scholarly journals Pressure Point Threshold and ME/CFS comorbidity as Indicators of Physiotherapy Response in Fibromyalgia

Author(s):  
Francisco Javier Falaguera-Vera ◽  
María Garcia-Escudero ◽  
Javier Bonastre-Férez ◽  
Mario Zacarés ◽  
Elisa Oltra

Current pharmacological treatments of Fibromyalgia (FM) are merely symptom palliative, as clinical trials have so far failed to provide overall benefits without associated harms. Polypharmacy often leads to patient´s health deterioration and chronic drug use to an eventual lack of patient´s response. Emerging evidence support that physiotherapy treatments based on mechanical triggers improve FM symptoms and therefore could be used for therapeutic purposes by themselves, or in combination with current pharmacological treatments, as part of integrative medicine programs. However, a paucity of studies rigorously and systematically evaluating this possibility exists. This study uses scores from validated standardized questionnaires, algometer pressure point threshold (PPT) readings and responses from a custom self-developed questionnaire to determine the impact of a pressure-controlled manual protocol on FM hyperalgesia/allodynia, fatigue and patient´s quality of life. The results show that patient´s baseline sensitivity to pain inversely correlates with treatment response in FM. Moreover, patients presenting comorbid ME/CFS do not seem to respond to the applied therapy as those presenting FM only. Thus, pre-treatment PPTs and ME/CFS comorbidity may serve as indicators to predict patient´s response to physiotherapy programs based on mechanical triggers, as the one evaluated here. These unexpected findings grant further explorations including the study of gene expression profiles associating to patient´s treatment response in the blood collection of samples generated by this study.

Author(s):  
Francisco Javier Falaguera-Vera ◽  
María Garcia-Escudero ◽  
Javier Bonastre-Férez ◽  
Mario Zacarés ◽  
Elisa Oltra

Current pharmacological treatments of Fibromyalgia (FM) are merely symptom palliative, as clinical trials have so far failed to provide overall benefits without associated harms. Polypharmacy often leads to patient’s health deterioration and chronic drug use to an eventual lack of patient’s response. Emerging evidence supports that physiotherapy treatments based on mechanical triggers improve FM symptoms and therefore could be used for therapeutic purposes by themselves or in combination with current pharmacological treatments, as part of integrative medicine programs. However, a paucity of studies rigorously and systematically evaluating this possibility exists. This study uses scores from validated standardized questionnaires, algometer pressure point threshold (PPT) readings and responses from a custom self-developed questionnaire to determine the impact of a pressure-controlled custom manual protocol on FM hyperalgesia/allodynia, fatigue and patient’s quality of life. The results show that patient’s baseline sensitivity to pain inversely correlates with treatment response in FM. Moreover, post-stratification analysis unexpectedly reveals that patients presenting comorbid ME/CFS do not seem to respond to the applied therapy as those presenting FM only. Therefore, pre-treatment PPTs and ME/CFS comorbidity may serve as indicators to predict patient’s response to physiotherapy programs based on mechanical triggers. Further exploration of these findings is granted. In addition, the study of gene expression profiles in the blood collection generated by this study should help unveil the molecular mechanisms behind patient’s differential response to manual therapy.


2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Xin Mao ◽  
Tracy Chaplin ◽  
Bryan D. Young

Sézary syndrome (SS) is a rare variant of primary cutaneous T-cell lymphoma. Little is known about the underlying pathogenesis of S. To address this issue, we used Affymetrix 10K SNP microarray to analyse 13 DNA samples isolated from 8 SS patients and qPCR with ABI TaqMan SNP genotyping assays for the validation of the SNP microarray results. In addition, we tested the impact of SNP loss of heterozygosity (LOH) identified in SS cases on the gene expression profiles of SS cases detected with Affymetrix GeneChip U133A. The results showed: (1) frequent SNP copy number change and LOH involving 1, 2p, 3, 4q, 5q, 6, 7p, 8, 9, 10, 11, 12q, 13, 14, 16q, 17, and 20, (2) reduced SNP copy number at FAT gene (4q35) in 75% of SS cases, and (3) the separation of all SS cases from normal control samples by SNP LOH gene clusters at chromosome regions of 9q31q34, 10p11q26, and 13q11q12. These findings provide some intriguing information for our current understanding of the molecular pathogenesis of this tumour and suggest the possibility of presence of functional SNP LOH in SS tumour cells.


2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Ben Holmes ◽  
Seung Ho Jung ◽  
Jing Lu ◽  
Jessica A. Wagner ◽  
Liudmilla Rubbi ◽  
...  

Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Zhi Chai ◽  
Yafei Lyu ◽  
Qiuyan Chen ◽  
Cheng-Hsin Wei ◽  
Lindsay Snyder ◽  
...  

Abstract Objectives To characterize and compare the impact of vitamin A (VA) deficiency on gene expression patterns in the small intestine (SI) and the colon, and to discover novel target genes in VA-related biological pathways. Methods vitamin A deficient (VAD) mice were generated by feeding VAD diet to pregnant C57/BL6 dams and their post-weaning offspring. Total mRNA extracted from SI and colon were sequenced using Illumina HiSeq 2500 platform. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and Weighted Gene Co-expression Network Analysis (WGCNA) were performed to characterize expression patterns and co-expression patterns. Results The comparison between vitamin A sufficient (VAS) and VAD groups detected 49 and 94 DEGs in SI and colon, respectively. According to GO information, DEGs in the SI demonstrated significant enrichment in categories relevant to retinoid metabolic process, molecule binding, and immune function. Immunity related pathways, such as “humoral immune response” and “complement activation,” were positively associated with VA in SI. On the contrary, in colon, “cell division” was the only enriched category and was negatively associated with VA. WGCNA identified modules significantly correlated with VA status in SI and in colon. One of those modules contained five known retinoic acid targets. Therefore we have prioritized the other module members (e.g., Mbl2, Mmp9, Mmp13, Cxcl14 and Pkd1l2) to be investigated as candidate genes regulated by VA. Comparison of co-expression modules between SI and colon indicated distinct VA effects on these two organs. Conclusions The results show that VA deficiency alters the gene expression profiles in SI and colon quite differently. Some immune-related genes (Mbl2, Mmp9, Mmp13, Cxcl14 and Pkd1l2) may be novel targets under the control of VA in SI. Funding Sources NIH training grant and NIH research grant. Supporting Tables, Images and/or Graphs


2015 ◽  
Vol 41 (6) ◽  
pp. 640-645 ◽  
Author(s):  
Ghadeer Thalji ◽  
Lyndon F. Cooper ◽  
Salvador Nares

The objective of this study was to evaluate the impact of smoking on the early molecular events involved in peri-implant healing at either a micro-roughened or a micro-roughened with superimposed nanofeatures surface implant in humans. Twenty-one subjects, 10 smokers and 11 nonsmokers received 4 mini-implants (2.2 × 5.0 mm; 2 of each surface). After 3 and 7 days, paired mini-implants were retrieved by reverse threading and RNA isolated from implant adherent cells. Whole genome microarrays were used interrogate the gene expression profiles. The study failed to identify differences in the gene expression profiles of implant adherent cells at this early stage of osseointegration (up to day 7) comparing smoker and nonsmoker individuals.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1281-1281
Author(s):  
Wolfgang Wagner ◽  
Rainer Saffrich ◽  
Ute Wirkner ◽  
Volker Eckstein ◽  
Jonathon Blake ◽  
...  

Abstract Cell-cell contact between stem cells and cellular determinants of the microenvironment plays an essential role in the regulation of self-renewal and differentiation. The stromal cell line derived from murine fetal liver (AFT024) has been shown to support maintenance of primitive human hematopoietic progenitor cells (HPC) in vitro. We have studied the interaction between HPC (defined as CD34+/CD38− umbilical cord blood cells) and AFT024 and the impact of co-cultivation on the behavior and gene expression of HPC. By time lapse microscopy the mobility and behavior of CD34+/CD38− cells were monitored. Approximately 30% of the CD34+/CD38− cells adhered to the cellular niche through an uropod. CD44 and CD34 were co-localized at the site of contact. Gene expression profiles of CD34+/CD38− cells were then compared upon co-cultivation either with or without AFT024. After cultivation for 16h, 20h, 48h or 72h the HPC were separated form the feeder layer cells by a second FAC-Sort. Differential gene expression was analyzed using our Human Genome cDNA Microarray of over 51,145 ESTs. Among the genes with the highest up-regulation in contact with AFT024 were several genes involved in cell adhesion, proliferation and DNA-modification including tubulin genes, ezrin, complement component 1 q subcomponent 1 (C1QR1), proto-oncogene proteins c-fos and v-fos, proliferating cell nuclear antigen (PCNA), HLA-DR, gamma-glutamyl hydrolase (GGH), minichromosome maintenance deficient 6 (MCM6), uracil-DNA glycolase (UNG) and DNA-methyltransferase 1 (DNMT1). In contrast, genes that were down-regulated after contact with AFT024 included collagenase type iv (MMP2), elastin (ELN) and hemoglobin genes. Differential expression of six genes was confirmed by RT-PCR. Other authors have reported on the differential gene expression profiles of CD34+ cells derived from the bone marrow versus those from G-CSF mobilized blood. As CD34+ cells from the bone marrow might represent cells exposed to the natural HPC niche we have then compared our findings with these experiments. In these comparisons we identified several overlapping genes that are involved in regulation of cell cycle and DNA repair including PCNA, DNMT1, MCM6, MCM2, CDC28 protein kinase regulatory subunit 1B (CKS1B), Topoisomerase II (TOP2a), DNA Ligase 1 (LIG1) and DNA mismatch repair protein MLH1. All these genes were up-regulated among CD34+/CD38− cells upon co-culture with AFT024, as well as among CD34+ cells derived from the bone marrow versus those from peripheral blood. Our studies support the hypothesis that intimate contact and adhesive interaction of HPC with their niche profoundly influenced their proliferative potential and their differentiation program.


2010 ◽  
Vol 28 (26) ◽  
pp. 4038-4044 ◽  
Author(s):  
Elizabeth J. Folkerd ◽  
Mitch Dowsett

To review the influence of sex hormones on the progression of breast, prostate, gynecologic, and colorectal cancer. The literature was reviewed in an informal manner utilizing the authors' prior knowledge to collate the current evidence for the involvement of sex hormones, particularly estrogens and androgens in the progression of a range of hormonally responsive cancers. In particular, the effect of treatment involving hormone withdrawal treatment was considered strong evidence for involvement. The impact of basal levels of endogenous steroids was considered. Data from clinical trials indicate the efficacy of therapeutic interventions that result in ablation or antagonism of host steroids for a range of cancers. Demonstration of the correlation of the completeness of withdrawal with clinical outcome together with direct evidence of progression from studies looking at the influence of tissue and circulating levels of sex hormones more recently in conjunction with gene expression profiles all provide compelling evidence for the involvement of steroids in the progression of disease. The involvement of steroids in the progression of cancer in hormone-sensitive tissues is well established and an important target for therapy.


2017 ◽  
Author(s):  
Rayna M. Harris ◽  
Hsin-Yi Kao ◽  
Juan Marcos Alarcón ◽  
Hans A. Hofmann ◽  
André A. Fenton

AbstractSingle-neuron gene expression studies may be especially important for understanding nervous system structure and function because of the neuron-specific functionality and plasticity that defines functional neural circuits. Cellular dissociation is a prerequisite technical manipulation for single-cell and single cell-population studies, but the extent to which the cellular dissociation process affects neural gene expression has not been determined. This information is necessary for interpreting the results of experimental manipulations that affect neural function such as learning and memory. The goal of this research was to determine the impact of chemical cell dissociation on brain transcriptomes. We compared gene expression of microdissected samples from the dentate gyrus (DG), CA3, and CA1 subfields of the mouse hippocampus either prepared by a standard tissue homogenization protocol or subjected to a chemical cellular dissociation procedure. We report that compared to homogenization, chemical cellular dissociation alters about 350 genes or 2% of the hippocampal transcriptome. While only a few genes canonically implicated in long-term potentiation (LTP) and fear memory change expression levels in response to the dissociation procedure, these data indicate that sample preparation can affect gene expression profiles, which might confound interpretation of results depending on the research question. This study is important for the investigation of any complex tissues as research effort moves from subfield level analysis to single cell analysis of gene expression.


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