Panel Discussion: The State of Play for Parental Choice

Transcript of panel The State of Play for Parental Choice, presented at 2013 CHEC Conference, Notre Dame, IN

Introduction to the Focus Section: 2013 Catholic Higher Education Collaborative (CHEC) Conference on Catholic School Financing

Introduction to the Focus Section

A Better Touch: C-tactile Fibers Related Activity is Associated to Pain Reduction During Temporal Summation of Second Pain

C-tactile (CT) fibers, responsible for the so-called “affective” touch (AT), have drawn a fair amount of attention within the scientific community for their marked social dimension. However, while the pain-relieving potential of discriminative touch (DT) has been documented, proofs of the analgesic properties of AT are still scarce. Additionally, no study has so far tested its possible pain-relieving effect on a clinically-relevant model. Temporal summation of second pain (TSSP), otherwise referred to as “wind-up,” relies on repetitive stimulation of C-nociceptors and it is thought to reflect central sensitization, a process linked to many chronic pain conditions. In the present experimental, within participants, design we induced TSSP through trains of ascending and descending repetitive heat stimulation. Forty-two healthy participants’ pain was measured during 2 different tactile stimulations (stroking velocities AT: 10 cm/s; DT: 0.3 cm/s) or without concomitant tactile input. Since measures of pleasantness of the tactile stimulation have been found to strongly correlate with C-tactile fibers’ firing rate, these, together with participants’ body awareness, were also taken into account. Our results show that AT brought about a decrease of our participants’ pain as opposed to both DT and no touch, while DT did not produce any significant pain reduction. Thus, only AT successfully modulated wind-up. As expected, AT was perceived as more pleasant than DT, while a clear relationship between body awareness and pain was found only during DT. Targeting CT fibers could pave the way to new treatments for chronic pain conditions whose aetiology depend on abnormal C-nociceptors’ physiology. Perspective: This study extends previous findings on the analgesic potential of affective touch, documenting a clear pain reduction during temporal summation of second pain (TSSP). Since TSSP is thought to reflect central sensitization, the psychophysiological mechanisms of affective touch could be exploited for new chronic pain treatments

Estudo da história da radioatividade e sua inserção nos livros didáticos do ensino médio

Neste trabalho analisamos a descoberta da radioatividade, partindo da história relata em livros e artigos, considerando os fatos que foram atribuídos a esta descoberta. A descoberta da radioatividade apresenta muitas versões alternativas em diversos livros didáticos, como se trata de um tema trabalhado em Física Moderna, é uma história que inúmeras vezes pode confundir os alunos, pelo fato dessa descoberta ser pouco trabalhada pelos professores ou mesmo não ser trabalhada. A análise geral dos livros nos mostra que em sua maioria estes exemplares não descrevem como a radioatividade foi descoberta e a evolução deste conceito. Os livros que falam sobre a sua descoberta apontam um cientista como o “descobridor” da radioatividade, o que tentamos evitar, já que muitos cientistas estudavam materiais radioativos e também podem ter sido os “descobridores” desse conceito. Também temos os livros que descrevem apenas a importância dos raios x, mencionando seus benefícios e malefícios para a sociedade, sem citar a radioatividade. Então, o que pretendemos com o trabalho é mostrar como ocorreu a descoberta da radioatividade e como esta descoberta é descrita nos livros didáticos. Bem como analisar os livros que descrevem o descobrimento de uma forma errônea

Novel method for assessing age-related differences in the temporal summation of pain

Temporal summation (TS) of pain protocols typically involve the delivery of brief repetitive noxious stimuli held at a constant intensity and measuring the consequent increase in the perceived intensity of pain sensations. To date, no studies have examined the effect of a TS protocol on the perceived spatial dimensions of the pain experience and its interaction with age. This study used a new TS protocol that examined changes in the perceived size of the painful area in 22 younger adults and 20 older adults. Four trials of ten brief heat pulses delivered at a constant intensity were administered on the volar forearm. Interpulse intervals (IPIs) were 2.5 seconds or 3.5 seconds. Subjects rated the peak pain intensity (trials 1 and 3) or the size of the painful area (trials 2 and 4) after each pulse on a 0-100 scale. The magnitude of summation was calculated for each trial. Three seconds and 6 seconds after delivering the last heat pulse, the subjects rated the intensity or the size of any remaining pain (aftersensations). The results indicated that older adults compared to younger adults exhibited significantly greater summation of size ratings for the 2.5-second and 3.5-second IPI trials and size of pain aftersensations at 3 seconds following the 2.5-second IPI TS trial. These results suggest that aging is associated with enhanced endogenous facilitation of the perceived size of pain. The potential clinical and mechanistic implications of enhanced TS of size of pain remain unknown and warrant further investigation

An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker

Chronic widespread musculoskeletal pain (CWP) is common, having a population prevalence of 10%. This study aimed to define the biological basis of the CWP/body mass association by using a systems biology approach. Adult female twins (n=2,444) from the TwinsUK registry who had extensive clinical, anthropometric, and "omic" data were included. Non-targeted metabolomics screening including 324 metabolites was carried out for CWP and body composition, assessed by DXA. The biological basis of these associations were explored through GWAS and replicated in an independent population sample (KORA study, n=2,483). A causal role for the genetic variants identified was sought in CWP using a Mendelian randomisation study design. Fat mass/height was the body composition variable most strongly associated with CWP (TwinsUK p=2.4x10 and KORA p=1.59x10). Of 324 metabolites examined, epiandrosterone sulphate (EAS) was highly associated with both CWP (p=1.05 x 10 in TwinsUK and p=3.70x10 in KORA) and fat mass/height. GWAS of EAS identified imputed SNP rs1581492 at 7q22.1 to be strikingly associated with EAS levels (p ≤2.49 x10) and this result was replicated in KORA (p=2.12x10). Mendelian randomization by rs1581492 genotype showed that EAS is unlikely to be causally related to CWP. Using an agnostic omics approach to focus on the association of CWP with BMI, we have confirmed a steroid hormone association and identified a genetic variant upstream of the CYP genes which likely controls this response. This study suggests that steroid hormone abnormalities result from pain rather than causing it, and EAS may provide a biomarker which identifies subgroups at risk of CWP

Increased spatial dimensions of repetitive heat and cold stimuli in older women

Protocols of temporal summation (TS) of pain typically involve the delivery of brief repetitive noxious pulses of a constant intensity while measuring the perceived intensity of pain after each pulse. The size percept of noxious repetitive stimulation has been poorly characterized. Furthermore, no studies have investigated age differences in TS of cold pain. The current study examined TS of pain intensity and the perceived size of the painful area during repetitive noxious heat and cold pulses in healthy younger (n = 104) and older adults (n = 40). Trials of 10 brief repetitive noxious heat or cold pulses were delivered to the upper extremities. Participants rated the perceived size of the painful area or intensity of pain after each pulse. The magnitude of change for the size percept and intensity for pain were calculated for each trial. The results indicated that older adults experienced greater TS of the size percept of cold stimuli compared with younger adults. Additionally, older women experienced greater TS of the size percept of heat stimuli compared with older men and all younger participants. No overall age or sex differences were found in the TS of pain intensity for cold or heat trials. These results suggest dysfunctional modulation of the spatial percept of the painful stimuli by older adults, and in particular older women, during repetitive noxious thermal pulses

Trophoblast Differentiation Affects Crucial Nutritive Functions of Placental Membrane Transporters.

Cytotrophoblasts are progenitor cells that proliferate and fuse to form the multinucleated syncytiotrophoblast layer, implicated in placental endocrine and transport functions. While membrane transporters play a critical role in the distribution of nutrients, hormones, and xenobiotics at the maternal-fetal interface, their selectivity to the syncytiotrophoblast layer is poorly characterized. We aimed to evaluate the regulation of placental transporters in response to trophoblast differentiation in vitro. Experiments were carried out in isolated primary human trophoblast cells before and after syncytialization. Gene expression of six molecular markers and thirty membrane transporters was investigated by qPCR analysis. Subsequently, functional expression was evaluated for proteins involved in the transplacental transfer of essential nutrients i.e., cholesterol (ABCA1, ABCG1), glucose (SLC2A1), leucine (SLC3A2, SLC7A5), and iron (transferrin receptor, TfR1). We identified that human chorionic gonadotropin, placental lactogen, endoglin, and cadherin-11 serve as optimal gene markers for the syncytialization process. We showed that trophoblast differentiation was associated with differential gene expression (mostly up-regulation) of several nutrient and drug transporters. Further, we revealed enhanced protein expression and activity of ABCG1, SLC3A2, SLC7A5, and TfR1 in syncytialized cells, with ABCA1 and GLUT1 displaying no change. Taken together, these results indicate that the syncytiotrophoblast has a dominant role in transporting essential nutrients cholesterol, leucine, and iron. Nonetheless, we present evidence that the cytotrophoblast cells may also be linked to transport functions that could be critical for the cell fusion processes. Our findings collectively yield new insights into the cellular functions associated with or altered by the trophoblast fusion. Importantly, defective syncytialization could lead to nutrient transfer imbalance, ultimately compromising fetal development and programming

Functional reorganization of monoamine transport systems during villous trophoblast differentiation: evidence of distinct differences between primary human trophoblasts and BeWo cells.

BACKGROUND Three primary monoamines-serotonin, norepinephrine, and dopamine-play major roles in the placenta-fetal brain axis. Analogously to the brain, the placenta has transport mechanisms that actively take up these monoamines into trophoblast cells. These transporters are known to play important roles in the differentiated syncytiotrophoblast layer, but their status and activities in the undifferentiated, progenitor cytotrophoblast cells are not well understood. Thus, we have explored the cellular handling and regulation of monoamine transporters during the phenotypic transitioning of cytotrophoblasts along the villous pathway. METHODS Experiments were conducted with two cellular models of syncytium development: primary trophoblast cells isolated from the human term placenta (PHT), and the choriocarcinoma-derived BeWo cell line. The gene and protein expression of membrane transporters for serotonin (SERT), norepinephrine (NET), dopamine (DAT), and organic cation transporter 3 (OCT3) was determined by quantitative PCR and Western blot analysis, respectively. Subsequently, the effect of trophoblast differentiation on transporter activity was analyzed by monoamine uptake into cells. RESULTS We present multiple lines of evidence of changes in the transcriptional and functional regulation of monoamine transporters associated with trophoblast differentiation. These include enhancement of SERT and DAT gene and protein expression in BeWo cells. On the other hand, in PHT cells we report negative modulation of SERT, NET, and OCT3 protein expression. We show that OCT3 is the dominant monoamine transporter in PHT cells, and its main functional impact is on serotonin uptake, while passive transport strongly contributes to norepinephrine and dopamine uptake. Further, we show that a wide range of selective serotonin reuptake inhibitors affect serotonin cellular accumulation, at pharmacologically relevant drug concentrations, via their action on both OCT3 and SERT. Finally, we demonstrate that BeWo cells do not well reflect the molecular mechanisms and properties of healthy human trophoblast cells. CONCLUSIONS Collectively, our findings provide insights into the regulation of monoamine transport during trophoblast differentiation and present important considerations regarding appropriate in vitro models for studying monoamine regulation in the placenta