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Intermittent hemodialysis (IH) is an important therapy in the context of kidney dysfunction in dogs. However, its impact on pro-inflammatory cytokines is unclear. This study assessed IL-1β, IL-6, and TNF-α serum concentrations in dogs with chronic kidney disease (CKD) undergoing one session of IH without bypass (IH group, n = 4) and with bypass (IH + bypass group, n = 4). The control group (CG) included four healthy dogs. Cytokine levels were measured before, during, and after the first IH session. Comparative analyses of each cytokine within each group and time point were performed, along with a global comparison between groups. No significant changes were observed in cytokines across evaluation times in the IH groups. IL-1β was significantly higher post-session in the IH and IH + bypass groups compared to CG. Globally, IL-1β and TNF-α concentrations were significantly higher in the IH (11.41 pg/mL (10–16.17) and 2 pg/mL (2–88.54), respectively) and IH + bypass groups (10 pg/mL (10–10) and 2 pg/mL (2–215.5), respectively) compared to CG (0.96 pg/mL (0–3.56) and 0 pg/mL (0–0.003), respectively). The IH group also showed elevated IL-6 concentration (0.1 ng/mL (0.1–0.5)) compared to CG (0 ng/mL (0–0.1)). Higher IL-1β and IL-6 concentrations were observed in the IH group (11.41 pg/mL (10–16.17) and 0.1 ng/mL (0.1–0.1), respectively) compared to the IH + bypass group (10 pg/mL (10–10) and 0.1 ng/mL (0.1–0.5), respectively). In conclusion, a single IH session, with or without bypass, did not increase pro-inflammatory cytokines in CKD dogs with uremic syndrome but maintained the inflammatory state. Dogs undergoing IH without bypass may receive a stronger stimulus for cytokine release.

Abstract Background Chiropractors and chiropractic students commonly report low back pain (LBP). However, the burden of LBP in this occupational group has not been synthesized in the literature. This systematic review aims to describe the epidemiology of LBP in chiropractors and chiropractic students. Methods We searched MEDLINE, Embase, CINAHL, and PsycINFO from inception to May 1, 2023. Eligible studies were cross-sectional, cohort, or case–control studies investigating the prevalence, incidence, associated factors, or risk factors of LBP in chiropractors or chiropractic students. Reviewers independently screened articles and assessed risk of bias using the appropriate JBI Checklists for the observational study design. We descriptively synthesized studies that were rated as low or moderate risk of bias. Results Of 2012 citations screened, we included 2 cross-sectional studies in the evidence synthesis (1 study rated as moderate risk of bias on chiropractors, and 1 rated as low risk of bias on chiropractic students). For chiropractors, the 12-month prevalence of work-related overuse injuries to the low back was 35.6% (95% CI 29.1, 42.0) in women and 22.4% (95% CI 16.3, 29.6) in men. The 12-month prevalence of work-related acute physical injuries to the low back in chiropractors were 3.4% (95% CI 1.6, 6.8) for women and 0.7% (95% CI 0.1, 3.7) for men. Among chiropractic students, the 1-week prevalence of LBP was 69% (95% CI 64.8, 73.0). This was higher among female students (72.5%, 95% CI 67.1, 77.4) and lower among male students (64%, 95% CI 57.0, 70.6). Conclusion There is limited high-quality evidence on the epidemiology of LBP in chiropractors and chiropractic students. Our systematic review provides a synthesis of the body of literature, highlighting that chiropractors and chiropractic students commonly report LBP. Future high-quality research is needed to address the incidence, associated factors, and risk factors of LBP.

Abstract Background Research enables a profession to establish its cultural authority, validate its professional roles and ensure ongoing improvement in the quality of its academic programming. Despite the clear importance of research, a mature research culture has eluded the chiropractic profession. A fostering institutional culture that enables, values, and supports research activity is essential to building research capacity. Our study aimed to collect information about the existing research capacity and culture at the Canadian Memorial Chiropractic College (CMCC) and explore the views, attitudes and experiences of faculty members regarding research. Methods We conducted a sequential explanatory mixed methods study with quantitative priority between April and July, 2023. Quantitative data were collected using the Research Capacity and Culture (RCC) tool. Survey results guided the qualitative data collected from four faculty focus groups with varying levels of research experience. Quantitative data were analyzed using descriptive statistics by domain and stratified by research education and workload. The qualitative data were thematically analyzed and then integrated with the quantitative results to provide deeper meaning to the results. Results The faculty survey response rate was 42% (59/144). Attributes at the organization or department level were consistently rated as either moderate or high; however, research skills at an individual level were more variable and influenced by factors such as research workload and highest research-related academic qualification. Qualitative focus group data were categorized under four themes: institutional factors, resource allocation, career pathways and personal factors. Lower scores for survey items related to mentorship, research planning and ensuring faculty research career pathways, as well as the identified workload and time-related barriers (e.g., other work roles and desire for work/life balance) for engaging in research were supported by each of the four themes. Research motivators included keeping the brain stimulated, developing skills and increasing job satisfaction. Conclusion The quantitative and qualitative information in this study provides a baseline evaluation for RCC and identifies key factors impacting RCC at the CMCC. This information is critical for planning, developing, implementing, and evaluating future interventions to enhance research capacity. Ultimately, these efforts are aimed at maturing the research culture of the chiropractic profession.

Abstract Neutrophils (PMNs) are key players of innate immune responses through the release of cytoplasmic granule content and the formation of neutrophil extracellular traps (NETs). RNASET2 is an acidic ribonuclease, recently proposed as an alarmin signal associated with inflammatory responses. Here we show that, along the neutrophil maturation cascade, RNASET2 is expressed in segmented and mature PMNs. In human PMNs, RNASET2 colocalized with primary and tertiary granules and was found to be associated with NETs following PMA or Nigericin stimulation. Similarly, activation of PMNs by soluble immune complexes, a hallmark of several autoimmune diseases, also induced RNASET2-associated NETs. Genome-wide association studies recently identified RNASET2 among a cluster of genes associated with increased susceptibility to develop autoimmune diseases, including rheumatoid arthritis (RA). RNASET2 was found expressed by PMNs and macrophages infiltrating inflamed joints in a murine model of RA (K/BxN Serum-Transfer-Induced Arthritis, STIA), by immunostaining. Similar results were found in synovial biopsies of RA patients with active disease. In addition, we demonstrate that RNASET2 circulating levels correlated with the onset and the severity of disease in two mouse models of inflammatory arthritis, STIA and CIA (Collagen-Induced Arthritis) and in serum of RA patients. These results show that PMNs are an important source of RNASET2 and that its circulating levels are associated with RA development suggesting a role for RNASET2 in the pathogenesis of immune-mediated diseases.

Abstract Background The physiological relevance of cell-to-cell communication mediated by small extracellular vesicle-encapsulated microRNAs (sEV-miRNAs) remains debated because of the limiting representativity of specific miRNAs within the extracellular pool. We hypothesize that sEV-miRNA non-canonical function consisting of the stimulation of Toll-like receptor 7 (TLR7) may rely on a global shift of the sEV cargo rather than on the induction of one or few specific miRNAs. Psoriasis represents an ideal model to test such hypothesis as it is driven by overt activation of TLR7-expressing plasmacytoid dendritic cells (pDCs) following keratinocyte damage. Methods To mimic the onset of psoriasis, keratinocytes were treated with a cocktail of psoriatic cytokines or UV-irradiated. SmallRNA sequencing was performed on sEVs released by healthy and UV-treated keratinocytes. sEV-miRNAs were analyzed for nucleotide composition as well as for the presence of putative TLR7-binding triplets. Primary human pDCs where stimulated with sEVs +/- inhibitors of TLR7 (Enpatoran), of sEV release (GW4869 + manumycin) and of TLR7-mediated pDC activation (anti-BDCA-2 antibody). Secretion of type I IFNs and activation of CD8+T cells were used as readouts. qPCR on psoriatic and healthy skin biopsies was conducted to identify induced miRNAs. Results sEV-miRNAs released by damaged keratinocytes revealed a significantly higher content of TLR7-activating sequences than healthy cells. As expected, differential expression analysis confirmed the presence of miRNAs upregulated in psoriatic skin, including miR203a. More importantly, 76.5% of induced miRNAs possessed TLR7-binding features and among these we could detect several previously demonstrated TLR7 ligands. In accordance with this in silico analysis, sEVs from damaged keratinocytes recapitulated key events of psoriatic pathogenesis by triggering pDCs to release type I interferon and activate cytotoxic CD8+T cells in a TLR7- and sEV-dependent manner. Discussion Our results demonstrate that miR203a is just one paradigmatic TLR7-activating miRNA among the hundreds released by UV-irradiated keratinocytes, which altogether trigger pDC activation in psoriatic conditions. This represents the first evidence that cell damage shifts the miRNA content of sEVs towards a TLR7-activating cargo capable to propagate inflammation and immunity, offering strong support to the physiological role of systemic miRNA-based cell-to-cell communication.

Background: Despite the high frequency of tinnitus and its impact on wellbeing, little is known about its economic burden, and, to our knowledge, no data are available on out-of-pocket (OOP) expenses. Methods: In 2022, a survey was conducted on OOP costs of tinnitus. We enrolled 679 participants with slight, moderate, and severe tinnitus in Italy, United Kingdom, Netherlands, Germany, and Spain. We estimated annual OOP expenses for tinnitus-related healthcare visits, treatments, medications, and alternative medicine practices. Prevalence of tinnitus in the general population, obtained from a representative survey we conducted in Europe in 2017–2018, was used to generalize costs for people with any tinnitus at the national level. Results: OOP expenses were 368€ (95% confidence intervals [CI], 78€–690€), 728€ (95% CI, 316€–1,288€), and 1,492€ (95% CI, 760€–2,688€) for slight, moderate, and severe tinnitus, respectively, with annual expenditure of 565€ for people with any tinnitus: 209€ for healthcare visits; 93€ for treatments; 16€ for drugs; 64€ for hearing supporting systems; and 183€ for acupuncture, homeopathy, and osteopathy. Individuals with slight, moderate, and severe tinnitus expressed a willingness to invest 1.6, 4.3, and 7.0 times their monthly income, respectively, to achieve complete relief from tinnitus. Conclusion: This study offers for the first time insights into the OOP expenses incurred by individuals with tinnitus. OOP expenses exhibited substantial variations based on severity status, accounting for more than 17 billion € in the countries considered. In terms of financial burden, these findings align tinnitus to the recognized leading disabilities, including back pain and migraine.

Abstract Background Despite increases in musculoskeletal disorders (MSD) in Canada, evidence suggests utilization of chiropractic services has remained relatively stable over time. Understanding the extent to which chiropractors are consulted and factors associated with their utilization may suggest factors related to accessing care. We assessed the change in prevalence and characteristics of Canadians seeking chiropractic care across two time periods 2001–2010 and 2015–2018. Methods We used national cross-sectional data from seven cycles of the Canadian Community Health Survey between 2001 and 2018. The survey included Canadians aged 12 years and older living in private dwellings in all provinces and territories. National annual weighted prevalence and age-standardized weighted prevalence (and 95% confidence intervals) of chiropractic utilization were calculated. We calculated prevalence of chiropractic utilization stratified by demographic, socioeconomic, lifestyle and health-related variables. Crude linear trends and change in prevalence from 2001 to 2010 were assessed using linear regression models. Results The national annual prevalence of Canadians consulting a chiropractor in the previous 12 months slightly increased from 11.0% (95% CI 10.8, 11.3) in 2001 to 11.4% (95%CI 11.1, 11.7) in 2010, and in those reporting receiving regular health care from a chiropractor from 7.5% (95%CI 7.2, 7.7) in 2015 to 7.9% (95%CI 7.7, 8.2) in 2018. Prevalence of utilization varied by province, highest in the Western provinces but lowest in Atlantic provinces. The age-specific prevalence of chiropractic utilization was highest in those aged 35–49 years and remained stable over time, except for slight increase in those aged 65–79 years. A higher percentage of Canadians identifying as white, Canadian-born, in the highest quintile of household income, overweight, physically active and in excellent health reported seeking chiropractic services. The most common reported chronic conditions measured in the survey among Canadians consulting chiropractors were chronic back problems, arthritis, fibromyalgia and headaches. Conclusion The national prevalence of utilization of chiropractic services among Canadians slightly increased over time but varied by province and respondents’ socioeconomic and health characteristics. Chronic back problems were the most common reported chronic condition. This comprehensive population-based study on chiropractic utilization in Canada can be used to inform decisions concerning health human resources and access to rehabilitation care for MSD.

Aim: Diabetic polyneuropathy is the most described complication in patients with diabetes mellitus. A significant percentage of these patients experience disabling neuropathic pain (painful diabetic polyneuropathy). Small nerve fibers are primarily responsible for peripheral nociception, but objectively assessing its function is challenging. The primary objective of this study was to explore the task execution and outcomes of intra-epidermal electrical stimulation technique that combines nociceptive detection thresholds (NDT) and evoked potentials (EPs) in patients with diabetes. We compared the results of diabetic patients, both with and without painful diabetic polyneuropathy, with those of healthy controls to explore potential clinically relevant information. Methods: The NDT-EP method was applied to 38 patients with diabetes (18 with and 20 without chronic painful neuropathy) and 38 age- and sex-matched healthy controls. Individual mean NDTs, psychometric slopes, EP amplitudes, and the effect of the stimuli on EP amplitudes were analyzed and compared between groups using linear regression. Results: The findings revealed significantly lower detection rates, higher NDTs, and lower psychometric slopes in patients with painful diabetic polyneuropathy than in healthy controls. Both patient groups significantly exhibited lower mean EP amplitudes than healthy controls, which were not linked to pulse amplitudes but influenced by stimulus detection. Conclusions: This study showed altered NDT-EP outcomes in patients with painful diabetic polyneuropathy. Whereas the task execution, NDTs, and psychometric slopes may provide valuable insights into small fiber dysfunction, pulse amplitudes seemed not differently encoded in neurophysiological responses to intra-epidermal electrical stimulation near the detection threshold compared to controls. Future studies should investigate whether the altered NDT-EP outcomes could quantify small fiber dysfunction in patients with diabetes mellitus. We recommend further exploration of NDT-EP measures in other patient groups with nociceptive dysfunction.