Body Dissatisfaction and Health Risk Behaviors Among Middle School Girls.

BACKGROUND: Previous studies demonstrate a relationship between body dissatisfaction and substance use and suicidal ideation among older adolescent girls and young women while less documentation exists for early adolescence. This study explored the relationship between reported weight loss attempts and substance use history and suicidal thoughts among younger female adolescents. METHODS: Participants (n = 1656) were middle school female students who participated in the 2019 Youth Behaviors Risk Survey. Participants were coded as "Trying to lose weight" and "Not trying to lose weight." Two hierarchal multiple binary logistic regressions were conducted, 1 for each of the dependent variables: (1) substance use history and (2) suicidality. RESULTS: Fifty-seven percent of the participants were trying to lose weight, 40% reported suicidal thoughts and 45% reported substance use history. Trying to lose weight was a significant predictor for both substance use (p < .01) and suicidality (p < .001). CONCLUSIONS: Body dissatisfaction and its association with risky health behaviors highlight the need for prevention education at earlier ages while reinforcing the need for availability of school counselors.

Disrupting the opportunity narrative: navigating transformation in times of uncertainty and crisis.

COVID-19 posed threats for health and well-being directly, but it also revealed and exacerbated social-ecological inequalities, worsening hunger and poverty for millions. For those focused on transforming complex and problematic system dynamics, the question was whether such devastation could create a formative moment in which transformative change could become possible. Our study examines the experiences of change agents in six African countries engaged in efforts to create or support transformative change processes. To better understand the relationship between crisis, agency, and transformation, we explored how they navigated their changed conditions and the responses to COVID-19. We document three impacts: economic impacts, hunger, and gender-based violence and we examine how they (re)shaped the opportunity contexts for change. Finally, we identify four kinds of uncertainties that emerged as a result of policy responses, including uncertainty about the: (1) robustness of preparing a system to sustain a transformative trajectory, (2) sequencing and scaling of changes within and across systems, (3) hesitancy and exhaustion effects, and (4) long-term effects of surveillance, and we describe the associated change agent strategies. We suggest these uncertainties represent new theoretical ground for future transformations research. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-023-01340-1.

Six-month outcomes of the CODES randomised controlled trial of cognitive behavioural therapy for dissociative seizures: A secondary analysis.

PURPOSE: The CODES Trial for adults with dissociative seizures had a predesignated 12-month post-randomisation follow-up point for outcome evaluation. We undertook an exploratory, unplanned, secondary analysis to evaluate the effectiveness of cognitive behavioural therapy plus standardised medical care (CBT+SMC) compared to SMC alone at 6 months post-randomisation, i.e., closer to the end of treatment. METHODS: The analysis of 6-month data followed our previous method of using multiple imputation and an intention-to-treat approach to analyse variables 12 months post-randomisation. RESULTS: The original trial primary outcome of monthly seizure frequency showed greater benefit from CBT+SMC than SMC-alone at 6 months (at p < 0.05). Of 13 comparable previously-defined secondary outcomes, 12 showed a significant between group effect (p < 0.05) in favour of the CBT intervention at 6 months. The average effect size of the comparable previously-defined primary and secondary continuous outcomes was 0.33 at 6 months vs 0.26 at 12 months. The estimated Incidence Rate Ratio (IRR) quantifying monthly seizure reduction was IRR = 0.72 (95%CI from 0.55 to 0.93) at 6 months compared to IRR = 0.78 at 12 months. CONCLUSION: DS-specific CBT (plus SMC) produced evidence of significant benefits at 6 months post- randomisation (around which time CBT was complete) compared to SMC alone; for the majority of these outcomes, better results following CBT (plus SMC) had previously been reported at 12 months. Our pattern of results suggests that short- and longer-term follow-ups are necessary to understand treatment effects in this disorder. Studies only providing short-term follow-up data should be interpreted with caution.

Cognitive-behavioural therapy compared with standardised medical care for adults with dissociative non-epileptic seizures: the CODES RCT.

BACKGROUND: Dissociative (non-epileptic) seizures are potentially treatable by psychotherapeutic interventions; however, the evidence for this is limited. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of dissociative seizure-specific cognitive-behavioural therapy for adults with dissociative seizures. DESIGN: This was a pragmatic, multicentre, parallel-arm, mixed-methods randomised controlled trial. SETTING: This took place in 27 UK-based neurology/epilepsy services, 17 liaison psychiatry/neuropsychiatry services and 18 cognitive-behavioural therapy services. PARTICIPANTS: Adults with dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous year and meeting other eligibility criteria were recruited to a screening phase from neurology/epilepsy services between October 2014 and February 2017. After psychiatric assessment around 3 months later, eligible and interested participants were randomised between January 2015 and May 2017. INTERVENTIONS: Standardised medical care consisted of input from neurologists and psychiatrists who were given guidance regarding diagnosis delivery and management; they provided patients with information booklets. The intervention consisted of 12 dissociative seizure-specific cognitive-behavioural therapy 1-hour sessions (plus one booster session) that were delivered by trained therapists, in addition to standardised medical care. MAIN OUTCOME MEASURES: The primary outcome was monthly seizure frequency at 12 months post randomisation. The secondary outcomes were aspects of seizure occurrence, quality of life, mood, anxiety, distress, symptoms, psychosocial functioning, clinical global change, satisfaction with treatment, quality-adjusted life-years, costs and cost-effectiveness. RESULTS: In total, 698 patients were screened and 368 were randomised (standardised medical care alone, n = 182; and cognitive-behavioural therapy plus standardised medical care, n = 186). Primary outcome data were obtained for 85% of participants. An intention-to-treat analysis with multivariate imputation by chained equations revealed no significant between-group difference in dissociative seizure frequency at 12 months [standardised medical care: median of seven dissociative seizures (interquartile range 1-35 dissociative seizures); cognitive-behavioural therapy and standardised medical care: median of four dissociative seizures (interquartile range 0-20 dissociative seizures); incidence rate ratio 0.78, 95% confidence interval 0.56 to 1.09; p = 0.144]. Of the 16 secondary outcomes analysed, nine were significantly better in the arm receiving cognitive-behavioural therapy at a p-value < 0.05, including the following at a p-value ≤ 0.001: the longest dissociative seizure-free period in months 7-12 inclusive post randomisation (incidence rate ratio 1.64, 95% confidence interval 1.22 to 2.20; p = 0.001); better psychosocial functioning (Work and Social Adjustment Scale, standardised treatment effect -0.39, 95% confidence interval -0.61 to -0.18; p < 0.001); greater self-rated and clinician-rated clinical improvement (self-rated: standardised treatment effect 0.39, 95% confidence interval 0.16 to 0.62; p = 0.001; clinician rated: standardised treatment effect 0.37, 95% confidence interval 0.17 to 0.57; p < 0.001); and satisfaction with treatment (standardised treatment effect 0.50, 95% confidence interval 0.27 to 0.73; p < 0.001). Rates of adverse events were similar across arms. Cognitive-behavioural therapy plus standardised medical care produced 0.0152 more quality-adjusted life-years (95% confidence interval -0.0106 to 0.0392 quality-adjusted life-years) than standardised medical care alone. The incremental cost-effectiveness ratio (cost per quality-adjusted life-year) for cognitive-behavioural therapy plus standardised medical care versus standardised medical care alone based on the EuroQol-5 Dimensions, five-level version, and imputed data was £120,658. In sensitivity analyses, incremental cost-effectiveness ratios ranged between £85,724 and £206,067. Qualitative and quantitative process evaluations highlighted useful study components, the importance of clinical experience in treating patients with dissociative seizures and potential benefits of our multidisciplinary care pathway. LIMITATIONS: Unlike outcome assessors, participants and clinicians were not blinded to the interventions. CONCLUSIONS: There was no significant additional benefit of dissociative seizure-specific cognitive-behavioural therapy in reducing dissociative seizure frequency, and cost-effectiveness over standardised medical care was low. However, this large, adequately powered, multicentre randomised controlled trial highlights benefits of adjunctive dissociative seizure-specific cognitive-behavioural therapy for several clinical outcomes, with no evidence of greater harm from dissociative seizure-specific cognitive-behavioural therapy. FUTURE WORK: Examination of moderators and mediators of outcome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05681227 and ClinicalTrials.gov NCT02325544. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 43. See the NIHR Journals Library website for further project information.

Dissociative seizures resemble epileptic seizures or faints, but can be distinguished from them by trained doctors. Dissociation is the medical word for a 'trance-like' or 'switching off' state. People with dissociative seizures commonly have other psychological or physical problems. Quality of life may be low. The condition accounts for about one in every six patients seen in hospitals because of seizures. We wanted to find out if people with dissociative seizures receiving standardised treatment would also benefit from a talking therapy, called cognitive­behavioural therapy, made specific to this disorder. We did a randomised controlled trial to find out if people with dissociative seizures given standardised treatment and cognitive­behavioural therapy (talking therapy) would do better than those given standardised treatment alone. Standardised treatment of dissociative seizures began with careful diagnosis from a neurologist and then further assessment and treatment from a psychiatrist. In total, 368 people with dissociative seizures participated, with half receiving standardised treatment alone and half having talking therapy plus standardised treatment. We measured seizures and psychological and physical health in both trial groups. We also investigated whether or not cognitive­behavioural therapy was good value for money. After 12 months, patients in both trial groups seemed to have fewer monthly seizures, but there was no advantage in the talking therapy group. Patients in the talking therapy group had more consecutive days without seizures, reporting less impact from them in everyday situations. Patients in the talking therapy group, and their doctors, considered improvements to be better, and patients in this group reported greater satisfaction with treatment. However, the talking therapy was expensive and not as cost-effective as hoped. Interviews with patients and study clinicians showed that they valued aspects of both treatments and of the care provided by the multidisciplinary teams. Overall, cognitive­behavioural therapy designed for dissociative seizures plus standardised treatment was not better at reducing the total numbers of seizures reported, but did produce several positive benefits for participants compared with standardised treatment alone.

Sexual Health Services in Schools: A Successful Community Collaborative.

School-based health centers (SBHCs) are an essential part of a comprehensive approach to address the health needs of youth. SBHCs that provide sexual health services (SHS) show promising results in improving reproductive health outcomes among youth. Despite the positive impact SBHCs can have, few school districts have SBHCs, and even fewer provide SHS. This article describes a successful 5-year project to provide SHS through SBHCs in a large county in the southeast United States. A community collaborative, including the schools, health department, community agencies and a local university, was created to address the project goals and objectives. Various steps were taken to plan for the SBHCs, including documenting community support for SHS offered through SBHCs, identifying school sites for SBHCs, and the process for offering pregnancy, STD (sexually transmitted disease), and HIV testing, treatment, and referrals. Protocols for clinic flow, testing, staffing, training, and student recruitment were developed. The staff at the SBHCs were successful in recruiting students to attend educational sessions and to receive testing and treatment. Student feedback was overwhelmingly positive. Lessons learned about the importance of the partnership's collaboration, using recommended clinic protocol, ensuring clear communication with school staff, and employing youth friendly recruitment and clinic practices are shared.

Psychological and demographic characteristics of 368 patients with dissociative seizures: data from the CODES cohort.

BACKGROUND: We examined demographic, clinical, and psychological characteristics of a large cohort (n = 368) of adults with dissociative seizures (DS) recruited to the CODES randomised controlled trial (RCT) and explored differences associated with age at onset of DS, gender, and DS semiology. METHODS: Prior to randomisation within the CODES RCT, we collected demographic and clinical data on 368 participants. We assessed psychiatric comorbidity using the Mini-International Neuropsychiatric Interview (M.I.N.I.) and a screening measure of personality disorder and measured anxiety, depression, psychological distress, somatic symptom burden, emotional expression, functional impact of DS, avoidance behaviour, and quality of life. We undertook comparisons based on reported age at DS onset (<40 v. ⩾40), gender (male v. female), and DS semiology (predominantly hyperkinetic v. hypokinetic). RESULTS: Our cohort was predominantly female (72%) and characterised by high levels of socio-economic deprivation. Two-thirds had predominantly hyperkinetic DS. Of the total, 69% had ⩾1 comorbid M.I.N.I. diagnosis (median number = 2), with agoraphobia being the most common concurrent diagnosis. Clinical levels of distress were reported by 86% and characteristics associated with maladaptive personality traits by 60%. Moderate-to-severe functional impairment, high levels of somatic symptoms, and impaired quality of life were also reported. Women had a younger age at DS onset than men. CONCLUSIONS: Our study highlights the burden of psychopathology and socio-economic deprivation in a large, heterogeneous cohort of patients with DS. The lack of clear differences based on gender, DS semiology and age at onset suggests these factors do not add substantially to the heterogeneity of the cohort.

Depression in High School: Lesbian, Gay, and Bisexual Identity as a Moderator of Sexual Assault.

BACKGROUND: Depression continues to be a public health crisis for young adults. For high school students, past research has identified trauma as a significant predictor of depression. Congruent with the theory of cumulative stress, the present study hypothesized that the effect of sexual assault on depression would be stronger among lesbian, gay, and bisexual (LGB) students than among their straight peers. METHODS: Using the Youth Risk Behavior Survey completed by students attending Duval County Public Schools in Florida (N = 3053), this study used secondary data analysis to conduct 2 regression analyses, one for boys and one for girls. RESULTS: LGB status was associated with 3-fold increase in the odds of reporting depression for both boys and girls. History of sexual assault was associated with a significant increase in reporting depression. There was also a significant interaction effect between sexual orientation and history of sexual assault among male students only (p < .05). Contrary to the hypothesis, the effect was stronger among straight boys than among LGB boys. CONCLUSION: Minority students continue to evidence greater risks for depression. Opportunities for systemic changes to address these include training teachers, banning conversion therapy, and implementing comprehensive sex education.

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme.

Characteristics of 698 patients with dissociative seizures: A UK multicenter study.

OBJECTIVE: We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology. METHODS: We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non-Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations. RESULTS: In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self-reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two-thirds were unemployed. SIGNIFICANCE: Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.

Sleep State Dependence of Optogenetically evoked Responses in Neuronal Nitric Oxide Synthase-positive Cells of the Cerebral Cortex.

Slow-wave activity (SWA) in the electroencephalogram during slow-wave sleep (SWS) varies as a function of sleep-wake history. A putative sleep-active population of neuronal nitric oxide synthase (nNOS)-containing interneurons in the cerebral cortex, defined as such by the expression of Fos in animals euthanized after protracted deep sleep, may be a local regulator of SWA. We investigated whether electrophysiological responses to activation of these cells are consistent with their role of a local regulator of SWA. Using a Cre/loxP strategy, we targeted the population of nNOS interneurons to express the light-activated cation channel Channelrhodopsin2 and the histological marker tdTomato in mice. We then performed histochemical and optogenetic studies in these transgenic mice. Our studies provided histochemical evidence of transgene expression and electrophysiological evidence that the cerebral cortex was responsive to optogenetic manipulation of these cells in both anesthetized and behaving mice. Optogenetic stimulation of the cerebral cortex of animals expressing Channelrhodopsin2 in nNOS interneurons triggered an acute positive deflection of the local field potential that was followed by protracted oscillatory events only during quiet wake and slow wave sleep. The response during wake was maximal when the electroencephalogram (EEG) was in a negative polarization state and abolished when the EEG was in a positive polarization state. Since the polarization state of the EEG is a manifestation of slow-wave oscillations in the activity of underlying pyramidal neurons between the depolarized (LFP negative) and hyperpolarized (LFP positive) states, these data indicate that sleep-active cortical neurons expressing nNOS function in sleep slow-wave physiology.

Support for Offering Sexual Health Services Through School-Based Health Clinics.

BACKGROUND: Numerous studies document support for sexuality education in the schools. However, there is a dearth of research assessing support for sexual health services offered through school-based health clinics (SBHCs). The purpose of this study was to assess voter support for offering 3 sexual health services (STI/HIV testing, STI/HIV treatment, condom distribution) through SBHCs. METHODS: The survey was developed after review of existing surveys on support for sexuality education and sexual health services. The university's Public Opinion Research Laboratory used random-digit-dialing to administer the survey to participants (N = 311) including residential and cell phone numbers. RESULTS: Most participants were supportive of offering sexual health services at both middle schools (MS) and high schools (HS): testing for STIs/HIV (61% MS, 76% HS), treatment for STIs/HIV (60% MS, 75% HS), and provision of condoms (44% MS, 63% HS). Analyses showed significant differences in support for sexual health services by a few demographic variables, opinions about sexuality education, and the percentage of students perceived to have had sexual intercourse. CONCLUSIONS: Results document support for offering sexual health services through SBHCs. These findings may benefit other communities looking to implement similar clinics. Such services have great potential for positively impacting the sexual health of youth.

Manipulating neuronal activity in the mouse brain with ultrasound: A comparison with optogenetic activation of the cerebral cortex.

Low-intensity focused ultrasound induces neuronal activation via mechanisms that remain to be elucidated. We recorded local field potential fluctuations in the motor cortex in response to ultrasound stimulation of the somatosensory barrel cortex, comparing them to those recorded in response to optogenetic stimulation of interneurons and pyramidal neurons of the somatosensory cortex in the same animals. Comparison of the waveform produced by ultrasound stimulation to those produced by optogenetic stimulation revealed similarities between ultrasound-induced responses and optogenetically-induced responses to pyramidal cell stimulation, but not interneuron stimulation, which may indicate that ultrasound stimulation is mediated by excitation of cerebral cortical pyramidal neurons. Comparison of post mortem evoked responses to responses in living tissue confirmed the necessity for excitable tissue in the evoked response. Collectively, these experiments demonstrate an excitation-dependent response to low-frequency transdural ultrasound stimulation of cerebral cortical neuronal activity.

Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease.

Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primate models will be an important step in clinical development of cell therapy. Here, we analyzed cynomolgus monkey (CM) iPSC-derived midbrain dopamine neurons for up to 2 years following autologous transplantation in a Parkinson's disease (PD) model. In one animal, with the most successful protocol, we found that unilateral engraftment of CM-iPSCs could provide a gradual onset of functional motor improvement contralateral to the side of dopamine neuron transplantation, and increased motor activity, without a need for immunosuppression. Postmortem analyses demonstrated robust survival of midbrain-like dopaminergic neurons and extensive outgrowth into the transplanted putamen. Our proof of concept findings support further development of autologous iPSC-derived cell transplantation for treatment of PD.

New evidence: data documenting parental support for earlier sexuality education.

BACKGROUND: Numerous studies document support for sexuality education to be taught in high school, and often, in middle school. However, little research has been conducted addressing support for sexuality education in elementary schools. METHODS: As part of the state Behavioral Risk Factor Surveillance System (BRFSS) Survey administration, the Florida Department of Health conducted the Florida Child Health Survey (FCHS) by calling back parents who had children in their home and who agreed to participate (N = 1715). RESULTS: Most parents supported the following sexuality education topics being taught specifically in elementary school: communication skills (89%), human anatomy/reproductive information (65%), abstinence (61%), human immunodeficiency virus (HIV)/sexually transmitted infections (STIs) (53%), and gender/sexual orientation issues (52%). Support was even greater in middle school (62-91%) and high school (72-91%) for these topics and for birth control and condom education. Most parents supported comprehensive sexuality education (40.4%), followed by abstinence-plus (36.4%) and abstinence-only (23.2%). Chi-square results showed significant differences in the type of sexuality education supported by almost all parent demographic variables analyzed including sex, race, marital status, and education. CONCLUSIONS: Results add substantial support for age-appropriate school-based sexuality education starting at the elementary school level, the new National Sexuality Education Standards, and funding to support evidence-based abstinence-plus or comprehensive sexuality education.

Improved cell therapy protocols for Parkinson's disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons.

The main motor symptoms of Parkinson's disease are due to the loss of dopaminergic (DA) neurons in the ventral midbrain (VM). For the future treatment of Parkinson's disease with cell transplantation it is important to develop efficient differentiation methods for production of human iPSCs and hESCs-derived midbrain-type DA neurons. Here we describe an efficient differentiation and sorting strategy for DA neurons from both human ES/iPS cells and non-human primate iPSCs. The use of non-human primate iPSCs for neuronal differentiation and autologous transplantation is important for preclinical evaluation of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate iPSC (PiPSC)-derived DA neurons. According to our results, NCAM(+) /CD29(low) sorting enriched VM DA neurons from pluripotent stem cell-derived neural cell populations. NCAM(+) /CD29(low) DA neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC-derived NCAM(+) /CD29(low) DA neurons were able to restore motor function of 6-hydroxydopamine (6-OHDA) lesioned rats 16 weeks after transplantation. The transplanted sorted cells also integrated in the rodent brain tissue, with robust TH+/hNCAM+ neuritic innervation of the host striatum. One year after autologous transplantation, the primate iPSC-derived neural cells survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH-positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC-derived cell transplantation therapies in the future.

Sleep slow-wave activity regulates cerebral glycolytic metabolism.

Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1-4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cortex demonstrates that it increases during enforced wakefulness. In spontaneous sleep/wake cycles, lactate concentration builds during wakefulness and rapid eye movement sleep and declines during NREMS. The rate at which lactate concentration declines during NREMS is proportional to the magnitude of electroencephalographic (EEG) activity at frequencies of <10 Hz. The induction of 1-Hz oscillations, but not 10-Hz oscillations, in the electroencephalogram by optogenetic stimulation of cortical pyramidal cells during wakefulness triggers a decline in lactate concentration. We conclude that cerebral SWA promotes a decline in the rate of glycolysis in the cerebral cortex. These results demonstrate a cellular energetic function for sleep SWA, which may contribute to its restorative effects on brain function.

Sexual behaviors of middle school students: 2009 Youth Risk Behavior Survey results from 16 locations.

BACKGROUND: The potential negative consequences of engaging in sexual risk behaviors at a young age are well documented. Unfortunately, there is a dearth of information about the prevalence of sexual behaviors among middle school students. This article provides an overview of the sexual risk behaviors of middle school students from 16 districts and states throughout the country, and examines these risks by demographic variables. METHODS: In 2009, 10 states and 6 districts administered the Youth Risk Behavior Survey-Middle School and included sexual behavior questions. Data were examined using the Centers for Disease Control and Prevention's Youth Online database. Frequencies were run for 4 sexual behaviors and an HIV/AIDS education question for each location. A series of t-tests were calculated for these 5 items by gender, age, and race for each location. RESULTS: Data show that 5-20% of sixth graders and 14-42% of eighth graders have engaged in sexual intercourse. A concerning percentage of students have also engaged in other sexual risk behaviors and many are not receiving HIV/AIDS education. Additionally, there were significant differences by gender, race, and age. CONCLUSION: Consistent with previous studies, males, minorities, and older students are more likely to engage in sexual risk behaviors. There is also variation in the percentage of students engaging in sexual behaviors across locations. Sexual risk reduction education is important for middle school youth, particularly for minorities, males and those from southern and/or larger, urban cities as those are the populations with generally higher sexual risk behaviors.

Simultaneous electroencephalography, real-time measurement of lactate concentration and optogenetic manipulation of neuronal activity in the rodent cerebral cortex.

Although the brain represents less than 5% of the body by mass, it utilizes approximately one quarter of the glucose used by the body at rest(1). The function of non rapid eye movement sleep (NREMS), the largest portion of sleep by time, is uncertain. However, one salient feature of NREMS is a significant reduction in the rate of cerebral glucose utilization relative to wakefulness(2-4). This and other findings have led to the widely held belief that sleep serves a function related to cerebral metabolism. Yet, the mechanisms underlying the reduction in cerebral glucose metabolism during NREMS remain to be elucidated. One phenomenon associated with NREMS that might impact cerebral metabolic rate is the occurrence of slow waves, oscillations at frequencies less than 4 Hz, in the electroencephalogram(5,6). These slow waves detected at the level of the skull or cerebral cortical surface reflect the oscillations of underlying neurons between a depolarized/up state and a hyperpolarized/down state(7). During the down state, cells do not undergo action potentials for intervals of up to several hundred milliseconds. Restoration of ionic concentration gradients subsequent to action potentials represents a significant metabolic load on the cell(8); absence of action potentials during down states associated with NREMS may contribute to reduced metabolism relative to wake. Two technical challenges had to be addressed in order for this hypothetical relationship to be tested. First, it was necessary to measure cerebral glycolytic metabolism with a temporal resolution reflective of the dynamics of the cerebral EEG (that is, over seconds rather than minutes). To do so, we measured the concentration of lactate, the product of aerobic glycolysis, and therefore a readout of the rate of glucose metabolism in the brains of mice. Lactate was measured using a lactate oxidase based real time sensor embedded in the frontal cortex. The sensing mechanism consists of a platinum-iridium electrode surrounded by a layer of lactate oxidase molecules. Metabolism of lactate by lactate oxidase produces hydrogen peroxide, which produces a current in the platinum-iridium electrode. So a ramping up of cerebral glycolysis provides an increase in the concentration of substrate for lactate oxidase, which then is reflected in increased current at the sensing electrode. It was additionally necessary to measure these variables while manipulating the excitability of the cerebral cortex, in order to isolate this variable from other facets of NREMS. We devised an experimental system for simultaneous measurement of neuronal activity via the elecetroencephalogram, measurement of glycolytic flux via a lactate biosensor, and manipulation of cerebral cortical neuronal activity via optogenetic activation of pyramidal neurons. We have utilized this system to document the relationship between sleep-related electroencephalographic waveforms and the moment-to-moment dynamics of lactate concentration in the cerebral cortex. The protocol may be useful for any individual interested in studying, in freely behaving rodents, the relationship between neuronal activity measured at the electroencephalographic level and cellular energetics within the brain.

Pilot of a computer-based brief multiple-health behavior intervention for college students.

OBJECTIVE: Given the documented multiple health risks college students engage in, and the dearth of effective programs addressing them, the authors developed a computer-based brief multiple-health behavior intervention. This study reports immediate outcomes and feasibility of a pilot of this program. PARTICIPANTS: Two hundred students attending a midsized university participated. METHODS: Participants were randomly assigned to the intervention or control program, both delivered via computer. Immediate feedback was collected with the computer program. RESULTS: Results indicate that the intervention had an early positive impact on alcohol and cigarette use intentions, as well as related constructs underlying the Behavior-Image Model specific to each of the 3 substances measured. Based on the implementation process, the program proved to be feasible to use and acceptable to the population. CONCLUSION: Results support the potential efficacy of the intervention to positively impact behavioral intentions and linkages between health promoting and damaging behaviors among college students.