Upper back pain in postmenopausal women and associated physical characteristics

The physical characteristics of postmenopausal women that are associated with upper back pain are not well-understood. The aim of this cross-sectional study was to identify the physical characteristics associated with presence and severity of upper back pain in healthy postmenopausal women. Self-reported upper back pain presence (within the previous month) and severity (numerical rating scale) were examined against the physical characteristics: height; weight; body mass index; breast size; breast ptosis; upper back extensor muscle endurance (isometric chest raise test); head, shoulder and upper back posture (photogrammetry); thoracic extension mobility (photogrammetry); bone mineral density (dual-energy x-ray absorptiometry (DXA)); body composition (DXA); and thoracic kyphosis, thoracic osteoarthritis and thoracic vertebral fracture (all radiography). A multivariable logistic regression model, adjusted for age, was built using physical characteristics with a significant univariate association with upper back pain. Censored Tobit regression, adjusted for age, was used to examine each physical characteristic against upper back pain severity. Postmenopausal women (n = 119) with a mean (SD) age of 61.4 (7.0) years participated in the study. After adjusting for age, the physical characteristics independently associated with upper back pain were: height (OR: 0.50, 95% CI: 0.31–0.79); and upper back extensor muscle endurance (OR: 0.46, 95%CI: 0.28–0.75). This model explained 31% of the variance in upper back pain (p<0.001). After adjusting for age, being taller and having better upper back extensor muscle endurance were associated with lower odds for upper back pain. After adjusting for age, differences in upper back pain severity were explained by upper back extensor muscle endurance (p = <0.001) and lean mass (p = 0.01). Conclusion: As a modifiable physical characteristic of postmenopausal women with upper back pain, upper back extensor muscle endurance is worth considering clinically

PL - 039 Heat Shock Proteins in human single skeletal muscle fibres resist age associated alterations and differentially respond to high-intensity exercise training

Objective Heat shock proteins (HSPs) are ubiquitously expressed proteins that help preserve cellular homeostasis. Within mammalian skeletal muscle three of the better characterised HSPs are HSP72, HSP27 and αB-crystallin. Among other roles, these three HSPs are involved in regulation of muscle mass and function and may be of importance in ageing. HSP’s are fibre-type dependent in rat skeletal muscle and thus examining these proteins in humans should be completed on the single fibre level, particularly in ageing where maladaptations primarily occur in Type II fibres. High-Intensity Training (HIT) is a commonly used method to improve muscle health and function in the elderly, but HSP adaptability to training has not yet been investigated. &nbsp; Methods This study examined isolated single muscle fibre segments collected from freeze-dried vastus lateralis muscle samples from young (25 /- 3 year old) and older (70 /- 4 year old) healthy individuals. &nbsp;A further sample was collected from the older individuals following 12 weeks of HIT, where they performed 4 x 4 min @ ~90-95% of peak heart rate (HR), with 4 min active recovery at 50-60% peak HR Results Basal expression of HSP’s in skeletal muscle: HSP70 tended to be higher in Type I fibres compared to Type II in young adults (p=0.08) and was higher in Type I compared to Type II fibres of older adults (p=0.03). HSP27 abundance was higher in Type I fibres compared to Type II in young adults (p=0.01) and tended to be higher in Type I compared to Type II fibres in older adults (p=0.07). The abundance of αβ-crystallin was more abundant in Type I fibres compared to Type II in both young and older adults (p&lt;0.05). &nbsp;Preliminary data revealed that the abundance of pABCser59 and pHSP2782 displayed no fibre-type specific abundances in either young or older adults. Age effects on HSP’s: There was no difference in the abundance of HSP70, HSP27, ABC or pHSP2782 between young and older adults in either Type I or Type II fibres. There was an increase in the abundance of pABCser59 in Type I fibres in older adults compared to Type I fibres of young adults (p=0.03), with no difference in Type II fibres. Effects of HIT on HSP’s: &nbsp;HIT in the older individuals increased the abundance of HSP70 in Type I fibres (p&lt;0.01) but not Type II. HIT tended to decrease the abundance of HSP27 in Type I fibres (0.92±0.66, p=0.06) and tended to increase the abundance of αβ-crystallin in Type I fibres (1.03±1.51 p=0.07). Conclusions These results revealed that in healthy, older individuals, the basal levels of HSP27, ABC or pHSP2782 are not different to those in young adults in either Type I or Type II fibres. This could indicate that the muscle from the older individuals was not compromised. &nbsp;Interestingly, in response to HIT there were varying changes between these HSP’s, and of note these occurred only in Type I fibres. &nbsp;Given that during HIT Type II fibres would be activated to a greater extent, it appears that the recovery phases of the HIT were most responsive to HSPs

Evidence That a TRPA1-Mediated Murine Model of Temporomandibular Joint Pain Involves NLRP3 Inflammasome Activation

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-14, pub-electronic 2021-10-23Publication status: PublishedFunder: Versus Arthritis; Grant(s): 21541This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) in murine temporomandibular joint (TMJ) inflammatory hyperalgesia and the influence of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. Two distinct murine models of TMJ pain and inflammation (zymosan and CFA) were established. Spontaneous pain-like behaviours were observed as unilateral front paw cheek wipes. Ipsilateral cheek blood flow was used as a measure of ongoing inflammation, which, to our knowledge, is a novel approach to assessing real-time inflammation in the TMJ. Joint tissue and trigeminal ganglia were collected for ex vivo investigation. Both zymosan and CFA induced a time-dependent increase in hyperalgesia and inflammation biomarkers. Zymosan induced a significant effect after 4 h, correlating with a significantly increased IL-1β protein expression. CFA (50 µg) induced a more sustained response. The TRPA1 receptor antagonist A967079 significantly inhibited hyper-nociception. The NLRP3 inhibitor MCC950 similarly inhibited hyper-nociception, also attenuating inflammatory markers. In the trigeminal ganglia, CFA-induced CGRP expression showed trends of inhibition by A967079, whilst lba1 immunofluorescence was significantly inhibited by A967079 and MCC950, where the effect of TRPA1 inhibition lasted up to 14 days. Our results show that stimulation of TRPA1 is key to the TMJ pain. However, the inflammasome inhibitor exhibited similar properties in attenuating these pain-like behaviours, in addition to some inflammatory markers. This indicates that in addition to the therapeutic targeting of TRPA1, NLRP3 inhibition may provide a novel therapeutic strategy for TMJ inflammation and pain

Shipping blood to a central laboratory in multicenter clinical trials: effect of ambient temperature on specimen temperature, and effects of temperature on mononuclear cell yield, viability and immunologic function

<p>Abstract</p> <p>Background</p> <p>Clinical trials of immunologic therapies provide opportunities to study the cellular and molecular effects of those therapies and may permit identification of biomarkers of response. When the trials are performed at multiple centers, transport and storage of clinical specimens become important variables that may affect lymphocyte viability and function in blood and tissue specimens. The effect of temperature during storage and shipment of peripheral blood on subsequent processing, recovery, and function of lymphocytes is understudied and represents the focus of this study.</p> <p>Methods</p> <p>Peripheral blood samples (n = 285) from patients enrolled in 2 clinical trials of a melanoma vaccine were shipped from clinical centers 250 or 1100 miles to a central laboratory at the sponsoring institution. The yield of peripheral blood mononuclear cells (PBMC) collected before and after cryostorage was correlated with temperatures encountered during shipment. Also, to simulate shipping of whole blood, heparinized blood from healthy donors was collected and stored at 15°C, 22°C, 30°C, or 40°C, for varied intervals before isolation of PBMC. Specimen integrity was assessed by measures of yield, recovery, viability, and function of isolated lymphocytes. Several packaging systems were also evaluated during simulated shipping for the ability to maintain the internal temperature in adverse temperatures over time.</p> <p>Results</p> <p>Blood specimen containers experienced temperatures during shipment ranging from -1 to 35°C. Exposure to temperatures above room temperature (22°C) resulted in greater yields of PBMC. Reduced cell recovery following cryo-preservation as well as decreased viability and immune function were observed in specimens exposed to 15°C or 40°C for greater than 8 hours when compared to storage at 22°C. There was a trend toward improved preservation of blood specimen integrity stored at 30°C prior to processing for all time points tested. Internal temperatures of blood shipping containers were maintained longer in an acceptable range when warm packs were included.</p> <p>Conclusions</p> <p>Blood packages shipped overnight by commercial carrier may encounter extreme seasonal temperatures. Therefore, considerations in the design of shipping containers should include protecting against extreme ambient temperature deviations and maintaining specimen temperature above 22°C or preferably near 30°C.</p

Physiotherapy students' perspectives of online e-learning for interdisciplinary management of chronic health conditions: A qualitative study

© 2016 Gardner et al. Background: To qualitatively explore physiotherapy students' perceptions of online e-learning for chronic disease management using a previously developed, innovative and interactive, evidence-based, e-learning package: Rheumatoid Arthritis for Physiotherapists e-Learning (RAP-eL). Methods: Physiotherapy students participated in three focus groups in Perth, Western Australia. Purposive sampling was employed to ensure maximum heterogeneity across age, gender and educational background. To explore students' perspectives on the advantages and disadvantages of online e-learning, ways to enhance e-learning, and information/learning gaps in relation to interdisciplinary management of chronic health conditions, a semi-structured interview schedule was developed. Verbatim transcripts were analysed using inductive methods within a grounded theory approach to derive key themes. Results: Twenty-three students (78 % female; 39 % with previous tertiary qualification) of mean (SD) age 23 (3.6) years participated. Students expressed a preference for a combination of both online e-learning and lecture-style learning formats for chronic disease management, citing flexibility to work at one's own pace and time, and access to comprehensive information as advantages of e-learning learning. Personal interaction and ability to clarify information immediately were considered advantages of lecture-style formats. Perceived knowledge gaps included practical application of interdisciplinary approaches to chronic disease management and developing and implementing physiotherapy management plans for people with chronic health conditions. Conclusions: Physiotherapy students preferred multi-modal and blended formats for learning about chronic disease management. This study highlights the need for further development of practically-oriented knowledge and skills related to interdisciplinary care for people with chronic conditions among physiotherapy students. While RAP-eL focuses on rheumatoid arthritis, the principles of learning apply to the broader context of chronic disease management

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival