Ca2+-dependent changes in cyclic GMP levels are not correlated with opening and closing of the light-dependent permeability of toad photoreceptors.

We have measured the levels of 3',5'-guanosine monophosphate (cyclic GMP) in isolated retinas from toad to investigate their correlation to the opening and closing of the light-dependent permeability of photoreceptors. When Ca2+-induced changes in cyclic GMP concentration are compared with the Ca2+-induced changes in the permeability of photoreceptor light-dependent channel, four quantitative dissimilarities are noted. First, when extracellular Ca2+ ([Ca2+]o) is reduced from normal physiological levels to between 10(-6) and 10(-7) M, the light-dependent permeability is increased, but cyclic GMP levels are not significantly changed. Second, when [Ca2+]o is increased from 1.8 to 20 mM, the light-dependent permeability is suppressed, but cyclic GMP levels are decreased by only 10-15%, about one-quarter the decrease that can be obtained with bright illumination. Third, when [Ca2+]o is increased from 10(-8) M to 20 mM, the light-dependent permeability is closed rapidly, but the cyclic GMP decrease is slow. Fourth, when [Ca2+]o is lowered to 10(-8) M, the sensitivity of the light-dependent permeability to steady illumination is decreased by three to four orders of magnitude, but the sensitivity of the light-dependent decrease in cyclic GMP is not significantly affected. These observations indicate that there is no simple correlation between cyclic GMP levels and the permeability of the light-dependent channels and that Ca2+ can affect the conductance in the absence of changes in cyclic GMP content

Cerebellar-dependent delay eyeblink conditioning in adolescents with Specific Language Impairment

Cerebellar impairments have been hypothesized as part of the pathogenesis of Specific Language Impairment (SLI), although direct evidence of cerebellar involvement is sparse. Eyeblink Conditioning (EBC) is a learning task with well documented cerebellar pathways. This is the first study of EBC in affected adolescents and controls. 16 adolescent controls, 15 adolescents with SLI, and 12 adult controls participated in a delay EBC task. Affected children had low general language performance, grammatical deficits but no speech impairments. The affected group did not differ from the control adolescent or control adult group, showing intact cerebellar functioning on the EBC task. This study did not support cerebellar impairment at the level of basic learning pathways as part of the pathogenesis of SLI. Outcomes do not rule out cerebellar influences on speech impairment, or possible other forms of cerebellar functioning as contributing to SLI

Behavioral determinants as predictors of return to work after long-term sickness absence: an application of the theory of planned behavior

Background The aim of this prospective, longitudinal cohort study was to analyze the association between the three behavioral determinants of the theory of planned behavior (TPB) model-attitude, subjective norm and self-efficacy-and the time to return-to-work (RTW) in employees on long-term sick leave. Methods The study was based on a sample of 926 employees on sickness absence (maximum duration of 12 weeks). The employees filled out a baseline questionnaire and were subsequently followed until the tenth month after listing sick. The TPB-determinants were measured at baseline. Work attitude was measured with a Dutch language version of the Work Involvement Scale. Subjective norm was measured with a self-structured scale reflecting a person's perception of social support and social pressure. Self-efficacy was measured with the three subscales of a standardised Dutch version of the general self-efficacy scale (ALCOS): willingness to expend effort in completing the behavior, persistence in the face of adversity, and willingness to initiate behavior. Cox proportional hazards regression analyses were used to identify behavioral determinants of the time to RTW. Results Median time to RTW was 160 days. In the univariate analysis, all potential prognostic factors were significantly associated (P < 0.15) with time to RTW: work attitude, social support, and the three subscales of self-efficacy. The final multivariate model with time to RTW as the predicted outcome included work attitude, social support and willingness to expend effort in completing the behavior as significant predictive factors. Conclusions This prospective, longitudinal cohort-study showed that work attitude, social support and willingness to expend effort in completing the behavior are significantly associated with a shorter time to RTW in employees on long-term sickness absence. This provides suggestive evidence for the relevance of behavioral characteristics in the prediction of duration of sickness absence. It may be a promising approach to address the behavioral determinants in the development of interventions focusing on RTW in employees on long-term sick leave

The effects of socioeconomic status and indices of physical environment on reduced birth weight and preterm births in Eastern Massachusetts

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors.Methods: A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes ( birth weight, small for gestational age and preterm births), in a two-level hierarchical model.Results: We found effects of both individual ( education, race, prenatal care index) and area-based ( median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outcomes and a strong confounder for both area-based SEM and indices of physical environment. The effects of traffic and land use differed by level of education and median household income.Conclusion: Overall, the findings of the study suggested greater likelihood of reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health.This work is supported by the Harvard Environmental Protection Agency (EPA) Center, Grants R827353 and R-832416, and National Institute for Environmental Health Science (NIEHS) ES-0002

The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex.

The inner centromere is a region on every mitotic chromosome that enables specific biochemical reactions that underlie properties, such as the maintenance of cohesion, the regulation of kinetochores and the assembly of specialized chromatin, that can resist microtubule pulling forces. The chromosomal passenger complex (CPC) is abundantly localized to the inner centromeres and it is unclear whether it is involved in non-kinase activities that contribute to the generation of these unique chromatin properties. We find that the borealin subunit of the CPC drives phase separation of the CPC in vitro at concentrations that are below those found on the inner centromere. We also provide strong evidence that the CPC exists in a phase-separated state at the inner centromere. CPC phase separation is required for its inner-centromere localization and function during mitosis. We suggest that the CPC combines phase separation, kinase and histone code-reading activities to enable the formation of a chromatin body with unique biochemical activities at the inner centromere

Between-airport heterogeneity in air toxics emissions associated with individual cancer risk thresholds and population risks

Abstract Background Airports represent a complex source type of increasing importance contributing to air toxics risks. Comprehensive atmospheric dispersion models are beyond the scope of many applications, so it would be valuable to rapidly but accurately characterize the risk-relevant exposure implications of emissions at an airport. Methods In this study, we apply a high resolution atmospheric dispersion model (AERMOD) to 32 airports across the United States, focusing on benzene, 1,3-butadiene, and benzo [a]pyrene. We estimate the emission rates required at these airports to exceed a 10-6 lifetime cancer risk for the maximally exposed individual (emission thresholds) and estimate the total population risk at these emission rates. Results The emission thresholds vary by two orders of magnitude across airports, with variability predicted by proximity of populations to the airport and mixing height (R2 = 0.74–0.75 across pollutants). At these emission thresholds, the population risk within 50 km of the airport varies by two orders of magnitude across airports, driven by substantial heterogeneity in total population exposure per unit emissions that is related to population density and uncorrelated with emission thresholds. Conclusion Our findings indicate that site characteristics can be used to accurately predict maximum individual risk and total population risk at a given level of emissions, but that optimizing on one endpoint will be non-optimal for the other.</p

Term birth weight and ambient air pollutant concentrations during pregnancy, among women living in Monroe County, New York

Increased ambient air pollutant concentrations during pregnancy have been associated with reduced birth weight, but the etiologically relevant pregnancy time window(s) is/are unclear. In 76,500 singleton births in Monroe County, NY (2005–2016), who were 37–42 gestational weeks at delivery, we used generalized linear models to regress term birth weight against mean gestational month pollutant concentrations, adjusting for mean temperature, and maternal, infant, and medical service use characteristics. Overall, there were no clear patterns of term birth weight change associated with increased concentrations of any pollutant across gestational months. However, among Hispanic women only, increases in all pollutants, except O3, in multiple gestational months, were associated with decreased term birth weight. Each 3.25 µg/m3 increase in PM2.5 concentration in the 6th gestational month was associated with a −20.4 g (95% CI = −34.0, −6.8) reduction in term birth weight among Hispanic women, but a 4.1 g (95% CI = −2.5, 10.8) increase among non-Hispanic mothers (p for interaction &lt; 0.001). Although ambient air pollutant concentrations during pregnancy were not associated with reduced term birth weight among women of all ethnicities living in Monroe County, this observed association in Hispanic mothers may be a result of less exposure misclassification and bias (due to closer residential proximity to the monitoring site)

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

Giant sacral schwannoma: A report of six cases

Sacral and presacral schwannomas are often found incidentally, because they present with vague symptoms or symptomless. Schwannoma occurring in this area occasionally presents with enormous dimensions, known as a giant schwannoma. The tumor removal is a surgical challenge due to the difficult approach and abundant vascularity. The aim of this study is to review cases of giant sacral schwannomas focusing the surgical management and outcome. Six patients with sacral and presacral schwannoma were treated surgically. The patients included two males and four females, and the mean age was 47.8 years. All patients experienced pain at the time of presentation. The tumors were classified as intraosseous type in one case, dumb-bell type in four cases, and retroperitoneal type in one case. The tumors were removed with a piecemeal subtotal excision in three patients, a partial excision in two patients, and enucleation in one patient. The surgeries were performed by the combination of an anterior and posterior approach in three patients, a posterior approach in two patients, and an anterior approach in one patient. The mean surgical time was 7.8 hrs, and the mean blood loss was 2572 g. The tumor recurred in one patient after the partial excision and was removed completely in a second surgery. No patient, including the patient who underwent the second surgery, presented with pain and obvious neurological deficit at the final follow-up. The surgical treatment of the giant sacral schwannoma with a piecemeal subtotal excision can achieve a good outcome, avoiding unnecessary neurological deficit