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Purpose: Evolving evidence demonstrates the role of epigenetics in the pathogenesis of osteoarthritis (OA), whereas in terms of mechanism, DNA methylation has received the highest attention thus far. This systematic review summarizes the current knowledge of DNA methylation and its influence on the pathogenesis of OA. Methods: A protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases between 1 January 2015 and 31 January 2021, to identify associations between DNA methylation and articular chondrocytes in OA. Results: We identified 23 gene-specific studies and 28 genome-wide methylation analyses. Gene-specific studies focused on pro-inflammatory markers in OA, demonstrating that DNA hypomethylation in the promoter region results in overexpression and hypermethylation is linked to gene silencing. Others reported on the association between OA risk genes and DNA methylation. Genome-wide methylation studies reported on differentially methylated regions (DMRs) comparing OA and non-OA chondrocytes. DMRs were seen in hip OA and knee OA chondrocytes. Conclusion: The current body of literature demonstrates the potential and crucial role of DNA methylation in the pathogenesis and progression of OA. This knowledge contributes to the understanding of the pathomechanisms behind OA at gene-specific and genome-wide levels. The observed differences in DNA methylation between healthy and diseased tissues indicate the occurrence of changes in DNA methylation. Based on this, future research in this field that explores the characteristics of potentially reversible changes in DNA methylation may lead to opportunities for causative treatment options for OA.

Muhammad B Qureshi,1 Jose O Garcia,1 Jaxon Quillen,2 Carolyn Mead-Harvey,2 Christina Wentz,3 Cherie B Nau,4 Muriel Schornack,4 Keith Baratz,4 Sanjay V Patel,4 Joanne Shen5 1Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA; 2Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA; 3Illinois College of Optometry, Chicago, IL, USA; 4Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA; 5Department of Ophthalmology, Mayo Clinic, Scottsdale, AZ, USACorrespondence: Joanne Shen, Department of Ophthalmology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, USA, 85259, Tel +1 480-301-8085, Fax +1 480-301-7326, Email shen.joanne@mayo.eduPurpose: To compare baseline characteristics and treatment of chronic ocular graft-versus-host disease (oGVHD) patients in two treatment locations.Patients and Methods: Patients diagnosed with definite chronic oGVHD between September 1, 2014 and September 20, 2021 at two locations were identified. IRB-approved retrospective chart review was conducted for the following data: demographic information, ocular surface disease index (OSDI), corneal fluorescein staining (CFS), and treatment(s) used. Differences by site were assessed using Pearson’s Chi-Square tests and two-sample t-tests; differences by time were assessed using paired t-tests.Results: At baseline, Clinic 1 (C1) patients had a worse mean OSDI score (47.8 vs 36.3, p = 0.011) and CFS in both OD (1.3 vs 0.8, p = 0.005) and OS (1.3 vs 0.6, p < 0.001) compared to Clinic 2 (C2). Comparing baseline to endpoint, C1 patients experienced an improvement in OSDI (− 17.26, p < 0.001), CFS OD (− 0.50, p < 0.001), and CFS OS (− 0.51, p < 0.001) at C1. Change in OSDI, CFS OD, or CFS OS was not statistically significant at C2. Despite similar follow-up length, C1 demonstrated more clinic visits (10.4 vs 3.4, p < 0.001) and more treatment trials (4.9 vs 2.4, p < 0.001) compared to C2. Punctal plugs (85.5% vs 61.2%, p = 0.002), punctal cautery (69.7% vs 28.6%, p < 0.001), topical steroids (72.4% vs 22.4%, p < 0.001), and autologous serum tears (AST) (52.6% vs 8.2%, p < 0.001) were used more frequently at C1 than at C2.Conclusion: oGVHD patients at C1 experienced significant improvement in OSDI and corneal fluorescein staining and compared to patients at C2, had more frequent follow-up and use of punctal plugs, punctal cautery, topical steroids, and AST.Keywords: graft-versus-host disease, GVHD, chronic GVHD, dry eye disease, ocular GVHD, keratoconjunctivitis sicca, KCS

BackgroundThe one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration. This study aims to investigate whether the negative impact of BMC on bone healing in this technique is due to the CD8+ cell population.Materials and methodsA 5 mm femoral defect was created in 25 male Sprague-Dawley rats, divided into three groups (G1-G3). BMC were isolated from syngenic donor rats, with CD8+ lymphocytes removed magnetically from the BMC fraction in one group. The defects were filled with bone chips and wrapped with differently treated hADM: G1 received native hADM, G2 received hADM+BMC, and G3 received hADM+BMC-CD8. After 8 weeks, the femurs were evaluated through radiological, biomechanical, and histological examinations.ResultsBone defects and bone mineral density (BMD) were significantly improved in G3 (hADM+BMC-CD8) compared to G2 (hADM+BMC). Bone volume, bone formation, and median bending stiffness were higher in G3. Immunohistological analysis showed a significant decrease in CD8 cell count in G3, with a lower percentage of IFNγ-producing cells compared to G2.ConclusionDepleting CD8+ cells from BMC before colonizing hADM significantly improved bone healing, likely due to changes in the local mediator environment. This suggests that preoperative colonization with CD8+-depleted BMC could enhance the one-step membrane technique.

Introduction: Streptococcus pneumoniae is the most common cause of bacterial meningitis and meningoencephalitis in humans. The bacterium produces numerous virulence determinants; among them, hydrogen peroxide (H2O2) and pneumolysin (Ply) contribute to bacterial cytotoxicity. Microglia, the resident phagocytes in the brain, are distinct from other macrophages, and we thus compared their susceptibility to pneumococcal toxicity and their ability to phagocytose pneumococci with those of bone-marrow-derived macrophages (BMDMs). Methods: Microglia and BMDMs were co-incubated with S. pneumoniae D39 to analyze the survival of phagocytes by fluorescence microscopy, bacterial growth by quantitative plating, and phagocytosis by an antibiotic protection assay. Ply was detected by hemolysis assay and Western blot analysis. Results: We found that microglia were killed during pneumococcal infection with a wild-type and an isogenic ply-deficient mutant, whereas the viability of BMDMs was not affected by pneumococci. Treatment with recombinant Ply showed a dose-dependent cytotoxic effect on microglia and BMDMs. However, high concentrations of recombinant Ply were required, and under the chosen experimental conditions, Ply was not detectable in the supernatant during infection of microglia. Inactivation of H2O2 by exogenously added catalase abolished its cytotoxic effect. Consequently, infection of microglia with pneumococci deficient for the pyruvate oxidase SpxB, primarily producing H2O2, resulted in reduced killing of microglia. Conclusion: Taken together, in the absence of Ply, H2O2 caused cell death in primary phagocytes in concentrations produced by pneumococci.

Kelps are important habitat-forming species in shallow marine environments, providing critical habitat, structure, and productivity for temperate reef ecosystems worldwide. Many kelp species are currently endangered by myriad pressures, including changing water temperatures, invasive species, and anthropogenic threats. This situation necessitates advanced methods to detect kelp density, which would allow tracking density changes, understanding ecosystem dynamics, and informing evidence-based management strategies. This study introduces an innovative approach to detect kelp density with multibeam echosounder water column data. First, these data are filtered into a point cloud. Then, a range of variables are derived from these point cloud data, including average acoustic energy, volume, and point density. Finally, these variables are used as input to a Random Forest model in combination with bathymetric variables to classify sand, bare rock, sparse kelp, and dense kelp habitats. At 5 m resolution, we achieved an overall accuracy of 72.5% with an overall Area Under the Curve of 0.874. Notably, our method achieved high accuracy across the entire multibeam swath, with only a 1 percent point decrease in model accuracy for data falling within the part of the multibeam water column data impacted by sidelobe artefact noise, which significantly expands the potential of this data type for wide-scale monitoring of threatened kelp ecosystems.

Background: To meet the World Health Organization goal of reducing physical inactivity by 15% by 2030, a multisectoral system approach is urgently needed to promote physical activity (PA). We report the process of and findings from a codesigned systems mapping project to present determinants of PA in the context of urban New South Wales, Australia. Methods: A participatory conceptual mapping workshop was held in May 2023 with 19 participants working in education, transportation, urban planning, community, health, and sport and recreation. Initial maps were developed and refined using online feedback from the participants. Interviews were conducted with 10 additional policymakers from relevant sectors to further refine the maps. Results: Two systems maps were cocreated, identifying over 100 variables influencing PA and their interconnections. Five settings emerged from the adults' map—social and community, policy, built environment and transportation, health care, and workplace—and 4 for the young people's map—family, school, transportation, and community and environment. The maps share similarities, such as regarding potential drivers within the transportation, community, and built environment sectors; however, the young people's map has a specific focus on the school setting and the adults' map on workplace and health care settings. Interviews with policymakers provided further unique insights into understanding and intervening in the PA system. Conclusions: This codesigned participatory systems mapping process, supplemented by stakeholder interviews, provided a unique opportunity to bring together stakeholders across sectors to understand the complexity within the PA system and begin to identify leverage points for tackling physical inactivity in New South Wales. [ABSTRACT FROM AUTHOR]

Background: In hospital- and community-acquired central nervous system infections, resistant Gram-positive bacteria are an increasing therapeutic challenge. The present approach does not attempt to identify rapidly bactericidal therapies for susceptible pathogens but aims to improve methods to find antibiotic regimens for multi-resistant pathogens that are effective in vivo in spite of reduced in vitro susceptibility in culture media. Methods: Antibiotic susceptibility was tested in cerebrospinal fluid (CSF) and Mueller–Hinton broth (Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis) or brain–heart infusion (Streptococcus pneumoniae). Results: Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were either lower in CSF than in broth or equal in CSF and broth. The difference between MICs in CSF and broth was prominent with gentamicin, levofloxacin, linezolid (staphylococci), and vancomycin (staphylococci and pneumococcus), whereas it was absent with ampicillin (E. faecalis), penicillin G (S. pneumoniae), linezolid (enterococcus and pneumococcus), and vancomycin (enterococcus). In no case was the MIC or MBC higher in CSF than in broth. Conclusions: Several antibiotics possess an antibacterial effect in CSF at lower concentrations than the MICs determined in broth, i.e., MICs in broth underestimate in situ susceptibility in CSF.

Abstract Background Firearm injury is a significant public health concern in the United States. Methods Data on fatal and nonfatal firearm injuries were obtained from a cohort of N = 7,473,650 members of Kaiser Permanente Southern California, a large integrated healthcare system between 2010 and 2020. Age-adjusted rates of combined fatal and nonfatal firearm injury per 100,000 members were calculated by year, with the 2010 US census as the reference population. Trends were evaluated using Poisson or negative binomial regression. Results There was an increasing trend in overall firearm injuries between 2010 and 2020 among adults in this large integrated healthcare system (p

Key Clinical Message Hypophyseal dysfunction may be overlooked by the currently generally accepted laboratory routine for the differential diagnosis in patients suffering from symptoms of depression or dementia. Abstract Hypothyroidism is an important cause of depression and potentially reversible cognitive impairment. Whereas the determination of the plasma concentration of thyrotropin (TSH) is generally considered part of the laboratory screening tests for dementia, the measurement of total or free triiodothyronine (T3, FT3), thyroxine (T4, FT4) and cortisol in plasma does not belong to the routine diagnostic workup in patients with depression or suspected dementia. In an 87‐year‐old lady suffering from increasingly poor general health, decreased fluid and food intake, mood depression and lack of energy, three measurements of plasma TSH produced normal values. A cranial computed tomography (cCT) 2 days prior to hospital admission had been assessed as apparently normal. A second cCT performed following a loss of consciousness complicated by tongue bite showed a hypophyseal tumor. Then, low plasma levels of FT3, FT4 and cortisol were found. Following hormone replacement and transsphenoidal tumor resection, the patient recovered rapidly. The present case report illustrates the pitfalls of measuring merely the TSH level in the detection of thyroid and hypophyseal dysfunction.

In this perspective, the authors give their view on the developments and experiences on communicating on (nano)materials safety. We would like to share our experiences with the scientific community in order to make them useful for future communication activities. We present the long-term work of the science communication projects DaNa, DaNa2.0 and DaNa4.0, running from 2009 to 2023. Starting in the early 2000s with the beginnings of nanotechnology research, communication on the safety of nanomaterials with the public was still very new and faced the projects with many challenges. Today, science communication is indispensable for the dissemination of scientific findings and a fact-based approach like the DaNa “Knowledge Base Materials” creates a trustworthy dialogue with the public. This long-term project series has made a significant contribution to communication on the safety of nanomaterials, perhaps even the largest among publicly funded project series worldwide.

BackgroundThe increasing number of requests for help for acutely ill patients and their management is a major problem in the health systems of many countries, but especially in Germany. Rescue coordination centers and ambulances in Germany are increasingly overloaded. As a result, rides as a part of rescue operations have been increasing in length for years, yet a relevant proportion of these operations represent low-acuity calls (LACs). The basic objective of this pilot study is the quantitative analysis of the potential misuse of requests to the rescue control center. Indications for alternative treatment options and how to handle these treatment options in nonacute, non–life-threatening health conditions, such as minor injuries or minor infectious diseases, will be assessed. The identification of these LACs is vital in order to prevent health care resources in emergency medical care becoming inadequate. ObjectiveThe overarching goal of this study is to determine the percentage of unnecessary rescue missions on site and subsequently to obtain an impression of the paramedics’ assessment of alternative treatment options or alternative methods of rescue transportation. MethodsThis will be an exploratory, noninterventional, cross-sectional study with a quantitative approach. The study is multicentric, with 21 ambulances in 12 different locations. The data for this study were collected via a questionnaire, newly developed for this study, for rescue personnel. Additionally, secondary data from the responsible control center will be linked and processed in an initial descriptive analysis. This descriptive analysis will form the basis for a subsequent variance analysis. ResultsData collection started as projected on September 18, 2023, and was ongoing until end of November 2023. We expect the documentation of several thousand rescue operations. We expect the following study results: (1) many unnecessary rescue operations, (2) immediate on-site assessment of correct care and treatment, and (3) patients’ reasons for calling a rescue coordination center. ConclusionsTo our knowledge, this is the first observational study in which acute rescue operations are recorded on site. The focus of this study is on the trained paramedics’ assessment of whether rescue operations are necessary or not. Additionally, alternative treatments, such as out-of-hours care service or primary care service, are shown for each individual case. The study also intends to cover the question of which factors are relevant and statistically significantly connected to the misuse of ambulances. Trial RegistrationGerman Register for Clinical Studies (Deutsches Register für Klinische Studien) DRKS00032510; https://drks.de/search/en/trial/DRKS00032510 International Registered Report Identifier (IRRID)DERR1-10.2196/54002