Comorbid Conditions, Mental Health and Cognitive Functions in Adults with Fibromyalgia

This study examined age group differences across adulthood in comorbid conditions, mental health, and cognitive function in people with fibromyalgia. Participants completed an online survey about how fibromyalgia affects their everyday life. Chi square analyses were conducted to examine associations between age groups and (a) comorbid conditions and (b) severity of anxiety and depression. ANOVA analyses examined age group differences on aspects of self-report cognitive function. The greatest prevalence of comorbid conditions was found in middle adulthood. Early adulthood was associated with more cases of severe anxiety with the lowest number of cases being in the oldest age group. Middle adulthood was associated with worse self-report pain compared to the youngest age group. Older adults showed better self-report cognitive function compared to younger adults. Distinct age profiles based on comorbid conditions, mental health, and symptom severity across adulthood in fibromyalgia have been demonstrated

Patients' perspective of the effectiveness and acceptability of pharmacological and non-pharmacological treatments of fibromyalgia.

Background and aims Fibromyalgia is a complex condition characterised by widespread pain, sleep disturbance, fatigue and cognitive impairment, with a global mean prevalence estimated at 2.7%. There are inconsistencies in guidelines on the treatment of fibromyalgia leading to dissatisfaction from patients and healthcare professionals. This study investigated patient-reported outcomes of pharmacological and non-pharmacological treatment usage and effectiveness with an assessment of acceptability. Methods Nine hundred and forty-one participants completed a self-administered anonymous questionnaire giving quantitative data of demographics, treatment usage and treatment outcomes. Participant-reported effectiveness and side effects were compared in the following treatment classes: analgesics, antidepressants, gabapentinoids, gastrointestinal treatments, activity interventions, dietary-based treatments, and psychological, physical and alternative therapies. Participants also reported whether they knew about or had tried different treatments. Results The results from the online survey indicated that the range of mean effectiveness ratings were similar for pharmacological and non-pharmacological treatments, whereas non-pharmacological treatments had lower side effects ratings and higher acceptability relative to pharmacological treatments. Participants were not aware of some treatment options. Conclusions The results show lower side effects ratings and higher acceptability for non-pharmacological treatments compared to pharmacological treatments despite similar effectiveness ratings. Implications This article presents results from a large online survey on fibromyalgia patient perspectives of pharmacological and non-pharmacological treatments. Results will inform healthcare professionals and patients about optimal treatments based on ratings of effectiveness, side effects and acceptability that are tailored to patient symptom profiles. Some participants were unaware of treatment options highlighting the importance of patient education allowing collaboration between patients and healthcare professionals to find optimal treatments

Interactions of periodontal pathogens with megakaryocytic cells and platelets

Introduction: Cardiovascular disease (CVD) is a leading cause of morbidity, accounting for around 17.3 million deaths worldwide. Recent studies have linked periodontitis to CVD with the periodonto-pathogens Porphyromonas gingivalis and Tannerella forsythia thought to contribute and exacerbate atherosclerosis through interactions with platelets. To date, while platelet activation following challenge with periodonto-pathogens has been reported, the underlying mechanisms of these interactions are yet to be elucidated. The aim of this study is to determine how periodonto-pathogens interact with platelets using both megakaryocytic cells and isolated platelets. Methods: To characterise expression levels of surface markers including ubiquitously expressed platelet-specific markers (CD41, CD42b) and platelet activation markers (CD62P, PAC-1), a multi-colour flow cytometry panel was developed using undifferentiated megakaryocytic cells CHRF-288-11 before validation using platelets isolated from healthy donors. Changes in levels of surface markers following bacterial challenge both with megakaryocytic cells and isolated platelets were determined using flow cytometry. Interaction with pathogens was visualised by platelet aggregometry and fluorescence microscopy using pathogen-specific antibodies. Results and conclusions: Both pathogens invaded megakaryocytic cells as visualised by immunofluorescence microscopy. The pathogens also bound platelets causing increased levels of aggregation and upregulated expression of activation markers including in CD62P in flow cytometric assays

Headspace analysis of mesothelioma cell lines differentiates biphasic and epithelioid sub-types.

Malignant mesothelioma (MM) is an incurable cancer. MM is often misdiagnosed, with a poor 5-year survival and limited treatment options. The discovery of endogenous volatile organic compounds (VOCs) is required in order to accelerate the development of a breath test as an alternative to conventional MM diagnosis. For the first time, this study used solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) to identify VOCs released directly from the biphasic MM cell line MSTO-211H and the epithelioid MM cell line NCI-H28 as well as the non-malignant mesothelial cell line MET-5A. Multivariate statistical analysis showed separation between MSTO-211H, NCI-H28 and MET-5A results. 2-ethyl-1-hexanol was significantly increased in both MSTO-211H and NCI-H28 cells compared to MET-5A controls. In addition, ethyl propionate and cyclohexanol were significantly increased in MSTO-211H cells and dodecane was significantly increased in NCI-H28 cells. This is the first study reporting headspace analysis of these MM cell lines and the first to consider the effects of mesothelioma sub-type on VOC profile. Current results further highlight the potential for a diagnostic mesothelioma breath test as well as providing proof of concept for the differentiation between biphasic and epithelioid mesothelioma based on VOC profiles

Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines.

Background: Mortality rates for leukemia are high despite considerable improvements in treatment. Since polyphenols exert pro-apoptotic effects in solid tumors, our study investigated the effects of polyphenols in haematological malignancies. The effect of eight polyphenols (quercetin, chrysin, apigenin, emodin, aloe-emodin, rhein, cis-stilbene and trans-stilbene) were studied on cell proliferation, cell cycle and apoptosis in four lymphoid and four myeloid leukemic cells lines, together with normal haematopoietic control cells. Methods: Cellular proliferation was measured by CellTiter-Glo® luminescent assay; and cell cycle arrest was assessed using flow cytometry of propidium iodide stained cells. Apoptosis was investigated by caspase-3 activity assay using flow cytometry and apoptotic morphology was confirmed by Hoescht 33342 staining. Results: Emodin, quercetin, and cis-stilbene were the most effective polyphenols at decreasing cell viability (IC50 values of 5-22 µM, 8-33 µM, and 25-85 µM respectively) and inducing apoptosis (AP50 values (the concentration which 50% of cells undergo apoptosis) of 2-27 µM, 19-50 µM, and 8-50 µM respectively). Generally, lymphoid cell lines were more sensitive to polyphenol treatment compared to myeloid cell lines, however the most resistant myeloid (KG-1a and K562) cell lines were still found to respond to emodin and quercetin treatment at low micromolar levels. Non-tumor cells were less sensitive to all polyphenols compared to the leukemia cells. Conclusions: These findings suggest that polyphenols have anti-tumor activity against leukemia cells with differential effects. Importantly, the differential sensitivity of emodin, quercetin, and cis-stilbene between leukemia and normal cells suggests that polyphenols are potential therapeutic agents for leukemia

"Not all in my head": a qualitative exploration of living with fibromyalgia and its treatments (Oral presentation)

Background: Fibromyalgia is a complex condition which causes pain, sleep disturbance, fatigue and distress, limits the capacity to work and damages relationships. Aetiological and diagnostic uncertainty and the lack of effective treatments further complicate the lives of patients. To develop effective and acceptable interventions it is essential to understand the patient's expectations and perceptions of their experiences and existing treatment options. Methods: 14 people with fibromyalgia, recruited via online support networks, participated in in-depth interviews about their experiences of living with and being treated for fibromyalgia. Data collection and analysis were guided by an interpretative phenomenological approach Findings: Six themes were generated: Inauthenticity of Fibromyalgia; An Unconventional healthcare experience; Re-creating support networks; Challenging the working identity; Threatening the family dynamic and Fighting, accepting or accommodating? The theme Inauthenticity of Fibromyalgia was central and underpinned these participant accounts, leading to the repeated assertion that fibromyalgia wasn’t simply "in their head". Discussion: Analyses suggested that chronic illness threatens identity, and disrupts lifestyle, roles and relationships, challenges which are exacerbated when the illness is not adequately recognised. Leventhal's Self-Regulation Model highlights the importance of individual and social interpretations in coping with illness. These findings suggested that the perception of contested authenticity of fibromyalgia was a dominating feature of these participants' lives and treatment experiences. The results informed the design of a national survey to capture variations in symptoms, experiences and treatments from a larger, national sample. Outcomes will help guide the development, targeting and trial of an intervention based upon user perspectives

Elemental Mapping of Human Malignant Mesothelioma Tissue Samples Using High-Speed LA-ICP-TOFMS Imaging.

This is the first report of the use of laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) to analyze human malignant pleural mesothelioma (MPM) samples at the cellular level. MPM is an aggressive, incurable cancer associated with asbestos exposure, with a long latency and poor overall survival. Following careful optimization of the laser fluence, the simultaneous ablation of soft biological tissue and hard mineral fibers was possible, allowing the spatial detection of elements such as Si, Mg, Ca, and Fe, which are also present in the glass substrate. A low-dispersion LA setup was employed, which provided the high spatial resolution necessary to identify the asbestos fibers and fiber fragments in the tissue and to characterize the metallome at the cellular level (a pixel size of 2 μm), with a high speed (at 250 Hz). The multielement LA-ICP-TOFMS imaging approach enabled (i) the detection of asbestos fibers/mineral impurities within the MPM tissue samples of patients, (ii) the visualization of the tissue structure with the endogenous elemental pattern at high spatial resolution, and (iii) obtaining insights into the metallome of MPM patients with different pathologies in a single analysis run. Asbestos and other mineral fibers were detected in the lung and pleura tissue of MPM patients, respectively, based on their multielement pattern (Si, Mg, Ca, Fe, and Sr). Interestingly, strontium was detected in asbestos fibers, suggesting a link between this potential toxic element and MPM pathogenesis. Furthermore, monitoring the metallome around the talc deposit regions (characterized by elevated levels of Al, Mg, and Si) revealed significant tissue damage and inflammation caused by talc pleurodesis. LA-ICP-TOFMS results correlated to Perls' Prussian blue and histological staining of the corresponding serial sections. Ultimately, the ultra-high-speed and high-spatial-resolution capabilities of this novel LA-ICP-TOFMS setup may become an important clinical tool for simultaneous asbestos detection, metallome monitoring, and biomarker identification

Needles in haystacks: using fast-response LA chambers and ICP-TOF-MS to identify asbestos fibres in malignant mesothelioma models

Malignant mesothelioma is an aggressive cancer associated with exposure to asbestos. Diagnosis of mesothelioma and other related lung diseases remains elusive due to difficulties surrounding identification and quantification of asbestos fibres in lung tissue. This article presents a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method to identify asbestos fibres in cellular models of mesothelioma. Use of a high-speed laser ablation system enabled rapid imaging of the samples with a lateral resolution of 3 μm, whilst use of a prototype time-of-flight ICP-MS provided pseudo-simultaneous detection of the elements between mass 23 (Na) and mass 238 (U). Three forms of asbestos fibre (actinolite, amosite and crocidolite) were distinguished from a non-asbestos control (wollastonite) based on their elemental profile, which demonstrated that LA-ICP-MS could be a viable technique for identification of asbestos fibres in clinical research samples

Emerging applications in mass spectrometry imaging; enablers and roadblocks

© 2020 The Authors. Mass spectrometry imaging (MSI) is a powerful and versatile technique able to investigate the spatial distribution of multiple non-labelled endogenous and exogenous analytes simultaneously, within a wide range of samples. Over the last two decades, MSI has found widespread application for an extensive range of disciplines including pre-clinical drug discovery, clinical applications and human identification for forensic purposes. Technical advances in both instrumentation and software capabilities have led to a continual increase in the interest in MSI; however, there are still some limitations. In this review, we discuss the emerging applications in MSI that significantly impact three key areas of mass spectrometry (MS) research—clinical, pre-clinical and forensics—and roadblocks to the expansion of use of MSI in these areas

Laser ablation inductively coupled plasma mass spectrometry as a novel clinical imaging tool to detect asbestos fibres in malignant mesothelioma.

RATIONALE: Malignant pleural mesothelioma is an extremely aggressive and incurable malignancy associated with prior exposure to asbestos fibres. Difficulties remain in relation to early diagnosis, notably due to impeded identification of asbestos in lung tissue. This study describes a novel laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging approach to identify asbestos within mesothelioma models with clinical significance. METHODS: Human mesothelioma cells were exposed to different types of asbestos fibres and prepared on plastic slides for LA-ICP-MS analysis. No further sample preparation was required prior to analysis, which was performed using an NWR Image 266nm laser ablation system coupled to an Element XR sector-field ICP mass spectrometer, with a lateral resolution of 2 μm. Data was processed using LA-ICP-MS ImageTool v1.7 with the final graphic production made using DPlot Software. RESULTS: Four different mineral fibres were successfully identified within the mesothelioma samples based on some of the most abundant elements that make up these fibres (Si, Mg and Fe). Using LA-ICP-MS as an imaging tool provided information on the spatial distribution of the fibres at cellular level, which is essential in asbestos detection within tissue samples. Based on the metal counts generated by the different types of asbestos, different fibres can be identified based on shape, size, and elemental composition. Detection of Ca was attempted but requires further optimisation. CONCLUSION: Asbestos fibres detection in the lung tissues is very useful, if not necessary, to complete the pathological diagnosis of asbestos-related malignancies in medicolegal field. For the first time, this study demonstrates the successful application of LA-ICP-MS imaging to identify asbestos fibres and other mineral fibres within mesothelioma samples. Ultimately, high-resolution, fast-speed LA-ICP-MS analysis has the potential to be integrated into clinical workflow to aid earlier detection and stratification of mesothelioma patient samples