Advance Care Planning in Asia: A Systematic Narrative Review of Healthcare Professionals’ Knowledge, Attitude, and Experience

Objective: The value of advance care planning (ACP) for patients with life-limiting illnesses is widely recognized but Asian health care professionals' (HCPs') perspectives on ACP have received little systematic attention. We aim to synthesize evidence regarding Asian HCPs’ knowledge of, attitudes toward, and experiences with ACP. Design: Systematic review with narrative synthesis and stepwise thematic analysis. Setting and Participants: HCPs in southern, eastern, and southeastern Asia. Methods: Studies from inception to September 2019 were identified from English-language searches of Embase, MEDLINE, Web of Science, and Google Scholar with reference-chaining and hand-searching. Two investigators independently screened and assessed the risk of bias in all original studies reporting HCPs’ knowledge of, attitudes toward, and experiences with ACP, including their perspectives toward barriers and facilitators of ACP. Results: Fifty-one studies were included; 42 were quantitative, 43 had been conducted in high-income countries, and 36 were of good quality. Twenty-six studies operationalized ACP as the completion of an advance directive rather than a value-exploration process. Thirteen studies reported knowledge, 44 attitudes, 29 experiences, and 36 barriers and facilitators of ACP. Asian HCPs addressed the essential role of families in ACP. They acknowledge the importance of ACP but rarely engage the patient in it. They considered ACP difficult to initiate, partly because of their lack of knowledge and skills in ACP, personal uneasiness to conduct ACP, fear of conflicts with family members and their legal consequences, and the lack of a standard system for ACP. Most studies indicated HCPs’ low engagement and late initiation of ACP. Conclusions and Implications: Despite acknowledging its importance, Asian HCPs felt that engaging in ACP is challenging. Capacity building for ACP in Asia should focus on culturally adapting ACP models concerning the essential role of the family in Asia, education for HCPs and the public, and providing institutional support for ACP

International consensus recommendations on the diagnostic work-up for malformations of cortical development

Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. MCDs place a substantial burden on affected individuals, their families and societies worldwide, as these individuals can experience lifelong drug-resistant epilepsy, cerebral palsy, feeding difficulties, intellectual disability and other neurological and behavioural anomalies. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and aetiology, thereby hampering timely and adequate management. In this article, the international MCD network Neuro-MIG provides consensus recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs with the aim of improving patient management worldwide. We reviewed the literature on clinical presentation, aetiology and diagnostic approaches for the main MCD subtypes and collected data on current practices and recommendations from clinicians and diagnostic laboratories within Neuro-MIG. We reached consensus by 42 professionals from 20 countries, using expert discussions and a Delphi consensus process. We present a diagnostic workflow that can be applied to any individual with MCD and a comprehensive list of MCD-related genes with their associated phenotypes. The workflow is designed to maximize the diagnostic yield and increase the number of patients receiving personalized care and counselling on prognosis and recurrence risk

RANTES/CCL5 and Risk for Coronary Events: Results from the MONICA/KORA Augsburg Case-Cohort, Athero-Express and CARDIoGRAM Studies

BACKGROUND: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. METHODS AND FINDINGS: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). CONCLUSIONS: High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies

The potential diagnostic yield of whole exome sequencing in pregnancies complicated by fetal ultrasound anomalies

Introduction: The aim of this retrospective cohort study was to determine the potential diagnostic yield of prenatal whole exome sequencing in fetuses with structural anomalies on expert ultrasound scans and normal chromosomal microarray results. Material and methods: In the period 2013-2016, 391 pregnant women with fetal ultrasound anomalies who received normal chromosomal microarray results, were referred for additional genetic counseling and opted for additional molecular testing pre- and/or postnatally. Most of the couples received only a targeted molecular test and in 159 cases (40.7%) whole exome sequencing (broad gene panels or open exome) was performed. The results of these molecular tests were evaluated retrospectively, regardless of the time of the genetic diagnosis (prenatal or postnatal). Results: In 76 of 391 fetuses (19.4%, 95% CI 15.8%-23.6%) molecular testing provided a genetic diagnosis with identification of (likely) pathogenic variants. In the majority of cases (91.1%, 73/76) the (likely) pathogenic variant would be detected by prenatal whole exome sequencing analysis. Conclusions: Our retrospective cohort study shows that prenatal whole exome sequencing, if offered by a clinical geneticist, in addition to chromosomal microarray, would notably incre

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±

Methods to detect spatial biases in tracking studies caused by differential representativeness of individuals, populations and time

Este artículo contiene 20 páginas, 6 figuras, 4 tablas.Aim: Over the last decades, the study of movement through tracking data has grown exceeding the expectations of movement ecologists. This has posed new challenges, specifically when using individual tracking data to infer higher- level distributions (e.g. population and species). Sources of variability such as individual site fidelity (ISF), en-vironmental stochasticity over time, and space-use variability across species ranges must be considered, and their effects identified and corrected, to produce accurate estimates of spatial distribution using tracking data. Innovation: We developed R functions to detect the effect of these sources of vari-ability in the distribution of animal groups when inferred from individual tracking data. These procedures can be adapted for their use in most tracking datasets and tracking techniques. We demonstrated our procedures with simulated datasets and showed their applicability on a real-world dataset containing 1346 year- round migratory trips from 805 individuals of three closely related seabird species breeding in 34 colonies in the Mediterranean Sea and the Atlantic Ocean, spanning 10 years. We detected an effect of ISF in one of the colonies, but no effect of the environmental stochasticity on the distribution of birds for any of the species. We also identified among-colony variability in nonbreeding space use for one species, with significant effects of popu-lation size and longitude. Main conclusions: This work provides a useful, much- needed tool for researchers using animal tracking data to model species distributions or establish conservation measures. This methodology may be applied in studies using individual tracking data to accurately infer the distribution of a population or species and support the deline-ation of important areas for conservation based on tracking data. This step, designed to precede any analysis, has become increasingly relevant with the proliferation of studies using large tracking datasets that has accompanied the globalization process in science driving collaborations and tracking data sharing initiatives.We thank the following institutions for funding: EU H2020 pro-gramme through grant 634495; Seventh Framework Programme (Research Executive Agency) through Marie Curie Career Integration Grant 618841 (FP7-PEOPLE-2013- CIG); ESFRI LifeWatch Project; LIFE programme of the European Commission through projects LIFE10 NAT/MT090 and LIFE11 NAT/IT/000093; Ministerio de Ciencia e Innovación/Ministerio de Economia y Competitividad (Spain) through projects CGL2009- 11278/BOS, CGL2013-42585-P, C G L 2 0 1 3 - 4 2 2 0 3 - R , C G L 2 0 16 - 7 8 5 3 0 - R a n d C G L 2 0 17- 8 52 10 - P ; Organismo Autónomo de Parques Nacionales (Spain) through pro-ject 1248/2014; Fundação para a Ciência e a Tecnologia (MCTES, Portugal) through projects MARE-UID/MAR/04292/2019; IF/00502/2013/CP1186/CT0003, PTDC/BIA-ANM/3743/2014, PTDC/MAR-PRO/0929/2014, UID/AMB/50017/2019 and UIDP/50017/2020 + UIDB/50017/2020 (to CESAM); Office Français de la Biodiversité (France), through the Programme PACOMM, Natura2000 en mer; Hellenic Bird Ringing Centre; MSDEC (Malta). VMP was supported by pre-doctoral contract BES-2014- 068025 of the Spanish Ministerio de Industria, Economía y Competitividad; MM by grant SFRH/BPD/47047/2008 from the Portuguese Foundation for Science and Technology; JMRG by Ph.D. grant AP2009-2163 from the Spanish Ministerio de Educación; GDO and MMü by Ornis italica and by the Regione Siciliana and Assessorato Risorse Agricole e Alimentari thoriugh a grant to the Ringing Unit of Palermo; VHP by grant SFRH/BPD/85024/2012 from the Portuguese Foundation for Science and Technology; VN by grant SFRH/BPD/88914/2012 from the Portuguese Foundation for Science and Technology; and JN by the Spanish National Programme Ramón y Cajal (RYC-2015- 17809); GK and SX were partially funded by the Operational Program “Environment and Sustainable Development” (EPPERAA) of the National Strategic Reference Framework (NSRF) 2007-2013, co- financed by the ERDF and Greek EDP; FdF by a Ph.D. grant from the Coordination for the Improvement of Higher Education Personnel (CAPES—Brazilian government agency; Bex Process 1307/13-4); ZZ by a PhD grant from the University of Barcelona (APIF/2012); MCF by a PhD grant from the University of Barcelona; and RR by post-doctoral contracts of the PLEAMAR programme from MINECO and Fundación Biodiversidad (2017/2349), and Ministerio de Ciencia, in-novación y Universidades (RYC-2017- 22055). This publication is part of the project I+D+i/PID2020-117155GB-I00, funded by MCIN/ AEI/10.13039/501100011033.Peer reviewe

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Clinical characteristics of women captured by extending the definition of severe postpartum haemorrhage with 'refractoriness to treatment': a cohort study

Background: The absence of a uniform and clinically relevant definition of severe postpartum haemorrhage hampers comparative studies and optimization of clinical management. The concept of persistent postpartum haemorrhage, based on refractoriness to initial first-line treatment, was proposed as an alternative to common definitions that are either based on estimations of blood loss or transfused units of packed red blood cells (RBC). We compared characteristics and outcomes of women with severe postpartum haemorrhage captured by these three types of definitions. Methods: In this large retrospective cohort study in 61 hospitals in the Netherlands we included 1391 consecutive women with postpartum haemorrhage who received either ≥4 units of RBC or a multicomponent transfusion. Clinical characteristics and outcomes of women with severe postpartum haemorrhage defined as persistent postpartum haemorrhage were compared to definitions based on estimated blood loss or transfused units of RBC within 24 h following birth. Adverse maternal outcome was a composite of maternal mortality, hysterectomy, arterial embolisation and intensive care unit admission. Results: One thousand two hundred sixty out of 1391 women (90.6%) with postpartum haemorrhage fulfilled the definition of persistent postpartum haemorrhage. The majority, 820/1260 (65.1%), fulfilled this definition within 1 h following birth, compared to 819/1391 (58.7%) applying the definition of ≥1 L blood loss and 37/845 (4.4%) applying the definition of ≥4 units of RBC. The definition persistent postpartum haemorrhage captured 430/471 adverse maternal outcomes (91.3%), compared to 471/471 (100%) for ≥1 L blood loss and 383/471 (81.3%) for ≥4 units of RBC. Persistent postpartum haemorrhage did not capture all adverse outcomes because of missing data on timing of initial, first-line treatment. Conclusion: The definition persistent postpartum haemo

KANDUNGAN KOLESTEROL SERUM DAN SIFAT DIGESTA TIKUS SPRAGUE DAWLEY HIPERKOLESTEROLEMIA YANG DIBERI PAKAN JAMUR TIRAM PUTIH (Pleurotus ostreatus) OLAHAN

This research were to study the effect of processed oyster mushrooms (Pleurotus ostreatus) on the cholesterol and digesta characteristics of Sprague Dawley hypercholesterolemic rats. Thirty of eight weeks old male Sprague Dawley rats were fed with standard diet AIN�93 for a week. The rats were made hypercholesterolemic by feeding 1 g pure cholesterol and 0,25 g of cholic acid for a week. The rats were divided into 5 groups and each group was treated with different diet. Group I, standar diet AIN�93 was fed to the rats as contro