Interaction of HPA axis genetics and early life stress shapes emotion recognition in healthy adults

Background: Early life stress (ELS) affects facial emotion recognition (FER), as well as the underlying brain network. However, there is considerable inter-individual variability in these ELS-caused alterations. As the hypothalamic-pituitary-adrenal (HPA) axis is assumed to mediate neural and behavioural sequelae of ELS, the genetic disposition towards HPA axis reactivity might explain differential vulnerabilities. Methods: An additive genetic profile score (GPS) of HPA axis reactivity was built from 6 SNPs in 3 HPA axisrelated genes (FKBP5, CRHR1, NR3C1). We studied two independent samples. As a proof of concept, GPS was tested as a predictor of cortisol increase to a psychosocial challenge (MIST) in a healthy community sample of n=40. For the main study, a sample of n=170 completed a video-based FER task and retrospectively reported ELS experiences in the Childhood Trauma Questionnaire (CTQ). Results: GPS positively predicted cortisol increase in the stress challenge over and above covariates. CTQ and genetic profile scores interacted to predict facial emotion recognition, such that ELS had a detrimental effect on emotion processing only in individuals with higher GPS. Post-hoc moderation analyses revealed that, while a less stress-responsive genetic profile was protective against ELS effects, individuals carrying a moderate to high GPS were affected by ELS in their ability to infer emotion from facial expressions. Discussion: These results suggest that a biologically informed genetic profile score can capture the genetic disposition to HPA axis reactivity and moderates the influence of early environmental factors on facial emotion recognition. Further research should investigate the neural mechanisms underlying this moderation. The GPS used here might prove a powerful tool for studying inter-individual differences in vulnerability to early life stress

Impact of socioeconomic differences on distributional cost-effectiveness analysis

Public health decision makers value interventions for their effects on overall health and health inequality. Distributional cost-effectiveness analysis (DCEA) incorporates health inequality concerns into economic evaluation by accounting for how parameters, such as effectiveness, differ across population groups. A good understanding of how and when accounting for socioeconomic differences between groups affects the assessment of intervention impacts on overall health and health inequality could inform decision makers where DCEA would add most value. We interrogated 2 DCEA models of smoking and alcohol policies using first national level and then local authority level information on various socioeconomic differences in health and intervention use. Through a series of scenario analyses, we explored the impact of altering these differences on the DCEA results. When all available evidence on socioeconomic differences was incorporated, provision of a smoking cessation service was estimated to increase overall health and increase health inequality, while the screening and brief intervention for alcohol misuse was estimated to increase overall health and reduce inequality. Ignoring all or some socioeconomic differences resulted in minimal change to the estimated impact on overall health in both models; however, there were larger effects on the estimated impact on health inequality. Across the models, there were no clear patterns in how the extent and direction of socioeconomic differences in the inputs translated into the estimated impact on health inequality. Modifying use or coverage of either intervention so that each population group matched the highest level improved the impacts to a greater degree than modifying intervention effectiveness. When local level socioeconomic differences were considered, the magnitude of the impacts was altered; in some cases, the direction of impact on inequality was also altered

VASCULAR LYMPHATIC MALFORMATION WITH UNCOMMON LOCALIZATION

Introdução: As malformações vasculares linfáticas são entidades raras que afetam os vasos linfáticos. Os autores relatam um caso clínico de uma malformação linfática abdomino-pélvica. Caso Clínico: 28 anos, Gesta 2, Para 1. Encaminhada à Unidade de Diagnóstico Pré-Natal, às 20 semanas, por imagem ecográfica sugestiva de malformação linfática abdomino-pélvica, confirmada por ressonância magnética fetal. Estudo citogenético fetal normal. Consulta de Cirurgia Pediátrica para informar o casal do prognóstico. Cesariana eletiva às 38 semanas. Observação do recém-nascido confirmou o diagnóstico pré-natal. A criança foi submetida, aos 18 meses, a esclerote¬rapia intralesional. Aos 4 anos, foi efetuada exérese cirúrgica da lesão por desenvolvimento de sintomas. Apresentou sempre desenvolvimento e crescimento normais. Discussão/Conclusões: O diagnóstico pré-natal é ecográfico; a ressonância magnética fetal permite confirmar o diagnóstico e define com maior rigor a extensão das lesões. Deve manter-se vigilância clínica e ecográfica, para deteção de sinais de descompensação ou hidrópsia e de compressão das estruturas adjacentes

Systematic expression analysis of plasticity-related genes in mouse brain development brings PRG4 into play

Background: Plasticity-related genes (Prgs/PRGs) or lipid phosphate phosphatase-related proteins (LPPRs) comprise five known members, which have been linked to neuronal differentiation processes, such as neurite outgrowth, axonal branching, or dendritic spine formation. PRGs are highly brain-specific and belong to the lipid phosphate phosphatases (LPPs) superfamily, which influence lipid metabolism by dephosphorylation of bioactive lipids. PRGs, however, do not possess enzymatic activity, but modify lipid metabolism in a way that is still under investigation. Results: We analyzed mRNA expression levels of all Prgs during mouse brain development, in the hippocampus, neocortex, olfactory bulbs, and cerebellum. We found different spatio-temporal expression patterns for each of the Prgs, and identified a high expression of the uncharacterized Prg4 throughout brain development. Unlike its close family members PRG3 and PRG5, PRG4 did not induce filopodial outgrowth in non-neuronal cell lines, and does not localize to the plasma membrane of filopodia. Conclusion: We showed PRG4 to be highly expressed in the developing and the adult brain, suggesting that it is of vital importance for normal brain function. Despite its similarities to other family members, it seems not to be involved in changes of cell morphology; instead, it is more likely to be associated with intracellular signaling

Dopamine and α-synuclein dysfunction in Smad3 null mice

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra (SN). Transforming growth factor-β1 (TGF-β1) levels increase in patients with PD, although the effects of this increment remain unclear. We have examined the mesostriatal system in adult mice deficient in Smad3, a molecule involved in the intracellular TGF-β1 signalling cascade.</p> <p>Results</p> <p>Striatal monoamine oxidase (MAO)-mediated dopamine (DA) catabolism to 3,4-dihydroxyphenylacetic acid (DOPAC) is strongly increased, promoting oxidative stress that is reflected by an increase in glutathione levels. Fewer astrocytes are detected in the ventral midbrain (VM) and striatal matrix, suggesting decreased trophic support to dopaminergic neurons. The SN of these mice has dopaminergic neuronal degeneration in its rostral portion, and the pro-survival Erk1/2 signalling is diminished in nigra dopaminergic neurons, not associated with alterations to p-JNK or p-p38. Furthermore, inclusions of α-synuclein are evident in selected brain areas, both in the perikaryon (SN and paralemniscal nucleus) or neurites (motor and cingulate cortices, striatum and spinal cord). Interestingly, these α-synuclein deposits are detected with ubiquitin and P^S129-α-synuclein in a core/halo cellular distribution, which resemble those observed in human Lewy bodies (LB).</p> <p>Conclusions</p> <p>Smad3 deficiency promotes strong catabolism of DA in the striatum (ST), decrease trophic and astrocytic support to dopaminergic neurons and may induce α-synuclein aggregation, which may be related to early parkinsonism. These data underline a role for Smad3 in α-synuclein and DA homeostasis, and suggest that modulatory molecules of this signalling pathway should be evaluated as possible neuroprotective agents.</p

Comparing smoking cessation to screening and brief intervention for alcohol in distributional cost effectiveness analysis to explore the sensitivity of results to socioeconomic inequalities characterised in model inputs.

A distribution of intervention impact across socioeconomic groups can be estimated from socioeconomic differences across a staircase from need (e.g. prevalence) up to intervention characteristics (e.g. effectiveness) using distributional cost effectiveness analysis (DCEA). The extent to which evidence on inequality at different steps of the staircase contributes to uncertainty in population level impact is not well understood. We used DCEAs in smoking cessation and alcohol interventions to explore how socioeconomic inequality in model inputs impacts upon final conclusions about health inequality and value for money

Removal of pharmaceutical compounds commonly-found in wastewater through a hybrid biological and adsorption process

[EN] Nowadays, alternative options to conventional wastewater treatment should be studied due to rising concerns emerged by the presence of pharmaceuticals compounds (PhCs) in the aquatic environment. In this work, a combined system including biological treatment by activated sludge plus adsorption with activated carbon is proposed to remove three selected drugs (acetaminophen (ACT), caffeine (CAF) and ibuprofen (IBU)) in a concentration of 2 mg L-1 of each one. For it three sequencing batch reactors (SBR) were operated. SBR-B treated a synthetic wastewater (SWW) without target drugs and SBR-PhC and SBR-PhC + AC operated with SWW doped with the three drugs, adding into SBR-PhC + AC 1.5 g L-1 of a mesoporous granular activated carbon. Results showed that the hybrid system SBR-activated carbon produced an effluent free of PhCs, which in addition had higher quality than that achieved in a conventional activated sludge treatment in terms of lower COD, turbidity and SMP concentrations. On the other hand, five possible routes of removal for target drugs during the biological treatment were studied. Hydrolysis, oxidation and volatilization pathways were negligible after 6 h of reaction time. Adsorption mute only was significant for ACT, which was adsorbed completely after 5 h of reaction, while only 1.9% of CAF and 5.6% of IBU were adsorbed. IBU was the least biodegradable compound.This work was supported by Spanish grants AICO/2018/292 of the Generalitat Valenciana.Ferrer-Polonio, E.; Fernández-Navarro, J.; Iborra-Clar, MI.; Alcaina-Miranda, MI.; Mendoza Roca, JA. (2020). Removal of pharmaceutical compounds commonly-found in wastewater through a hybrid biological and adsorption process. Journal of Environmental Management. 263:1-8. https://doi.org/10.1016/j.jenvman.2020.110368S18263Al-Khazrajy, O. S. A., & Boxall, A. B. A. (2016). Impacts of compound properties and sediment characteristics on the sorption behaviour of pharmaceuticals in aquatic systems. Journal of Hazardous Materials, 317, 198-209. doi:10.1016/j.jhazmat.2016.05.065Alygizakis, N. A., Gago-Ferrero, P., Borova, V. L., Pavlidou, A., Hatzianestis, I., & Thomaidis, N. S. (2016). Occurrence and spatial distribution of 158 pharmaceuticals, drugs of abuse and related metabolites in offshore seawater. Science of The Total Environment, 541, 1097-1105. doi:10.1016/j.scitotenv.2015.09.145Azimi, S. C., Shirini, F., & Pendashteh, A. (2019). Evaluation of COD and turbidity removal from woodchips wastewater using biologically sequenced batch reactor. Process Safety and Environmental Protection, 128, 211-227. doi:10.1016/j.psep.2019.05.043Boxall, A. B. A. (2004). The environmental side effects of medication. EMBO reports, 5(12), 1110-1116. doi:10.1038/sj.embor.7400307Carballa, M., Omil, F., & Lema, J. M. (2005). Removal of cosmetic ingredients and pharmaceuticals in sewage primary treatment. Water Research, 39(19), 4790-4796. doi:10.1016/j.watres.2005.09.018Couto, C. F., Lange, L. C., & Amaral, M. C. S. (2019). Occurrence, fate and removal of pharmaceutically active compounds (PhACs) in water and wastewater treatment plants—A review. Journal of Water Process Engineering, 32, 100927. doi:10.1016/j.jwpe.2019.100927Desbiolles, F., Malleret, L., Tiliacos, C., Wong-Wah-Chung, P., & Laffont-Schwob, I. (2018). Occurrence and ecotoxicological assessment of pharmaceuticals: Is there a risk for the Mediterranean aquatic environment? Science of The Total Environment, 639, 1334-1348. doi:10.1016/j.scitotenv.2018.04.351Dong, X., Zhou, W., & He, S. (2013). Removal of anaerobic soluble microbial products in a biological activated carbon reactor. Journal of Environmental Sciences, 25(9), 1745-1753. doi:10.1016/s1001-0742(12)60224-1Fan, H., Li, J., Zhang, L., & Feng, L. (2014). Contribution of sludge adsorption and biodegradation to the removal of five pharmaceuticals in a submerged membrane bioreactor. 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Journal of Environmental Chemical Engineering, 7(5), 103294. doi:10.1016/j.jece.2019.103294Hampel, M., Alonso, E., Aparicio, I., Bron, J. E., Santos, J. L., Taggart, J. B., & Leaver, M. J. (2010). Potential physiological effects of pharmaceutical compounds in Atlantic salmon (Salmo salar) implied by transcriptomic analysis. Environmental Science and Pollution Research, 17(4), 917-933. doi:10.1007/s11356-009-0282-6Krishnan, V., Ahmad, D., & Jeru, J. B. (2008). Influence of COD:N:P ratio on dark greywater treatment using a sequencing batch reactor. Journal of Chemical Technology & Biotechnology, 83(5), 756-762. doi:10.1002/jctb.1842Li, B., & Zhang, T. (2010). Biodegradation and Adsorption of Antibiotics in the Activated Sludge Process. Environmental Science & Technology, 44(9), 3468-3473. doi:10.1021/es903490hLin, A. Y.-C., Yu, T.-H., & Lateef, S. K. (2009). Removal of pharmaceuticals in secondary wastewater treatment processes in Taiwan. Journal of Hazardous Materials, 167(1-3), 1163-1169. doi:10.1016/j.jhazmat.2009.01.108Mezzelani, M., Gorbi, S., & Regoli, F. (2018). Pharmaceuticals in the aquatic environments: Evidence of emerged threat and future challenges for marine organisms. Marine Environmental Research, 140, 41-60. doi:10.1016/j.marenvres.2018.05.001Min, X., Li, W., Wei, Z., Spinney, R., Dionysiou, D. D., Seo, Y., … Xiao, R. (2018). Sorption and biodegradation of pharmaceuticals in aerobic activated sludge system: A combined experimental and theoretical mechanistic study. Chemical Engineering Journal, 342, 211-219. doi:10.1016/j.cej.2018.01.012Molina-Muñoz, M., Poyatos, J. M., Rodelas, B., Pozo, C., Manzanera, M., Hontoria, E., & Gonzalez-Lopez, J. (2010). Microbial enzymatic activities in a pilot-scale MBR experimental plant under different working conditions. Bioresource Technology, 101(2), 696-704. doi:10.1016/j.biortech.2009.08.071Namkung, E., & Rittmann, B. E. (1986). Soluble microbial products (SMP) formation kinetics by biofilms. Water Research, 20(6), 795-806. doi:10.1016/0043-1354(86)90106-5Palli, L., Spina, F., Varese, G. C., Vincenzi, M., Aragno, M., Arcangeli, G., … Gori, R. (2019). Occurrence of selected pharmaceuticals in wastewater treatment plants of Tuscany: An effect-based approach to evaluate the potential environmental impact. International Journal of Hygiene and Environmental Health, 222(4), 717-725. doi:10.1016/j.ijheh.2019.05.006Pan, M., & Chu, L. M. (2017). Transfer of antibiotics from wastewater or animal manure to soil and edible crops. Environmental Pollution, 231, 829-836. doi:10.1016/j.envpol.2017.08.051Patrolecco, L., Ademollo, N., Grenni, P., Tolomei, A., Barra Caracciolo, A., & Capri, S. (2013). Simultaneous determination of human pharmaceuticals in water samples by solid phase extraction and HPLC with UV-fluorescence detection. Microchemical Journal, 107, 165-171. doi:10.1016/j.microc.2012.05.035Peng, J., Wang, X., Yin, F., & Xu, G. (2019). Characterizing the removal routes of seven pharmaceuticals in the activated sludge process. Science of The Total Environment, 650, 2437-2445. doi:10.1016/j.scitotenv.2018.10.004Hamon, P., Villain, M., & Marrot, B. (2014). Determination of sorption properties of micropollutants: What is the most suitable activated sludge inhibition technique to preserve the biomass structure? Chemical Engineering Journal, 242, 260-268. doi:10.1016/j.cej.2013.07.117Pomiès, M., Choubert, J.-M., Wisniewski, C., & Coquery, M. (2013). Modelling of micropollutant removal in biological wastewater treatments: A review. Science of The Total Environment, 443, 733-748. doi:10.1016/j.scitotenv.2012.11.037Rabiet, M., Togola, A., Brissaud, F., Seidel, J.-L., Budzinski, H., & Elbaz-Poulichet, F. (2006). Consequences of Treated Water Recycling as Regards Pharmaceuticals and Drugs in Surface and Ground Waters of a Medium-sized Mediterranean Catchment. Environmental Science & Technology, 40(17), 5282-5288. doi:10.1021/es060528pSantos, J. L., Aparicio, I., Callejón, M., & Alonso, E. (2009). Occurrence of pharmaceutically active compounds during 1-year period in wastewaters from four wastewater treatment plants in Seville (Spain). Journal of Hazardous Materials, 164(2-3), 1509-1516. doi:10.1016/j.jhazmat.2008.09.073Thiebault, T., Chassiot, L., Fougère, L., Destandau, E., Simonneau, A., Van Beek, P., … Chapron, E. (2017). Record of pharmaceutical products in river sediments: A powerful tool to assess the environmental impact of urban management? Anthropocene, 18, 47-56. doi:10.1016/j.ancene.2017.05.006Vona, A., di Martino, F., Garcia-Ivars, J., Picó, Y., Mendoza-Roca, J.-A., & Iborra-Clar, M.-I. (2015). Comparison of different removal techniques for selected pharmaceuticals. 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Molecular Targets of Bis (7)-Cognitin and Its Relevance in Neurological Disorders: A Systematic Review

Background: The exact mechanisms involved in the pathogenesis of neurodegenerative conditions are not fully known. The design of drugs that act on multiple targets represents a promising approach that should be explored for more effective clinical options for neurodegenerative disorders. B7C is s synthetic drug that has been studied for over 20 years and represents a promising multi-target drug for the treatment of neurodegenerative disorders, such as AD.Aims: The present systematic review, thus, aims at examining existing studies on the effect of B7C on different molecular targets and at discussing the relevance of B7C in neurological disorders.Methods: A list of predefined search terms was used to retrieve relevant articles from the databases of Embase, Pubmed, Scopus, and Web of Science. The selection of articles was done by two independent authors, who were considering articles concerned primarily with the evaluation of the effect of B7C on neurological disorders. Only full-text articles written in English were included; whereas, systematic reviews, meta-analyses, book chapters, conference subtracts, and computational studies were excluded.Results: A total of 2,266 articles were retrieved out of which 41 articles were included in the present systematic review. The effect of B7C on molecular targets, including AChE, BChE, BACE-1, NMDA receptor, GABA receptor, NOS, and Kv4.2 potassium channels was evaluated. Moreover, the studies that were included assessed the effect of B7C on biological processes, such as apoptosis, neuritogenesis, and amyloid beta aggregation. The animal studies examined in the review focused on the effect of B7C on cognition and memory.Conclusions: The beneficial effects observed on different molecular targets and biological processes relevant to neurological conditions confirm that B7C is a promising multi-target drug with the potential to treat neurological disorders

Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Blood Plasma

In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients' plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management.ERDF - Competitive Factors Thematic Operational ProgrammeFCT/PTDC/ QUI/68017/2006FCOMP-01-0124-FEDER-007439SFRH/BD/ 63430/2009National UNESCO Committee - L'Oréal Medals of Honor for Women in Science 200Portuguese National NMR Network - RNRM

Estimating cancer incidence based on claims data from medical insurance systems in two areas lacking cancer registries in China.

BACKGROUND: We aimed to establish a Medical-Insurance-System-based Cancer Surveillance System (MIS-CASS) in China and evaluate the completeness and timeliness of this system through reporting cancer incidence rates using claims data in two regions in northern and southern China. METHODS: We extracted claims data from medical insurance systems in Hua County of Henan Province, and Shantou City in Guangdong Province in China from Jan 1, 2012 to Jun 30, 2019. These two regions have been considered to be high risk regions for oesophageal cancer. We developed a rigorous procedure to establish the MIS-CASS, which includes data extraction, cleaning, processing, case ascertainment, privacy protection, etc. Text-based diagnosis in conjunction with ICD-10 codes were used to determine cancer diagnosis. FINDINGS: In 2018, the overall age-standardised (Segi population) incidence rates (ASR World) of cancer in Hua County and Shantou City were 167·39/100,000 and 159·78/100,000 respectively. In both of these areas, lung cancer and breast cancer were the most common cancers in males and females respectively. Hua County is a high-risk region for oesophageal cancer (ASR World: 25·95/100,000), whereas Shantou City is not a high-risk region for oesophageal cancer (ASR World: 11·43/100,000). However, Nanao island had the highest incidence of oesophageal cancer among all districts and counties in Shantou (ASR World: 36·39/100,000). The age-standardised male-to-female ratio for oesophageal cancer was lower in Hua County than in Shantou (1·69 vs. 4·02). A six-month lag time was needed to report these cancer incidences for the MIS-CASS. INTERPRETATION: MIS-CASS efficiently reflects cancer burden in real-time, and has the potential to provide insight for improvement of cancer surveillance in China. FUNDING: The National Key R&D Program of China (2016YFC0901404), the Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (XXZ0204), the Sanming Project of Shenzhen (SZSM201612061), and the Shantou Science and Technology Bureau (190829105556145, 180918114960704)