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This chapter explores dual senses of “being there,” as existential fact and corollary method, and suggests some reasons why and how an ecological framework provides an effective approach to unpacking the culture–mind–brain nexus. First, an ecological analysis brings the lens of evolutionary design to bear on human biology (brain), function (mind), and behavior (culture). Second, it taps reliance of developmental processes on nested timelines of interaction with context that drive physical (body/brain), functional (mind), and behavioral (enculturation) development across the life course. Third, it hones in on conditions created by humans’ reliance on culture, thereby creating their own ecologies that, in turn, generate tremendous human diversity. Being there can also play a valuable research role. Three case studies explore that role in interaction with existing bodies of knowledge, major societal and scientific questions, and studies with novel human cultures and ecologies. They also sketch an arc of inquiry that integrates biomarkers and health outcomes with measures of psychosocial dynamics and life course development into population research embedded in community and cultural settings. A dialectical ecologically informed approach that fluidly deploys diverse modes of research may be particularly effective for tackling the large questions and challenges that humans confront.
Breast cancer is the most commonly diagnosed malignancy among women and accounts for about 25% of all new cancer cases and 13% of all cancer deaths in Canadian women. It is a highly heterogeneous disease, encompassing multiple tumour entities, each characterised by distinct morphology, behaviour and clinical implications. Moreover, different breast tumour subtypes have different risk factors, clinical presentation, histopathological features, outcome and response to systemic therapies. Therefore, any strategies capable of the stratification of breast cancer by clinically relevant subtypes are an important requirement for personalised and targeted treatment. Therefore, in the advancement towards the concept of precision medicine that takes individual patient variability into account, several investigators have focused on the identification of effective clinical breast cancer biomarkers that interrogate key aberrant pathways potentially targetable with molecular targeted or immunological therapies.
Methods and materials:
This paper reports on a review of 11 current clinical and emerging biomarkers used in screening for early detection and diagnosis, to stratify patients by disease subtype, to identify patients’ risk for metastatic disease and subsequent relapse, to monitor patient response to specific treatment and to provide clinicians the possibility of prospectively identifying groups of patients who will benefit from a particular treatment.
The future holds promising for the use of effective clinical breast cancer biomarkers for early detection and personalised patient-specific targeted treatment and increased patient survival. Breast cancer biomarkers can potentially assist in early-staged, non-invasive, sensitive and specific breast cancer detection and screening, provide clinically useful information for identification of patients with a greater likelihood of benefiting from the specific treatment, offer a better understanding of the metastatic process in cancer patients, predict disease and for patients with the established disease can assist define the nature of the disease, monitor the success of treatment and guide the clinical management of the disease.
Recent advances on milk exosomes (EXO), cargoes in cell−cell communication, explored their role within and between individuals, including in dairy species. The potential use of EXO as biomarkers of disease and metabolic conditions adds significant interest to the study of EXO in milk. Although several researches have been carried out on circulating miRNA in the milk, less information is available about milk-derived exosomal miRNAs, which are stable over time and resistant to digestion and milk processing. EXO are taken up by recipient cells through specific mechanisms, which enable the selective delivery of cargoes. This suggests that EXO cargoes can be used as biomarkers of health. Nevertheless, methodological limitations and potential applications of milk EXO in dairy ruminants must be considered. The paucity of studies that associate the EXO cargo to specific challenges deserves further investigations to unravel the variation of miRNA and proteins cargo in relation to metabolic imbalance and infectious disease of the mammary gland.
Zn is an essential nutrient for humans; however, a sensitive biomarker to assess Zn status has not been identified. The objective of this study was to determine the reliability and sensitivity of Zn transporter and metallothionein (MT) genes in peripheral blood mononuclear cells (PBMCs) to Zn exposure ex vivo and to habitual Zn intake in human subjects. In study 1, human PBMCs were cultured for 24 h with 0–50 µm ZnSO4 with or without 5 µm N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), and mRNA expression of SLC30A1-10, SLC39A1-14, MT1 subtypes (A, B, E, F, G, H, L, M and X), MT2A, MT3 and MT4 mRNA was determined. In study 2, fifty-four healthy male and female volunteers (31·9 (sd 13·8) years, BMI 25·7 (sd 2·9) kg/m2) completed a FFQ, blood was collected, PBMCs were isolated and mRNA expression of selected Zn transporters and MT isoforms was determined. Study 1: MT1E, MT1F, MT1G, MT1H, MT1L, MT1M, MT1X, MT2A and SLC30A1 increased with increasing concentrations of Zn and declined with the addition of TPEN. Study 2: Average daily Zn intake was 16·0 (sd 5·3) mg/d (range: 9–31 mg/d), and plasma Zn concentrations were 15·5 (SD 2·8) μmol/l (range 11–23 μmol/l). PBMC MT2A was positively correlated with dietary Zn intake (r 0·306, P = 0·03) and total Zn intake (r 0·382, P < 0·01), whereas plasma Zn was not (P > 0·05 for both). Findings suggest that MT2A mRNA in PBMCs reflects dietary Zn intake in healthy adults and may be a component in determining Zn status.
Chest pain is one of the most common reasons for 999 calls and transfers to the emergency department (ED). In these patients, acute myocardial infarction (AMI) is often the diagnosis that clinicians are seeking to exclude. However, only a minority of those patients have AMI, causing a substantial financial burden to health services. Cardiac troponin (cTn) is the reference standard biomarker for the diagnosis of AMI. Several commercially available point-of-care (POC) cTn assays are portable and could feasibly be used in an ambulance. The aim of this paper is to systematically review existing evidence for the use of POC cTn assays in the prehospital setting to rule out AMI.
A systematic search was conducted on EMBASE, MEDLINE, and CINAHL Plus databases, reference lists, and relevant grey literature, including combinations of the relevant terms. Papers published in English language since the year 2000 were eligible for inclusion. A narrative synthesis of the evidence was then undertaken.
The initial search and cross-referencing revealed a total of 350 papers, of which 243 were excluded. Seven papers were included in the systematic literature review.
Current evidence does not support the use of POC troponin assays to exclude AMI due to issues with diagnostic accuracy and insufficient high-quality evidence.
The aim of the current study was to evaluate the accuracy of the new software eAT24 used to assess dietary intake in the National Food, Nutrition and Physical Activity Survey (IAN-AF) against urinary biomarkers: N (nitrogen), K (potassium) and Na (sodium).
We conducted a cross-sectional study. Two non-consecutive 24-h dietary recalls (24-HDR) were applied, and a 24-h urine sample was collected. We examined differences between estimates from dietary and urine measures, Pearson correlation coefficients were calculated and the Bland–Altman plots were drawn. Multiple linear regression was used to evaluate the factors associated with the difference between estimates.
Sub-sample from the Portuguese IAN-AF sampling frame.
Ninety-five adults (men and women) aged 18–84 years.
The estimated intake calculated using the dietary recall data was lower than that estimated from urinary excretion for the three biomarkers studied (protein 94·3 v. 100·4 g/d, K 3212 v. 3416 mg/d and Na 3489 v. 4003 mg/d). Considering 2 d of recall, the deattenuated correlation coefficients were 0·33, 0·64 and 0·26 for protein, K and Na, respectively. For protein, differences between dietary and urinary estimates varied according to BMI (β = −1·96, P = 0·017). The energy intake and 24-h urine volume were significantly associated with the difference between estimates for protein (β = 0·03, P < 0·001 and β = −0·02, P = 0·002, respectively), K (β = 0·71, P < 0·001 and β = −0·42, P = 0·040, respectively) and Na (β = 1·55, P < 0·001 and β = −0·81, P = 0·011, respectively).
The new software eAT24 performed well in estimating protein and K intakes, but lesser so in estimating Na intake, using two non-consecutive 24-HDR.
Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.
Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.
Urine collection methodologies were developed within home settings.
Different cohorts of free-living volunteers.
Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.
This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.
The efficiency of in vitro embryo production technologies would be improved by the development of suitable non-invasive biomarkers that allow the selection of good quality cumulus–oocyte complexes (COCs). The present study used whole, single oocyte culture to investigate whether the expression levels of follicle-stimulating hormone receptor (FSHR), insulin-like factor 1 receptor (IGF1R) and three steroidogenesis-related enzymes (CYP11al, CYP19al and HSD3β) in cumulus cells reflected the developmental competence of COCs. Cumulus cells were collected from single COCs before maturation culture and relative mRNA levels were assessed using real-time PCR. The analysis indicated that mRNAs for FSHR, IGF1R, CYP11al and HSD3β were present at higher levels in cumulus cells from COCs that failed to form blastocysts compared with cumulus cells from COCs that formed blastocysts. Moreover, FSHR and IGF1R mRNA levels were positively correlated with those of genes for steroidogenesis-related enzymes. In conclusion, poor developmental competence of COCs was related to higher expression of FSHR, IGF1R, CYP11al and HSD3β in cumulus cells, which may indicate the advanced differentiation of cumulus cells into granulosa cells.
In areas endemic for Leishmania infantum, an asymptomatic infection may be an indicator of the extent of transmission. The main goal of this study was to evaluate the applicability of measuring circulating immunological biomarkers as an alternative strategy to characterize and monitor L. infantum asymptomatic infections in combination with serological methods. To this end, 179 children from a region endemic for visceral leishmaniasis (VL), aged 1–10 years old, selected from a cross-sectional study, were identified as asymptomatic (n = 81) or uninfected (n = 98) by qPCR and/or serological tests (ELISA using L. infantum soluble antigen and rK39), and, together with serum samples of children diagnosed with VL (n = 43), were subjected to avidity tests and cytokine levels measurement. Avidity rates (AR) ranging from 41 to 70% were found in 29 children (66%) from the asymptomatic group. On the other hand, high AR (above 70%) were observed in 27 children (64%) from the VL group. Logistic Regression and Classification and Regression Tree (CART) analyses demonstrated that lower AR and IFN-γ production associated with higher IL-17A levels were hallmarks in asymptomatic L. infantum infections. Therefore, this study proposes an association of immunological biomarkers that can be used as a complementary strategy for the characterization and monitoring of asymptomatic VL infections in children living in endemic areas.
The influence of dietary habits on health/disease is well-established. Accurate dietary assessment is essential to understand metabolic pathways/processes involved in this relationship. In recent years, biomarker discovery has become a major area of interest for improving dietary assessment. Well-established nutrient intake biomarkers exist; however, there is growing interest in identifying and using biomarkers for more accurate and objective measurements of food intake. Metabolomics has emerged as a key tool used for biomarker discovery, employing techniques such as NMR spectroscopy, or MS. To date, a number of putatively identified biomarkers were discovered for foods including meat, cruciferous vegetables and legumes. However, many of the results are associations only and lack the desired validation including dose–response studies. Food intake biomarkers can be employed to classify individuals into consumers/non-consumers of specific foods, or into dietary patterns. Food intake biomarkers can also play a role in correcting self-reported measurement error, thus improving dietary intake estimates. Quantification of food intake was previously performed for citrus (proline betaine), chicken (guanidoacetate) and grape (tartaric acid) intake. However, this area still requires more investigation and expansion to a range of foods. The present review will assess the current literature of identified specific food intake biomarkers, their validation and the variety of biomarker uses. Addressing the utility of biomarkers and highlighting gaps in this area is important to advance the field in the context of nutrition research.
We examined whether change in added sugar intake is associated with change in δ13C, a novel sugar biomarker, in thirty-nine children aged 5–10 years selected from a Colorado (USA) prospective cohort of children at increased risk for type 1 diabetes. Reported added sugar intake via FFQ and δ13C in erythrocytes were measured at two time points a median of 2 years apart. Change in added sugar intake was associated with change in the δ13C biomarker, where for every 1-g increase in added sugar intake between the two time points, there was an increase in δ13C of 0⋅0082 (P = 0⋅0053), independent of change in HbA1c and δ15N. The δ13C biomarker may be used as a measure of compliance in an intervention study of children under the age of 10 years who are at increased risk for type 1 diabetes, in which the goal was to reduce dietary sugar intake.
Introduction: Mild Traumatic Brain Injury (mTBI) is a common problem: each year in Canada, its incidence is estimated at 500-600 cases per 100 000. Between 10 and 56% of mTBI patients develop persistent post-concussion symptoms (PPCS) that can last for more than 90 days. It is therefore important for clinicians to identify patients who are at risk of developing PPCS. We hypothesized that blood biomarkers drawn upon patient arrival to the Emergency Department (ED) could help predict PPCS. The main objective of this project was to measure the association between four biomarkers and the incidence of PPCS 90 days post mTBI. Methods: Patients were recruited in seven Canadian ED. Non-hospitalized patients, aged ≥14 years old with a documented mTBI that occurred ≤24 hrs of ED consultation, with a GCS ≥13 at arrival were included. Sociodemographic and clinical data as well as blood samples were collected in the ED. A standardized telephone questionnaire was administered at 90 days post ED visit. The following biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA): S100B protein, Neuron Specific Enolase (NSE), cleaved-Tau (c-Tau) and Glial fibrillary acidic protein (GFAP). The primary outcome measure was the presence of persistent symptoms at 90 days after mTBI, as assessed using the Rivermead Post-Concussion symptoms Questionnaire (RPQ). A ROC curve was constructed for each biomarker. Results: 1276 patients were included in the study. The median age for this cohort was 39 (IQR 23-57) years old, 61% were male and 15% suffered PPCS. The median values (IQR) for patients with PPCS compared to those without were: 43 pg/mL (26-67) versus 42 pg/mL (24-70) for S100B protein, 50 pg/mL (50-223) versus 50 pg/mL (50-199) for NSE, 2929 pg/mL (1733-4744) versus 3180 pg/mL (1835-4761) for c-Tau and 1644 pg/mL (650-3215) versus 1894 pg/mL (700-3498) for GFAP. For each of these biomarkers, Areas Under the Curve (AUC) were 0.495, 0.495, 0.51 and 0.54, respectively. Conclusion: Among mTBI patients, S100B protein, NSE, c-Tau or GFAP during the first 24 hours after trauma do not seem to be able to predict PPCS. Future research testing of other biomarkers is needed in order to determine their usefulness in predicting PPCS when combined with relevant clinical data.
Major depressive episodes (MDEs) show diverse cortisol level alterations. Heterogeneity in symptom profiles, symptom severity and cortisol specimens may explain these heterogeneous results. Less severely ill out-patients with a non-melancholic MDE (NM-MDE) may have a variation in the rhythm of cortisol secretion rather than in its concentration.
Cortisol measures were taken (a) over a short-term period (12 h) by measuring daily salivary output using the area under the curve with respect to the ground (AUCg) and (b) over a long-term period (3 months) in hair. Additionally, cortisol reactivity measures in saliva – the cortisol awakening response and the 30 min delta cortisol secretion after awakening (DELTA) – were investigated in 19 patients with a melancholic MDE (M-MDE) and 52 with a NM-MDE, and in 40 matched controls who were recruited from the UK and Chile. Depression severity scores were correlated with different cortisol measures.
The NM-MDE group showed a decreased AUCg in comparison with controls (P = 0.02), but normal cortisol reactivity and long-term cortisol levels. The M-MDE group did not exhibit any significant cortisol alterations nor an association with depression severity scores. Higher Hamilton Rating Scale for Depression score was linked with decreased hair cortisol concentration (HCC, P = 0.05) and higher DELTA (P = 0.04) in NM-MDEs, whereas decreased HCC was the sole alteration associated with out-patients with severe M-MDEs.
The contrasting short- and long-term cortisol output results are compatible with an alteration in the rhythm of cortisol secretion in NM-MDEs. This alteration may consist of large and/or intense episodes of hypercortisolaemia in moderate NM-MDEs and frequent, but brief and sharp early-morning DELTAs in its severe form. These changes may reflect the effects of environmental factors or episodes of nocturnal hypercortisolaemia that were not measured by the short-term samples used in this study.
To develop a scale to assess health motivation influencing food choices and to explore its performance in the associations with food intakes and nutritional biomarkers.
Psychometric study using cross-sectional self-report questionnaires and nutritional biomarkers.
Multi-centre investigation conducted in ten European cities.
2954 adolescents who were included in the HELENA study and completed the Food Choices and Preferences (FCP) questionnaire.
Nineteen out of 124 items of the FCP questionnaire were in the same dimension. Sixteen presented adequate parameters for the Scale of evaluatiOn of Food choIcEs (SOFIE). The scores were positively associated with the intakes of cereals, dairy products, meats and eggs, and fish, as well as with blood concentrations of vitamin C, β-carotene, n-3 fatty acids, cobalamin, holo-transcobalamin and folate; scores were negatively associated with the intake of alcohol.
SOFIE can improve the assessment of motivation influencing food choices based on items with the best performance and is proposed as a new measure to health-related studies.
Late-life depression is highly heterogeneous in clinical presentation, and is also commonly resistant to treatment. While some cases are a continuation of the chronic course of illness beginning in early adulthood, a large number of persons will have a first episode of depression in later life following alife-time of relatively good mental health. While incident cases of major depression tend to decrease with age, the number of persons with clinically significant depressive symptomatology rises. À distinction has often been made between early-onset and late-onset depression, however, there is no conclusive evidence to suggest these are distinct clinical entities. On the other hand observations from a fifteen year prospective population study of psychiatric disorder in the elderly (the ESPRIT Study) supports the alternative idea that depression may be divided into sub-types according to postulated aetiology; for example depression with a strong genetic component, related to hormonal changes, the consequence of trauma; the result of cerebrovascular insult. Exposure to these putative causes may be more common at different points in the life span, thus suggesting age-differences. Our research further suggests that even cases of depression appearing for the first time in late-life, may be initially triggered by risk factors occurring decades before. Our findings suggest, for example, that childhood events may lead to changes in the biology of stress management, which continue throughout life, increasing vulnerability to depression and persisting even after effective treatment of symptoms. Together these observations suggest it may be more meaningful to classify depression in the elderly according to probable principle precipitating factors rather than age.
The current study elucidates the relations between alexithymia and several biological components of the Metabolic Syndrome (MS). We hypothesized that various facets of the alexithymia construct are differentially related to single components characterizing the MS.
Investigated were N = 101 patients with MS. To establish the diagnosis of MS according to IDFC criteria, both laboratory (lipid profile, fasting plasma glucose, type 2 diabetes) and non-laboratory (blood pressure, waist circumference, BMI) tests were included. Alexithymia was measured using the Toronto Alexithymia Scale (TAS-20).
Based on alexithymia scores, patients were classified as low- (TAS-20 score ≤ 51; N = 31), moderate- (51 < TAS-20 score < 61; N = 33), or high-alexithymic (TAS-20 score ≥ 61; N = 37). The amount of moderate and high alexithymic patients proved highly significant amongst patients with MS with readily established diabetes type 2. The alexithymia score showed overall correlations with diabetes type 2 (r = 0.380, p < 0.001) and triglyceride levels (r = 0.214, p < 0.016). Correlations with non-laboratory measures were significant for high blood pressure levels (r = 0.233, p < 0.010). Linear regression models confirmed the existence of linear causal relationships for the observed correlations.
The present results suggest that the alexithymia trait is related to specific biological marker variables in the metabolic syndrome. Alexithymia may, according to our study, contribute to the aggravation of the MS.
Epidemiological studies show mixed findings for serum vitamin B12 (B12) and both cognitive and regional volume outcomes. No studies to date have comprehensively examined, in non-supplemented individuals, serum B12 level associations with neurodegeneration, hypometabolism and cognition across the Alzheimerʼs disease (AD) spectrum. Serum B12 was assayed from the Alzheimerʼs Disease Neuroimaging Initiative (ADNI) and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL). Voxel-wise analyses regressed B12 levels against regional grey matter (GM) volume and glucose metabolism (P < 0·05, family-wise corrected). For ADNI GM, there were thirty-nine cognitively normal (CN), seventy-three mild cognitive impairment (MCI) and thirty-one AD participants. For AIBL GM, there were 311 CN, fifty-nine MCI and thirty-one AD participants. Covariates were age, sex, baseline diagnosis, APOE4 status and BMI. In ADNI, higher B12 was negatively associated with GM in the right precuneus and bilateral frontal gyri. When diagnostic groups were examined separately, only participants with MCI, or above an established cut-off for cerebrospinal fluid (CSF) total tau showed such associations. In AIBL, higher B12 was associated with more GM in the right amygdala and right superior temporal pole, which largely seemed to be driven by CN participants that constituted most of the sample. Our results suggest that B12 may show different patterns of association based on clinical status and, for ADNI, AD CSF biomarkers. Accounting for these factors may clarify the relationship between B12 with neural outcomes in late-life.
Trend analyses based on dietary records suggest decreases in the intakes of total sugar (TS), added and free sugar since 2005 among children and adolescents in Germany. In terms of age trends, TS intake decreased with increasing age. However, self-reported sugar intake in epidemiological studies is criticised, as it may be prone to bias due to selective underreporting. Furthermore, adolescents are more susceptible to underreporting than children. We thus analysed time and age trends in urinary fructose excretion (FE), sucrose excretion (SE) and the sum of both (FE + SE) as biomarkers for sugar intake among 8·5–16·5-year-old adolescents. Urinary sugar excretion was measured by UPLC-MS/MS in 997 24-h urine samples collected from 239 boys and 253 girls participating in the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study cohort between 1990 and 2016. Time and age trends of log-transformed FE, SE and FE + SE were analysed using polynomial mixed-effects regression models. Between 1990 and 2016, FE as well as FE + SE decreased (linear time trend: P = 0·0272 and P < 0·0001, respectively). A minor increase in excretion during adolescence was confined to FE (linear age trend: P = 0·0017). The present 24-h excretion measurements support a previously reported dietary record-based decline in sugar intake since 2005. However, the previously seen dietary record-based decrease in TS from childhood to late adolescence was not confirmed by our biomarker analysis, suggesting a constant sugar intake for the period of adolescence.
Neuroblastoma is the most common extracranial solid tumour of infancy and accounts for about 6–10% of paediatric cancers. It has a biologically and clinically heterogeneous behaviour that ranges from spontaneous regression to cases of highly aggressive metastatic disease that could be unresponsive to standard therapy. In recent years, there have been several investigations into the development of various diagnostic, predictive and prognostic biomarkers towards personalised and targeted management of the disease.
Materials and Methods:
This paper reports on the review of current clinical and emerging biomarkers used in risk assessment, screening for early detection and diagnosis, prognostication and monitoring of the response of treatment of neuroblastoma in paediatric patients.
Tumour markers can significantly improve diagnosis; however, the invasive, unpleasant and inconvenient nature of current tissue biopsies limits their applications, especially in paediatric patients. Therefore, the development of a non-invasive, reliable high accurate and personalised diagnostic tool capable of early detection and rapid response is the most promising step towards advanced cancer management from tumour diagnosis, therapy to patient monitoring and represents an important step towards the promise of precision, personalised and targeted medicine. Liquid biopsy assay with wide ranges of clinical applications is emerging to hold incredible potential for advancing cancer treatment and has greater promise for diagnostic purposes, identification and tracking of tumour-specific alterations during the course of the disease and to guide therapeutic decisions.