Attentional bias and treatment adherence in substitute-prescribed opiate users

BACKGROUND: Attentional bias (AB) is implicated in the development and maintenance of substance dependence and in treatment outcome. We assessed the effects of attentional bias modification (ABM), and the relationship between AB and treatment adherence in opiate dependent patients. METHOD: An independent groups design was used to compare 23 opiate dependent patients with 21 healthy controls. Participants completed an AB task before either a control or an ABM task designed to train attention away from substance-related stimuli. Pre- and post-ABM AB and craving were assessed to determine any changes. Relationships between treatment adherence (‘using on top’ of prescribed opiates or not) and AB, craving and psychopathology were also examined. RESULTS: There was no baseline difference in AB between patients and controls, and no significant effect of ABM on AB or substance craving. However, treatment adherent patients who did not use illicit opiates on top of their prescribed opiates had statistically significantly greater AB away from substance-related stimuli than both participants using on top and controls, and reported significantly lower levels of craving than non-treatment adherent patients. CONCLUSION: Whilst we did not find any significant effects of ABM on AB or craving, patients who were treatment adherent differed from both those who were not and from controls in their attentional functioning and substance craving. These findings are the first to suggest that AB may be a within-treatment factor predictive of adherence to pharmacological treatment and potentially of recovery in opiate users

“It’s just a theory”: trainee science teachers’ misunderstandings of key scientific terminology

Background: This article presents the findings from a survey of 189 pre-service science teachers who were asked to provide definitions of key scientific terms ('theory'; 'fact'; 'law'; 'hypothesis'). The survey was a scoping and mapping exercise to establish the range and variety of definitions. Methods: Graduates on a pre-service science teacher training course were asked to complete a short, free response survey and define key science terminology a >95% response rate was achieved and respondents definitions were categorised according to a best fit model. Results: In some cases, definitions contrary to accepted scientific meanings were given. In other cases, terminology was defined in a wholly non-scientific way, e.g., one-fifth of the respondents defined a ‘law’ in the context of rules that govern society rather than in a scientific context. Science graduates’ definitions and their understanding of key terminology is poor despite their study of science in formal university settings (with many respondents being recent science graduates). Conclusions: Key terminology in science, such as 'theory', 'law', 'fact', 'hypothesis', tends not to be taught and defined with consideration for the differences in meaning that different audiences/users give to them. This article calls for better instruction for pre-service science teachers’ in the importance of accurate and precise definitions of key science terminology in order to better differentiate between the scientific and colloquial usage of key terms

Silibinin induces mitochondrial NOX4-mediated endoplasmic reticulum stress response and its subsequent apoptosis

Background: Silibinin, a biologically active compound of milk thistle, has chemopreventive effects on cancer cell lines. Recently it was reported that silibinin inhibited tumor growth through activation of the apoptotic signaling pathway. Although various evidences showed multiple signaling pathways of silibinin in apoptosis, there were no reports to address the clear mechanism of ROS-mediated pathway in prostate cancer PC-3 cells. Several studies suggested that reactive oxygen species (ROS) play an important role in various signaling cascades, but the primary source of ROS was currently unclear. Methods: The effect of silibinin was investigated on cell growth of prostate cell lines by MTT assay. We examined whether silibinin induced apoptosis through production of ROS using flow cytometry. Expression of apoptosis-, endoplasmic reticulum (ER)-related protein and gene were determined by western blotting and RT-PCR, respectively. Results: Results showed that silibinin triggered mitochondrial ROS production through NOX4 expression and finally led to induce apoptosis. In addition, mitochondrial ROS caused ER stress through disruption of Ca2+ homeostasis. Co-treatment of ROS inhibitor reduced the silibinin-induced apoptosis through the inhibition of NOX4 expression, resulting in reduction of both Ca2+ level and ER stress response. Conclusions: Taken together, silibinin induced mitochondrial ROS-dependent apoptosis through NOX4, which is associated with disruption of Ca2+ homeostasis and ER stress response. Therefore, the regulation of NOX4, mitochondrial ROS producer, could be a potential target for the treatment of prostate cancer.ope

White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

BACKGROUND: Tumor associated macrophages (TAMs) are present in high density in solid tumors. TAMs share many characteristics with alternatively activated macrophages, also called M2. They have been shown to favor tumor development and a role in chemoresistance has also been suggested. Here, we investigated the effects of M2 in comparison to M1 macrophages on cancer cell sensitivity to etoposide. METHODS: We set up a model of macrophage polarization, starting from THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate). Once differentiated (M0 macrophages), they were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). To mimic the communication between cancer cells and TAMs, M0, M1 or M2 macrophages and HepG2 or A549 cancer cells were co-cultured during respectively 16 (HepG2) or 24 (A549) hours, before etoposide exposure for 24 (HepG2) or 16 (A549) hours. After the incubation, the impact of etoposide on macrophage polarization was studied and cancer cell apoptosis was assessed by western-blot for cleaved caspase-3 and cleaved PARP-1 protein, caspase activity assay and FACS analysis of Annexin V and PI staining. RESULTS: mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages, which provide a new, easy and well-characterized model of polarized human macrophages. Etoposide-induced cancer cell apoptosis was markedly reduced in the presence of THP-1 M2 macrophages, while apoptosis was increased in cells co-cultured with M1 macrophages. On the other hand, etoposide did not influence M1 or M2 polarization. CONCLUSIONS: These results evidence for the first time a clear protective effect of M2 on the contrary to M1 macrophages on etoposide-induced cancer cell apoptosis

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Spatially structured genetic diversity of the Amerindian yam (Dioscorea trifida L.) assessed by SSR and ISSR markers in Southern Brazil

Dioscorea trifida L. (Dioscoreaceae) is among the economically most important cultivated Amerindian yam species, whose origin and domestication are still unresolved issues. in order to estimate the genetic diversity maintained by traditional farmers in Brazil, 53 accessions of D. trifida from 11 municipalities in the states of São Paulo, Santa Catarina, Mato Grosso and Amazonas were characterized on the basis of eight Simple Sequence Repeats (SSR) and 16 Inter Simple Sequence Repeats (ISSR) markers. the level of polymorphism among the accessions was high, 95 % for SSR and 75.8 % for ISSR. the SSR marker showed higher discrimination power among accessions compared to ISSR, with D parameter values of 0.79 and 0.44, respectively. Although SSR and ISSR markers led to dendrograms with different topologies, both separated the accessions into three main groups: I-Ubatuba-SP; II-Iguape-SP and Santa Catarina; and III-Mato Grosso. the accessions from Amazonas State were classified in group II with SSR and in a separate group with ISSR. Bayesian and principal coordinate analyzes conducted with both molecular markers corroborated the classification into three main groups. Higher variation was found within groups in the AMOVA analysis for both markers (66.5 and 60.6 % for ISSR and SSR, respectively), and higher Shannon diversity index was found for group II with SSR. Significant but low correlations were found between genetic and geographic distances (r = 0.08; p = 0.0007 for SSR and r = 0.16; p = 0.0002 for ISSR). Therefore, results from both markers showed a slight spatially structured genetic diversity in D. trifida accessions maintained by small traditional farmers in Brazil.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Luiz de Queiroz Coll Agr, Dept Genet, BR-13400970 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, BR-09972270 São Paulo, BrazilUniv Calif Davis, Dept Plant Sci MS1, Sect Crop & Ecosyst Sci, Davis, CA 95616 USAUniversidade Federal de São Paulo, Dept Biol Sci, BR-09972270 São Paulo, BrazilFAPESP: 2007/04805-2Web of Scienc

Recognition of Dynamic Facial Affect in Substitute Maintained Opiate Users

This thesis investigates the capacity to identify Emotional Facial Expressions (EFE) in people who have a history of using illicit substances. Part one is a systematic literature review that critically appraises the available research in this area. The studies reviewed investigate the acute, sub-acute and/or chronic effects of different levels of use of opiates, cannabis, MDMA, cocaine, methamphetamine, and multiple substances. Methodological constraints in this area of research make synthesis and interpretation of findings problematic. Despite this, the review highlights evidence of deficits in EFE recognition associated with substance use. These appear more marked for negative emotions, particularly fear and disgust. Part two is an empirical study that aims to investigate EFE recognition in opiate users. Substitute prescribed opiate users are compared with controls on performance on a dynamic EFE recognition task. The findings of this study suggest that there is a general deficit in sensitivity to EFEs in opiate uses and specific deficits in the recognition of neutral disgust and fear expressions. Part three is a critical appraisal focusing on the process of carrying out research with clinical populations and within substance use in particular. This considers the difficulties and benefits of integrating clinical practice and empirical research in the role of clinical psychologists