MicroRNA 497 modulates interleukin 1 signalling via the MAPK/ERK pathway

AbstractThe MAPK/ERK signalling pathway has been described to mediate IL-1 induction of target genes and is known to be regulated by microRNAs (miRNA). We describe a novel miRNA regulating the expression of the MEK1 gene and how it impacts IL-1 induced IL-6 transcription. miR-497 was predicted to target MEK1 3′UTR using bioinformatic tools. Transfection of miR-497 into HeLa cells inhibited MEK1 protein expression by 50%. In transient transfection experiments, the luciferase activity of a MEK1 3′UTR luciferase reporter construct was reduced in the presence of miR-497, and mutation of the predicted miR-497 binding site restored activity. miR-497 also decreased protein levels of RAF1 and ERK1 but not ERK2. Addition of miR-497 was further shown to inhibit IL-1 induced IL-6 gene transcription

Using mHealth App to Support TKR Decision Making for Knee Arthritis Patients

Introduction: Mobile health (mHealth) technology can be used to integrate into medical decision making for patients with advanced knee arthritis. We explored patient preferences on content and design of a mobile health app to facilitate daily symptom capture and summary feedback reporting, in order to inform treatment decisions, including use of total knee replacement surgery (TKR). Methods: We developed an Android-based smart phone app for knee arthritis patients to assess arthritis symptoms and individual readiness for TKR surgery. Patient focus groups were conducted to gather requirements for mHealth app development and to refine the design and content of the app. Clinician (physical therapist, surgeon) interviews were conducted to understand clinician expectations from the summary trend report generated by the app. Results: Sixteen patients attended focus groups with an average age of 67 and 63% female, and three clinicians participated in clinician interviews. The preliminary findings revealed that the patients preferred easy tap user interfaces to multi-tap or slider methods, and vertical question layout to horizontal orientation. Patients liked to be engaged by progress feedback reports and educational tips. Both patients and clinicians found a trended outcome summary report helpful which provides more precise details on whether and how the symptoms are changing over time. Discussion: User input can inform the design and implementation of mHealth technology to deliver tailored knowledge to patients through a user-defined, patient-centered smart phone app. The tool will support future knee arthritis patient decisions regarding the need for, and timing of TKR surgery

mHealth technologies for osteoarthritis self-management and treatment: A systematic review

Osteoarthritis is a common chronic disease that can be better treated with the help of self-management interventions. Mobile health (mHealth) technologies are becoming a popular means to deliver such interventions. We reviewed the current state of research and development of mHealth technologies for osteoarthritis self-management to determine gaps future research could address. We conducted a systematic review of English articles and a survey of apps available in the marketplace as of 2016. Among 117 unique articles identified, 25 articles that met our inclusion criteria were reviewed in-depth. The app search identified 23 relevant apps for osteoarthritis self-management. Through the synthesis of three research themes (osteoarthritis assessment tools, osteoarthritis measurement tools, and osteoarthritis motion monitoring tools) that emerged from the current knowledge base, we provide a design framework to guide the development of more comprehensive osteoarthritis mHealth apps that facilitate self-management, decision support, and shared decision-making

Direct-to-Patient PRO Collection to Support Quality Improvement in TJR

Introduction: Patient-reported outcomes (PROs) are widely used in orthopedic clinical research to evaluate quality of care. However, it is difficult to capture complete post-operative PRO data through surgeon office visits. The UK and Sweden collect post-TJR PRO measures directly from patients in their homes. We compared two US post-operative PRO collection processes- PROs in clinic at scheduled office visits and direct-to-patient collection, to evaluate timing and completeness of both approaches. Methods: At a large TJR center that has collected PROs at office visits routinely for years, post-TJR patients complete a PRO survey on a computer at follow-up clinic visits. In contrast, the national FORCE-TJR cohort manages post-operative PRO surveys across dozens of offices by sending PROs to patients directly via web-based questionnaires or scannable paper forms. We calculated post-operative PRO response rates and timing from these two approaches and compared patient physical outcomes between them. Results: In the clinic, 892 patients had TJR surgery during the study period. Of these, 392 (44%) completed post-operative surveys; 115 (29%) between 5 months and 7 months after surgery, and 85 (22%) after 7 months. Direct to patient PRO surveys were centrally distributed in month 5 after surgery. Of 11,702 TJR patients, 8283 (71%) completed the PRO survey within 5 to 9 months post-op. Of these, 90% were returned between 5 and 7 months. SF36 PCS scores were comparable between these two approaches. Discussion: While PRO collection at the office visit can support individual patient care decisions, patients return to the surgeon office at varied time points after TJR based on their recovery progress and convenience. Direct to patient PRO collection with appropriate retention processes can lead to uniform data timing and optimal completeness. Quality monitoring programs will benefit from consistent data across providers and should consider these factors in designing PRO procedures

Translating clinical and patient-reported data to tailored shared decision reports with predictive analytics for knee and hip arthritis

INTRODUCTION: New informatics tools can transform evidence-based information to individualized predictive reports to serve shared decisions in clinic. We developed a web-based system to collect patient-reported outcomes (PROs) and medical risk factors and to compare responses to national registry data. The system generates predicted outcomes for individual patients and a report for use in clinic to support decisions. We present the report development, presentation, and early experience implementing this PRO-based, shared decision report for knee and hip arthritis patients seeking orthopedic evaluation. METHODS: Iterative patient and clinician interviews defined report content and visual display. The web-system supports: (a) collection of PROs and risk data at home or in office, (b) automated statistical processing of responses compared to national data, (c) individualized estimates of likely pain relief and functional gain if surgery is elected, and (d) graphical reports to support shared decisions. The system was implemented at 12 sites with 26 surgeons in an ongoing cluster randomized trial. RESULTS: Clinicians and patients recommended that pain and function as well as clinical risk factors (e.g., BMI, smoking) be presented to frame the discussion. Color and graphics support patient understanding. To date, 7891 patients completed the assessment before the visit and 56% consented to study participation. Reports were generated for 98% of patients and 68% of patients recalled reviewing the report with their surgeon. CONCLUSIONS: Informatics solutions can generate timely, tailored office reports including PROs and predictive analytics. Patients successfully complete the pre-visit PRO assessments and clinicians and patients value the report to support shared surgical decisions

Translating Comparative TJR Outcomes for Performance Improvement to Guide Surgical Quality Improvement

Background/Purpose: With the CMS decision to publicly report hospital-specific post-operative total joint replacement (TJR) complications and readmissions, orthopedic surgeons need new sources of post-operative outcome data to monitor and improve post-hospital care. The AHRQ funded research program, Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR), developed methods to capture longitudinal patient-reported outcomes (PROs) and comprehensive post-TJR medical and surgical events, and established a web reporting system to return comparative outcome reports to participating surgeons and hospitals in order to monitor and improve quality and outcomes. Methods: This national cohort/registry captures post-TJR measures directly from patients in their homes to assure uniform time, completion, and consistency for data comparisons across hospitals. Quarterly updated web reports deliver hospital- and surgeon-specific TJR outcomes compared with those of their peers and risk-adjusted national benchmarks on PROs as well as on post-operative event rates. Results: Our national cohort enrolled 25,000 patients from 150 diverse orthopedists in 22 US states with varied hospital and surgeon practices. The secure, HIPAA compliant website was established that presents summary and risk-adjusted comparative statistics for primary TJR for all enrolled patients. The website provides a downloadable and printable report and an Executive Summary of key pre-operative patient risk factors, post-operative events, and post-operative PROs enabling the providers to compare their outcomes to the other participating sites. Individual patient reports are available for surgeons with real-time scores and trended outcome data to facilitate patient and surgeon shared treatment decision making. Conclusion/Implications: A secure reporting website was established to disseminate comparative outcome reports to all participating hospitals and surgeons. Returning comparative outcome data to hospitals and surgeons encourages their active participation in this national registry and allows them to undstand their relative performance compared to peers while supporting practice-level quality monitoring and improvement efforts in patient care

Maternal vaccination as an additional approach to improve the protection of the nursling: Anti-infective properties of breast milk

Human milk constitutes a secretion with unique functions of both nourishing the nursling and providing protection against enteric and respiratory infections, mainly due to its content of secretory IgA antibodies but also due to the presence of a plethora of bioactive factors. Specific IgA antibodies are produced locally by plasma cells derived from B lymphocytes that migrate from other mucosae to the mammary gland during lactation, particularly from the gastrointestinal and respiratory tracts. Therefore, here, the authors will provide a comprehensive review of the content and functions of different nutritional and bioactive anti-infectious components from breast milk, such as oligosaccharides, lactoferrin, haptocorrin, α-lactalbumin, k-casein, lysozyme, lactoperoxidase, mucin, fatty acids, defensins, cytokines and chemokines, hormones and growth factors, complement proteins, leukocytes and nucleic acids, including microRNAs, among many others, and the induction of antibody responses in breast milk after maternal vaccination with several licensed vaccines, including the anti-SARS-CoV-2 vaccine preparations used worldwide. Currently, in the midst of the pandemic, maternal vaccination has re-emerged as a crucial source of passive immunity to the neonate through the placenta and breastfeeding, considering that maternal vaccination can induce specific antibodies if performed during pregnancy and after delivery. There have been some reports in the literature about milk IgA antibodies induced by bacterial antigens or inactivated virus vaccines, such as anti-diphtheria-tetanus-pertussis, anti-influenza viruses, anti-pneumococcal and meningococcal polysaccharide preparations. Regarding anti-SARS-CoV-2 vaccines, most studies demonstrate elevated levels of specific IgA and IgG antibodies in milk with virus-neutralizing ability after maternal vaccination, which represents an additional approach to improve the protection of the nursling during the entire breastfeeding period

Human Fecal Metabolism of Soyasaponin I

The metabolism of soyasaponin I (3-O-[alpha-L-rhamnopyranosyl-beta-D-galactopyranosyl-beta-D-glucuronopyranosyl]olean-12-ene-3beta,22beta,24-triol) by human fecal microorganisms was investigated. Fresh feces were collected from 15 healthy women and incubated anaerobically with 10 mmol soyasaponin I/g feces at 37 degrees C for 48 h. The disappearance of soyasaponin I in this in vitro fermentation system displayed apparent first-order rate loss kinetics. Two distinct soyasaponin I degradation phenotypes were observed among the subjects: rapid soyasaponin degraders with a rate constant k = 0.24 +/- 0.04 h(-)(1) and slow degraders with a k = 0.07 +/- 0.02 h(-)(1). There were no significant differences in the body mass index, fecal moisture, gut transit time, and soy consumption frequency between the two soyasaponin degradation phenotypes. Two primary gut microbial metabolites of soyasaponin I were identified as soyasaponin III (3-O-[beta-D-galactopyranosyl-beta-D-glucuronopyranosyl]olean-12-ene-3beta,22beta,24-triol) and soyasapogenol B (olean-12-ene-3beta,22beta,24-triol) by NMR and electrospray ionized mass spectroscopy. Soyasaponin III appeared within the first 24 h and disappeared by 48 h. Soyasapogenol B seemed to be the final metabolic product during the 48 h anaerobic incubation. These results indicate that dietary soyasaponins can be metabolized by human gut microorganisms. The sugar moieties of soyasaponins seem to be hydrolyzed sequentially to yield smaller and more hydrophobic metabolites