bluuebunny/crossref_metadata_2025 huggingface dataset:
Proximal Leg Weakness
Authors: Shaibani Aziz
Published: March 2018

Proximal leg weakness is a common presentation to neuromuscular clinics. Hip flexion, abduction, adduction, and rotation is mainly achieved by the iliopsoas, glutei, and obturator muscles. Hip pathology, especially when painless, may lead to diagnostic confusion that needs a good electromyogram (EMG) of these muscles to be cleared. Most myopathies present with painless proximal leg weakness (difficulty climbing stairs and arising out of a deep chair). chronic inflammatory demyelinating polyneuropathy (CIDP), diabetic amyotrophy, motor neuron diseases (MNDs), and lumbar plexitis may all present similarly. Pain is more typical of these conditions that myopathies. Students should be taught to avoid the assumption that proximal weakness is caused only by myopathies.
Quadriceps Weakness
Authors: Shaibani Aziz
Published: March 2018

Quadriceps muscles extend the knees and are important for walking and balance. Knee buckling (sudden giving away of the knees) is the most common presentation of quadriceps weakness. Knee buckling is common in the elderly, as it can also be caused by knee arthritis. Patients with quadriceps weakness often modify their lifestyle for years before they seek medical advice. Quadriceps muscles are very sensitive to immobility, and they may lose half their bulk within 2 weeks. On the other hand, they build mass quickly with exercise. Sometimes quadriceps muscles are selectively and severely involved, leading to early disability. Severe thigh pain, if it continues for a few weeks, may lead to disuse atrophy. Severe neuropathic thigh pain and atrophy are typically seen in diabetic amyotrophy. Other causes of thigh pain include L3 radiculopathy, meralgia paresthetica, and muscle infarction. Examination of the knee extension should always be part of neuromuscular evaluation.
Distal Arm Weakness
Authors: Shaibani Aziz
Published: March 2018

Distal arm weakness may be caused by involvement of the intrinsic hand muscles (interossi, thenar and hypothenar muscles, lumbricals) or extrinsic hands muscles (long fingers flexors and extensors). Amyotrophic lateral sclerosis (ALS) is typical of the former type, and inclusion body myositis (IBM) is typical for the later type. Incoordination of skilled finger movement due to cerebellar disease is associated with normal strength. Poor mobility due to joint pain and swelling should not be confused with muscle weakness. Mononeuropathies such as ulnar, radial, median, and anterior interosseus nerve lesions usually cause differential loss of function. Myasthenia gravis sometimes causes weakness of the wrist and finger extensors. A small but distinct group of distal hereditary myopathies should always be kept in mind. Progressive sensorimotor neuropathies are usually associated with sensory symptoms. Multifocal motor neuropathy can be a challenging diagnosis.
Distal Leg Weakness
Authors: Shaibani Aziz
Published: March 2018

Plantar flexion and extension weakness are usually neuromuscular in nature. Rarely, focal foot dystonia, ankle arthritis, and spasticity lead to diagnostic confusion. Painful, sequential foot drop is a common feature of vasculitis. Preserved extensor digitorum brevis (EDB) bulk in the face of foot drop is a feature of myopathy. Progressive, painless weakness of the foot flexion and extension with normal sensation and brisk deep tendon reflexes (DTRs) are typically seen in amyotrophic lateral sclerosis (ALS). In patients with chronic, bilateral foot drop, examination of the scapulae is essential to rule out scapuloperoneal syndrome and facioscapulohumeral muscular dystrophy (FSHD). In inflammatory neuropathies, distal leg weakness is the last to respond to therapy, and some residual deficit is common.
Fatigability
Authors: Shaibani Aziz
Published: March 2018

Undue fatigability is common in neuromuscular clinics, but nonneuromuscular causes are much more common than neuromuscular causes. Generalized fatigue is commonly caused by anemia, hypothyroidism, obstructive sleep apnea, depression, chronic fatigue syndrome (CFS), uremia, chronic obstructive pulmonary disease (COPD), and other diseases. Physiological fatigue is accentuated by neuromuscular disorders. Most strikingly, myasthenia gravis (MG) causes undue fatigue of the ocular, chewing, swallowing, and breathing muscles. However, amyotrophic lateral sclerosis (ALS), myopathies, and motor neuropathies are also associated with abnormal fatigue. Central causes like multiple sclerosis are notorious for fatigue. It is hard to measure fatigue because it is subjective and varies with the psychological status. Myasthenia hardly causes isolated fatigue.
Integrative Psychiatry and Brain Health
Authors: Weil Andrew
Published: March 2018

Part of the Weil Integrative Medicine Library, this volume provides a rational and evidence-based approach to the integrative therapy of mental disorders, integrating the principles of alternative and complementary therapies into the principles and practice of conventional psychiatry and psychology. Integrative Psychiatry and Brain Health examines what works and what doesn’t and offers practical guidelines for physicians to incorporate integrative medicine into their practice and to advise patients on reasonable and effective therapies. The text discusses areas of controversy and identifies areas of uncertainty where future research is needed. Chapters also cite the best available evidence for both the safety and the efficacy of all therapies discussed. The information is presented in accessible and easy-to-read formats, including clinical pearls and key points.
Key Nutrients for Normal Brain Health
Authors: Staid Rashna K.
Published: March 2018

Over the past several decades, there has been a sharp increase in psychiatric diseases but relatively little attention to improving poor nutritional patterns that affect mental health conditions. Long-term nutrient deprivation results in neuroinflammation, which contributes to causing mental illnesses such as depression, anxiety disorder, and schizophrenia. A growing body of research substantiates the benefits of supplementing many essential nutrients such as omega-3 fatty acids, vitamin D, the B complex vitamins, vitamin E, and the minerals magnesium, iron, zinc, choline, calcium, and selenium to help prevent and treat many mental illnesses. These nutrients are often limited in the standard Western diet. Importantly, it is not just one single nutrient that is important to optimizing brain health but all the nutrients working in concert in a healthy, well-balanced approach that helps to optimize brain function and prevent disease. This chapter reviews the various nutrients involved in maintaining optimal brain health.
The Role of Chiropractic in Mind–Body Health
Authors: Zabrecky George
Published: March 2018

The chiropractic approach is based on the principles that diseases, both psychiatric and medical, are caused by disturbances in the nervous system and that such disturbances are often related to musculoskeletal problems. Thus chiropractic therapies utilize an integrative approach to health and well-being that includes various spinal manipulations as well as an integrative approach to the patient. Chiropractic therapies are most well known for the management of chronic and acute pain, which frequently can be accompanied by anxiety and depression symptoms. There is little direct evidence that chiropractic care improves mental health outside of the benefits related to pain alleviation. However, based on the overall chiropractic model, chiropractic therapy can potentially benefit a wide variety of psychological symptoms, but more research is needed. This chapter reviews the principles of chiropractic care, particularly in the context of psychiatric conditions, and provides information for future clinical and research programs.
Homeopathy and Psychiatry
Authors: Merizald Bernardo A.
Published: March 2018

This chapter presents a review of the controversial topic of homeopathic medicine as it applies to mental health. It provides an overview of the origins, development, theory, application of, and research on homeopathy. There have been several case series and case reports published illustrating the range of mental health conditions that have allegedly been treated with homeopathy. The relationship between homeopathic medicines and placebo is addressed, as well as show the process of the individualized homeopathic consultation could be classified as a form of a psychotherapeutic interview with unique therapeutic potential. There is also a brief introduction of some of the most basic medicines used by homeopaths and their application.
Integrative Approaches to Depression
Authors: Wintering Nancy , Newberg Andrew B.
Published: March 2018

This chapter reviews the potential uses of integrative psychiatry and complementary and alternative medicine (CAM) approaches for the management of patients with mood disorders. Mood disorders are among the most prevalent mental health issues affecting people today. A variety of pharmacological and psychological interventions are available currently for patients with mood disorders, however, many seek CAM for treatment. CAM interventions can include vitamins and supplements, herbal and botanical remedies, meditation and spiritual practices, acupuncture, and dietary and healthy living lifestyle modification. There is increased public interest in the use of integrative therapies in mood disorders. An increasing number of randomized clinical trials have been conducted to evaluate the effectiveness of integrative interventions both as monotherapy and as adjunct therapeutic approaches to treat mood disorders. This chapter presents an overview of research regarding integrative treatment approaches for mood and affective disorders to provide clinical direction regarding the use of such interventions.
Deriving and Using A Risk Figure
Authors: McKinlay Gardner R. J , Amor David J
Published: March 2018

Risk is a central concept in genetic counseling. Risk is the probability that a particular event will happen. Risks may be discussed in terms of recurrence or of occurrence—the probability that an event will happen again, or that it will happen for the first time, respectively. Risk can also be presented as odds: the ratio of two mutually exclusive probabilities. This chapter provides a basic review of risk assessment, with a particular focus on its application to chromosome abnormalities. The concept of penetrance is introduced. The ways in which risk figures may be conveyed to patients in the clinic are discussed.
Complex Chromosomal Rearrangements
Authors: McKinlay Gardner R. J , Amor David J
Published: March 2018

Complex chromosome rearrangements (CCRs) include most of the rearrangements that would not be accounted for as “straightforward” classical categories. They may be translocations with three or more segments involved; or they may comprise a mix of translocation and, for example, inversion. Some can be extraordinarily complex. CCRs are classified as types I–IV, most falling into the “least complex” type I category, while types II–IV are grouped as “exceptional CCRs.” Many unbalanced CCRs have arisen de novo and imply no increased reproductive risk. The identification of the clinically normal balanced CCR carrier is less frequent, and for these people, the reproductive risks can be very high.
Autosomal Ring Chromosomes
Authors: McKinlay Gardner R. J , Amor David J
Published: March 2018

Ring chromosomes are uncommon. The typical physical phenotype comprises major dysmorphogenesis and intellectual deficiency, and reproduction is not usually a relevant issue. A ring chromosome is formed due to an end-to-end fusion of chromosome tips. Almost always, the end result is an imbalance and significant phenotypic abnormality. Rarely, however, this is not the case. In this chapter, genetic risks for ring carriers for whom procreation is a realistic likelihood are considered. This chapter distinguishes between those with a normal 46 chromosome count, one being a ring, and those with a 47 chromosome count, the additional chromosome being a (necessarily small) ring.
Uniparental Disomy and Disorders of Imprinting
Authors: McKinlay Gardner R. J , Amor David J
Published: March 2018

Uniparental disomy (UPD) is a fascinating pathogenetic mechanism, albeit that it is applicable to a small but important number of conditions. This chapter discusses the basis of UPD and the different mechanisms by which it may arise. It reviews the concept of epigenetics in this setting. This chapter considers UPD as it may have been observed in all the chromosomes, in some of which it appears to be without any effect, and others in which a UPD effect is well known, including the classic UPD conditions, of which Prader-Willi and Angelman syndromes are the archetypes. The differing reproductive risks in these different syndromes are noted.
Reproductive Failure
Authors: McKinlay Gardner R. J , Amor David J
Published: March 2018

Human conception and pregnancy is both a vulnerable and a robust process. It is vulnerable in that a large proportion of all conceptions are chromosomally abnormal, with the great majority of such pregnancies aborting. It is robust in that more than 99% of the time, a term pregnancy results in a chromosomally normal baby; unbalanced chromosomal abnormalities are seen in less than 1% of newborns. This chapter considers the somewhat surprising vulnerability of the human species to chromosome abnormality, from prior to, at, and following conception. A remarkable fraction of pregnancy loss is due to chromosomal imbalance, and there is an associated maternal age effect. This chapter considers the chromosomal contribution to miscarriage, fetal death in utero, and perinatal death. Recurrent pregnancy loss may have a chromosomal basis, and male and female infertility may relate to abnormality of, in particular, the sex chromosomes. The genetics of hydatidiform mole is reviewed.
Prenatal Testing Procedures
Authors: McKinlay Gardner R. J , Amor David J
Published: March 2018

This chapter is somewhat technical; it reviews the laboratory methodologies by which a prenatal diagnosis can be made and the clinical procedures whereby tissue is obtained. The main indications for prenatal cytogenetic diagnosis are the pregnant woman being of older childbearing age, parental heterozygosity for a chromosome rearrangement, the birth of a previous child with a chromosome defect, increased risk on maternal screening tests, and fetal anomaly detected on ultrasonography. The move to molecular methodology is noted. The remarkable advances in NIPT (noninvasive prenatal testing), such that this approach has now become routinely available, are canvassed. The chapter briefly discusses ethical questions in the delivery of prenatal diagnosis. It reviews the approaches in fetal chromosomal screening, by a combined ultrasound and blood biochemical analysis, and the secular changes associated with this.
Preimplantation Genetic Diagnosis
Authors: McKinlay Gardner R. J , Amor David J
Published: March 2018

Preimplantation genetic diagnosis allows recognition of a genetically abnormal embryo in the laboratory, and enables the choice, in principle, of selecting a normal embryo for transfer to the uterus. The methodologies are outlined in this chapter, noting the move toward day-5 blastocyst biopsy as the preferred time/stage. Next-generation sequencing is also discussed. The distinction is made between targeted diagnosis, as for example in the setting of a parental rearrangement, and preimplantation genetic screening, which may be offered to older women or those who, in any event, need recourse to in vitro fertilization. The improved diagnostic precision due to molecular methodology is noted.
Gonadal Cytogenetic Damage from Exposure to Extrinsic Agents
Authors: McKinlay Gardner R. J , Amor David J
Published: March 2018

This chapter is a compendium of what is known about the susceptibility, or resistance, of the gonad to agents that might seem candidates for possibly causing damage, and with particular reference to chromosomal status of gametes. A main focus is on cancer treatments. A majority of children and young adults who receive modern cancer treatment survive. Some treatments cause sterility, but in quite a number, fertility is unscathed, or at any rate, subsequently recovers. The chapter also references industrial, environmental, and recreational factors. A notable and substantially reassuring conclusion from these data is the apparent dearth of instances of an extrinsic factor having caused a chromosome abnormality in the sperm or egg of an exposed person.
Tobacco Use Among Prisoners
Authors: Clarke Jennifer , Reddy Manasa
Published: March 2018

Despite substantial reductions in the population prevalence of cigarette smoking in many developed countries, smoking remains normative among prisoners throughout the developed world. Furthermore, there has been little primary research on the efficacy of methods to reduce smoking in incarcerated populations. First, this chapter describes the epidemiology of tobacco smoking among inmates, including correlates of smoking in the general population, and drivers of smoking in prisons. Second, it considers current smoking policies and cessation services offered in prisons. Third, it reviews evidence-based strategies, both pharmacological and behavioral, for reducing tobacco consumption during and after incarceration, and details studies that have looked at prison settings specifically. Because best practices in facilities that permit smoking will resemble best practices in the community, the chapter focuses primarily on approaches in smoke-free facilities to reduce relapse to smoking after release. Finally, the chapter discusses challenges to treating tobacco addiction in prison settings.
Drug Use, HIV, and the High-Risk Environment of Prisons
Authors: Azbel Lyuba , Altice Frederick L.
Published: March 2018

Prisons often concentrate people with or at risk for HIV within them and, due to the high-risk environment within prison, further amplify disease. Suboptimal access to evidence-based HIV prevention and treatment within prisons, including opioid agonist therapies with methadone or buprenorphine, antiretroviral therapy, and needle/syringe programs, results in worsening of disease during incarceration. Effective transitional programs that address continuity of prevention and treatment of HIV and substance use disorders, along with other co-morbid conditions, are crucial to reduce the harms from incarceration. Such programs not only must provide access to these services within prison but also must ensure that the services are continued after release. This chapter reviews how prisons contribute to negative health consequences related to HIV and addiction, provides examples of settings where policies and services greatly influence the high-risk prison setting, and offers a number of strategies to improve HIV detection, treatment, and prevention.
Recidivism
Authors: Taxman Faye S. , Mun Mary
Published: March 2018

High rates of rearrest and recidivism, especially among drug-involved individuals, are of grave concern for the justice system and society at large. This chapter looks at the factors affecting recidivism rates of substance-involved individuals involved in the justice system. We begin by considering the complexity of measuring recidivism and the meaning of this concept; the term is fraught with difficulties due to the complexities of generalizing findings across studies with varying sampling frames and time-frames for follow-up, and differences in the types of recidivism events studied. Recent research illustrates that recidivism rates among drug users vary by drug of choice and are typically higher among individuals who use amphetamines, heroin, and/or cocaine. Recidivism rates may also vary depending on the presence of certain comorbid factors, although this is an emerging area of research. Factors that appear to elevate recidivism rates include personality disorders, co-occurring substance abuse and mental health disorders, other psychiatric disorders, and other serious mental illness. The location of an individual’s residence also appears to impact the recidivism rate, possibly mediated by the presence or absence of various protective factors in the community. While the nature of the relationship between drugs and crime is still unclear, the same is true for our understanding of recidivism among substance users in the justice system. There is a need for a greater understanding of the relationship between substance use and recidivism, in order to fill existing knowledge gaps.
Supply Reduction in Prison
Authors: Trestman Robert L. , Wall Ashbel.T.
Published: March 2018

Interdiction of addictive substances is a challenge in all settings. Prisons are no exception. Given the high prevalence of addictive disorders among prisoner populations the demand for illicit substances is very high. This chapter reviews the ways in which correctional staff have approached this concern, including a substantial focus on preventing illicit substances from entering the facility in the first place. This effort requires a broad array of interventions, including monitoring phone calls and mail; structuring and overseeing the visitation process; using trained canines; and employing intrusive searches any time a prisoner leaves the facility and returns. These efforts interface with an ongoing process to monitor prison activities for drugs that get past screening efforts. Random drug testing, canine tours of the facility, and an intricate system of informants, are each an element of effective monitoring activities. This chapter reviews the effectiveness and cost-effectiveness of such interventions, and considers the consequences of failure. Given that such consequences may include staff corruption and the development or growth of a prison drug economy, effective interdiction is a priority in every well-run facility.
Head and Neck Imaging
Authors: Anbarasu Arangasamy , Lane Jack
Published: March 2018

An essential introduction to the theory and practice of head and neck radiology, as well as a guide to choosing and performing imaging investigations and minimally invasive procedures.
The neck
Authors: Anbarasu Arangasamy , Lane Jack I.
Published: March 2018

This section covers the neck in detail considering the imaging techniques in this area. The whole neck is discussed including the sublingual space, retropharyngeal space, perivertebral space, and carotid space, alongside areas such as the Larynx, Lymph nodes, and Cystic neck lesions.
Imaging procedures and techniques
Authors: Anbarasu Arangasamy , Lane Jack I.
Published: March 2018

Biopsy of the central skull base and neck can be an intimidating procedure. However, the principles of biopsy in this region are similar to techniques used in all other areas of the body. The key to a successful biopsy is knowledge of the skull base and cervical anatomy, knowledge of your patient and familiarity with a limited number of biopsy tools.
Successful Microvascular Decompression For Trigeminal Neuralgia Secondary to a Persistent Trigeminal Artery
Authors: Ma Shunchang , Agarwalla Pankaj K , van Loveren Harry R , Agazzi Siviero
Published: March 2018

BACKGROUND AND IMPORTANCE

Persistent trigeminal artery (PTA) is a rare but important anatomic variant that contributes to trigeminal neuralgia (TN). Microvascular decompression (MVD) of the responsible vessel(s) away from the trigeminal nerve provides the most complete and durable relief from TN. The role and technique of MVD for TN associated with a PTA has not been fully defined in the literature. Furthermore, assessment of PTA anatomy intraoperatively with a microscope is challenging. We report the first 3-dimensional (3D) microscopic video and first intraoperative endoscopic video of a successful MVD of the trigeminal nerve in a patient who suffered TN from a tortuous, compressive PTA.

CLINICAL PRESENTATION

A 66-yr-old right-handed female presented with right facial pain in V2 and V3 distributions with a clinical picture of TN. Imaging demonstrated trigeminal nerve compression secondary to a PTA and MVD was performed with a 3D operative microscope and an endoscope. The PTA appeared to compress the nerve directly at the trigeminal porus and also had compressive superior cerebellar artery variant branches. The nerve was decompressed at all points of compression with Teflon pledgets along its entire cisternal length. Postoperatively, she is free with trigeminal pain episodes at 4-mo follow-up.

CONCLUSION

In cases of TN associated with a PTA, we recommend decompression along the entire length of the nerve wherever there is compression. Furthermore, we find both the operative microscope and particularly the endoscope useful to assess vascular anatomy intraoperatively.
Amisulpride Prevents Postoperative Nausea and Vomiting in Patients at High Risk
Authors: Kranke Peter , Bergese Sergio D. , Minkowitz Harold S. , Melson Timothy I. , Leiman David G. , Candiotti Keith A. , Liu Ngai , Eberhart Leopold , Habib Ashraf S. , Wallenborn Jan , Kovac Anthony L. , Diemunsch Pierre , Fox Gabriel , Gan Tong J.
Published: March 2018

Background

Postoperative nausea and vomiting causes distress for patients and can prolong care requirements. Consensus guidelines recommend use of multiple antiemetics from different mechanistic classes as prophylaxis in patients at high risk of postoperative nausea and vomiting. The prophylactic efficacy of the dopamine D2/D3 antagonist amisulpride in combination with other antiemetics was investigated.

Methods

This double-blind, randomized, placebo-controlled, international, multicenter trial was conducted in 1,147 adult surgical patients having three or four postoperative nausea and vomiting risk factors. Patients were randomized to receive either intravenous amisulpride (5 mg) or matching placebo at induction of general anesthesia, in addition to one standard, nondopaminergic antiemetic, most commonly ondansetron or dexamethasone. Vomiting/retching, nausea, and use of rescue medication were recorded for 24 h after wound closure. The primary endpoint was complete response, defined as no emesis or rescue medication use in the 24-h postoperative period.

Results

Complete response occurred in 330 of 572 (57.7%) of the amisulpride group and 268 of 575 (46.6%) of the control group (difference 11.1 percentage points; 95% CI, 5.3 to 16.8; P < 0.001). The incidences of emesis (13.8% vs. 20.0%, P = 0.003), any nausea (50.0% vs. 58.3%, P = 0.002), significant nausea (37.1% vs. 47.7%, P < 0.001), and rescue medication use (40.9% vs. 49.4%, P = 0.002) were significantly lower in the amisulpride group. Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently with amisulpride than with placebo.

Conclusions

Intravenous amisulpride was safe and effective as prophylaxis of postoperative nausea and vomiting when given in combination with an antiemetic from another class to adult patients at high risk for suffering postoperative nausea and vomiting undergoing elective surgery under inhalational general anesthesia.
Risk for Cervical Intraepithelial Neoplasia Grade 3 or Higher in Follow-Up of Women With a Negative Cervical Biopsy
Authors: Tverelv Liv Reidun , Sørbye Sveinung Wergeland , Skjeldestad Finn Egil
Published: March 2018

Objective

The Norwegian Cervical Cancer Screening Programme recommends follow-up of histologically confirmed normal/cervical intraepithelial neoplasia (CIN) 1 with combined cytology and human papillomavirus testing within 6 to 12 months. This study examines adherence to guidelines and subsequent risk for CIN 3+ within this subset of women.

Materials and Methods

Women aged 25 to 69 years attending the Norwegian Cervical Cancer Screening Programme in Norway's 2 northernmost counties were included. An exposed cohort with histologically confirmed normal/CIN 1 after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion or atypical squamous cells – cannot exclude high-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion enrolment cytology (n = 374) was compared with a nonexposed cohort with a normal enrolment cytology attending primary screening (N = 25,948). Risk calculations were stratified by outcomes of the first follow-up cytology. The study end point was CIN 3+ or censored at 78 months of follow-up.

Results

In the exposed cohort, the 42-month cumulative incidence of CIN 3+ was 9.4% (95% CI = 4.1–14.7) for women with an abnormal first follow-up cytology and 1.6% (95% CI = 0.0–3.4) for women with a normal first follow-up cytology versus 0.21% (95% CI = 0.15–0.27) in the nonexposed cohort (p < .01). The CIN 3+ risk was higher in the exposed cohort when the first follow-up cytology was abnormal (hazard ratio = 20.4, 95% CI = 11.2–37.1) compared with normal (hazard ratio = 4.7, 95% CI = 1.9–11.6) with the nonexposed cohort as reference.

Conclusions

After a negative cervical biopsy, a normal first follow-up cytology provided a CIN 3+ risk considered acceptable to recommend return to routine screening in 3 years. Cytology and human papillomavirus co-testing in post-colposcopy follow-up of negative biopsies may improve risk stratification.
NOTCH regulation of the endothelial cell phenotype
Authors: Mack Julia J. , Iruela-Arispe M. Luisa
Published: March 2018

Purpose of review

The formation of a hierarchical vascular network is a complex process that requires precise temporal and spatial integration of several signaling pathways. Amongst those, Notch has emerged as a key regulator of multiple steps that expand from endothelial sprouting to arterial specification and remains relevant in the adult. This review aims to summarize major concepts and rising hypotheses on the role of Notch signaling in the endothelium.

Recent findings

A wealth of new information has helped to clarify how Notch signaling cooperates with other pathways to orchestrate vascular morphogenesis, branching, and function. Endothelial vascular endothelial growth factor, C-X-C chemokine receptor type 4, and nicotinamide adenine dinucleotide phosphate oxidase 2 have been highlighted as key regulators of the pathway. Furthermore, blood flow forces during vascular development induce Notch1 signaling to suppress endothelial cell proliferation, enhance barrier function, and promote arterial specification. Importantly, Notch1 has been recently recognized as an endothelial mechanosensor that is highly responsive to the level of shear stress to enable differential Notch activation in distinct regions of the vessel wall and suppress inflammation.

Although it is well accepted that the Notch signaling pathway is essential for vascular morphogenesis, its contributions to the homeostasis of adult endothelium were uncovered only recently. Furthermore, its exquisite regulation by flow and impressive interface with multiple signaling pathways indicates that Notch is at the center of a highly interactive web that integrates both physical and chemical signals to ensure vascular stability.
Global Variation in Use of Enteral Nutrition for Pediatric Crohn Disease
Authors: Lawley Morgan , Wu Jessica W. , Navas‐López Victor M. , Huynh Hien Q. , Carroll Matthew W. , Chen Min , Medvedev Pavel , Day Andrew S. , Hussey Séamus , Sigall‐Boneh Rotem , Levine Arie , Wine Eytan
Published: March 2018

Objectives:

Exclusive enteral nutrition (EEN) is an effective induction treatment for pediatric Crohn disease. Given the center‐based variation in use and diversity in practice, we constructed a survey aimed at sharing experience and strategies in administering EEN, stimulating further research, and optimizing therapy.

Methods:

This survey was constructed after consultation with experts and designed to address key knowledge gaps. The survey was disseminated through the Pediatric IBD Porto Group of ESPGHAN, Canadian Children IBD Network, selective experts, and was sent twice through the Pediatric Gastrointestinal‐Bulletin Board (PEDGI‐BB). Data were collected into REDCap and analyzed using descriptive statistics.

Results:

In total, 146 participants from 26 countries completed the survey. Sixty‐five percentage of participants were general, non‐inflammatory bowel diseases (IBD)‐focused pediatric gastroenterologists, 21% were IBD‐focused, and 10% were dietitians. The most common indications (~90% use) were for ileocecal and ileocolonic disease (Paris L1 and L3). The most common duration was 8 weeks and 66% preferred oral to nasogastric administration. Most (63%) did not allow any additional intake and 69% instructed patients to continue partial enteral nutrition (EN) after completing treatment. Dietitians were identified as essential to EEN success while the primary challenges of EEN programs were adherence and lack of support. Regional and professional practice differences were observed in EEN indication, age, exclusivity, program structure/support, and cost coverage.

Conclusions:

We found significant variation in practice and use of EEN with several regional and professional differences. Global variation offers opportunities for research and improving care. This survey establishes a framework and provides resources for collaboration and information sharing.
Use of National Syphilis Surveillance Data to Develop a Congenital Syphilis Prevention Cascade and Estimate the Number of Potential Congenital Syphilis Cases Averted
Authors: Kidd Sarah , Bowen Virginia B. , Torrone Elizabeth A. , Bolan Gail
Published: March 2018

Background

Recent increases in reported congenital syphilis have led to an urgent need to identify interventions that will have the greatest impact on congenital syphilis prevention. We sought to create a congenital syphilis prevention cascade using national syphilis surveillance data to (1) estimate the proportion of potential congenital syphilis cases averted with current prevention efforts and (2) develop a classification framework to better describe why reported cases were not averted.

Methods

We reviewed national syphilis and congenital syphilis case report data from 2016, including pregnancy status of all reported female syphilis cases and data on prenatal care, testing, and treatment status of mothers of reported congenital syphilis cases to derive estimates of the proportion of pregnant women with syphilis who received prenatal care, syphilis testing, and adequate syphilis treatment at least 30 days before delivery, as well as the proportion of potential congenital syphilis cases averted.

Results

Among the 2508 pregnant women who were reported to have syphilis, an estimated 88.0% received prenatal care at least 30 days before delivery, 89.4% were tested for syphilis at least 30 days before delivery, and 76.9% received an adequate treatment regimen that began at least 30 days before delivery. Overall, an estimated 1928 (75.0%) potential congenital syphilis cases in the United States were successfully averted. Among states that reported at least 10 syphilis cases among pregnant women, the estimated proportion of potential congenital syphilis cases averted ranged from 55.0% to 92.3%.

Conclusions

Although the majority of potential congenital syphilis cases in the United States were averted in 2016, there was substantial geographic variation, and significant gaps in delivering timely prenatal care, syphilis testing, and adequate treatment to pregnant women with syphilis were identified. The congenital syphilis prevention cascade is a useful tool to quantify programmatic successes and identify where improvements are needed.
The Use of Central Pathology Review With Digital Slide Scanning in Advanced-stage Mycosis Fungoides and Sézary Syndrome
Authors: Gru Alejandro A. , Kim Jinah , Pulitzer Melissa , Guitart Joan , Battistella Maxime , Wood Gary S. , Cerroni Lorenzo , Kempf Werner , Willemze Rein , Pawade Joya , Querfeld Christiane , Schaffer Andras , Pincus Laura , Tetzlaff Michael , Duvic Madeleine , Scarisbrick Julia , Porcu Pierluigi , Mangold Aaron R. , DiCaudo David J. , Shinohara Michi , Hong Eric K. , Horton Bethany , Kim Youn H.
Published: March 2018

This pathology PILOT study aims to define the role and feasibility of centralized pathology review in a cohort of 75 patients from different centers in the United States and Europe using digital slide scanning. The pathologic material from 75 patients who had been diagnosed with mycosis fungoides/Sézary syndrome and were clinically staged as IIb or above was retrieved from 11 participating centers. Each pathology reviewer was provided with the pathologic diagnosis (by the referring pathologist), and the following list of histopathologic criteria (presence or absence) from the initial report: epidermotropism, folliculotropism (FT), large cell transformation, syringotropism, and granulomas. Patients with advance stage were selected for this study as this is a population where there is significant variability in the diagnosis of pathologic prognostic and predictive biomarkers. The slides were digitally scanned with an Aperio scanner and consensus review of cases occurred when major or minor discrepancies between the referral diagnosis and central pathology review occurred. Among the 75 cases, 70 (93.3%) had a final consensus diagnosis between the 3 central review pathologists. The overall agreement between the consensus review and the referring pathologist was 60%. The overall agreement was also higher between the reviewers and consensus review, compared with the referring pathologist and consensus. 65.3% of cases had some type of discrepancy (major or minor) between the outside and consensus review. Major discrepancies were seen in 34 of 73 cases (46.6%; 73 cases indicated a yes or no response). Minor discrepancies were seen in 32 of 75 (42.7%) of cases. Most of the major discrepancies were accounted by a difference in interpretation in the presence or absence of large cell transformation or FT. Most minor discrepancies were explained by a different interpretation in the expression of CD30. We found digital slide scanning to be a beneficial, reliable, and practical for a methodical approach to perform central pathology review in the context of a large clinical prospective study.
Low-Level Viremia Is Associated With Clinical Progression in HIV-Infected Patients Receiving Antiretroviral Treatment
Authors: Bernal Enrique , Gómez Jose M. , Jarrín Inma , Cano Alfredo , Muñoz Angeles , Alcaraz Antonia , Imaz Arkaitz , Iribarren Jose A. , Rivero María , Arazo Piedad , Gutiérrez Félix ,   CoRIS Study Group
Published: March 2018

Background:

The objective of this study was to investigate the long-term impact of low-level viremia (LLV) on all-cause mortality, AIDS and non-AIDS events (NAEs), and virological failure in patients receiving antiretroviral therapy (ART).

Methods:

We analyzed ART-naive adults from the cohort of the Spanish AIDS Research Network (CoRIS) who initiated ART from 2004 to 2015 and achieved plasma viral load (VL) below 50 copies per milliliter. LLV50-199 was defined as 2 consecutive VL between 50 and 199 copies per milliliter, and LLV200-499 as 2 consecutive VL between 50 and 499 copies per milliliter with at least one between 200 and 499 copies per milliliter. Multivariable Cox models were used to estimate the association of LLV with AIDS events/death, non-AIDS events, and virological failure.

Results:

Of 5986 patients included, 237 (4.0%) experienced LLV50-199 and 168 (2.8%) developed LLV200–499. One hundred seventy-one patients died or developed an AIDS event, 245 had any serious NAE and 280 had virological failure. LLV200-499 was strongly associated with a higher risk of both AIDS events/death [adjusted hazard ratio (aHR), 2.89; 95% confidence interval (CI), 1.41 to 5.92] and virological failure (aHR, 3.25; 95% CI: 1.77 to 5.99), whereas no differences were observed between LLV50-199 and no LLV neither for AIDS events/death (aHR, 1.84; 95% CI: 0.89 to 3.82) nor virological failure (aHR, 1.42; 95% CI: 0.78 to 2.58). LLV was not associated with the occurrence of any serious NAE.

Conclusions:

In this cohort, LLV200-499 was strongly associated with AIDS events/death and virological failure, but not with any serious NAE. Therefore, vigorous treatment should be implemented in patients with more than 200 copies per milliliter.
A post Gurney quantum mechanical perspective on the electrolysis of water: ion neutralization in solution
Authors: Guo Enyi , McKenzie David R.
Published: March 2018

Electron fluxes crossing the interface between a metallic conductor and an aqueous environment are important in many fields; hydrogen production, environmental scanning tunnelling microscopy, scanning electrochemical microscopy being some of them. Gurney (Gurney 1931Proc. R. Soc. Lond.134, 137 (doi:10.1098/rspa.1931.0187)) provided in 1931 a scheme for tunnelling during electrolysis and outlined conditions for it to occur. We measure the low-voltage current flows between gold electrodes in pure water and use the time-dependent behaviour at voltage switch-on and switch-off to evaluate the relative contribution to the steady current arising from tunnelling of electrons between the electrodes and ions in solution and from the neutralization of ions adsorbed onto the electrode surface. We ascribe the larger current contribution to quantum tunnelling of electrons to and from ions in solution near the electrodes. We refine Gurney's barrier scheme to include solvated electron states and quantify energy differences using updated information. We show that Gurney's conditions would prevent the current flow at low voltages we observe but outline how the ideas of Marcus (Marcus 1956J. Chem. Phys.24, 966–978 (doi:10.1063/1.1742723)) concerning solvation fluctuations enable the condition to be relaxed. We derive an average barrier tunnelling model and a multiple pathways tunnelling model and compare predictions with measurements of the steady-state current–voltage relation. The tunnelling barrier was found to be wide and low in agreement with other experimental studies. Applications as a biosensing mechanism are discussed that exploit the fast tunnelling pathways along molecules in solution.
Analysing causal structures with entropy
Authors: Weilenmann Mirjam , Colbeck Roger
Published: March 2018

A central question for causal inference is to decide whether a set of correlations fits a given causal structure. In general, this decision problem is computationally infeasible and hence several approaches have emerged that look for certificates of compatibility. Here, we review several such approaches based on entropy. We bring together the key aspects of these entropic techniques with unified terminology, filling several gaps and establishing new connections, all illustrated with examples. We consider cases where unobserved causes are classical, quantum and post-quantum, and discuss what entropic analyses tell us about the difference. This difference has applications to quantum cryptography, where it can be crucial to eliminate the possibility of classical causes. We discuss the achievements and limitations of the entropic approach in comparison to other techniques and point out the main open problems.
The mysteries of remote memory
Authors: Albo Zimbul , Gräff Johannes
Published: March 2018

Long-lasting memories form the basis of our identity as individuals and lie central in shaping future behaviours that guide survival. Surprisingly, however, our current knowledge of how such memories are stored in the brain and retrieved, as well as the dynamics of the circuits involved, remains scarce despite seminal technical and experimental breakthroughs in recent years. Traditionally, it has been proposed that, over time, information initially learnt in the hippocampus is stored in distributed cortical networks. This process—the standard theory of memory consolidation—would stabilize the newly encoded information into a lasting memory, become independent of the hippocampus, and remain essentially unmodifiable throughout the lifetime of the individual. In recent years, several pieces of evidence have started to challenge this view and indicate that long-lasting memories might alreadyab ovobe encoded, and subsequently stored in distributed cortical networks, akin to the multiple trace theory of memory consolidation. In this review, we summarize these recent findings and attempt to identify the biologically plausible mechanisms based on which a contextual memory becomes remote by integrating different levels of analysis: from neural circuits to cell ensembles across synaptic remodelling and epigenetic modifications. From these studies, remote memory formation and maintenance appear to occur through a multi-trace, dynamic and integrative cellular process ranging from the synapse to the nucleus, and represent an exciting field of research primed to change quickly as new experimental evidence emerges.

This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.
Dissociable temporal effects of bupropion on behavioural measures of emotional and reward processing in depression
Authors: Walsh Annabel E. L. , Browning Michael , Drevets Wayne C. , Furey Maura , Harmer Catherine J.
Published: March 2018

Antidepressants remediate negative biases in emotional processing early in treatment, prior to mood improvement. However, the effects on reward processing potentially relevant to the treatment of anhedonia are less clear. Here we investigate the early and sustained effects of the dopamine and noradrenaline reuptake inhibitor bupropion on behavioural measures of emotional and reward processing in currently depressed individuals. Forty-six currently depressed patients and 42 healthy controls participated in a repeated measures study, during which open-label bupropion was administered to only the patient group over a six week period without a placebo group. All participants completed the Emotional Test Battery and a probabilistic instrumental learning task at week 0, week 2 and week 6. Currently depressed patients displayed negative biases in emotional processing and blunted response bias for high-probability wins compared to the healthy controls at baseline. Bupropion was found to reduce the negative biases in emotional processing early in treatment, including a significant decrease in the percentage misclassification of other face emotions as sad and the number of negative self-referent words falsely recalled between baseline and week 2. Conversely, bupropion was found to initially further reduce the response bias for high-probability wins between baseline and week 2. This effect reversed with six weeks' bupropion treatment and reward processing was normalized compared to the healthy controls. Early in treatment, bupropion acts to reduce negative biases in emotional processing but exacerbates impaired reward processing. The beneficial actions of bupropion on reward processing then occur later in treatment. Such dissociation in the temporal effects of bupropion on emotional and reward processing has implications for the treatment of the different symptom domains of negative affect and anhedonia in depression.

This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.