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Journal of the International Society of... Oct 2020Despite a substantial body of research, no clear best practice guidelines exist for the assessment of hydration in athletes. Body water is stored in and shifted between... (Review)
Review
BACKGROUND
Despite a substantial body of research, no clear best practice guidelines exist for the assessment of hydration in athletes. Body water is stored in and shifted between different sites throughout the body complicating hydration assessment. This review seeks to highlight the unique strengths and limitations of various hydration assessment methods described in the literature as well as providing best practice guidelines.
MAIN BODY
There is a plethora of methods that range in validity and reliability, including complicated and invasive methods (i.e. neutron activation analysis and stable isotope dilution), to moderately invasive blood, urine and salivary variables, progressing to non-invasive metrics such as tear osmolality, body mass, bioimpedance analysis, and sensation of thirst. Any single assessment of hydration status is problematic. Instead, the recommended approach is to use a combination, which have complementary strengths, which increase accuracy and validity. If methods such as salivary variables, urine colour, vital signs and sensation of thirst are utilised in isolation, great care must be taken due to their lack of sensitivity, reliability and/or accuracy. Detailed assessments such as neutron activation and stable isotope dilution analysis are highly accurate but expensive, with significant time delays due to data analysis providing little potential for immediate action. While alternative variables such as hormonal and electrolyte concentration, bioimpedance and tear osmolality require further research to determine their validity and reliability before inclusion into any test battery.
CONCLUSION
To improve best practice additional comprehensive research is required to further the scientific understanding of evaluating hydration status.
Topics: Absorptiometry, Photon; Blood Physiological Phenomena; Body Mass Index; Body Water; Dehydration; Drinking; Electric Impedance; Hematocrit; Hormones; Humans; Neutron Activation Analysis; Osmolar Concentration; Saliva; Serum; Sodium; Sports; Tears; Thirst; Urinalysis; Vital Signs
PubMed: 33126891
DOI: 10.1186/s12970-020-00381-6 -
Journal of Advanced Research Feb 2023Increasing evidence demonstrates that the activation states and diverse spectrum of macrophage subtypes display dynamic heterogeneity in the tumor microenvironment,...
Integrated immunogenomic analysis of single-cell and bulk tissue transcriptome profiling unravels a macrophage activation paradigm associated with immunologically and clinically distinct behaviors in ovarian cancer.
INTRODUCTION
Increasing evidence demonstrates that the activation states and diverse spectrum of macrophage subtypes display dynamic heterogeneity in the tumor microenvironment, which plays a critical role in a variety of cancer types.
OBJECTIVES
To investigate the heterogeneity and the homeostasis of different macrophage subtypes, as well as their effect on biological and clinical manifestations of ovarian cancer (OV).
METHOD
Integrated immunogenomic analysis of single-cell and bulk tissuetranscriptome profiling was performed to systematically investigate the association between macrophage activation and prognostic and therapeutic efficacy. Consensus clustering analysis was used to define novel macrophage subtypes. An artificial neural network was used to simulate the dynamic activation of macrophages.
RESULTS
The pan-cohort results suggested that high relative infiltration abundance of M0 and M1 macrophages was associated with improved outcome and therapeutic efficacy. However, it was the opposite for M2 macrophages. Unsupervised consensus clustering analysis revealed two OV subgroups characterized by a balance between M0, M1 and M2 macrophages with distinct clinical and immunological behaviors. Finally, a macrophage polarization-derived artificial neural network model was proposed to serve as a robust prognostic factor and predictive biomarker for therapeutic efficacy, which was validated in different independent patient cohorts.
CONCLUSION
The present study provides a new understanding of macrophage heterogeneity and its association with OV prognosis and underlines the future clinical potential of a macrophage activation model for tumor prevention and treatment.
Topics: Humans; Female; Macrophage Activation; Macrophages; Transcriptome; Gene Expression Profiling; Ovarian Neoplasms; Tumor Microenvironment
PubMed: 36725186
DOI: 10.1016/j.jare.2022.04.006 -
Blood Advances Apr 2020Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell...
Human natural killer (NK) cells in peripheral blood perform many functions, and classification of specific subsets has been a longstanding goal. We report single-cell RNA sequencing of NK cells, comparing gene expression in unstimulated and interleukin (IL)-2-activated cells from healthy cytomegalovirus (CMV)-negative donors. Three NK cell subsets resembled well-described populations; CD56brightCD16-, CD56dimCD16+CD57-, and CD56dimCD16+CD57+. CD56dimCD16+CD57- cells subdivided to include a population with higher chemokine mRNA and increased frequency of killer-cell immunoglobulin-like receptor expression. Three novel human blood NK cell populations were identified: a population of type I interferon-responding NK cells that were CD56neg; a population exhibiting a cytokine-induced memory-like phenotype, including increased granzyme B mRNA in response to IL-2; and finally, a small population, with low ribosomal expression, downregulation of oxidative phosphorylation, and high levels of immediate early response genes indicative of cellular activation. Analysis of CMV+ donors established that CMV altered the proportion of NK cells in each subset, especially an increase in adaptive NK cells, as well as gene regulation within each subset. Together, these data establish an unexpected diversity in blood NK cells and provide a new framework for analyzing NK cell responses in health and disease.
Topics: Cytomegalovirus; Cytomegalovirus Infections; Humans; Killer Cells, Natural; Receptors, KIR; Sequence Analysis, RNA
PubMed: 32271902
DOI: 10.1182/bloodadvances.2019000699 -
Cancer Cell Oct 2023Unlike many other hematologic malignancies, Richter syndrome (RS), an aggressive B cell lymphoma originating from indolent chronic lymphocytic leukemia, is responsive to...
Unlike many other hematologic malignancies, Richter syndrome (RS), an aggressive B cell lymphoma originating from indolent chronic lymphocytic leukemia, is responsive to PD-1 blockade. To discover the determinants of response, we analyze single-cell transcriptome data generated from 17 bone marrow samples longitudinally collected from 6 patients with RS. Response is associated with intermediate exhausted CD8 effector/effector memory T cells marked by high expression of the transcription factor ZNF683, determined to be evolving from stem-like memory cells and divergent from terminally exhausted cells. This signature overlaps with that of tumor-infiltrating populations from anti-PD-1 responsive solid tumors. ZNF683 is found to directly target key T cell genes (TCF7, LMO2, CD69) and impact pathways of T cell cytotoxicity and activation. Analysis of pre-treatment peripheral blood from 10 independent patients with RS treated with anti-PD-1, as well as patients with solid tumors treated with anti-PD-1, supports an association of ZNF683 T cells with response.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; CD8-Positive T-Lymphocytes; Lymphoma, Large B-Cell, Diffuse; Gene Expression Regulation; Immunotherapy
PubMed: 37738974
DOI: 10.1016/j.ccell.2023.08.013 -
Cell Reports Sep 2020Single-nucleus RNA sequencing (snRNA-seq) is used as an alternative to single-cell RNA-seq, as it allows transcriptomic profiling of frozen tissue. However, it is...
Single-nucleus RNA sequencing (snRNA-seq) is used as an alternative to single-cell RNA-seq, as it allows transcriptomic profiling of frozen tissue. However, it is unclear whether snRNA-seq is able to detect cellular state in human tissue. Indeed, snRNA-seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimer's disease. Our comparison of microglia from single cells and single nuclei of four human subjects reveals that, although most genes show similar relative abundances in cells and nuclei, a small population of genes (∼1%) is depleted in nuclei compared to whole cells. This population is enriched for genes previously implicated in microglial activation, including APOE, CST3, SPP1, and CD74, comprising 18% of previously identified microglial-disease-associated genes. Given the low sensitivity of snRNA-seq to detect many activation genes, we conclude that snRNA-seq is not suited for detecting cellular activation in microglia in human disease.
Topics: Gene Expression Profiling; Humans; Microglia; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 32997994
DOI: 10.1016/j.celrep.2020.108189 -
Journal of Autism and Developmental... May 2023We examined parent activation in families with autistic children over time. Activation is one's belief, knowledge, and persistence in obtaining and managing one's care...
We examined parent activation in families with autistic children over time. Activation is one's belief, knowledge, and persistence in obtaining and managing one's care (e.g., patient activation) and others (e.g., parent activation) and is associated with better outcomes. Four aims were examined: the associations between baseline parent activation and follow up treatment/outcome, between changes in activation and changes in treatment/outcome, differences in activation and treatment/outcome across demographic groups (e.g., gender, race, ethnicity, and income) and comparison of results using three different assessment approaches of parent activation, the Guttman scale (standard approach) and two factor subscales (Yu et al., in J Autism Dev Disord 53:110-120, 2023). The first factor tapped into behaviors aligned with highly active, assertive parental actions (Factor 1: Activated). The second tapped into behaviors representative of uncertainty, passivity, being overwhelmed, with growing awareness of the need for activation (Factor 2: Passive). Findings varied with assessment methods applied. The two subscales assessment approach produced the strongest effect sizes. Baseline activation was related to improved child outcomes at follow-up for Factor 1: Activated and to poorer child outcomes at follow-up for Factor 2: Passive. Changes in activation were unrelated to changes in treatment/outcomes. Outcomes differed based on the activation assessment approach used. Against expectations, activation remained the same over time. Further, no differences in outcomes were observed based on race, ethnicity, or family income. The results suggest that parent activation may behave differently than patient activation based on prior studies. More research is warranted on activation of parents of autistic children.
PubMed: 37133611
DOI: 10.1007/s10803-023-05985-w -
Journal of Psychopharmacology (Oxford,... Feb 2020Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed actions of... (Clinical Trial)
Clinical Trial
Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression.
BACKGROUND
Psilocybin has shown promise as a treatment for depression but its therapeutic mechanisms are not properly understood. In contrast to the presumed actions of antidepressants, we recently found increased amygdala responsiveness to fearful faces one day after open-label treatment with psilocybin (25 mg) in 19 patients with treatment-resistant depression, which correlated with treatment efficacy.
AIMS
Aiming to further unravel the therapeutic mechanisms of psilocybin, the present study extends this basic activation analysis. We hypothesised changed amygdala functional connectivity, more precisely decreased amygdala-ventromedial prefrontal cortex functional connectivity, during face processing after treatment with psilocybin.
METHODS
Psychophysiological interaction analyses were conducted on functional magnetic resonance imaging data from a classic face/emotion perception task, with the bilateral amygdala and ventromedial prefrontal cortex time-series as physiological regressors. Average parameter estimates (beta weights) of significant clusters were correlated with clinical outcomes at one week.
RESULTS
Results showed decreased ventromedial prefrontal cortex-right amygdala functional connectivity during face processing post- (versus pre-) treatment; this decrease was associated with levels of rumination at one week. This effect was driven by connectivity changes in response to fearful and neutral (but not happy) faces. Independent whole-brain analyses also revealed a post-treatment increase in functional connectivity between the amygdala and ventromedial prefrontal cortex to occipital-parietal cortices during face processing.
CONCLUSION
These results are consistent with the idea that psilocybin therapy revives emotional responsiveness on a neural and psychological level, which may be a key treatment mechanism for psychedelic therapy. Future larger placebo-controlled studies are needed to examine the replicability of the current findings.
Topics: Adult; Amygdala; Brain Mapping; Depressive Disorder, Treatment-Resistant; Emotions; Facial Expression; Female; Hallucinogens; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neural Pathways; Photic Stimulation; Prefrontal Cortex; Psilocybin; Treatment Outcome
PubMed: 31941394
DOI: 10.1177/0269881119895520 -
Critical Reviews in Toxicology Apr 2022We conducted a critical review on biomarkers of environmental manganese (Mn) exposure to answer the following questions: 1) are there reliable biomarkers of internal Mn... (Review)
Review
We conducted a critical review on biomarkers of environmental manganese (Mn) exposure to answer the following questions: 1) are there reliable biomarkers of internal Mn exposure (Mn in biological matrices) associated with external metrics of Mn exposure (Mn in environmental media)? and 2) are there accurate reference values (RVs) for Mn in biological matrices? Three bibliographic databases were searched for relevant references and identified references were screened by two independent reviewers. Of the 6342 unique references identified, 86 articles were retained for data abstraction. Our analysis of currently available evidence suggests that Mn levels in blood and urine are not useful biomarkers of Mn exposure in non-occupational settings. The strength of the association between Mn in environmental media and saliva was variable. Findings regarding the utility of hair Mn as a biomarker of environmental Mn exposure are inconsistent. Measurements of Mn in teeth are technically challenging and findings on Mn in tooth components are scarce. In non-occupationally exposed individuals, bone Mn measurements using neutron activation analysis (IVNAA) are associated with large uncertainties. Findings suggest that Mn in nails may reflect Mn in environmental media and discriminate between groups of individuals exposed to different environmental Mn levels, although more research is needed. Currently, there is no strong evidence for any biological matrix as a valid biomarker of Mn exposure in non-occupational settings. Because of methodological limitations in studies aimed at derivation of RVs for Mn in biological materials, accurate RVs are scarce.
Topics: Biomarkers; Environmental Exposure; Hair; Humans; Manganese; Nails; Occupational Exposure
PubMed: 35894753
DOI: 10.1080/10408444.2022.2095979 -
Transfusion Medicine Reviews Oct 2019The complement system plays an important role in varying types of disease, ranging from inflammatory and autoimmune disorders to immune deficiency states. In addition,... (Review)
Review
The complement system plays an important role in varying types of disease, ranging from inflammatory and autoimmune disorders to immune deficiency states. In addition, new settings have emerged where complement analysis is of interest to monitor complement-directed therapy and aid identification of transplant complications. Therefore, it is critical that clinical laboratories offer optimized and timely complement analysis. This review presents a comprehensive overview of the most important complement analysis methods that are currently used. It also points to some areas within complement diagnostics where development is needed, for example, regarding certain analytes for which practical methods suitable for the routine laboratory are lacking. Furthermore, it contains a more detailed discussion on complement autoantibody assessment. The list of analyses providing clinically valuable information includes analysis of complement function, quantification of individual complement components and complement activation fragments, identification of autoantibodies to complement, as well as genetic complement analyses. There is still a shortage of commercially available methods suitable for high-throughput screening of complement deficiency and for assessment of complement activation, but development is under way. There is also ongoing work within the complement community to improve standardization of measurements, and recently, an extensive quality assurance program has been initiated.
Topics: Autoantibodies; Clinical Laboratory Techniques; Complement Activation; Complement Inactivating Agents; Complement System Proteins; High-Throughput Screening Assays; Humans; Indicators and Reagents; Quality Control
PubMed: 31672339
DOI: 10.1016/j.tmrv.2019.09.001 -
Scientific Data Dec 2023The UCLA Cosmochemistry Database was initiated as part of a data-rescue and -storage project aimed at archiving a variety of cosmochemical data acquired at University of...
The UCLA Cosmochemistry Database was initiated as part of a data-rescue and -storage project aimed at archiving a variety of cosmochemical data acquired at University of California, Los Angeles (UCLA). The data collection includes elemental compositions of extraterrestrial materials analyzed by UCLA cosmochemists over the last five decades. The analytical techniques include atomic absorption spectrometry (AAS) and neutron activation analysis (NAA) at UCLA. The data collection is stored on the Astromaterials Data System (Astromat). We provide both interactive tables and downloadable datasheets for users to access all data. The UCLA Cosmochemistry Database archives cosmochemical data that are essential tools for increasing our understanding of the nature and origin of extraterrestrial materials. Future studies can reference the data collection in the examination, analysis, and classification of newly acquired extraterrestrial samples.
PubMed: 38062064
DOI: 10.1038/s41597-023-02807-7