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1.
Commun Biol ; 4(1): 454, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846551

RESUMO

Nε-lysine acetylation in the ER lumen is a recently discovered quality control mechanism that ensures proteostasis within the secretory pathway. The acetyltransferase reaction is carried out by two type-II membrane proteins, ATase1/NAT8B and ATase2/NAT8. Prior studies have shown that reducing ER acetylation can induce reticulophagy, increase ER turnover, and alleviate proteotoxic states. Here, we report the generation of Atase1-/- and Atase2-/- mice and show that these two ER-based acetyltransferases play different roles in the regulation of reticulophagy and macroautophagy. Importantly, knockout of Atase1 alone results in activation of reticulophagy and rescue of the proteotoxic state associated with Alzheimer's disease. Furthermore, loss of Atase1 or Atase2 results in widespread adaptive changes in the cell acetylome and acetyl-CoA metabolism. Overall, our study supports a divergent role of Atase1 and Atase2 in cellular biology, emphasizing ATase1 as a valid translational target for diseases characterized by toxic protein aggregation in the secretory pathway.

2.
J Cardiovasc Dev Dis ; 8(2)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33671890

RESUMO

Robert Anderson has made a huge contribution to almost all aspects of morphology and understanding of congenital cardiac malformations, none more so than the group of anomalies that many of those in the practice of paediatric cardiology and adult congenital heart disease now call 'Atrioventricular Septal Defect' (AVSD). In 1982, with Anton Becker working in Amsterdam, their hallmark 'What's in a name?' editorial was published in the Journal of Thoracic and Cardiovascular Surgery. At that time most described the group of lesions as 'atrioventricular canal malformation' or 'endocardial cushion defect'. Perhaps more significantly, the so-called ostium primum defect was thought to represent a partial variant. It was also universally thought, at that time, that the left atrioventricular valve was no more than a mitral valve with a cleft in the aortic leaflet. In addition to this, lesions such as isolated cleft of the mitral valve, large ventricular septal defects opening to the inlet of the right and hearts with straddling or overriding tricuspid valve were variations of the atrioventricular canal malformation. Anderson and Becker emphasised the differences between the atrioventricular junction in the normal heart and those with a common junction for which they recommended the generic name, 'atrioventricular septal defect'. As I will discuss, over many years, they continued to work with clinical cardiologists and cardiac surgeons to refine diagnostic criteria and transform the classification and understanding of this complex group of anomalies. Their emphasis was always on accurate diagnosis and communication, which is conveyed in this review.

3.
Cardiol Young ; 31(2): 177-178, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33487193
4.
Eur J Public Health ; 31(1): 92-99, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332562

RESUMO

BACKGROUND: Evidence-based policies should underpin successful implementation of innovations within child health care. The EU-funded Models of Child Health Appraised project enabled research into effective methods to communicate research evidence. The objective of this study was to identify and categorize methods to communicate evidence-based research recommendations and means to tailor this to stakeholder audiences. METHODS: We conducted an online survey among national stakeholders in child health. Analysis of the most effective strategies to communicate research evidence and reach the target audience was carried out in order to ensure implementation of optimal child health care models at a national level. RESULTS: Representatives of stakeholders from 21 of the then 30 EU MS and EEA countries responded to the questionnaire. Three main approaches in defining the strategies for effective communication of research recommendations were observed, namely: dissemination of information, involvement of stakeholders and active attitude towards change expressed in actions. The target audience for communicating recommendations was divided into two layers: proximal, which includes those who are remaining in close contact with the child, and distal, which contains those who are institutionally responsible for high quality of child health services. They should be recipients of evidence-based results communicated by different formats, such as scientific, administrative, popular and personal. CONCLUSIONS: Influential stakeholders impact the process of effective research dissemination and guide necessary actions to strengthen the process of effective communication of recommendations. Communication of evidence-based results should be targeted to each audience's profile, both professional and non-professionals, by adjusting appropriate communication formats.

5.
Heart ; 106(18): 1432-1437, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32205313

RESUMO

OBJECTIVE: To describe the intervention spectrum, complexity, and safety outcomes of catheter-based interventions in a contemporary adult congenital heart disease (ACHD) tertiary cohort. METHODS: All patients over 16 years who underwent a catheter-based intervention for ACHD in our centre between 2000 and 2016 were included. Baseline demographics, clinical characteristics, indications for and complexity of intervention, procedural complications and early and mid-term mortality were analysed. RESULTS: Overall, 1644 catheter-based interventions were performed. Intervention complexity ranged from simple (67.5%) to intermediate (26.4%) and to high (6.1%). Commonly performed procedures were atrial septal defect (33.4%) and patent foramen ovale closure (26.1%) followed by coarctation of the aorta (11.1%) and pulmonary artery interventions (7.0%). Age at index intervention was 40±16 years, 758 (46.1%) patients were male, 73.2% in New York Heart Association (NYHA) class I, 20.2% in NYHA class II, whereas 6.6% in NYHA class III/IV. In-hospital mortality was 0.7%. Median postinterventional length of stay was 1 day. Complications occurred in 129 (7.9%) with major adverse events in 21 (1.3%). One-year postintervention survival rates were 98.7% (95% CI 98.2 to 99.2). Over the study period, there was a notable shift in intervention complexity, with a predominance of simple procedures performed in early years and more complex procedures in later years. Furthermore, the case mix during the study broadened (p<0.001) with new catheter-based interventions and a more individualised approach to therapy. CONCLUSION: This study shows an increasing complexity and expanding variability of ACHD catheter-based interventions, associated with low major complications, short hospital stays and low early and mid-term mortality. Ongoing investment in ACHD catheter interventions is warranted.

6.
Eur J Public Health ; 30(4): 693-697, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32206800

RESUMO

BACKGROUND: Population data, such as mortality and morbidity statistics, are essential for many reasons, including giving context for research, supporting action on health determinants, formulation of evidence-based policy for health care and outcome evaluation. However, when considering children, it is difficult to find such data, despite children comprising one-fifth of the European population and being in a key formative life stage and dependent on societal support. Moreover, it would be expected that there should be confidence in the key child health data available, with little to no discrepancy between recognized health statistic databases. METHODS: This study explored the main health databases in or including Europe to collate child mortality data, for both all-cause and specific-cause mortality. Tables were constructed for comparison of values and rankings. RESULTS: The results show that there are major differences in reported mortality data between two prominent health statistic databases, difference in coding systems, and unannounced changes within one of the databases. CONCLUSIONS: The lack of health data for children seems compounded by challenges to the trust and credibility, which are vital if these data are to have utility. Children and society are the losers, and resolution is needed as a priority.

7.
Front Neurosci ; 14: 203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210757

RESUMO

The developing nervous system is a complex yet organized system of neurons, glial support cells, and extracellular matrix that arranges into an elegant, highly structured network. The extracellular and intracellular events that guide axons to their target locations have been well characterized in many regions of the developing nervous system. However, despite extensive work, we have a poor understanding of how axonal growth cones interact with surrounding glial cells to regulate network assembly. Glia-to-growth cone communication is either direct through cellular contacts or indirect through modulation of the local microenvironment via the secretion of factors or signaling molecules. Microglia, oligodendrocytes, astrocytes, Schwann cells, neural progenitor cells, and olfactory ensheathing cells have all been demonstrated to directly impact axon growth and guidance. Expanding our understanding of how different glial cell types directly interact with growing axons throughout neurodevelopment will inform basic and clinical neuroscientists. For example, identifying the key cellular players beyond the axonal growth cone itself may provide translational clues to develop therapeutic interventions to modulate neuron growth during development or regeneration following injury. This review will provide an overview of the current knowledge about glial involvement in development of the nervous system, specifically focusing on how glia directly interact with growing and maturing axons to influence neuronal connectivity. This focus will be applied to the clinically-relevant field of regeneration following spinal cord injury, highlighting how a better understanding of the roles of glia in neurodevelopment can inform strategies to improve axon regeneration after injury.

8.
Child Care Health Dev ; 46(3): 390-396, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32050034

RESUMO

BACKGROUND: Children have the right to health and countries a duty under the United Nations Convention on the Rights of the Child to facilitate this. The European Union has emphasized the importance of investing in children, but at times this seems more wish than pragmatism. Furthermore, European statistical systems do not provide any relevant data, and the degree of unmet need has hitherto been unknown. However, new ad hoc household survey data have now been published by Eurostat showing the percentage of children with a purported unmet medical or dental need and the expressed reasons for this. METHOD: This paper critically reviews these data on children with a reported unmet medical or dental need to create an indication of the number of European children with unmet medical and dental needs, and the contributory factors. RESULTS: This paper calculates that some 1 million European children can be estimated to have an unmet medical need and 2 million children an unmet dental need, though the survey approach has some weaknesses. A probable overestimate of children affected in sample households offsets the likely failure to capture data about children in institutions, homeless, or in fractured families, or about multiple needs. The reported reasons for not obtaining treatments are a valuable first step in highlighting an important issue for Europe's children-measurement of service accessibility. CONCLUSION: Potentially over 3 million European Union children are failing to have their health needs and their rights met. If the incoming European Commission is serious about its predecessor's promise to invest in children and to take seriously their rights, action is needed to improve quantification of unmet need and to reduce suffering and potential lasting damage.

9.
J Neurochem ; 154(4): 404-423, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31945187

RESUMO

Nε-lysine acetylation of nascent glycoproteins within the endoplasmic reticulum (ER) lumen regulates the efficiency of the secretory pathway. The ER acetylation machinery consists of the membrane transporter, acetyl-CoA transporter 1 (AT-1/SLC33A1), and two acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Dysfunctional ER acetylation is associated with severe neurological diseases with duplication of AT-1/SLC33A1 being associated with autism spectrum disorder, intellectual disability, and dysmorphism. Neuron-specific AT-1 over-expression in the mouse alters neuron morphology and function, causing an autism-like phenotype, indicating that ER acetylation plays a key role in neurophysiology. As such, characterizing the molecular mechanisms that regulate the acetylation machinery could reveal critical information about its biology. By using structure-biochemistry approaches, we discovered that ATase1 and ATase2 share enzymatic properties but differ in that ATase1 is post-translationally regulated via acetylation. Furthermore, gene expression studies revealed that the promoters of AT-1, ATase1, and ATase2 contain functional binding sites for the neuron-related transcription factors cAMP response element-binding protein and the immediate-early genes c-FOS and c-JUN, and that ATase1 and ATase2 exhibit additional modes of transcriptional regulation relevant to aging and Alzheimer's disease. In vivo rodent gene expression experiments revealed that Atase2 is specifically induced following activity-dependent events. Finally, over-expression of either ATase1 or ATase2 was sufficient to increase the engagement of the secretory pathway in PC12 cells. Our results indicate important regulatory roles for ATase1 and ATase2 in neuron function with induction of ATase2 expression potentially serving as a critical event that adjusts the efficiency of the secretory pathway for activity-dependent neuronal functions.

10.
Eur J Public Health ; 30(3): 449-455, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642905

RESUMO

BACKGROUND: Low childhood immunization rates in Europe are causing concern and have triggered several EU initiatives. However, these are counter-factual as they make immunization a stand-alone issue and cut across best practice in integrated child health services. They also focus unduly on 'anti-vax' pressures, generalize 'vaccine hesitancy' and overlook practical difficulties and uncertainties encountered by parents in real world situations about presenting children for immunization. Meanwhile European expertize in child health electronic record systems and relevant standards are ignored despite their being a potentially sound foundation ripe for enhancement. METHODS: Situation and literature reviews, and cohesion of two European research projects, led to shared investigation. As a result, two cross-sectoral expert workshops were held to consider digital health standards for harmonizing integrated preventive child health including immunization, and the work of other stakeholders such as the World Health Organisation and the European Centre for Disease Control. RESULTS: Progress in child health information models and digital health standards was assessed, areas needing further standards development identified and desirable steps towards innovation in service delivery and record keeping agreed. CONCLUSION: The European Commission, member states and child health stakeholders should take an integrated approach to child health with immunization as a component. Service delivery should be sensitive to parental concerns and challenges, and the way child- and family-centric data are recorded and used should be enhanced. Services should be enabled by the International Patient Summary and related electronic health record standards and linkages, and evaluated to assess most effective systems and practice.

11.
Arch Dis Child ; 105(1): 40-46, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31270093

RESUMO

BACKGROUND AND OBJECTIVES: Adolescent sexual and reproductive health and rights (SRHR) are of particular relevance given their potential short-term or long-term health consequences. This study evaluates recommendations and policies regarding access to care in this area in 31 European countries (European Union (EU) plus Iceland, Norway and Switzerland). METHODS: As part of the EU funded Models of Child Health Appraised project, data were gathered using a 43-item questionnaire sent to experts responsible for collecting information in each country. RESULTS: Ten countries have not developed any formal policy or recommendation that guarantee the respect of confidentiality and the possibility of consulting a physician without parents knowing. Nearly half of the countries do not have centres specialised in adolescent healthcare, tackling comprehensive health issues or focusing specifically on SRH. Access to emergency contraception and information regarding pregnancy, including testing, is easy in most countries. However, oral contraception is delivered free of charge in only 10 countries. Twenty-three countries do not meet current standards in terms of providing policy-based pregnancy care, and only 13 have set up special programmes for pregnant adolescents. In only seven countries can adolescents definitely have their pregnancy terminated without their parents knowing (and in another seven countries in selected situations). CONCLUSION: The provision and availability of adolescent-friendly SRHR care are far from optimal in around half of the surveyed countries. These results call for the review and implementation of policies, specialised healthcare centres and training initiatives for primary care providers.


Assuntos
Serviços de Saúde do Adolescente/organização & administração , União Europeia , Necessidades e Demandas de Serviços de Saúde , Saúde Reprodutiva , Saúde Sexual , Aborto Legal , Adolescente , Saúde do Adolescente/ética , Anticoncepção , Feminino , Política de Saúde , Acesso aos Serviços de Saúde/organização & administração , Humanos , Masculino , Direitos do Paciente , Gravidez , Gravidez na Adolescência , Inquéritos e Questionários
12.
WMJ ; 119(4): 263-269, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33428837

RESUMO

PURPOSE: Medical student participation in professional medical societies is an understudied extracurricular activity. The purpose of this study is to assess student characteristics associated with participation and their attitudes toward professional medical societies. METHODS: A cross-sectional study using a 21-item survey questionnaire was administered to Wisconsin medical students in the fall of 2019. Regression analysis was used to find factors associated with participation. RESULTS: A total of 308 questionnaire responses were collected with a response rate of 17.4%. Sixty-three percent of respondents participated in a professional medical society, and the most important reasons for participating included professional development, networking, and advocacy. Participation was positively associated with age (OR = 1.16; 95% CI, 1.01 - 1.33); years of medical education (OR = 1.4; 95% CI, 1.18 - 1.69); number of memberships in professional medical societies (OR = 2.02; 95% CI, 1.61 - 2.53); number of extracurricular advocacy events attended outside of professional medical societies (OR = 1.62; 95% CI, 1.17 - 2.23); belief that participation is important for professional development (OR = 1.76; 95% CI, 1.39 - 2.23), patients (OR = 1.51; 95% CI, 1.23 - 1.86), and medical education (OR = 1.43; 95% CI, 1.19 - 1.71); and the desire to participate as a physician (OR = 1.53; 95% CI, 1.25 - 1.88). Participation was negatively associated with male gender (OR = 0.51; 95% CI, 0.27 - 0.95). CONCLUSIONS: Medical students who participate in professional medical societies believe participation supports their education, their patients, and their professional development. Further study is required to elucidate reasons for nonparticipation.

13.
Lancet Child Adolesc Health ; 3(12): e14, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31701896

Assuntos
Pediatria , Criança , Humanos
16.
Stud Health Technol Inform ; 262: 154-157, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31349289

RESUMO

Immunisation is a key preventive health measure for children. E-health applications have been used for over 50 years, yet still there is no harmonization or standardization, while uncoordinated policy initiatives proliferate. Two EU research projects (Trillium II and MOCHA) have come together with experts and stakeholders, and used EU-wide situation analysis research to seek to stimulate development of data and process standards as a harmonizing force in a supporting policy environment, putting the child as the central data collation unit.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Saúde da População , Vacinação , Criança , Europa (Continente) , Humanos
17.
Stud Health Technol Inform ; 262: 158-161, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31349290

RESUMO

A potentially useful resource for health promotion and guidance is eHealth. However, this field also presents challenges, and one of the most important obstacles is the lack of regulation, without which citizens including young people may be exposed to misleading or risky information and applications. The aim of this study was to investigate the extent of accreditation processes for mobile applications (apps) and websites in European countries, to determine whether regulation is on the agenda. A survey was conducted in 28 European Member States and 2 European Economic Area countries, between 2017 and 2018. Twenty-seven responses were collected. Six countries have accreditation processes for apps and eight countries have accreditation processes for websites. However, processes are fragmented and there is variety within and amongst countries.


Assuntos
Acreditação , Aplicativos Móveis , Telemedicina , Europa (Continente) , Promoção da Saúde
18.
BMC Public Health ; 19(1): 839, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248395

RESUMO

BACKGROUND: The main objective of this study was to explore the contextual determinants of child health policies. METHODS: The Horizon 2020 Models of Child Health Appraised (MOCHA) project has one Country Agent (CA) in all 30 EU and EEA countries. A questionnaire designed by MOCHA researchers as a semi-structured survey instrument asked CAs to identify and report the predominating public and professional discussions related to child health services within the last 5 years in their country and the various factors which may have influenced these. The survey was issued to CAs following validation by an independent Expert Advisory Board. The data were collected between July and December 2016. The data was qualitatively analysed using software Nvivo11 for data coding and categorization and constructing the scheme for identified processes or elements. RESULTS: Contextual determinants of children's health care and policy were grouped into four categories. 1) Socio-cultural determinants: societal activation, awareness, communication, trust, freedom, contextual change, lifestyle, tolerance and religion, and history. 2) Structural determinants which were divided into: a) external determinants related to elements indirectly correlated with health care and b) internal determinants comprising interdependent health care and policy processes. 3) International determinants such as cross-nationality of child health policy issues. 4) The specific situational determinants: events which contributed to intensification of debates which were reflected by behavioural, procedural, institutional and global factors. CONCLUSIONS: The influence of context across European countries, in the process of children's health policy development is clearly evident from our research. A number of key categories of determinants which influence child health policy have been identified and can be used to describe this context. Child health policy is often initiated in reaction to public discontentment. The multiple voices of society resulted, amongst others, in the introduction of new procedures, action plans and guidelines; raising levels of awareness, intensifying public scrutiny, increasing access and availability of services and provoking introduction of structural changes or withdrawing unfavourable changes.


Assuntos
Saúde da Criança , Política de Saúde , Formulação de Políticas , Criança , Serviços de Saúde da Criança , Europa (Continente) , Humanos , Pesquisa Qualitativa , Inquéritos e Questionários
19.
J Child Health Care ; 23(3): 343-357, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31132868

RESUMO

Children's rights to autonomy of choice are differently expressed throughout Europe. We explored differences regarding expressions of respect for children's autonomy throughout Europe, using the procedure of human papillomavirus (HPV) vaccination offer as indicator. We used a mixed methods approach, utilizing an expert survey within the frame of "Models of Child Health Appraised" (MOCHA), among all 30 European Union (EU) and European Economic Area states. A questionnaire was designed using vignettes regarding the vaccine provision. Thirty MOCHA country agents were invited to respond from June 2017 to April 2018. In total, 28 country agents responded. We studied the following themes: (i) provision of informed consent, (ii) parental and medical paternalism, (iii) relevance of the child's chronological age or maturity, and (iv) vaccination programs targeting boys. These are being handled differently across the region. We explored associations of these implemented practices with the national vaccine coverage rate across Europe. We used the processes of HPV vaccination to study child's autonomy, the paradigm change toward libertarian paternalism and issues of sex-equity. Interestingly, greater respect for children's autonomy tends to be associated with medium or high vaccination coverage rates and lower respect with lower rates. Respect and empowerment seem to have practical as well as moral benefits. Identifying and transferring the most suitable ethical approaches is crucial and should be strengthened.


Assuntos
Saúde da Criança , Vacinas contra Papillomavirus/administração & dosagem , Autonomia Pessoal , Respeito , Vacinação/normas , Criança , União Europeia , Feminino , Humanos , Masculino , Infecções por Papillomavirus/prevenção & controle , Paternalismo , Fatores Sexuais , Inquéritos e Questionários
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