Associations between maternal urinary iodine assessment, dietary iodine intakes and neurodevelopmental outcomes in the child: A Systematic Review

Abstract Objective Mild to moderate iodine deficiency during pregnancy has been associated with adverse neurodevelopmental outcomes in offspring. Few research studies to date combine assessment of urinary iodine (UIC and/or ICr), biomarkers that best reflect dietary intake, with reported dietary intake of iodine rich foods in their assessment of iodine deficiency. Thus, a systematic review was conducted to incorporate both these important measures. Design Using PRISMA guidelines, a comprehensive search was conducted in three electronic databases (EMBASE®, MedLine® and Web of Science®) from January 1970–March 2021. Quality assessment was undertaken using the Newcastle Ottawa Scale. Eligible studies included reported assessment of iodine status through urinary iodine (UIC and/or ICr) and/or dietary intake measures in pregnancy alongside neurodevelopmental outcomes measured in the children. Data extracted included study author, design, sample size, country, gestational age, child age at testing, cognitive tests, urinary iodine assessment (UIC in μg/L and/or ICr in μg/g), dietary iodine intake assessment and results of associations for the assessed cognitive outcomes. Results Twelve studies were included with nine reporting women as mild-moderately iodine deficient based on World Health Organization (WHO) cut-offs for urinary iodine measurements < 150 μg/l, as the median UIC value in pregnant women. Only four of the nine studies reported a negative association with child cognitive outcomes based on deficient urinary iodine measurements. Five studies reported urinary iodine measurements and dietary intakes with four of these studies reporting a negative association of lower urinary iodine measurements and dietary iodine intakes with adverse offspring neurodevelopment. Milk was identified as the main dietary source of iodine in these studies. Conclusion The majority of studies classified pregnant women to be mild-moderately iodine deficient based on urinary iodine assessment (UIC and/or ICr) and/or dietary intakes, with subsequent offspring neurodevelopment implications identified. Although a considerable number of studies did not report an adverse association with neurodevelopmental outcomes, these findings are still supportive of ensuring adequate dietary iodine intakes and urinary iodine monitoring throughout pregnancy due to the important role iodine plays within foetal neurodevelopment. This review suggests that dietary intake data may indicate a stronger association with cognitive outcomes than urinary iodine measurements alone. The strength of this review distinguishes results based on cognitive outcome per urinary iodine assessment strategy (UIC and/or ICr) with dietary data. Future work is needed respecting the usefulness of urinary iodine assessment (UIC and/or ICr) as an indicator of deficiency whilst also taking account of dietary intakes

Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor

A novel high-throughput label-free resonant waveguide grating (RWG) imager biosensor, the Epic® BenchTop (BT), was utilized to determine the dependence of cell spreading kinetics on the average surface density (vRGD) of integrin ligand RGD-motifs. vRGD was tuned over four orders of magnitude by co-adsorbing the biologically inactive PLL-g-PEG and the RGD-functionalized PLL-g-PEG-RGD synthetic copolymers from their mixed solutions onto the sensor surface. Using highly adherent human cervical tumor (HeLa) cells as a model system, cell adhesion kinetic data of unprecedented quality were obtained. Spreading kinetics were fitted with the logistic equation to obtain the spreading rate constant (r) and the maximum biosensor response (Δλmax), which is assumed to be directly proportional to the maximum spread contact area (Amax). r was found to be independent of the surface density of integrin ligands. In contrast, Δλmax increased with increasing RGD surface density until saturation at high densities. Interpreting the latter behavior with a simple kinetic mass action model, a 2D dissociation constant of 1753 ± 243 μm−2 (corresponding to a 3D dissociation constant of ~30 μM) was obtained for the binding between RGD-specific integrins embedded in the cell membrane and PLL-g-PEG-RGD. All of these results were obtained completely noninvasively without using any labels

Sonic Hedgehog Is a Chemoattractant for Midbrain Dopaminergic Axons

Midbrain dopaminergic axons project from the substantia nigra (SN) and the ventral tegmental area (VTA) to rostral target tissues, including the striatum, pallidum, and hypothalamus. The axons from the medially located VTA project primarily to more medial target tissues in the forebrain, whereas the more lateral SN axons project to lateral targets including the dorsolateral striatum. This structural diversity underlies the distinct functions of these pathways. Although a number of guidance cues have been implicated in the formation of the distinct axonal projections of the SN and VTA, the molecular basis of their diversity remains unclear. Here we investigate the molecular basis of structural diversity in mDN axonal projections. We find that Sonic Hedgehog (Shh) is expressed at a choice point in the course of the rostral dopaminergic projections. Furthermore, in midbrain explants, dopaminergic projections are attracted to a Shh source. Finally, in mice in which Shh signaling is inactivated during late neuronal development, the most medial dopaminergic projections are deficient

A train-the-trainer education and promotion program: chronic fatigue syndrome – a diagnostic and management challenge

<p>Abstract</p> <p>Background</p> <p>Chronic fatigue syndrome (CFS) is a complicated illness for providers and patients. Fewer than 20% of persons with CFS have been diagnosed and treated. For providers, compounding the issue are the challenges in making a diagnosis due to the lack of a biomedical marker.</p> <p>Methods</p> <p>The objective of the CFS diagnosis and management curriculum was to instruct core trainers as to the evaluation, diagnosis, and management of CFS. Over a two year period, 79 primary care physicians, physician assistants, and nurse practitioners from diverse regions in the U.S. participated as core trainers in a two day Train-the-Trainer (TTT) workshop. As core trainers, the workshop participants were expected to show increases in knowledge, self-efficacy, and management skills with the primary goal of conducting secondary presentations.</p> <p>Results</p> <p>The optimal goal for each core trainer to present secondary training to 50 persons in the health care field was not reached. However, the combined core trainer group successfully reached 2064 primary care providers. Eighty-two percent of core trainers responded "Very good" or "Excellent" in a post-tessurvey of self-efficacy expectation and CFS diagnosis. Data from the Chicago workshops showed significant improvement on the Primary Care Opinion Survey (p < 0.01) and on the Relevance and Responsibility Factors of the CAT survey (p = 0.03 and p = 0.04, respectively). Dallas workshop data show a significant change from pre- to post-test scores on the CFS Knowledge test (p = 0.001). Qualitative and process evaluation data revealed that target audience and administrative barriers impacted secondary training feasibility.</p> <p>Conclusion</p> <p>Data show the workshop was successful in meeting the objectives of increasing CFS knowledge and raising perceived self-efficacy towards making a diagnosis. The CFS TTT program informed an educational provider project by shifting the format for physicians to grand rounds and continuing medical education design while retaining TTT aspects for nurse practitioners and physicians assistants. Evaluations also indicate that secondary trainings may be more readily employed and accepted if administrative barriers are addressed early in the planning phases.</p

Alterations in integrin expression modulates invasion of pancreatic cancer cells

Background Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. Methods In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. Results Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin β1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. Conclusion Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma

A function blocking anti-mouse integrin α5β1 antibody inhibits angiogenesis and impedes tumor growth in vivo

<p>Abstract</p> <p>Background</p> <p>Integrins are important adhesion molecules that regulate tumor and endothelial cell survival, proliferation and migration. The integrin α5β1 has been shown to play a critical role during angiogenesis. An inhibitor of this integrin, volociximab (M200), inhibits endothelial cell growth and movement <it>in vitro</it>, independent of the growth factor milieu, and inhibits tumor growth <it>in vivo </it>in the rabbit VX2 carcinoma model. Although volociximab has already been tested in open label, pilot phase II clinical trials in melanoma, pancreatic and renal cell cancer, evaluation of the mechanism of action of volociximab has been limited because this antibody does not cross-react with murine α5β1, precluding its use in standard mouse xenograft models.</p> <p>Methods</p> <p>We generated a panel of rat-anti-mouse α5β1 antibodies, with the intent of identifying an antibody that recapitulated the properties of volociximab. Hybridoma clones were screened for analogous function to volociximab, including specificity for α5β1 heterodimer and blocking of integrin binding to fibronectin. A subset of antibodies that met these criteria were further characterized for their capacities to bind to mouse endothelial cells, inhibit cell migration and block angiogenesis <it>in vitro</it>. One antibody that encompassed all of these attributes, 339.1, was selected from this panel and tested in xenograft models.</p> <p>Results</p> <p>A panel of antibodies was characterized for specificity and potency. The affinity of antibody 339.1 for mouse integrin α5β1 was determined to be 0.59 nM, as measured by BIAcore. This antibody does not significantly cross-react with human integrin, however 339.1 inhibits murine endothelial cell migration and tube formation and elicits cell death in these cells (EC₅₀= 5.3 nM). In multiple xenograft models, 339.1 inhibited the growth of established tumors by 40–60% (<it>p </it>< 0.05) and this inhibition correlates with a concomitant decrease in vessel density.</p> <p>Conclusion</p> <p>The results herein demonstrate that 339.1, like volociximab, exhibits potent anti-α5β1 activity and confirms that inhibition of integrin α5β1 impedes angiogenesis and slows tumor growth <it>in vivo</it>.</p

Therapeutic emails

BACKGROUND: In this paper, we show how counselors and psychologists can use emails for online management of substance abusers, including the anatomy and content of emails that clinicians should send substance abusers. Some investigators have attempted to determine if providing mental health services online is an efficacious delivery of treatment. The question of efficacy is an empirical issue that cannot be settled unless we are explicitly clear about the content and nature of online treatment. We believe that it is not the communications via internet that matters, but the content of these communications. The purpose of this paper is to provide the content of our online counseling services so others can duplicate the work and investigate its efficacy. RESULTS: We have managed nearly 300 clients online for recovery from substance abuse. Treatment included individual counseling (motivational interviewing, cognitive-behavior therapy, relapse prevention assignments), participation in an electronic support group and the development of a recovery team. Our findings of success with these interventions are reported elsewhere. Our experience has led to development of a protocol of care that is described more fully in this paper. This protocol is based on stages of change and relapse prevention theories and follows a Motivational Interviewing method of counseling. CONCLUSION: The use of electronic media in providing mental health treatment remains controversial due to concerns about confidentiality, security and legal considerations. More research is needed to validate and generalize the use of online treatment for mental health problems. If researchers have to build on each others work, it is paramount that we share our protocols of care, as we have done in this paper