiver, a communication and health literacy framework, is introduced and consists of teaching healthcare providers to address caregiving types by finding disease information, assessing and integrating information, partnering with the caregiver, finding support, talking with the caregiver, and planning for caregiver self-care. Directions for future research are also summarized.
Screening and Brief Intervention
Authors: Fingerhood Michael I.
Published: September 2020

Screening and brief interventions for alcohol and other drugs are recommended by many expert guidelines. This is often followed by referral to treatment for those with a moderate–severe substance use disorder (SBIRT). Screening begins with asking about alcohol and other drug use; a number of instruments can help with this process. Brief intervention is a motivational process of assessing drug use, giving feedback, setting goals, arriving at a strategy for change, and providing a plan for follow-up. Research on SBIRT has yielded mixed results, with some evidence of efficacy, particularly for nondependent at-risk drinkers. Assessing an individual’s stage of change can help inform the approach to helping initiate recovery. Engaging and building rapport helps promote change by offering hope and encouragement, as well as treatment options. Relapse is a time for both patient and clinician to learn from mistakes and to correct them by strengthening treatment. Drug testing has limited utility for screening in unselected patient populations, but it can be useful in certain clinical situations and for monitoring individuals in treatment.
Alcohol
Authors: Fingerhood Michael I.
Published: September 2020

Approximately half of all Americans drink alcohol, with 6% classified as heavy drinkers. At low levels, alcohol causes euphoria and disinhibition; at higher levels, it causes sedation and impaired memory and coordination. Overdose is characterized by drowsiness, slurred speech, nausea, vomiting, and respiratory depression. Treatment is supportive. Withdrawal symptoms include tremors, seizures, and delirium and may be life-threatening. Diagnosis is based on the impact of alcohol use on an individual’s health, social functioning, and personal relationships. Levels of alcohol can be measured in the blood or breath. Medical complications include liver disease, hypertension, pancreatitis, dementia, and some cancers. Benzodiazepines can be used to treat moderate–severe alcohol withdrawal and to prevent delirium and seizures. Further treatment after withdrawal is required for long-term recovery. Brief advice is effective for problem drinkers. Self-help groups, counseling, and residential treatment help some with more severe problems. A number of pharmacotherapies are modestly effective, including naltrexone, acamprosate, topiramate, and gabapentin. Disulfiram may be effective for selected individuals.
Antidepressants
Authors: Ansari Arash , Osser David N.
Published: September 2020

The chapter on antidepressants discusses and reviews the use of tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors, as well as bupropion, mirtazapine, nefazodone, trazodone, and the newer antidepressants vilazodone and vortioxetine. It reviews each medication’s mechanism of action, clinical characteristics, potential medication interactions, adverse effects, and other risks. The chapter also reviews emerging pharmacotherapies such as ketamine, esketamine, and brexanolone. It also briefly discusses complementary and alternative pharmacotherapies. The chapter includes an in-depth discussion of the clinical use of antidepressants for the treatment of unipolar depression and other psychiatric and medical disorders. It also discusses the use of antidepressants in women of childbearing age, notably in regards to pregnancy and breastfeeding considerations. Finally, each chapter includes a table of antidepressants that includes each medication’s generic and brand names, usual adult doses, pertinent clinical comments, black box warnings, and FDA indications.
Treatments for Substance Use Disorders
Authors: Ansari Arash , Osser David N.
Published: September 2020

The chapter on treatments for substance use disorders discusses and reviews the use of medication-assisted treatments with (a) methadone, buprenorphine/naloxone, and naltrexone for opioid use disorders; (b) disulfiram, acamprosate, naltrexone, and several off-label medications for alcohol use disorders; and (c) nicotine replacement therapies, bupropion, and varenicline for tobacco use disorders. The chapter reviews the mechanisms of action, clinical characteristics, potential medication interactions, and adverse effects of these medications, followed by an in-depth discussion of their clinical use in these disorders. The chapter also briefly reviews several non-Food and Drug Administration (FDA)-approved medicines studied for cocaine, cannabis, and amphetamine use disorders. It also briefly discusses complementary and alternative pharmacotherapies, such as the use of cannabinoids. It also discusses the use of these medicines in women of childbearing age, notably for pregnancy and breastfeeding considerations. Finally, the chapter includes a table of approved substance use disorder medicines that includes each medicine’s generic and brand names, usual adult doses, pertinent clinical comments, black box warnings, and FDA indications.
Introduction to the neuropsychiatric examination
Authors: Silver Jonathan , Blum Sonja
Published: September 2020

The neuropsychiatric examination is designed to assess emotional, behavioural, and cognitive problems associated with neurological disorders and must be adjusted in relation to the patient’s symptoms, abilities, or impairments. This chapter describes the basic stages of the examination, focusing initially on its application for patients with milder symptoms, and then describing its use for patients with more severe cognitive and behavioural problems. It begins with the interview, in which information is gathered on the patient’s mental history, cognition, and family neuropsychiatric history to identify the likelihood of certain genetic conditions. A description is then given of the mental status examination, measuring the patient’s performance across cognitive domains, before the application of a brief neurological examination. A number of useful diagnostic tests are then discussed, along with the special considerations necessary for patients with post-traumatic amnesia, post-traumatic confusional state, and disorders of consciousness. The chapter contains case studies and learning points.
Genetics of neuropsychiatric disease
Authors: Bruno Stefania , Lahiri Nayana
Published: September 2020

To better understand the intricacies of genetic influences on neuropsychiatric disease, it is important first to have a grounding in the models of human inheritance and current diagnostic techniques. This chapter covers the fundamentals of genetic disorders, giving insights into chromosomal, single-gene, and mitochondrial disorders. Moreover, it explores the changing applications of genomic technologies, such as whole exome and whole genome sequencing, through the lens of their implications for neuropsychiatry. Clinical examples are provided to give an idea of the genetic underpinnings of Alzheimer’s disease, Parkinson’s disease, and other familiar disorders.
Neuropsychiatry curriculum and key clinical competencies
Authors: Sachdev Perminder S. , Mohan Adith
Published: September 2020

In many respects, neuropsychiatry (NP) and behavioural neurology (BN) can be seen as two different approaches to the same set of disorders and conditions. The treatment of many conditions, such as Tourette syndrome, requires an understanding of both. As such, while this chapter is focused on a curriculum for NP, it also identifies areas of relevance to BN to allow for the curriculum to be adapted to both. The goals and structure of an NP training programme are laid out, followed by a more comprehensive discussion of the course’s aims and the skills required to complete it, from the assessment and management of neuropsychiatric patients to neurorehabilitation. Finally the key competencies are outlined, with examples drawn from the core skills module and then modules specific to sub-specialties and certain types of disorder which bridge the fields of NP and BN such as neurocognitive disorders, movement disorders, and substance-related psychiatric disorders.
Brain injury
Authors: Agrawal Niruj
Published: September 2020

Acquired brain injuries (ABIs) can be categorized as traumatic or non-traumatic brain injuries. Traumatic brain injuries (TBIs), sub-classified as either open or closed TBIs, depending on whether there is a fracture of the skull or a breach of the dura mater, are typically caused by a physical impact such as blunt trauma or a fall. Non-TBIs can be caused by cerebrovascular events, infections, or chemical factors. This chapter predominantly focuses on TBIs, exploring techniques to measure their extent, such as the Glasgow Coma Scale (GCS), and the aetiology of TBIs. Moreover, the long-term effects of TBIs are explored, such as anxiety disorders which often present themselves in their aftermath and the likelihood for TBI-induced personality change. The associated effects of non-TBIs are then examined, specifically with reference to anoxic brain injuries and those induced by drugs or alcohol.
Neuropsychiatric aspects of epilepsy
Authors: Mula Marco , Yogarajah Mahinda
Published: September 2020

Epilepsy is one of the commonest neurological disorders, affecting approximately 50 million people worldwide, and it is now recognized as a disorder of the brain characterized not only by recurrent seizures, but also by its neurobiological, cognitive, psychological, and social consequences. In general, psychiatric disorders show a uniformly increased prevalence in epilepsy, as compared to the general population. This chapter focuses on major axis I disorders encountered in adults with epilepsy, namely mood and anxiety disorders and psychoses, with special emphasis on differential diagnosis and treatment. The contribution of epilepsy treatment, such as epilepsy surgery and antiepileptic drugs, is also discussed. Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but they are not caused by ictal epileptiform activity. PNES represent another frequently encountered condition in neuropsychiatric clinics. Epidemiology, differential diagnosis and management of PNES are discussed.
Neuropsychiatric aspects of movement disorders
Authors: Cavanna Andrea E. , Rickards Hugh
Published: September 2020

Changes in movement and posture often coexist with changes in mood, cognition, and arousal in a range of brain disorders. A holistic neuropsychiatric view is needed to diagnose, manage, and research these conditions in order to discover causes and effective treatments and to design appropriate management strategies. Limitations related to the dualistic nature of the language used in this area need to be addressed in order to improve science and care.
Neuropsychiatry of stroke and transient ischaemic attack
Authors: Chun Yvonne , McWhirter Laura , Carson Alan
Published: September 2020

Stroke is one of the leading causes of death and disability both in the United Kingdom and worldwide. Approximately one-fifth of strokes are preceded by a transient ischaemic attack (TIA), with TIA patients being at greatest risk of stroke in the days immediately following TIA onset. This chapter examines the clinical presentation of stroke, along with methods of managing and preventing it. It then explores the neuropsychiatric sequelae of stroke, such as anxiety, depression, psychosis, and apathy. Case studies are then provided as examples of the commonest neuropsychiatric comorbidities of stroke.
Neuropsychiatric aspects of CNS tumours in adults
Authors: Mitchell Alex J. , Hopwood Audrey
Published: September 2020

A brain tumour is the most feared cancer diagnosis by the general public. Primary brain tumours account for about 1.5% of all new cases of cancer, and 2.5% of all cancer deaths. However, most brain tumours are, in fact, metastases from other cancer sites. Brain tumours cause considerable psychological and psychiatric complications, as well as a burden for caregivers, and hence a reduction in overall quality of life. Around 90% of patients will suffer neuropsychiatric complications, and in around 20%, these are the presenting symptoms. Neuropsychiatric complications often improve following brain tumour treatment, such as radiotherapy, but can also deteriorate. New therapeutic techniques have improved survival and are gradually improving quality of life. However, this is only effective if neuropsychiatric complications are recognized and addressed.
Functional neurological disorders
Authors: Edwards Mark , Cope Sarah R. , Agrawal Niruj
Published: September 2020

Referred to by the ancient Greeks as ‘Hysteria’, functional neurological disorders (FNDs) are one of the most prevalent diagnoses made in neurology clinics. Nonetheless, in part, due to the uncertainty regarding the potential voluntariness of such conditions, diagnostic and treatment services for FNDs are underdeveloped by comparison to those for other causes of neurological symptoms. This chapter discusses historical approaches to the classification and approach to FNDs, before moving on to contemporary treatments for it. Various treatments are then described with regard to certain forms of FNDs, such as the effects of cognitive behavioural therapy (CBT) and psychodynamic interpersonal therapy on functional non-epileptic attacks and multidisciplinary inpatient treatment, physiotherapy, and hypnosis on functional motor disorder. Finally, the relative lack of treatment options for functional cognitive disorder (FCD) is discussed, along with the initial findings of a pilot randomized controlled trial for it.
Neuropsychiatry of aggression
Authors: (Shoumi) Deb Shoumitro , Deb Tanya
Published: September 2020

Conditions affecting the central nervous system, such as trauma or degenerative illness, often lead to neurobehavioural disorders. One of the most difficult of these to treat is aggression. Outwardly directed aggression can be divided into two types—reactive and proactive—the first of which is less structured and generally presents with visible anger, while the latter is structured and premeditated. While there exists no specific diagnostic criteria for either type of aggression, the closest that exist are intermittent explosive disorder (IED) for the former and conduct disorder (CD), which has been known to evolve into personality disorders (PDs), for the latter. This chapter explores the relation between aggression and other neuropsychiatric conditions, beginning with its neurobiological underpinnings. It then describes assessment methods, such as the Behaviour itself, Medical/ organic issues, Person showing the behaviour, Psychiatric/psychological issues, and Social/ occupational/ personal issues (BMPPS) model, before discussing treatments, both pharmacological and non-pharmacological. For the former, the effectiveness of various medications is discussed, from antipsychotics to mood stabilizers.
Neuropsychiatry in the criminal courts
Authors: Eastman Nigel , Poole Norman A. , Kopelman Michael D.
Published: September 2020

Given neuropsychiatric expertise can be called upon at any stage of the criminal legal process, there exists a range of criminal legal constructs on which an expert might be invited to offer an opinion, each with its own distinct mapping exercise. This chapter outlines the law as it relates to both psychiatry and neuropsychiatry, before going on to describe the practicalities of a forensic neuropsychiatric assessment. Finally, the manner in which the expert’s neuropsychiatric findings relate to the validity of a case are explored such as a defendant’s fitness to plead, their potential to malinger, or their mental capacity for intent at the time of the offence. Due to the impact such expert testimony can make on the course of the trial, a significant history of practice and a strong understanding of the ethical implications are necessary.
Inference, causality, and interpretation
Authors: Lang Iain
Published: September 2020

Understanding causality and interpreting evidence in public health practice can be challenging. This chapter describes some of the key concepts involved, including association, causation, bias, confounding, and error. Although understanding the causes of things is a key public health skill, just as important are being aware of the limits to our understanding of what causes things, being able to communicate these limits to other people, and being able to make decisions even when the information we have is incomplete or inconclusive. This chapter will introduce you to some of the main concepts in this area, help you understand how the inferences we can draw from data are shaped, and give you some insight into the limits of the conclusions we can draw from the available evidence.
Investigating alleged clusters
Authors: Saunders Patrick , Kibble Andrew J. , Burls Amanda , Saunders AT
Published: September 2020

This chapter aims to: describe the methodological and communication challenges in investigating allegations of environmentally related disease clusters; provide public health practitioners with a structured and systematic approach to preparing for, and responding effectively and appropriately to, such allegations.
Safeguarding and promoting health in the workplace
Authors: Kales Stefanos N. , Chin Michael S.
Published: September 2020

After reading this chapter you will be able to understand: the nature and scope of occupational health practice; how illness and injury prevention in the workplace contribute to general public health.
Public health practice in primary care
Authors: Gillam Steve
Published: September 2020

Having read this chapter, you should: understand why effective systems of primary care—entailing universal health coverage—are integral to delivering public health objectives; know those public health interventions that primary care professionals provide; be able to define those elements of primary care that need strengthening in order to deliver public health objectives; appreciate how the skills of public health and primary care practitioners complement and contrast with one another.
Regulation
Authors: Gostin Lawrence
Published: September 2020

The objectives of this chapter are to help you understand: the impact of legislation, regulations, and litigation on the public’s health; the powers, duties, and restraints imposed by the law on public health officials; the potential of legal change to improve the public’s health; the role of international law and institutions in securing public health in the face of increasing globalization.
Effective meetings
Authors: Jessop Edmund
Published: September 2020

This chapter presents guidance on how to ensure a meeting is effective and steps to set up and run meetings.
Governance and accountability
Authors: Pearson Virginia
Published: September 2020

Reading this chapter will: improve your understanding of the principles of governance and accountability; help you recognize potential shortcomings in systems that may result in risk to individuals; improve your knowledge of how to reduce risk through creating assurance that those systems are working effectively.
Business planning
Authors: Gogarty Mike
Published: September 2020

This chapter will help you: understand the fundamentals of business planning; develop an effective business case
Recovering from acute heart events
Authors: Corrà Ugo , Schmid Jean-Paul
Published: September 2020

Despite extraordinary advances in pharmacological and interventional therapies, cardiac rehabilitation (CR) and secondary prevention programmes have maintained a class I indication with level of evidence A in patients after acute coronary syndrome (ACS) and a class I recommendation with level of evidence B in patients after surgical revascularization and with chronic ischaemic heart disease (IHD). In post-acute or chronic heart failure (New York Heart Association (NYHA) class II–III, both with reduced or preserved ejection fraction (EF)), CR has a class I recommendation with level of evidence A. In patients with recent valvular heart surgery, there is an important indication for CR intervention early after surgery. Once admitted to CR, patients should have their clinical status assessed or reviewed before starting any activities, particularly exercise training. Assessment should cover medical history, personal goals and preferences, physical parameters, disease-specific status, disease management, psychosocial health, risk factors, functional exercise capacity, health-related quality of life (HRQoL), and the impact of physical deconditioning of comorbidities. Previous exercise levels, aids used, goals, and residual exercise capacity/function should also be considered. If patients are not clinically stable, CR interventions should be deferred. However, if patients are stable, intervention should be started as soon as possible after an acute cardiac event after appropriate functional assessment.
Return to work
Authors: Reibis Rona , Völler Heinz
Published: September 2020

The vocational reintegration of patients after an acute cardiac event is a crucial step towards complete convalescence from both the social and individual point of view. Residual job ability (partial, total/temporary, or permanent disability) depends on existing cardiac, psycho-cognitive and professional barriers. Return to work (RTW) rates are determined by left ventricular function, residual ischaemia, and heart rhythm stability, as well as by the occupational requirement profile, such as blue- or white-collar work, night shifts, and the ability to commute. Psychosocial factors, including depression, self-perceived health situation, and pre-existing cognitive impairment, determine the reintegration rate to a significant extent. Patients at risk of poor vocational outcomes should be identified early in the rehabilitation process in order to avoid failure of reintegration and to prevent social and professional exclusion with adverse psychological and financial consequences.
The Galactic cosmic ray intensity at the evolving Earth and young exoplanets
Authors: Rodgers-Lee D , Vidotto A A , Taylor A M , Rimmer P B , Downes T P
Published: September 2020

Cosmic rays may have contributed to the start of life on the Earth. Here, we investigate the evolution of the Galactic cosmic ray spectrum at the Earth from ages t = 0.6−6.0 Gyr. We use a 1D cosmic ray transport model and a 1.5D stellar wind model to derive the evolving wind properties of a solar-type star. At $t=1\,$ Gyr, approximately when life is thought to have begun on the Earth, we find that the intensity of ∼GeV Galactic cosmic rays would have been ∼10 times smaller than the present-day value. At lower kinetic energies, Galactic cosmic ray modulation would have been even more severe. More generally, we find that the differential intensity of low-energy Galactic cosmic rays decreases at younger ages and is well described by a broken power law in solar rotation rate. We provide an analytic formula of our Galactic cosmic ray spectra at the Earth’s orbit for different ages. Our model is also applicable to other solar-type stars with exoplanets orbiting at different radii. Specifically, we use our Galactic cosmic ray spectrum at 20 au for $t=600\,$ Myr to estimate the penetration of cosmic rays in the atmosphere of HR 2562b, a directly imaged exoplanet orbiting a young solar-type star. We find that the majority of particles <0.1 GeV are attenuated at pressures ≳10−5 bar and thus do not reach altitudes below ∼100 km. Observationally constraining the Galactic cosmic ray spectrum in the atmosphere of a warm Jupiter would in turn help constrain the flux of cosmic rays reaching young Earth-like exoplanets.
Particle acceleration by interstellar plasma shock waves in non-uniform background magnetic field
Authors: Rashed-Mohassel P , Ghorbanalilu M
Published: September 2020

Particle acceleration by plasma shock waves is investigated for a magnetized plasma cloud propagating in a non-uniform background magnetic field by means of analytical and numerical calculations. The mechanism studied here is mainly, magnetic trapping acceleration (MTA) which is previously investigated for a cloud moving through the uniform interstellar magnetic field (IMF). In this work, the acceleration is studied for a cloud moving in an antiparallel background field with spatial variations along the direction of motion. For negative variation, the cloud moves towards an antiparallel magnetic field with an increasing intensity, the trapped particle moves to locations with higher convective electric field and therefore gains more energy over time. For positive variation, the background field decreases to zero and changes into a parallel field with an increasing intensity. It is concluded that, when the background field vanishes, the MTA mechanism ceases and the particle escapes into the space. This leads to a bouncing acceleration which further increases energy of the gyrating particle. The two processes are followed by a shock drift acceleration, where due to the background magnetic field gradient, the particle drifts along the electric field and gains energy. Although for positive variation, three different mechanisms are involved, energy gain is less than in the case of a uniform background field.
Proton core behaviour inside magnetic field switchbacks
Authors: Woolley Thomas , Matteini Lorenzo , Horbury Timothy S , Bale Stuart D , Woodham Lloyd D , Laker Ronan , Alterman Benjamin L , Bonnell John W , Case Anthony W , Kasper Justin C , Klein Kristopher G , Martinović Mihailo M , Stevens Michael
Published: September 2020

During Parker Solar Probe’s first two orbits, there are widespread observations of rapid magnetic field reversals known as switchbacks. These switchbacks are extensively found in the near-Sun solar wind, appear to occur in patches, and have possible links to various phenomena such as magnetic reconnection near the solar surface. As switchbacks are associated with faster plasma flows, we questioned whether they are hotter than the background plasma and whether the microphysics inside a switchback is different to its surroundings. We have studied the reduced distribution functions from the Solar Probe Cup instrument and considered time periods with markedly large angular deflections to compare parallel temperatures inside and outside switchbacks. We have shown that the reduced distribution functions inside switchbacks are consistent with a rigid velocity space rotation of the background plasma. As such, we conclude that the proton core parallel temperature is very similar inside and outside of switchbacks, implying that a temperature–velocity (T–V) relationship does not hold for the proton core parallel temperature inside magnetic field switchbacks. We further conclude that switchbacks are consistent with Alfvénic pulses travelling along open magnetic field lines. The origin of these pulses, however, remains unknown. We also found that there is no obvious link between radial Poynting flux and kinetic energy enhancements suggesting that the radial Poynting flux is not important for the dynamics of switchbacks.
Large-scale simulations of H and He reionization and heating driven by stars and more energetic sources
Authors: Eide Marius B , Ciardi Benedetta , Graziani Luca , Busch Philipp , Feng Yu , Di Matteo Tiziana
Published: September 2020

We present simulations of cosmic reionization and reheating from z = 18 to z = 5, investigating the role of stars (emitting soft UV-photons), nuclear black holes (BHs, with power-law spectra), X-ray binaries (XRBs, with hard X-ray dominated spectra), and the supernova-associated thermal bremsstrahlung of the diffuse interstellar medium (ISM, with soft X-ray spectra). We post-process the hydrodynamical simulation MassiveBlack-II (MBII) with multifrequency ionizing radiative transfer. The source properties are directly derived from the physical environment of MBII, and our only real free parameter is the ionizing escape fraction fesc. We find that, among the models explored here, the one with an escape fraction that decreases with decreasing redshift yields results most in line with observations, such as of the neutral hydrogen fraction and the Thomson scattering optical depth. Stars are the main driver of hydrogen reionization and consequently of the thermal history of the intergalactic medium (IGM). We obtain 〈xH ii〉 = 0.99998 at z = 6 for all source types, with volume-averaged temperatures $\langle \, T \rangle \sim 20\,000$ K. BHs are rare and negligible to hydrogen reionization, but conversely they are the only sources that can fully ionize helium, increasing local temperatures by ∼104 K. The thermal and ionization state of the neutral and lowly ionized hydrogen differs significantly with different source combinations, with ISM and (to a lesser extent) XRBs, playing a significant role and, as a consequence, determining the transition from absorption to emission of the 21-cm signal from neutral hydrogen.
Formation and evolution of the local interstellar environment: combined constraints from nucleosynthetic and X-ray data
Authors: Fujimoto Yusuke , Krumholz Mark R , Inutsuka Shu-ichiro , Boss Alan P , Nittler Larry R
Published: September 2020

Several observations suggest that the Solar system has been located in a region affected by massive stellar feedback for at least a few Myr; these include detection of live 60Fe in deep-sea archives and Antarctic snow, the broad angular distribution of 26Al around the Galactic plane seen in all-sky γ-ray maps, and the all-sky soft X-ray background. However, our position inside the Galactic disc makes it difficult to fully characterize this environment, and our limited time baseline provides no information about its formation history or relation to large-scale galactic dynamics. We explore these questions by using an N-body + hydrodynamics simulation of a Milky-Way-like galaxy to identify stars on Sun-like orbits whose environments would produce conditions consistent with those we observe. We find that such stars are uncommon but not exceptionally rare. These stars are found predominantly near the edges of spiral arms, and lie inside kpc-scale bubbles that are created by multiple generations of star formation in the arm. We investigate the stars’ trajectories and find that the duration of the stay in the bubble ranges from 20 to 90 Myr. The duration is governed by the crossing time of stars across the spiral arm. This is generally shorter than the bubble lifetime, which is ∼100 Myr as a result of the continuous gas supply provided by the arm environment.
miRNASNP-v3: a comprehensive database for SNPs and disease-related variations in miRNAs and miRNA targets
Authors: Liu Chun-Jie , Fu Xin , Xia Mengxuan , Zhang Qiong , Gu Zhifeng , Guo An-Yuan
Published: September 2020

MicroRNAs (miRNAs) related single-nucleotide variations (SNVs), including single-nucleotide polymorphisms (SNPs) and disease-related variations (DRVs) in miRNAs and miRNA-target binding sites, can affect miRNA functions and/or biogenesis, thus to impact on phenotypes. miRNASNP is a widely used database for miRNA-related SNPs and their effects. Here, we updated it to miRNASNP-v3 (http://bioinfo.life.hust.edu.cn/miRNASNP/) with tremendous number of SNVs and new features, especially the DRVs data. We analyzed the effects of 7 161 741 SNPs and 505 417 DRVs on 1897 pre-miRNAs (2630 mature miRNAs) and 3′UTRs of 18 152 genes. miRNASNP-v3 provides a one-stop resource for miRNA-related SNVs research with the following functions: (i) explore associations between miRNA-related SNPs/DRVs and diseases; (ii) browse the effects of SNPs/DRVs on miRNA-target binding; (iii) functional enrichment analysis of miRNA target gain/loss caused by SNPs/DRVs; (iv) investigate correlations between drug sensitivity and miRNA expression; (v) inquire expression profiles of miRNAs and their targets in cancers; (vi) browse the effects of SNPs/DRVs on pre-miRNA secondary structure changes; and (vii) predict the effects of user-defined variations on miRNA-target binding or pre-miRNA secondary structure. miRNASNP-v3 is a valuable and long-term supported resource in functional variation screening and miRNA function studies.
Mechanism of efficient double-strand break repair by a long non-coding RNA
Authors: Thapar Roopa , Wang Jing L , Hammel Michal , Ye Ruiqiong , Liang Ke , Sun Chengcao , Hnizda Ales , Liang Shikang , Maw Su S , Lee Linda , Villarreal Heather , Forrester Isaac , Fang Shujuan , Tsai Miaw-Sheue , Blundell Tom L , Davis Anthony J , Lin Chunru , Lees-Miller Susan P , Strick Terence R , Tainer John A
Published: September 2020

Mechanistic studies in DNA repair have focused on roles of multi-protein DNA complexes, so how long non-coding RNAs (lncRNAs) regulate DNA repair is less well understood. Yet, lncRNA LINP1 is over-expressed in multiple cancers and confers resistance to ionizing radiation and chemotherapeutic drugs. Here, we unveil structural and mechanistic insights into LINP1’s ability to facilitate non-homologous end joining (NHEJ). We characterized LINP1 structure and flexibility and analyzed interactions with the NHEJ factor Ku70/Ku80 (Ku) and Ku complexes that direct NHEJ. LINP1 self-assembles into phase-separated condensates via RNA–RNA interactions that reorganize to form filamentous Ku-containing aggregates. Structured motifs in LINP1 bind Ku, promoting Ku multimerization and stabilization of the initial synaptic event for NHEJ. Significantly, LINP1 acts as an effective proxy for PAXX. Collective results reveal how lncRNA effectively replaces a DNA repair protein for efficient NHEJ with implications for development of resistance to cancer therapy.
Blood Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate as Pathophysiological Correlates of Chronic Pain: Analyses Using a National Sample of Midlife Adults in the United States
Authors: Li Rui , Chapman Benjamin P , Smith Shannon M
Published: September 2020

Objective

Identifying biomarkers is a priority in translational chronic pain research. Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, are adrenocortical steroids in the blood with neuroprotective properties that also produce sex hormones. They may capture key sex-specific neuroendocrine mechanisms of chronic pain.

Design

Cross-sectional study.

Methods

Using data from 1,216 community-dwelling adults aged 34–84 from the Midlife in the United States (MIDUS) cohort, we examined blood DHEA and DHEA-S levels in association with chronic pain in men and women, adjusting for demographics, chronic diseases, medications including opioids, and psychosocial factors. If an association was found, we further explored dose-response relationships by the number of pain locations and the degree of pain interference.

Results

In women, chronic pain was associated with 0.072 lower (95% confidence interval [CI], –0.127 to –0.017) log10 DHEA-S µg/dL, with pain in one to two locations associated with 0.068 lower (95% CI, –0.131 to –0.006) and in three or more locations 0.071 lower (95% CI, –0.148 to 0.007) log10 DHEA-S (P for trend = 0.074). Furthermore for women, low-interference pain was associated with 0.062 lower (95% CI, –0.125 to –0.000), whereas high-interference pain was associated with 0.138 lower (95% CI, –0.233 to –0.043) log10 DHEA-S (P for trend = 0.004). Chronic pain was not associated with DHEA or DHEA-S levels in men or DHEA levels in women.

Conclusions

Chronic pain and its functional interference correspond to lower blood DHEA-S levels in women.
A novel phage display vector for selection of target-specific peptides
Authors: Chang Alex , Ting Joey P , Espada Alfonso , Broughton Howard , Molina-Martin Manuel , Afshar Sepideh
Published: September 2020

Intrinsic low display level of polypeptides on phage is a fundamental and limiting hurdle in successful isolation of target-specific binders by phage display technology. To circumvent this challenge, we optimized the copy number of peptides displayed on the phage surface using type 33 phage vector. We randomized the first 67 amino acids of the wild type PIII to identify mutants that would result in its reduced expression. Consequently, the display level was improved by 30-fold due to higher incorporation of the synthetic PIII–peptide fusion protein on the phage surface. Utilization of this novel phage vector should provide a solid basis for the discovery of therapeutic peptides.