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1.
Proc Natl Acad Sci U S A ; 117(16): 9064-9073, 2020 04 21.
Article in English | MEDLINE | ID: mdl-32273388

ABSTRACT

The invasive behavior of glioblastoma is essential to its aggressive potential. Here, we show that pleckstrin homology domain interacting protein (PHIP), acting through effects on the force transduction layer of the focal adhesion complex, drives glioblastoma motility and invasion. Immunofluorescence analysis localized PHIP to the leading edge of glioblastoma cells, together with several focal adhesion proteins: vinculin (VCL), talin 1 (TLN1), integrin beta 1 (ITGB1), as well as phosphorylated forms of paxillin (pPXN) and focal adhesion kinase (pFAK). Confocal microscopy specifically localized PHIP to the force transduction layer, together with TLN1 and VCL. Immunoprecipitation revealed a physical interaction between PHIP and VCL. Targeted suppression of PHIP resulted in significant down-regulation of these focal adhesion proteins, along with zyxin (ZYX), and produced profoundly disorganized stress fibers. Live-cell imaging of glioblastoma cells overexpressing a ZYX-GFP construct demonstrated a role for PHIP in regulating focal adhesion dynamics. PHIP silencing significantly suppressed the migratory and invasive capacity of glioblastoma cells, partially restored following TLN1 or ZYX cDNA overexpression. PHIP knockdown produced substantial suppression of tumor growth upon intracranial implantation, as well as significantly reduced microvessel density and secreted VEGF levels. PHIP copy number was elevated in the classical glioblastoma subtype and correlated with elevated EGFR levels. These results demonstrate PHIP's role in regulating the actin cytoskeleton, focal adhesion dynamics, and tumor cell motility, and identify PHIP as a key driver of glioblastoma migration and invasion.


Subject(s)
Brain Neoplasms/pathology , Focal Adhesions/pathology , Glioblastoma/pathology , Intracellular Signaling Peptides and Proteins/metabolism , Neovascularization, Pathologic/pathology , Actin Cytoskeleton/metabolism , Animals , Brain/pathology , Brain Neoplasms/blood supply , Brain Neoplasms/genetics , Cell Adhesion/genetics , Cell Line, Tumor , Cell Movement/genetics , Cohort Studies , Disease Progression , Female , Gene Dosage , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Glioblastoma/blood supply , Glioblastoma/genetics , Humans , Intracellular Signaling Peptides and Proteins/genetics , Intravital Microscopy , Mice , Microscopy, Confocal , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Neovascularization, Pathologic/genetics , Time-Lapse Imaging , Vinculin/metabolism , Xenograft Model Antitumor Assays
2.
J Pediatr Nurs ; 31(1): 92-8, 2016.
Article in English | MEDLINE | ID: mdl-26382965

ABSTRACT

A novel form of expressive arts therapy was developed in a pediatric unit and received enthusiastic support from hospital staff and family members because of their impressions that the children were calmer following therapy, as well as throughout the remainder of the hospital stay. A pilot study was conducted to assess the feasibility of quantifying such impressions by measuring changes in the children's mood by self-report. Twenty-five children (mean age 8.34 years, SD 3.77) were recruited for the study, coming from diverse social-economic backgrounds, ethnicities, and an array of medical diagnoses. The results document improvements in mood for children following therapy sessions, compared to children in a wait-list control group. Additionally, a meta-analysis examining external influences and changes in salivary cortisol levels measured before and after therapy sessions illustrates the importance of considering aspects of the clinical setting when assessing the effectiveness of this and other expressive arts therapies for reducing stress during hospitalization.


Subject(s)
Art Therapy/organization & administration , Child, Hospitalized/psychology , Quality of Life , Adolescent , Art , Child , Child, Preschool , Cohort Studies , Female , Humans , Male , Pilot Projects , Program Development , Program Evaluation , Stress, Psychological/therapy
3.
Front Psychol ; 15: 1347499, 2024.
Article in English | MEDLINE | ID: mdl-38298517

ABSTRACT

Introduction: Salivary alpha-amylase (sAA) is considered a marker of autonomic nervous system activity in stress research, and atypical waking sAA responses have been reported for traumatized individuals. Lucid dreams, characterized by a dreamer's awareness of their dream state while remaining asleep, have shown promising preliminary evidence of their potential to enhance mental health. This study's objective was to evaluate sAA in relation to healing lucid dreams. Methods: Participants experiencing PTSD symptoms attended a six-day workshop delivered via live video designed to teach techniques for transforming trauma through dreamwork and dream lucidity. Participants (n = 20) collected saliva samples each morning, immediately upon awakening (Time 1) and 30 min afterward (Time 2). sAA levels were determined by enzymatic assay, and the waking sAA slope was calculated as the difference of Time 2 minus Time 1. Participants completed dream reports each morning, with a dream classified as a 'healing lucid dream' when they reported attaining lucidity and remembered their intention to manifest a healing experience within the dreamscape. Results: Of eight participants experiencing healing lucid dreams, four were able to provide usable saliva samples. Statistical tests on these four participants were not significant because of low power. However, nonsignificant positive associations were observed between experiencing more healing lucid dreams and increased waking sAA slope. Conclusion: The results did not reveal a consistent effect of healing lucid dreams on waking sAA slope. Identifying meaningful patterns in this relationship will require larger samples and more stringent control over saliva collection procedures in future studies.

4.
Proc Natl Acad Sci U S A ; 107(43): 18616-21, 2010 Oct 26.
Article in English | MEDLINE | ID: mdl-20926749

ABSTRACT

Most patients who die from cancer succumb to treatment-refractory advanced metastatic progression. Although the early stages of tumor metastasis result in the formation of clinically silent micrometastatic foci, its later stages primarily reflect the progressive, organ-destructive growth of already advanced metastases. Early-stage metastasis is regulated by multiple factors within tumor cells as well as by the tumor microenvironment (TME). In contrast, the molecular determinants that control advanced metastatic progression remain essentially uncharacterized, precluding the development of therapies targeted against it. Here we show that the TME, functioning in part through platelet endothelial cell adhesion molecule 1 (PECAM-1), drives advanced metastatic progression and is essential for progression through its preterminal end stage. PECAM-1-KO and chimeric mice revealed that its metastasis-promoting effects are mediated specifically through vascular endothelial cell (VEC) PECAM-1. Anti-PECAM-1 mAb therapy suppresses both end-stage metastatic progression and tumor-induced cachexia in tumor-bearing mice. It reduces proliferation, but not angiogenesis or apoptosis, within advanced tumor metastases. Because its antimetastatic effects are mediated by binding to VEC rather than to tumor cells, anti-PECAM-1 mAb appears to act independently of tumor type. A modified 3D coculture assay showed that anti-PECAM-1 mAb inhibits the proliferation of PECAM-1-negative tumor cells by altering the concentrations of secreted factors. Our studies indicate that a complex interplay between elements of the TME and advanced tumor metastases directs end-stage metastatic progression. They also suggest that some therapeutic interventions may target late-stage metastases specifically. mAb-based targeting of PECAM-1 represents a TME-targeted therapeutic approach that suppresses the end stages of metastatic progression, until now a refractory clinical entity.


Subject(s)
Neoplasms, Experimental/secondary , Platelet Endothelial Cell Adhesion Molecule-1/physiology , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/pharmacology , Apoptosis , Bone Marrow Transplantation , Cachexia/therapy , Cell Line, Tumor , Cell Proliferation , Disease Progression , Endothelial Cells/physiology , Female , Humans , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Mice, Nude , Mice, Transgenic , Neoplasms, Experimental/blood supply , Neoplasms, Experimental/pathology , Neoplasms, Experimental/therapy , Neovascularization, Pathologic , Paracrine Communication , Phenotype , Platelet Endothelial Cell Adhesion Molecule-1/genetics , Platelet Endothelial Cell Adhesion Molecule-1/immunology
5.
J Nerv Ment Dis ; 200(10): 891-6, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22986277

ABSTRACT

This study examined the changes in cortisol levels and psychological distress symptoms of 83 nonclinical subjects receiving a single hour long intervention. Subjects were randomly assigned to either an emotional freedom technique (EFT) group, a psychotherapy group receiving a supportive interviews (SI), or a no treatment (NT) group. Salivary cortisol assays were performed immediately before and 30 minutes after the intervention. Psychological distress symptoms were assessed using the symptom assessment-45. The EFT group showed statistically significant improvements in anxiety (-58.34%, p < 0.05), depression (-49.33%, p < 0.002), the overall severity of symptoms (-50.5%, p < 0.001), and symptom breadth (-41.93%, p < 0.001). The EFT group experienced a significant decrease in cortisol level (-24.39%; SE, 2.62) compared with the decrease observed in the SI (-14.25%; SE, 2.61) and NT (-14.44%; SE, 2.67) groups (p < 0.03). The decrease in cortisol levels in the EFT group mirrored the observed improvement in psychological distress.


Subject(s)
Emotions/physiology , Hydrocortisone/metabolism , Psychotherapy , Stress, Psychological/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Anxiety/metabolism , Depression/metabolism , Female , Humans , Hydrocortisone/analysis , Male , Middle Aged , Saliva/chemistry
6.
J Integr Complement Med ; 28(1): 87-95, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35085021

ABSTRACT

Introduction: Personal development workshops are increasingly popular. This study evaluated the relationships between the measures of well-being, interconnectedness, and extended perception in various workshops and explored which kinds of workshops and individual characteristics predicted changes in these outcomes. Materials and Methods: In a prospective, uncontrolled, within-participant design study, adult participants completed questionnaires and online tasks before and after personal development workshops. Three analyses were conducted: (1) examining the relationships between measures by using only pre-workshop measures using Spearman correlations; (2) exploring change scores pre- to post-workshop and workshop using Wilcoxon signed-rank test; (3) assessing workshop format and content, and individual characteristics as predictors of those change scores multivariate nonparametric regression. The following outcomes were collected: Well-being-Arizona Integrative Outcomes Scale, positive and negative affect, Dispositional Positive Emotions Scale-Compassion subscale, Sleep Quality Scale, Numeric Pain Rating Scale; Interconnectedness-Cloninger Self-Transcendence Scale, Inclusion of Nature in Self and Inclusion of the Other in Self; and Extended perception tasks-Intuition Jar, Quick Remote Viewing, Psychokinesis Bubble, and Time Estimation. The following potential predictor variables were collected: demographic, mental health, psychiatric and meditation history, Single General Self-Rated Health Question, Brief Five-Factor Inventory-10, and the Noetic Experience and Belief Scale. Workshop leaders also selected which format and content characteristics applied to their workshop. Results: Interconnectedness measures were significantly and positively correlated with well-being (ρ: 0.27 to 0.33), positive affect (ρ: 0.20 to 0.27), and compassion (ρ: 0.21 to 0.32), and they were negatively correlated with sleep disturbance (ρ: -0.13 to -0.16) and pain (ρ: -0.11 to -0.16). Extended perception task performance was not correlated with interconnectedness or well-being. General personal development workshops improved subjective interconnectedness, well-being, positive emotion, and compassion, and they reduced sleep disturbances, negative emotion, and pain (all p's < 0.00005). The lecture (p = 0.03), small groups (p = 0.001), pairs (p = 0.01), and discussion (p = 0.03) workshop formats were significant predictors of well-being outcomes. The workshop content categories of meditation (p = 0.0002) and technology tools (p = 0.01) were also predictive of well-being outcomes, with meditation being the most consistent predictor of positive well-being changes. Conscientiousness was the only significant individual characteristic predictor (p = 0.002), although it was associated with increases in some well-being measures and decreases in others. Conclusions: This study provides preliminary evidence for the positive relationship between the subjective sense of interconnectedness and multiple well-being measures and the beneficial effects of some personal development workshops.


Subject(s)
Meditation , Sleep Quality , Adult , Emotions , Humans , Prospective Studies , Surveys and Questionnaires
7.
BMC Res Notes ; 15(1): 256, 2022 Jul 16.
Article in English | MEDLINE | ID: mdl-35842710

ABSTRACT

OBJECTIVE: Human gene expression studies typically rely on peripheral blood samples as a cellular source, however there are numerous situations in which venipuncture is contraindicated. To this end, an oral rinse-based method for collecting salivary neutrophils as a cellular source for gene expression analyses was previously developed and shown in a pilot study with five male participants to yield mRNA expression results comparable to those obtained from peripheral blood samples. The objective of the current study was to characterize the generalizability of the oral rinse-based method by analyzing unpublished RNA quality data obtained through a parent study that collected salivary neutrophil samples using the method from a larger sample size and including both men and women. RESULTS: The 260/280 nm absorbance ratios of the RNA obtained from 48 participants using the oral rinse-based method were within the expected range (average = 1.88 ± 0.16) for the majority of the samples, and no significant differences in RNA quality were found between participants' health, age group, or gender. Together with published data confirming the integrity of RNA obtained using the same method, these results support the feasibility of using this noninvasive method for obtaining samples for human gene expression analyses.


Subject(s)
Neutrophils , Saliva , Feasibility Studies , Female , Gene Expression , Humans , Male , Mouthwashes , Pilot Projects , RNA/genetics
8.
Explore (NY) ; 18(3): 264-271, 2022.
Article in English | MEDLINE | ID: mdl-33712359

ABSTRACT

INTRODUCTION: It is commonly believed that psychic ability, like many mental and physical traits, runs in families. This suggests the presence of a genetic component. If such a component were found, it would constitute a biological marker of psychic ability and inform environmental or pharmacologic means of enhancing or suppressing this ability. METHODS: A case-control study design was used to evaluate differences between psychic cases and non-psychic controls. Over 3,000 candidates globally were screened through two online surveys to locate people who claimed they and other family members were psychic. Measures of relevance to the claimed abilities (e.g., absorption, empathy, schizotypy) were collected and based on those responses, individuals with indications of psychotic or delusional tendencies were excluded from further consideration. Eligible candidates were then interviewed and completed additional screening tests. Thirteen individuals were selected as the final "psychic cases," and ten age-, sex-, and ethnicity-matched individuals with no claims of psychic ability were selected as controls. DNA from the saliva of these 23 participants was subjected to whole-exome sequencing. Two independent bioinformatics analyses were blindly applied to the sequenced data, one focusing exclusively on protein-coding sequences and another that also included some adjacent noncoding sequences. RESULTS: Sequencing data were obtained for all samples, except for one in the control group that did not pass the quality controls and was not included in further analyses. After unblinding the datasets, none of the protein-coding sequences (i.e., exons) showed any variation that discriminated between cases and controls. However, a difference was observed in the intron (i.e., non-protein-coding region) adjacent to an exon in the TNRC18 gene (Trinucleotide Repeat-Containing Gene 18 Protein) on chromosome 7. This variation, an alteration of GG to GA, was found in 7 of 9 controls and was absent from all psychic cases. DISCUSSION: The most conservative interpretation of these results is that they result from random population sampling. However, when the results are considered in relation to other lines of evidence, the results are more provocative. Further research is justified to replicate and extend these findings.


Subject(s)
Exome , Case-Control Studies , Exome/genetics , Humans , Exome Sequencing
9.
Explore (NY) ; 17(1): 40-44, 2021.
Article in English | MEDLINE | ID: mdl-33008779

ABSTRACT

INTRODUCTION: Outcomes of medical treatments tend to be highly variable. Some of the underlying variance is due to well-known factors such as age, gender, ethnicity, and effects of local weather. There are also less obvious influences including variations in solar wind, the Earth's geomagnetic field, and the interplanetary magnetic field. This study explored possible effects of these local and solar/geomagnetic variables on the outcomes of energy medicine treatments. The context was a pilot clinical trial involving 17 energy medicine practitioners who treated a total of 190 participants presenting with hand and wrist pain. METHODS: Eighteen environmental variables were correlated against changes in subjective pain and against changes in objective measures of nerve conduction velocity. RESULTS: The results showed that local barometric pressure, interplanetary magnetic field, lunar illumination, proton fluence, electron fluence, and solar radio flux showed statistically significant relationships with these health outcomes (at p < 0.05 or better) before correction for multiple comparison corrections. The variable of barometric pressure had a robust correlation with nerve conduction velocity, surviving adjustment for false discovery rate among the 18 variables at p < 0.05. DISCUSSION: This study lends support for future research into local weather, and potentially also to fluctuations in the solar/geomagnetic environment environmental measures as potential sources of variation in energy medicine sessions.


Subject(s)
Magnetic Fields , Humans
10.
Explore (NY) ; 17(1): 45-49, 2021.
Article in English | MEDLINE | ID: mdl-33032911

ABSTRACT

INTRODUCTION: Previously reported experiments suggest that aspects of the physical environment, in particular measures of negentropy (i.e., order) associated with the statistical outputs of truly random number generators, may be affected during periods of focused mental attention. The present study was designed to conceptually replicate those reports during energy medicine sessions. METHOD: A custom-built "quantum noise generator" (QNG) was used to continuously record and digitize (at 1 KHz) 16 independent channels of random samples (i.e., noise) produced by electron tunneling and avalanche effects in Zener diodes. One metric was developed to quantify temporal dependencies in the noise samples aggregated across the 16 channels, and a second metric was formed that measured spatial dependencies among the 16 channels. The two metrics were combined into a single "spacetime" variable used to measure fluctuations in entropy during 110 half-hour energy medicine sessions. As a control, the same measure was examined in data recorded eight hours after each energy medicine session took place, when no one was in the laboratory. RESULTS: QNG data recorded during the half-hour sessions showed significant deviations from chance expectation, with a peak deviation observed at 24 minutes into the half-hour (z = 4.24, p < 0.00003, two-tail), and with deviations associated with p < 0.05 from 20 to 29 min, after correction for multiple comparisons. By comparison, data recorded eight hours after each session showed uniformly null results. This outcome is consistent with previously reported studies, suggesting that during periods of focused attention negentropic deviations emerge in random physical systems. Counterarguments to this interpretation are discussed, as well as recommendations for future studies.


Subject(s)
Attention , Medicine , Biology , Humans , Thermodynamics
11.
Explore (NY) ; 17(1): 27-31, 2021.
Article in English | MEDLINE | ID: mdl-33109499

ABSTRACT

Previously reported experiments suggest that healing intention focused toward water, or merely taking place in the vicinity of water, affects the hydrogen-oxygen (HO) covalent bonds. This claim was explored in the context of a clinical energy medicine pilot study involving 17 practitioners and 190 participants. In a "direct" test, samples of water were directly treated by the practitioners; in an "indirect" test, aliquots attached to lanyards were worn by practitioners and participants as they were engaged in healing sessions. Samples of laboratory-grade distilled water and Fiji brand water were used in the tests, and the water was analyzed using an Attenuated Total Reflection (ATR) Fourier Transform Infrared (FTIR) spectrometer equipped with a liquid nitrogen-cooled detector. The comparison of interest was the ensemble average spectrum recorded during pre- vs. post-intentional healing periods in the primary infrared absorption portion of the water spectrum. The analyses indicated that distilled water directly treated by the practitioners resulted in a change in the HO bond at the wavenumber 3200 cm-1 (p < 0.03, two-tailed). No effect was observed with the Fiji water. The distilled water in aliquots worn by practitioners also resulted in a significant change at the same wavenumber (p = 0.0004, two-tailed). No effects were observed in Fiji water aliquots worn by practitioners or participants, or in distilled water worn by participants. This study contributes to previously reported observations suggesting that the structure of water reacts in an anomalous way to healing intentions. Such effects appear to involve some form of energetic influence, but that is not yet well established. Nor is it certain that the observed effect can only be due to intention; it is conceivable, for example, that an unidentified environmental factor may have been responsible for the observed comparisons. However, given similar results observed in several experiments so far, including the present study, further research seems warranted.


Subject(s)
Water , Humans , Pilot Projects , Spectroscopy, Fourier Transform Infrared
12.
Explore (NY) ; 17(1): 70-78, 2021.
Article in English | MEDLINE | ID: mdl-33132081

ABSTRACT

INTRODUCTION: Some "energy medicine" modalities, such as Reiki, continue to show evidence for efficacy, but the underlying mechanisms of action are still uncertain. To help illuminate possible mechanisms, this exploratory mixed-method study using qualitative and quantitative analyses investigated: 1) How do energy medicine sessions function from the perspective of a seer, i.e., an individual trained in techniques to enable perception of purported subtle energies, and 2) Do any of these observations correlate with changes in participants' subjective pain? METHOD: One seer reported observations during 30-minute energy medicine sessions delivered by 17 practitioners to participants experiencing chronic hand or wrist pain. Data were coded using an inductive approach, followed by thematic and descriptive analyses. Content analysis was used to assign whether each code was mentioned by the seer for each participant, generating 119 binary variables, one for each code. The relationship between these binary variables and change in participant pain scores after the energy medicine session and three weeks later were explored using linear regression models. RESULTS: The qualitative thematic analysis identified six major themes from the seer's notes: "Experience of the Practitioner," "Experience of the Participant," "Space and Other Beings" (referring to the qualities of the physical space the energy medicine session occurred in and ostensible non-physical beings present during session), "Participant-Practitioner Relationship," "Healing Process," and "Attributes of Energy." The energy medicine methods used varied for each participant, according to the practitioners' perceptions of each individual's needs. The linear regression models yielded significant associations between changes in pain scores and various codes, including energy color, practitioner touch and the presence of ostensible non-physical beings supporting the session, although their significance did not persist after correction for multiple comparisons. DISCUSSION: Future studies investigating the mechanisms of energy medicine may benefit from including perceptions by seers in their outcome measures.


Subject(s)
Therapeutic Touch , Humans , Pain , Perception , Research Design
13.
Explore (NY) ; 17(1): 11-21, 2021.
Article in English | MEDLINE | ID: mdl-33162335

ABSTRACT

INTRODUCTION: The term "energy medicine" describes healing modalities that manipulate or channel purported subtle energies associated with the body. The objectives of this pilot study were to determine the feasibility of studying energy medicine for people with carpal tunnel pain and gathering relevant preliminary data. METHODS: Following a prospective, within-participant design, participants were recruited to experience a 30 min treatment from one of 17 energy medicine practitioners. Of 374 adults experiencing carpal tunnel pain who were screened for the study, 190 received an energy medicine treatment. Practitioners delivered treatments at close distance, some with and some without light, stationary touch. Outcome measures were collected before, during, and immediately after the treatment, and three weeks later. The primary outcome measure was self-reported pain. Secondary subjective measures included credibility regarding energy medicine and expectancy regarding the efficacy of treatments, pain interference, sleep quality, well-being, mood, and sense of personal transformation. Physiological measures included median nerve conduction velocity, heart rate variability, heart rate synchrony (between the participant and practitioner), and expression levels of neuroinflammation-related genes. RESULTS: On average, self-reported current pain scores decreased 2.0 points post-session and 1.3 points at three weeks compared to baseline values using a 0-10 point scale with 10 denoting worst pain (F(2, 565) = 3.82 p <0.000005). This effect was not influenced by the participants' level of expectancy or credibility regarding the energy medicine modality. Well-being, negative emotion, and sleep quality scores significantly improved at the follow-up visit. Multiple heart rate variability measures significantly changed reflecting increased parasympathetic activity which may indicate decreased stress. No other secondary outcome showed significant change. DISCUSSION: Studying the administration of energy medicine to people with carpal tunnel pain is feasible, although requiring a documented carpal tunnel syndrome diagnosis proved to be prohibitive for recruitment. Our finding of preliminary evidence for positive effects in pain and pain-related outcomes after a single session of energy medicine warrants further controlled investigation.


Subject(s)
Hand , Wrist , Adult , Humans , Pain , Pilot Projects , Prospective Studies , Treatment Outcome
14.
Glob Adv Health Med ; 8: 2164956119832500, 2019.
Article in English | MEDLINE | ID: mdl-30828482

ABSTRACT

BACKGROUND: There are over 100 published studies of a therapy called Emotional Freedom Techniques (EFT). This popular form of energy psychology combines elements of established methods like cognitive therapy with acupressure. Our group reported the first evidence of its mechanisms of action at the molecular level, showing that it can influence levels of the stress hormone cortisol. OBJECTIVES: Given recent advances in molecular genomics that have identified noncoding ribonucleic acid (RNA) molecules as important regulators of gene expression, the aim of this study is to explore the possibility that microRNAs play a role in mediating the effects of EFT. METHODS: We measured microRNA levels in stored blood samples from our previous study in which veterans were randomized into an EFT group receiving EFT and treatment as usual throughout a 10-week intervention period, and a control group receiving only treatment as usual during the intervention period and then receiving EFT. A broad panel of 800 microRNAs was probed using a multiplexed, direct hybridization, and detection system. RESULTS: All of the microRNA targets were expressed at low levels and most were below thresholds established by negative control probes. Baseline variability was determined using samples collected from the control group at the start and end of the intervention period, and used to filter out targets that were too noisy under control conditions to be able to distinguish a response to treatment. Analysis of the remaining viable targets found a general trend of reduced expression following EFT, compared to expression levels in samples from the control group during the intervention period. The most notable decreases in expression levels were found for 2 microRNAs: let-7b and let-7c, although no significance was found after adjusting for multiple comparisons. CONCLUSIONS: These preliminary data support the feasibility of measuring microRNA expression level changes that correlate with effective EFT therapy.

15.
F1000Res ; 8: 1741, 2019.
Article in English | MEDLINE | ID: mdl-32518623

ABSTRACT

Background: Belief in the paranormal is widespread worldwide. Recent surveys suggest that subjective experiences of the paranormal are common. A concise instrument that adequately evaluates beliefs as distinct from experiences does not currently exist. To address this gap, we created the Noetic Experiences and Beliefs Scale (NEBS) which evaluates belief and experience as separate constructs. Methods: The NEBS is a 20-item survey with 10 belief and 10 experience items rated on a visual analog scale from 0-100. In an observational study, the survey was administered to 361 general population adults in the United States and a subsample of 96 one month later. Validity, reliability and internal consistency were evaluated. A confirmatory factor analysis was conducted to confirm the latent variables of belief and experience. The survey was then administered to a sample of 646 IONS Discovery Lab participants to evaluate divergent validity and confirm belief and experience as latent variables of the model in a different population. Results: The NEBS demonstrated convergent validity, reliability and internal consistency (Cronbach's alpha Belief 0.90; Experience 0.93) and test-retest reliability (Belief: r = 0.83 ; Experience: r = 0.77). A confirmatory factor analysis model with belief and experience as latent variables demonstrated a good fit. The factor model was confirmed as having a good fit and divergent validity was established in the sample of 646 IONS Discovery Lab participants. Conclusions: The NEBS is a short, valid, and reliable instrument for evaluating paranormal belief and experience.


Subject(s)
Parapsychology , Psychometrics , Adult , Factor Analysis, Statistical , Humans , Reproducibility of Results , Surveys and Questionnaires , United States
16.
Cancer Res ; 66(8): 4223-32, 2006 Apr 15.
Article in English | MEDLINE | ID: mdl-16618745

ABSTRACT

Malignant gliomas are almost uniformly fatal and display exquisite radiation resistance. Glioma cells lacking wild-type (WT) p53 function are more susceptible to radiation-induced apoptosis than their isogenic counterparts expressing WT p53. We explored the mechanisms of such apoptosis and found that, in the absence of WT p53, radiation increases caspase-8 expression and activity. Inhibition of caspase-8 expression using caspase-8 antisense or small interfering RNA (siRNA) oligonucleotides partially blocks radiation-induced apoptosis. In contrast, inhibition of the mitochondrial death pathway by expression of Bcl-2 has no effect on radiation-induced caspase-8 activity or apoptosis. Our data indicate that, in contrast to commonly accepted models of p53-dependent radiation-induced apoptosis, in our cell system, radiation relies on caspase-8 activity to help mediate p53-independent cell death. In a system of inducible E2F1 activity, E2F1 activated caspase-8 and, accordingly, decreased cellular viability, effects that were abolished by caspase-8 siRNA. In this model, in the absence of WT p53, p21Cip1 is not induced, and E2F1 activity is sustained and allows transcription and activation of caspase-8. This model may explain why p53 mutations in adult gliomas paradoxically correlate with improved survival and enhanced response to radiation.


Subject(s)
Apoptosis/radiation effects , Caspases/physiology , Glioma/enzymology , Apoptosis/physiology , Caspase 8 , Caspases/biosynthesis , Caspases/genetics , Caspases/radiation effects , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p21/metabolism , E2F1 Transcription Factor/metabolism , Enzyme Induction/radiation effects , Glioma/pathology , Glioma/radiotherapy , Humans , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Transcription, Genetic/radiation effects , Tumor Suppressor Protein p53/physiology
17.
Am J Health Promot ; 32(1): 112-122, 2018 Jan.
Article in English | MEDLINE | ID: mdl-27520015

ABSTRACT

PURPOSE: To assess the feasibility of measuring changes in gene expression associated with post-traumatic stress disorder (PTSD) treatment using emotional freedom techniques (EFT). DESIGN: Participants were randomized into an EFT group receiving EFT and treatment as usual (TAU) throughout a 10-week intervention period and a group receiving only TAU during the intervention period and then receiving EFT. SETTING: A community clinic and a research institute in California. PARTICIPANTS: Sixteen veterans with clinical levels of PTSD symptoms. INTERVENTION: Ten hour-long sessions of EFT. MEASURES: Messenger RNA levels for a focused panel of 93 genes related to PTSD. The Symptom Assessment 45 questionnaire, Hospital Anxiety and Depression Scale, Insomnia Severity Scale, SF-12v2 for physical impairments, and Rivermead Postconcussion Symptoms Questionnaire. ANALYSIS: Pre-, posttreatment, and follow-up mean scores on questionnaires were assessed using repeated measures 1-way analysis of variance. A Student t test and post hoc analyses were performed on gene expression data. RESULTS: Post-traumatic stress disorder symptoms declined significantly in the EFT group (-53%, P < .0001). Participants maintained their gains on follow-up. Significant differential expression of 6 genes was found ( P < .05) when comparing the expression levels before and after the intervention period in participants receiving EFT. CONCLUSION: Study results identify candidate gene expression correlates of successful PTSD treatment, providing guidelines for the design of further studies aimed at exploring the epigenetic effects of EFT.


Subject(s)
Cognitive Behavioral Therapy/methods , Stress Disorders, Post-Traumatic/genetics , Stress Disorders, Post-Traumatic/rehabilitation , Veterans/psychology , Adult , Aged , California , Epigenesis, Genetic , Female , Humans , Male , Middle Aged , Pilot Projects
18.
Anticancer Res ; 27(5A): 3173-8, 2007.
Article in English | MEDLINE | ID: mdl-17970058

ABSTRACT

BACKGROUND: The use of camptothecin (CPT) derivatives is limited by severe toxicity associated with the instability of their chemical structure. We have developed a stable CPT derivative (CPT417) and have investigated its biological activity in comparison to the currently used CPT analogs. MATERIALS AND METHODS: The anticancer effects of CPT417 were assessed in vitro, with glioblastoma and colon cancer cell lines, and in vivo with mice bearing mammary adenocarcinoma tumors implanted subcutaneously in the flank. Cytotoxicity was assessed using vital dye exclusion, timelapse microscopy and colony formation. RESULTS: CPT417 and topotecan inhibited glioblastoma cell growth at comparable levels and both compounds inhibited clonogenicity of colon cancer cells more effectively than irinotecan. CPT417 showed a much greater inhibition of mammary tumor growth compared to topotecan, both by intraperitoneal and oral administration. CONCLUSION: CPT417 shows dramatically reduced toxicity and an enhanced antitumor activity compared to topotecan.


Subject(s)
Antineoplastic Agents/pharmacology , Camptothecin/analogs & derivatives , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Animals , Camptothecin/pharmacology , Cell Growth Processes/drug effects , Cell Line, Tumor , Colonic Neoplasms/drug therapy , Colonic Neoplasms/pathology , Glioblastoma/drug therapy , Glioblastoma/pathology , Humans , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Inbred C3H , Topotecan/pharmacology
19.
Explore (NY) ; 3(4): 386-90, 2007.
Article in English | MEDLINE | ID: mdl-17681259

ABSTRACT

OBJECTIVE: To test whether healing treatments by biofield practitioners can protect normal human brain cells against cell death induced by oxidative stress. DESIGN: Cultured human brain cells were exposed to increasing concentrations of hydrogen peroxide and cell death was quantified by computerized time-lapse microscopy. Biofield treatments were delivered to cells from a short distance in 24 independent experiments. Six highly experienced biofield practitioners each participated, all with exceptional reputations within their respective communities (4 independent experiments each). An equal number of control experiments involving no healing intervention were conducted to provide a measure of intrinsic variability of the experimental system. Experiments were conducted with blinding applied to each of the scientists and randomized sample assignment. INTERVENTION: Healing treatments were delivered to cells from a short distance by a single practitioner, before and after exposure to hydrogen peroxide, for a total of 30 minutes. OUTCOME MEASURE: Cell death was quantified over a 4-hour period following experimental treatments. RESULTS: We found no significant difference in cell death rates between treatment and control groups.


Subject(s)
Brain/metabolism , Cell Death , Mental Healing , Cells, Cultured , Double-Blind Method , Humans , Models, Biological , Oxidative Stress
20.
Anticancer Res ; 36(11): 5845-5848, 2016 11.
Article in English | MEDLINE | ID: mdl-27793907

ABSTRACT

BACKGROUND/AIM: We developed a novel camptothecin analogue, CPT417, that yields reduced toxicity compared to other analogues used in chemotherapeutic regimens. In this pilot study, we assessed the activity of CPT417 against glioblastoma multiforme (GBM) cells and glioma stem cells. MATERIALS AND METHODS: The human U251 GBM cell line and normal human astrocytes were cultured in parallel for clonogenic survival analysis following exposure to increasing concentrations of CPT417. Cell viability of a glioma stem cell line was assessed 5 days after exposure to a range of CPT417 concentrations. RESULTS: CPT417 completely inhibited clonogenic survival of GBM cells at 10 nM, whereas this concentration only inhibited astrocytes by approximately 50%. Cell viability analysis of glioma stem cell cultures yielded a half-maximal response at 15 nM. CONCLUSION: CPT417 acts selectively against GBM cells at concentrations that are at least an order of magnitude below reported values for related alkylating agents in clinical use.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Camptothecin/pharmacology , Glioblastoma/pathology , Cell Line, Tumor , Humans , Pilot Projects
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