Cardiovascular risk biomarkers and metabolically unhealthy status in prepubertal children: Comparison of definitions

Background and aims: The early onset of cardio-metabolic abnormalities, known as metabolically unhealthy (MU) status, is highly associated with obesity and cardiovascular disease (CVD), as well as with increased morbidity and mortality later in life. Given the lack of a consensus MU classification for prepubertal children, we aimed to compare available MU definitions in terms of their association with CVD risk biomarkers. Methods and results: A total of 930 prepubertal children (622 with overweight/obesity, 462 males) aged 5–10.9 years were recruited, anthropometric measures were taken and biomarkers were analyzed. Children were classified using eight MU definitions based on different cut-offs for blood pressure, triacylglycerides, high-density lipoprotein cholesterol, glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU prevalence in children with overweight/obesity ranged between 30% and 60% across definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of adiponectin were lower, in MU compared to MH children with overweight/obesity. Linear regression analyses confirmed the contribution of MPO and tPAI-1 concentrations to MU status, with most significant results derived from definitions that use age and sex-specific criteria and that account for HOMA-IR. Conclusion: Plasma concentrations of MPO and tPAI-1 are increased in prepubertal MU children irrespective of having normal-weight or overweight/obesity. Inclusion of age and sex-specific cut-offs for cardio-metabolic components as well as insulin resistance criteria increases the quality of MU definitions as seen by their stronger association with CVD biomarkers concentrations

Quantifying the speech-gesture relation with massive multimodal datasets: informativity in time expressions

The development of large-scale corpora has led to a quantum leap in our understanding of speech in recent years. By contrast, the analysis of massive datasets has so far had a lim- ited impact on the study of gesture and other visual communicative behaviors. We utilized the UCLA-Red Hen Lab multi-billion-word repository of video recordings, all of them showing communicative behavior that was not elicited in a lab, to quantify speech-gesture co-occur- rence frequency for a subset of linguistic expressions in American English. First, we objec- tively establish a systematic relationship in the high degree of co-occurrence between gesture and speech in our subset of expressions, which consists of temporal phrases. Sec- ond, we show that there is a systematic alignment between the informativity of co-speech gestures and that of the verbal expressions with which they co-occur. By exposing deep, systematic relations between the modalities of gesture and speech, our results pave the way for the data-driven integration of multimodal behavior into our understanding of human communication

Women's psychological experiences of physiological childbirth: a meta-synthesis

Objective: To synthesise qualitative studies on women's psychological experiences of physiological childbirth. Design: Meta-synthesis. Methods: Studies exploring women's psychological experiences of physiological birth using qualitative methods were eligible. The research group searched the following databases: MEDLINE, CINAHL, PsycINFO, PsycARTICLES, SocINDEX and Psychology and Behavioural Sciences Collection. We contacted the key authors searched reference lists of the collected articles. Quality assessment was done independently using the Critical Appraisal Skills Programme (CASP) checklist. Studies were synthesised using techniques of meta-ethnography. Results: Eight studies involving 94 women were included. Three third order interpretations were identified: 'maintaining self-confidence in early labour', 'withdrawing within as labour intensifies' and 'the uniqueness of the birth experience'. Using the first, second and third order interpretations, a line of argument developed that demonstrated 'the empowering journey of giving birth' encompassing the various emotions, thoughts and behaviours that women experience during birth. Conclusion: Giving birth physiologically is an intense and transformative psychological experience that generates a sense of empowerment. The benefits of this process can be maximised through physical, emotional and social support for women, enhancing their belief in their ability to birth and not disturbing physiology unless it is necessary. Healthcare professionals need to take cognisance of the empowering effects of the psychological experience of physiological childbirth. Further research to validate the results from this study is necessary. PROSPERO registration number CRD4201603707

Tumor-Associated Microbiome: Where Do We Stand?

The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome-microbe communities located either in the tumor or within its body compartment-seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies

Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism

Background: The marine n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to improve treatment of type 2 diabetic (T2D) patients remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA?+?DHA and the insulin-sensitizing drug pioglitazone in overweight/obese T2D patients already treated with metformin.Methods: In a parallel-group, four-arm, randomized trial, 69 patients (66 % men) were assigned to 24-week-intervention using: (i) corn oil (5 g/day; Placebo), (ii) pioglitazone (15 mg/day; Pio), (iii) EPA?+?DHA concentrate (5 g/day, containing ~2.8 g EPA?+?DHA; Omega-3), or (iv) pioglitazone and EPA?+?DHA concentrate (Pio&amp; Omega-3). Data from 60 patients were used for the final evaluation. At baseline and after intervention, various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures, EPA?+?DHA content in serum phospholipids was evaluated using shotgun lipidomics and mass spectrometry, and hyperinsulinemic-euglycemic clamp and meal test were also performed. Indirect calorimetry was conducted after the intervention. Primary endpoints were changes from baseline in insulin sensitivity evaluated using hyperinsulinemic-euglycemic clamp and in serum triacylglycerol concentrations in fasting state. Secondary endpoints included changes in fasting glycemia and glycated hemoglobin (HbA1c), changes in postprandial glucose, free fatty acid and triacylglycerol concentrations, metabolic flexibility assessed by indirect calorimetry, and inflammatory markers.Results: Omega-3 and Pio&amp; Omega-3 increased EPA?+?DHA content in serum phospholipids. Pio and Pio&amp; Omega-3 increased body weight and adiponectin levels. Both fasting glycemia and HbA1c were increased by Omega-3, but were unchanged by Pio&amp; Omega-3. Insulin sensitivity was not affected by Omega-3, while it was improved by Pio&amp; Omega-3. Fasting triacylglycerol concentrations and inflammatory markers were not significantly affected by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by Pio&amp; Omega-3.Conclusion: Besides preventing a modest negative effect of n-3 fatty acids on glycemic control, the combination of pioglitazone and EPA?+?DHA can be used to improve lipid metabolism in T2D patients on stable metformin therapy.Trial registration: EudraCT number 2009-011106-42.<br/

Cross-sectional survey of the wish to die among palliative patients in Spain: one phenomenon, different experiences

Objective Cultural backgrounds and values have a decisive impact on the phenomenon of the wish to die (WTD), and examination of this in Mediterranean countries is in its early stages. The objectives of this study were to establish the prevalence of WTD and to characterise this phenomenon in our cultural context. Methods A cross-sectional study with consecutive advanced inpatients was conducted. Data about WTD (Assessing Frequency & Extent of Desire to Die (AFFED) interview) and anxiety and depression (Edmonton Symptom Assessment System-revised (ESAS-r)) were collected through two face-to-face clinical encounters. Data were analysed with descriptive statistics, χ2 and analysis of variance. Results 201 patients participated and 165 (82%) completed both interviews. Prevalence of WTD was 18% (36/201) in the first interview and 16% (26/165) in the second interview (p=0.25). After the first interview, no changes in depression (p=0.60) or anxiety (p=0.90) were detected. The AFFED shows different experiences within WTD: 11% of patients reported a sporadic experience, while 7% described a persistent experience. Thinking about hastening death (HD) appeared in 8 (22%) out of 36 patients with WTD: 5 (14%) out of 36 patients considered this hypothetically but would never take action, while 3 (8%) out of 36 patients had a more structured idea about HD. In this study, no relation was detected between HD and frequency of the appearance of WTD (p=0.12). Conclusions One in five patients had WTD. Our findings suggest the existence of different experiences within the same phenomenon, defined according to frequency of appearance and intention to hasten death. A linguistically grounded model is proposed, differentiating the experiences of the ‘wish’ or ‘desire’ to die, with or without HD ideation

tumor infiltrating lymphocytes tils and pdl1 expression as prescreening enrichment biomarkers of clinical benefit to immune checkpoint inhibitors ci in early clinical trials ect

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phase i ii study of spartalizumab pdr001 an anti pd1 mab in patients with advanced melanoma or non small cell lung cancer

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Birth as a neuro-psycho-social event: An integrative model of maternal experiences and their relation to neurohormonal events during childbirth

Background Psychological aspects of labor and birth have received little attention within maternity care service planning or clinical practice. The aim of this paper is to propose a model demonstrating how neurohormonal processes, in particular oxytocinergic mechanisms, not only control the physiological aspects of labor and birth, but also contribute to the subjective psychological experiences of birth. In addition, sensory information from the uterus as well as the external environment might influence these neurohormonal processes thereby influencing the progress of labor and the experience of birth. Methodology In this new model of childbirth, we integrated the findings from two previous systematic reviews, one on maternal plasma levels of oxytocin during physiological childbirth and one meta-synthesis of women's subjective experiences of physiological childbirth. Findings The neurobiological processes induced by the release of endogenous oxytocin during birth influence maternal behaviour and feelings in connection with birth in order to facilitate birth. The psychological experiences during birth may promote an optimal transition to motherhood. The spontaneous altered state of consciousness, that some women experience, may well be a hallmark of physiological childbirth in humans. The data also highlights the crucial role of one-to-one support during labor and birth. The physiological importance of social support to reduce labor stress and pain necessitates a reconsideration of many aspects of modern maternity care. Conclusion By listening to women’s experiences and by observing women during childbirth, factors that contribute to an optimized process of labor, such as the mothers’ wellbeing and feelings of safety, may be identified. These observations support the integrative role of endogenous oxytocin in coordinating the neuroendocrine, psychological and physiological aspects of labor and birth, including oxytocin mediated. decrease of pain, fear and stress, support the need for midwifery one-to-one support in labour as well as the need for maternity care that optimizes the function of these neuroendocrine processes even when birth interventions are used. Women and their partners would benefit from understanding the crucial role that endogenous oxytocin plays in the psychological and neuroendocrinological process of labor

Exploring the Immunogenicity of Noncanonical HLA-I Tumor Ligands Identified through Proteogenomics

Purpose: Tumor antigens are central to antitumor immunity. Recent evidence suggests that peptides from noncanonical (nonC) aberrantly translated proteins can be presented on HLA-I by tumor cells. Here, we investigated the immunogenicity of nonC tumor HLA-I ligands (nonC-TL) to better understand their contribution to cancer immunosurveillance and their therapeutic applicability. Experimental Design: Peptides presented on HLA-I were iden-tified in 9 patient-derived tumor cell lines from melanoma, gyneco-logic, and head and neck cancer through proteogenomics. A total of 507 candidate tumor antigens, including nonC-TL, neoantigens, cancer-germline, or melanocyte differentiation antigens, were tested for T-cell recognition of preexisting responses in patients with cancer. Donor peripheral blood lymphocytes (PBL) were in vitro sensitized against 170 selected nonC-TL to isolate antigen-specific T-cell recep-tors (TCR) and evaluate their therapeutic potential.Rudolf Virchow Center, Center for Integrative and Transla- tional Bioimaging, Julius-Maximilians-University Wueurorzburg, Wueurorzburg, German