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1.
Br J Hosp Med (Lond) ; 85(4): 1-12, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38708974

RESUMO

People experience life and interact with others in many ways. The term 'neurodivergence' refers to variations from what is considered typical. Research and education into conditions that cooccur with neurodivergence are essential in shaping clinicians' approaches to people who may present with a wide range of symptoms. Neurodivergence may influence a person's style of communication, learning, attitudes, and behaviour, and they often experience inequity and rejection. This review highlights the huge burden of cooccurring conditions carried by neurodivergent women and girls whose medical issues have largely gone under the radar. We suggest how clinicians might increase their awareness of diagnosis and management of their problems with mutual benefit.


Assuntos
Saúde Mental , Humanos , Feminino , Adolescente , Transtornos Mentais/diagnóstico
2.
Curr Oncol ; 31(3): 1645-1655, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38534958

RESUMO

BACKGROUND: The risk factors for acute care utilization in gynecologic oncology patients are poorly understood. This study aimed to evaluate risk factors for the utilization of our centre's acute care radiation nursing clinic (RNC) by gynecologic oncology patients receiving radiotherapy (RT). METHODS: This was a retrospective cohort study of gynecological cancer patients treated with RT at an academic cancer centre between 1 August 2021 and 31 January 2022. Data on socio-demographics, clinical and treatment characteristics, and RNC visits were collected and summarized by descriptive statistics. The Wilcoxon rank sum test and chi-squared test/Fisher's exact test were used for comparisons of continuous and categorical variables, respectively. RESULTS: RT was delivered to 180 patients, of whom 42 (23%) received concurrent chemoradiation (CCR). Compared to those receiving RT alone, patients receiving CCR had higher rates of RNC utilization (55% vs. 19%, p < 0.001). Within the CCR cohort, patients who presented to the RNC were more likely to be unpartnered (43% vs. 11%, p = 0.04), receive a referral to Psychosocial Oncology (39% vs. 5.3%, p = 0.01), and experience treatment interruptions (52% vs. 16%, p = 0.02). There were no associations between RNC visits and age, disease site, or distance from the cancer centre. CONCLUSIONS: The receipt of CCR and specific psychosocial risk factors were associated with increased RNC utilization. Targeted strategies and early intervention to better meet the supportive care and psychosocial needs of this vulnerable population are needed.


Assuntos
Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/terapia , Estudos Retrospectivos , Assistência Ambulatorial , Fatores de Risco , Instituições de Assistência Ambulatorial
3.
Autism ; 28(4): 816-830, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38145308

RESUMO

LAY ABSTRACT: Difficulties with mental health and low levels of well-being are more common among autistic girls and women than non-autistic people, but we do not fully understand why. Research does not focus enough on what autistic girls and women could tell us about this. This review aims to summarise the studies where autistic girls and women explain things that affect their mental health and well-being to help us understand how to prevent these difficulties from developing. Three research databases were searched to find possibly relevant studies. There were 877 studies found, which two researchers screened according to particular criteria. They found 52 studies that could be included in this review. One researcher evaluated the quality of these studies and extracted the key information from them. This review summarises the views of 973 autistic girls and women aged between 13 and 70+. The findings from the 52 studies were analysed, and we found many factors that affect the mental health and well-being of autistic girls and women. These factors fall into two categories: (1) difficulties living in a world not designed for autistic people and (2) the impact of stigma due to being autistic.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Adolescente , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Saúde Mental , Emoções , Pesquisadores
4.
PLoS Negl Trop Dis ; 17(12): e0011815, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38096317

RESUMO

BACKGROUND: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, with at least two African countries having now stopped MDA as they approach verification of elimination. It is essential that accurate data for active transmission are used to assist in making the critical decision to stop MDA, since missing low levels of transmission and infection can lead to continued spread or recrudescence of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Current World Health Organization guidelines for MDA stopping decisions and post-treatment surveillance include screening pools of the Simulium blackfly vector for the presence of O. volvulus larvae using a PCR-ELISA-based molecular technique. In this study, we address the potential of an updated, practical, standardized molecular diagnostic tool with increased sensitivity and species-specificity by comparing several candidate qPCR assays. When paired with heat-stable reagents, a qPCR assay with a mitochondrial DNA target (OvND5) was found to be more sensitive and species-specific than an O150 qPCR, which targets a non-protein coding repetitive DNA sequence. The OvND5 assay detected 19/20 pools of 100 blackfly heads spiked with a single L3, compared to 16/20 for the O150 qPCR assay. CONCLUSIONS/SIGNIFICANCE: Given the improved sensitivity, species-specificity and resistance to PCR inhibitors, we identified OvND5 as the optimal target for field sample detection. All reagents for this assay can be shipped at room temperature with no loss of activity. The qPCR protocol we propose is also simpler, faster, and more cost-effective than the current end-point molecular assays.


Assuntos
Volvo Intestinal , Onchocerca volvulus , Oncocercose , Simuliidae , Animais , Humanos , DNA Mitocondrial , Ivermectina/uso terapêutico , Onchocerca/genética , Onchocerca volvulus/genética , Oncocercose/tratamento farmacológico , Simuliidae/parasitologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-37913700

RESUMO

Blue mussels (Mytilus sp.) are an economically important species for European aquaculture. Their importance as a food source is expected to increase in the coming net-zero society due to their low environmental footprint; however, their production is affected by anthropogenic stressors and climate change. During reproduction, lipids are key molecules for mussels as they are the main source of energy on which newly hatched embryos depend in the first days of their development. In this work, blue mussels of different origins are analysed, focusing on the differences in lipid composition between the ovary (BMO) and the testis (BMT). The lipidome of blue mussel gonads (BMG) is studied here by combining traditional lipid profiling methods, such as fatty acid and lipid class analysis, with untargeted liquid chromatography-mass spectrometry (LC-MS) lipidomics. The approach used here enabled the identification of 770 lipid molecules from 23 different lipid classes in BMG. BMT, which consists of billions of spermatocytes, had greater amounts of cell membrane and membrane lipid components such as FA18:0, C20 polyunsaturated fatty acids (PUFA), free sterols (ST), ceramide phosphoethanolamines (CerPE), ceramide aminoethylphosphonates (CAEP), cardiolipins (CL), glycerophosphocholines (PC), glycerophosphoethanolamines (PE) and glycerophosphoserines (PS). In BMO, saturated fatty acids (FA14:0 and FA16:0), monounsaturated fatty acids (MUFA) and other storage components such as C18-PUFA accumulated in triradylglycerolipids (TG) and alkyldiacylglycerols (neutral plasmalogens, TG O-), which, together with terpenes, wax esters and cholesterol esters, make up most of oocytes yolk reserves. BMO also had higher levels of ceramides (Cer) and generally alkyl/alkenyl glycerophospholipids (mainly plasmanyl/plasmenyl PC), suggesting a role for these lipids in vitellogenesis. Non-methylene interrupted dienoic fatty acids (NMID FA), typically found in plasmalogens, were the only membrane-forming PUFA predominantly detected in BMO. The results of this study are of great importance for clarifying the lipid composition of BMG and provide an important basis for future studies on the reproductive physiology of these organisms.


Assuntos
Mytilus edulis , Mytilus , Masculino , Feminino , Animais , Lipidômica , Plasmalogênios , Caracteres Sexuais , Ácidos Graxos , Ácidos Graxos Insaturados , Gônadas , Ceramidas/análise
6.
Autism ; : 13623613231205629, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37846479

RESUMO

LAY ABSTRACT: Autistic people live with more mental and physical health conditions and, on average, die younger than non-autistic people. Despite widespread commitments to tackling these issues, autistic people still report various barriers to accessing healthcare. This article aims to explore the area in depth, from the perspective of autistic people. This research benefits from being led by autistic people, for autistic people - all of the researchers are autistic, and most of us are also medical doctors. Data, in the form of written comments and stories, were collected as part of a large survey. Here, we explored these for common themes and possible deeper meaning within the experiences. People who took part reported a variety of barriers. Here, our article gives voice to their stories, in their own words. Themes included: early barriers; communication mismatch; doubt - in oneself and from doctors; helplessness and fear; and healthcare avoidance and adverse health outcomes. Our findings allowed us to create a model that aimed to understand and explain the reported barriers in the context of the previously known consequences. We also built on wider autism theories to explain our findings in more depth.

7.
Cell ; 186(18): 3747-3752, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37657415

RESUMO

A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.


Assuntos
Transtorno Autístico , Pesquisa Biomédica , Humanos , Pesquisa Biomédica/ética , Comportamento , Pesquisa Participativa Baseada na Comunidade
8.
Front Psychiatry ; 14: 1160994, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37533891

RESUMO

Introduction: Medicine may select for autistic characteristics. As awareness and diagnosis of autism are growing, more medical students and doctors may be discovering they are autistic. No studies have explored the experiences of autistic doctors. This study aimed to fill that gap. Methods: This is a cross-sectional study. A participatory approach was used to identify the need for the project and to modify a pre-existing survey for use exploring the experiences of autistic doctors. Results: We received 225 responses. 64% had a formal diagnosis of autism. The mean age of receiving a formal diagnosis was 36 (range 3-61). Most were currently working as doctors (82%). The most common specialties were general practice / family medicine (31%), psychiatry (18%), and anesthesia (11%). Almost half of those working had completed specialty training (46%) and 40% were current trainees. 29% had not disclosed being autistic to anyone at work. 46% had requested adjustments in the workplace but of these, only half had them implemented.Three quarters had considered suicide (77%), one quarter had attempted suicide (24%) and half had engaged in self-harm (49%). 80% reported having worked with another doctor they suspected was autistic, but only 22% reported having worked with another doctor they knew was autistic. Having never worked with a potentially autistic colleague was associated with having considered suicide.Most preferred to be called "autistic doctors" (64%). Most considered autism to be a difference (83%). Considering autism to be a disorder was associated with preference for the term "doctors with autism," and with having attempted suicide. Conclusion: Autistic doctors reported many challenges in the workplace. This may have contributed to a culture of nondisclosure. Mental health was poor with high rates of suicidal ideation, self-harm, and prior suicide attempts. Despite inhospitable environments, most were persevering and working successfully. Viewing autism as a disorder was associated with prior suicide attempts and a preference for person-first language. A neurodiversity-affirmative approach to autism may lead to a more positive self-identity and improved mental health. Furthermore, providing adequate supports and improving awareness of autistic medical professionals may promote inclusion in the medical workforce.

9.
Eur J Med Genet ; 66(9): 104810, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37478903

RESUMO

Equitable and just genetic research and clinical translation require an examination of the ethical questions pertaining to vulnerable and marginalized communities. Autism research and advocate communities have expressed concerns over current practices of genetics research, urging the field to shift towards paradigms and practices that ensure benefits and avoid harm to research participants and the wider autistic community. Building upon a framework of bioethical principles, we provide the background for the concerns and present recommendations for ethically sustainable and justice-oriented genetic and genomic autism research. With the primary goal of enhancing the health, well-being, and autonomy of autistic persons, we make recommendations to guide priority setting, responsible research conduct, and informed consent practices. Further, we discuss the ethical challenges particularly pertaining to research involving highly vulnerable individuals and groups, such as those with impaired cognitive or communication ability. Finally, we consider the clinical translation of autism genetics studies, including the use of genetic testing. These guidelines, developed by an interdisciplinary working group comprising autistic and non-autistic individuals, will aid in leveraging the potential of genetics research to enhance the quality of life of autistic individuals and are widely applicable across stigmatized traits and vulnerable communities.


Assuntos
Transtorno Autístico , Humanos , Transtorno Autístico/genética , Qualidade de Vida , Consentimento Livre e Esclarecido , Testes Genéticos , Genômica
10.
Med Educ ; 57(10): 971-979, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37264701

RESUMO

BACKGROUND: Increasing recognition of autism is reflected in the growing awareness of autistic health care providers. Regulatory bodies including the UK General Medical Council and the UK Medical Schools Council have published guidance fostering inclusion. Whilst many autistic doctors and students are thriving, many may not disclose their diagnosis unless difficulties arise, which perpetuates stereotypes. No studies have explored the experiences of autistic medical students. We aimed to do this. METHODS: This was an interpretive phenomenological study. Autistic medical students were recruited using Facebook announcements. Participants underwent audio-recorded, loosely structured interviews. Recordings were transcribed verbatim and underwent an interpretive phenomenological analysis. RESULTS: Five participated from five different UK medical schools. Constructed themes included: Autistic profiles and stereotypes-'I'm a lot better with patients than I am with my peers, with staff, which is hard for a lot of people to understand'; sensory processing and the learning environment-'noises really hurt my ears … It actually hurts'; me, myself and masking-'so, medicine's hard. But I'm also studying myself and I'm figuring myself out and that degree is harder'; the social world-'I always feel like I'm watching my back'; and navigating the system-'[they say] "but you're going to be a doctor one day, so you need to get used to it"'. CONCLUSION: Participants longed for understanding and support from their medical schools. They reported experiences of isolation, bullying and anxiety. Most felt themselves to be victims of the system, whereby they were expected to adapt themselves in order to appear non-autistic. When participants reported not coping due to being autistic, most were advised to 'take time out'. None were offered personalised adjustments to their learning environment. All reported strengths associated with being autistic. This supports the assertion that autistic people can be safe, effective and skilled doctors.


Assuntos
Transtorno Autístico , Estudantes de Medicina , Humanos , Emoções , Ansiedade , Aprendizagem
11.
Br J Hosp Med (Lond) ; 84(4): 1-9, 2023 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-37127416

RESUMO

Autistic people experience significant health disparities and reduced life expectancy. Barriers to accessing healthcare are associated with adverse health outcomes. Autism training and healthcare professionals' knowledge about autism is variable, and heterogeneity among autistic people leads to additional educational and clinical complexities. Autism remains nebulous for many practitioners, who are unclear about communication differences, access needs or life experiences common to autistic people. Healthcare environments can be challenging for all patients but autistic people may require specific accommodations to allow equitable access. The authors have developed a simple framework which may facilitate equitable clinical services at all points of access and care, using the acronym 'SPACE'. This encompasses five core autistic needs: Sensory needs, Predictability, Acceptance, Communication and Empathy. Three additional domains are represented by physical space, processing space and emotional space. This simple yet memorable framework encompasses commonalities shared by autistic people.


Assuntos
Transtorno Autístico , Humanos , Transtorno Autístico/psicologia , Atenção à Saúde , Comunicação , Pessoal de Saúde , Empatia
13.
Sci Rep ; 13(1): 3937, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36894641

RESUMO

Fenretinide is a synthetic retinoid that can prevent obesity and improve insulin sensitivity in mice by directly altering retinol/retinoic acid homeostasis and inhibiting excess ceramide biosynthesis. We determined the effects of Fenretinide on LDLR-/- mice fed high-fat/high-cholesterol diet ± Fenretinide, a model of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Fenretinide prevented obesity, improved insulin sensitivity and completely inhibited hepatic triglyceride accumulation, ballooning and steatosis. Moreover, Fenretinide decreased the expression of hepatic genes driving NAFLD, inflammation and fibrosis e.g. Hsd17b13, Cd68 and Col1a1. The mechanisms of Fenretinide's beneficial effects in association with decreased adiposity were mediated by inhibition of ceramide synthesis, via hepatic DES1 protein, leading to increased dihydroceramide precursors. However, Fenretinide treatment in LDLR-/- mice enhanced circulating triglycerides and worsened aortic plaque formation. Interestingly, Fenretinide led to a fourfold increase in hepatic sphingomyelinase Smpd3 expression, via a retinoic acid-mediated mechanism and a further increase in circulating ceramide levels, linking induction of ceramide generation via sphingomyelin hydrolysis to a novel mechanism of increased atherosclerosis. Thus, despite beneficial metabolic effects, Fenretinide treatment may under certain circumstances enhance the development of atherosclerosis. However, targeting both DES1 and Smpd3 may be a novel, more potent therapeutic approach for the treatment of metabolic syndrome.


Assuntos
Aterosclerose , Fenretinida , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Ceramidas/metabolismo , Dieta Hiperlipídica , Fenretinida/farmacologia , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Esfingomielina Fosfodiesterase/metabolismo , Tretinoína/farmacologia , Receptores de LDL/metabolismo
15.
J Psychosoc Nurs Ment Health Serv ; 61(8): 34-41, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36853040

RESUMO

The purpose of the current qualitative descriptive study was to describe the experiences of women who have endured intimate partner abuse using the theoretical framework of posttraumatic growth (PTG). Women (N = 14) who reported emotional and/or physical abuse by their male partners were interviewed. Five themes were identified: Acknowledging the Abusive Relationship; Fear of Him: Threats, Control, Pain, and Isolation; Accepting Support: Grabbing the Life Preserver; Rediscovering Myself: Digging Deep; and Appreciating Life and Helping Others. Findings have practical implications for nurses who are in pivotal positions to educate and influence others about the possibility of PTG following partner abuse. Nurses can help women find their way through this trauma and teach others about coping, healing, and recovery. [Journal of Psychosocial Nursing and Mental Health Services, 61(8), 34-41.].


Assuntos
Violência por Parceiro Íntimo , Crescimento Psicológico Pós-Traumático , Maus-Tratos Conjugais , Humanos , Masculino , Feminino , Violência por Parceiro Íntimo/psicologia , Maus-Tratos Conjugais/psicologia , Emoções , Adaptação Psicológica
16.
Int J Mol Sci ; 24(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36834818

RESUMO

CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.


Assuntos
Resistência à Insulina , Proteínas Proto-Oncogênicas c-cbl , Animais , Camundongos , Metabolismo Energético , Insulina/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias Musculares/metabolismo , Células Musculares/metabolismo , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Respiração Celular
17.
Nurs Womens Health ; 27(1): 15-24, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36529258

RESUMO

OBJECTIVE: To describe the experiences of women who have had a close brush with death and the elements of posttraumatic growth as a result of their experiences. DESIGN: Using a theoretical framework of posttraumatic growth, we conducted a qualitative descriptive study with interviews of women who have had a close brush with death. SETTING: Women were interviewed in the environment of their choosing: in their home, at a coffee shop, or over the telephone. PARTICIPANTS: Twelve women ages 35 to 79 years from the United States participated in the study, all of whom reported having a close brush with death. METHOD: Interviews were conducted using a semistructured interview guide derived from the theoretical framework. RESULTS: Five themes emerged from the data: My Trauma Experience, My Will to Live, SupportWas Important, Putting the Pieces of My Life Back Together, and Near-Death Experiences. Participants reported having experienced various elements of posttraumatic growth. Many attributed their posttraumatic growth to a myriad of factors such as having a supportive network, their belief in God as a source of strength, and the will to live. Others credited health care professionals for quality care and encouragement. CONCLUSION: Knowledge development regarding posttraumatic growth can enhance nursing practice in the care of women as they navigate life after trauma. Nurses and other health care providers are in strategic positions to educate women about the possibility of posttraumatic growth after adversity. They can help women find their path with a strong voice after trauma. Women who have experienced posttraumatic growth can teach others about healing, coping, empathy, compassion, and the importance of human connection.


Assuntos
Crescimento Psicológico Pós-Traumático , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Adaptação Psicológica , Empatia , Pesquisa Qualitativa
18.
Radiother Oncol ; 178: 109437, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36481383

RESUMO

BACKGROUND AND PURPOSE: Patients with anal squamous cell carcinoma (SCC) are treated with sphincter-preserving radiation therapy and concurrent chemotherapy, achieving excellent oncologic outcomes. Patients, however, may experience treatment-related morbidity including sexual dysfunction. The objective of this systematic review was to review the literature on sexual dysfunction in female patients treated for anal cancer and to identify knowledge gaps. MATERIALS AND METHODS: This systematic review was registered in PROSPERO prior to initiation. Databases searched included MEDLINE, Embase, PubMed, Cochrane, and Google Scholar. There were no restrictions on the study time period. Studies were limited to English. All study designs were included except review articles, letters to the editor, and case reports with less than ten patients. RESULTS: In total, 1801 studies were retrieved and 19 met the inclusion criteria, including: 13 cross-sectional surveys, 3 prospective studies, 1 longitudinal intervention study, 1 retrospective chart review, 1 case control study. Sexual function was assessed using the female sexual functioning index (FSFI), EORTC-QLQ-CR30 and -CR38; response rates were low (<50 % in most studies). Sexual dysfunction was reported by up to 85 % of women; the most common symptoms being dyspareunia (17-65 %), vaginal dryness (22-88 %), and loss of libido (38-95 %). Gastrointestinal issues, such as bowel problems, and body image concerns additionally affected sexual function and quality of life. CONCLUSION: Sexual dysfunction is a common issue affecting most female patients treated for anal cancer and there is a paucity of evidence on the management of this important survivorship issue. There is additionally a lack of ethnic, economic, and educational diversity and there are no studies addressing the unique needs of LGBTQ individuals - future studies should make a concerted effort to include a diverse patient population.


Assuntos
Neoplasias do Ânus , Disfunções Sexuais Fisiológicas , Humanos , Feminino , Qualidade de Vida , Estudos de Casos e Controles , Estudos Retrospectivos , Estudos Transversais , Estudos Prospectivos , Neoplasias do Ânus/radioterapia , Disfunções Sexuais Fisiológicas/etiologia
19.
J Extracell Vesicles ; 11(12): e12295, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36544284

RESUMO

Age-related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the retinal pigment epithelium (RPE) and photoreceptors atrophy and/or retinal and choroidal angiogenesis. Here we use AMD patient-specific RPE cells with the Complement Factor H Y402H high-risk polymorphism to perform a comprehensive analysis of extracellular vesicles (EVs), their cargo and role in disease pathology. We show that AMD RPE is characterised by enhanced polarised EV secretion. Multi-omics analyses demonstrate that AMD RPE EVs carry RNA, proteins and lipids, which mediate key AMD features including oxidative stress, cytoskeletal dysfunction, angiogenesis and drusen accumulation. Moreover, AMD RPE EVs induce amyloid fibril formation, revealing their role in drusen formation. We demonstrate that exposure of control RPE to AMD RPE apical EVs leads to the acquisition of AMD features such as stress vacuoles, cytoskeletal destabilization and abnormalities in the morphology of the nucleus. Retinal organoid treatment with apical AMD RPE EVs leads to disrupted neuroepithelium and the appearance of cytoprotective alpha B crystallin immunopositive cells, with some co-expressing retinal progenitor cell markers Pax6/Vsx2, suggesting injury-induced regenerative pathways activation. These findings indicate that AMD RPE EVs are potent inducers of AMD phenotype in the neighbouring RPE and retinal cells.


Assuntos
Vesículas Extracelulares , Degeneração Macular , Humanos , Epitélio Pigmentado da Retina/metabolismo , Vesículas Extracelulares/metabolismo , Retina/metabolismo , Retina/patologia , Degeneração Macular/metabolismo , Fenótipo
20.
Eur J Psychotraumatol ; 13(2): 2128028, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276556

RESUMO

Background: Moral injury is defined as the strong emotional and cognitive reactions following events which clash with someone's moral code, values or expectations. During the COVID-19 pandemic, increased exposure to Potentially Morally Injurious Events (PMIEs) has placed healthcare workers (HCWs) at risk of moral injury. Yet little is known about the lived experience of cumulative PMIE exposure and how NHS staff respond to this. Objective: We sought to rectify this knowledge gap by qualitatively exploring the lived experiences and perspectives of clinical frontline NHS staff who responded to COVID-19. Methods: We recruited a diverse sample of 30 clinical frontline HCWs from the NHS CHECK study cohort, for single time point qualitative interviews. All participants endorsed at least one item on the 9-item Moral Injury Events Scale (MIES) [Nash et al., 2013. Psychometric evaluation of the moral injury events scale. Military Medicine, 178(6), 646-652] at six month follow up. Interviews followed a semi-structured guide and were analysed using reflexive thematic analysis. Results: HCWs described being routinely exposed to ethical conflicts, created by exacerbations of pre-existing systemic issues including inadequate staffing and resourcing. We found that HCWs experienced a range of mental health symptoms primarily related to perceptions of institutional betrayal as well as feeling unable to fulfil their duty of care towards patients. Conclusion: These results suggest that a multi-facetted organisational strategy is warranted to prepare for PMIE exposure, promote opportunities for resolution of symptoms associated with moral injury and prevent organisational disengagement. HIGHLIGHTS Clinical frontline healthcare workers (HCWs) have been exposed to an accumulation of potentially morally injurious events (PMIEs) throughout the COVID-19 pandemic, including feeling betrayed by both government and NHS leaders as well as feeling unable to provide duty of care to patients.HCWs described the significant adverse impact of this exposure on their mental health, including increased anxiety and depression symptoms and sleep disturbance.Most HCWs interviewed believed that organisational change within the NHS was necessary to prevent excess PMIE exposure and promote resolution of moral distress.


Antecedentes: El daño moral se define como las fuertes reacciones emocionales y cognitivas que siguen a los eventos que chocan con el código moral de una persona, sus valores o expectativas. Durante la pandemia de COVID-19, el aumento de la exposición a Eventos Potencialmente Dañinos para la Moral (PMIEs, por su sigla en inglés) ha puesto a los trabajadores de la salud (HCWs, por su sigla en inglés) en riesgo de daño moral. Aún se conoce poco sobre la experiencia vivida de la exposición acumulada a PMIE y cómo el personal del Servicio Nacional de Salud de Inglaterra (NHS en su sigla en inglés) responde a esto.Objetivo: Buscamos rectificar esta brecha de conocimiento a través de la exploración cualitativa de las experiencias vividas y perspectivas del personal clínico de primera línea de NHS que respondió al COVID-19.Métodos: Reclutamos una muestra diversa de 30 HCWs clínicos de primera línea de la cohorte del estudio CHECK del NHS, para entrevistas cualitativas de una sola vez. Todos los participantes aprobaron al menos un ítem de los 9 de la Escala de Eventos de Daño Moral (MIES) [Nash y cols., 2013. Psychometric evaluation of the moral injury events scale. Military Medicine, 178(6), 646­652] en el seguimiento a los 6 meses. Las entrevistas siguieron una guía semi-estructurada y fueron analizadas utilizando análisis temático reflexivo.Resultados: Los HCWs describieron estar expuestos de forma rutinaria a conflictos éticos, creados por exacerbación de problemas sistémicos pre-existentes que incluían falta de personal y de recursos. Encontramos que los HCWs experimentaron un rango de síntomas de salud mental primariamente relacionados a percepciones de traición institucional y al sentirse incapaces de cumplir con su deber de cuidado hacia los pacientes.Conclusión: Estos resultados sugieren que se requiere una estrategia organizacional multifacética para preparar para la exposición a PMIE fomentar oportunidades de resolución de los síntomas asociados al daño moral y prevenir la separación organizacional.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Pandemias , Pessoal de Saúde/psicologia , Princípios Morais
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