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1.
Analyst ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712606

RESUMO

Plant hormones are important in the control of physiological and developmental processes including seed germination, senescence, flowering, stomatal aperture, and ultimately the overall growth and yield of plants. Many currently available methods to quantify such growth regulators quickly and accurately require extensive sample purification using complex analytic techniques. Herein we used ultra-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) to create and validate the prediction of hormone concentrations made using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectral profiles of both freeze-dried ground leaf tissue and extracted xylem sap of Japanese knotweed (Reynoutria japonica) plants grown under different environmental conditions. In addition to these predictions made with partial least squares regression, further analysis of spectral data was performed using chemometric techniques, including principal component analysis, linear discriminant analysis, and support vector machines (SVM). Plants grown in different environments had sufficiently different biochemical profiles, including plant hormonal compounds, to allow successful differentiation by ATR-FTIR spectroscopy coupled with SVM. ATR-FTIR spectral biomarkers highlighted a range of biomolecules responsible for the differing spectral signatures between growth environments, such as triacylglycerol, proteins and amino acids, tannins, pectin, polysaccharides such as starch and cellulose, DNA and RNA. Using partial least squares regression, we show the potential for accurate prediction of plant hormone concentrations from ATR-FTIR spectral profiles, calibrated with hormonal data quantified by UHPLC-HRMS. The application of ATR-FTIR spectroscopy and chemometrics offers accurate prediction of hormone concentrations in plant samples, with advantages over existing approaches.

2.
JBI Evid Synth ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38596866

RESUMO

OBJECTIVE: The proposed review will describe the characteristics, enablers, and barriers to the community health and well-being assessment (CHWA) component of the health promotion practice cycle. INTRODUCTION: CHWA guides health promotion action in communities and populations. A "critical" approach to CHWA can be adopted, which addresses the social, political, cultural, economic, commercial, and environmental determinants of health and well-being to enhance health equity for priority communities and populations. Although tools exist to guide such a critical approach, little is known about the extent to which these tools are being used or the barriers and enablers to applying best practice CHWA. Such evidence is needed to inform future health promotion CHWA and research. INCLUSION CRITERIA: This review will consider literature that describes CHWA conducted in health promotion practice, focusing on an organizational, social, or geographical community or population. Literature that focuses on clinical practice or a specific health condition will be excluded. METHODS: Scopus, PubMed, Web of Science, and CINAHL (EBSCOhost) will be searched to identify peer-reviewed articles. Google Scholar and Google, as well as Public Health, Health & Medical, and Nursing and Allied Health (ProQuest) databases will be searched for gray literature. Articles will be screened and data extracted by 2 or more independent reviewers. The data extraction tool will be developed by the reviewers based on the JBI template and a critical health promotion approach to CHWA. Data will be analyzed and presented as frequency tables and narrative summaries of the characteristics, enablers, and barriers to CHWA. DETAILS OF THE PROTOCOL ARE AVAILABLE ON OPEN SCIENCE FRAMEWORK: osf.io/jq8th/.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38170837

RESUMO

AIMS: Sexual activity and intimacy improve quality of life for heart attack survivors. After a heart attack, patients frequently experience sexual dysfunction and anxiety about resuming sexual activity. However, most health professionals do not discuss sex or intimacy with their patients. The aim of this research was to explore the perceptions and practices of Australian health professionals in discussing sexual activity and intimacy with heart attack survivors and the barriers to achieving this. METHODS AND RESULTS: This study employed a cross-sectional study design and online self-administered survey questionnaire. Study participants were a convenience sample of Australian health professionals working with cardiac patients, including general practitioners, cardiologists, cardiac rehabilitation specialists, registered nurses, and allied health professionals. Data were analysed using descriptive statistics and cross-tabulations to understand the different perspectives of health professional groups and the overall sample. Of 252 respondents, almost all believed discussing sex and intimacy with heart attack survivors was important, yet less than a quarter reported regularly doing so. About three-quarters reported feeling comfortable discussing sex and intimacy with either men or women, with half comfortable to do so with patients from diverse cultures. Barriers included lack of time, privacy, consumer resources, and protocols to guide discussions. CONCLUSION: This research supports the need for structural changes such as a clinical protocol, longer and more private consultations, staff training, and culturally appropriate patient-oriented resources to support health professionals to guide discussions about sexual activity and intimacy with patients who have had a heart attack.

4.
Aust J Prim Health ; 30(1): NULL, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38081070

RESUMO

BACKGROUND: Sexual activity and intimacy contribute to wellbeing throughout adult life, including after a heart attack. Providing support and information about sexual activity and intimacy after a heart attack is recognised as part of a comprehensive approach to cardiac rehabilitation. Previous research shows that patients expect health professionals to initiate discussions about sexual activity and intimacy, but that this seldom occurs. METHODS: Drawing on qualitative survey responses from a range of Australian health professionals working in cardiac care and rehabilitation, this research examined their perspectives on discussing sexual activity and intimacy with their patients, and patients' partners. Using a social constructionist approach, thematic analysis was used to identify themes expressed by participants. RESULTS: Discussions about sexual activity and intimacy after heart attack were perceived as nebulous and taboo. The predominance of an illness - rather than wellness - framing of these discussions and a tendency for health professionals to make judgement calls contributed to discussions not occurring. Health professionals also identified a range of intrapersonal, interpersonal and structural obstacles to discussions, including embarrassment, fear of patients' embarrassment, a lack of role clarity, the absence of a clear protocol or training to guide practice, and a lack of time, privacy and patient resources. CONCLUSIONS: Such discussions require normalisation, careful timing, sufficient time and adequate privacy. Staff training, a protocol and appropriate patient resources are needed to support health professionals to initiate discussions. Further research is required that investigates the impact of specific resources and training on health professionals' practice and patient outcomes.


Assuntos
Infarto do Miocárdio , Sexualidade , Adulto , Humanos , Sexualidade/fisiologia , Austrália , Comportamento Sexual , Parceiros Sexuais , Pesquisa Qualitativa
5.
Chronic Stress (Thousand Oaks) ; 7: 24705470231215001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38024327

RESUMO

Background: Females are twice as likely to experience post-traumatic stress disorder (PTSD) than males, yet specific factors contributing to this greater risk are not fully understood. Our clinical and recent preclinical findings suggest a role for the metabotropic glutamate receptor 5 (mGlu5) in PTSD and differential involvement between males and females. Methods: Here, we further investigate whether mGlu5 receptor availability may contribute to individual and sex differences in PTSD susceptibility by quantifying receptor availability using the mGlu5 receptor-specific radiotracer, [18F]FPEB, and positron emission tomography in male (n = 16) and female (n = 16) rats before and after traumatic footshock exposure (FE) and assessment of stress-enhanced fear learning (SEFL) susceptibility, as compared with no-shock controls (CON; n = 7 male; n = 8 female). Results: Overall, FE rats displayed greater fear generalization as compared with CON (p < .001). Further, greater mGlu5 receptor availability at baseline (p = .003) and post-test (p = .005) was significantly associated with expression of the SEFL phenotype. Notably, FE female rats displayed a shift to more passive coping (ie, freezing), and displayed greater SEFL susceptibility (p = .01), and had lower baseline mGlu5 availability (p = .03) relative to their FE male rat counterparts. Conclusion: Results are consistent with clinical findings of higher mGlu5 receptor availability in PTSD, and add to growing evidence implicating these receptors in the pathophysiology of PTSD and sex-differences in susceptibility for this disorder.

6.
Pediatr Pulmonol ; 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37401889

RESUMO

INTRODUCTION: Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children's Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders. METHODS: This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.S. Clinical data are collected and managed using the Research Electronic Data Capture (REDCap) electronic data platform. RESULTS: We report the study design and selected elements of the initial Registry enrollment cohort, which includes 683 subjects with a broad range of chILD diagnoses. The most common diagnosis reported was neuroendocrine cell hyperplasia of infancy, with 155 (23%) subjects. Components of underlying disease biology were identified by enrolling sites, with cohorts of interstitial fibrosis, immune dysregulation, and airway disease being most commonly reported. Prominent morbidities affecting enrolled children included home supplemental oxygen use (63%) and failure to thrive (46%). CONCLUSION: This Registry is the largest longitudinal chILD cohort in the United States to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders.

7.
JBI Evid Synth ; 21(11): 2264-2271, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37435684

RESUMO

OBJECTIVE: This scoping review will explore how critical health promotion is characterized in the health promotion literature. INTRODUCTION: Critical health promotion has emerged as a social justice approach to health promotion to address the persistent global issue of health inequity. Whilst critical health promotion is not conceptually new and the term has been used in the literature, albeit sparingly, this approach has not been adopted as standard health promotion practice, compromising the advancement of health equity. Given that language shapes the understanding and practice of health promotion, it is imperative to explore how critical health promotion is characterized in the literature to increase uptake of the approach. INCLUSION CRITERIA: This review will consider sources that explore critical health promotion and are explicitly positioned as health promotion sources. METHODS: Scopus, CINAHL (EBSCOhost), PubMed, Global Health (CABI), and the Public Health Database (ProQuest) will be searched to identify relevant full-text papers, including original research, reviews, editorials, and opinion papers. Searches of Google Scholar, Google, and ProQuest Dissertations & Theses Global (ProQuest) will be undertaken to identify gray literature. No language or date restrictions will be applied. Two reviewers will screen sources and extract data using a tool that will be pilot tested, modified, and revised, as necessary. Analysis will involve basic frequency counts and descriptive qualitative content analysis through basic coding. The results will be presented in tables, charts, and word clouds, accompanied by a narrative summary.


Assuntos
Promoção da Saúde , Literatura de Revisão como Assunto , Humanos , Bases de Dados Factuais
8.
BMJ Open ; 13(7): e072404, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37419645

RESUMO

INTRODUCTION: Mental well-being is a global public health priority with increasing mental health conditions having substantial burden on individuals, health systems and society. 'Stepped care', where services are provided at an intensity to meet the changing needs of the consumer, is the chosen approach to mental health service delivery in primary healthcare in Australia for its efficiencies and patient outcomes; yet limited evidence exists on how the programme is being rolled out and its impact in practice. This protocol outlines a data linkage project to characterise and quantify healthcare service utilisation and impacts among a cohort of consumers of a national mental health stepped care programme in one region of Australia. METHODS AND ANALYSIS: Data linkage will be used to establish a retrospective cohort of consumers of mental health stepped care services between 1 July 2020 and 31 December 2021 in one primary healthcare region in Australia (n=approx. 12 710). These data will be linked with records from other healthcare service data sets (eg, hospitalisations, emergency department presentations, community-based state government-delivered mental healthcare, hospital costs). Four areas for analysis will include: (1) characterising the nature of mental health stepped care service use; (2) describing the cohort's sociodemographic and health characteristics; (3) quantifying broader service utilisation and associated economic costs; and (4) assessing the impact of mental health stepped care service utilisation on health and service outcomes. ETHICS AND DISSEMINATION: Approval from the Darling Downs Health Human Research Ethics Committee (HREA/2020/QTDD/65518) has been granted. All data will be non-identifiable, and research findings will be disseminated through peer-reviewed journals, conference presentations and industry meetings.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Humanos , Estudos Retrospectivos , Austrália , Aceitação pelo Paciente de Cuidados de Saúde
9.
Case Rep Crit Care ; 2023: 1699770, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228424

RESUMO

Diagnosis and management of SARS-CoV-2 infection in immunocompromised patients are extremely challenging. These patients can have atypical clinical courses, and there is a paucity of data regarding clinical features, diagnostic findings, and the safety and efficacy of available therapeutic agents used to treat COVID-19 in these patients. In this case series, we report atypical COVID-19 presentations in 4 immunocompromised pediatric patients who were admitted with acute respiratory failure after an initial diagnosis of COVID-19 a few weeks earlier. All patients included in this cohort showed persistent worsening respiratory symptoms for several weeks before hospital presentation. While they manifested common COVID-19 sequelae, they also had rare COVID-19-related pathognomonic and radiographic features developed along their hospital course. Multiple therapeutic agents were used in their COVID-19 management, including corticosteroids, remdesivir, and monoclonal antibodies. All three patients who have received concurrent therapy with remdesivir, hydrocortisone, and monoclonal antibodies survived, and only one patient died as a direct complication of COVID-19 ARDS with secondary pulmonary mucormycosis. Our outcomes suggest the potential benefit of remdesivir use in combination with hydrocortisone and monoclonal antibodies in the management of severe COVID-19 ARDS in this group, as well as the importance of close surveillance and early administration of broad empirical antimicrobial and antifungal coverage if clinically indicated in this high-risk population.

10.
Front Public Health ; 11: 1121932, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37026119

RESUMO

Background: The origins of health promotion are based in critical practice; however, health promotion practice is still dominated by selective biomedical and behavioral approaches, which are insufficient to reduce health inequities resulting from the inequitable distribution of structural and systemic privilege and power. The Red Lotus Critical Health Promotion Model (RLCHPM), developed to enhance critical practice, includes values and principles that practitioners can use to critically reflect on health promotion practice. Existing quality assessment tools focus primarily on technical aspects of practice rather than the underpinning values and principles. The aim of this project was to develop a quality assessment tool to support critical reflection using the values and principles of critical health promotion. The purpose of the tool is to support the reorientation of health promotion practice toward a more critical approach. Research design: We used Critical Systems Heuristics as the theoretical framework to develop the quality assessment tool. First, we refined the values and principles in the RLCHPM, then created critical reflective questions, refined the response categories, and added a scoring system. Results: The Quality Assessment Tool for Critical Health Promotion Practice (QATCHEPP) includes 10 values and associated principles. Each value is a critical health promotion concept, and its associated principle provides a description of how the value is enacted in professional practice. QATCHEPP includes a set of three reflective questions for each value and associated principle. For each question, users score the practice as strongly, somewhat, or minimally/not at all reflective of critical health promotion practice. A percentage summary score is generated with 85% or above indicative of strongly critical practice, 50% ≤ 84% is somewhat critical practice, and < 50% minimally or does not reflect critical practice. Conclusion: QATCHEPP provides theory-based heuristic support for practitioners to use critical reflection to assess the extent to which practice aligns with critical health promotion. QATCHEPP can be used as part of the Red Lotus Critical Promotion Model or as an independent quality assessment tool to support the orientation of health promotion toward critical practice. This is essential to ensure that health promotion practice contributes to enhancing health equity.


Assuntos
Promoção da Saúde , Garantia da Qualidade dos Cuidados de Saúde , Humanos
12.
Sci Rep ; 13(1): 4841, 2023 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-36964175

RESUMO

Psychotic disorders are highly heterogeneous. Understanding relationships between symptoms will be relevant to their underlying pathophysiology. We apply dimensionality-reduction methods across two unique samples to characterize the patterns of symptom organization. We analyzed publicly-available data from 153 participants diagnosed with schizophrenia or schizoaffective disorder (fBIRN Data Repository and the Consortium for Neuropsychiatric Phenomics), as well as 636 first-episode psychosis (FEP) participants from the Prevention and Early Intervention Program for Psychosis (PEPP-Montreal). In all participants, the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were collected. Multidimensional scaling (MDS) combined with cluster analysis was applied to SAPS and SANS scores across these two groups of participants. MDS revealed relationships between items of SAPS and SANS. Our application of cluster analysis to these results identified: 1 cluster of disorganization symptoms, 2 clusters of hallucinations/delusions, and 2 SANS clusters (asocial and apathy, speech and affect). Those reality distortion items which were furthest from auditory hallucinations had very weak to no relationship with hallucination severity. Despite being at an earlier stage of illness, symptoms in FEP presentations were similarly organized. While hallucinations and delusions commonly co-occur, we found that their specific themes and content sometimes travel together and sometimes do not. This has important implications, not only for treatment, but also for research-particularly efforts to understand the neurocomputational and pathophysiological mechanism underlying delusions and hallucinations.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Delusões/diagnóstico , Transtornos Psicóticos/psicologia , Esquizofrenia/diagnóstico , Esquizofrenia/complicações , Alucinações/psicologia
13.
J Neurosci ; 43(3): 458-471, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36216504

RESUMO

Model-free and model-based computations are argued to distinctly update action values that guide decision-making processes. It is not known, however, if these model-free and model-based reinforcement learning mechanisms recruited in operationally based instrumental tasks parallel those engaged by pavlovian-based behavioral procedures. Recently, computational work has suggested that individual differences in the attribution of incentive salience to reward predictive cues, that is, sign- and goal-tracking behaviors, are also governed by variations in model-free and model-based value representations that guide behavior. Moreover, it is not appreciated if these systems that are characterized computationally using model-free and model-based algorithms are conserved across tasks for individual animals. In the current study, we used a within-subject design to assess sign-tracking and goal-tracking behaviors using a pavlovian conditioned approach task and then characterized behavior using an instrumental multistage decision-making (MSDM) task in male rats. We hypothesized that both pavlovian and instrumental learning processes may be driven by common reinforcement-learning mechanisms. Our data confirm that sign-tracking behavior was associated with greater reward-mediated, model-free reinforcement learning and that it was also linked to model-free reinforcement learning in the MSDM task. Computational analyses revealed that pavlovian model-free updating was correlated with model-free reinforcement learning in the MSDM task. These data provide key insights into the computational mechanisms mediating associative learning that could have important implications for normal and abnormal states.SIGNIFICANCE STATEMENT Model-free and model-based computations that guide instrumental decision-making processes may also be recruited in pavlovian-based behavioral procedures. Here, we used a within-subject design to test the hypothesis that both pavlovian and instrumental learning processes were driven by common reinforcement-learning mechanisms. Sign-tracking and goal-tracking behaviors were assessed in rats using a pavlovian conditioned approach task, and then instrumental behavior was characterized using an MSDM task. We report that sign-tracking behavior was associated with greater model-free, but not model-based, learning in the MSDM task. These data suggest that pavlovian and instrumental behaviors may be driven by conserved reinforcement-learning mechanisms.


Assuntos
Reforço Psicológico , Recompensa , Ratos , Masculino , Animais , Aprendizagem , Motivação , Condicionamento Operante , Sinais (Psicologia)
15.
Orthod Craniofac Res ; 26(3): 415-424, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36458927

RESUMO

OBJECTIVES: Antidepressants, specifically Selective Serotonin Re-uptake Inhibitors (SSRIs), that alter serotonin metabolism are currently the most commonly prescribed drugs for the treatment of depression. There is some evidence to suggest these drugs contribute to birth defects. As jaw development is often altered in craniofacial birth defects, the purpose of this study was to interrogate the effects of in utero SSRI exposure in a preclinical model of mandible development. MATERIALS AND METHODS: Wild-type C57BL6 mice were used to produce litters that were exposed in utero to an SSRI, Citalopram (500 µg/day). Murine mandibles from P15 pups were analysed for a change in shape and composition. RESULTS: Analysis indicated an overall shape change with total mandibular length and ramus height being shorter in exposed pups as compared to controls. Histomorphometric analysis revealed that first molar length was longer in exposed pups while third molar length was shorter in exposed as compared to control. Histological investigation of molars and surrounding periodontium revealed no change in collagen content of the molar in exposed pups, some alteration in collagen composition in the periodontium, increased alkaline phosphatase in molars and periodontium and decreased mesenchymal cell marker presence in exposed mandibles. CONCLUSION: The results of this study reveal SSRI exposure may interrupt mandible growth as well as overall dental maturation in a model of development giving insight into the expectation that children exposed to SSRIs may require orthodontic intervention.


Assuntos
Inibidores Seletivos de Recaptação de Serotonina , Serotonina , Animais , Camundongos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Serotonina/metabolismo , Camundongos Endogâmicos C57BL , Citalopram/efeitos adversos , Mandíbula/metabolismo
16.
Adv Health Sci Educ Theory Pract ; 28(1): 243-277, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35689133

RESUMO

INTRODUCTION: Implementation of interprofessional education (IPE) is recognised as challenging, and well-designed programs can have differing levels of success depending on implementation quality. The aim of this review was to summarise the evidence for implementation of IPE, and identify challenges and key lessons to guide faculty in IPE implementation. METHODS: Five stage scoping review of methodological characteristics, implementation components, challenges and key lessons in primary studies in IPE. Thematic analysis using a framework of micro (teaching), meso (institutional), and macro (systemic) level education factors was used to synthesise challenges and key lessons. RESULTS: Twenty-seven primary studies were included in this review. Studies were predominantly descriptive in design and implementation components inconsistently reported. IPE was mostly integrated into curricula, optional, involved group learning, and used combinations of interactive and didactic approaches. Micro level implementation factors (socialisation issues, learning context, and faculty development), meso level implementation factors (leadership and resources, administrative processes), and macro level implementation factors (education system, government policies, social and cultural values) were extrapolated. Sustainability was identified as an additional factor in IPE implementation. CONCLUSION: Lack of complete detailed reporting limits evidence of IPE implementation, however, this review highlighted challenges and yielded key lessons to guide faculty in the implementation of IPE.


Assuntos
Currículo , Educação Interprofissional , Humanos , Escolaridade , Docentes , Liderança
17.
Neuropsychopharmacology ; 48(3): 489-497, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36100654

RESUMO

Clinical investigations suggest involvement of the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of fear learning that underlies trauma-related disorders. Here, we utilized a 4-day fear learning paradigm combined with positron emission tomography (PET) to examine the relationship between mGluR5 availability and differences in the response of rats to repeated footshock exposure (FE). Specifically, on day 1, male (n = 16) and female (n = 12) rats received 15 footshocks and were compared with control rats who did not receive footshocks (n = 7 male; n = 4 female). FE rats were classified as low responders (LR) or high responders (HR) based on freezing to the context the following day (day 2). PET with [18F]FPEB was used to calculate regional mGluR5 binding potential (BPND) at two timepoints: prior to FE (i.e., baseline), and post-behavioral testing. Additionally, we used an unbiased proteomics approach to assess group and sex differences in prefrontal cortex (PFC) protein expression. Post-behavioral testing we observed decreased BPND in LR females, but increased BPND in HR males relative to baseline. Further, individuals displaying the greatest freezing during the FE context memory test had the largest increases in PFC BPND. Males and females displayed unique post-test molecular profiles: in males, the greatest differences were between FE and CON, including upregulation of mGluR5 and related molecular networks in FE, whereas the greatest differences among females were between the LR and HR groups. These findings suggest greater mGluR5 availability increases following footshock exposure may be related to greater contextual fear memory. Results additionally reveal sex differences in the molecular response to footshock, including differential involvement of mGluR5-related molecular networks.


Assuntos
Receptor de Glutamato Metabotrópico 5 , Animais , Feminino , Masculino , Ratos , Tomografia por Emissão de Pósitrons/métodos , Receptor de Glutamato Metabotrópico 5/metabolismo , Fatores Sexuais
18.
Sci Transl Med ; 14(669): eabq4433, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322631

RESUMO

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Sepse , Adulto , Humanos , Criança , Perfilação da Expressão Gênica , Sepse/genética , Transcriptoma/genética
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