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1.
Drug Alcohol Rev ; 43(1): 199-212, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37881163

ABSTRACT

INTRODUCTION: The proliferation of alcohol outlets has led to increased physical availability of alcohol, harmful alcohol consumption and related harm in Nigeria. This study explored alcohol licensing legislations and licensing systems across local government councils (LGC) in South-West, Nigeria. METHODS: Twenty-four LGCs across three states participated in the study. Data were generated from: (i) documents containing LGC liquor licensing legislations; and (ii) semi-structured interviews conducted with 50 LGC officials (16 legislative council clerks and 34 finance officers [director of finance, rate officers and revenue collectors]) were thematically analysed using NVivo. RESULTS: Nine of the sampled LGC enacted liquor licence bylaws. These mostly specified categories of liquor licences issued and licensing fees. None of the liquor licence bylaw contained regulations for controlling physical availability of alcohol and outlet density. Finance officials were licensing officers and there were no licensing committees across the LGCs. The LGC officials were unanimous in stating that generating revenue from licensing fees was the main objective for licensing alcohol outlets. The LGCs licensed alcohol outlets indiscriminately and failed to regulate outlet density. DISCUSSION AND CONCLUSION: The absence of regulations for controlling outlet density has implications for physical availability of alcohol in Nigeria. Our findings strongly suggest the need to develop national liquor licensing legislation with public health objectives and implementing regulations for controlling temporal and spatial availability of alcohol. Each LGC should inaugurate a licensing committee with clearly defined roles and responsibilities for licensing stakeholders such as LGC health officials, law enforcement agencies and community members.


Subject(s)
Alcohol Drinking , Licensure , Humans , Nigeria , Alcoholic Beverages , Ethanol , Commerce
2.
Alcohol Alcohol ; 58(6): 628-636, 2023 Nov 11.
Article in English | MEDLINE | ID: mdl-37706528

ABSTRACT

AIM: The physical availability of alcohol is a modifiable determinant of alcohol consumption and related harm. However, Nigeria currently does not have national regulations restricting the physical availability of alcohol. The study measured alcohol outlet density and marketing in Abeokuta, Nigeria. METHODS: A descriptive community design was employed. Seven wards in Abeokuta South local government were surveyed street by street for functional alcohol outlets and nearby public institutions (schools and worship centres). Outlet characteristics were documented, and the location of outlets and public institutions was geocoded using a global positioning system app. The density and proximity of outlets and public institutions were analysed using QGIS 3.22. RESULTS: Four hundred and seventy-six alcohol outlets and 194 public institutions (82 schools, 87 churches, and 25 mosques) were sampled across the 7 wards. The most common type of alcohol premises and outlets was on/off-premises and liquor/non-alcoholic drinks stores. Alcohol banners on liquor store lintels were the most prevalent marketing item. Alcohol outlet density ranged from 8.06 to 200 per km2. The smallest average distance between alcohol outlets was 28 m in Sodeke, while Ago Egun/Ijesa had the highest number of outlets and on/off premises. The shortest distance from an outlet to a school was 18.77 m in Ijaiye and 44 (14.7%) schools were located within ≤100 m of an outlet. CONCLUSIONS: Findings indicate high alcohol density, resulting in short distances between alcohol outlets and public institutions in Abeokuta South local government area. These results underscore the importance of implementing evidence-based alcohol availability policies in Nigeria.


Subject(s)
Alcoholic Beverages , Commerce , Humans , Nigeria/epidemiology , Alcohol Drinking/epidemiology , Ethanol , Marketing , Residence Characteristics
4.
Cancer Discov ; 13(3): 632-653, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36399432

ABSTRACT

Advanced prostate cancers comprise distinct phenotypes, but tumor classification remains clinically challenging. Here, we harnessed circulating tumor DNA (ctDNA) to study tumor phenotypes by ascertaining nucleosome positioning patterns associated with transcription regulation. We sequenced plasma ctDNA whole genomes from patient-derived xenografts representing a spectrum of androgen receptor active (ARPC) and neuroendocrine (NEPC) prostate cancers. Nucleosome patterns associated with transcriptional activity were reflected in ctDNA at regions of genes, promoters, histone modifications, transcription factor binding, and accessible chromatin. We identified the activity of key phenotype-defining transcriptional regulators from ctDNA, including AR, ASCL1, HOXB13, HNF4G, and GATA2. To distinguish NEPC and ARPC in patient plasma samples, we developed prediction models that achieved accuracies of 97% for dominant phenotypes and 87% for mixed clinical phenotypes. Although phenotype classification is typically assessed by IHC or transcriptome profiling from tumor biopsies, we demonstrate that ctDNA provides comparable results with diagnostic advantages for precision oncology. SIGNIFICANCE: This study provides insights into the dynamics of nucleosome positioning and gene regulation associated with cancer phenotypes that can be ascertained from ctDNA. New methods for classification in phenotype mixtures extend the utility of ctDNA beyond assessments of somatic DNA alterations with important implications for molecular classification and precision oncology. This article is highlighted in the In This Issue feature, p. 517.


Subject(s)
Circulating Tumor DNA , Prostatic Neoplasms , Male , Humans , Circulating Tumor DNA/genetics , Nucleosomes/genetics , Precision Medicine , Prostatic Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Phenotype
5.
Nat Commun ; 13(1): 7475, 2022 12 03.
Article in English | MEDLINE | ID: mdl-36463275

ABSTRACT

Cell-free DNA (cfDNA) has the potential to inform tumor subtype classification and help guide clinical precision oncology. Here we develop Griffin, a framework for profiling nucleosome protection and accessibility from cfDNA to study the phenotype of tumors using as low as 0.1x coverage whole genome sequencing data. Griffin employs a GC correction procedure tailored to variable cfDNA fragment sizes, which generates a better representation of chromatin accessibility and improves the accuracy of cancer detection and tumor subtype classification. We demonstrate estrogen receptor subtyping from cfDNA in metastatic breast cancer. We predict estrogen receptor subtype in 139 patients with at least 5% detectable circulating tumor DNA with an area under the receive operator characteristic curve (AUC) of 0.89 and validate performance in independent cohorts (AUC = 0.96). In summary, Griffin is a framework for accurate tumor subtyping and can be generalizable to other cancer types for precision oncology applications.


Subject(s)
Cell-Free Nucleic Acids , Neoplasms , Humans , Cell-Free Nucleic Acids/genetics , Nucleosomes/genetics , Neoplasms/diagnosis , Neoplasms/genetics , Receptors, Estrogen , Precision Medicine
6.
J Trauma Stress ; 35(5): 1460-1471, 2022 10.
Article in English | MEDLINE | ID: mdl-35733296

ABSTRACT

This study examined posttraumatic stress disorder (PTSD), complex PTSD, depression, and anxiety among U.K. rail workers. A cross-sectional survey examining exposure to seven psychosocial hazards (bullying/harassment; verbal abuse; physical and sexual assault; and hearing about, seeing the aftermath of, or witnessing a fatality), working conditions, physical health, and the impact of COVID-19 was administered to 3,912 participants. Outcome measures were the ITQ, PHQ-9, and GAD-7. Among trauma-exposed participants, 24.3% met the criteria for PTSD or CPTSD; 38.6% and 29.2% of all participants scored in the moderate-to-severe range on the PHQ-9 and GAD-7, respectively. Data were analyzed using logistic and linear regression. Bullying/harassment was positively associated with GAD-7 scores, f2 = .001, and PTSD and CPTSD, ORs = 1.83-2.02. Hearing about and witnessing a fatality were associated with PTSD and CPTSD, ORs = 1.77-2.10. Poorer ergonomics at work were positively associated with PHQ-9 and GAD-7 scores, f2 = .001. Higher job satisfaction was associated with lower odds of PTSD and CPTSD, ORs = 0.87-0.91, and negatively associated with PHQ-9 and GAD-7 scores, f2 = .008-.01. Work intensity was associated with PTSD and CPTSD, ORs = 1.79-1.83, and positively associated with PHQ-9 and GAD-7 scores, f2 = .02-.03. Reporting more physical health problems was associated with PTSD, OR = 1.07, and positively associated with GAD-7 and PHQ-9 scores, f2 = .008-.01. The results suggest bullying/harassment and work intensity are important variables in employee mental health and could drive future research and industry initiatives.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Humans , Anxiety/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Electrolytes , International Classification of Diseases , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology
8.
EMBO J ; 41(10): e109202, 2022 05 16.
Article in English | MEDLINE | ID: mdl-35451102

ABSTRACT

Nonsense-mediated mRNA decay (NMD) is governed by the three conserved factors-UPF1, UPF2, and UPF3. While all three are required for NMD in yeast, UPF3B is dispensable for NMD in mammals, and its paralog UPF3A is suggested to only weakly activate or even repress NMD due to its weaker binding to the exon junction complex (EJC). Here, we characterize the UPF3A/B-dependence of NMD in human cell lines deleted of one or both UPF3 paralogs. We show that in human colorectal cancer HCT116 cells, NMD can operate in a UPF3B-dependent and -independent manner. While UPF3A is almost dispensable for NMD in wild-type cells, it strongly activates NMD in cells lacking UPF3B. Notably, NMD remains partially active in cells lacking both UPF3 paralogs. Complementation studies in these cells show that EJC-binding domain of UPF3 paralogs is dispensable for NMD. Instead, the conserved "mid" domain of UPF3 paralogs is consequential for their NMD activity. Altogether, our results demonstrate that the mammalian UPF3 proteins play a more active role in NMD than simply bridging the EJC and the UPF complex.


Subject(s)
Nonsense Mediated mRNA Decay , RNA-Binding Proteins , Exons , HCT116 Cells , Humans , RNA Helicases/genetics , RNA Helicases/metabolism , RNA-Binding Proteins/metabolism , Trans-Activators/genetics , Trans-Activators/metabolism
9.
Addiction ; 117(8): 2200-2214, 2022 08.
Article in English | MEDLINE | ID: mdl-35315170

ABSTRACT

BACKGROUND AND AIMS: Alcohol use increases throughout adolescence. Emergency department (ED) attendance is an opportunity for alcohol screening and brief intervention (ASBI), which is effective for adults. This trial evaluated the effectiveness and cost-effectiveness of ASBI compared with screening alone (SA) in high-risk adolescents. DESIGN, SETTING AND PARTICIPANTS: Multi-centre, three-group, single-blind, individually randomized trial with follow-ups after 6 and 12 months in 10 ED settings in England. From October 2014 to May 2015 we screened 3327 adolescents aged 14 to 18 years, of whom 756 (22.7%) scored at least 3 on the Alcohol Use Disorders Identification Test: consumption (AUDIT-C) and consented to participate in this trial. Mean age was 16.1 years; 50.2% were female and 84.9% were white. INTERVENTIONS: Interventions were personalized feedback and brief advice (PFBA), personalized feedback plus electronic brief intervention (eBI) and SA. MEASURES: The primary outcome was the weekly alcohol consumed in standard UK units (8 g ethanol) at 12 months post-randomization, derived from extended AUDIT-C. Economic outcomes included quality of life and service use, from perspectives of both the National Health Service and personal social services (NHS&PSS) and society. FINDINGS: At 12 months, mean weekly consumption was 2.99 [95% confidence interval (CI) = 2.38-3.70] standard units for the SA group, 3.56 (95% CI = 2.90, 4.32) for PFBA and 3.18 (95% CI = 2.50, 3.97) for eBI, showing no significant differences. The PFBA group consumed mean 0.57 (-0.36, 1.70) units more than SA; and eBIs consumed 0.19 (-0.71, 1.30) more. Bayes factors suggested lack of effectiveness explained non-significance. From the NHS&PSS perspective, economic analysis showed that PFBA and eBI were not cost-effective compared with SA: PFBA yielded incremental cost-effectiveness ratio of £6213 (-£736 843, £812 884), with the intervention having 54% probability of being cost-effective compared with SA at the £20 000 WTP threshold. CONCLUSIONS: In emergency departments in England, neither personalized feedback and brief advice nor personalized feedback plus electronic brief intervention showed evidence of being effective or cost-effective when compared with screening alone in reducing alcohol consumption among adolescents.


Subject(s)
Alcoholism , Crisis Intervention , Adolescent , Adult , Alcohol Drinking/prevention & control , Alcoholism/diagnosis , Alcoholism/therapy , Bayes Theorem , Cost-Benefit Analysis , Electronics , Emergency Service, Hospital , Female , Humans , Male , Quality of Life , Single-Blind Method , State Medicine
10.
J Ment Health ; 31(5): 692-698, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34565267

ABSTRACT

BACKGROUND: Meeting psychological needs for autonomy, competence and relatedness as described by Self-Determination Theory (SDT) has been associated with increased well-being and job satisfaction in mental health staff and improved care outcomes for patients. AIMS: The study investigated whether psychological need satisfaction predicted stress, turnover intention and job satisfaction in health care assistants (HCA) working in inpatient mental health hospitals in the United Kingdom including full time (FT) and temporary agency worker (TAW) staff. METHODS: A cross-sectional survey explored need satisfaction between FT (n = 63) and TAW (n = 39) staff using the Work-Related Basic Need Satisfaction Scale. Multiple regression was used to explore whether satisfaction of the needs for autonomy, competence and relatedness predicted scores on measures of stress, job satisfaction and turnover intention. RESULTS: Results were comparable between FT and TAW staff. Autonomy was the need least satisfied, a need which predicted self-reported job satisfaction, stress and turnover intention. Relatedness also predicted job satisfaction and turnover intention. CONCLUSIONS: Recommendations are made to explore experiences of (and barriers to) autonomy and relatedness in inpatient HCA staff to target and improve autonomy and relatedness in this workforce. Implications of doing so are considered at a staffing, organisational and patient level.


Subject(s)
Job Satisfaction , State Medicine , Cross-Sectional Studies , Hospitals, Psychiatric , Humans , Inpatients , Intention , Mental Health , Personal Satisfaction , Surveys and Questionnaires , Workplace/psychology
11.
PLoS One ; 16(6): e0252900, 2021.
Article in English | MEDLINE | ID: mdl-34111184

ABSTRACT

BACKGROUND: Khat is a plant that is used for its amphetamine-like stimulant properties. However, although khat is very popular in Eastern Africa, Arabian Peninsula, and the Middle East, there is still a lack of studies researching the possible neurobehavioral impairment derived from khat use. METHODS: A systematic review was conducted to identify studies that assessed the effects of khat use on neurobehavioral functions. MedLine, Scopus, Cochrane, Web of Science and Open Grey literature were searched for relevant publications from inception to December 2020. Search terms included (a) khat and (b) several cognitive domains. References from relevant publications and grey literature were also reviewed to identify additional citations for inclusion. RESULTS: A total of 142 articles were reviewed, 14 of which met the inclusion criteria (nine human and five rodent studies). Available human studies suggest that long term khat use is associated with significant deficits in several cognitive domains, including learning, motor speed/coordination, set-shifting/response inhibition functions, cognitive flexibility, short term/working memory, and conflict resolution. In addition, rodent studies indicated daily administration of khat extract resulted in dose-related impairments in behavior such as motor hyperactivity and decreased cognition, mainly learning and memory. CONCLUSIONS: The findings presented in this review indicates that long-term khat use may be contributing to an impairment of neurobehavioral functions. However, gaps in literature were detected that future studies could potentially address to better understand the health consequences of khat use.


Subject(s)
Catha/adverse effects , Cognition Disorders/chemically induced , Hyperkinesis/chemically induced , Memory Disorders/chemically induced , Animals , Dose-Response Relationship, Drug , Humans , Negotiating
12.
Trop Anim Health Prod ; 53(2): 203, 2021 Mar 11.
Article in English | MEDLINE | ID: mdl-33694001

ABSTRACT

To evaluate the optimum age of straw addition to starter diet on growth of calves, 40 Holstein calves (36.7 ± 4.96 kg) were assigned at 3 days of age to 1 of 4 treatments in a completely randomized design. Dietary treatments (% of dry matter) were as follows: control starter without any wheat straw (WS) inclusion until weaning (WS0); 90% calf starter concentrate (CSC) + 10% chopped WS offered from day 3 of age to weaning (WS3); 90% CSC + 10% chopped WS offered from day 21 of age to weaning (WS21); and 90% CSC + 10% chopped WS offered from day 40 of age to weaning (WS40). After weaning at 60 days of age, all calves received the same diet until finished at day 72 of age. Solid feed intake was affected by treatments whereby either pre- or post-weaning starter intake was greater for calves fed WS (P < 0.01), and WS3 fed calves had lower starter intake compared to WS21 and WS40 (P < 0.01). Weaning weight was the greatest for WS21 treatment compared to other groups (P < 0.01), although all forage fed calves were heavier than WS0 (P < 0.01). Accordingly, average daily gain also showed a similar pattern (P < 0.01). Without any difference at post-weaning, pre-weaning glucose was lowest in WS0 calves (P < 0.01). There were no effects of treatment on number of days that calves experienced a negative health criterion. In conclusion, we concluded that WS inclusion at d 21 of age is recommendable based on weaning and final BW.


Subject(s)
Animal Feed , Animals, Newborn , Diet/veterinary , Animals , Body Weight , Cattle , Dietary Supplements , Female , Time Factors , Weaning
13.
J Stud Alcohol Drugs ; 82(1): 60-65, 2021 01.
Article in English | MEDLINE | ID: mdl-33573723

ABSTRACT

OBJECTIVE: Alcohol labeling raises consumers' awareness of a product's composition and the risks associated with alcohol consumption. We identified mandatory elements and health warnings in alcohol regulations in Nigeria and evaluated selected product labels on alcoholic beverages produced in Nigeria to determine their compliance with the requirements. METHOD: A descriptive case study was used. Labeling requirements were extracted from two alcohol regulations and one related document retrieved from the website of the National Agency for Food and Drug Administration and Control (NAFDAC). The information on the product labels of 59 selected beers and spirit drinks produced in Nigeria was assessed based on six mandatory elements: list of ingredients, allergens, nutritional information, percentage of alcohol by volume (ABV), "drink responsibly" statement, and age restrictions. Five health warnings were also assessed: standard drinks per container, drinking guidelines, link to an alcohol education website, a "drinking during pregnancy" logo/text, and drink driving logo/text. RESULTS: Different regulations exist for beer and spirit drinks in Nigeria. Health warnings are not mandatory on labels of alcoholic beverages. No single product label included all six mandatory elements. Four mandatory elements--list of ingredients, ABV, drink responsibly statement, and age restrictions--were present on 61% of the product labels examined. CONCLUSIONS: The alcohol labeling regulations in Nigeria fall short of the World Health Organization labeling recommendations. The alcohol industry does not fully comply with labeling requirements in Nigeria. Enhanced labeling inclusive of health warnings should be mandatory as a strategy to create awareness of alcohol-related risks while monitoring industry-labeling practices to ensure compliance.


Subject(s)
Alcohol Drinking/adverse effects , Alcoholic Beverages , Product Labeling/standards , Beer/legislation & jurisprudence , Ethanol/administration & dosage , Humans , Industry/legislation & jurisprudence , Nigeria , Policy , Risk
14.
Int J Drug Policy ; 93: 103113, 2021 07.
Article in English | MEDLINE | ID: mdl-33487528

ABSTRACT

BACKGROUND: Alcohol consumption and related harm increase rapidly from the age of 12 years. We evaluated whether alcohol screening and brief intervention is effective and cost-effective in delaying hazardous or harmful drinking amongst low-risk or abstaining adolescents attending Emergency Departments (EDs). METHODS: This ten-centre, three-arm, parallel-group, single-blind, pragmatic, individually randomised trial screened ED attenders aged between 14 and 17 years for alcohol consumption. We sampled at random one third of those scoring at most 2 on AUDIT-C who had access to the internet and, if aged under 16, were Gillick competent or had informed consent from parent or guardian. We randomised them between: screening only (control intervention); one session of face-to-face Personalised Feedback and Brief Advice (PFBA); and PFBA plus an electronic brief intervention (eBI) on smartphone or web. We conducted follow-up after six and 12 months. The principal outcomes were alcohol consumed over the 3 months before 12-month follow up, measured by AUDIT-C; and quality-adjusted life-years. FINDINGS: Between October 2014 and May 2015, we approached 5,016 eligible patients of whom 3,326 consented to be screened and participate in the trial; 2,571 of these were low-risk drinkers or abstainers, consuming an average 0.14 units per week. We randomised: 304 to screening only; 285 to PFBA; and 294 to PFBA and eBI. We found no significant difference between groups, notably in weekly alcohol consumption: those receiving screening only drank 0.10 units (95% confidence interval 0.05 to 0.18); PFBA 0.12 (0.06 to 0.21); PFBA and eBI 0.10 (0.05 to 0.19). INTERPRETATION: While drinking levels remained low in this population, this trial found no evidence that PFBA with or without eBI was more effective than screening alone in reducing or delaying alcohol consumption.


Subject(s)
Alcoholism , Crisis Intervention , Adolescent , Alcohol Drinking/prevention & control , Cost-Benefit Analysis , Emergency Service, Hospital , Humans , Single-Blind Method
15.
Front Neurosci ; 14: 667, 2020.
Article in English | MEDLINE | ID: mdl-32848531

ABSTRACT

In resource-constrained environments, such as low-power edge devices and smart sensors, deploying a fast, compact, and accurate intelligent system with minimum energy is indispensable. Embedding intelligence can be achieved using neural networks on neuromorphic hardware. Designing such networks would require determining several inherent hyperparameters. A key challenge is to find the optimum set of hyperparameters that might belong to the input/output encoding modules, the neural network itself, the application, or the underlying hardware. In this work, we present a hierarchical pseudo agent-based multi-objective Bayesian hyperparameter optimization framework (both software and hardware) that not only maximizes the performance of the network, but also minimizes the energy and area requirements of the corresponding neuromorphic hardware. We validate performance of our approach (in terms of accuracy and computation speed) on several control and classification applications on digital and mixed-signal (memristor-based) neural accelerators. We show that the optimum set of hyperparameters might drastically improve the performance of one application (i.e., 52-71% for Pole-Balance), while having minimum effect on another (i.e., 50-53% for RoboNav). In addition, we demonstrate resiliency of different input/output encoding, training neural network, or the underlying accelerator modules in a neuromorphic system to the changes of the hyperparameters.

16.
PLoS Genet ; 16(6): e1008830, 2020 06.
Article in English | MEDLINE | ID: mdl-32502192

ABSTRACT

Many post-transcriptional mechanisms operate via mRNA 3'UTRs to regulate protein expression, and such controls are crucial for development. We show that homozygous mutations in two zebrafish exon junction complex (EJC) core genes rbm8a and magoh leads to muscle disorganization, neural cell death, and motor neuron outgrowth defects, as well as dysregulation of mRNAs subjected to nonsense-mediated mRNA decay (NMD) due to translation termination ≥ 50 nts upstream of the last exon-exon junction. Intriguingly, we find that EJC-dependent NMD also regulates a subset of transcripts that contain 3'UTR introns (3'UI) < 50 nts downstream of a stop codon. Some transcripts containing such stop codon-proximal 3'UI are also NMD-sensitive in cultured human cells and mouse embryonic stem cells. We identify 167 genes that contain a conserved proximal 3'UI in zebrafish, mouse and humans. foxo3b is one such proximal 3'UI-containing gene that is upregulated in zebrafish EJC mutant embryos, at both mRNA and protein levels, and loss of foxo3b function in EJC mutant embryos significantly rescues motor axon growth defects. These data are consistent with EJC-dependent NMD regulating foxo3b mRNA to control protein expression during zebrafish development. Our work shows that the EJC is critical for normal zebrafish development and suggests that proximal 3'UIs may serve gene regulatory function in vertebrates.


Subject(s)
Forkhead Transcription Factors/metabolism , Gene Expression Regulation, Developmental , Neurogenesis/genetics , Nonsense Mediated mRNA Decay/genetics , RNA-Binding Proteins/metabolism , Zebrafish Proteins/metabolism , 3' Untranslated Regions/genetics , Animals , Animals, Genetically Modified , Axons/physiology , Codon, Terminator , Datasets as Topic , Embryo, Nonmammalian , Exons/genetics , Gene Regulatory Networks/genetics , Homozygote , Humans , Introns/genetics , Mice , Muscle, Skeletal/innervation , Mutagenesis , Mutation , Neuronal Outgrowth/genetics , Nuclear Proteins/genetics , Peptide Chain Termination, Translational , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , RNA-Seq , Sequence Alignment , Up-Regulation , Zebrafish/genetics , Zebrafish/growth & development
17.
RNA ; 26(9): 1216-1233, 2020 09.
Article in English | MEDLINE | ID: mdl-32467309

ABSTRACT

In eukaryotic cells, proteins that associate with RNA regulate its activity to control cellular function. To fully illuminate the basis of RNA function, it is essential to identify such RNA-associated proteins, their mode of action on RNA, and their preferred RNA targets and binding sites. By analyzing catalogs of human RNA-associated proteins defined by ultraviolet light (UV)-dependent and -independent approaches, we classify these proteins into two major groups: (i) the widely recognized RNA binding proteins (RBPs), which bind RNA directly and UV-crosslink efficiently to RNA, and (ii) a new group of RBP-associated factors (RAFs), which bind RNA indirectly via RBPs and UV-crosslink poorly to RNA. As the UV crosslinking and immunoprecipitation followed by sequencing (CLIP-seq) approach will be unsuitable to identify binding sites of RAFs, we show that formaldehyde crosslinking stabilizes RAFs within ribonucleoproteins to allow for their immunoprecipitation under stringent conditions. Using an RBP (CASC3) and an RAF (RNPS1) within the exon junction complex (EJC) as examples, we show that formaldehyde crosslinking combined with RNA immunoprecipitation in tandem followed by sequencing (xRIPiT-seq) far exceeds CLIP-seq to identify binding sites of RNPS1. xRIPiT-seq reveals that RNPS1 occupancy is increased on exons immediately upstream of strong recursively spliced exons, which depend on the EJC for their inclusion.


Subject(s)
Binding Sites/genetics , Protein Binding/genetics , RNA/chemistry , RNA/genetics , Ribonucleoproteins/genetics , Ribonucleoproteins/metabolism , Cell Line , Eukaryotic Cells/metabolism , Exons/genetics , HEK293 Cells , Humans , Immunoprecipitation/methods , RNA Splicing/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Transcriptome/genetics
18.
J Psychosom Res ; 132: 109964, 2020 05.
Article in English | MEDLINE | ID: mdl-32114179

ABSTRACT

OBJECTIVE: Social and occupational functioning are important for psychological health. However, quantitative research has suggested that these areas can be adversely affected by multiple chemical sensitivity (MCS). This systematic review therefore sought to explore what qualitative research has suggested about how people with MCS perceive it to affect their social and occupational functioning. METHOD: Journal articles were included if they were 1) peer reviewed 2) qualitative or mixed methods 3) published in English 4) reported qualitative findings relevant to the review. Studies were excluded if they were 1) descriptive only 2) primarily concerned with environmental intolerances other than chemicals or 3) focussed on specific populations such as veterans. Quality was assessed using the National Institute for Health and Care Excellence (NICE, 2018) qualitative quality criteria. However, quality was not used to determine eligibility for inclusion. Six databases (CINAHL, Medline, PsychArticles, PsychInfo, Scopus and Web of Science) were searched between the 24th of February 2019 and 2nd of March 2019. RESULTS: Having removed duplicates, database searches identified 388 potential articles. Thirteen of these articles were eligible for inclusion. Following review, no more articles were included from the reference lists of these studies. Meta-aggregation of the findings identified seven categories. These were synthesised into three themes; 'limited access', 'loss & anxiety' and 'seeking engagement'. CONCLUSIONS: The findings suggested that MCS limits some people's social and occupational functioning. The results warrant further research, and, the development of prevention and intervention strategies. Studies predominantly recruited United States and Canadian females and had several limitations.


Subject(s)
Mental Health/standards , Multiple Chemical Sensitivity/epidemiology , Occupational Health/standards , Aged , Female , Humans , Middle Aged , Qualitative Research
19.
PLoS One ; 14(6): e0217855, 2019.
Article in English | MEDLINE | ID: mdl-31188852

ABSTRACT

AIMS: To explore adolescents' experiences of consenting to, and participating in, alcohol intervention trials when attending for emergency care. METHODS: In-depth semi-structured interviews with 27 adolescents (16 males; aged 14-17 years (Mage = 15.7)) who had taken part in one of two linked brief alcohol intervention trials based in 10 accident and emergency departments in England. Interviews were transcribed verbatim and subject to thematic analysis. RESULTS: Research and intervention methods were generally found to be acceptable though confidentiality was important and parental presence could hinder truthful disclosures regarding alcohol use. Participants discussed the importance of being involved in research that was relevant to them and recognised alcohol consumption as a normative part of adolescence, highlighting the importance of having access to appropriate health information. Beyond this, they recognised the benefits and risks of trial participation for themselves and others with the majority showing a degree of altruism in considering longer term implications for others as well as themselves. CONCLUSIONS: Alcohol screening and intervention in emergency care is both acceptable and relevant to adolescents but acceptability is reliant on confidentiality being assured and may be inhibited by parental presence. TRIAL REGISTRATION: ISRCTN Number: 45300218.


Subject(s)
Alcohol Drinking/psychology , Early Medical Intervention/organization & administration , Patient Participation/psychology , Adolescent , Alcohol Drinking/prevention & control , Confidentiality , Counseling , Early Medical Intervention/ethics , Emergency Medical Services , Emergency Treatment/psychology , England , Female , Humans , Male , Practice Guidelines as Topic , Qualitative Research , Research Design , Surveys and Questionnaires
20.
J Public Health (Oxf) ; 41(1): e53-e60, 2019 03 01.
Article in English | MEDLINE | ID: mdl-29590416

ABSTRACT

OBJECTIVE: To estimate and compare the optimal cut-off score of Alcohol Use Disorders Identification Test (AUDIT) and AUDIT-C in identifying at-risk alcohol consumption, heavy episodic alcohol use, ICD-10 alcohol abuse and alcohol dependence in adolescents attending ED in England. DESIGN: Opportunistic cross-sectional survey. SETTING: 10 emergency departments across England. PARTICIPANTS: Adolescents (n = 5377) aged between their 10th and 18th birthday who attended emergency departments between December 2012 and May 2013. MEASURES: Scores on the AUDIT and AUDIT-C. At-risk alcohol consumption and monthly episodic alcohol consumption in the past 3 months were derived using the time-line follow back method. Alcohol abuse and alcohol dependence was assessed in accordance with ICD-10 criteria using the MINI-KID. FINDINGS: AUDIT-C with a score of 3 was more effective for at-risk alcohol use (AUC 0.81; sensitivity 87%, specificity 97%), heavy episodic use (0.84; 76%, 98%) and alcohol abuse (0.98; 91%, 90%). AUDIT with a score of 7 was more effective in identifying alcohol dependence (0.92; 96%, 94%). CONCLUSIONS: The 3-item AUDIT-C is more effective than AUDIT in screening adolescents for at-risk alcohol use, heavy episodic alcohol use and alcohol abuse. AUDIT is more effective than AUDIT-C for the identification of alcohol dependence.


Subject(s)
Alcoholism/diagnosis , Psychiatric Status Rating Scales/standards , Adolescent , Alcoholism/epidemiology , Child , Cross-Sectional Studies , Emergency Service, Hospital , England/epidemiology , Female , Humans , Male , Sensitivity and Specificity
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