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Physical literacy development in early childhood, viewed by many as the foundation for lifelong physical activity engagement, is significantly influenced by parents. Our aim was to explore parents' understanding of physical literacy and gain insight into their perspectives on physical literacy promotion. We recruited 18 parents of children between 5 and 8 years old in Australia. Using semistructured interviews and thematic analysis, we identified several key issues regarding parents' understanding and implementation of physical literacy. Parents expressed interest in improving their implementation of physical literacy practices and had (often unintentionally) provided support for physical literacy subcomponents in the past. However, they described difficulties prioritizing physical literacy above other parental demands and expressed conflicting perceptions regarding where the responsibility should lie for developing their child's physical literacy (e.g., at home or at school). To ensure that the physical literacy "message" reaches parents, we encourage physical literacy promoters to consider the target (e.g., responsibility, priorities, and awareness) of their promotional strategies. Further investigation into the influence of sociocultural and economic factors on parents' understanding and application of physical literacy is warranted.
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Alfabetización , Padres , Niño , Humanos , Preescolar , Australia , Ejercicio Físico , Instituciones AcadémicasRESUMEN
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 Cuidado Intensivo Neonatal , Pruebas en el Punto de Atención , Investigación Cualitativa , Humanos , Recién Nacido , Antibacterianos/efectos adversos , Femenino , Masculino , Ototoxicidad , Actitud del Personal de Salud , Personal de Enfermería en Hospital , Adulto , Sistemas de Atención de Punto , Pruebas GenéticasRESUMEN
PURPOSE: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. PATIENTS AND METHODS: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. RESULTS: Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P = .0006) and 0.0% (P < .0001), respectively. Patients whose tumors contained exon 11 KIT mutations had a longer event-free and overall survival than those whose tumors expressed either exon 9 KIT mutations or had no detectable kinase mutation. CONCLUSION: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. PDGFRA mutations can explain response and sensitivity to imatinib in some GISTs lacking KIT mutations.
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Civet coffee is produced with coffee beans that have passed through the digestive tract of civets which are then processed for drinking. Outlets, known as civet coffee tourism plantations are popular tourist attractions in Bali, Indonesia. These outlets keep caged civets for public viewing and sell civet coffee. We assessed civet welfare in 29 civet coffee tourism plantations to assess husbandry factors, the five freedoms and body condition scores. We also assessed civet welfare in eight wildlife markets where civets are sourced for civet coffee tourism and calculated turnover of civets. We found 99 civets in civet coffee tourism plantations and 136 in markets, where. Annually between 400 and 800 civets are sold. Welfare standards do not meet the Indonesian laws and regulations. Diet, hygiene, presence of water and mobility affected body condition scores and no civet met all of the five freedoms. Enforcement of welfare and trade laws is needed to improve civet welfare, and to curb the illegal civet trade. Tourists frequenting civet coffee tourism plantations should be made aware of the low welfare standards to inform their choice about supporting this industry.
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BACKGROUND: Undergraduate podiatry degrees are designed to enable students to become professional podiatrists. To be successful students must manage academic and practical activity to ultimately acquire a professional identity. Little is known about the practices and processes which underpin the acquisition of a professional podiatry identity. It is the aim of this paper to begin to address this absence of knowledge. Community of Practice theory, arguably the dominant contemporary learning theory, represents identity shift as an interaction of imagination, engagement and alignment which enables students to successfully participate in higher education, and ultimately, the professional context. This success is underpinned through assisting students to develop an enabling identity in their learning and doing. METHODS: Here we present findings that emerged from a yearlong ethnography in a successful higher education podiatry department. The project followed students and staff in the classroom and the clinic and explored their experiences through interviews. RESULTS: The findings suggest that the journey to professional identity is facilitated through meaningful learning relationships between staff and students and clarity around professional practices. Here we discuss how those relationships form and enable undergraduates to become podiatrists. CONCLUSIONS: Our findings offer a model for the transition from student to professional and highlight the importance of relationship and experience in becoming a podiatrist. There is a paucity of research around not only podiatry but also other allied health professions around this topic and given the increasing emphasis around employability skills in HE, more research in a range of contexts is needed.
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Podiatría , Estudiantes , Humanos , Técnicos Medios en Salud , Práctica ProfesionalRESUMEN
Over the years, efforts in bioinspired soft robotics have led to mobile systems that emulate features of natural animal locomotion. This includes combining mechanisms from multiple organisms to further improve movement. In this work, we seek to improve locomotion in soft, amphibious robots by combining two independent mechanisms: sea star locomotion gait and gecko adhesion. Specifically, we present a sea star-inspired robot with a gecko-inspired adhesive surface that is able to crawl on a variety of surfaces. It is composed of soft and stretchable elastomer and has five limbs that are powered with pneumatic actuation. The gecko-inspired adhesion provides additional grip on wet and dry surfaces, thus enabling the robot to climb on 25° slopes and hold on statically to 51° slopes.
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The Blood Profiling Atlas in Cancer (BLOODPAC) Consortium is a collaborative effort involving stakeholders from the public, industry, academia, and regulatory agencies focused on developing shared best practices on liquid biopsy. This report describes the results from the JFDI (Just Freaking Do It) study, a BLOODPAC initiative to develop standards on the use of contrived materials mimicking cell-free circulating tumor DNA, to comparatively evaluate clinical laboratory testing procedures. Nine independent laboratories tested the concordance, sensitivity, and specificity of commercially available contrived materials with known variant-allele frequencies (VAFs) ranging from 0.1% to 5.0%. Each participating laboratory utilized its own proprietary evaluation procedures. The results demonstrated high levels of concordance and sensitivity at VAFs of >0.1%, but reduced concordance and sensitivity at a VAF of 0.1%; these findings were similar to those from previous studies, suggesting that commercially available contrived materials can support the evaluation of testing procedures across multiple technologies. Such materials may enable more objective comparisons of results on materials formulated in-house at each center in multicenter trials. A unique goal of the collaborative effort was to develop a data resource, the BLOODPAC Data Commons, now available to the liquid-biopsy community for further study. This resource can be used to support independent evaluations of results, data extension through data integration and new studies, and retrospective evaluation of data collection.
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ADN Tumoral Circulante , Neoplasias Hematológicas , Neoplasias , Humanos , Estudios Retrospectivos , Neoplasias/genética , Biopsia Líquida/métodosRESUMEN
Conservationists speculated on potential benefits to wildlife of lockdown restrictions because of the COVID-19 pandemic but voiced concern that restrictions impeded nature conservation. We assessed the effects of lockdown restrictions on biodiversity conservation in South Africa, a biodiverse country with economic inequality and reliance on wildlife resources. We solicited expert opinion using the IUCN's Threats Classification Scheme to structure a questionnaire and illustrated responses with individual case studies from government parastatal and non-governmental conservation organisations. The most highly reported threats were biological resource use, residential/commercial developments, invasive species, and human intrusions. The trends reported by 90 survey respondents were supported by case studies using environmental compliance data from parastatal conservation organisations. Lack of tourism revenue and funding were cited as hindrances to conservation. Mechanisms to prevent environmental degradation in the face of global emergencies must be implemented and 'ring-fenced' to ensure conservation is not a casualty during future global crises.
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COVID-19 , Conservación de los Recursos Naturales , Animales , Humanos , Animales Salvajes , Control de Enfermedades Transmisibles/legislación & jurisprudencia , COVID-19/prevención & control , Sudáfrica , Encuestas y CuestionariosRESUMEN
BACKGROUND: Lower limb venous disease can cause significant pain, loss of mobility, and can be detrimental to an individual's quality of life. Manifestations of venous disease often pose a substantially negative impact on patients and place a high demand on finite healthcare resources. Whilst this problem is internationally recognised, most research and discourse has predominantly focussed on treatment of leg ulceration and prevention of recurrence. Prevention of lower limb venous disease progression to the first ulceration has received far less attention. Overall, the care of this condition appears to rest in the domain of medicine and nursing yet podiatry, a profession with responsibility for the lower limb and foot, is conspicuous by its absence from the literature. METHODS: An ethnographic approach was used to gather data from 26 participants through observation, semi-structured interviews, and a focus group interview. Qualitative analysis was conducted using the framework approach. RESULTS: The findings revealed an identity crisis within the podiatry profession. Evidence emerged of ritual and routine practices that did not include lower limb venous disease. External control over practice limited the professional autonomy of podiatrists determining their own activities. Inter-professional relationships with nursing, and perceptions of boundaries that venous disease was a nursing role were also found to be limiting factors. CONCLUSIONS: This research revealed that podiatry does not occupy a substantive role in contributing to the early identification and prevention of lower limb venous disease. Policy, education, research and practice changes are all required to enhance the contribution of podiatry to reduce the burden of this disease.
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Podiatría , Humanos , Calidad de Vida , Extremidad Inferior , Pie , EscolaridadRESUMEN
AIM: To explore how inter-professional collaboration in the teaching and learning of research skills prepares undergraduate students for their professional roles in healthcare via an evaluation of inter-professional research modules from the student perspective. PARTICIPANTS AND SETTINGS: Participants were selected from a university in the North of England where all undergraduate Healthcare students were taught Research and Evidence Based Practice (EBP) through interprofessional education (n = 400). METHODS: Quantitative data was collected using an adapted Attitudes Towards Interprofessional Education Scale and internally-designed pilot instruments. Qualitative data was also collected via open comment to evaluate the taught research module. RESULTS: 50 students completed the survey pre-module and 49 students completed the survey post-module. The participants' views towards inter-professional education (IPE) are generally positive: the median responses of 4 single-item measures assessing inter-professional learning on 7-point Likert scales were 5 or above (where higher scores represented more positive perceptions). Scores on the Attitudes towards Interprofessional Education scale also generally represented positive opinions, with a mean post-test score of 58.8 on a scale from 5 to 75, with higher scores indicating greater levels of positivity. No evidence for a statistically significant improvement from the pre- to post- 3rd year experience of the IPE/research theme was revealed. Qualitative data identified six themes: promoting team working, developing awareness of other health care professional's roles, polarising research and practice, multidisciplinary team (MDT) working or not working, logistical issues and developing research skills. CONCLUSIONS: This study raised questions about the appropriateness of "unnatural" pairings for undertaking research projects. Whilst the students valued working together in the research process, they do not appear to have perceived a universal benefit to their inter-professional clinical practice.
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Conducta Cooperativa , Relaciones Interprofesionales , Actitud del Personal de Salud , Estudios Transversales , Práctica Clínica Basada en la Evidencia , Humanos , EstudiantesRESUMEN
Importance: Aminoglycosides are commonly prescribed antibiotics used for the treatment of neonatal sepsis. The MT-RNR1 m.1555A>G variant predisposes to profound aminoglycoside-induced ototoxicity (AIO). Current genotyping approaches take several days, which is unfeasible in acute settings. Objective: To develop a rapid point-of-care test (POCT) for the m.1555A>G variant before implementation of this technology in the acute neonatal setting to guide antibiotic prescribing and avoid AIO. Design, Setting, and Participants: This pragmatic prospective implementation trial recruited neonates admitted to 2 large neonatal intensive care units between January 6, 2020, and November 30, 2020, in the UK. Interventions: Neonates were tested for the m.1555A>G variant via the rapid POCT on admission to the neonatal intensive care unit. Main Outcomes and Measures: The primary outcome assessed the proportion of neonates successfully tested for the variant of all infants prescribed antibiotics. Secondary outcomes measured whether implementation was negatively associated with routine clinical practice and the performance of the system. The study was statistically powered to detect a significant difference between time to antibiotic administration before and after implementation of the MT-RNR1 POCT. Results: A total of 751 neonates were recruited and had a median (range) age of 2.5 (0-198) days. The MT-RNR1 POCT was able to genotype the m.1555A>G variant in 26 minutes. Preclinical validation demonstrated a 100% sensitivity (95% CI, 93.9%-100.0%) and specificity (95% CI, 98.5%-100.0%). Three participants with the m.1555A>G variant were identified, all of whom avoided aminoglycoside antibiotics. Overall, 424 infants (80.6%) receiving antibiotics were successfully tested for the variant, and the mean time to antibiotics was equivalent to previous practice. Conclusions and Relevance: The MT-RNR1 POCT was integrated without disrupting normal clinical practice, and genotype was used to guide antibiotic prescription and avoid AIO. This approach identified the m.1555A>G variant in a practice-changing time frame, and wide adoption could significantly reduce the burden of AIO.
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Aminoglicósidos , Ototoxicidad , Aminoglicósidos/efectos adversos , Antibacterianos/efectos adversos , Genotipo , Humanos , Lactante , Recién Nacido , Cuidado Intensivo Neonatal , Sistemas de Atención de Punto , Estudios ProspectivosRESUMEN
With the change to one scientific name for fungal taxa, generic names typified by species with sexual or asexual morph types are being evaluated to determine which names represent the same genus and thus compete for use. In this paper generic names of the Agaricomycotina (Basidiomycota) were evaluated to determine synonymy based on their type. Forty-seven sets of sexually and asexually typified names were determined to be congeneric and recommendations are made for which generic name to use. In most cases the principle of priority is followed. However, 16 generic names are recommended for use that do not have priority and thus need to be protected: Aleurocystis over Matula; Armillaria over Acurtis and Rhizomorpha; Asterophora over Ugola; Botryobasidium over Acladium, Allescheriella, Alysidium, Haplotrichum, Physospora, and Sporocephalium; Coprinellus over Ozonium; Coprinopsis over Rhacophyllus; Dendrocollybia over Sclerostilbum and Tilachlidiopsis; Diacanthodes over Bornetina; Echinoporia over Echinodia; Neolentinus over Digitellus; Postia over Ptychogaster; Riopa over Sporotrichum; Scytinostroma over Artocreas, Michenera, and Stereofomes; Tulasnella over Hormomyces; Typhula over Sclerotium; and Wolfiporia over Gemmularia and Pachyma. Nine species names are proposed for protection: Botryobasidium aureum, B. conspersum, B. croceum, B. simile, Pellicularia lembosporum (syn. B. lembosporum), Phanerochaete chrysosporium, Polyporus metamorphosus (syn. Riopa metamorphosa), Polyporus mylittae (syn. Laccocephalum mylittae), and Polyporus ptychogaster (syn. Postia ptychogaster). Two families are proposed for protection: Psathyrellaceae and Typhulaceae. Three new species names and 30 new combinations are established, and one lectotype is designated.
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INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss. METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice. ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study. TRIAL REGISTRATION NUMBER: ISRCTN13704894. PROTOCOL VERSION: V 1.3.
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Sordera , Farmacogenética , Audición , Humanos , Recién Nacido , Estudios Observacionales como Asunto , Pruebas en el Punto de Atención , Estudios ProspectivosRESUMEN
Aim: The study sought to determine the patterns of N-glycan profiles among Type 2 diabetes mellitus (T2DM) patients over a 6-month period. Materials & methods: Biochemical and clinical data were obtained from 253 T2DM patients at baseline and follow-up. Ultra-performance liquid chromatography and statistical methods were applied for N-glycan profiling. Results: The coefficients of variation were 28% and 29% at baseline and follow-up, respectively, whereas the range of N-glycan variability was from 11% to 56%. Apart from GP1 (FA2) and GP29 (FA3G3S [3,3,3]3), the intra-individual variations of N-glycan peaks were not statistically significant. Conclusion: N-glycan profiles were stable over 6-month period in T2DM patients and could be used to monitor biochemical changes in relation with T2DM comorbidities.
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Diabetes Mellitus Tipo 2/metabolismo , Polisacáridos/sangre , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Femenino , Estudios de Seguimiento , Ghana/epidemiología , Glicosilación , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
A 37-year-old woman presented to her local district general hospital with a cough, pleuritic chest pain and intermittent cyanosis. Eight months prior, she underwent a successful pericardial window for recurrent, symptomatic pericardial effusions. On presentation she was hypoxic but haemodynamically stable. Her chest radiograph raised the suspicion of a diaphragmatic hernia, confirmed by CT imaging. This identified herniation through the diaphragm of the transverse colon and left lobe of the liver resulting in cardiac compression and right ventricular dysfunction. She continued to deteriorate and required emergency intubation to allow safe transfer to a tertiary upper gastrointestinal unit. She underwent a laparotomy and repair of the diaphragmatic hernia with an uneventful inpatient recovery. In the literature, diaphragmatic liver herniation is a recognised complication secondary to trauma or congenital defects, however, to our knowledge, there are currently no cases described following pericardial windowing.
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Hernia Diafragmática Traumática/etiología , Derrame Pericárdico/cirugía , Técnicas de Ventana Pericárdica/efectos adversos , Adulto , Síndrome de Down/complicaciones , Femenino , Humanos , Derrame Pericárdico/complicaciones , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: Nanofiltration entails the filtering of protein solutions through membranes with pores of nanometric sizes that have the capability to effectively retain a wide range of viruses. STUDY DESIGN AND METHODS: Data were collected from 754 virus validation studies (individual data points) by Plasma Protein Therapeutics Association member companies and analyzed for the capacity of a range of nanofilters to remove viruses with different physicochemical properties and sizes. Different plasma product intermediates were spiked with viruses and filtered through nanofilters with different pore sizes using either tangential or dead-end mode under constant pressure or constant flow. Filtration was performed according to validated scaled-down laboratory conditions reflecting manufacturing processes. Effectiveness of viral removal was assessed using cell culture infectivity assays or polymerase chain reaction (PCR). RESULTS: The nanofiltration process demonstrated a high efficacy and robustness for virus removal. The main factors affecting nanofiltration efficacy are nanofilter pore size and virus size. The capacity of nanofilters to remove smaller, nonenveloped viruses was dependent on filter pore size and whether the nanofiltration process was integrated and designed with the intention to provide effective parvovirus retention. Volume filtered, operating pressure, and total protein concentration did not have a significant impact on the effectiveness of virus removal capacity within the investigated ranges. CONCLUSIONS: The largest and most diverse nanofiltration data collection to date substantiates the effectiveness and robustness of nanofiltration in virus removal under manufacturing conditions of different plasma-derived proteins. Nanofiltration can enhance product safety by providing very high removal capacity of viruses including small non-enveloped viruses.
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Proteínas Sanguíneas/aislamiento & purificación , Plasma , Ultrafiltración , Virus , Proteínas Sanguíneas/uso terapéutico , Humanos , Plasma/química , Plasma/virologíaRESUMEN
Obesity and hypertension are public health problems associated with cardiovascular events worldwide. Bus drivers, whose lifestyle is primarily sedentary and characterized by poor eating habits are at increased risk. This study determined the prevalence and lifestyle-related risk factors of obesity and hypertension among Inter-Regional Metromass Bus Drivers (IRMBDs) in Ghana. This cross-sectional study recruited 527 professional drivers from Metromass Bus stations in Accra and Kumasi Metropolis, Ghana. Structured questionnaires were administered to obtain socio-demographic and lifestyle characteristics from all participants. Anthropometric measurements including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and blood pressure (BP) were determined. The prevalence of unrecognized hypertension was 38.7%. The prevalence of obesity using BMI, WC, and WHR as obesity indices were 19.0%, 19.9%, and 19.4%, respectively. Use of sleep inhibitors, long-duration sitting and eating late at night were independent risk factors for obesity, regardless of the obesity index used (p < 0.05). Physical inactivity, high caloric intake and eating at stressful periods were independent risk factors for obesity based on WC and WHR measurements (p < 0.05). Ageing, smoking history, alcoholic beverage intake, sleep inhibitor drug use, high calorie intake, long-duration sitting, eating late and under stressful conditions were independent risk factors for hypertension (p < 0.05). There is a high prevalence of unrecognized hypertension and obesity among IRMBDs which were associated with individual lifestyle and behaviours. Increased awareness through educational and screening programs will trigger lifestyle modifications that will reduce cardio-metabolic disease onset and offer clues for better disease predictive, preventive and personalized medicine.
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Optimal oxidative stress (OS) is important throughout pregnancy; however, an increased OS may alter placental angiogenesis culminating in an imbalanced of angiogenic growth mediators (AGMs). Suboptimal Health Status (SHS), a physical state between health and disease, may be associated with increased OS and unbalanced AGMs. In this study, we explored the association between SHS, biomarkers of OS (BOS) and AGMs among normotensive pregnant women (NTN-PW) in a Ghanaian Suboptimal Health Cohort Study (GHOACS). This comparative GHOACS recruited 593 NTN-PW from the Komfo Anokye Teaching Hospital, Ghana. SHS was measured using a Suboptimal Health Status Questionnaire-25 (SHSQ-25). Along with the subjective SHS measure, objective BOS: 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-epiprostaglandinF2 alpha (8-epi-PGF2α), total antioxidant capacity (TAC), and AGMs: vascular endothelial growth factor-A (VEGF-A), soluble fms-like tyrosine kinase receptor 1 (sFlt-1), placental growth factor (PIGF) and soluble endoglin (sEng) were evaluated. Compared to optimal health NTN-PW, levels of PlGF, VEGF-A and TAC were significantly (p < 0.05) reduced and negatively associated with SHS whilst sEng, sFlt-1, 8-epiPGF2α, 8-OHdG, and combined ratios of sFlt-1/PlGF, 8-epiPGF2α/PlGF, 8-OHdG/PlGF, and sEng/PlGF were significantly increased and positively associated with SHS. The first quartile for PIGF (2.79-fold) and VEGF-A (5.35-fold), and the fourth quartile for sEng (4.31-fold), sFlt-1 (1.84-fold), 8-epiPGF2α (2.23-fold), 8-OHdG (1.90-fold) and urinary 8-OHdG (1.95-fold) were independently associated with SHS (p < 0.05). SHS is associated with increased OS and unbalanced AGMs. Early identification of SHS-related OS and unbalanced AGMs may inform clinicians of the need for therapeutic options.
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Inhibidores de la Angiogénesis/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Adolescente , Adulto , Inhibidores de la Angiogénesis/farmacología , Estudios Transversales , Femenino , Ghana , Humanos , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
Type 2 diabetes mellitus (T2DM) is a common complex trait arising from interactions among multiple environmental, genomic, and postgenomic factors. We report here the first attempt to investigate the association between immunoglobulin G (IgG) N-glycan patterns, T2DM, and their clinical risk factors in an Australian population. N-glycosylation of proteins is one of the most frequently observed co- and post-translational modifications, reflecting, importantly, the real-time status of the interplay between the genomic and postgenomic factors. In a community-based case-control study, 849 participants (217 cases and 632 controls) were recruited from an urban community in Busselton, Western Australia. We applied the ultraperformance liquid chromatography method to analyze the composition of IgG N-glycans. We then conducted Spearman's correlation analyses to explore the association between glycan biomarker candidates and clinical risk factors. We performed area under the curve (AUC) analysis of the receiver operating characteristic curves by fivefold cross-validation for clinical risk factors, IgG glycans, and their combination. Two directly measured and four derived glycan peaks were significantly associated with T2DM, after correction for extensive clinical confounders and false discovery rate, thus suggesting that IgG N-glycan traits are highly correlated with T2DM clinical risk factors. Moreover, adding the IgG glycan profiles to fasting blood glucose in the logistic regression model increased the AUC from 0.799 to 0.859. The AUC for IgG glycans alone was 0.623 with a 95% confidence interval 0.580-0.666. In addition, our study provided new evidence of diversity in T2DM complex trait by IgG N-glycan stratification. Six IgG glycan traits were firmly associated with T2DM, which reflects an increased proinflammatory and biological aging status. In summary, our study reports novel associations between the IgG N-glycome and T2DM in an Australian population and the putative role of proinflammatory mechanisms. Furthermore, IgG N-glycomic alterations offer future prospects as inflammatory biomarker candidates for T2DM diagnosis, and monitoring of T2DM progression to cardiovascular disease or renal failure.
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Diabetes Mellitus Tipo 2/metabolismo , Inmunoglobulina G/metabolismo , Polisacáridos/metabolismo , Anciano , Australia , Biomarcadores/metabolismo , Femenino , Glicosilación , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Aim: The study sought to apply N-glycosylation profiles to understand the interplay between suboptimal health status (SHS) and metabolic syndrome (MetS). Materials & methods: In this study, 262 Ghanaians were recruited from May to July 2016. After completing a health survey, plasma samples were collected for clinical assessments while ultra performance liquid chromatography was used to measure plasma N-glycans. Results: Four glycan peaks were found to predict case status (MetS and SHS) using a step-wise Akaike's information criterion logistic regression model selection. This model yielded an area under the curve of MetS: 83.1% (95% CI: 78.0-88.1%) and SHS: 67.1% (60.6-73.7%). Conclusion: Our results show that SHS is a significant, albeit modest, risk factor for MetS and N-glycan complexity was associated with MetS.