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Solutions to complex and unprecedented global challenges are urgently needed. Overcoming these challenges requires input and innovative solutions from all experts, including Early Career Ocean Professionals (ECOPs). To achieve diverse inclusion from ECOPs, fundamental changes must occur at all levels-from individuals to organizations. Drawing on insights from across the globe, we propose 5 actionable pillars that support the engagement of ECOPs in co-design processes that address ocean sustainability: sharing knowledge through networks and mentorship, providing cross-boundary training and opportunities, incentivizing and celebrating knowledge co-design, creating inclusive and participatory governance structures, and catalyzing culture change for inclusivity. Foundational to all actions are the cross-cutting principles of justice, equity, diversity, and inclusivity. In addition, the pillars are cross-boundary in nature, including collaboration and innovation across sectors, disciplines, regions, generations, and backgrounds. Together, these recommendations provide an actionable and iterative path toward inclusive engagement and intergenerational exchange that can develop ocean solutions for a sustainable future.
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Conservação dos Recursos Naturais , Humanos , Oceanos e MaresRESUMO
AIM: To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity. DESIGN: An interpretive, descriptive, qualitative interview study. METHODS: Data were collected using semi-structured interviews undertaken between January and November 2020. Participants were neonatal intensive care nursing staff taking part in the Pharmacogenetics to Avoid Loss of Hearing trial. RESULTS: Thematic analysis resulted in four themes: perceived clinical utility; the golden hour; point-of-care device; training and support. Recommendations were made to streamline the protocol and ongoing training and support were considered key to incorporating the test into routine care. CONCLUSION: Exploring the views of nurses involved in the delivery of the point-of-care test was essential in its implementation. By the study endpoint, all participants could see the value of routine clinical introduction of the point-of care test. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses are in a key position to support the delivery of point-of-care genetic testing into mainstream settings. This study has implications for the successful integration of other genetic point-of-care tests in acute healthcare settings. IMPACT: The study will help to tailor the training and support required for routine deployment of the genetic point-of-care test. The study has relevance for nurses involved in the development and delivery of genetic point-of-care tests in other acute hospital settings. REPORTING METHOD: This qualitative study adheres to the Standards for Reporting Qualitative Research EQUATOR guidelines and utilizes COREQ and SRQR checklists. PATIENT OR PUBLIC CONTRIBUTION: All staff working on the participating neonatal intensive care units were trained to use the genetic point-of-care test. All inpatients on the participating units were eligible to have testing via the point-of-care test. The Pharmacogenetics to Avoid Loss of Hearing Patient and Public Involvement and Engagement group provided valuable feedback. TRIAL AND PROTOCOL REGISTRATION: Registered within the University of Manchester. Ethics approval reference numbers: IRAS: 253102 REC reference: 19/NW/0400. Also registered with the ISRCTN ref: ISRCTN13704894.
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Antibacterianos , Unidades de Terapia Intensiva Neonatal , Testes Imediatos , Pesquisa Qualitativa , Humanos , Recém-Nascido , Antibacterianos/efeitos adversos , Feminino , Masculino , Ototoxicidade , Atitude do Pessoal de Saúde , Recursos Humanos de Enfermagem Hospitalar , Adulto , Sistemas Automatizados de Assistência Junto ao Leito , Testes GenéticosRESUMO
MOTIVATION: InterARTIC is an interactive web application for the analysis of viral whole-genome sequencing (WGS) data generated on Oxford Nanopore Technologies (ONT) devices. A graphical interface enables users with no bioinformatics expertise to analyze WGS experiments and reconstruct consensus genome sequences from individual isolates of viruses, such as SARS-CoV-2. InterARTIC is intended to facilitate widespread adoption and standardization of ONT sequencing for viral surveillance and molecular epidemiology. RESULTS: We demonstrate the use of InterARTIC for the analysis of ONT viral WGS data from SARS-CoV-2 and Ebola virus, using a laptop computer or the internal computer on an ONT GridION sequencing device. We showcase the intuitive graphical interface, workflow customization capabilities and job-scheduling system that facilitate execution of small- and large-scale WGS projects on any common virus. AVAILABILITY AND IMPLEMENTATION: InterARTIC is a free, open-source web application implemented in Python that executes best-practice command line workflows from the ARTIC network. The application can be downloaded as a set of pre-compiled binaries that are compatible with all common Linux distributions, Windows with Linux subsystems, MacOSX and ARM systems. All code can be found on GitHub at https://github.com/Psy-Fer/interARTIC/ and documentation can be found at https://github.com/Psy-Fer/interARTIC/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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COVID-19 , Sequenciamento por Nanoporos , Nanoporos , Humanos , SARS-CoV-2/genética , Software , Genoma ViralRESUMO
Changes to the structure of nodes of Ranvier in the normal-appearing white matter (NAWM) of multiple sclerosis (MS) brains are associated with chronic inflammation. We show that the paranodal domains in MS NAWM are longer on average than control, with Kv1.2 channels dislocated into the paranode. These pathological features are reproduced in a model of chronic meningeal inflammation generated by the injection of lentiviral vectors for the lymphotoxin-α (LTα) and interferon-γ (IFNγ) genes. We show that tumour necrosis factor (TNF), IFNγ, and glutamate can provoke paranodal elongation in cerebellar slice cultures, which could be reversed by an N-methyl-D-aspartate (NMDA) receptor blocker. When these changes were inserted into a computational model to simulate axonal conduction, a rapid decrease in velocity was observed, reaching conduction failure in small diameter axons. We suggest that glial cells activated by pro-inflammatory cytokines can produce high levels of glutamate, which triggers paranodal pathology, contributing to axonal damage and conduction deficits.
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Esclerose Múltipla/patologia , Nós Neurofibrosos/patologia , Substância Branca/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axônios/patologia , Encéfalo/patologia , Sinapses Elétricas/patologia , Sinapses Elétricas/efeitos da radiação , Feminino , Humanos , Inflamação/patologia , Masculino , Microglia/patologia , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Bainha de Mielina/patologia , Neuroglia/patologia , Neuroimunomodulação/imunologia , Neuroimunomodulação/fisiologia , Nós Neurofibrosos/fisiologia , Substância Branca/diagnóstico por imagem , Substância Branca/imunologiaRESUMO
Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease of variable clinical severity that is caused by mutations in the survival motor neuron 1 (SMN1) gene. Despite its name, SMN is a ubiquitous protein that functions within and outside the nervous system and has multiple cellular roles in transcription, translation, and proteostatic mechanisms. Encouragingly, several SMN-directed therapies have recently reached the clinic, albeit this has highlighted the increasing need to develop combinatorial therapies for SMA to achieve full clinical efficacy. As a subcellular site of dysfunction in SMA, mitochondria represents a relevant target for a combinatorial therapy. Accordingly, we will discuss our current understanding of mitochondrial dysfunction in SMA, highlighting mitochondrial-based pathways that offer further mechanistic insights into the involvement of mitochondria in SMA. This may ultimately facilitate translational development of targeted mitochondrial therapies for SMA. Due to clinical and mechanistic overlaps, such strategies may also benefit other motor neuron diseases and related neurodegenerative disorders.
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Mitocôndrias/fisiologia , Atrofia Muscular Espinal/fisiopatologia , Animais , Humanos , Mitocôndrias/genética , Neurônios Motores/fisiologia , Atrofia Muscular Espinal/genética , Mutação/genética , Proteínas do Complexo SMN/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: Patient and public involvement (PPI) in research improves relevance to end users and improves processes including recruitment participants. PPI in our research has gone from being non-existent to ubiquitous over a few years. We provide critical reflections on the benefits and challenges of PPI. DESIGN: Case studies are reported according to a modified GRIP2 framework; the aims, methodology, impact of PPI and critical reflections on each case and our experiences with PPI in general. STUDY SAMPLE: We report five UK projects that included PPI from teenagers, families, people living with dementia, autistic people, and people from South Asian and d/Deaf communities. RESULTS: Our experience has progressed from understanding the rationale to grappling methodologies and integrating PPI in our research. PPI took place at all stages of research, although commonly involved input to design including recruitment and development of study materials. Methodologies varied between projects, including PPI co-investigators, advisory panels and online surveys. CONCLUSION: On-going challenges include addressing social exclusion from research for people that lack digital access following increasing on-line PPI and involvement from underserved communities. PPI was initially motivated by funders; however the benefits have driven widespread PPI, ensuring our research is relevant to people living with hearing loss.
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Defense of reproductive choice is an important motivation in women's self-protection psychology for which the "staying alive theory" cannot fully account. Evidence indicates that some elements of women's self-protection psychology function to protect reproductive choice rather than survival, or may be equally well explained by either motivation. Integrating perspectives will result in greater explanatory breadth and precision in theory testing.
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Reprodução , Direitos da Mulher , Feminino , Humanos , MotivaçãoRESUMO
Sustained exposure to pro-inflammatory cytokines in the leptomeninges is thought to play a major role in the pathogenetic mechanisms leading to cortical pathology in multiple sclerosis (MS). Although the molecular mechanisms underlying neurodegeneration in the grey matter remain unclear, several lines of evidence suggest a prominent role for tumour necrosis factor (TNF). Using cortical grey matter tissue blocks from post-mortem brains from 28 secondary progressive MS subjects and ten non-neurological controls, we describe an increase in expression of multiple steps in the TNF/TNF receptor 1 signaling pathway leading to necroptosis, including the key proteins TNFR1, FADD, RIPK1, RIPK3 and MLKL. Activation of this pathway was indicated by the phosphorylation of RIPK3 and MLKL and the formation of protein oligomers characteristic of necrosomes. In contrast, caspase-8 dependent apoptotic signaling was decreased. Upregulation of necroptotic signaling occurred predominantly in macroneurons in cortical layers II-III, with little expression in other cell types. The presence of activated necroptotic proteins in neurons was increased in MS cases with prominent meningeal inflammation, with a 30-fold increase in phosphoMLKL+ neurons in layers I-III. The density of phosphoMLKL+ neurons correlated inversely with age at death, age at progression and disease duration. In vivo induction of chronically elevated TNF and INFγ levels in the CSF in a rat model via lentiviral transduction in the meninges, triggered inflammation and neurodegeneration in the underlying cortical grey matter that was associated with increased neuronal expression of TNFR1 and activated necroptotic signaling proteins. Exposure of cultured primary rat cortical neurons to TNF induced necroptosis when apoptosis was inhibited. Our data suggest that neurons in the MS cortex are dying via TNF/TNFR1 stimulated necroptosis rather than apoptosis, possibly initiated in part by chronic meningeal inflammation. Neuronal necroptosis represents a pathogenetic mechanism that is amenable to therapeutic intervention at several points in the signaling pathway.
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Substância Cinzenta/patologia , Esclerose Múltipla Crônica Progressiva/patologia , Necroptose/fisiologia , Neurônios/patologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Animais , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Feminino , Substância Cinzenta/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Receptores do Fator de Necrose Tumoral/metabolismo , Transdução de Sinais/fisiologiaRESUMO
Meningeal inflammation strongly associates with demyelination and neuronal loss in the underlying cortex of progressive MS patients, thereby contributing significantly to clinical disability. However, the pathological mechanisms of meningeal inflammation-induced cortical pathology are still largely elusive. By extensive analysis of cortical microglia in post-mortem progressive MS tissue, we identified cortical areas with two MS-specific microglial populations, termed MS1 and MS2 cortex. The microglial population in MS1 cortex was characterized by a higher density and increased expression of the activation markers HLA class II and CD68, whereas microglia in MS2 cortex showed increased morphological complexity and loss of P2Y12 and TMEM119 expression. Interestingly, both populations associated with inflammation of the overlying meninges and were time-dependently replicated in an in vivo rat model for progressive MS-like chronic meningeal inflammation. In this recently developed animal model, cortical microglia at 1-month post-induction of experimental meningeal inflammation resembled microglia in MS1 cortex, and microglia at 2 months post-induction acquired a MS2-like phenotype. Furthermore, we observed that MS1 microglia in both MS cortex and the animal model were found closely apposing neuronal cell bodies and to mediate pre-synaptic displacement and phagocytosis, which coincided with a relative sparing of neurons. In contrast, microglia in MS2 cortex were not involved in these synaptic alterations, but instead associated with substantial neuronal loss. Taken together, our results show that in response to meningeal inflammation, microglia acquire two distinct phenotypes that differentially associate with neurodegeneration in the progressive MS cortex. Furthermore, our in vivo data suggests that microglia initially protect neurons from meningeal inflammation-induced cell death by removing pre-synapses from the neuronal soma, but eventually lose these protective properties contributing to neuronal loss.
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Córtex Cerebral/patologia , Meninges/patologia , Microglia/patologia , Esclerose Múltipla/patologia , Doenças Neurodegenerativas/patologia , Doenças Neuroinflamatórias/patologia , Neurônios/patologia , Adulto , Idoso , Animais , Morte Celular , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Feminino , Humanos , Meninges/imunologia , Microglia/classificação , Microglia/imunologia , Microglia/metabolismo , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Doenças Neurodegenerativas/imunologia , Fenótipo , RatosRESUMO
The circumvention of female reproductive choice via rape is a costly and evolutionarily persistent threat to women's reproductive fitness. This is argued to have generated selection pressure for a precautionary threat management system for rape avoidance among women. Such a system would regulate women's fear of rape as a functional emotional response to inputs providing information about the current risk and reproductive cost of rape. Fear of rape is expected to subsequently motivate adaptive behavior to avoid threats to one's reproductive choice. The current research tested key tenets of this proposed system and found that women report greater fear of rape as a function of characteristics that alter the likelihood of being victimized, including being younger, living in a neighborhood perceived as dangerous, living in close proximity to family, and having been the victim of a sexual assault in the past. We also discuss mixed and null results with respect to the role of relationship status and mate value. In turn, fear of rape was associated with behavior expected to reduce one's risk of being victimized. Specifically, women who were more fearful of rape reported consuming true crime media with greater frequency and indicated that this consumption was specifically motivated by the desire to learn strategies to prevent or escape an attack. Overall, results were fairly consistent with a threat management system approach and may help to explain why fear of rape is a powerful feature of women's psychology.
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Vítimas de Crime , Estupro , Crime , Medo , Feminino , HumanosRESUMO
AIMS: Obesity-related complications have been identified across the entire childbearing journey. This study investigated changes in obesity prevalence and their impact on obstetric outcomes in a regional hospital in Victoria, Australia. METHODS: All women delivering during 1 January 2010 and 31 December 2016 were eligible to participate. Trends over time and outcomes were assessed on body mass indices (BMI). Incidences of complications were compared by BMI categories. The effect of obesity on hospital length of stay (LoS) was further assessed using the Generalised Estimating Equations approach. RESULTS: During the study period a total of 6661 women of whom 27.5% were overweight, and 16.1, 7.7, and 5.5% were respectively obese class I, class II, and class III, contributed to 8838 births. An increased trend over time in the prevalence of obesity (BMI > 35.0) (P = 0.041) and a decreased trend for vaginal deliveries for the whole sample (P = 0.003) were found. Multiple adverse outcomes were associated with increasing maternal BMI including increased risk of gestational diabetes, gestational hypertension, preeclampsia, emergency caesarean section, shoulder dystocia, macrosomia, and admission to special care. The multivariable analysis showed no associations between LoS and BMI. CONCLUSIONS: Over a short period of seven years, this study provides evidence of a significant trend toward more obesity and fewer vaginal births in a non-urban childbearing population, with increasing trends of poorer health outcomes. Assessing needs and risk factors tailored to this population is crucial to ensuring a model of care that safeguards a sustainable and effective regional maternity health service.
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Parto Obstétrico/estatística & dados numéricos , Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Índice de Massa Corporal , Cesárea/estatística & dados numéricos , Diabetes Gestacional/epidemiologia , Feminino , Macrossomia Fetal/epidemiologia , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Tempo de Internação , Sobrepeso/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Prevalência , Estudos Retrospectivos , Fatores de Risco , Vitória/epidemiologiaRESUMO
BACKGROUND: Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases. METHODS: To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls. RESULTS: Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared with controls. Increased meningeal inflammation was found to be associated with a shift in the balance of TNF signalling away from TNFR1/TNFR2 and NFkB-mediated anti-apoptotic pathways towards TNFR1- and RIPK3-mediated pro-apoptotic/pro-necroptotic signalling in the grey matter, which was confirmed by RT-PCR analysis. TNFR1 was found expressed preferentially on neurons and oligodendrocytes in MS cortical grey matter, whereas TNFR2 was predominantly expressed by astrocytes and microglia. CONCLUSIONS: We suggest that the inflammatory milieu generated in the subarachnoid space of the multiple sclerosis meninges by infiltrating immune cells leads to increased demyelinating and neurodegenerative pathology in the underlying grey matter due to changes in the balance of TNF signalling.
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Córtex Cerebral/metabolismo , Substância Cinzenta/metabolismo , Meninges/metabolismo , Esclerose Múltipla/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Córtex Cerebral/patologia , Feminino , Substância Cinzenta/patologia , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , Meninges/patologia , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Esclerose Múltipla/patologia , Transcriptoma/fisiologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
Absorption spectra of films of N2O, in the range 115-160 nm, are presented for deposition temperatures between 33 K and 64 K. Observed shifts in the absorption energy vs. deposition temperature are analysed in terms of the temperature-dependent spontaneously electrical ('spontelectric') fields present in the films. Using a simple electrostatic theory, we suggest that (i) spectra are associated with Wannier-Mott excitons, (ii) the action of the electric field upon the excitons suffers a blockade at ≤54 K for the C-state and ≤52 K for the D-state of N2O, (iii) the blockade may be attributed to structural defects, which trap excitons, limiting their size and (iv) films form with defect-free regions containing 324 ± 3, 168 ± 46 and 95 ± 1 molecules of N2O at 54 K, 52 K and 50 K respectively, yielding an experimental indication of the scale size of regular periodicity associated with Wannier-Mott excitons. Results demonstrate how the spontelectric effect can be used as a tool for exploring the structure of solids and give a graphic image of the structural changes that take place close to the known phase change at 47 K/48 K.
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Multiple sclerosis (MS) frequently starts near the lateral ventricles, which are lined by subventricular zone (SVZ) progenitor cells that can migrate to lesions and contribute to repair. Because MS-induced inflammation may decrease SVZ proliferation and thus limit repair, we studied the role of galectin-3 (Gal-3), a proinflammatory protein. Gal-3 expression was increased in periventricular regions of human MS in post-mortem brain samples and was also upregulated in periventricular regions in a murine MS model, Theiler's murine encephalomyelitis virus (TMEV) infection. Whereas TMEV increased SVZ chemokine (CCL2, CCL5, CCL, and CXCL10) expression in wild type (WT) mice, this was inhibited in Gal-3(-/-) mice. Though numerous CD45+ immune cells entered the SVZ of WT mice after TMEV infection, their numbers were significantly diminished in Gal-3(-/-) mice. TMEV also reduced neuroblast and proliferative SVZ cell numbers in WT mice but this was restored in Gal-3(-/-) mice and was correlated with increased numbers of doublecortin+ neuroblasts in the corpus callosum. In summary, our data showed that loss of Gal-3 blocked chemokine increases after TMEV, reduced immune cell migration into the SVZ, reestablished SVZ proliferation and increased the number of progenitors in the corpus callosum. These results suggest Gal-3 plays a central role in modulating the SVZ neurogenic niche's response to this model of MS.
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Encéfalo/metabolismo , Galectina 3/metabolismo , Esclerose Múltipla/metabolismo , Doença Autoimune do Sistema Nervoso Experimental/metabolismo , Neurogênese , Nicho de Células-Tronco/fisiologia , Adolescente , Adulto , Idoso , Animais , Encéfalo/imunologia , Encéfalo/patologia , Movimento Celular , Criança , Feminino , Galectina 3/genética , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Doença Autoimune do Sistema Nervoso Experimental/imunologia , Doença Autoimune do Sistema Nervoso Experimental/patologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Poliomielite/metabolismo , Poliomielite/patologia , Theilovirus , Adulto JovemRESUMO
Before the COVID-19 pandemic, the prevalence and severity of psychiatric disorders among sexual and gender diverse (SGD) young people was greater than in their heterosexual/cisgender peers. We systematically reviewed literature examining the prevalence, severity, and risk factors for psychiatric disorders among SGD young people aged 25 and under during the pandemic. Four databases (MEDLINE, PsycInfo, Scopus and Web of Science) were searched. Eligibility criteria were studies assessing prevalence rates, mean symptomology scores and risk factors of psychiatric disorders using contemporaneous screening measures or diagnosis. Thirteen studies of mixed quality were identified. Most studies indicated SGD young people were at high risk of experiencing several psychiatric disorders including depressive and generalised anxiety disorder compared to the general population. This group also experienced more severe symptomology of various psychiatric disorders compared to their heterosexual/cisgender peers. Risk factors included those specific to the pandemic along with factors that led to greater risk before the pandemic. This systematic review has indicated evidence of heightened risk of psychiatric disorders among SGD young people during the COVID-19 pandemic. It is important for clinicians to acknowledge the needs of SGD young people, working with them to co-develop more inclusive care as they deal with the pandemic's fallout.
Why was the study done?Before the COVID-19 pandemic, the prevalence and severity of psychiatric disorders in sexual and gender diverse (SGD) young people was greater than in their heterosexual/cisgender peers, based on several risk factors. Research using validated screening measures assessed whether this continued during the pandemic. Yet, these studies have not been brought together in an organised fashion to provide a comprehensive summary of this evidence.What did the researchers do?We reviewed literature examining the prevalence, severity, and risk factors for psychiatric disorders among SGD young people aged 25 and under during the pandemic. Eligibility criteria were studies assessing prevalence rates, mean symptomology scores or risk factors of psychiatric disorders using contemporaneous screening measures or diagnosis.What did the researchers find?Thirteen studies of mixed quality were identified. Most studies indicated SGD young people were more likely to report experiencing several psychiatric disorders including depressive and generalised anxiety disorders compared to the general population. SGD young people also experienced more severe symptomology of various psychiatric disorders compared to their heterosexual/cisgender peers. Risk factors included those specific to the pandemic along with factors that existed before the pandemic.What do the findings mean?This review suggests SGD young people were at greater risk of psychiatric disorders during the COVID-19 pandemic. Clinicians should acknowledge the needs of SGD young people, working with them to co-develop more inclusive care as they deal with the pandemic's fallout.
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COVID-19 , Transtornos Mentais , Minorias Sexuais e de Gênero , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Fatores de Risco , Transtornos Mentais/epidemiologia , Prevalência , Adolescente , Minorias Sexuais e de Gênero/psicologia , Adulto Jovem , Índice de Gravidade de Doença , Feminino , Masculino , AdultoRESUMO
BACKGROUND: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder with known acute and longstanding physical health complications in children and young people (CYP) and commonly presents to paediatricians. OBJECTIVE: To systematically review the published literature on physical health complications in CYP with ARFID using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: A systematic search of PubMed, Embase, Web of Science, PsycINFO and Cochrane Library was performed on 14 February 2024. Studies reporting physical health complications in CYP ≤25 years with ARFID were included. We pooled studies for meta-analysis comparing ARFID with healthy controls or anorexia nervosa (AN). RESULTS: Of 9058 studies found in searches, we included 132 studies. We found evidence for low weight, nutritional deficiencies and low bone mineral density. CYP with ARFID can present across the weight spectrum; however, the majority of CYP with ARFID were within the healthy weight to underweight range. Most studies reported normal range heart rates and blood pressures in ARFID, but some CYP with ARFID do experience bradycardia and hypotension. CYP with ARFID had higher heart rates than AN (weighted mean difference: 12.93 bpm; 95% CI: 8.65 to 17.21; n=685); heterogeneity was high (I2: 81.33%). CONCLUSION: There is a broad range of physical health complications associated with ARFID requiring clinical consideration. Many CYP with ARFID are not underweight yet still have complications. Less cardiovascular complications found in ARFID compared with AN may be related to chronicity. PROSPERO REGISTRATION NUMBER: CRD42022376866.
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Transtorno Alimentar Restritivo Evitativo , Humanos , Criança , Adolescente , Adulto JovemRESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive childhood-onset neuromuscular disease with a carrier frequency of ~1:50. Mitochondrial abnormalities are widespread in patients with SMA. Disease carriers for SMA (i.e., the parents of patients with SMA) are viewed as asymptomatic for SMA disease. As far as we are aware, mitochondria have not been previously examined in SMA carriers, yet as they are maternally inherited, mitochondrial function in SMA carriers has putative implications for disease pathogenesis. METHODS: Fibroblast cell lines derived from SMA carriers and controls were obtained from two different sources and cultured under standard conditions. The mitochondrial membrane potential, reactive oxygen species (ROS) production, citrate synthase activity, and bioenergetic analysis were examined as measures of mitochondrial function. The mitochondrial genome was also sequenced in a subset of the fibroblast cell lines to identify any mitochondrial DNA variants. RESULTS: Here, we show a depolarized mitochondrial membrane potential, increased levels of reactive oxygen species, and reduced citrate synthase activity in SMA carriers compared with controls. A likely pathogenic variant in the MT-CO3 gene (which encodes subunit III of cytochrome c oxidase) was also identified in a paternal carrier. CONCLUSIONS: This study was conducted as a preliminary investigation of mitochondrial function in SMA carriers. Our findings suggest that disease carriers of SMA show differences in mitochondrial function, indicative of a subclinical mitochondrial phenotype. Further investigation in a larger sample set is warranted.
Spinal muscular atrophy (SMA) is a disease that mostly affects children in which the muscles become weaker over time, and often leads to death in untreated individuals. It is caused by a defective gene that children often inherit from their parents. The parents of children with SMA are known as disease carriers if they do not show any symptoms of SMA themselves. We studied skin cells from the parents of people with SMA and found changes in a component of the cells called the mitochondria. These changes are not normally present in healthy individuals. Further work is needed to fully understand the implications of our findings for those with SMA and their parents.
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BACKGROUND: Point of care tests (POCTs) have the potential to improve the urinary tract infection (UTI) diagnostic pathway, as they can provide a diagnosis quickly in near-patient settings, and some also identify causative pathogens/antimicrobial sensitivity. OBJECTIVES: To assess the clinical impact, accuracy, and technical characteristics of POCT for diagnosing UTI. METHODS OF DATA SYNTHESIS: Narrative summary and bivariate random effects meta-analyses to estimate summary sensitivity and specificity. DATA SOURCES: Five electronic databases, two clinical trial registries, study reports and review reference lists, and websites. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials/non-randomized studies and diagnostic test accuracy studies published since 2000. PARTICIPANTS: People with suspected UTI. TESTS: Rapid tests (results <40 minutes): Astrego PA-100 system, Lodestar DX, Uriscreen, UTRiPLEX. Culture tests (results <24 hours): Flexicult Human, ID Flexicult, Diaslide, Dipstreak, Chromostreak, Uricult, Uricult Trio, Uricult Plus. REFERENCE STANDARD: Any. ASSESSMENT OF RISK OF BIAS: Risk of Bias-2, Quality Assessment of Diagnostic Accuracy Studies-2, Quality Assessment of Diagnostic Accuracy Studies-C. RESULTS: Two randomized controlled trials evaluated Flexicult Human (one against standard care; one against ID Flexicult). No difference was reported in antibiotic use concordant with culture results (OR 0.84 95% CI 0.58-1.20) or appropriate antibiotic prescribing (OR 1.44 95% CI 1.03-1.99). Initial antibiotic prescribing was lower with Flexicult than standard care (OR 0.56 95% CI 0.35-0.88). No difference for other measures of antibiotic use, symptom duration, patient enablement, or resource use. Fifteen studies reported accuracy data. Limited data were available, with most POCT evaluated in single studies or not evaluated at all. Uriscreen (four studies), Uricult Trio (three studies), Flexicult Human (four studies), and ID Flexicult (two studies) had modest sensitivity and specificity. POCTs were easier to use and interpret than standard culture. CONCLUSIONS: There is currently insufficient evidence to support the use of POCTs in UTI diagnosis. Due to the rapid development of POCT, this review should be updated regularly.
Assuntos
Testes Imediatos , Infecções Urinárias , Humanos , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Resultado do Tratamento , Antibacterianos/uso terapêutico , Sensibilidade e EspecificidadeRESUMO
Introduction: Nurses, comprising the largest profession in healthcare, play a significant role in the identification and management of mental health disorders in hospitals. Objectives: The study assessed the knowledge and attitudes of non-psychiatric nurses and their encounters with depressive patients throughout their careers. Methods: This was a cross-sectional descriptive study with 400 non-psychiatric nurses from different hospitals in the Kurdistan Region of Iraq during October and November 2022. The independent Student's t-test, one-way analysis of variance, and binary logistic regression were used to assess possible factors associated with knowledge and attitude toward depression. Results: In this study, 400 non-psychiatric nurses were examined, revealing a mean age of 31.57 ± 8.59â years. Their mean scores for knowledge and attitude toward depression were 5.41 out of a maximum of 11 (standard deviation 1.15) and 5.15 out of 18 (standard deviation 1.83), respectively. Notably, differences in mean knowledge scores were observed concerning participant marital status (P = .044), while disparities in mean attitude scores are related to participant gender (P = .010). Upon binary logistic regression analysis, none of the independent variables exhibited an association with good knowledge. Nevertheless, gender emerged as a significant factor influencing attitude toward depression (odds ratio: 0.51; 95% confidence interval: 0.30-0.86; P = .012). Subsequently, in the multivariate binary logistic regression analysis, gender sustained significance (adjusted odds ratio: 0.573; 95% confidence interval: 0.348-0.942; P = .028) as the key variable impacting attitudes toward depression among non-psychiatric nurses. Conclusion: Based on the results of this study, nurses have insufficient awareness and management skills for depression. It has been experienced and reported that nurses lack knowledge and an attitude toward depression management. The study highlights a significant gap in nurses' skills for managing depression, urging the immediate improvement of training programs. Customizing these programs to enhance nurses' abilities in identifying and managing depression is crucial.