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1.
Inquiry ; 61: 469580241274030, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39237853

RESUMEN

There are few validated contextual measures predicting adoption of evidence-based programs. Variation in context at clinical sites can hamper dissemination. We examined organizational characteristics of Veterans Affairs hospitals implementing STRIDE, a hospital walking program, and characteristics' influences on program adoption. Using a parallel mixed-method design, we describe context and organizational characteristics by program adoption. Organizational characteristics included: organizational resilience, implementation climate, organizational readiness to implement change, highest complexity sites versus others, material support, adjusted length of stay (LOS) above versus below national median, and improvement experience. We collected intake forms at hospital launch and qualitative interviews with staff members at 4 hospitals that met the initial adoption benchmark, defined as completing supervised walks with 5+ unique hospitalized Veterans during months 5 to 6 after launch with low touch implementation support. We identified that 31% (n = 11 of 35) of hospitals met adoption benchmarks. Seven percent of highest complexity hospitals adopted compared to 48% with lower complexity. Forty-three percent that received resources adopted compared to 29% without resources. Thirty-six percent of hospitals with above-median LOS adopted compared to 23% with below-median. Thirty-five percent with at least some implementation experience adopted compared to 0% with very little to no experience. Adopters reported higher organizational resilience than non-adopters (mean = 23.5 [SD = 2.6] vs 22.7 [SD = 2.6]). Adopting hospitals reported greater organizational readiness to change than those that did not (mean = 4.2 [SD = 0.5] vs 3.8 [SD = 0.6]). Qualitatively, all sites reported that staff were committed to implementing STRIDE. Participants reported additional barriers to adoption including challenges with staffing and delays associated with hiring staff. Adopters reported that having adequate staff facilitated implementation. Implementation climate did not have an association with meeting STRIDE program adoption benchmarks in this study. Contextual factors which may be simple to assess, such as resource availability, may influence adoption of new programs without intensive implementation support.


Asunto(s)
Benchmarking , Humanos , Estados Unidos , Hospitales de Veteranos/organización & administración , Tiempo de Internación , United States Department of Veterans Affairs/organización & administración , Cultura Organizacional , Caminata , Hospitalización , Limitación de la Movilidad
3.
Emerg Nurse ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39323308

RESUMEN

Although the phenomenon of crowding in emergency departments (EDs) is not new, it remains a significant problem for patients, ED staff and the wider healthcare system. Crowding in EDs, which is also called overcrowding, has been widely explored in the literature, but there are relatively few studies of the subject from an emergency nurse perspective. This article reports the findings of a literature review that aimed to explore the effects of crowding on nurses working in EDs. Four key themes were identified from a synthesis of 16 articles included in the review: staffing and skill mix; inadequate care and the effect on nurses' well-being and stress levels; violence in the ED; and hospital metrics and patient flow. Further research is required to explore in more depth the effects of ED crowding on emergency nurses and to address the multiple factors that perpetuate the phenomenon.

4.
Eur J Hum Genet ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090236

RESUMEN

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Accurate cancer risk assessment approaches could increase rates of early CRC diagnosis, improve health outcomes for patients and reduce pressure on diagnostic services. The faecal immunochemical test (FIT) for blood in stool is widely used in primary care to identify symptomatic patients with likely CRC. However, there is a 6-16% noncompliance rate with FIT in clinic and ~90% of patients over the symptomatic 10 µg/g test threshold do not have CRC. A polygenic risk score (PRS) quantifies an individual's genetic risk of a condition based on many common variants. Existing PRS for CRC have so far been used to stratify asymptomatic populations. We conducted a retrospective cohort study of 50,387 UK Biobank participants with a CRC symptom in their primary care record at age 40+. A PRS based on 201 variants, 5 genetic principal components and 22 other risk factors and markers for CRC were assessed for association with CRC diagnosis within 2 years of first symptom presentation using logistic regression. Associated variables were included in an integrated risk model and trained in 80% of the cohort to predict CRC diagnosis within 2 years. An integrated risk model combining PRS, age, sex, and patient-reported symptoms was predictive of CRC development in a testing cohort (receiver operating characteristic area under the curve, ROCAUC: 0.76, 95% confidence interval: 0.71-0.81). This model has the potential to improve early diagnosis of CRC, particularly in cases of patient noncompliance with FIT.

5.
Genome Med ; 16(1): 85, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956711

RESUMEN

BACKGROUND: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. METHODS: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. RESULTS: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. CONCLUSIONS: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors.


Asunto(s)
Envejecimiento , Metilación de ADN , Longevidad , Humanos , Animales , Metilación de ADN/efectos de los fármacos , Longevidad/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Descubrimiento de Drogas/métodos , Senescencia Celular/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Drosophila , Células Cultivadas , Sirolimus/farmacología
6.
Front Genet ; 15: 1242636, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633407

RESUMEN

Allogeneic hematopoietic cell transplantation (HCT) is used to treat many blood-based disorders and malignancies, however it can also result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier to reduce incidence of aGVHD by improving donor selection. Genome-wide DNA methylation was assessed in a discovery cohort of 288 HCT donors selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD. We applied a machine learning algorithm to identify CpG sites predictive of aGVHD. Receiver operating characteristic (ROC) curve analysis of these sites resulted in a classifier with an encouraging area under the ROC curve (AUC) of 0.91. To test this classifier, we used an independent validation cohort (n = 288) selected using the same criteria as the discovery cohort. Attempts to validate the classifier failed with the AUC falling to 0.51. These results indicate that donor DNA methylation may not be a suitable predictor of aGVHD in an HCT setting involving unrelated donors, despite the initial promising results in the discovery cohort. Our work highlights the importance of independent validation of machine learning classifiers, particularly when developing classifiers intended for clinical use.

7.
JMIR Serious Games ; 12: e51508, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669680

RESUMEN

BACKGROUND: Finding enjoyable and effective long-term approaches to rehabilitation for improving the upper limb (UL) function of people with multiple sclerosis (MS) is challenging. Using virtual reality (VR) could be a solution to this challenge; however, there is a lack of reporting on the views of people with MS and clinicians on VR-based approaches and recommendations for games for rehabilitation. OBJECTIVE: This study aims to identify common UL problems and their related current therapeutic approaches for people with MS, and to explore the opinions of people with MS and specialist clinicians on VR and obtain suggestions for the development and design of VR games. METHODS: Separate focus groups were conducted with people with MS, recruited through the MS Society UK's research network, and clinicians, recruited through the MS Trust Therapists in MS network. A total of 10 people with MS (2 focus groups) and 8 clinicians (5 physiotherapists, 2 occupational therapists, and 1 MS nurse in 2 focus groups) were involved. The focus groups were recorded and transcriptions were analyzed using theme-based content analysis. RESULTS: People with MS commonly reported that their UL problems interfered with activities of daily living and resulted in the loss of meaningful hobbies such as writing. Many people with MS neglected UL exercise and found strategies for adapting to the UL impairments. Similarly, clinicians stated UL rehabilitation was neglected within their service and that it was challenging to find interesting treatment strategies. VR was suggested by both participant groups as a solution, as it was convenient for people with MS to access and it could provide a more engaging and disguised approach to exercise. There were shared concerns with cybersickness and disengagement with using VR approaches. Both groups agreed games should be meaningful and adaptable for users but suggested different VR activities, with clinicians suggesting games directly reflecting activities of daily living and people with MS suggesting more abstract activities. CONCLUSIONS: VR was well received by both people with MS and clinicians for UL rehabilitation. Recommendations were made for the development of VR rehabilitation games which are personalized and customizable for the varying abilities of people with MS.

8.
Front Sociol ; 9: 1334633, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38414508

RESUMEN

This article seeks to understand the first-hand experiences of people with sickle cell, a recessively inherited blood disorder, who were identified as clinically extremely vulnerable during the COVID-19 pandemic. Part of a larger sequential mixed-methods study, this article uses a selective sample of eight qualitative semi-structured interviews, which were analysed using interpretative phenomenological analysis (IPA). The first stage of IPA focused on practical concerns participants had correlated to understanding shielding and their feelings about being identified as clinically extremely vulnerable. In a secondary stage of analysis, we examined the emotions that it brought forth and the foundations of those based on discriminations. This article adds to our theoretical understanding of embodiment and temporality with respect to chronicity and early ageing. It explains how people with sickle cell disorders have an embodied ethics of crisis and expertise. It also elucidates how people's experiences during the pandemic cannot be seen in void but illustrates ableism, racism, and ageism in society writ large.

9.
G3 (Bethesda) ; 14(2)2024 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-38113034

RESUMEN

How genetic and phenotypic variation are maintained has long been one of the fundamental questions in population and quantitative genetics. A variety of factors have been implicated to explain the maintenance of genetic variation in some contexts (e.g. balancing selection), but the potential role of epigenetic regulation to influence population dynamics has been understudied. It is well recognized that epigenetic regulation, including histone methylation, small RNA expression, and DNA methylation, helps to define differences between cell types and facilitate phenotypic plasticity. In recent years, empirical studies have shown the potential for epigenetic regulation to also be heritable for at least a few generations without selection, raising the possibility that differences in epigenetic regulation can act alongside genetic variation to shape evolutionary trajectories. Heritable differences in epigenetic regulation that arise spontaneously are termed "epimutations." Epimutations differ from genetic mutations in 2 key ways-they occur at a higher rate and the loci at which they occur often revert back to their original state within a few generations. Here, we present an extension of the standard population genetic model with selection to incorporate epigenetic variation arising via epimutation. Our model assumes a diploid, sexually reproducing population with random mating. In addition to spontaneous genetic mutation, we included parameters for spontaneous epimutation and back-epimutation, allowing for 4 potential epialleles at a single locus (2 genetic alleles, each with 2 epigenetic states), each of which affect fitness. We then analyzed the conditions under which stable epialleles were maintained. Our results show that highly reversible epialleles can be maintained in long-term equilibrium under neutral conditions in a manner that depends on the epimutation and back-epimutation rates, which we term epimutation-back-epimutation equilibrium. On the other hand, epialleles that compensate for deleterious mutations cause deviations from the expectations of mutation-selection balance by a simple factor that depends on the epimutation and back-epimutation rates. We also numerically analyze several sets of fitness parameters for which large deviations from mutation-selection balance occur. Together, these results demonstrate that transient epigenetic regulation may be an important factor in the maintenance of both epigenetic and genetic variation in populations.


Asunto(s)
Metilación de ADN , Epigénesis Genética , Mutación , Alelos , Variación Genética
10.
Endocr Rev ; 45(3): 343-350, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38123518

RESUMEN

Midgut neuroendocrine neoplasms (NENs) are one of the most common subtypes of NEN, and their incidence is rising globally. Despite being the most frequently diagnosed malignancy of the small intestine, little is known about their underlying molecular biology. Their unusually low mutational burden compared to other solid tumors and the unexplained occurrence of multifocal tumors makes the molecular biology of midgut NENs a particularly fascinating field of research. This review provides an overview of recent advances in the understanding of the interplay of the genetic, epigenetic, and transcriptomic landscape in the development of midgut NENs, a topic that is critical to understanding their biology and improving treatment options and outcomes for patients.


Asunto(s)
Neoplasias Intestinales , Tumores Neuroendocrinos , Humanos , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/metabolismo , Neoplasias Intestinales/genética , Neoplasias Intestinales/metabolismo , Neoplasias Intestinales/patología , Animales , Epigénesis Genética
11.
BMC Womens Health ; 23(1): 601, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37964236

RESUMEN

BACKGROUND: Female genital cosmetic surgery (FGCS) changes the structure and appearance of healthy external genitalia. We aimed to identify discourses that help explain and rationalise FGCS and to derive from them possibilities for informing clinical education. METHODS: We interviewed 16 health professionals and 5 non-health professionals who deal with women's bodies using a study-specific semi-structured interview guide. We analysed transcripts using a three-step iterative process: identifying themes relevant to indications for FGCS, identifying the discourses within which they were positioned, and categorising and theorising discourses. RESULTS: We identified discourses that we categorised within four themes: Diversity and the Normal Vulva (diversity was both acknowledged and rejected); Indications for FGCS (Functional, Psychological, Appearance); Ethical Perspectives; and Reasons Women Seek FGCS (Pubic Depilation, Media Representation, Pornography, Advertising Regulations, Social Pressure, Genital Unfamiliarity). CONCLUSIONS: Vulvar aesthetics constitute a social construct to which medical practice and opinion contribute and by which they are influenced; education and reform need to occur on all fronts. Resources that not only establish genital diversity but also challenge limited vulvar aesthetics could be developed in consultation with women, healthcare practitioners, mental health specialists, and others with knowledge of social constructs of women's bodies.


Asunto(s)
Cirugía Plástica , Humanos , Femenino , Cirugía Plástica/psicología , Belleza , Procedimientos Quirúrgicos Ginecológicos , Vulva/cirugía , Investigación Cualitativa
12.
bioRxiv ; 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37873136

RESUMEN

In recent decades, genome-wide association studies (GWAS) have been the major approach to understand the biological basis of individual differences in traits and diseases. However, GWAS approaches have proven to have limited predictive power to explain individual differences, particularly for complex traits and diseases in which environmental factors play a substantial role in their etiology. Indeed, individual differences persist even in genetically identical individuals, although fully separating genetic and environmental causation is difficult or impossible in most organisms. To understand the basis of individual differences in the absence of genetic differences, we measured two quantitative reproductive traits in 180 genetically identical young adult Caenorhabditis elegans roundworms in a shared environment and performed single-individual transcriptomics on each worm. We identified hundreds of genes for which expression variation was strongly associated with reproductive traits, some of which depended on prior environmental experience and some of which was random. Multiple small sets of genes together were highly predictive of reproductive traits across individuals, explaining on average over half and over a quarter of variation in the two traits. We manipulated mRNA levels of predictive genes using RNA interference to identify a set of causal genes, demonstrating the utility of this approach for both prediction and understanding underlying biology. Finally, we found that the chromatin environment of predictive genes was enriched for H3K27 trimethylation, suggesting that individual gene expression differences underlying critical traits may be driven in part by chromatin structure. Together, this work shows that individual differences in gene expression that arise independently of underlying genetic differences are both predictive and causal in shaping reproductive traits at levels that equal or exceed genetic variation.

13.
Endocr Oncol ; 3(1): e220094, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37529774

RESUMEN

Diabetes and cancer are two heterogenous diseases which are rapidly increasing in prevalence globally. A link between these two non-communicable diseases was first identified over 100 years ago; however, recent epidemiological studies and advances in genomic research have provided greater insight into the association between diabetes and cancer. Epidemiological studies have suggested that individuals with diabetes have an increased risk of several types of cancer (including liver, pancreas, colorectal, breast, and endometrial) and an increased risk of cancer mortality. However, this increased risk is not observed in all cancers, for example, there is a reduced risk of prostate cancer in individuals with diabetes. It has also been observed that cancer patients have an increased risk of developing diabetes, highlighting that the relationship between these diseases is not straightforward. Evidence of a shared genetic aetiology along with numerous lifestyle and clinical factors have made it challenging to establish if the relationship between the two diseases is causal or a result of confounding factors. This review takes a pan-cancer approach to highlight the complexities of the interactions between type 2 diabetes and cancer development, indicating where advances in genomic research have enabled a greater insight into these two diseases.

14.
Int J MS Care ; 25(4): 176-185, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37469335

RESUMEN

BACKGROUND: Evidence of the benefits of dance for people with Parkinson disease is well established, but only recently has dance been investigated for people with multiple sclerosis (MS). The purpose of this review was to identify and evaluate the feasibility and effectiveness of dance interventions to improve functional, psychosocial, and participation outcomes in people with MS. METHODS: Eight databases and gray literature sources were searched from inception to March 2022. Quantitative, mixed-methods, and qualitative studies evaluating dance interventions for adults with MS were included. Included studies were critically appraised using the Mixed Methods Appraisal Tool, and results were analyzed through a parallel-results convergent synthesis. RESULTS: Thirteen studies were included, with a total of 174 participants. Various dance genres were investigated, and only 1 mild adverse event was reported. Four to 12 weeks of twice-weekly, 60-minute dance sessions were feasible in those with mild to moderate relapsing-remitting MS. Positive effects were identified mainly in motor outcomes, with qualitative themes indicating psychological and social benefits. CONCLUSIONS: A variety of dance interventions are likely feasible and potentially beneficial for people with mild to moderate relapsing-remitting MS, but studies were generally of low-moderate quality. High-quality studies are needed to determine the effectiveness of dance interventions for people with MS, including those with progressive forms of MS and higher levels of disability.

15.
Neuroendocrinology ; 113(9): 915-923, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36907174

RESUMEN

INTRODUCTION: Small intestinal neuroendocrine tumours (siNETs) are rare neoplasms which present with low mutational burden and can be subtyped based on copy number variation (CNV). Currently, siNETs can be molecularly classified as having chromosome 18 loss of heterozygosity (18LOH), multiple CNVs (MultiCNV), or no CNVs. 18LOH tumours have better progression-free survival when compared to MultiCNV and NoCNV tumours, however, the mechanism underlying this is unknown, and clinical practice does not currently consider CNV status. METHODS: Here, we use genome-wide tumour DNA methylation (n = 54) and gene expression (n = 20 matched to DNA methylation) to better understand how gene regulation varies by 18LOH status. We then use multiple cell deconvolution methods to analyse how cell composition varies between 18LOH status and determine potential associations with progression-free survival. RESULTS: We identified 27,464 differentially methylated CpG sites and 12 differentially expressed genes between 18LOH and non-18LOH (MultiCNV + NoCNV) siNETs. Although few differentially expressed genes were identified, these genes were highly enriched with the differentially methylated CpG sites compared to the rest of the genome. We identified differences in tumour microenvironment between 18LOH and non-18LOH tumours, including CD14+ infiltration in a subset of non-18LOH tumours which had the poorest clinical outcomes. CONCLUSIONS: We identify a small number of genes which appear to be linked to the 18LOH status of siNETs, and find evidence of potential epigenetic dysregulation of these genes. We also find a potential prognostic marker for worse progression-free outcomes in the form of higher CD14 infiltration in non-18LOH siNETs.


Asunto(s)
Neoplasias Intestinales , Tumores Neuroendocrinos , Humanos , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Multiómica , Variaciones en el Número de Copia de ADN/genética , Cromosomas Humanos Par 18 , Neoplasias Intestinales/genética , Metilación de ADN/genética , Pérdida de Heterocigocidad/genética , Microambiente Tumoral
16.
Pharmacoepidemiol Drug Saf ; 32(1): 66-72, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36111444

RESUMEN

PURPOSE: Our objective was to describe differences in telemedicine use among women with metastatic breast cancer (mBC) by race, age, and geographic region. METHODS: This was a retrospective cohort study of women with recurrent or de novo mBC treated in US community cancer practices that initiated a new line of therapy between March 2020 and February 2021. Multivariable modified Poisson regression models were used to calculate adjusted rate ratios (RR) and robust 95% confidence intervals (CI) associated with telemedicine visits within 90 days of therapy initiation. RESULTS: Overall, among 3412 women with mBC, 751 (22%) patients had telemedicine visits following therapy initiation, with lower risks observed among older women (<50 years: 24%; 50-64 years: 22%; 65-74 years: 21%; ≥75 years: 20%). Greater telemedicine use was observed among Asian women (35%) compared to White (21%), Black (18%), and Hispanic (21%) women. Fewer telemedicine visits occurred in Southern (12%) and Midwestern (17%) states versus Northeastern (37%) or Western (36%) states. In multivariable models, women ages ≥75 years had significantly lower risks of telemedicine visits (RR = 0.76, 95% CI 0.62-0.95) compared to ages <50 years. Compared to patients in Northeastern states, women in Midwestern (RR = 0.46, 95% CI 0.37-0.57) and Southern (RR = 0.31, 95% CI 0.26-0.37) states had significantly lower risks of telemedicine visits; but not women in Western states (RR = 0.96, 95% CI 0.83-1.12). No statistically significant differences in telemedicine use were found between racial groups in overall multivariable models. CONCLUSIONS: In this study of community cancer practices, older mBC patients and those living in Southern and Midwestern states were less likely to have telemedicine visits. Preferences for communication and delivery of care may have implications for measurement of exposures and endpoints in pharmacoepidemiologic studies of cancer patients.


Asunto(s)
Neoplasias de la Mama , COVID-19 , Telemedicina , Humanos , Anciano , Persona de Mediana Edad , Femenino , COVID-19/epidemiología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Pandemias , Estudios Retrospectivos
17.
Genetics ; 223(2)2023 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-36449523

RESUMEN

Early-life malnutrition increases adult disease risk in humans, but the causal changes in gene regulation, signaling, and metabolism are unclear. In the roundworm Caenorhabditis elegans, early-life starvation causes well-fed larvae to develop germline tumors and other gonad abnormalities as adults. Furthermore, reduced insulin/IGF signaling during larval development suppresses these starvation-induced abnormalities. How early-life starvation and insulin/IGF signaling affect adult pathology is unknown. We show that early-life starvation has pervasive effects on adult gene expression which are largely reversed by reduced insulin/IGF signaling following recovery from starvation. Early-life starvation increases adult fatty-acid synthetase fasn-1 expression in daf-2 insulin/IGF signaling receptor-dependent fashion, and fasn-1/FASN promotes starvation-induced abnormalities. Lipidomic analysis reveals increased levels of phosphatidylcholine in adults subjected to early-life starvation, and supplementation with unsaturated phosphatidylcholine during development suppresses starvation-induced abnormalities. Genetic analysis of fatty-acid desaturases reveals positive and negative effects of desaturation on development of starvation-induced abnormalities. In particular, the ω3 fatty-acid desaturase fat-1 and the Δ5 fatty-acid desaturase fat-4 inhibit and promote development of abnormalities, respectively. fat-4 is epistatic to fat-1, suggesting that arachidonic acid-containing lipids promote development of starvation-induced abnormalities, and supplementation with ARA enhanced development of abnormalities. This work shows that early-life starvation and insulin/IGF signaling converge on regulation of adult lipid metabolism, affecting stem-cell proliferation and tumor formation.


Asunto(s)
Proteínas de Caenorhabditis elegans , Inanición , Humanos , Animales , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Metabolismo de los Lípidos , Insulina/metabolismo , Inanición/genética
18.
Cell Rep ; 41(2): 111473, 2022 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-36223742

RESUMEN

Nutrient availability governs growth and quiescence, and many animals arrest development when starved. Using C. elegans L1 arrest as a model, we show that gene expression changes deep into starvation. Surprisingly, relative expression of germline-enriched genes increases for days. We conditionally degrade the large subunit of RNA polymerase II using the auxin-inducible degron system and analyze absolute expression levels. We find that somatic transcription is required for survival, but the germline maintains transcriptional quiescence. Thousands of genes are continuously transcribed in the soma, though their absolute abundance declines, such that relative expression of germline transcripts increases given extreme transcript stability. Aberrantly activating transcription in starved germ cells compromises reproduction, demonstrating important physiological function of transcriptional quiescence. This work reveals alternative somatic and germline gene-regulatory strategies during starvation, with the soma maintaining a robust transcriptional response to support survival and the germline maintaining transcriptional quiescence to support future reproductive success.


Asunto(s)
Proteínas de Caenorhabditis elegans , Inanición , Animales , Caenorhabditis elegans/fisiología , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Regulación del Desarrollo de la Expresión Génica , Células Germinativas/metabolismo , Ácidos Indolacéticos/metabolismo , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Inanición/metabolismo
19.
BMJ Open ; 12(9): e057141, 2022 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-36153017

RESUMEN

OBJECTIVE: To understand the psychological and social impact of shielding on people with sickle cell disorders and their carers in the Midlands region of England. This region was badly affected during the pandemic, with the city of Birmingham having some of the highest rates of COVID-19 deaths. DESIGN: A mixed-methods project with a quantitative survey on shielding and adapted SF36 V.2 questionnaire, which was supplemented by qualitative semistructured interviews analysed using interpretive phenomenological analysis (IPA). PARTICIPANTS: Fifty-one participants who were predominantly of Black Caribbean or Black African heritage anonymously took part in the online survey. We supplemented this with eight in-depth semistructured interviews with adults with sickle cell disorders using IPA. RESULTS: The adapted 36-Item Short Form Survey (SF36) version 2 (V. 2) survey indicated worse quality of life and mental health. The open-ended questions from the adapted survey also identified shielding concerns about hospital care, pain management and knowledge of sickle cell by healthcare professionals. From the interviews, it emerged that the racialised element of the pandemic caused significant psychological distress for a population group that had to regularly access hospitals. It was noted that psychological health needs both during a pandemic and outside of it were poorly understood and became invisible in services. The psychological impact of experiences of hospital care as well as growing up with an invisible chronic condition were important to understand psychologically.


Asunto(s)
Anemia de Células Falciformes , COVID-19 , Distrés Psicológico , Adulto , Anemia de Células Falciformes/terapia , COVID-19/epidemiología , Atención a la Salud , Humanos , Pandemias , Calidad de Vida
20.
Health Soc Care Community ; 30(6): e5083-e5094, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35915919

RESUMEN

Lifeline Australia operates crisis support services through Lifeline Crisis Supporters. An integral part of their role is to conduct online suicide risk assessments with help-seekers. However, there is limited literature regarding suicide risk assessment practices for this population. This study aimed to examine how suicide prevention training, vicarious trauma and fears impacted suicide risk assessment behaviours of Lifeline Crisis Supporters. A cross-sectional survey design was used to recruit a volunteer convenience sample of 125 Lifeline Australia Crisis Supporters (75.2% females; Mage  = 54.9) in 2018 to participate in an online survey. Findings revealed that those with more suicide-specific training had less risk assessment-related fears, and that fears were not related to attitudes towards suicide prevention. There was no significant relationship between vicarious trauma and amount of training or years of experience in the role. Further, participants with higher levels of vicarious trauma demonstrated significantly more negative attitudes towards suicide prevention. Overall, training appears to be a significant factor in suicide risk assessment practice behaviours of Lifeline Crisis Supporters, highlighting a need for ongoing training and support for them. This research also suggests that whilst fears exist, they do not significantly impair Lifeline Crisis Supporters' ability to undertake suicide risk assessment.


Asunto(s)
Desgaste por Empatía , Suicidio , Femenino , Humanos , Persona de Mediana Edad , Masculino , Intervención en la Crisis (Psiquiatría) , Líneas Directas , Estudios Transversales , Medición de Riesgo , Miedo
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