Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms

A wealth of research over the past 2 decades has expanded our understanding of the impact of early‐life adversity on physiological function and, consequently, health and wellbeing in later life. Early‐life adversity increases the risk of developing a number of disorders, such as chronic pain, fibromyalgia, and irritable bowel syndrome. Although much of the research has examined the impact of physical maltreatment, an increasing number of studies have been published over the past few years examining the effect of childhood psychological stress and trauma on the development of various types of chronic pain conditions. We review the clinical and preclinical data examining the link among early‐life psychological stress, altered nociceptive behavior, and chronic pain in later life. Evidence supporting a role for certain key neurobiological substrates, including the hypothalamic‐pituitary‐adrenal axis; monoaminergic, opioidergic, endocannabinoid and immune systems; and epigenetic mechanisms in the association between early‐life psychological stress and chronic pain, is provided. Greater understanding of the impact of early‐life stress may inform the development of personalized treatments for chronic pain in later life and strategies to prevent its onset in susceptible individuals. © 2016 Wiley Periodicals, Inc.
Sex‐dependent consequences of neonatal brain hypoxia‐ischemia in the rat

Neonatal hypoxia‐ischemia (HI) is an important cause of neurological deficits in humans, and the Levine‐Rice model of experimental HI in the rat mimics the human brain lesion and the following sensory motor deficits and cognitive disabilities. With the growing evidence that sex influences all levels of brain functions, this Mini‐Review highlights studies in which sex was a controlled variable and that provided evidence of sexual dimorphism in behavioral outcome, extension of brain damage, mechanisms of lesion, and treatment efficacy in the rat neonatal HI model. It was shown that 1) females have greater memory deficits; 2) cell death is dependent mainly on caspase activation in females; 3) males are more susceptible to oxidative stress; and 4) treatments acting on distinct cell death pathways afford sex‐dependent neuroprotection. These tentative conclusions, along with growing evidence from other fields of neurobiology, support the need for scientists to design their experiments considering sex as an important variable; otherwise, important knowledge will continue to be missed. It is conceivable that sex can influence the development of efficacious therapeutic tools to treat neonates suffering from brain HI. © 2016 Wiley Periodicals, Inc.
Appropriate Time to Establish Baseline Responses for Brain stem Auditory Evoked Potentials During Microvascular Decompression for Hemifacial Spasm

Purpose: To evaluate the appropriate time to establish baseline responses for brain stem auditory evoked potentials (BAEPs) during microvascular decompression for hemifacial spasm and its implications on the alarm criteria and outcomes. Methods: Overall, 61 patients who had intraoperative monitoring with BAEP during microvascular decompression were retrospectively identified. The latencies and amplitudes of wave V before skin incision and at dura opening (before major manipulation) were compared with the latency and amplitude of wave V at change start (first alarm reported to the surgeon). Also, the results with respect to postoperative outcomes were evaluated. Results: More alarms would have been communicated to the surgeon when baseline values were set at the beginning of the procedure, when compared with baseline values reset at dura opening (before major manipulation). Conclusions: Significant variations in BAEP latency exist before any major manipulations during microvascular decompression. Despite a false-negative case, baselines can be set before any major manipulations (e.g., just before dura opening), with an understanding of the etiology of changes to BAEPs during microvascular decompression. Significance: This is the first study to establish that during intraoperative BAEP monitoring, baselines that are reset before any significant manipulations are performed, rather than at the beginning of the procedure, have a higher level of sensitivity with regards to hearing outcomes.
Sex differences in brain‐derived neurotrophic factor signaling and functions

Brain‐derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays a critical role in numerous neuronal activities. Recent studies have indicated that some functions or action mechanisms of BDNF vary in a sex‐dependent manner. In particular, BDNF content in some brain parts and the tendency to develop BDNF deficiency‐related diseases such as depression are greater in female animals. With the support of relevant studies, it has been suggested that sex hormones or steroids can modulate the activities of BDNF, which may account for its functional discrepancy in different sexes. Indeed, the cross‐talk between BDNF and sex steroids has been detected for decades, and some sex steroids, such as estrogen, have a positive regulatory effect on BDNF expression and signaling. Thus, the sex of animal models that are used in studying the functions of BDNF is critical. This Mini‐Review summarizes our current findings on the differences in expression, signaling, and functions of BDNF between sexes. We also discuss the potential mechanisms for mediating these differential responses, with a specific emphasis on sex steroids. By presenting and discussing these findings, we seek to encourage researchers to take sex influences into consideration when designing experiments, interpreting results, and drawing conclusions. © 2016 Wiley Periodicals, Inc.
Sex, hormones, and genotype interact to influence psychiatric disease, treatment, and behavioral research

Sex differences exist in the vulnerability, incidence, manifestation, and treatment of numerous neurological and psychiatric diseases. Despite this observation prominent in the literature, little consideration has been given to possible sex differences in outcome in both preclinical and clinical research. This Mini‐Review highlights evidence supporting why studying sex differences matter for advances in brain health as well as improving treatment for neurological and psychiatric disease. Additionally, we discuss some statistical and methodological considerations in evaluating sex differences as well as how differences in the physiology of the sexes can contribute to sex difference in disease incidence and manifestation. Furthermore, we review literature demonstrating that the reproductive experience in the female can render the female brain differentially vulnerable to disease across age. Finally, we discuss how genes interact with sex to influence disease risk and treatment and argue that sex must be considered in precision medicine. Together the evidence reviewed here supports the inclusion of males and females at all levels of neuroscience research. © 2016 Wiley Periodicals, Inc.
Socioeconomic Factors Influence Physical Activity and Sport in Quebec Schools.

BACKGROUND School environments providing a wide selection of physical activities and sufficient facilities are both essential and formative to ensure young people adopt active lifestyles. We describe the association between school opportunities for physical activity and socioeconomic factors measured by low-income cutoff index, school size (number of students), and neighborhood population density. METHODS A cross-sectional survey using a 2-stage stratified sampling method built a representative sample of 143 French-speaking public schools in Quebec, Canada. Self-administered questionnaires collected data describing the physical activities offered and schools' sports facilities. Descriptive and bivariate analyses were performed separately for primary and secondary schools. RESULTS In primary schools, school size was positively associated with more intramural and extracurricular activities, more diverse interior facilities, and activities promoting active transportation. Low-income primary schools were more likely to offer a single gym. Low-income secondary schools offered lower diversity of intramural activities and fewer exterior sporting facilities. High-income secondary schools with a large school size provided a greater number of opportunities, larger infrastructures, and a wider selection of physical activities than smaller low-income schools. CONCLUSIONS Results reveal an overall positive association between school availability of physical and sport activity and socioeconomic factors.
Differential expression of cytoskeletal regulatory factors in the adolescent prefrontal cortex: Implications for cortical development

The prevalence of depression, anxiety, schizophrenia, and drug and alcohol use disorders peaks during adolescence. Further, up to 50% of “adult” mental health disorders emerge in adolescence. During adolescence, the prefrontal cortex (PFC) undergoes dramatic structural reorganization, in which dendritic spines and synapses are refined, pruned, and stabilized. Understanding the molecular mechanisms that underlie these processes should help to identify factors that influence the development of psychiatric illness. Here we briefly discuss the anatomical connections of the medial and orbital prefrontal cortex (mPFC and OFC, respectively). We then present original findings suggesting that dendritic spines on deep‐layer excitatory neurons in the mouse mPFC and OFC prune at different adolescent ages, with later pruning in the OFC. In parallel, we used Western blotting to define levels of several cytoskeletal regulatory proteins during early, mid‐, and late adolescence, focusing on tropomyosin‐related kinase receptor B (TrkB) and β1‐integrin–containing receptors and select signaling partners. We identified regional differences in the levels of several proteins in early and midadolescence that then converged in early adulthood. We also observed age‐related differences in TrkB levels, both full‐length and truncated isoforms, Rho‐kinase 2, and synaptophysin in both PFC subregions. Finally, we identified changes in protein levels in the dorsal and ventral hippocampus that were distinct from those in the PFC. We conclude with a general review of the manner in which TrkB‐ and β1‐integrin–mediated signaling influences neuronal structure in the postnatal brain. Elucidating the role of cytoskeletal regulatory factors throughout adolescence may identify critical mechanisms of PFC development. © 2016 Wiley Periodicals, Inc.
Author Response: Concerns About Utility and Cost-Effectiveness of Continuous Critical-Care EEG.

To the Editor: I read with interest the consensus statement on indications of continuous critical-care EEG in critically ill adults and children (Herman et al., 2015). The authors conclude that there is increasing evidence that secondary injuries such as seizures and ischemia can worsen neurologic outcome. Then, they acknowledge that no prospective studies have yet demonstrated that treatment of EEG-identified changes improves neurologic outcome. Discussing this evidence supporting the use of continuous critical-care EEG to identify seizures, the Task Force claims that nonconvulsive seizures and nonconvulsive status epilepticus are associated with other signs of neurologic injury, such as increased intracranial pressure, increased edema, and mass effect. The association of nonconvulsive seizures and nonconvulsive status epilepticus with increased mortality and risk of poor neurologic outcome is also mentioned. The problem of circular reasoning is not touched: The electrographic changes and these other signs of neurologic injury could be just an expression of more severe underlying insult leading to poorer outcomes. It has been argued that an independent association between the severity of electrographic changes and worse outcomes would support antiseizure drug management (Payne et al., 2014). However, an independent association does not necessarily indicate a causal and direct role for seizures on the process of brain injury. Even assuming that seizure-induced excitotoxic injury does occur, another crucial question remains unanswered: what should be the electrographic aim of antiseizure treatment? The desirable patterns of burstsuppression or complete suppression were precisely those associated with worst outcomes when detected before treatment. Before these and other issues are elucidated, the precept of nonmaleficence should be contemplated, considering (a) the possible adverse effects of high-dose antiseizure drugs, (b) the risk of transporting a critically ill patient to a center where continuous critical-care EEG is available, and (c) the costs of maintaining expensive material and personnel facilities.
Improving School Experiences for Adolescents With Type 1 Diabetes.

BACKGROUND Diabetes mellitus (diabetes) is one of the most common metabolic diseases in children worldwide and the incidence of type 1 diabetes (T1D) is growing. T1D is complicated to manage and adolescents with diabetes face unique, age-specific challenges. The purpose of this article is to discuss ways in which schools can create a positive environment and improve the experiences and outcomes for adolescents with T1D. METHODS The Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PubMed databases were searched and yielded a total of 27 articles that were used in this integrative literature review. RESULTS Common concerns identified by students with T1D and their parents included a lack of full-time school nurses, lack of teacher knowledge of diabetes, lack of access to diabetes tools, lack of freedom to perform diabetes self-care, lack of nutritional information in cafeterias, and lack of communication between parents and school personnel. Students who are unable to attend school on a daily basis may not be able to achieve their academic potential. CONCLUSIONS Implications for school health including specifics for school nurses, teachers, students, and school environment were identified.
Misconceptions regarding basic thermodynamics and enzyme kinetics have led to erroneous conclusions regarding the metabolic importance of lactate dehydrogenase isoenzyme expression

Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate involving the coenzyme NAD+. Part of the foundation for the proposed shuttling of lactate from astrocytes to neurons during brain activation is the differential distribution of LDH isoenzymes between the two cell types. In this short review, we outline the basic kinetic properties of the LDH isoenzymes expressed in neurons and astrocytes, and argue that the distribution of LDH isoenzymes does not in any way govern directional flow of lactate between the two cellular compartments. The two main points are as follows. First, in line with the general concept of chemical catalysis, enzymes do not influence the thermodynamic equilibrium of a chemical reaction but merely the speed at which equilibrium is obtained. Thus, differential distribution of LDH isoenzymes with different kinetic parameters does not predict which cells are producing and which are consuming lactate. Second, the thermodynamic equilibrium of the reaction is toward the reduced substrate (i.e., lactate), which is reflected in the concentrations measured in brain tissue, suggesting that the reaction is at near‐equilibrium at steady state. To conclude, the cellular distribution of LDH isoenzymes is of little if any consequence in determining any directional flow of lactate between neurons and astrocytes. © 2017 Wiley Periodicals, Inc.
Student Voices: Perspectives on Peer-to-Peer Sexual Health Education.

BACKGROUND This process study is a companion to a randomized evaluation of a school-based, peer-led comprehensive sexual health education program, Teen Prevention Education Program (Teen PEP), in which 11th- and 12th-grade students are trained by school health educators to conduct informative workshops with ninth-grade peers in schools in North Carolina. The process study was designed to understand youth participants' perspectives on the program in order to gain insight into program effectiveness. METHODS This is a mixed-methods study in 7 schools, with online surveys (N = 88) and 8 focus groups with peer educators (N = 116), end-of-program surveys (N = 1122), 8 focus groups with ninth-grade workshop participants (N = 89), and observations of the Teen PEP class and workshops during the semester of implementation in each school, 2012-2014. RESULTS Both peer educators and ninth graders perceived benefits of participating in Teen PEP across a range of domains, including intentions, skills, and knowledge and that the peer education modality was important in their valuation of the experience. CONCLUSIONS Our findings suggest that the peer-led comprehensive sexual health education approach embodied in Teen PEP can be an important educational mechanism for teaching students information and skills to promote sexual health.
Sustained activation of ERK1/2 MAPK in Schwann cells causes corneal neurofibroma

Recent studies have shown that constitutive activation of extracellular signal‐regulated kinases 1 and 2 (ERK1/2) in Schwann cells (SCs) increases myelin thickness in transgenic mice. In this secondary analysis, we report that these transgenic mice develop a postnatal corneal neurofibroma with the loss of corneal transparency by age six months. We show that expansion of non‐myelinating SCs, under the control of activated ERK1/2, also drive myofibroblast differentiation that derives from both SC precursors and resident corneal keratocytes. Further, these mice also harbor activated mast cells in the central cornea, which contributes to pathological corneal neovascularization and fibrosis. This breach of corneal avascularity and immune status is associated with the growth of the tumor pannus, resulting in a corneal stroma that is nearly four times its normal size. In corneas with advanced disease, some axons became ectopically myelinated, and the disruption of Remak bundles is evident. To determine whether myofibroblast differentiation was linked to vimentin, we examined the levels and phosphorylation status of this fibrotic biomarker. Concomitant with the early upregulation of vimentin, a serine 38‐phosphorylated isoform of vimentin (pSer38vim) increased in SCs, which was attributed primarily to the soluble fraction of protein—not the cytoskeletal portion. However, the overexpressed pSer38vim became predominantly cytoskeletal with the growth of the corneal tumor. Our findings demonstrate an unrecognized function of ERK1/2 in the maintenance of corneal homeostasis, wherein its over‐activation in SCs promotes corneal neurofibromas. This study is also the first report of a genetically engineered mouse that spontaneously develops a corneal tumor.
Patterns of Nerve Conduction Abnormalities in Severe Carpal Tunnel Syndrome

Summary: Nerve conduction study findings in severe carpal tunnel syndrome have seldom been systematically investigated. The authors determined the persistence of each nerve conduction study parameter in severe carpal tunnel syndrome. Subjects were prospectively-collected 30 hands from 23 carpal tunnel syndrome patients, with an orthodromic sensory nerve action potential (SNAP) amplitude of the median nerve of 1 &mgr;V or less, or with an compound muscle action potentials (CMAPs) of the abductor pollicis brevis (APB) of 2 mV or less. Compound muscle action potentials of APB and second lumbricalis (2L) and orthodromic and antidromic SNAPs at the index finger were measured. As results, 2L-CMAP was obtainable for all but one hand, APB-CMAP for 20, orthodromic SNAP for 18, and antidromic SNAP for 13 hands. Four hands with preserved APB-CMAPs lacked SNAPs, whereas three hands with preserved orthodromic or antidromic SNAPs lacked APB-CMAPs. The mixed-nerve action potential at the wrist following orthodromic palm stimulation was identified in only 3 of 18 hands investigated. Orthodromic SNAP has an advantage that contamination by CMAPs is entirely lacking, and the authors documented its much higher persistence than previous studies because of their more detailed methods. Such different criteria of no response of SNAP between researchers should be taken notice in the grading system of carpal tunnel syndrome.
Neuroendocrine profile in a rat model of psychosocial stress: relation to oxidative stress.

AIMS Psychosocial stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis). Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress response and in the pathogenesis of neurologic and psychiatric diseases. NADPH oxidases (NOXs) are a major source of reactive oxygen species (ROS) in the central nervous system. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine alterations in a rat model of chronic psychosocial stress, the social isolation. RESULTS Significant elevations in the hypothalamic levels of corticotropin-releasing factor and plasmatic adrenocorticotropic hormone were observed from 4 weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at a later time point of social isolation (7 weeks). Alteration in the exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8-hydroxy-2-deoxyguanosine [8OhdG] and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after 2 weeks), but later (after 7 weeks) in the adrenal gland. A 3-week treatment with the antioxidant/NOX inhibitor apocynin stopped the progression of isolation-induced alterations of the HPA-axis. Rats with a loss-of-function mutation in the NOX2 subunit p47(phox) were totally protected from the alterations of the neuroendocrine profile, behavior, and increased NOX2 mRNA expression induced by social isolation. INNOVATION We demonstrate that psychosocial stress induces early elevation of NOX2-derived oxidative stress in the hypothalamus and consequent alterations of the HPA-axis, leading ultimately to an altered behavior. CONCLUSION Pharmacological targeting of NOX2 might be of crucial importance for the treatment of psychosocial stress-induced psychosis.