Caspase-11 Mediates Neutrophil Chemotaxis and Extracellular Trap Formation During Acute Gouty Arthritis Through Alteration of Cofilin Phosphorylation

Gout is characterized by attacks of arthritis with hyperuricemia and monosodium urate (MSU) crystal-induced inflammation within joints. Innate immune responses are the primary drivers for tissue destruction and inflammation in gout. MSU crystals engage the Nlrp3 inflammasome, leading to the activation of caspase-1 and production of IL-1β and IL-18 within gout-affected joints, promoting the influx of neutrophils and monocytes. Here, we show that caspase-11−/− mice and their derived macrophages produce significantly reduced levels of gout-specific cytokines including IL-1β, TNFα, IL-6, and KC, while others like IFNγ and IL-12p70 are not altered. IL-1β induces the expression of caspase-11 in an IL-1 receptor-dependent manner in macrophages contributing to the priming of macrophages during sterile inflammation. The absence of caspase-11 reduced the ability of macrophages and neutrophils to migrate in response to exogenously injected KC in vivo. Notably, in vitro, caspase-11−/− neutrophils displayed random migration in response to a KC gradient when compared to their WT counterparts. This phenotype was associated with altered cofilin phosphorylation. Unlike their wild-type counterparts, caspase-11−/− neutrophils also failed to produce neutrophil extracellular traps (NETs) when treated with MSU. Together, this is the first report demonstrating that caspase-11 promotes neutrophil directional trafficking and function in an acute model of gout. Caspase-11 also governs the production of inflammasome-dependent and -independent cytokines from macrophages. Our results offer new, previously unrecognized functions for caspase-11 in macrophages and neutrophils that may apply to other neutrophil-mediated disease conditions besides gout

Does usage of monetary incentive impact the involvement in surveys? A systematic review and meta-analysis of 46 randomized controlled trials

Background: Surveys are an effective method for collecting a large quantity of data. However, incomplete responses to these surveys can affect the validity of the studies and introduce bias. Recent studies have suggested that monetary incentives may increase survey response rates. We intended to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of monetary incentives on survey participation. Methods: A systematic search of electronic databases was conducted to collect studies assessing the impact of monetary incentives on survey participation. The primary outcome of interest was the response rates to incentives: money, lottery, and voucher. We used the Cochrane Collaboration tool to assess the risk of bias in randomized trials. We calculated the rate ratio (RR) with its 95% confidence interval (95% CI) using Review Manager Software (version 5.3). We used random-effects analysis and considered the data statistically significant with a P-value \u3c 0.05. Results: Forty-six RCTs were included. A total of 109,648 participants from 14 countries were involved. The mean age of participants ranged from 15 to more than 60 years, with 27.5% being males, 16.7% being females, and the other 55.8% not reported. Our analysis showed a significant increase in response rate in the incentive group compared to the control group, irrespective of the incentive methods. Money was the most efficient way to increase the response rate (RR: 1.25; 95% CI: 1.16,1.35; P = \u3c 0.00001) compared to voucher (RR: 1.19; 95% CI: 1.08,1.31; P = \u3c 0.0005) and lottery (RR: 1.12; 95% CI: 1.03,1.22; P = \u3c 0.009). Conclusion: Monetary incentives encourage the response rate in surveys. Money was more effective than vouchers or lotteries. Therefore, researchers may include money as an incentive to improve the response rate while conducting surveys

Does usage of monetary incentive impact the involvement in surveys? A systematic review and meta-analysis of 46 randomized controlled trials.

BackgroundSurveys are an effective method for collecting a large quantity of data. However, incomplete responses to these surveys can affect the validity of the studies and introduce bias. Recent studies have suggested that monetary incentives may increase survey response rates. We intended to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of monetary incentives on survey participation.MethodsA systematic search of electronic databases was conducted to collect studies assessing the impact of monetary incentives on survey participation. The primary outcome of interest was the response rates to incentives: money, lottery, and voucher. We used the Cochrane Collaboration tool to assess the risk of bias in randomized trials. We calculated the rate ratio (RR) with its 95% confidence interval (95% CI) using Review Manager Software (version 5.3). We used random-effects analysis and considered the data statistically significant with a P-value ResultsForty-six RCTs were included. A total of 109,648 participants from 14 countries were involved. The mean age of participants ranged from 15 to more than 60 years, with 27.5% being males, 16.7% being females, and the other 55.8% not reported. Our analysis showed a significant increase in response rate in the incentive group compared to the control group, irrespective of the incentive methods. Money was the most efficient way to increase the response rate (RR: 1.25; 95% CI: 1.16,1.35; P = ConclusionMonetary incentives encourage the response rate in surveys. Money was more effective than vouchers or lotteries. Therefore, researchers may include money as an incentive to improve the response rate while conducting surveys

Histologic findings associated with laser interstitial thermotherapy for glioblastoma multiforme

Abstract Background Laser-interstitial thermal therapy (LITT) has been supported by some authors as an ablative treatment of glioblastoma multiforme (GBM). Although the effects of LITT have been modeled in vivo, the histologic effects in a clinical circumstance have not been described. We analyzed tissue from a patient who underwent LITT as primary treatment for GBM. Case presentation A 62-year-old male was diagnosed with a left temporal GBM and underwent LITT at an outside institution. Despite corticosteroid therapy, the patient was referred with increasing headache and acalculia associated with progressive peritumoral edema two weeks after LITT procedure. En bloc resection of the enhancing lesion and adjacent temporal lobe was performed with steroid-independent symptom resolution (follow-up, > 2 years). Histologic analysis revealed three distinct histologic zones concentrically radiating from the center of the treatment site. An acellular central region of necrosis (Zone 1) was surrounded by a rim of granulation tissue with macrophages (CD68) (Zone 2; mean thickness, 1.3 ± 0.3 mm [±S.D.]). Viable tumor cells (identified by Ki-67, p53 and Olig2 immunohistochemistry) were found (Zone 3) immediately adjacent to granulation tissue. The histologic volume of thermal tissue ablation/granulation was consistent with preoperative (pre-resection) magnetic resonance (MR)-imaging. Conclusion These findings are the first in vivo in humans to reveal that LITT causes a defined pattern of tissue necrosis, concentric destruction of tumor and tissue with viable tumor cells just beyond the zones of central necrosis and granulation. Furthermore, MR-imaging appears to be an accurate surrogate of tissue/tumor ablation in the early period (2 weeks) post-LITT treatment. Surgery is an effective strategy for patients with post-LITT swelling which does not respond to steroids

Synovial fluid-induced aggregation occurs across Staphylococcus aureus clinical isolates and is mechanistically independent of attached biofilm formation

Rapid synovial fluid-induced aggregation of Staphylococcus aureus is currently being investigated as an important factor in the establishment of periprosthetic joint infections (PJIs). Pathogenic advantages of aggregate formation have been well documented in vitro, including recalcitrance to antibiotics and protection from host immune defenses. The objective of the present work was to determine the strain dependency of synovial fluid-induced aggregation by measuring the degree of aggregation of 21 clinical S. aureus isolates cultured from either PJI or bloodstream infections using imaging and flow cytometry. Furthermore, by measuring attached bacterial biomass using a conventional crystal violet assay we assessed whether there is a correlation between the aggregative phenotype and surface-associated biofilm formation. While all of the isolates were stimulated to aggregate upon exposure to bovine synovial fluid (BSF) and human serum (HS), the extent of aggregation was highly variable between individual strains. Interestingly, the PJI isolates aggregated significantly more upon BSF exposure than those isolated from bloodstream infections. While we were able to stimulate biofilm formation with all of the isolates in growth media, supplementation with either synovial fluid or human serum inhibited bacterial surface attachment over a 24-hour incubation. Surprisingly, there was no correlation between the degree of synovial fluid-induced aggregation and quantity of surface-associated biofilm as measured by a conventional biofilm assay without host fluid supplementation. Taken together, synovial fluid-induced aggregation appears to be widespread among S. aureus strains and mechanistically independent of biofilm formation

Migration patterns of undergraduate medical students in elective exchanges: a prospective online survey

Background: An international and global medical education programme can help to develop health professionals' skillsets and can be a career-defining factor during the progression from student to practising physician. Our aim is to analyse migration patterns of medical students for elective exchanges and identify intentions for continued migration. Specifically, our objectives were to determine the most popular countries and specialty types that students in the medical and health professions intend to go for elective exchanges; to assess the different factors that contribute to a student's choice to migrate for an elective; and to assess factors leading to the intent of permanent migration after completion of study at the home institution. Methods: Our research deals with experiential learning in a global health setting through analysis of the trends and patterns of medical students pursuing medical electives worldwide. We used a multilingual online questionnaire, completed by students from 15 different countries across a timeframe of 1 month (April 2018). American, European, Asian, and African universities who are part of the Global Educational Exchange in the Medical and Health professions (GEMx) sent an email with the link to the questionnaire to their medical students. The questionnaire was conducted electronically and participants, who were selected via the school's respective student databases, were asked to complete the survey after their electives had been completed. Findings: We analysed responses from 363 students from 15 countries (15 from Kenya; 116 Italy; 20 Nigeria; 16 Rwanda; 5 Ireland; 74 India; 53 Egypt; 47 Indonesia; 11 Mexico; and one response each from Israel, Germany, the Democratic Republic of the Congo, Qatar, Algeria, and Canada). Country mean ages ranged between 21 years and 25 years; 224 respondents (61·7%) were women. The most popular destination country for an elective was the USA (72 students from 10 countries). The most popular specialty types were surgery (74, 20·4%) and internal medicine (56, 15·4%). Students cited expanded medical training (26 [42·6%]) an enhanced CV (18 [29·5%]), and broadened research opportunities (5 [8·2%]) as the most important motivations for choosing an elective exchange to another country. Of those who intended permanent migration (101 [27·8%]), the most frequently cited reason for this migration was the expansion of opportunities in a desired specialty (41 [40·6%]) while the main factor deterring students from permanent migration was the desire to disseminate the acquired learning to native home country health-care providers and systems (159, 60·4%). Interpretation: Students' elective experiences abroad not only significant steer the course of their careers as medical professionals, but are also crucial in creating a more holistic educational experience when combined with their home institution's curriculum. Global electives are an initiative that all schools should dedicate resources to pursuing. The elective process is vastly scalable and can be applied at medical schools in all regions of the world. Funding: None