Emerging biomarkers and metabolomics for assessing toxic nephropathy and acute kidney injury (AKI) in neonatology

Identification of novel drug-induced toxic nephropathy and acute kidney injury (AKI) biomarkers has been designated as a top priority by the American Society of Nephrology. Increasing knowledge in the science of biology and medicine is leading to the discovery of still more new biomarkers and of their roles in molecular pathways triggered by physiological and pathological conditions. Concomitantly, the development of the so-called “omics” allows the progressive clinical utilization of a multitude of information, from those related to the human genome (genomics) and proteome (proteomics), including the emerging epigenomics, to those related to metabolites (metabolomics). In preterm newborns, one of the most important factors causing the pathogenesis and the progression of AKI is the interaction between the individual genetic code, the environment, the gestational age, and the disease. By analyzing a small urine sample, metabolomics allows to identify instantly any change in phenotype, including changes due to genetic modifications. The role of liquid chromatography-mass spectrometry (LC-MS), proton nuclear magnetic resonance (1H NMR), and other emerging technologies is strategic, contributing basically to the sudden development of new biochemical and molecular tests. Urine neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (KIM-1) are closely correlated with the severity of kidney injury, representing noninvasive sensitive surrogate biomarkers for diagnosing, monitoring, and quantifying kidney damage. To become routine tests, uNGAL and KIM-1 should be carefully tested in multicenter clinical trials and should be measured in biological fluids by robust, standardized analytical methods

Urinary 1H-NMR Metabolic Signature in Subjects Undergoing Colonoscopy for Colon Cancer Diagnosis

Metabolomics represents a promising non-invasive approach that can be applied to identify biochemical changes in colorectal cancer patients (CRC) and is potentially useful for diagnosis and follow-up. Despite the literature regarding metabolomics CRC-specific profiles, discrimination between metabolic changes specifically related to CRC and intra-individual variability is still a problem to be solved. This was a preliminary case-control study, in which 1H-NMR spectroscopy combined with multivariate statistical analysis was used to profile urine metabolites in subjects undergoing colonoscopy for colon cancer diagnosis. To reduce intra-individual variability, metabolic profiles were evaluated in participants’ urine samples, collected just before the colonoscopy and after a short-term dietary regimen required for the endoscopy procedure. Data obtained highlighted different urinary metabolic profiles between CRC and unaffected subjects (C). The metabolites altered in the CRC urine (acetoacetate, creatine, creatinine, histamine, phenylacetylglycine, and tryptophan) significantly correlated with colon cancer and discriminated with accuracy CRC patients from C patients (receiver operator characteristic (ROC) curve with an area under the curve (AUC) of 0.875; 95% CI: 0.667–1). These results confirm that urinary metabolomic analysis can be a valid tool to improve CRC diagnosis, prognosis, and response to therapy, representing a noninvasive approach that could precede more invasive tests

Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life.

BACKGROUND: Perinatal asphyxia is a severe clinical condition affecting around four million newborns worldwide. It consists of an impaired gas exchange leading to three biochemical components: hypoxemia, hypercapnia and metabolic acidosis. METHODS: The aim of this longitudinal experimental study was to identify the urine metabolome of newborns with perinatal asphyxia and to follow changes in urine metabolic profile over time. Twelve babies with perinatal asphyxia were included in this study; three babies died on the eighth day of life. Total-body cooling for 72 hours was carried out in all the newborns. Urine samples were collected in each baby at birth, after 48 hours during hypothermia, after the end of the therapeutic treatment (72 hours), after 1 week of life, and finally after 1 month of life. Urine metabolome at birth was considered the reference against which to compare metabolic profiles in subsequent samples. Quantitative metabolic profiling in urine samples was measured by gas chromatography mass spectrometry (GC-MS). The statistical approach was conducted by using the multivariate analysis by means of principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). Pathway analysis was also performed. RESULTS: The most important metabolites depicting each time collection point were identified and compared each other. At birth before starting therapeutic hypothermia (TH), urine metabolic profiles of the three babies died after 7 days of life were closely comparable each other and significantly different from those in survivors. CONCLUSIONS: In conclusion, a plethora of data have been extracted by comparing the urine metabolome at birth with those observed at each time point collection. The modifications over time in metabolites composition and concentration, mainly originated from the depletion of cellular energy and homeostasis, seems to constitute a fingerprint of perinatal asphyxia

The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients

Background: CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. Methods: Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). Results: A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction 65 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction 65 20% to predict DCR (p = 0.002) and PFS (p < 0.001). Conclusion: The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab

Promoting fit bodies, healthy eating and physical activity among Indigenous Australian men: a study protocol

Background: Overall the physical health of Indigenous men is among the worst in Australia. Research has indicated that modifiable lifestyle factors, such as poor nutrition and physical inactivity, appear to contribute strongly to these poor health conditions. To effectively develop and implement strategies to improve the health of Australia&rsquo;s Indigenous peoples, a greater understanding is needed of how Indigenous men perceive health, and how they view and care for their bodies. Further, a more systematic understanding of how sociocultural factors affect their health attitudes and behaviours is needed. This article presents the study protocol of a communitybased investigation into the factors surrounding the health and body image of Indigenous Australian men.Methods and design: The study will be conducted in a collaborative manner with Indigenous Australian men using a participatory action research framework. Men will be recruited from three locations around Australia (metropolitan, regional, and rural) and interviewed to understand their experiences and perspectives on a number of issues related to health and health behaviour. The information that is collected will be analysed using modified grounded theory and thematic analysis. The results will then be used to develop and implement community events in each location to provide feedback on the findings to the community, promote health enhancing strategies, and determine future action and collaboration.Discussion: This study will explore both risk and protective factors that affect the health of Indigenous Australian men. This knowledge will be disseminated to the wider Indigenous community and can be used to inform future health promotion strategies. The expected outcome of this study is therefore an increased understanding of health and health change in Indigenous Australian men, the development of strategies that promote healthy eating and positive patterns of physical activity and, in the longer term, more effective and culturally-appropriate interventions to improve health.<br /

Embodiment and body awareness in meditators

[EN] Mindfulness practice consists of focusing attention in an intentional way on the experience of the present moment, including bodily sensations, thoughts or feelings, and the environment, with an attitude of acceptance and without judging. The body and, especially, body awareness are key elements in mindfulness. Embodiment or the feeling of being located within one's physical body is a related concept, and it is composed of the sense of ownership, location, and agency of the body. The rubber hand illusion (RHI) is an experimental paradigm that has been used to understand the mechanisms of embodiment, and evidence shows that body awareness modulates this illusion. To our knowledge, no studies have analyzed embodiment processes in meditators. The aim of this study is to use the RHI to analyze the mechanisms of embodiment and its relationship with body awareness and mindfulness in meditators and non-meditators. The sample was composed of long-term meditators (n = 15) and non-meditators (n = 15). Objective and self-report measures for embodiment with the RHI and self-report questionnaires of body awareness and mindfulness were administered. One-way ANOVA revealed significant differences between groups in sense of agency in the rubber hand. Meditators experienced less sense of agency in the rubber hand than non-meditators. Pearson's correlations showed that this lower sense of agency in the rubber hand was associated with higher body awareness and mindfulness. Results highlight the role of body awareness and mindfulness in embodiment mechanisms. This study has clinical implications, especially in psychopathological disorders that can be influenced by disturbances in these processes.The authors would like to acknowledge the "BODYTA" project (Spanish Ministry of Economy and Competitiveness, PSI2014-51928-R), "PROMOSAM" (Spanish Ministry of Economy and Competitiveness, PSI2014-56303-REDT), and "Excellence Research Program PROMETEO II" (Generalitat Valenciana, Conselleria de Educacion, Cultura y Deporte, PROMETEOII/2013/003). CIBERobn is an initiate of the ISCIII. PROMOSAM Excellence in Research Program (PSI2014-56303-REDT), MINECO, Spain.Cebolla, A.; Miragall, M.; Palomo, P.; Llorens Rodríguez, R.; Soler, J.; Demarzo, M.; García Campayo, J.... (2016). Embodiment and body awareness in meditators. Mindfulness. 7(6):1297-1305. https://doi.org/10.1007/s12671-016-0569-xS1297130576Aguado, J., Luciano, J. V., Cebolla, A., Serrano-Blanco, A., Soler, J., & García-Campayo, J. (2015). Bifactor analysis and construct validity of the five facet mindfulness questionnaire (FFMQ) in non-clinical Spanish samples. Frontiers in Psychology, 6, 404.Arzy, S., Thut, G., Mohr, C., Michel, C. M., & Blanke, O. (2006). Neural basis of embodiment: distinct contributions of temporoparietal junction and extrastriate body area. The Journal of Neuroscience, 26(31), 8074–8081.Baer, R. A., Smith, G. T., Hopkins, J., Krietemeyer, J., & Toney, L. (2006). Using self-report assessment methods to explore facets of mindfulness. Assessment, 13(1), 27–45.Bishop, S. R., Lau, M., Shapiro, S., Carlson, L., Anderson, N. D., Carmody, J., et al. (2004). Mindfulness: a proposed operational definition. Clinical Psychology: Science and Practice, 11(3), 230–241.Bornemann, B., Herbert, B. M., Mehling, W. E., & Singer, T. (2015). Differential changes in self-reported aspects of interoceptive awareness through 3 months of contemplative training. Frontiers in Psychology, 5, 1504.Botvinick, M., & Cohen, J. (1998). Rubber hands “feel” touch that eyes see. Nature, 391(6669), 756–756.Calsius, J., Courtois, I., Stiers, J., & De Bie, J. (2015). How do fibromyalgia patients with alexithymia experience their body? A qualitative approach. SAGE Open, 5, 1–10.Cascio, C. J., Foss-Feig, J. H., Burnette, C. P., Heacock, J. L., & Cosby, A. A. (2012). The rubber hand illusion in children with autism spectrum disorders: delayed influence of combined tactile and visual input on proprioception. Autism, 16(4), 406–419.Cebolla, A., Garcia-Palacios, A., Soler, J., Guillen, V., Baños, R., & Botella, C. (2012). Psychometric properties of the Spanish validation of the Five Facets of Mindfulness Questionnaire (FFMQ). The European Journal of Psychiatry, 26(2), 118–126.Cebolla, A., Vara, M. D., Miragall, M., Palomo, P., & Baños, R. M. (2015). Embodied mindfulness: review of the body’s participation in the changes associated with the practice of mindfulness. Actas españolas de Psiquiatría, 43, 36–41.Cioffi, D. (1991). Sensory awareness versus sensory impression: affect and attention interact to produce somatic meaning. Cognition & Emotion, 5(4), 275–294.Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale: Lawrence Erlbaum Associates Inc.Craig, A. D. (2009). How do you feel—now? The anterior insula and human awareness. Nature Reviews Neuroscience, 10(1), 59–70.Dreeben, S. J., Mamberg, M. H., & Salmon, P. (2013). The MBSR body scan in clinical practice. Mindfulness, 4(4), 394–401.Dummer, T., Picot-Annand, A., Neal, T., & Moore, C. (2009). Movement and the rubber hand illusion. Perception, 38(2), 271.Dunn, B. D., Galton, H. C., Morgan, R., Evans, D., Oliver, C., Meyer, M., et al. (2010). Listening to your heart. How interoception shapes emotion experience and intuitive decision making. Psychological Science, 21(12), 1835–1844.Ehrsson, H. H., Spence, C., & Passingham, R. E. (2004). That’s my hand! Activity in premotor cortex reflects feeling of ownership of a limb. Science, 305(5685), 875–877.Eshkevari, E., Rieger, E., Longo, M. R., Haggard, P., & Treasure, J. (2012). Increased plasticity of the bodily self in eating disorders. Psychological Medicine, 42(04), 819–828.Farb, N., Daubenmier, J. J., Price, C. J., Gard, T., Kerr, C., Dunn, B., et al. (2015). Interoception, contemplative practice, and health. Frontiers in Psychology, 6, 763.Fox, K. C., Zakarauskas, P., Dixon, M., Ellamil, M., Thompson, E., Christoff, K., et al. (2012). Meditation experience predicts introspective accuracy. PLoS ONE, 7(9), e45370.Grossman, P., Tiefenthaler-Gilmer, U., Raysz, A., & Kesper, U. (2007). Mindfulness training as an intervention for fibromyalgia: evidence of postintervention and 3-year follow-up benefits in well-being. Psychotherapy and Psychosomatics, 76(4), 226–233.Holmes, N. P., Snijders, H. J., & Spence, C. (2006). Reaching with alien limbs: visual exposure to prosthetic hands in a mirror biases proprioception without accompanying illusions of ownership. Perception & Psychophysics, 68(4), 685–701.Hölzel, B. K., Ott, U., Gard, T., Hempel, H., Weygandt, M., Morgen, K., et al. (2008). Investigation of mindfulness meditation practitioners with voxel-based morphometry. Social Cognitive and Affective Neuroscience, 3(1), 55–61.Hölzel, B. K., Lazar, S. W., Gard, T., Schuman-Olivier, Z., Vago, D. R., & Ott, U. (2011). How does mindfulness meditation work? Proposing mechanisms of action from a conceptual and neural perspective. Perspectives on Psychological Science, 6(6), 537–559.Kalckert, A., & Ehrsson, H. H. (2012). Moving a rubber hand that feels like your own: a dissociation of ownership and agency. Frontiers in Human Neuroscience, 6, 40.Karnath, H. O., & Baier, B. (2010). Right insula for our sense of limb ownership and self-awareness of actions. Brain Structure and Function, 214(5-6), 411–417.Keizer, A., Smeets, M. A., Postma, A., van Elburg, A., & Dijkerman, H. C. (2014). Does the experience of ownership over a rubber hand change body size perception in anorexia nervosa patients? Neuropsychologia, 62, 26–37.Kerr, C. E., Sacchet, M. D., Lazar, S. W., Moore, C. I., & Jones, S. R. (2013). Mindfulness starts with the body: somatosensory attention and top-down modulation of cortical alpha rhythms in mindfulness meditation. Frontiers in Human Neuroscience, 7, 12.Lakhan, S. E., & Schofield, K. L. (2013). Mindfulness-based therapies in the treatment of somatization disorders: a systematic review and meta-analysis. PLoS ONE, 8(8), e71834.Lazar, S. W., Kerr, C. E., Wasserman, R. H., Gray, J. R., Greve, D. N., Treadway, M. T., et al. (2005). Meditation experience is associated with increased cortical thickness. Neuroreport, 16(17), 1893–1897.Longo, M. R., Schüür, F., Kammers, M. P., Tsakiris, M., & Haggard, P. (2008). What is embodiment? A psychometric approach. Cognition, 107(3), 978–998.McManus, F., Surawy, C., Muse, K., Vazquez-Montes, M., & Williams, J. M. G. (2012). A randomized clinical trial of mindfulness-based cognitive therapy versus unrestricted services for health anxiety (hypochondriasis). Journal of Consulting and Clinical Psychology, 80(5), 817–828.Mehling, W. E., Gopisetty, V., Daubenmier, J., Price, C. J., Hecht, F. M., & Stewart, A. (2009). Body awareness: construct and self-report measures. PLoS ONE, 4(5), e5614.Mehling, W. E., Price, C., Daubenmier, J. J., Acree, M., Bartmess, E., & Stewart, A. (2012). The multidimensional assessment of interoceptive awareness (MAIA). PLoS ONE, 7(11), e48230.Mirams, L., Poliakoff, E., Brown, R. J., & Lloyd, D. M. (2013). Brief body-scan meditation practice improves somatosensory perceptual decision making. Consciousness and Cognition, 22(1), 348–359.Moseley, G. L., Olthof, N., Venema, A., Don, S., Wijers, M., Gallace, A., et al. (2008). Psychologically induced cooling of a specific body part caused by the illusory ownership of an artificial counterpart. Proceedings of the National Academy of Sciences, 105(35), 13169–13173.Mussap, A. J., & Salton, N. (2006). A ‘rubber-hand’ illusion reveals a relationship between perceptual body image and unhealthy body change. Journal of Health Psychology, 11(4), 627–639.Naranjo, J. R., & Schmidt, S. (2012). Is it me or not me? Modulation of perceptual-motor awareness and visuomotor performance by mindfulness meditation. BMC Neuroscience, 13(1), 88.Parkin, L., Morgan, R., Rosselli, A., Howard, M., Sheppard, A., Evans, D., et al. (2014). Exploring the relationship between mindfulness and cardiac perception. Mindfulness, 5(3), 298–313.Pollatos, O., Kurz, A. L., Albrecht, J., Schreder, T., Kleemann, A. M., Schöpf, V., et al. (2008). Reduced perception of bodily signals in anorexia nervosa. Eating Behaviors, 9(4), 381–388.Quezada-Berumen, L., González-Ramírez, M. T., Cebolla, A., Soler, J., & García-Campayo, J. (2014). Conciencia corporal y mindfulness: Validación de la versión española de la escala de conexión corporal (SBC). Actas Españolas de Psiquiatría, 42(2), 57–67.Rohde, M., Di Luca, M., & Ernst, M. O. (2011). The rubber hand illusion: feeling of ownership and proprioceptive drift do not go hand in hand. PLoS One, 6(6), e21659.Schauder, K. B., Mash, L. E., Bryant, L. K., & Cascio, C. J. (2015). Interoceptive ability and body awareness in autism spectrum disorder. Journal of Experimental Child Psychology, 131, 193–200.Sze, J. A., Gyurak, A., Yuan, J. W., & Levenson, R. W. (2010). Coherence between emotional experience and physiology: does body awareness training have an impact? Emotion, 10(6), 803–814.Teper, R., & Inzlicht, M. (2013). Meditation, mindfulness and executive control: the importance of emotional acceptance and brain-based performance monitoring. Social Cognitive and Affective Neuroscience, 8(1), 85–92.Thakkar, K. N., Nichols, H. S., McIntosh, L. G., & Park, S. (2011). Disturbances in body ownership in schizophrenia: evidence from the rubber hand illusion and case study of a spontaneous out-of-body experience. PLoS One, 6(10), e27089.Tran, U. S., Glück, T. M., & Nader, I. W. (2013). Investigating the Five Facet Mindfulness Questionnaire (FFMQ): construction of a short form and evidence of a two‐factor higher order structure of mindfulness. Journal of Clinical Psychology, 69(9), 951–965.Tsakiris, M., & Haggard, P. (2005). The rubber hand illusion revisited: visuotactile integration and self-attribution. Journal of Experimental Psychology: Human Perception and Performance, 31(1), 80.Tsakiris, M., Tajadura-Jiménez, A., & Costantini, M. (2011). Just a heartbeat away from one’s body: interoceptive sensitivity predicts malleability of body-representations. Proceedings of the Royal Society of London B: Biological Sciences, 278(1717), 2470–2476.Van Ravesteijn, H., Lucassen, P. L. B. J., Bor, H., Van Weel, C., & Speckens, A. (2013). Mindfulness-based cognitive therapy for patients with medically unexplained symptoms: a randomized controlled trial. Psychotherapy and Psychosomatics, 82(5), 299–310

Antifungal susceptibility of invasive yeast isolates in Italy: the GISIA3 study in critically ill patients

<p>Abstract</p> <p>Background</p> <p>Yeasts are a common cause of invasive fungal infections in critically ill patients. Antifungal susceptibility testing results of clinically significant fungal strains are of interest to physicians, enabling them to adopt appropriate strategies for empiric and prophylactic therapies. We investigated the antifungal susceptibility of yeasts isolated over a 2-year period from hospitalised patients with invasive yeast infections.</p> <p>Methods</p> <p>638 yeasts were isolated from the blood, central venous catheters and sterile fluids of 578 patients on general and surgical intensive care units and surgical wards. Etest strips and Sensititre panels were used to test the susceptibility of the isolates to amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, posaconazole and voriconazole in 13 laboratories centres (LC) and two co-ordinating centres (CC). The Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method was used at the CCs for comparison.</p> <p>Results</p> <p>Etest and Sensititre (LC/CC) MIC₉₀values were, respectively: amphotericin B 0.5/0.38, 1/1 mg/L; anidulafungin 2/1.5 and 1/1 mg/L; caspofungin 1/0.75 and 0.5/0.5 mg/L; fluconazole 12/8 and 16/16 mg/L; itraconazole 1/1.5, 0.5/0.5 mg/L; posaconazole 0.5 mg/L and voriconazole 0.25 mg/L for all. The overall MIC₉₀values were influenced by the reduced susceptibility of <it>Candida parapsilosis </it>isolates to echinocandins and a reduced or lack of susceptibility of <it>Candida glabrata </it>and <it>Candida krusei </it>to azoles, in particular fluconazole and itraconazole. Comparison of the LC and CC results showed good Essential Agreement (90.3% for Etest and 92.9% for Sensititre), and even higher Categorical Agreement (93.9% for Etest and 96% for Sensititre); differences were observed according to the species, method, and antifungal drug. No cross-resistance between echinocandins and triazoles was detected.</p> <p>Conclusions</p> <p>Our data confirm the different antifungal susceptibility patterns among species, and highlight the need to perform antifungal susceptibility testing of clinically relevant yeasts. With the exception of a few species (e.g. <it>C. glabrata </it>for azoles and <it>C. parapsilosis </it>for echinocandins), the findings of our study suggest that two of the most widely used commercial methods (Etest and Sensititre) provide valid and reproducible results.</p

Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD