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1.
Gut ; 73(6): 897-909, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38553042

RESUMEN

Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett's oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett's oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett's oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett's-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett's oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment.


Asunto(s)
Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Esófago de Barrett/terapia , Esófago de Barrett/patología , Esófago de Barrett/diagnóstico , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/etiología , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adenocarcinoma/diagnóstico , Esofagoscopía/métodos , Estadificación de Neoplasias , Progresión de la Enfermedad , Factores de Riesgo , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Lesiones Precancerosas/diagnóstico
2.
Biochem Soc Trans ; 52(1): 65-74, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38385583

RESUMEN

Oxidative stress, an imbalance between pro-oxidant and antioxidant status, favouring the pro-oxidant state is a result of increased production of reactive oxygen species (ROS) or inadequate antioxidant protection. ROS are produced through several mechanisms in cells including during mitochondrial oxidative phosphorylation. Increased mitochondrial-derived ROS are associated with mitochondrial dysfunction, an early event in age-related diseases such as Alzheimer's diseases (ADs) and in metabolic disorders including diabetes. AD post-mortem investigations of affected brain regions have shown the accumulation of oxidative damage to macromolecules, and oxidative stress has been considered an important contributor to disease pathology. An increase in oxidative stress, which leads to increased levels of superoxide, hydrogen peroxide and other ROS in a potentially vicious cycle is both causative and a consequence of mitochondrial dysfunction. Mitochondrial dysfunction may be ameliorated by molecules with antioxidant capacities that accumulate in mitochondria such as carotenoids. However, the role of carotenoids in mitigating mitochondrial dysfunction is not fully understood. A better understanding of the role of antioxidants in mitochondrial function is a promising lead towards the development of novel and effective treatment strategies for age-related diseases. This review evaluates and summarises some of the latest developments and insights into the effects of carotenoids on mitochondrial dysfunction with a focus on the antioxidant properties of carotenoids. The mitochondria-protective role of carotenoids may be key in therapeutic strategies and targeting the mitochondria ROS is emerging in drug development for age-related diseases.


Asunto(s)
Antioxidantes , Enfermedades Mitocondriales , Humanos , Antioxidantes/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Carotenoides/metabolismo , Carotenoides/farmacología , Estrés Oxidativo , Enfermedades Mitocondriales/metabolismo
3.
Clin Child Psychol Psychiatry ; 29(2): 661-673, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37773596

RESUMEN

BACKGROUND: Existing literature implies there may be gaps in post-treatment support for young people with cancer. This service evaluation explored the needs and experiences of young people when ending cancer treatment in a UK children's hospital to inform service provisions. METHODS: Semi-structured interviews were conducted with nine young people, aged 13-18 years, who had finished active cancer treatment and were receiving follow-up care. The data was analysed using thematic analysis. RESULTS: Four main themes were developed: being in the dark (i.e. limited awareness of what happens when treatment ends); separation from the hospital (i.e. the loss of valued support from staff); consequences of cancer (i.e. managing ongoing psychological and physical effects); and getting back to normal life (i.e. shifting from hospital to everyday life). CONCLUSIONS: Recommendations for improving clinical practice were made. Greater preparedness for ending treatment could be achieved by clearly setting out ongoing care arrangements, providing resource packs, having opportunities to mark the end of treatment, and offering peer support. To identify specific post-treatment needs, there should be an end of treatment multidisciplinary review and space for young people to share how they are feeling in follow-up medical appointments.


Asunto(s)
Neoplasias , Aceptación de la Atención de Salud , Niño , Humanos , Adolescente , Investigación Cualitativa , Neoplasias/terapia , Neoplasias/psicología
4.
Psychol Psychother ; 97(1): 157-172, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37811853

RESUMEN

OBJECTIVE: The aim of this study was to explore the relationship between affective disturbances and aberrant salience in the context of childhood trauma, attachment, and mentalization in an analogue study. METHODS: Using a cross-sectional design, an online community sample completed self-report measures of key variables. Structural equation modelling was used to test childhood trauma's influence on aberrant salience via a set of intermediate risk factors (depression, negative schizotypy, and insecure attachment). These intermediate risk factors were assumed to lead to the proximal risk factors of aberrant salience (i.e., disorganized schizotypy and disorganized attachment) depending on the vulnerability of mentalizing capacity to elevated stress. RESULTS: The sample (N = 1263) was 78% female and aged between 18 and 35 years. The tested models closely fitted the observed data, revealing significant pathways from childhood trauma to aberrant salience via the hypothesized pathways. The direct effect of childhood trauma on aberrant salience was significant. CONCLUSION: Findings suggest that the pathway to aberrant salience may be characterized by disorganization of self-state and intersubjectivity as a function of diminishment in mentalizing ability. This may relate to changes in attachment organization and socio-cognitive capacity, which could constitute possible risk factors signalling development of aberrant salience.


Asunto(s)
Experiencias Adversas de la Infancia , Mentalización , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Masculino , Estudios Transversales , Factores de Riesgo , Autoinforme
5.
Retina ; 44(5): 837-843, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38109714

RESUMEN

PURPOSE: To analyze the choroidal parameters of patients with chronic central serous chorioretinopathy (cCSC) and the association with central serous chorioretinopathy susceptibility genes. METHODS: The choroidal vascular index (CVI) was obtained by binarizing spectral domain optical coherence tomography enhanced depth images of patients with cCSC and healthy age-matched controls. Patients with cCSC were genotyped for three central serous chorioretinopathy susceptibility single-nucleotide polymorphisms: rs4844392 ( mir-29b-2/CD46 ), rs1329428 ( CFH ), and rs2379120 (upstream GATA5 ). RESULTS: One hundred three eyes with cCSC and 53 control eyes were included. There was a significant increase in the subfoveal choroidal area in both the affected (2.4 ± 0.6 mm 2 ) and fellow (2.2 ± 0.6 mm 2 ) eyes of patients with cCSC compared with controls (1.8 ± 0.5 mm 2 , P < 0.0001 and P < 0.0001). The CVI was reduced in patients with cCSC 63.5% ± 3.1% compared with controls 65.4% ± 2.3% ( P < 0.001) and also in the affected compared with the fellow eyes 64.6% ± 2.9% ( P < 0.01). There was a significant association between CVI in the cCSC group and presence of the risk single-nucleotide polymorphisms rs2379120 at GATA5 ( P < 0.01). CONCLUSION: The relative reduction of CVI in patients with cCSC may suggest a persistence of vessel hyperpermeability over dilation in chronic disease. GATA5 is associated with CVI in patients with cCSC and therefore may have a role in choroidal vascularity.


Asunto(s)
Coriorretinopatía Serosa Central , Coroides , Angiografía con Fluoresceína , Polimorfismo de Nucleótido Simple , Tomografía de Coherencia Óptica , Humanos , Coriorretinopatía Serosa Central/genética , Coriorretinopatía Serosa Central/diagnóstico , Masculino , Femenino , Tomografía de Coherencia Óptica/métodos , Persona de Mediana Edad , Coroides/irrigación sanguínea , Enfermedad Crónica , Angiografía con Fluoresceína/métodos , Adulto , Genotipo , Anciano , Factor H de Complemento/genética , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Predisposición Genética a la Enfermedad
6.
Clin Child Psychol Psychiatry ; : 13591045231216134, 2023 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-38041611

RESUMEN

BACKGROUND: Almost a quarter of children and young people (CYP) in England have a long-term health condition (LTC), which increases the risk of developing mental health difficulties. There is a lack of understanding regarding the routine provision and efficacy of mental health interventions for CYP with LTCs within Children and Young People's Mental Health Services (CYPMHS). METHODS: This study analysed national service-reported data in England from two secondary datasets. Data were submitted by services between 2011 and 2019. We evaluated data on the presence or absence of a serious physical health or neurological issue, and which interventions were offered. RESULTS: A total of 789 CYP had serious physical health issues and 635 had neurological issues. The most common interventions delivered to CYP in either group have some evidence in the literature. Most CYP showed improvements across a range of outcomes. CONCLUSIONS: This study found that prevalence rates and psychological intervention and outcome data were widely under-reported across both datasets, posing questions about their utility for this population. Such data would benefit from triangulation with data from other sources to understand pathways of care for these young people and the extent to which clinical datasets underreport the number of CYP with LTCs.


Almost a quarter of children and young people (CYP) in England have a long-term health condition (LTC), such as asthma, diabetes, or epilepsy. We know that these young people are at increased risk of developing mental health difficulties. It is important these young people are able to access safe and effective treatments for their mental health. Therefore, they are sometimes referred to Children and Young People's Mental Health Services (CYPMHS) for appropriate treatment. However, at the moment, not much is known about the types of mental health support these services offer to children with co-existing physical health needs, or if this support is effective. The aim of this study was to try and find this out. We used data that had already been collected from mental health services across England. We looked at specific parts of this data that gave us information about the type of mental health treatments delivered to children with a long-term health condition. We separated long-term health conditions into two categories: physical health, such as diabetes or asthma; and neurological, such as epilepsy. In the sample we looked at, a range of mental health treatments were delivered to young people in both groups. Encouragingly, many of the young people's mental health improved. However, a lot of information we would hope to find was not available in the datasets. Also, the number of children with a long-term health condition was much lower than we expected. This might have been for a number of reasons, which we recommend other future research tries to find out. Going forward, it is important to think about how to make sure that accurate information about these children is collected from mental health services. This will help ensure that the right decisions are made for the care of young people with long-term health conditions.

7.
Strabismus ; 31(3): 220-235, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37870065

RESUMEN

PURPOSE/BACKGROUND: Visual acuity (VA) screening in children primarily detects low VA and amblyopia between 3 and 6 years of age. Photoscreening is a low-cost, lower-expertise alternative which can be carried out on younger children and looks instead for refractive amblyopia risk factors so that early glasses may prevent or mitigate the conditions. The long-term benefits and costs of providing many children with glasses in an attempt to avoid development of amblyopia for some of them needs clarification. This paper presents a framework for modeling potential post-referral costs of different screening models once referred children reach specialist services. METHODS: The EUSCREEN Screening Cost-Effectiveness Model was used together with published literature to estimate referral rates and case mix of referrals from different screening modalities (photoscreening and VA screening at 2, 3-4 years and 4-5 years). UK 2019-20 published National Health Service (NHS) costings were used across all scenarios to model the comparative post-referral costs to the point of discharge from specialist services. Potential costs were compared between a) orthoptist, b) state funded ophthalmologist and c) private ophthalmologist care. RESULTS: Earlier VA screening and photoscreening yield higher numbers of referrals because of lower sensitivity and specificity for disease, and a different case mix, compared to later VA screening. Photoscreening referrals are a mixture of reduced VA caused by amblyopia and refractive error, and children with amblyopia risk factors, most of which are treated with glasses. Costs relate mainly to the secondary care providers and the number of visits per child. Treatment by an ophthalmologist of a referral at 2 years of age can be more than x10 more expensive than an orthoptist service receiving referrals at 5 years, but outcomes can still be good from referrals aged 5. CONCLUSIONS: All children should be screened for amblyopia and low vision before the age of 6. Very early detection of amblyopia refractive risk factors may prevent or mitigate amblyopia for some affected children, but population-level outcomes from a single high-quality VA screening at 4-5 years can also be very good. Total patient-journey costs incurred by earlier detection and treatment are much higher than if screening is carried out later because younger children need more professional input before discharge, so early screening is less cost-effective in the long term. Population coverage, local healthcare models, local case-mix, public health awareness, training, data monitoring and audit are critical factors to consider when planning, evaluating, or changing any screening programme.


Asunto(s)
Ambliopía , Errores de Refracción , Selección Visual , Niño , Humanos , Preescolar , Ambliopía/diagnóstico , Ambliopía/terapia , Ambliopía/epidemiología , Medicina Estatal , Errores de Refracción/diagnóstico , Errores de Refracción/terapia , Errores de Refracción/epidemiología , Costos de la Atención en Salud
8.
Sci Rep ; 13(1): 17173, 2023 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-37821525

RESUMEN

L-DOPA is deficient in the developing albino eye, resulting in abnormalities of retinal development and visual impairment. Ongoing retinal development after birth has also been demonstrated in the developing albino eye offering a potential therapeutic window in humans. To study whether human equivalent doses of L-DOPA/Carbidopa administered during the crucial postnatal period of neuroplasticity can rescue visual function, OCA C57BL/6 J-c2J OCA1 mice were treated with a 28-day course of oral L-DOPA/Carbidopa at 3 different doses from 15 to 43 days postnatal age (PNA) and for 3 different lengths of treatment, to identify optimum dosage and treatment length. Visual electrophysiology, acuity, and retinal morphology were measured at 4, 5, 6, 12 and 16 weeks PNA and compared to untreated C57BL/6 J (WT) and OCA1 mice. Quantification of PEDF, ßIII-tubulin and syntaxin-3 expression was also performed. Our data showed impaired retinal morphology, decreased retinal function and lower visual acuity in untreated OCA1 mice compared to WT mice. These changes were diminished or eliminated when treated with higher doses of L-DOPA/Carbidopa. Our results demonstrate that oral L-DOPA/Carbidopa supplementation at human equivalent doses during the postnatal critical period of retinal neuroplasticity can rescue visual retinal morphology and retinal function, via PEDF upregulation and modulation of retinal synaptogenesis, providing a further step towards developing an effective treatment for albinism patients.


Asunto(s)
Albinismo , Levodopa , Humanos , Ratones , Animales , Levodopa/farmacología , Levodopa/uso terapéutico , Carbidopa/farmacología , Carbidopa/uso terapéutico , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Albinismo/metabolismo
9.
Frontline Gastroenterol ; 14(4): 273-281, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37409330

RESUMEN

In 2016, the British Society of Gastroenterology (BSG) published comprehensive guidelines for obtaining consent for endoscopic procedures. In November 2020, the General Medical Council (GMC) introduced updated guidelines on shared decision making and consent. These guidelines followed the Montgomery ruling in 2015, which changed the legal doctrine determining what information should be given to a patient before a medical intervention. The GMC guidance and Montgomery ruling expand on the role of shared decision making between the clinician and patient, explicitly highlighting the importance of understanding the values of the patient. In November 2021, the BSG President's Bulletin highlighted the 2020 GMC guidance and the need to incorporate patient -related factors into decision making. Here, we make formal recommendations in support of this communication, and update the 2016 BSG endoscopy consent guidelines. The BSG guideline refers to the Montgomery legislation, but this document expands on the findings and gives proposals for how to incorporate it into the consent process. The document is to accompany, not replace the recent GMC and BSG guidelines. The recommendations are made in the understanding that there is not a single solution to the consent process, but that medical practitioners and services must work together to ensure that the principles and recommendations laid out below are deliverable at a local level. The 2020 GMC and 2016 BSG guidance had patient representatives involved throughout the process. Further patient involvement was not sought here as this update is to give practical advice on how to incorporate these guidelines into clinical practice and the consent process. This document should be read by endoscopists and referrers from primary and secondary care.

10.
Front Immunol ; 14: 1153915, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37153549

RESUMEN

Macrophage infiltration into adipose tissue is a key pathological factor inducing adipose tissue dysfunction and contributing to obesity-induced inflammation and metabolic disorders. In this review, we aim to present the most recent research on macrophage heterogeneity in adipose tissue, with a focus on the molecular targets applied to macrophages as potential therapeutics for metabolic diseases. We begin by discussing the recruitment of macrophages and their roles in adipose tissue. While resident adipose tissue macrophages display an anti-inflammatory phenotype and promote the development of metabolically favorable beige adipose tissue, an increase in pro-inflammatory macrophages in adipose tissue has negative effects on adipose tissue function, including inhibition of adipogenesis, promotion of inflammation, insulin resistance, and fibrosis. Then, we presented the identities of the newly discovered adipose tissue macrophage subtypes (e.g. metabolically activated macrophages, CD9+ macrophages, lipid-associated macrophages, DARC+ macrophages, and MFehi macrophages), the majority of which are located in crown-like structures within adipose tissue during obesity. Finally, we discussed macrophage-targeting strategies to ameliorate obesity-related inflammation and metabolic abnormalities, with a focus on transcriptional factors such as PPARγ, KLF4, NFATc3, and HoxA5, which promote macrophage anti-inflammatory M2 polarization, as well as TLR4/NF-κB-mediated inflammatory pathways that activate pro-inflammatory M1 macrophages. In addition, a number of intracellular metabolic pathways closely associated with glucose metabolism, oxidative stress, nutrient sensing, and circadian clock regulation were examined. Understanding the complexities of macrophage plasticity and functionality may open up new avenues for the development of macrophage-based treatments for obesity and other metabolic diseases.


Asunto(s)
Tejido Adiposo , Macrófagos , Enfermedades Metabólicas , Obesidad , Tejido Adiposo/inmunología , Macrófagos/clasificación , Macrófagos/inmunología , Obesidad/inmunología , Obesidad/terapia , Enfermedades Metabólicas/inmunología , Enfermedades Metabólicas/terapia , Humanos , Inflamación/inmunología , Inflamación/terapia , Adipogénesis/inmunología , Polaridad Celular
11.
J Youth Adolesc ; 52(7): 1433-1447, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37148440

RESUMEN

Excessive screen time among adolescents is discussed as a significant public health concern. Identifying adolescent longitudinal patterns of time spent on regularly-used media screens and understanding their young adulthood mental health and behavioral issue correlates may help inform strategies for improving these outcomes. This study aimed to characterize joint developmental patterns of time spent on videogames, surfing/chatting the Internet, and TV/DVDs during adolescence (at ages 11, 13, 15, 17) and their associations with mental health (i.e., depression, anxiety, suicidal ideation, and self-injury) and behavioral issues (i.e., substance use, delinquency, aggression) in early adulthood (at age 20). A parallel-process latent class growth analysis was used to model data from a diverse community-ascertained sample of youth in Zurich, Switzerland (n = 1521; 51.7% males). Results suggested that a five-class model best fitted the data: (1) low-screen use, 37.6%; (2) increasing chatting/surfing, 24.0%; (3) moderate-screen use, 18.6%; (4) early-adolescence screen use, 9.9%; and (5) increasing videogame and chatting/surfing, 9.9%. After adjusting for baseline levels of outcomes (primarily at age 11), the trajectory groups differed in their associations with adulthood outcomes of mental health and behavioral problems, indicating the importance of problematic screen usage patterns in predicting these outcomes. Future research to test the directionality of these associations will be important. These findings suggest which patterns of screen use may be a marker for later mental health and behavioral issues in different domains.


Asunto(s)
Salud Mental , Tiempo de Pantalla , Masculino , Humanos , Adolescente , Adulto Joven , Adulto , Niño , Femenino , Estudios Longitudinales , Ansiedad , Trastornos de Ansiedad
12.
J Pediatr Hematol Oncol Nurs ; 40(6): 411-419, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37194310

RESUMEN

Background: The purpose of this research was to understand the experience of parenting a child receiving dexamethasone during maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Previous research has shown that dexamethasone's high level of toxicity causes many physical, behavioral, and emotional side effects, which reduce the quality of life during ALL treatment. Less is known about the experience of parenting a child receiving dexamethasone and the impact on the parent-child relationship. Methods: In-depth semi-structured interviews were conducted with 12 parents and data was analyzed using Interpretative Phenomenological Analysis. Results: Four superordinate themes emerged: "a child on steroids is not your child": the behavioral and emotional changes in the child and their relationships; "you have to do what you have to do": adapting parenting to manage dexamethasone; "it breaks your heart … it's a horrible medicine": the emotional impact of parenting a child on dexamethasone; and, "it's the worst week ever": finding ways to cope with the challenges of dexamethasone. Discussion A preparatory intervention for parents beginning the dexamethasone journey focused on likely challenges, managing boundary setting and discipline, and their own emotional struggles, could be beneficial. Research into the impact on siblings could further understand the systemic influence of dexamethasone and help develop further interventions.


Asunto(s)
Responsabilidad Parental , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Responsabilidad Parental/psicología , Calidad de Vida , Quimioterapia de Mantención , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Dexametasona/uso terapéutico
13.
Antioxidants (Basel) ; 12(3)2023 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-36978982

RESUMEN

Endothelial dysfunction is implicated in the development and aggravation of cardiovascular complications. Among the endothelium-released vasoactive factors, hydrogen sulfide (H2S) has been investigated for its beneficial effects on the vasculature through anti-inflammatory and redox-modulating regulatory mechanisms. Reduced H2S bioavailability is reported in chronic diseases such as cardiovascular disease, diabetes, atherosclerosis and preeclampsia, suggesting the value of investigating mechanisms, by which H2S acts as a vasoprotective gasotransmitter. We explored whether the protective effects of H2S were linked to the mitochondrial health of endothelial cells and the mechanisms by which H2S rescues apoptosis. Here, we demonstrate that endothelial dysfunction induced by TNF-α increased endothelial oxidative stress and induced apoptosis via mitochondrial cytochrome c release and caspase activation over 24 h. TNF-α also affected mitochondrial morphology and altered the mitochondrial network. Post-treatment with the slow-releasing H2S donor, GYY4137, alleviated oxidising redox state, decreased pro-caspase 3 activity, and prevented endothelial apoptosis caused by TNF-α alone. In addition, exogenous GYY4137 enhanced S-sulfhydration of pro-caspase 3 and improved mitochondrial health in TNF-α exposed cells. These data provide new insights into molecular mechanisms for cytoprotective effects of H2S via the mitochondrial-driven pathway.

14.
J Periodontal Res ; 58(3): 634-645, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36919895

RESUMEN

BACKGROUND AND OBJECTIVE: Plaque-induced gingival inflammation (gingivitis) is ubiquitous in humans. The epithelial barrier reacts to the presence of oral bacteria and induces inflammatory cascades. The objective of this study was to investigate the mechanism by which the small molecule micronutrient curcumin could decrease inflammatory response in vitro to oral bacterium heat-killed Fusobacterium nucleatum as curcumin could be a useful compound for combatting gingivitis already consumed by humans. METHODS: H400 oral epithelial cell line was pre-conditioned with curcumin and the production of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and translocation of transcription factors was used to monitor inflammatory responses. Haem oxygenase (HO-1) expression and molecules that HO-1 releases were evaluated for their potential to reduce the quantity of cytokine production. Immunofluorescence microscopy and Western blotting were used to evaluate changes in transcription factor and enzyme location. RESULTS: Pre-conditioning of H400 cells with a sub-apoptotic concentration of curcumin (20 µM) attenuated secretion of Granulocyte-Macrophage - Colony-Stimulating Factor (GM-CSF) and reduced NFkB nuclear translocation. This pre-conditioning caused an increase in nuclear Nrf2; an initial drop (at 8 h) followed by an adaptive increase (at 24 h) in glutathione; and an increase in haem oxygenase (HO-1) expression. Inhibition of HO-1 by SnPPIX prevented the curcumin-induced attenuation of GM-CSF production. HO-1 catalyses the breakdown of haem to carbon monoxide, free iron and biliverdin: the HO-1/CO anti-inflammatory pathway. Elevations in carbon monoxide, achieved using carbon monoxide releasing molecule-2 (CORM2) treatment alone abrogated F. nucleatum-induced cytokine production. Biliverdin is converted to bilirubin by biliverdin reductase (BVR). This pleiotropic protein was found to increase in cell membrane expression upon curcumin treatment. CONCLUSION: Curcumin decreased inflammatory cytokine production induced by Fusobacterium nucleatum in H400 oral epithelial cells. The mechanism of action appears to be driven by the increase of haem oxygenase and the production of carbon monoxide.


Asunto(s)
Curcumina , Gingivitis , Humanos , Curcumina/farmacología , Hemo-Oxigenasa 1/metabolismo , Citocinas/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Biliverdina/farmacología , Monóxido de Carbono/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismo , Células Epiteliales/metabolismo
15.
Res Child Adolesc Psychopathol ; 51(6): 847-858, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36749476

RESUMEN

Growing evidence has suggested that parental mental illness and child internalizing and externalizing problems tend to co-occur and engender risk for adverse child outcomes; however, there is considerable heterogeneity in their joint developmental trajectories. This study aimed to evaluate the joint developmental trajectories of maternal and paternal psychological distress and child internalizing and externalizing problems from early childhood to middle adolescence. Given that suicide and self-harm are major public health issues in adolescence and often occur in the context of other mental health issues, we also examined the association between these joint trajectories and these outcomes in adolescence. Parallel-process latent class growth analysis was applied to 14 years of follow-up data from a large-scale, nationally representative sample of youths participating in the UK's Millennium Cohort Study (MCS; n = 12,520, 50.9% male). Results showed the best-fitting solution had four trajectory classes: (1) low symptoms, 59.0%; (2) moderate symptoms in children, 22.5%; (3) notable symptoms in fathers, 10.7%; and (4) co-occurring maternal and child symptoms, 7.8%. The trajectory groups differed in their self-harm and suicide attempts in adolescence, underscoring the possible importance of the roles of both parental distress and child problem behaviors processes in these outcomes. Future studies will be valuable to rigorously test the directionality and the respective roles of parents and children in this association. Our findings suggest the need for two-generation mental health intervention programs that are tailored based on co-developmental trajectory group membership.


Asunto(s)
Trastornos Mentales , Conducta Autodestructiva , Humanos , Niño , Masculino , Preescolar , Adolescente , Femenino , Intento de Suicidio , Estudios de Cohortes , Padres , Conducta Autodestructiva/epidemiología
16.
Methods Mol Biol ; 2588: 41-58, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36418681

RESUMEN

Chronic inflammatory diseases are the major causes of mortality in humans and recent research has improved our understanding of the major impact of lifestyle factors upon inflammatory diseases and conditions. One of the most influential of these is nutrition, which may drive both pro-inflammatory as well as anti-inflammatory cascades at molecular and cellular levels. There are a variety of model systems that may be employed to investigate the impact of micronutrients and macronutrients upon inflammatory pathways, many of which operate through oxidative stress, either at the level of controlling the redox state of the cell and downstream redox-regulated gene transcription factors, and other acting as free radical generating or scavenging agents. This chapter focuses upon biological sample preparation prior to assay and details methods for analyzing certain antioxidant micronutrients and biomarkers of oxidative stress.


Asunto(s)
Antioxidantes , Micronutrientes , Humanos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Estrés Oxidativo , Biomarcadores/metabolismo , Oxidación-Reducción
17.
Clin Psychol Psychother ; 30(2): 486-490, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36494180

RESUMEN

Developing effective treatment options for negative symptoms of psychotic disorders remains a major unmet treatment need and area for further research. In a recent uncontrolled study by the main author, Metacognition Training (MCT) for negative symptoms was found to lead to fewer negative symptoms, less stigma and increased self-rated reflective ability. As the analysis examined negative symptoms as a whole, we here performed an additional analysis on individual negative symptom items as recent research has suggested that negative symptoms are best conceptualized through a five-factor model. It was found that the intervention led to changes specifically on sociality and blunted affect (with large effect sizes), which might reflect changes in both intrapersonal and interpersonal (meta)cognitive processes.


Asunto(s)
Metacognición , Trastornos Psicóticos , Humanos , Trastornos Psicóticos/terapia , Resultado del Tratamiento , Conducta Social , Trastornos del Humor
18.
Gut ; 72(1): 12-26, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36229172

RESUMEN

GI endoscopy is highly resource-intensive with a significant contribution to greenhouse gas (GHG) emissions and waste generation. Sustainable endoscopy in the context of climate change is now the focus of mainstream discussions between endoscopy providers, units and professional societies. In addition to broader global challenges, there are some specific measures relevant to endoscopy units and their practices, which could significantly reduce environmental impact. Awareness of these issues and guidance on practical interventions to mitigate the carbon footprint of GI endoscopy are lacking. In this consensus, we discuss practical measures to reduce the impact of endoscopy on the environment applicable to endoscopy units and practitioners. Adoption of these measures will facilitate and promote new practices and the evolution of a more sustainable specialty.


Asunto(s)
Gastroenterología , Humanos , Consenso , Endoscopía Gastrointestinal
20.
J Med Screen ; 30(2): 62-68, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36205109

RESUMEN

OBJECTIVE: For cost-effectiveness comparison of child vision and hearing screening programmes, methods and data should be available. We assessed the current state of data collection and its availability in Europe. METHODS: The EUSCREEN Questionnaire, conducted in 2017-2018, assessed paediatric vision and hearing screening programmes in 45 countries in Europe. For the current study, its items on data collection, monitoring and evaluation, and six of eleven items essential for cost-effectiveness analysis: prevalence, sensitivity, specificity, coverage, attendance and loss to follow-up, were reappraised with an additional questionnaire. RESULTS: The practice of data collection in vision screening was reported in 36% (N = 42) of countries and in hearing screening in 81% (N = 43); collected data were published in 12% and 35%, respectively. Procedures for quality assurance in vision screening were reported in 19% and in hearing screening in 26%, research of screening effectiveness in 43% and 47%, whereas cost-effectiveness analysis was performed in 12% for both. Data on prevalence of amblyopia were reported in 40% and of hearing loss in 77%, on sensitivity of screening tests in 17% and 14%, on their specificity in 19% and 21%, on coverage of screening in 40% and 84%, on attendance in 21% and 37%, and on loss to follow-up in 12% and 40%, respectively. CONCLUSIONS: Data collection is insufficient in hearing screening and even more so in vision screening: data essential for cost-effectiveness comparison could not be reported from most countries. When collection takes place, this is mostly at a local level for quality assurance or accountability, and data are often not accessible. The resulting inability to compare cost-effectiveness among screening programmes perpetuates their diversity and inefficiency.


Asunto(s)
Ambliopía , Selección Visual , Niño , Humanos , Análisis Costo-Beneficio , Detección Precoz del Cáncer , Ambliopía/diagnóstico , Pruebas Auditivas/métodos , Audición
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