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Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.

BackgroundThyroid dysfunction is associated with cognitive impairment, mood disturbance, and postnatal depression. Sufficient thyroid hormone synthesis requires adequate intake of iodine, selenium, and iron. Iodine deficiency was historically a problem for New Zealand, and initiatives were introduced to overcome the problem: (1) mandatory fortification of all bread (except organic) with iodized salt (2009) and (2) provision of subsidized iodine supplements for pregnant and breastfeeding women (2010). Subsequent to these initiatives, most adults and children have adequate iodine status; however, status among breastfeeding women and their infants remains unclear. This paper outlines the methodology of the Mother and Infant Nutrition Investigation (MINI) study: an observational longitudinal cohort study of breastfeeding women and their infants. ObjectiveThis study will determine (1) women’s iodine intake and status among supplement users and nonusers; (2) women’s intake and status of iodine, selenium, and iron relating to thyroid function; (3) associations between women’s selenium status, thyroid function, and postnatal depression; (4) infants’ iodine and selenium status relating to first year neurodevelopment. MethodsBreastfeeding women aged over 16 years with a healthy term singleton infant were recruited from Manawatu, New Zealand. Participants attended study visits 3, 6, and 12 months postpartum. Maternal questionnaires investigated supplement use before and after birth, iodine knowledge, and demographic information. Dietary assessment and urine, blood, and breast milk samples were taken to measure iodine, selenium, and iron intake/status. The Edinburgh Postnatal Depression Scale was used repeatedly to screen for postnatal depression. Thyroid hormones (free triiodothyronine, free thyroxine, thyroid stimulating hormone, thyroglobulin, antithyroglobulin antibodies, and antithyroid peroxidase) were measured in blood samples, and thyroid gland volume was measured by ultrasound at 6 months postpartum. Infant iodine and selenium concentrations were determined in urine. The Ages and Stages Questionnaire was used to assess infant development at 4, 8, and 12 months. ResultsData collection was completed. Biological samples analysis, excluding nail clippings, is complete. Data analysis and presentation of the results will be available after 2020. ConclusionsThis study will provide data on the current iodine status of breastfeeding women. It will also provide a greater understanding of the three essential minerals required for optimal thyroid function among breastfeeding women. The prospective longitudinal design allows opportunities to examine women’s mental health and infant neurodevelopment throughout the first year, a crucial time for both mothers and their infants. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12615001028594; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369324 International Registered Report Identifier (IRRID)DERR1-10.2196/18560

Computed tomographic coronary artery calcium scanning enables cardiovascular risk stratification; however, exposing patients to high radiation levels is an ongoing concern. New-generation computed tomographic systems use lower radiation doses than older systems do. To quantify comparative doses of radiation exposure, we prospectively acquired images from 220 patients with use of a 64-slice GE LightSpeed VCT scanner (control group, n=110) and a 256-slice GE Revolution scanner (study group, n=110). The groups were matched for age, sex, and body mass index; statistical analysis included t tests and linear regression. The mean dose-length product was 21% lower in the study group than in the control group (60.2 ± 27 vs 75.9 ± 22.6 mGy·cm; P

Background and aimThe association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA).Patients and methodsHIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time.ConclusionWe describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

This study explored how prospective elementary teachers developed mathematics teaching that used the cultural, linguistic, and cognitive resources from home and community settings to promote learning school mathematics with robotics. Drawing on lesson planning artifacts and written reflections following lesson enactments, the authors describe how prospective teachers made progress toward more equitable mathematics teaching by connecting mathematics learning and robotics, leveraging community funds of knowledge in mathematics instruction with robotics, and designing for transdisciplinary connections. Analyses showed how robotics can support planning for a range of elementary mathematics concepts -- including counting, multiplicative reasoning, distance, and sequence -- and may encourage leveraging students' sense of place to make mathematics learning more accessible for every student. These findings suggest that mathematics teacher educators and teachers should consider using innovative tools not typically seen in classrooms, such as robotics, in mathematics instruction as they work to support a focus on reasoning and sense making and make connections to children's community and cultural funds of knowledge.

Prostaglandin E2 imparts diverse physiological effects on multiple airway cells through its actions on four distinct E-type prostanoid (EP) receptor subtypes (EP1-EP4). Gs-coupled EP2 and EP4 receptors are expressed on airway smooth muscle (ASM), yet their capacity to regulate the ASM contractile state remains subject to debate. We used EP2 and EP4 subtype-specific agonists (ONO-259 and ONO-329, respectively) in cell- and tissue-based models of human ASM contraction--magnetic twisting cytometry (MTC), and precision-cut lung slices (PCLSs), respectively--to study the EP2 and EP4 regulation of ASM contraction and signaling under conditions of histamine or methacholine (MCh) stimulation. ONO-329 was superior (<0.05) to ONO-259 in relaxing MCh-contracted PCLSs (log half maximal effective concentration [logEC50]: 4.9 x 10-7 vs. 2.2 x 10-6; maximal bronchodilation ± SE, 35 ± 2% vs. 15 ± 2%). However, ONO-259 and ONO-329 were similarly efficacious in relaxing histamine-contracted PCLSs. Similar differential effects were observed in MTC studies. Signaling analyses revealed only modest differences in ONO-329- and ONO-259-induced phosphorylation of the protein kinase A substrates VASP and HSP20, with concomitant stimulation with MCh or histamine. Conversely, ONO-259 failed to inhibit MCh-induced phosphorylation of the regulatory myosin light chain (pMLC20) and the F-actin/G-actin ratio (F/G-actin ratio) while effectively inhibiting their induction by histamine. ONO-329 was effective in reversing induced pMLC20 and the F/G-actin ratio with both MCh and histamine. Thus, the contractile-agonist-dependent differential effects are not explained by changes in the global levels of phosphorylated protein kinase A substrates but are reflected in the regulation of pMLC20 (cross-bridge cycling) and F/G-actin ratio (actin cytoskeleton integrity, force transmission), implicating a role for compartmentalized signaling involving muscarinic, histamine, and EP receptor subtypes. [ABSTRACT FROM AUTHOR]

Background and Purpose: β-Adrenoceptor agonists relieve airflow obstruction by activating β2 -adrenoceptors, which are G protein-coupled receptors (GPCRs) expressed on human airway smooth muscle (HASM) cells. The currently available β-adrenoceptor agonists are balanced agonists, however, and signal through both the stimulatory G protein (Gs )- and β-arrestin-mediated pathways. While Gs signalling is beneficial and promotes HASM relaxation, β-arrestin activation is associated with reduced Gs efficacy. In this context, biased ligands that selectively promote β2 -adrenoceptor coupling to Gs signalling represent a promising strategy to treat asthma. Here, we examined several β-adrenoceptor agonists to identify Gs -biased ligands devoid of β-arrestin-mediated effects.Experimental Approach: Gs -biased ligands for the β2 -adrenoceptor were identified by high-throughput screening and then evaluated for Gs interaction, Gi interaction, cAMP production, β-arrestin interaction, GPCR kinase (GRK) phosphorylation of the receptor, receptor trafficking, ERK activation, and functional desensitization of the β2 -adrenoceptor.Key Results: We identified ractopamine, dobutamine, and higenamine as Gs -biased agonists that activate the Gs /cAMP pathway upon β2 -adrenoceptor stimulation while showing minimal Gi or β-arrestin interaction. Furthermore, these compounds did not induce any receptor trafficking and had reduced GRK5-mediated phosphorylation of the β2 -adrenoceptor. Finally, we observed minimal physiological desensitization of the β2 -adrenoceptor in primary HASM cells upon treatment with biased agonists.Conclusion and Implications: Our work demonstrates that Gs -biased signalling through the β2 -adrenoceptor may prove to be an effective strategy to promote HASM relaxation in the treatment of asthma. Such biased compounds may also be useful in identifying the molecular mechanisms that determine biased signalling and in design of safer drugs. [ABSTRACT FROM AUTHOR]