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1.
Dialogues Health ; 4: 100161, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38516218

RESUMEN

This cross-sectional, descriptive study conducted on in June 2022 reviewed 100 TikTok videos using the hashtag #africansinukriane that depicted discrimination against Black people attempting to flee Ukraine at the onset of the war in February 2022. Two of the 16 themes were significant and present in over 50% of videos: raising awareness (67%) and racial discrimination (64%). Videos with elements of physical contact (N = 16, 76.2%), violence (N = 12, 75%), and dehumanization (N = 11, 68.8%) had higher shares than overall media shares. Less than 10% of the videos included dark humor (8%), sharing helpful resources (7%), and appreciation of countries that offered support (5%). Results indicate that videos that include raising awareness (p = .02), racial discrimination (p = .001), on-scene clips or war scenes (p = .007), physical contact (p = .006), and denied entry (p = .022). Their estimated differences in locations indicate that all of these themes were related to higher median shares of the videos. This study supports that TikTok is a place where marginalized groups can raise awareness about injustice and create counternarratives. This study exemplifies international anti-blackness with implications for health marketing and communication, human rights efforts, refugee health, and targeted mental health and policy support for those displaced by war.

2.
Sci Rep ; 14(1): 1203, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216609

RESUMEN

In this paper we present a mathematical modelling framework for chiral phenomena associated with rotational motions, highlighting the combination of gyroscopic action with gravity. We discuss new ideas of controlling gravity-induced waves by a cluster of gyroscopic spinners. For an elementary gravitational spinner, the transient oscillations are accompanied by a full classification and examples, linked to natural phenomena observed in planetary motion. Applications are presented in the theory of chiral metamaterials, and of the dynamic response of such materials to external loads.

3.
J Affect Disord ; 346: 21-27, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-37940050

RESUMEN

BACKGROUND: Women with bipolar disorder (BD) are at high risk of postpartum psychosis (PP). The factors that increase risk of PP among women with BD are not fully understood. Here, we examine whether sleep disruption in the perinatal period (poor sleep quality in late pregnancy and sleep deprivation related to childbirth) is associated with PP in a longitudinal study of pregnant women with BD. METHODS: Participants were 76 pregnant women with lifetime DSM-5 bipolar I disorder or schizoaffective-BD, followed from week 12 of pregnancy to 12 weeks postpartum. Demographics and lifetime psychopathology were assessed at baseline via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry). Psychopathology and sleep disruption within the current perinatal period were assessed in the third trimester and at 12 weeks postpartum. Data were supplemented by clinician questionnaires and case-note review. RESULTS: After controlling for prophylactic use of mood stabilising medication, the loss of at least one complete night of sleep across labour/delivery was associated with five times the odds of experiencing PP compared to no or less than one night of sleep loss across labour/delivery (OR 5.19, 95 % CI 1.45-18.54; p = 0.011). Sleep quality in late pregnancy was not associated with PP, and perinatal sleep disruption was not associated with postpartum depression. LIMITATIONS: Lack of objective measures of sleep factors. CONCLUSIONS: In the context of other aetiological factors, severe sleep loss associated with childbirth/the immediate postpartum may act as a final trigger of PP. These findings could have important clinical implications for risk prediction and prevention of PP.


Asunto(s)
Trastorno Bipolar , Depresión Posparto , Trastornos Psicóticos , Trastornos Puerperales , Embarazo , Femenino , Humanos , Trastorno Bipolar/epidemiología , Estudios Longitudinales , Parto , Trastornos Psicóticos/epidemiología , Trastornos Puerperales/epidemiología , Periodo Posparto , Sueño , Reino Unido/epidemiología
4.
Soc Sci Med ; 331: 116098, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37480697

RESUMEN

This paper uses precarity as a framework to understand the vulnerabilities experienced by those living with or caring for someone living with dementia. Drawing on qualitative interview data from the Improving the Experience of Dementia and Enhancing Active Life (IDEAL) programme, we attend to our participants' reflections on how they manage the condition and the wider circumstances in which this occurs. To interrogate the utility of precarity, we focus on our participants' descriptions of needs and challenges and set these alongside both the wider contexts in which they seek or offer care (formal and informal) and the sets of values attributed to different ways of living with dementia. Building on the work of Portacolone, our analysis identified four interconnected themes: uncertainty; experiences of support and services; independence and personhood; and cumulative pressures and concerns. We develop this analysis by reviewing how our themes reflect, extend, or depart from previously identified markers of precarity and consider the specific ways in which these markers shape the lives of those living with dementia.


Asunto(s)
Demencia , Humanos , Demencia/terapia , Incertidumbre , Cuidadores , Investigación Cualitativa
5.
Psychol Med ; 53(8): 3345-3354, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35074035

RESUMEN

BACKGROUND: Sleep disturbances are important symptoms to monitor in people with bipolar disorder (BD) but the precise longitudinal relationships between sleep and mood remain unclear. We aimed to examine associations between stable and dynamic aspects of sleep and mood in people with BD, and assess individual differences in the strength of these associations. METHODS: Participants (N = 649) with BD-I (N = 400) and BD-II (N = 249) provided weekly self-reports of insomnia, depression and (hypo)mania symptoms using the True Colours online monitoring tool for 21 months. Dynamic structural equation models were used to examine the interplay between weekly reports of insomnia and mood. The effects of clinical and demographic characteristics on associations were also assessed. RESULTS: Increased variability in insomnia symptoms was associated with increased mood variability. In the sample as a whole, we found strong evidence of bidirectional relationships between insomnia and depressive symptoms but only weak support for bidirectional relationships between insomnia and (hypo)manic symptoms. We found substantial variability between participants in the strength of prospective associations between insomnia and mood, which depended on age, gender, bipolar subtype, and a history of rapid cycling. CONCLUSIONS: Our results highlight the importance of monitoring sleep in people with BD. However, researchers and clinicians investigating the association between sleep and mood should consider subgroup differences in this relationship. Advances in digital technology mean that intensive longitudinal data on sleep and mood are becoming increasingly available. Novel methods to analyse these data present an exciting opportunity for furthering our understanding of BD.


Asunto(s)
Trastorno Bipolar , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Trastorno Bipolar/complicaciones , Estudios Longitudinales , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Afecto , Sueño
6.
Philos Trans A Math Phys Eng Sci ; 380(2231): 20210385, 2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-35858077

RESUMEN

The analysis of wave patterns in a structure which possesses periodicity in the spatial and temporal dimensions is presented. The topic of imperfect chiral interfaces is also considered. Although causality is fundamental for physical processes, natural wave phenomena can be observed when a wave is split at a temporal interface. A wave split at a spatial interface is a more common occurrence; however, when the coefficients of the governing equations are time-dependent, the temporal interface becomes important. Here, the associated frontal waves are studied, and regimes are analysed where the growth of the solution in time is found. Imperfect interfaces, across which the displacements are discontinuous, are also considered in the vector case of chiral elastic systems. Analytical study and asymptotic approximations are supplied with illustrative numerical examples. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)'.

7.
Heart Lung ; 55: 89-101, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35504241

RESUMEN

BACKGROUND: Around 36,000 cardiac operations are undertaken in the United Kingdom annually, with most procedures undertaken via median sternotomy. Wound complications occur in up to 8% of operations, with an associated mortality rate of around 47% in late or undetected cases. OBJECTIVE: To undertake a systematised literature review to identify pre-operative, peri-operative and post-operative risk factors associated with sternal wound complications. METHODS: Healthcare databases were searched for articles written in the English language and published between 2013 and 2021. Inclusion criteria were quantitative studies involving patients undergoing median sternotomy for cardiac surgery; sternal complications and risk factors. RESULTS: 1360 papers were identified, with 25 included in this review. Patient-related factors included: high BMI; diabetes; comorbidities; gender; age; presenting for surgery in a critical state; predictive risk scores; vascular disease; severe anaemia; medication such as steroids or α-blockers; and previous sternotomy. Peri-operative risk increased with specific types and combinations of surgical procedures. Sternal reopening was also associated with increased risk of sternal wound infection. Post-operative risk factors included a complicated recovery; the need for blood transfusions; respiratory complications; renal failure; non-diabetic hyperglycaemia; sternal asymmetry and sepsis. CONCLUSION: Pre, peri and post-operative risk factors increase the risk of sternal wound complications in cardiac surgery. Generic risk assessment tools are primarily designed to provide mortality risk scores, with their ability to predict risk of wound infection questionable. Tools that incorporate factors throughout the operative journey are required to identify patients at risk of surgical wound infection.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Esternotomía , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Humanos , Estudios Retrospectivos , Factores de Riesgo , Esternotomía/efectos adversos , Esternotomía/métodos , Esternón/cirugía , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/cirugía
8.
People Nat (Hoboken) ; 4(1): 32-43, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35450207

RESUMEN

1. Many infectious pathogens spend a significant portion of their life cycles in the environment or in animal hosts, where ecological interactions with natural enemies may influence pathogen transmission to people. Yet, our understanding of natural enemy opportunities for human disease control is lacking, despite widespread uptake and success of natural enemy solutions for pest and parasite management in agriculture. 2. Here we explore three reasons why conserving, restoring, or augmenting specific natural enemies in the environment could offer a promising complement to conventional clinical strategies to fight environmentally mediated pathogens and parasites. (1) Natural enemies of human infections abound in nature, largely understudied and undiscovered. (2) Natural enemy solutions could provide ecological options for infectious disease control where conventional interventions are lacking. And, (3) Many natural enemy solutions could provide important co-benefits for conservation and human well-being. 3. We illustrate these three arguments with a broad set of examples whereby natural enemies of human infections have been used or proposed to curb human disease burden, with some clear successes. However, the evidence base for most proposed solutions is sparse, and many opportunities likely remain undiscovered, highlighting opportunities for future research.

9.
Heart Lung ; 52: 16-21, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34823051

RESUMEN

BACKGROUND: During the SARS-COV-2 (COVID-19) pandemic efforts to reduce virus transmission resulted in non-emergency patients being deterred from seeking help. The number of patients presenting with acute cardiac conditions reduced, significantly OBJECTIVES: To explore the decision-making process, and influential factors in that process, of patients and their family during an acute cardiac event. METHODS: A qualitative research design was employed using purposive sampling of patients who experienced an acute cardiac event during the social containment mandates. Semi-structured interviews were conducted, with thematic analysis of interview transcripts. RESULTS: Twenty-five participants were recruited from three UK hospitals. Themes identified were reliance on informal support network, lack of awareness of cardiac symptoms leading to delayed help-seeking, and an indirect COVID-19 effect (e.g. avoiding treatment). CONCLUSIONS: These results highlight the need for informed public health messages, targeting patients and their support networks, that allow those in need of treatment to access care.


Asunto(s)
COVID-19 , Enfermedades Cardiovasculares , Toma de Decisiones , Aceptación de la Atención de Salud , Enfermedad Aguda , COVID-19/epidemiología , Enfermedades Cardiovasculares/terapia , Hospitales , Humanos , Pandemias , Aceptación de la Atención de Salud/psicología , Investigación Cualitativa , Reino Unido/epidemiología
10.
Procedia Manuf ; 55: 571-579, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34746336

RESUMEN

This paper examines a novel way of training Lean Manufacturing Systems and Tools utilising an Industry 4.0 methodology during the SARS-COVID2 Pandemic of 2020. Currently, it is challenging for the Integrated Production Systems Team, responsible for carrying out training on the Lean principles, to undertake the training safely and without the risk of possible disease transmission. This is due to the usual close quarters training carried out in the Engine Manufacturing Centre. Schools, Colleges and Universities have adapted and utilised technology and moved to an Industry 4.0 digitalised approach to learning and development. This is therefore an opportunity for manufacturing to follow suit and create digitised solutions to training and development opportunities, to ensure that the employees within the manufacturing facility have adequate knowledge on the Lean principles.

11.
Perioper Med (Lond) ; 10(1): 20, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34127080

RESUMEN

BACKGROUND: Group education is increasing in popularity as a means of preparing patients for surgery. In recent years, these 'surgery schools' have evolved from primarily informing patients of what to expect before and after surgery, to providing support and encouragement for patients to 'prehabilitate' prior to surgery, through improving physical fitness, nutrition and emotional wellbeing. METHOD: A survey aimed at clinicians delivering surgery schools was employed to capture a national overview of activity to establish research and practice priorities in this area. The survey was circulated online via the Enhanced Recovery after Surgery UK Society and the Centre for Perioperative Care mailing lists as well as social media. RESULTS: There were 80 responses describing 28 active and 4 planned surgery schools across the UK and Ireland. Schools were designed and delivered by multidisciplinary teams, contained broadly similar content and were well attended. Most were funded by the National Health Service. The majority included aspects of prehabilitation most commonly the importance of physical fitness. Seventy five percent of teams collected patient outcome data, but less than half collected data to establish the clinical effectiveness of the school. Few describe explicit inclusion of evidence-based behavior change techniques, but collaboration and partnerships with community teams, gyms and local charities were considered important in supporting patients to make changes in health behaviors prior to surgery. CONCLUSION: It is recommended that teams work with patients when designing surgery schools and use evidence-based behavior change frameworks and techniques to inform their content. There is a need for high-quality research studies to determine the clinical effectiveness of this type of education intervention.

12.
Anaesthesia ; 76(9): 1207-1211, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33538015

RESUMEN

Group pre-operative education has usually been limited to conditioning expectations and providing education. Prehabilitation has highlighted modifiable lifestyle factors that are amenable to change and may improve clinical outcomes. We instituted a pre-operative 'Fit-4-Surgery School' for patients scheduled for major surgery, to educate and promote healthy behaviour. We evaluated patients' views having attended the school, and after surgery we asked how it had changed their behaviour with a lifestyle questionnaire. The school was launched in May 2016 and was attended by 586/1017 (58%) of invited patients. Patients who did not attend: lived further away, median (IQR [range]) 8 (4-19 [0-123]) miles vs. 5 (3-14 [0-172]) miles, p < 0.001; and were more deprived, Index of Multiple Deprivation Rank decile median (IQR [range]), 6 (4-8 [1-10]) vs. 7 (4-9 [1-10]), p = 0.04. Of the 492/586 (84%) participants who completed an evaluation questionnaire, 462 (94%) would recommend the school to a friend having surgery and 296 (60%) planned lifestyle changes. After surgery, 232/586 (40%) completed a behavioural change questionnaire, 106 (46%) of whom reported changing at least one lifestyle factor, most commonly by increasing exercise. The pre-operative school was acceptable to patients.


Asunto(s)
Procedimientos Quirúrgicos Electivos , Educación en Salud/métodos , Promoción de la Salud/métodos , Cuidados Preoperatorios/métodos , Evaluación de Programas y Proyectos de Salud/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto Joven
13.
Philos Trans A Math Phys Eng Sci ; 378(2162): 20190350, 2020 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-31760898

RESUMEN

In this paper, we demonstrate a new approach to control flexural elastic waves in a structured chiral plate. The main focus is on creating one-way interfacial wave propagation at a given frequency by employing double resonators in a doubly periodic flexural system. The resonators consist of two beams attached to gyroscopic spinners, which act to couple flexural and rotational deformations, hence inducing chirality in the system. We show that this elastic structure supports one-way flexural waves, localized at an interface separating two sub-domains with gyroscopes spinning in opposite directions, but with otherwise identical properties. We demonstrate that a special feature of double resonators is in the directional control of wave propagation by varying the value of the gyricity, while keeping the frequency of the external time-harmonic excitation fixed. Conversely, for the same value of gyricity, the direction of wave propagation can be reversed by tuning the frequency of the external excitation. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 2)'.

14.
BMC Psychiatry ; 19(1): 395, 2019 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-31830938

RESUMEN

BACKGROUND: Bipolar disorder has been associated with several personality traits, cognitive styles and affective temperaments. Women who have bipolar disorder are at increased risk of experiencing postpartum psychosis, however little research has investigated these traits and temperaments in relation to postpartum psychosis. The aim of this study is to establish whether aspects of personality, cognitive style and affective temperament that have been associated with bipolar disorder also confer vulnerability to postpartum psychosis over and above their known association with bipolar disorder. METHODS: Personality traits (neuroticism, extraversion, schizotypy and impulsivity), cognitive styles (low self-esteem and dysfunctional attitudes) and affective temperaments (including cyclothymic and depressive temperaments) were compared between two groups of parous women with DSM-IV bipolar I disorder: i) 284 with a lifetime history of postpartum psychosis within 6 weeks of delivery (PP group), ii) 268 without any history of mood episodes with onset during pregnancy or within 6 months of delivery (no perinatal mood episode, No PME group). RESULTS: After controlling for current mood state, and key demographic, clinical and pregnancy-related variables, there were no statistically significant differences between the PP and No PME groups on any of the personality, cognitive style or affective temperament measures. CONCLUSIONS: Personality traits, cognitive styles and affective temperaments previously shown to be associated with bipolar disorder in general were not specifically associated with the occurrence of postpartum psychosis. These factors may not be relevant for predicting risk of postpartum psychosis in women with bipolar disorder.


Asunto(s)
Trastorno Bipolar/psicología , Cognición , Trastornos del Humor/psicología , Personalidad , Periodo Posparto/psicología , Trastornos Psicóticos/psicología , Adulto , Anciano , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/epidemiología , Cognición/fisiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Trastornos del Humor/epidemiología , Personalidad/fisiología , Inventario de Personalidad , Periodo Posparto/fisiología , Embarazo , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Factores de Riesgo , Temperamento/fisiología , Adulto Joven
15.
Philos Trans A Math Phys Eng Sci ; 377(2156): 20190154, 2019 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-31474205

RESUMEN

In this paper, we study the spectral properties of a finite system of flexural elements connected by gyroscopic spinners. We determine how the eigenfrequencies and eigenmodes of the system depend on the gyricity of the spinners. In addition, we present a transient numerical simulation that shows how a gyroscopic spinner attached to the end of a hinged beam can be used as a 'stabilizer', reducing the displacements of the beam. We also discuss the dispersive properties of an infinite periodic system of beams with gyroscopic spinners at the junctions. In particular, we investigate how the band-gaps of the structure can be tuned by varying the gyricity of the spinners. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 1)'.

16.
BMC Public Health ; 19(1): 240, 2019 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-30819125

RESUMEN

BACKGROUND: Evidence suggests that the use of alcohol among older adults (defined as those aged 50+) has increased in recent years, with people aged 55-64 now more likely to exceed the recommended weekly guidelines than any other age group. METHODS/ DESIGN: This is a quasi-experimental study with a before-after design. A postal questionnaire will be sent to 76,000 people aged 50 and over registered with a general practice in five different 'demonstration' (intervention) and control areas in the UK. Multiple interventions will then be delivered in demonstration areas across the UK. At the end of the programme, a postal questionnaire will be sent to the same individuals who completed it pre-programme to establish if there has been a reduction in alcohol use, at-risk drinking and alcohol related problems. Qualitative interviews with clients and staff will explore how the interventions were experienced; how they may work to bring about change and to identify areas for practice improvements. DISCUSSION: This study protocol describes a multi-level, multi-intervention prevention-to-treatment programme which aims to reduce alcohol-related harm in people aged 50 and over.


Asunto(s)
Consumo de Bebidas Alcohólicas/prevención & control , Consumo de Bebidas Alcohólicas/psicología , Envejecimiento Saludable/fisiología , Envejecimiento Saludable/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
17.
Proc Math Phys Eng Sci ; 475(2232): 20190313, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31892832

RESUMEN

This paper addresses fundamental questions arising in the theory of Bloch-Floquet waves in chiral elastic lattice systems. This area has received a significant attention in the context of 'topologically protected' waveforms. Although practical applications of chiral elastic lattices are widely appreciated, especially in problems of controlling low-frequency vibrations, wave polarization and filtering, the fundamental questions of the relationship of these lattices to classical waveforms associated with longitudinal and shear waves retain a substantial scope for further development. The notion of chirality is introduced into the systematic analysis of dispersive elastic waves in a doubly-periodic lattice. Important quantitative characteristics of the dynamic response of the lattice, such as lattice flux and lattice circulation, are used in the analysis along with the novel concept of 'vortex waveforms' that characterize the dynamic response of the chiral system. We note that the continuum concepts of pressure and shear waves do not apply for waves in a lattice, especially in the case when the wavelength is comparable with the size of the elementary cell of the periodic structure. Special critical regimes are highlighted when vortex waveforms become dominant. Analytical findings are accompanied by illustrative numerical simulations.

18.
Proc Math Phys Eng Sci ; 474(2215): 20180132, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30100810

RESUMEN

We demonstrate a new method of achieving topologically protected states in an elastic hexagonal system of trusses by attaching gyroscopic spinners, which bring chirality to the system. Dispersive features of this medium are investigated in detail, and it is shown that one can manipulate the locations of stop-bands and Dirac points by tuning the parameters of the spinners. We show that, in the proximity of such points, uni-directional interfacial waveforms can be created in an inhomogeneous lattice and the direction of such waveforms can be controlled. The effect of inserting additional soft internal links into the system, which is thus transformed into a heterogeneous triangular lattice, is also investigated, as the hexagonal lattice represents the limit case of the heterogeneous triangular lattice with soft links. This work introduces a new perspective in the design of periodic media possessing non-trivial topological features.

19.
Proc Math Phys Eng Sci ; 474(2211): 20170590, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29662337

RESUMEN

The paper includes novel results for the scattering and localization of a time-harmonic flexural wave by a semi-infinite herringbone waveguide of rigid pins embedded within an elastic Kirchhoff plate. The analytical model takes into account the orientation and spacing of the constituent parts of the herringbone system, and incorporates dipole approximations for the case of closely spaced pins. Illustrative examples are provided, together with the predictive theoretical analysis of the localized waveforms.

20.
Mol Psychiatry ; 23(9): 1900-1910, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-28848234

RESUMEN

Alcohol use disorder (AUD) is a common and chronic disorder with substantial effects on personal and public health. The underlying pathophysiology is poorly understood but strong evidence suggests significant roles of both genetic and epigenetic components. Given that alcohol affects many organ systems, we performed a cross-tissue and cross-phenotypic analysis of genome-wide methylomic variation in AUD using samples from 3 discovery, 4 replication, and 2 translational cohorts. We identified a differentially methylated region in the promoter of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes. Biological validation showed that PCSK9 promoter methylation is conserved across tissues and positively correlated with expression. Replication in AUD datasets confirmed PCSK9 hypomethylation and a translational mouse model of AUD showed that alcohol exposure leads to PCSK9 downregulation. PCSK9 is primarily expressed in the liver and regulates low-density lipoprotein cholesterol (LDL-C). Our finding of alcohol-induced epigenetic regulation of PCSK9 represents one of the underlying mechanisms between the well-known effects of alcohol on lipid metabolism and cardiovascular risk, with light alcohol use generally being protective while chronic heavy use has detrimental health outcomes.


Asunto(s)
Alcoholismo/genética , Proproteína Convertasa 9/efectos de los fármacos , Proproteína Convertasa 9/genética , Adulto , Alcoholismo/fisiopatología , Animales , LDL-Colesterol/metabolismo , Metilación de ADN/genética , Epigénesis Genética/genética , Epigenómica/métodos , Etanol/efectos adversos , Etanol/metabolismo , Femenino , Regulación de la Expresión Génica/genética , Humanos , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Masculino , Ratones , Fenotipo , Regiones Promotoras Genéticas/genética , Proproteína Convertasa 9/fisiología , Ratas , Ratas Wistar
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