Psychosocial treatments targeting the positive valence system (PVS) in depression and anxiety demonstrate efficacy in enhancing positive affect (PA), but response to treatment varies. We examined ...whether individual differences in neural activation to positive and negative valence incentive cues underlies differences in benefitting from a PVS-targeted treatment. Individuals with clinically elevated depression and/or anxiety (N = 88, ages 18 to 55) participated in one of two randomized, waitlist-controlled trials of Amplification of Positivity (AMP; NCT02330627, NCT03196544), a cognitive and behavioral intervention targeting the PVS. Participants completed a monetary incentive delay (MID) task during fMRI acquisition at baseline measuring neural activation to the possibility of gaining or losing money. Change in PA from before to after treatment was assessed using the Positive and Negative Affect Schedule. No significant associations were observed between baseline neural activation during gain anticipation and AMP-related changes in PA in regions of interest (striatum and insula) or whole-brain analyses. However, higher baseline striatal and insula activation during loss anticipation was associated with greater increases in PA post-AMP. This study provides preliminary evidence suggesting neural reactivity to negative valence cues may inform who stands to benefit most from treatments targeting the PVS.
•Depression and anxiety disorders evince positive valence system (PVS) dysfunction.•Amplification of Positivity (AMP) is an emerging intervention targeting the PVS.•We examined neural predictors of change in positive affect after AMP.•Neural activation during gain anticipation did not predict outcomes.•Higher activation during loss anticipation predicted greater AMP treatment gains.
Positive valence system (PVS) deficits are increasingly recognized as important treatment targets for depression and anxiety. Emerging behavioral treatments designed to upregulate the PVS show ...initial promise; however, neural mechanisms underlying these approaches remain unknown. This study investigated neural reward-processing-related changes following Amplification of Positivity (AMP)—a treatment designed to enhance positive thinking, emotions and behaviors through positive activity interventions (Clinicaltrials.gov: NCT02330627).
Individuals with depression and/or anxiety (N = 29) were randomized to 10 sessions of AMP (n = 16) or waitlist (WL; n = 13). Participants completed a monetary incentive delay task during fMRI at baseline and post-assessment. Hypothesis-driven region of interest (ventral striatum, insula, anterior cingulate) and exploratory whole-brain activation and connectivity analyses evaluated pre-to-post changes for AMP vs. WL when anticipating potential monetary gain or loss.
No between-group brain activation changes emerged in regions of interest or whole-brain analyses. Increased neural connectivity from pre-to-post-treatment was observed in AMP vs. WL, including ventral striatum, anterior insula, and anterior cingulate connectivity with prefrontal, limbic, occipital and parietal regions—predominantly during loss anticipation.
This preliminary study is the first to examine neural mechanisms of positive activity interventions in depression and anxiety and suggests that AMP may strengthen brain connectivity in reward processing, attention, and emotion regulation networks.
Abstract
The apelin receptor (APJ), a receptor for apelin and elabela/apela, induces vasodilation and vasoconstriction in blood vessels. However, the prolonged effects of increased APJ-mediated ...signalling, involving vasoconstriction, in smooth muscle cells have not been fully characterized. Here, we investigated the vasoactive effects of APJ gain of function under the control of the smooth muscle actin (SMA) gene promoter in mice. Transgenic overexpression of APJ (SMA-APJ) conferred sensitivity to blood pressure and vascular contraction induced by apelin administration in vivo. Interestingly, ex vivo experiments showed that apelin markedly increased the vasoconstriction of isolated aorta induced by noradrenaline (NA), an agonist for α- and β-adrenergic receptors, or phenylephrine, a specific agonist for α1-adrenergic receptor (α1-AR). In addition, intracellular calcium influx was augmented by apelin with NA in HEK293T cells expressing APJ and α1A-AR. To examine the cooperative action of APJ and α1A-AR in the regulation of vasoconstriction, we developed α1A-AR deficient mice using a genome-editing technique, and then established SMA-APJ/α1A-AR-KO mice. In the latter mouse line, aortic vasoconstriction induced by a specific agonist for α1A-AR, A-61603, were significantly less than in SMA-APJ mice. These results suggest that the APJ-enhanced response requires α1A-AR to contract vessels coordinately.
Elemental concentrations in vegetation are of critical importance, whether establishing plant essential element concentrations (toxicity vs. deficiency) or investigating deleterious elements (e.g., ...heavy metals) differentially extracted from the soil by plants. Traditionally, elemental analysis of vegetation has been facilitated by acid digestion followed by quantification via inductively coupled plasma (ICP) or atomic absorption (AA) spectroscopy. Previous studies have utilized portable X-ray fluorescence (PXRF) spectroscopy to quantify elements in soils, but few have evaluated the vegetation. In this study, a PXRF spectrometer was employed to scan 228 organic material samples (thatch, deciduous leaves, grasses, tree bark, and herbaceous plants) from smelter-impacted areas of Romania, as well as National Institute of Standards and Technology (NIST) certified reference materials, to demonstrate the application of PXRF for elemental determination in vegetation. Samples were scanned in three conditions: as received from the field (moist), oven dry (70 °C), and dried and powdered to pass a 2 mm sieve. Performance metrics of PXRF models relative to ICP atomic emission spectroscopy were developed to asses optimal scanning conditions. Thatch and bark samples showed the highest mean PXRF and ICP concentrations (e.g., Zn, Pb, Cd, Fe), with the exceptions of K and Cl. Validation statistics indicate that the stable validation predictive capacity of PXRF increased in the following order: oven dry intact < field moist < oven dried and powdered. Even under field moist conditions, PXRF could reasonably be used for the determination of Zn (coefficient of determination, R2val 0.86; residual prediction deviation, RPD 2.72) and Cu (R2val 0.77; RPD 2.12), while dried and powdered samples allowed for stable validation prediction of Pb (R2val 0.90; RPD 3.29), Fe (R2val 0.80; RPD 2.29), Cd (R2val 0.75; RPD 2.07) and Cu (R2val 0.98; RPD of 8.53). Summarily, PXRF was shown to be a useful approach for quickly assessing the elemental concentration in vegetation. Future PXRF/vegetation research should explore additional elements and investigate its usefulness in evaluating phytoremediation effectiveness.
•PXRF was used to scan different vegetation types at variable moisture.•PXRF accurately quantified Pb, Fe, Cd, and Cu for dry, powder samples.•PXRF reasonably determined Zn and Cu for field moist samples.
Inflammation has been associated with preterm delivery and adverse neonatal outcomes such as cerebral palsy and chronic lung disease. However, no study to date has simultaneously examined a wide ...range of inflammatory mediators and their relationship to gestational age. We sought to describe the distribution of immune biomarkers in cord blood across gestational age and to investigate the association between biomarker level patterns and preterm birth.
As part of a large-scale molecular epidemiological study of preterm birth conducted at Boston Medical Center, this study analyzed both clinical and biomarker data from 927 births. Twenty-seven biomarkers were simultaneously quantified by immunoassay. The associations between the quartiles of 27 biomarkers and 3 gestational groups (< or =32, 33-36, and > or =37 weeks) were analyzed. Biomarkers found to be significant were further analyzed for dose-response correlation with preterm birth by logistic regression, adjusted for pertinent demographic and clinical factors.
The 27 biomarkers could be classified into 1 of 3 groups: (1) biomarkers increased in preterm birth (interleukin IL-2, IL-4, IL-5, IL-8, IL-10, monocyte chemoattractant protein 1, macrophage inflammatory protein MIP-1alpha, MIP-1beta, soluble IL-6 receptor alpha, tumor necrosis factor alpha, soluble tumor necrosis factor receptor I, and TREM-1 triggering receptor expressed on myeloid cells 1); (2) biomarkers decreased in preterm birth (brain-derived neurotrophic factor, IL-1beta, IL-18, matrix metalloproteinase 9, and neurotrophin 3); and (3) biomarkers not associated with preterm birth (IL-6, IL-12, IL-17, granulocyte/macrophage colony-stimulating factor, interferon gamma, macrophage migration inhibitory factor, neurotrophin 4, RANTES regulated on activation, normal T-cell expressed and secreted, transforming growth factor beta, and tumor necrosis factor beta).
Biomarkers have different directions of association with prematurity; for significant biomarkers, the strength of association increases with biomarker concentration. Our results provide important information that could be used to guide additional studies aimed at determining mechanisms that contribute to preterm birth.
•PXRF elemental water data aligned well with ICP data.•Fe, Mn, Zn, and K showed strongest ICP-PXRF relationship.•PXRF quantifies wide elemental concentrations in solution.•Development of a ...low-density PXRF water mode is recommended.
A rapid method for in-situ elemental composition analysis of metal-laden water would be indispensable for studying polluted water. Current analytical lab methods to determine water quality include flame atomic absorption spectrometry (FAAS), atomic absorption spectrophotometry (AAS), electrothermal atomic absorption spectrometry (EAAS), and inductively coupled plasma (ICP) spectroscopy. However only two field methods, colorimetry and absorptiometry, exist for elemental analysis of water. Portable X-ray fluorescence (PXRF) spectrometry is an effective method for elemental analysis of soil, sediment, and other matrices. However, the accuracy of PXRF is known to be affected while scanning moisture-laden soil samples. This study sought to statistically establish PXRF’s predictive ability for various elements in water at different concentrations relative to inductively coupled plasma atomic emission spectroscopy (ICP-AES). A total of 390 metal-laden water samples collected from leaching columns of mine tailings in South Africa were analyzed via PXRF and ICP-AES. The PXRF showed differential effectiveness in elemental quantification. For the collected water samples, the best relationships between ICP and PXRF elemental data were obtained for K and Cu (R2 = 0.92). However, when scanning ICP calibration solutions with elements in isolation, PXRF results indicated near perfect agreement; Ca, K, Fe, Cu and Pb produced an R2 of 0.99 while Zn and Mn produced an R2 of 1.00. The utilization of multiple PXRF (stacked) beams produced stronger correlation to ICP relative to the use of a single beam in isolation. The results of this study demonstrated the PXRF's ability to satisfactorily predict the composition of metal-laden water as reported by ICP for several elements. Additionally this study indicated the need for a “Water Mode” calibration for the PXRF and demonstrates the potential of PXRF for future study of polluted or contaminated waters.
We sought to determine whether placental markers of intrauterine inflammation were associated with poor weight gain among premature infants in the neonatal period.
We reviewed 697 preterm births ...prospectively enrolled as part of an ongoing molecular epidemiological study. Placental markers and serial weight gain were analyzed for premature infants who were hospitalized for >/=21 days (N = 256). Placentas were examined for maternal inflammatory response (MIR), defined as subchorionitis, chorioamnionitis, deciduitis, or free membranitis, and fetal inflammatory response (FIR), defined as inflammation extending to the umbilical cord or chorionic plate. Multivariate linear regression and stratified analyses were performed.
Decreases in weight gain at day 21 were associated with the presence of either MIR or FIR (beta coefficient = -4.63 +/- 1.41; P = .001). The association was stronger with FIR than MIR (P for trend = .0027) and persisted in the remaining hospitalized infants at day 28 (n = 223; beta coefficient = -5.53 +/- 1.85; P = .0028). Mean body weights were similar among the 3 groups by corrected age of 36 weeks or discharge, whichever came first. Associations between placental inflammation and poor growth persisted among infants with prenatal corticosteroid exposure and/or neonatal complications and remained marginally significant in the nonexposed groups. Among infants without intrauterine growth restriction, significant association persisted (n = 186; beta coefficient = -5.68 +/- 1.56; P = .0003).
Placental inflammation is associated with poor neonatal growth. MIR and FIR may be useful markers for identifying infants at risk for postnatal growth failure.