microRNA-132 regulates gene expression programs involved in microglial homeostasis

microRNA-132 (miR-132), a known neuronal regulator, is one of the most robustly downregulated microRNAs (miRNAs) in the brain of Alzheimer's disease (AD) patients. Increasing miR-132 in AD mouse brain ameliorates amyloid and Tau pathologies, and also restores adult hippocampal neurogenesis and memory deficits. However, the functional pleiotropy of miRNAs requires in-depth analysis of the effects of miR-132 supplementation before it can be moved forward for AD therapy. We employ here miR-132 loss- and gain-of-function approaches using single-cell transcriptomics, proteomics, and in silico AGO-CLIP datasets to identify molecular pathways targeted by miR-132 in mouse hippocampus. We find that miR-132 modulation significantly affects the transition of microglia from a disease-associated to a homeostatic cell state. We confirm the regulatory role of miR-132 in shifting microglial cell states using human microglial cultures derived from induced pluripotent stem cells

Overexpression of circulating MiR-30b-5p identifies advanced breast cancer

Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Background Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Methods Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. Results MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. Conclusions MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients’ monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.Research Center of Portuguese Oncology Institute of Porto (PI 74-CI-IPOP-19-2016). JL and CSG are supported by a PhD fellowship from FCT - Fundação para a Ciência e Tecnologia (SFRH/ BD/132751/2017 and SFRH/BD/92786/2013, respectively). SS is supported by a PhD fellowship IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027. BMC is funded by FCT-Fundação para a Ciência e a Tecnologia (IF/00601/2012

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Priorities to inform research on marine plastic pollution in Southeast Asia

This is the final version. Available from Elsevier via the DOI in this record. Southeast Asia is considered to have some of the highest levels of marine plastic pollution in the world. It is therefore vitally important to increase our understanding of the impacts and risks of plastic pollution to marine ecosystems and the essential services they provide to support the development of mitigation measures in the region. An interdisciplinary, international network of experts (Australia, Indonesia, Ireland, Malaysia, the Philippines, Singapore, Thailand, the United Kingdom, and Vietnam) set a research agenda for marine plastic pollution in the region, synthesizing current knowledge and highlighting areas for further research in Southeast Asia. Using an inductive method, 21 research questions emerged under five non-predefined key themes, grouping them according to which: (1) characterise marine plastic pollution in Southeast Asia; (2) explore its movement and fate across the region; (3) describe the biological and chemical modifications marine plastic pollution undergoes; (4) detail its environmental, social, and economic impacts; and, finally, (5) target regional policies and possible solutions. Questions relating to these research priority areas highlight the importance of better understanding the fate of marine plastic pollution, its degradation, and the impacts and risks it can generate across communities and different ecosystem services. Knowledge of these aspects will help support actions which currently suffer from transboundary problems, lack of responsibility, and inaction to tackle the issue from its point source in the region. Being profoundly affected by marine plastic pollution, Southeast Asian countries provide an opportunity to test the effectiveness of innovative and socially inclusive changes in marine plastic governance, as well as both high and low-tech solutions, which can offer insights and actionable models to the rest of the world.Natural Environment Research CouncilNational Research Foundation, Prime Minister’s Office (Singapore

Degradação do betão por reacções sulfáticas internas. Metodologia para o seu diagnóstico e prognóstico

Submitted by António Santos Silva ([email protected]) on 2009-09-25T14:33:22Z No. of bitstreams: 1 artigo ASCP09_SSilva.pdf: 528699 bytes, checksum: 4c89a3851723077377d39c46a8d475f3 (MD5)Rejected by [email protected]([email protected]), reason: conformr combinado rejeito para corrigir Amélia on 2009-09-25T15:19:02Z (GMT)Submitted by António Santos Silva ([email protected]) on 2009-09-25T15:31:58Z No. of bitstreams: 1 artigo ASCP09_SSilva.pdf: 528699 bytes, checksum: 4c89a3851723077377d39c46a8d475f3 (MD5)Approved for entry into archive by [email protected]([email protected]) on 2009-10-08T11:12:06Z (GMT) No. of bitstreams: 1 artigo ASCP09_SSilva.pdf: 528699 bytes, checksum: 4c89a3851723077377d39c46a8d475f3 (MD5)Made available in DSpace on 2009-10-08T11:12:14Z (GMT). No. of bitstreams: 1 artigo ASCP09_SSilva.pdf: 528699 bytes, checksum: 4c89a3851723077377d39c46a8d475f3 (MD5) Previous issue date: 2009-07Made available in DSpace on 2010-04-27T07:26:25Z (GMT). No. of bitstreams: 2 license.txt: 1838 bytes, checksum: b36eb1b6e3b4db40f8bf94ce5a306b38 (MD5) artigo ASCP09_SSilva.pdf: 528699 bytes, checksum: 4c89a3851723077377d39c46a8d475f3 (MD5) Previous issue date: 2009-07Made available in DSpace on 2014-10-20T16:32:21Z (GMT). No. of bitstreams: 2 artigo ASCP09_SSilva.pdf: 528699 bytes, checksum: 4c89a3851723077377d39c46a8d475f3 (MD5) license.txt: 1838 bytes, checksum: b36eb1b6e3b4db40f8bf94ce5a306b38 (MD5) Previous issue date: 2009-07Made available in DSpace on 2017-04-12T16:13:50Z (GMT). No. of bitstreams: 2 license.txt: 1838 bytes, checksum: b36eb1b6e3b4db40f8bf94ce5a306b38 (MD5) artigo ASCP09_SSilva.pdf: 528699 bytes, checksum: 4c89a3851723077377d39c46a8d475f3 (MD5) Previous issue date: 2009-07Os autores agradecem à Fundação para a Ciência e Tecnologia (FCT) o apoio financeiro no âmbito do projecto EXREACT (Mitigação de reacções deletérias expansivas internas em estruturas de betão, PTDC/CTM/65243/2006), e ao projecto DURATINET (Durable Tranport Infrastructures in the Atlantic Área Network) do Programa Operacional Espaço Atlântico 2007-2013, co-financiado pelo FEDER.60203-209ppDM/NMM20091 a 3 de Julh

The Application of Fluorescence Microscopy and Scanning Electron Microscopy in the Detection of Delayed Ettringite Formation in Concrete

The degradation of concrete structures caused by delayed ettringite formation (DEF) is a problem that nowadays affects many concrete structures worldwide. This pathology is due to the formation of an expansive compound – ettringite - inside the material. This is a hydrated calcium sulphoaluminate produced by the chemical reaction between sulphate ions, calcium hydroxide and alumina present in the Portland cement paste. This product, normally formed during the hydration of cement, presents an acicular morphology (needles) that can be observed by scanning electron microscopy (SEM). However, DEF can also be formed after the setting of the cement causing, in this case, a deleterious expansion of the concrete. This secondary ettringite can also be produced after an excessive heating of the concrete, caused by a high amount of cement or by the use of heat cure. SEM has been used to distinguish between expansive and non expansive ettringite based normally in morphology analysis, since the former is characterized by a compressed or compact nature where the needle shapes disappear or are welded together. Furthermore, the use of other techniques, like X-ray diffraction or micro-XRF, has been limited because the compressed or compact ettringite is badly crystallized or even amorphous and the elemental composition is similar and therefore it is difficult to detect. This article presents a methodology for the diagnosis of DEF using polished concrete thin sections and combining polarised and fluorescence light optical microscopy with SEM-EDS