Parent clinical trial priorities for fragile X syndrome: a best-worst scaling.

An expansion in the availability of clinical drug trials for genetic neurodevelopmental conditions is underway. Delineating patient priorities is key to the success of drug development and clinical trial design. There is a lack of evidence about parent decision-making in the context of clinical drug trials for genetic neurodevelopmental conditions. We assessed parents' priorities when making a decision whether to enroll their child with fragile X syndrome (FXS) in a clinical drug trial. An online survey included a best-worst scaling method for parents to prioritize motivating and discouraging factors for child enrollment. Parents were recruited through the National Fragile X Foundation and FRAXA. Sequential best-worst with conditional logit analysis was used to determine how parents prioritize motivating and discouraging factors about trial enrollment decisions. Respondents (N = 354) were largely biological mothers (83%) of an individual with FXS who ranged in age from under 5 to over 21 years. The highest motivating factor was a trial to test a drug targeting the underlying FXS mechanism (coeff = 3.28, p < 0.001), followed by the potential of the drug to help many people (coeff = 3.03, p < 0.001). Respondents rated requirement of blood draws (coeff = -3.09, p < 0.001), loss of access to the drug post trial (coeff = -3.01, p < 0.001), and drug side effects (coeff = -2.96, p < 0.001) as most discouraging. The priorities defined by parents can be incorporated into evidence-based trial design and execution to enhance the enrollment process

Climate change adaptation in aquaculture

This study conducts the first systematic literature review of climate change adaptation in aquaculture. We address three specific questions: (i) What is aquaculture adapting to? (ii) How is aquaculture adapting? and (iii) What research gaps need to be addressed? We identify, characterise and examine case studies published between 1990 and 2018 that lie at the intersection of the domains of climate change, adaptation and aquaculture. The main areas of documented climate change impacts relate to extreme events and the general impacts of climate change on the aquaculture sector. Three categories of adaptation to climate change are identified: coping mechanisms at the local level (e.g. water quality management techniques), multilevel adaptive strategies (e.g. changing culture practices) and management approaches (e.g. adaptation planning, community‐based adaptation). We identify four potential areas for future research: research on inland aquaculture adaptation; studies at the household level; whether different groups of aquaculture farmers (e.g. indigenous people) face and adapt differently to climate change; and the use of GIS and remote sensing as cost‐effective tools for developing adaptation strategies and responses. The study brings essential practical and theoretical insights to the aquaculture industry as well as to climate change adaptation research across the globe

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

A Randomized Community-based Intervention Trial Comparing Faith Community Nurse Referrals to Telephone-Assisted Physician Appointments for Health Fair Participants with Elevated Blood Pressure

To measure the effect of faith community nurse referrals versus telephone-assisted physician appointments on blood pressure control among persons with elevated blood pressure at health fairs. Randomized community-based intervention trial conducted from October 2006 to October 2007 of 100 adults who had an average blood pressure reading equal to or above a systolic of 140 mm Hg or a diastolic of 90 mm Hg obtained at a faith community nurse-led church health event. Participants were randomized to either referral to a faith community nurse or to a telephone-assisted physician appointment. The average enrollment systolic blood pressure (SBP) was 149 ± 14 mm Hg, diastolic blood pressure (DBP) was 87 ± 11 mm Hg, 57% were uninsured and 25% were undiagnosed at the time of enrollment. The follow-up rate was 85% at 4 months. Patients in the faith community nurse referral arm had a 7 ± 15 mm Hg drop in SBP versus a 14 ± 15 mm Hg drop in the telephone-assisted physician appointment arm (p = 0.04). Twenty-seven percent of the patients in the faith community nurse referral arm had medication intensification compared to 32% in the telephone-assisted physician appointment arm (p = 0.98). Church health fairs conducted in low-income, multiethnic communities can identify many people with elevated blood pressure. Facilitating physician appointments for people with elevated blood pressure identified at health fairs confers a greater decrease in SBP than referral to a faith community nurse at four months

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

Under- treatment and under diagnosis of hypertension: a serious problem in the United Arab Emirates

BACKGROUND: Hypertension, notably untreated or uncontrolled, is a major risk factor for cardiovascular diseases (CVD) morbidity and mortality. In countries in transition, little is known about the epidemiology of hypertension, and its biochemical correlates. This study was carried out in Al Ain, United Arab Emirates, to characterize self-reported (SR) normotensives and hypertensives in terms of actual hypertension status, demographic variables, CVD risk factors, treatment, and sequalae. METHODS: A sample, stratified by SR hypertensive status, of 349 SR hypertensives (Mean age ± SD; 50.8 ± 9.2 yrs; Male: 226) and 640 SR normotensives (42.9 ± 9.3 yrs, Male: 444) among nationals and expatriates was used. Hypertensives and normotensive subjects were recruited from various outpatient clinics and government organizations in Al-Ain city, United Arab Emirates (UAE) respectively. Anthropometric and demographic variables were measured by conventional methods. RESULTS: Both under-diagnosis of hypertension (33%) and under-treatment (76%) were common. Characteristics of undiagnosed hypertensives were intermediate between normotensives and SR hypertensives. Under-diagnosis of hypertension was more common among foreigners than among nationals. Risk factors for CVD were more prevalent among SR hypertensives. Obesity, lack of exercise and smoking were found as major risk factors for CVD among hypertensives in this population. CONCLUSION: Hypertension, even severe, is commonly under-diagnosed and under-treated in the UAE. Preventive strategies, better diagnosis and proper treatment compliance should be emphasized to reduce incidence of CVD in this population

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023

Worth the ‘EEfRT’? The Effort Expenditure for Rewards Task as an Objective Measure of Motivation and Anhedonia

Background: Of the putative psychopathological endophenotypes in major depressive disorder (MDD), the anhedonic subtype is particularly well supported. Anhedonia is generally assumed to reflect aberrant motivation and reward responsivity. However, research has been limited by a lack of objective measures of reward motivation. We present the Effort-Expenditure for Rewards Task (EEfRT or ‘‘effort’’), a novel behavioral paradigm as a means of exploring effort-based decision-making in humans. Using the EEfRT, we test the hypothesis that effort-based decision-making is related to trait anhedonia. Methods/Results: 61 undergraduate students participated in the experiment. Subjects completed self-report measures of mood and trait anhedonia, and completed the EEfRT. Across multiple analyses, we found a significant inverse relationship between anhedonia and willingness to expend effort for rewards. Conclusions: These findings suggest that anhedonia is specifically associated with decreased motivation for rewards, and provide initial validation for the EEfRT as a laboratory-based behavioral measure of reward motivation and effort-base

Patterns of Childhood Trauma and Psychological Distress among Injecting Heroin Users in China

Background: Childhood trauma has been reported as a possible cause of future substance abuse in some countries. This study reports the prevalence of childhood trauma and examines its association with psychological distress among injecting drug users from mainland China. Methodology: The study was conducted in three government-operated drug rehabilitation facilities in Shanghai, China in 2007. The Early Trauma Inventory Self Report-Short Form (ETISR-SF) was used to evaluate 4 types (general, emotional, physical and sexual) and severity of childhood trauma, and the Symptom Checklist-90-Revised (SCL-90-R) to evaluate psychological distress. Principal Findings: Among 341 injecting drug users who completed the study, about 80 % reported one or more types o