Factors associated with clinical responses to spinal manipulation in patients with non-specific thoracic back pain: A prospective cohort study

Introduction: The management of musculoskeletal disorders is complex and requires a multidisciplinary approach. Manual therapies, such as spinal manipulative therapy (SMT), are often recommended as an adjunct treatment and appear to have demonstrable effects on pain and short-term disability in several spinal conditions. However, no definitive mechanism that can explain these effects has been identified. Identifying relevant prognostic factors is therefore recommended for people with back pain. Objective: The main purpose of this study was to identify short-term candidate prognostic factors for clinically significant responses in pain, disability and global perceived change (GPC) following a spinal manipulation treatment in patients with non-specific thoracic back pain. Methods: Patients seeking care for thoracic spine pain were invited to participate in the study. Pain levels were recorded at baseline, post-intervention, and 1 week after a single session of SMT. Disability levels were collected at baseline and at 1-week follow-up. GPC was collected post-intervention and at 1-week follow-up. Biomechanical parameters of SMT, expectations for improvement in pain and disability, kinesiophobia, anxiety levels as well as perceived comfort of spinal manipulative therapy were assessed. Analysis: Differences in baseline characteristics were compared between patients categorized as responders or non-responders based on their pain level, disability level, and GPC at each measurement time point. Binary logistic regression was calculated if the statistical significance level of group comparisons (responder vs. non-responders) was equal to, or <0.2 for candidate prognostic factors.Results: 107 patients (62 females and 45 males) were recruited. Mean peak force averaged 450.8 N with a mean thrust duration of 134.9 ms. Post-intervention, comfort was associated with pain responder status (p < 0.05) and GPC responder status (p < 0.05), while expectation of disability improvement was associated with GPC responder status (p < 0.05). At follow-up, comfort and expectation of pain improvement were associated with responder GPC status (p < 0.05). No association was found between responder pain, disability or GPC status and biomechanical parameters of SMT at any time point. Discussion: No specific dosage of SMT was associated with short-term clinical responses to treatment. However, expectations of improvement and patient comfort during SMT were associated with a positive response to treatment

Factors associated with back pain in children aged 6 to 12 years of age, an eight months prospective study

Associated factors of back pain (BP) development before puberty and its persistence are poorly documented. We investigated the association and possible temporality between prior BP history (PBPH), muscular endurance (ME), aerobic capacity (AC), sport activity variables (SAV) and BP in children aged 6 to 12. We collected baseline characteristics (demographics, PBPH, ME, AC and SAV) of children from three primary schools in Canada. Parents replied to weekly text messages regarding their children BP status over an 8-month period. Logistic regression models were adjusted for potential confounders. Data from 242 children (46% female; 8.6 ± 1.7 years) were included. Over the 8-month survey BP prevalence was 48.1%, while the cumulative incidence was 31.9%. The occurrence of at least one BP event was associated with PBPH [OR (IC 95%) = 6.33 (2.35–17.04)] and high AC [2.89 (1.21–6.90)]. High AC was also associated with the development of a first BP episode [2.78 (1.09–7.07)], but ME and SAV were not. BP appears to be relatively common before puberty. BP history seems to be strongly associated with BP recurrence in children. Aerobic capacity is associated with first BP episode development

Headache-related clinical features in teleworkers and their association with coping strategies during the COVID-19 pandemic

Abtract Objectives The objectives were (1) to describe and compare headache-related clinical features between teleworkers with migraine and those with tension-type headache (TTH) and (2) to determine the association between coping strategies and headache frequency, and intensity in the context of the COVID-19 pandemic. Methods This cross-sectional online survey was conducted with 284 teleworkers (127 with migraine and 157 with TTH). Sociodemographic data, information related to work factors, headache clinical features, coping strategies used during the COVID-19 pandemic, and headache-related clinical features were compared between headache profiles. Bivariate logistic regression analyses were used to determine the association between coping strategies and headache frequency, and intensity. Results Results showed that teleworkers with migraine had longer and more painful headache episodes than teleworkers with TTH (ps < 0.001). Higher migraine frequency was associated with the use of the denial coping strategy (p = 0.006) while lower migraine intensity was associated with planning (p = 0.046) and the use of positive reframing (p = 0.025). Higher TTH frequency was associated with the use of venting, self-blame, and behavioral disengagement (ps < 0.007) while higher TTH intensity was associated with substance use and behavioral disengagement (ps < 0.030). All associations remained significant after adjusting for BMI as a covariate. Discussion/conclusion Teleworkers with migraine had more intense and longer headache episodes than teleworkers with TTH. This could be explained by the fact that a greater proportion of individuals suffering from migraine experienced headaches prior to the beginning of the pandemic compared with teleworkers suffering from TTH. Regarding coping strategies, both primary headache profiles were associated with different types of coping strategies. Most of the coping strategies associated with headache frequency or intensity were maladaptive except for planning and positive reframing that were found to be inversely associated with migraine intensity

Factors associated with headache and neck pain among telecommuters – a five days follow-up

The current sanitary crisis brought on by the COVID-19 recently forced a large proportion of workers to adopt telecommuting with limited time to plan transition. Given that several work-related risk factors are associated with headache and neck pain, it seems important to determine those associated with headache and neck pain in telecommuters

Verticalization of bacterial biofilms

Biofilms are communities of bacteria adhered to surfaces. Recently, biofilms of rod-shaped bacteria were observed at single-cell resolution and shown to develop from a disordered, two-dimensional layer of founder cells into a three-dimensional structure with a vertically-aligned core. Here, we elucidate the physical mechanism underpinning this transition using a combination of agent-based and continuum modeling. We find that verticalization proceeds through a series of localized mechanical instabilities on the cellular scale. For short cells, these instabilities are primarily triggered by cell division, whereas long cells are more likely to be peeled off the surface by nearby vertical cells, creating an "inverse domino effect". The interplay between cell growth and cell verticalization gives rise to an exotic mechanical state in which the effective surface pressure becomes constant throughout the growing core of the biofilm surface layer. This dynamical isobaricity determines the expansion speed of a biofilm cluster and thereby governs how cells access the third dimension. In particular, theory predicts that a longer average cell length yields more rapidly expanding, flatter biofilms. We experimentally show that such changes in biofilm development occur by exploiting chemicals that modulate cell length.Comment: Main text 10 pages, 4 figures; Supplementary Information 35 pages, 15 figure

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Phase II Multicenter Clinical Trial of Pulmonary Metastasectomy and Isolated Lung Perfusion with Melphalan in Patients with Resectable Lung Metastases

IntroductionThe 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20–50%). Local recurrence rate is high (48–66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control.MethodsFrom 2006 to 2011, 50 patients, 28 male, median age 57 years (15–76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37°C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan–Meier method.ResultsOperative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3–63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% ± 9% and 36% ± 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values.ConclusionCompared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma

Immunogenicity and safety of a quadrivalent high-dose inactivated influenza vaccine compared with a standard-dose quadrivalent influenza vaccine in healthy people aged 60 years or older: a randomized Phase III trial

A quadrivalent high-dose inactivated influenza vaccine (IIV4-HD) is licensed for adults 6565&nbsp;y of age based on immunogenicity and efficacy studies. However, IIV4-HD has not been evaluated in adults aged 60\u201364&nbsp;y. This study compared immunogenicity and safety of IIV4-HD with a standard-dose quadrivalent influenza vaccine (IIV4-SD) in adults aged 6560&nbsp;y. This Phase III, randomized, modified double-blind, active-controlled study enrolled 1,528 participants aged 6560&nbsp;y, randomized 1:1 to a single injection of IIV4-HD or IIV4-SD. Hemagglutination inhibition (HAI) geometric mean titers (GMTs) were measured at baseline and D 28 and seroconversion assessed. Safety was described for 180&nbsp;d after vaccination. The primary immunogenicity objective was superiority of IIV4-HD versus IIV4-SD, for all four influenza strains 28&nbsp;d post vaccination in participants aged 60\u201364 and 6565&nbsp;y. IIV4-HD induced a superior immune response versus IIV4-SD in terms of GMTs in participants aged 60\u201364 y and those aged 6565&nbsp;y for all four influenza strains. IIV4-HD induced higher GMTs in those aged 60\u201364 y than those aged 6565 y. Seroconversion rates were higher for IIV4-HD versus IIV4-SD in each age-group for all influenza strains. Both vaccines were well tolerated in participants 6560&nbsp;y of age, with no safety concerns identified. More solicited reactions were reported with IIV4-HD than with IIV4-SD. IIV4-HD provided superior immunogenicity versus IIV4-SD and was well tolerated in adults aged 6560 y. IIV4-HD is assumed to offer improved protection against influenza compared with IIV4-SD in adults aged 6560 y, as was previously assessed for adults aged 6565&nbsp;y