Involvement of Mechanical Cues in the Migration of Cajal-Retzius Cells in the Marginal Zone During Neocortical Development.

Emerging evidence points to coordinated action of chemical and mechanical cues during brain development. At early stages of neocortical development, angiogenic factors and chemokines such as CXCL12, ephrins, and semaphorins assume crucial roles in orchestrating neuronal migration and axon elongation of postmitotic neurons. Here we explore the intrinsic mechanical properties of the developing marginal zone of the pallium in the migratory pathways and brain distribution of the pioneer Cajal-Retzius cells. These neurons are generated in several proliferative regions in the developing brain (e.g., the cortical hem and the pallial subpallial boundary) and migrate tangentially in the preplate/marginal zone covering the upper portion of the developing cortex. These cells play crucial roles in correct neocortical layer formation by secreting several molecules such as Reelin. Our results indicate that the motogenic properties of Cajal-Retzius cells and their perinatal distribution in the marginal zone are modulated by both chemical and mechanical factors, by the specific mechanical properties of Cajal-Retzius cells, and by the differential stiffness of the migratory routes. Indeed, cells originating in the cortical hem display higher migratory capacities than those generated in the pallial subpallial boundary which may be involved in the differential distribution of these cells in the dorsal-lateral axis in the developing marginal zone.

Utility of Galleria mellonella larvae for evaluating nanoparticle toxicology.

The use of nanoparticles in consumer products is currently on the rise, so it is important to have reliable methods to predict any associated toxicity effects. Traditional in vitro assays fail to mimic true physiological responses of living organisms against nanoparticles whereas murine in vivo models are costly and ethically controversial. For these reasons, this study aimed to evaluate the efficacy of Galleria mellonella as an alternative, non-rodent in vivo model for examining nanoparticle toxicity. Silver, selenium, and functionalized gold nanoparticles were synthesized, and their toxicity was assessed in G. mellonella larvae. The degree of acute toxicity effects caused by each type of NP was efficiently detected by an array of indicators within the larvae: LD50 calculation, hemocyte proliferation, NP distribution, behavioral changes, and histological alterations. G. mellonella larvae are proposed as a nanotoxicological model that can be used as a bridge between in vitro and in vivo murine assays in order to obtain better predictions of NP toxicity.

Involvement of Cellular Prion Protein in α-Synuclein Transport in Neurons.

The cellular prion protein, encoded by the gene Prnp, has been reported to be a receptor of ß-amyloid. Their interaction is mandatory for neurotoxic effects of ß-amyloid oligomers. In this study, we aimed to explore whether the cellular prion protein participates in the spreading of α-synuclein. Results demonstrate that Prnp expression is not mandatory for α-synuclein spreading. However, although the pathological spreading of α-synuclein can take place in the absence of Prnp, α-synuclein expanded faster in PrPC-overexpressing mice. In addition, α-synuclein binds strongly on PrPC-expressing cells, suggesting a role in modulating the effect of α-synuclein fibrils.

Emotional reactions to pain predict psychological distress in adult patients with Sickle Cell Disease (SCD).

Differentiating somatic from emotional influences on the experience of chronic pain has been of interest to clinicians and researchers for many years. Although prior research has not well specified these pathways at the anatomical level, some evidence, both theoretical and empirical, suggest that emotional reactions influence the experience of disease and non-disease-related pains. Other studies suggest that treatments directed at negative emotional responses reduce suffering associated with pain. The current study was conducted to explore the influence of emotional reactions to pain as a predictor of psychological distress in a sample of adult Blacks with Sickle Cell Disease (SCD). Using cross-sectional survey data, we evaluated whether negative emotional reactions to the experience of pain were predictive of psychological distress after controlling for the somatic dimension of pain and age in n = 67 Black patients with Sickle Cell Disease (SCD). Results showed that greater negative emotion associated with pain predicted Somatization (p < .01), Anxiety (p < .05), Phobic Anxiety (p < .05), and Psychoticism (p < .05). Increased negative emotion associated with pain was also predictive of the General Symptoms Index (p < .05) and the Positive Symptoms Total from the SCL-90-R (p < .01). We believe the current study demonstrates that negative emotional reactions to the experience of pain in adults with SCD are predictive of psychological distress above and beyond the influences of age and the direct nociceptive experience. We also believe these data to be valuable in conceptualizing the allocation of treatment resources toward a proactive approach with early identification of patients who are responding poorly for the purpose of potentially reducing later psychopathology. A deeper understanding of the ways that subpopulations cope with chronic disease-related pain may produce models that can be ultimately generalized to the consumers of the majority of healthcare resources.

Neurocognitive testing and functioning in adults sickle cell disease.

The impact of cerebrovascular events (CVE) on cognitive functioning in adults with sickle cell disease is not well understood. Sequelae of CVEs can adversely impact their quality of life. We reviewed neurocognitive presentation and testing in adults with sickle cell disease. We evaluated the frequency of complaints of memory disturbance using survey methodology in a sample of 109 adult patients with sickle cell disease (48 males, 61 females). A subsample of 24 patients also received a memory questionnaire where specific cognitive functions were assessed. Overall, we found that males and females did not differ in the frequency of experienced memory disturbance during painful crises. However, the frequency of men reporting that their ability to remember where they place common objects such as keys (p = 0.017) and remembering the item they intended to buy in a grocery store or pharmacy (p = 0.048) was worse now compared to when they were in high school and was greater when compared to women. The frequency of men who reported their memory was worse now than when they were in high school (p = 0.051) was also greater than in women. We concluded that memory dysfunction predicts global monthly presentation of pain. We suggest incorporating cost-effective neurocognitive screening measures as a standard of practice in sickle cell disease.

Opioid management and dependency among adult patients with sickle cell disease.

While pain is one of the most debilitating symptoms of sickle cell disease, narcotics remain an effective although controversial widely practiced intervention. Vaso-occlusive crises are the most common cause for seeking pharmacological treatment. The influence of stigmatization and pseudo addiction in emergency departments and outpatient clinics was reviewed. We analyzed patterns of narcotic utilization in a sample of 63 adult patients with sickle cell disease to determine if their psychological functioning and reports of pain differed as a function of the primary narcotics they were taking for oral pain management. Fifty-one percent of patients reported treatment of Oxycodone, 35% OxyContin, 24% methadone and 11% morphine. Patients who were treated with Oxycodone reported greater sensory reactions to pain (p = 0.001), visual analog scale (VAS) (p = 0.02), and averaged weekly pain intensity ratings than patients who did not use this medication. There were no differences in pain or affective response in patients treated with OxyContin, methadone or morphine. We suggest there are clear differences between the reports of pain in patients with sickle cell disease taking short-acting narcotics for pain management as compared to those who are not, a pattern that does not distinguish patients who are managed with long-acting preparations. We discuss the relevance of addressing narcotic management in the context of the perception of health care providers and patients with sickle cell disease.

Somatization in the conceptualization of sickle cell disease.

The unpredictable nature of sickle cell disease (SCD) and its social and environmental consequences can produce an unhealthy and almost exclusive focus on physical functioning. At the upper range of this focus on health concerns is somatization. In the current study, using 156 adult patients (55.13% female, 86) with SCD, mean age 35.59 +/- 12.73, we explored the relationship of somatization to pain. We found somatization to be predictive of pain severity and current pain intensity as well as a range of averaged indices of pain over time (p < .0001). We further found somatization to be predictive of a range of negative psychological experiences to include depression, anxiety, and hostility (p < .0001). We interpret these data to suggest that patients with SCD who have a propensity to focus exclusively on their health or are more sensitive to minor changes in their health status (somatization) may also be more likely to report greater concerns about their health and higher ratings of pain.

Psychologic factors in the development of complex regional pain syndrome: history, myth, and evidence.

OBJECTIVE: The present paper examines the literature that addresses psychologic aspects involved in complex regional pain syndrome from a historic perspective to provide a rationale for the emergence of psychologic theories to explain its pathogenesis. The support of such perspective is then analyzed through the review of evidence-based studies. METHODS: A review of the literature from a historic perspective was presented since its first description to the present time, including the clinical presentation and associated symptoms. An evidence-based approach was used to review the literature on complex regional pain syndrome and psychologic factors associated with the etiology or as predictors in the development of the disorder. RESULTS: After reviewing the literature on the history and the myths associated with complex regional pain syndrome, a hypothesis is provided based on an analysis of the Zeitgeist in the development of the psychologic theory associated with the disorder. We also concluded there is no evidence to support a linear relationship that establishes a psychologic predisposition to develop the disorder. DISCUSSION: An analysis of the Zeitgeist when complex regional pain syndrome was first described helps to understand the long-standing theories associated with a psychological theory of its etiology. This understanding should help to undermine the perpetuation of such claims which may contribute to undertreatment and misdiagnosis. To be consistent with todays Zeitgeist we must incorporate psychologic aspects, which while not causal in nature or exclusive of complex regional pain syndrome, are strongly associated with a wide spectrum of chronic pain disorders.

Depression, suicidal ideation, and attempts in black patients with sickle cell disease.

There is a strong relationship between suicidal ideation, suicide attempts, and depression. Rates of successful suicides are relatively high among the chronically ill compared to other populations but are reduced with treatment. Depression and suicide rates also often differ among blacks as compared to other populations. Using survey methods, we evaluated self-reported rates of depression, suicidal ideation, and suicide attempts in 30 male and 37 female black patients with sickle cell disease (SCD). SCD is a condition characterized by chronic, unpredictable pains and psychosocial distress. Thirty-six percent of the sample self-reported depression in the past 30 days, while 22 percent of the sample exhibited scores on the Beck Depression Inventory indicative of mild or greater depression (mean BDI, 8.31 +/- 7.79). Twenty-nine percent of patients indicated an episode of suicidal ideation and 8%, a suicidal attempt in their lifetime. Thirty-three percent reported treatment by a mental health professional. We conclude that there is a continuing need for mental health services in the management of depressed affect and risk for suicide among patients with SCD. Standards of clinical care must remain flexible to accommodate the mental health needs of this population of patients.

Pain coping in Latino populations.

UNLABELLED: Although there has been a rapid increase in Latino populations in the United States over the last 10 years, health research with Latino cultural groups is sorely lacking. In the area of pain-coping research, one consequence of the limited research is that very little is known about pain coping among Latinos. The purpose of this paper is to review the existing literature on pain coping in Latino populations, and to propose new directions for the future study of pain coping in Latino populations. This review is divided into 4 sections. In the first section, the challenges of defining Latino populations are discussed. In the second section, the current literature on pain coping in Latinos is reviewed. Third, we discuss the implications of existing findings for pain-coping assessment and pain treatment. Finally, we offer ideas for future research on pain coping in Latino populations. PERSPECTIVE: In this review article, we identify gaps in our current understanding of pain coping in Latino cultural groups, and associated implications for pain assessment and treatment. We also highlight potential directions for future pain-coping research with Latino populations.

Neuropsychological effects and attitudes in patients following electroconvulsive therapy.

The current study examined the effects of electroconvulsive therapy (ECT) on neuropsychological test performance. Forty-six patients completed brief neuropsychological and psychological testing before and after receiving ECT for the treatment of recalcitrant and severe depression. Neuropsychological testing consisted of the Levin Selective Reminding Test (Levin) and Wechsler Memory Scale-Revised Edition (WMS-R). Self-report measures included the Beck Depression Inventory (BDI), the Short-Term Memory Questionnaire (STMQ), and several other measures of emotional functioning and patient attitudes toward ECT. The mean number of days between pre-ECT and post-ECT testing was 24. T-test revealed a significant decrease in subjective ratings of depression as rated by the BDI, t(45) = 9.82, P < 0.0001 (Pre-BDI = 27.9 +/- 20.2; post-BDI = 13.5 +/- 9.7). Objective ratings of memory appeared impaired following treatment, and patients' self-report measures of memory confirmed this decline. More specifically, repeated measures MANOVA [Wilks Lambda F(11,30) = 4.3, p < 0.001] indicated significant decreases for measures of immediate recognition memory (p < 0.005), long-term storage (p < 0.05), delayed prose passage recall (p < 0.0001), percent retained of prose passages (p < 0.0001), and percent retained of visual designs (p < 0.0001). In addition, the number of double mentions on the Levin increased (p < 0.02). This study suggests that there may be a greater need to discuss the intermittent cognitive risks associated with ECT when obtaining informed consent prior to treatment. Further that self-reports of cognitive difficulties may persist even when depression has remitted. However, patients may not acknowledge or be aware of changes in their memory functioning, and post-ECT self-reports may not be reliable.

Misestimation of peer tobacco use: understanding disparities in tobacco use.

Blacks experience disproportionately elevated rates of tobacco-related morbidity and mortality. Blacks experience delayed smoking initiation relative to other racial/ethnic groups, highlighting the importance of examining smoking correlates occurring in late adolescence/early adulthood. The current study reports data collected as part of an ongoing collaborative effort to assess alcohol and drug use on the campuses of historically black colleges and universities (HBCUs). Two-thousand, two-hundred, seventy-seven African-American subjects, aged 20.3 +/- 3.9 (range 18-53), completed the CORE Alcohol and Drug survey and a brief demographic questionnaire. Results indicated that 90% of all subjects overestimated the rate of smoking among their peers. Overestimating was associated with a > 80% increase in the risk of smoking. These data highlight the need to correct misinformation regarding smoking norms among students at some HBCUs.

Fear of movement (kinesiophobia), pain, and psychopathology in patients with sickle cell disease.

OBJECTIVES: Fear of movement (ie, kinesiophobia) has emerged as a significant predictor of pain-related outcomes including disability and psychologic distress across various types of pain (eg, back pain, headache, fibromyalgia, complex regional pain syndrome). However, no research has examined the prevalence of kinesiophobia in adults with sickle cell disease (SCD). The purpose of this study was to assess the degree of kinesiophobia reported by African American men and women with SCD and to determine whether kinesiophobia is related to pain and psychologic distress in this population. METHODS: Sixty-seven men and women with SCD recruited from a comprehensive sickle cell treatment program in a large academic medical center completed questionnaires that assess fear of movement, pain and pain interference, and psychologic distress. RESULTS: Participants reported levels of kinesiophobia (M=30.48, SD=7.55) that were comparable to those obtained for patients with low back pain and fibromyalgia. Although pain levels did not differ by sex, men reported greater kinesiophobia than women (P=0.02). As hypothesized, higher levels of kinesiophobia were associated with greater psychologic distress, particularly Phobic Anxiety (r=0.35), Psychoticism (r=0.29), Somatization (r=0.45), Anxiety (r=0.35), Obsessive-compulsive (r=0.34), Interpersonal Sensitivity (r=0.25), Depression (r=0.29), and all 3 summary indices of the SCL-90-R (all Ps<0.05). DISCUSSION: Although and historically, pain associated with SCD has not been considered in the context of fear of movement, findings suggest that both kinesiophobia and sex are relevant constructs for consideration in understanding pain-related outcomes in SCD. Though our results require replication, this study suggests that greater kinesiophobia is associated with greater pain and psychologic distress.

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD).

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.

Reconsideration of the training of psychiatrists and mental health professionals: helping to make soup.

For many years, we have known of deficits in our system of training mental health professionals, particularly in recognizing and integrating diversity. Recently, we have begun to understand that our literature must more authentically reflect the experiences of all people that we serve. The current paper suggests that a comprehensive biopsychosocial conceptualization of normal and abnormal behavior for all individuals is necessary to truly begin to reduce mental health disparities. The authors argue that factors such as racial, ethnic and cultural differences must be integrated into research before the literature will begin to change in a fashion that is beneficial to the mental health training process.

Parental substance abuse, reports of chronic pain and coping in adult patients with sickle cell disease.

There is increasing interest from a social learning perspective in understanding the role of parental factors on adult health behaviors and health outcomes. Our review revealed no studies, to date, that have evaluated the effects of parental substance abuse on reports of chronic pain and coping in adult patients with sickle cell disease (SCD). We explored the effects of parental substance (alcohol or drug) abuse on reports of the sensory, affective and summary indices of pain in 67 adult patients, mean age 38.9 (13.5), with SCD. We also explored the effects of parental substance abuse on psychopathology associated with pain and active coping. Twenty-four percent of patients reported that their parent(s) abused substances. Patients whose parent(s) were characterized as substance abusers reported greater sensory (p=0.02), affective (p=0.01) and summary (VAS; p=0.02) indices of pain as compared to their counterparts, whose parent(s) were not characterized as substance abusers. Patients did not differ in average age, education or the propensity to respond in a socially acceptable manner. There was a significant trend towards patients who characterized their parents as abusers scoring higher than their counterparts on active coping. We propose a Social Learning Theory to explain the current findings and suggest a need for additional prospective research to simultaneously explore biological (genetic) and social factors that influence the interpretation, experience and reporting of chronic pain in adult patients with chronic disease.

A brief review of the pathophysiology, associated pain, and psychosocial issues in sickle cell disease.

Sickle cell disease (SCD) is the most common genetic disorder of the blood. The disease produces significantly abnormal hemoglobin (Hgb) molecules in red blood cells (RBCs). The sickling of RBCs occurs when partially or totally deoxygenated Hgb molecules distort their normal disk shape, producing stiff, sticky, sickle-shaped cells that obstruct small blood vessels and produce vasoocclusion as well as the disruption of oxygen to body tissues. Because tissue damage can occur at multiple foci, patients with SCD are at risk for other medical complications including, but not limited to, delayed growth and sexual maturation; acute and chronic pulmonary dysfunction; stroke; aseptic necrosis of the hip, shoulders, or both; sickle cell retinopathy; dermal ulcers; and severe chronic pain. The chronicity of the illness combined with frequent hospitalizations for pain and other medical management can contribute significantly to impaired psychosocial functioning, altered intra- and interpersonal relationships, and reduced quality of life. Unlike previous qualitative reviews of SCD, this article describes the relevant clinical and research data on the relation between psychosocial functioning and SCD in adult and child populations. The authors discuss the significant role of psychosocial issues in the trajectory and management of the disease and conclude that understanding the pathophysiology of SCD without thoroughly understanding the equally important psychosocial influences is misunderstanding SCD.

Moderate chronic pain, weight and dietary intake in African-American adult patients with sickle cell disease.

In this exploratory study, we evaluated weight status and dietary intake patterns during painful episodes in adult patients with SCD. Specifically, we explored the relation between pain severity and body mass index (BMI), and we tested the hypothesis that dietary intake would be reduced and dietary content altered during periods of increased pain. We conducted an analysis of survey data from 62 patients involved in a longitudinal evaluation of the relationship of medical and psychosocial factors to pain. Nearly half of patients with SCD were overweight, and 20% were obese. BMI was positively related to interference associated with pain. Although BMI was not statistically associated with reported pain severity, >40% of patients reported that they perceived their pain to be affected by their weight. Less than 20% of patients reported that they perceived that their weight affected their pain. Regarding dietary patterns, the majority of patients reported eating less during episodes of pain and significantly decreasing their intake of fats and proteins. We conclude that there is a need to better understand the relation among weight, dietary patterns and pain in patients with SCD in order to provide patients with accurate education and effective treatment recommendations for managing their disease and reducing current and future risks of lifestyle and disease-related morbidities.