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Clinically, multimodal therapies are adopted worldwide for the management of cancer, which continues to be a leading cause of death. In recent years, immunotherapy has firmly established itself as a new paradigm in cancer care that activates the body's immune defense to cope with cancer. Immunotherapy has resulted in significant breakthroughs in the treatment of stubborn tumors, dramatically improving the clinical outcome of cancer patients. Multiple forms of cancer immunotherapy, including immune checkpoint inhibitors (ICIs), adoptive cell therapy and cancer vaccines, have become widely available. However, the effectiveness of these immunotherapies is not much satisfying. Many cancer patients do not respond to immunotherapy, and disease recurrence appears to be unavoidable because of the rapidly evolving resistance. Moreover, immunotherapies can give rise to severe off-target immune-related adverse events. Strategies to remove these hindrances mainly focus on the development of combinatorial therapies or the exploitation of novel immunotherapeutic mediations. Nanomaterials carrying anticancer agents to the target site are considered as practical approaches for cancer treatment. Nanomedicine combined with immunotherapies offers the possibility to potentiate systemic antitumor immunity and to facilitate selective cytotoxicity against cancer cells in an effective and safe manner. A myriad of nano-enabled cancer immunotherapies are currently under clinical investigation. Owing to gaps between preclinical and clinical studies, nano-immunotherapy faces multiple challenges, including the biosafety of nanomaterials and clinical trial design. In this review, we provide an overview of cancer immunotherapy and summarize the evidence indicating how nanomedicine-based approaches increase the efficacy of immunotherapies. We also discuss the key challenges that have emerged in the era of nanotechnology-based cancer immunotherapy. Taken together, combination nano-immunotherapy is drawing increasing attention, and it is anticipated that the combined treatment will achieve the desired success in clinical cancer therapy. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is a highly malignant and metastatic form of cancer. The global incidence of and mortality from LC is steadily increasing; the mean 5-year overall survival (OS) rate for LC is less than 20%. This frustrating situation may be attributed to the fact that the pathogenesis of LC remains poorly understood and there is still no cure for mid to advanced LC. Methylation at the N6-position of adenosine (N6mA) of RNA (m(6)A) is widely present in human tissues and organs, and has been found to be necessary for cell development and maintenance of homeostasis. However, numerous basic and clinical studies have demonstrated that RNA m(6)A is deregulated in many human malignancies including LC. This can drive LC malignant characteristics such as proliferation, stemness, invasion, epithelial-mesenchymal transition (EMT), metastasis, and therapeutic resistance. Intriguingly, an increasing number of studies have also shown that eliminating RNA m(6)A dysfunction can exert significant anti-cancer effects on LC such as suppression of cell proliferation and viability, induction of cell death, and reversal of treatment insensitivity. The current review comprehensively discusses the therapeutic potential of RNA m(6)A and its underlying molecular mechanisms in LC, providing useful information for the development of novel LC treatment strategies. [ABSTRACT FROM AUTHOR]

Background: At present, only a few studies have explored electroencephalography (EEG) microstates of patients with obsessive–compulsive disorder (OCD) and the results are inconsistent. Additionally, the nonlinear features of EEG microstate sequences contain rich information about the brain, yet how the nonlinear features of EEG microstate sequences abnormally change in patients with OCD is still unknown. Methods: Resting-state EEG data were collected from 48 OCD patients and macheted 48 healthy controls (HC). Subsequently, EEG microstate analysis was used to extract the microstate temporal parameters (duration, occurrence, coverage) and nonlinear features of EEG microstate sequences (sample entropy, Lempel–Ziv complexity, Hurst index). Finally, the temporal parameters and nonlinear features of EEG microstate sequences were sent to three kinds of machine learning models to classify OCD patients. Results: Both groups obtained four typical EEG microstate topographies. The duration of microstates A, B, and C in OCD patients decreased significantly, while the occurrence of microstate D increased significantly compared to HC. Sample entropy and Lempel–Ziv complexity of microstate sequences in OCD patients increased significantly, while Hurst index decreased significantly compared to HC. The classification accuracy using the nonlinear features of microstate sequences reached up to 85%, significantly higher than that based on microstate temporal parameter models. Conclusion: This study provides supplementary findings on EEG microstates in OCD patients with a larger sample size. We found that the nonlinear features of EEG microstate sequences in OCD patients can serve as potential electrophysiological biomarkers for distinguishing OCD patients. [ABSTRACT FROM AUTHOR]

Background: Optimal management of Rockwood type III acromioclavicular joint (ACJ) dislocation is still debated. Our aim is to conduct a meta-analysis of clinical studies evaluating the functional outcomes of operative versus conservative treatment for Rockwood type III ACJ dislocation. Methods: We conducted a systematic search across PubMed, EMBASE, Web of Science, and the Cochrane Library, including only randomized controlled trials (RCTs) focusing exclusively on type III ACJ dislocation. A total of 244 patients from four studies were included. Outcomes measured included Constant scores (CS), coracoclavicular distance (CCD), pain, and complication rates. Heterogeneity was assessed and managed to ensure robust conclusions. Results: The pooled results showed no significant difference in long-term functional outcomes, measured by CS, between surgical and conservative treatments (MD: 4.82, 95% CI: -6.42 to 16.06, P = 0.400). Surgical treatment provided better early pain relief and superior CCD at all follow-up points but did not improve long-term outcomes. Complication rates were similar for both treatments, though surgical intervention had a higher incidence of posttraumatic osteoarthritis and hardware-related issues. Conservative treatment resulted in fewer complications and comparable long-term results. Conclusions: Based on the evidence, while surgical treatment may offer early benefits in pain relief and CCD improvement, it does not enhance long-term functional outcomes and is associated with higher specific complication rates. Conservative treatment provides a viable alternative with fewer complications and similar long-term outcomes. These findings highlight the need for individualized treatment plans based on patient-specific factors and suggest further high-quality, long-term studies to refine management strategies for Type III AC joint dislocations. [ABSTRACT FROM AUTHOR]

Background: Extrachromosomal circular DNA (eccDNA), a novel class of DNA with a circular topological structure, is present in a variety of cancer cells and tissues and may play broad roles in processes ranging from aging to cancer cell heterogeneity through multiple mechanisms. EccDNA has been characterized by profile, structure and function in several prominent studies but its effect on hydroquinone (HQ)-induced malignantly transformed cells (TK6-HQ) is still elusive. Methods: Circle-seq was applied to determine the eccDNA counts and characteristics of TK6-HQ cells. DNA-fluorescence in situ hybridization was used to measure the abundance of eccDNA_DTX1. Differential gene expression analysis was carried out by RNA-seq. Gene expression was quantified by wertern blot and qPCR. Decircularization of eccDNA_DTX1 was achieved by CRISPR/Cas9. Tumorigenicity was evaluated by xenograft assay in BALB/c nude mice. Results: In this study, we characterized the structure of eccDNAs and the function of DTX1-containing eccDNA (eccDNA_DTX1) in TK6-HQ cells. A total of 669,179 eccDNAs were identified, including 901 eccDNAs with different counts. Most of the eccDNAs were < 1000 bp in length and were enriched in four periodic peaks starting at 186 bp with an interval of ~ 180 bp. The genomic distribution of eccDNAs confirmed that eccDNAs could be observed across all chromosomes and had greater enrichment on chromosomes 17, 19, 20, and 22, with abundant Alu repeat elements, introns and CpG islands. By combining the results of the integrated circle-seq analysis of eccDNAs with those from the RNA-seq analysis (differentially expressed genes, 1064 upregulated and 427 downregulated), the authors showed that the transcription of 20 potential coding genes might be driven by eccDNAs. Finally, the knockdown of eccDNA_DTX1 by CRISPR/Cas9 inhibited the growth of TK6-HQ cells in vitro and in vivo by inhibiting the transcription of DTX1 and promoting ferroptosis, and ferroptosis inhibior, Ferrostatin-1, abrogated the proliferation inhibition of eccDNA_DTX1 knockdown. Conclusions: EccDNA_DTX1 promotes cell growth in hydroquinone-induced malignantly transformed cells by regulating the transcription of DTX1 and ferroptosis. This study profiles eccDNA characteristics and defines the role and mechanism of eccDNA_DTX1 for the first time, shedding new light on the relationship between eccDNAs and carcinogenesis. [ABSTRACT FROM AUTHOR]

Aim: This study aims to assess the effectiveness of therapy of human synovial membrane-derived MSCs (SM-MSC) from OA grade IV patients in treating knee OA. Methods: SM-MSC were isolated from patients undergoing total knee replacement surgery, cultured to the fourth passage, and characterized using flow cytometry. Differentiation potential was assessed through lineage-specific staining. Osteoarthritis was induced in 24 Wistar rats via monosodium iodoacetate (MIA). The rats were divided into three groups: negative control, OA control, and OA treated with SM-MSC. Radiological, histopathological, and molecular analyses were conducted to evaluate cartilage repair and gene expression. Results: Flow cytometry confirmed the MSC phenotype of SM-MSC, and successful differentiation was observed. Radiological and histopathological analyses showed significant improvement in the SM-MSC treated group, with reduced cartilage damage and higher Safranin O staining compared to the OA control group. Gene expression analysis indicated increased type-2 collagen (COL-2) expression in the SM-MSC treated group, although MMP-13 levels remained unchanged across all groups. Conclusion: Human SM-MSCs from OA grade IV patients significantly improved cartilage repair in an OA rat model, demonstrating their potential as a therapeutic option for OA. To enhance long-term efficacy and anti-inflammatory effects, further studies are needed to optimize treatment protocols, including injection frequency and dosage. [ABSTRACT FROM AUTHOR]

The primary issues in treating type 1 diabetes mellitus (T1DM) through the transplantation of healthy islets or islet β-cells are graft rejection and a lack of available donors. Currently, the majority of approaches use cell encapsulation technology and transplant replacement cells that can release insulin to address transplant rejection and donor shortages. However, existing encapsulation materials merely serve as carriers for islet cell growth. A new treatment approach for T1DM could be developed by creating a smart responsive material that encourages the formation of islet cell spheroids to replicate their 3D connections in vivo and controls the release of insulin aggregates. In this study, we used microfluidics to create thermally sensitive porous scaffolds made of poly(N-isopropyl acrylamide)/graphene oxide (PNIPAM/GO). The material was carefully shrunk under near-infrared light, enriched with mouse insulinoma pancreatic β cells (β-TC-6 cells), encapsulated, and cultivated to form 3D cell spheroids. The controlled contraction of the thermally responsive porous scaffold regulated insulin release from the spheroids, demonstrated using the glucose-stimulated insulin release assay (GSIS), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence assay. Eventually, implantation of the spheroids into C57BL/6 N diabetic mice enhanced the therapeutic effect, potentially offering a novel approach to the management of T1DM. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway. Methods: We conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways. Results: Our results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8+ TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic. Conclusions: The study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8+ TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells. [ABSTRACT FROM AUTHOR]

Background: Oral function tests have been shown to reliably detect impaired bulbar function in adults with spinal muscular atrophy (SMA). Although not routinely recorded, it is known that persons with SMA are affected to varying degrees. Detecting differences in bite and tongue force, endurance, and maximum mouth opening has become particularly promising since the introduction of causal therapy for SMA. This study aimed to compare oral function among adult persons with SMA with different SMA types, walking abilities, and treatment status to a healthy control group. Methods: Data from oral function tests conducted on 58 persons with SMA and 45 healthy individuals were analyzed. Differences in oral function between SMA subgroups were pairwise tested and compared to the healthy control group using Wilcoxon rank sum tests. Results: In an overall comparison, three out of five oral function tests revealed lower values for the SMA group compared to the control group. Subgroup analyses indicated lower scores for most oral function tests in non-ambulatory, untreated patients with SMA type 2 compared to controls. Ambulatory, treated patients with SMA type 3 achieved strength and endurance values comparable to those of healthy individuals. Conclusions: The impairment of oral function varies across persons with SMA. Routine measurement of oral function is warranted to determine individual bulbar involvement stages. Further evaluation should be scheduled if indicators such as restricted maximum mouth opening arise. Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/register/de/trial/DRKS00015842/preview. [ABSTRACT FROM AUTHOR]

Background: Plasma p-tau217 has emerged as the most promising blood-based marker (BBM) for the detection of Alzheimer Disease (AD) pathology, yet few studies have evaluated plasma p-tau217 performance in memory clinic settings. We examined the performance of plasma p-tau217 for the detection of AD using a high-sensitivity immunoassay in individuals undergoing diagnostic lumbar puncture (LP). Methods: Paired plasma and cerebrospinal fluid (CSF) samples were analysed from the TIMC-BRAiN cohort. Amyloid (Aβ) and Tau (T) pathology were classified based on established cut-offs for CSF Aβ42 and CSF p-tau181 respectively. High-sensitivity electrochemiluminescence (ECL) immunoassays were performed on paired plasma/CSF samples for p-tau217, p-tau181, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light (NfL) and total tau (t-tau). Biomarker performance was evaluated using Receiver-Operating Curve (ROC) and Area-Under-the-Curve (AUC) analysis. Results: Of 108 participants (age: 69 ± 6.5 years; 54.6% female) with paired samples obtained at time of LP, 64.8% (n = 70/108) had Aβ pathology detected (35 with Mild Cognitive Impairment and 35 with mild dementia). Plasma p-tau217 was over three-fold higher in Aβ + (12.4 pg/mL; 7.3—19.2 pg/mL) vs. Aβ- participants (3.7 pg/mL; 2.8—4.1 pg/mL; Mann–Whitney U = 230, p < 0.001). Plasma p-tau217 exhibited excellent performance for the detection of Aβ pathology (AUC: 0.91; 95% Confidence Interval [95% CI]: 0.86–0.97)—greater than for T pathology (AUC: 0.83; 95% CI: 0.75–0.90; z = 1.75, p = 0.04). Plasma p-tau217 outperformed plasma p-tau181 for the detection of Aβ pathology (z = 3.24, p < 0.001). Of the other BBMs, only plasma GFAP significantly differed by Aβ status which significantly correlated with plasma p-tau217 in Aβ + (but not in Aβ-) individuals. Application of a two-point threshold at 95% and 97.5% sensitivities & specificities may have enabled avoidance of LP in 58–68% of cases. Conclusions: Plasma p-tau217 measured using a high-sensitivity ECL immunoassay demonstrated excellent performance for detection of Aβ pathology in a real-world memory clinic cohort. Moving forward, clinical use of plasma p-tau217 to detect AD pathology may substantially reduce need for confirmatory diagnostic testing for AD pathology with diagnostic LP in specialist memory services. [ABSTRACT FROM AUTHOR]

Background: Monocytes and macrophages play an indispensable role in maintaining intestinal homeostasis and modulating mucosal immune responses in inflammatory bowel disease (IBD). Although numerous studies have described macrophage properties in IBD, the underlying mechanisms whereby the monocyte-macrophage lineage modulates intestinal homeostasis during gut inflammation remain elusive. Main body: In this review, we decipher the cellular and molecular mechanisms governing the generation of intestinal mucosal macrophages and fill the knowledge gap in understanding the origin, maturation, classification, and functions of mucosal macrophages in intestinal niches, particularly the phagocytosis and bactericidal effects involved in the elimination of cell debris and pathogens. We delineate macrophage-mediated immunoregulation in the context of producing pro-inflammatory and anti-inflammatory cytokines, chemokines, toxic mediators, and macrophage extracellular traps (METs), and participating in the modulation of epithelial cell proliferation, angiogenesis, and fibrosis in the intestine and its accessory tissues. Moreover, we emphasize that the maturation of intestinal macrophages is arrested at immature stage during IBD, and the deficiency of MCPIP1 involves in the process via ATF3-AP1S2 signature. In addition, we confirmed the origin potential of IL-1B+ macrophages and defined C1QB+ macrophages as mature macrophages. The interaction crosstalk between the intestine and the mesentery has been described in this review, and the expression of mesentery-derived SAA2 is upregulated during IBD, which contributes to immunoregulation of macrophage. Moreover, we also highlight IBD-related susceptibility genes (e.g., RUNX3, IL21R, GTF2I, and LILRB3) associated with the maturation and functions of macrophage, which provide promising therapeutic opportunities for treating human IBD. Conclusion: In summary, this review provides a comprehensive, comprehensive, in-depth and novel description of the characteristics and functions of macrophages in IBD, and highlights the important role of macrophages in the molecular and cellular process during IBD. [ABSTRACT FROM AUTHOR]

Background: Chronic pain was associated with a higher risk of mental disorders (e.g., depression and anxiety). However, the role of 24-h movement behaviors in the association remains unclear. Methods: A total of 72,800 participants with accelerometer data and free of mental disorders from the UK Biobank were analyzed. The compositional mediation model and isotemporal substitution model were used to explore the associations between chronic pain, 24-h movement behaviors, and the incidence of overall mental disorders, depression, and anxiety. Results: With a median follow-up of 13.36 years, participants with chronic pain had a higher rate of incident overall mental disorders (hazard ratio (HR): 1.281, 95% confidence interval (CI): 1.219 to 1.344), anxiety (HR: 1.391, 95% CI: 1.280 to 1.536), and depression (HR: 1.703, 95% CI: 1.551 to 1.871). Increased sedentary behavior (SB) and reduced moderate-to-vigorous physical activity (MVPA) caused by chronic pain both increased the risk of mental disorders. Twenty-four-hour movement behaviors explained the relationship between chronic pain and overall mental disorders, depression, and anxiety by 10.77%, 5.70%, and 6.86%, respectively. Interaction effects were found between MVPA and chronic pain when predicting the incidence of depression and between MVPA, sleep (SLP), and chronic pain when predicting the incidence of mental disorders. People with chronic pain would recommend at least 0.5 h per day of MVPA and 7 h per day of SLP and restricting SB below 11.5 h per day. Conclusions: Twenty-four-hour movement behaviors played a significant mediating role in the association between chronic pain and mental disorders. Individuals with chronic pain should engage in more MVPA, less sedentary behavior, and have 7-h sleep per day. [ABSTRACT FROM AUTHOR]

Background: Identifying the DNA-binding specificities of transcription factors (TF) is central to understanding gene networks that regulate growth and development. Such knowledge is lacking in oomycetes, a microbial eukaryotic lineage within the stramenopile group. Oomycetes include many important plant and animal pathogens such as the potato and tomato blight agent Phytophthora infestans, which is a tractable model for studying life-stage differentiation within the group. Results: Mining of the P. infestans genome identified 197 genes encoding proteins belonging to 22 TF families. Their chromosomal distribution was consistent with family expansions through unequal crossing-over, which were likely ancient since each family had similar sizes in most oomycetes. Most TFs exhibited dynamic changes in RNA levels through the P. infestans life cycle. The DNA-binding preferences of 123 proteins were assayed using protein-binding oligonucleotide microarrays, which succeeded with 73 proteins from 14 families. Binding sites predicted for representatives of the families were validated by electrophoretic mobility shift or chromatin immunoprecipitation assays. Consistent with the substantial evolutionary distance of oomycetes from traditional model organisms, only a subset of the DNA-binding preferences resembled those of human or plant orthologs. Phylogenetic analyses of the TF families within P. infestans often discriminated clades with canonical and novel DNA targets. Paralogs with similar binding preferences frequently had distinct patterns of expression suggestive of functional divergence. TFs were predicted to either drive life stage-specific expression or serve as general activators based on the representation of their binding sites within total or developmentally-regulated promoters. This projection was confirmed for one TF using synthetic and mutated promoters fused to reporter genes in vivo. Conclusions: We established a large dataset of binding specificities for P. infestans TFs, representing the first in the stramenopile group. This resource provides a basis for understanding transcriptional regulation by linking TFs with their targets, which should help delineate the molecular components of processes such as sporulation and host infection. Our work also yielded insight into TF evolution during the eukaryotic radiation, revealing both functional conservation as well as diversification across kingdoms. [ABSTRACT FROM AUTHOR]

Background: Videoconferencing is considered an alternative to face-to-face consultations and a possibility to help overcome access-to-care barriers in mental health care services. Barriers to child and adolescent mental health services are particularly apparent in the case of children and adolescents receiving child welfare services. This scoping review aims to provide an overview of research on videoconferencing in the mental health treatment of children and adolescents receiving support from child welfare services. Methods: This scoping review follows the review framework outlined by the Joanna Briggs Institute. The following databases were searched from January 2012 to April 2024: Scopus, Web of Science, PubMed, PsycINFO (Ovid), CINAHL Plus, Social Services Abstracts (ProQuest), Sociological Abstracts (ProQuest), and Google Scholar. Results: The search yielded 4322 unique records and resulted in the inclusion of 22 articles that met the inclusion criteria. The studies originated from Denmark, England, Australia, Norway, Canada, Chile, and the USA, and were grouped into four areas: (1) videoconferencing to increase access to mental health treatment for vulnerable groups (2) young people's perspectives (3) videoconferencing in interdisciplinary collaborative meetings, and (4) use, awareness, and acceptance of videoconferencing among health and social care providers. Conclusions: This scoping review shows that if videoconferencing in mental health care is to become an established and trusted method aimed at children and adolescents receiving child welfare services, several unresolved and potentially negative issues need attention and more research. This particularly applies to whether videoconferencing decreases or exacerbates inequalities in access to mental health services. A further question is whether new barriers are raised by screen-based treatment to threaten good therapeutic relationships, and by extension treatment quality and clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aims to provide an overview of the current knowledge on the role of the metaverse, augmented reality, and virtual reality in reverse shoulder arthroplasty. Methods: A systematic review was performed using the PRISMA guidelines. A comprehensive review of the applications of the metaverse, augmented reality, and virtual reality in in-vivo intraoperative navigation, in the training of orthopedic residents, and in the latest innovations proposed in ex-vivo studies was conducted. Results: A total of 22 articles were included in the review. Data on navigated shoulder arthroplasty was extracted from 14 articles: seven hundred ninety-three patients treated with intraoperative navigated rTSA or aTSA were included. Also, three randomized control trials (RCTs) reported outcomes on a total of fifty-three orthopedics surgical residents and doctors receiving VR-based training for rTSA, which were also included in the review. Three studies reporting the latest VR and AR-based rTSA applications and two proof of concept studies were also included in the review. Conclusions: The metaverse, augmented reality, and virtual reality present immense potential for the future of orthopedic surgery. As these technologies advance, it is crucial to conduct additional research, foster development, and seamlessly integrate them into surgical education to fully harness their capabilities and transform the field. This evolution promises enhanced accuracy, expanded training opportunities, and improved surgical planning capabilities. [ABSTRACT FROM AUTHOR]

The concept of "stemness" incorporates the molecular mechanisms that regulate the unlimited self-regenerative potential typical of undifferentiated primitive cells. These cells possess the unique ability to navigate the cell cycle, transitioning in and out of the quiescent G0 phase, and hold the capacity to generate diverse cell phenotypes. Stem cells, as undifferentiated precursors endow with extraordinary regenerative capabilities, exhibit a heterogeneous and tissue-specific distribution throughout the human body. The identification and characterization of distinct stem cell populations across various tissues have revolutionized our understanding of tissue homeostasis and regeneration. From the hematopoietic to the nervous and musculoskeletal systems, the presence of tissue-specific stem cells underlines the complex adaptability of multicellular organisms. Recent investigations have revealed a diverse cohort of non-hematopoietic stem cells (non-HSC), primarily within bone marrow and other stromal tissue, alongside established hematopoietic stem cells (HSC). Among these non-HSC, a rare subset exhibits pluripotent characteristics. In vitro and in vivo studies have demonstrated the remarkable differentiation potential of these putative stem cells, known by various names including multipotent adult progenitor cells (MAPC), marrow-isolated adult multilineage inducible cells (MIAMI), small blood stem cells (SBSC), very small embryonic-like stem cells (VSELs), and multilineage differentiating stress enduring cells (MUSE). The diverse nomenclatures assigned to these primitive stem cell populations may arise from different origins or varied experimental methodologies. This review aims to present a comprehensive comparison of various subpopulations of multipotent/pluripotent stem cells derived from stromal tissues. By analysing isolation techniques and surface marker expression associated with these populations, we aim to delineate the similarities and distinctions among stromal tissue-derived stem cells. Understanding the nuances of these tissue-specific stem cells is critical for unlocking their therapeutic potential and advancing regenerative medicine. The future of stem cells research should prioritize the standardization of methodologies and collaborative investigations in shared laboratory environments. This approach could mitigate variability in research outcomes and foster scientific partnerships to fully exploit the therapeutic potential of pluripotent stem cells. [ABSTRACT FROM AUTHOR]

Background: Disturbances alter the diversity and composition of microbial communities. Yet a generalized empirical assessment of microbiome responses to disturbance across different environments is needed to understand the factors driving microbiome recovery, and the role of the environment in driving these patterns. Results: To this end, we combined null models with Bayesian generalized linear models to examine 86 time series of disturbed mammalian, aquatic, and soil microbiomes up to 50 days following disturbance. Overall, disturbances had the strongest effect on mammalian microbiomes, which lost taxa and later recovered their richness, but not their composition. In contrast, following disturbance, aquatic microbiomes tended away from their pre-disturbance composition over time. Surprisingly, across all environments, we found no evidence of increased compositional dispersion (i.e., variance) following disturbance, in contrast to the expectations of the Anna Karenina Principle. Conclusions: This is the first study to systematically compare secondary successional dynamics across disturbed microbiomes, using a consistent temporal scale and modeling approach. Our findings show that the recovery of microbiomes is environment-specific, and helps to reconcile existing, environment-specific research into a unified perspective. FPVwQXB65-N4idcpgwJZ6_ Video Abstract [ABSTRACT FROM AUTHOR]

Background: Hypoxia/reoxygenation (H/R) induces cardiomyocyte ferroptosis, a core remodeling event in myocardial ischemia/reperfusion injury. Methyltransferase-like 14 (METTL14) emerges as a writer of N6-methyladenosine (m6A) modification. This study was conducted to decipher the role of METTL14 in H/R-induced cardiomyocyte ferroptosis. Methods: Mouse cardiomyocytes HL-1 were cultured and underwent H/R treatment. The degree of ferroptosis after H/R treatment was appraised by the cell counting kit-8 assay, assay kits (ROS/GSH/Fe2+), and Western blotting (GPX4/ACSL4). The intracellular expressions of METTL14, pri-miR-146a-5p, miR-146a-5p, or adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) were examined by real-time quantitative polymerase chain reaction or Western blotting, with m6A quantification analysis and RNA immunoprecipitation to determine the total m6A level and the expression of pri-miR-146a-5p bound to DiGeorge critical region 8 (DGCR8) and m6A-modified pri-miR-146a-5p. The binding of miR-146a-5p to APPL1 was testified by the dual-luciferase assay. Results: H/R treatment induced cardiomyocyte ferroptosis (increased ROS, Fe2+, and ACSL4 and decreased GSH and GPX4) and upregulated METTL14 expression. METTL14 knockdown attenuated H/R-induced cardiomyocyte ferroptosis. METTL14 induced the recognition of pri-miR-146a-5p by DGCR8 by increasing m6A modification on pri-miR-146a-5p, which promoted the conversion of pri-miR-146a-5p into miR-146a-5p and further repressed APPL1 transcription. miR-146a-5p upregulation or APPL1 downregulation limited the inhibitory effect of METTL14 downregulation on H/R-induced cardiomyocyte ferroptosis. Conclusion: METTL14 promoted miR-146a-5p expression through the recognition and processing of pri-miR-146a-5p by DGCR8, which repressed APPL1 transcription and triggered H/R-induced cardiomyocyte ferroptosis. [ABSTRACT FROM AUTHOR]

Background: Triatoma garciabesi and T. guasayana are considered secondary vectors of Trypanosoma cruzi and frequently invade rural houses in central Argentina. Wing and head structures determine the ability of triatomines to disperse. Environmental changes exert selective pressures on populations of both species, promoting changes in these structures that could have consequences for flight dispersal. The aim of this study was to investigate the relationship between a gradient of anthropization and phenotypic plasticity in flight-related traits. Methods: The research was carried out in Cruz del Eje and Ischilín departments (Córdoba, Argentina) and included 423 individuals of the two species of triatomines. To measure the degree of anthropization, a thematic map was constructed using supervised classification, from which seven landscapes were selected, and nine landscape metrics were extracted and used in a hierarchical analysis. To determine the flight capacity and the invasion of dwellings at different levels of anthropization for both species, entomological indices were calculated. Digital images of the body, head and wings were used to measure linear and geometric morphometric variables related to flight dispersion. One-way ANOVA and canonical variate analysis (CVA) were used to analyze differences in size and shape between levels of anthropization. Procrustes variance of shape was calculated to analyze differences in phenotypic variation in heads and wings. Results: Hierarchical analysis was used to classify the landscapes into three levels of anthropization: high, intermediate and low. The dispersal index for both species yielded similar results across the anthropization gradient. However, in less anthropized landscapes, the density index was higher for T. garciabesi. Additionally, in highly anthropized landscapes, females and males of both species exhibited reduced numbers. Regarding phenotypic changes, the size of body, head and wings of T. garciabesi captured in the most anthropized landscapes was greater than for those captured in less anthropized landscapes. No differences in body size were observed in T. guasayana collected in the different landscapes. However, males from highly anthropized landscapes had smaller heads and wings than those captured in less anthropized landscapes. Both wing and head shapes varied between less and more anthropogenic environments in both species. Conclusions: Results of the study indicate that the flight-dispersal characteristics of T. garciabesi and T. guasayana changed in response to varying degrees of anthropization. [ABSTRACT FROM AUTHOR]

Background: Community-driven invasion, also known as community coalescence, occurs widely in natural ecosystems. Despite that, our knowledge about the process and mechanisms controlling community-driven invasion in soil ecosystems is lacking. Here, we performed a set of coalescence experiments in soil microcosms and assessed impacts up to 60 days after coalescence by quantifying multiple traits (compositional, functional, and metabolic) of the invasive and coalescent communities. Results: Our results showed that coalescences significantly triggered changes in the resident community's succession trajectory and functionality (carbohydrate metabolism), even when the size of the invasive community is small (~ 5% of the resident density) and 99% of the invaders failed to survive. The invasion impact was mainly due to the high suppression of constant residents (65% on average), leading to a lose-lose situation where both invaders and residents suffered with coalescence. Our results showed that surviving residents could benefit from the coalescence, which supports the theory of "competition-driven niche segregation" at the microbial community level. Furthermore, the result showed that both short- and long-term coalescence effects were predicted by similarity and unevenness indexes of compositional, functional, and metabolic traits of invasive communities. This indicates the power of multi-level traits in monitoring microbial community succession. In contrast, the varied importance of different levels of traits suggests that competitive processes depend on the composition of the invasive community. Conclusions: Our results shed light on the process and consequence of community coalescences and highlight that resource competition between invaders and residents plays a critical role in soil microbial community coalescences. These findings provide valuable insights for understanding and predicting soil microbial community succession in frequently disturbed natural and agroecosystems. DpDvMjk1dTeXPyYscPCMZP Video Abstract [ABSTRACT FROM AUTHOR]

Background: Immigrants are exposed to numerous risk factors that may contribute to the development of chronic musculoskeletal pain. Recent political and environmental crises in North Africa and the Middle East have led to an increase in immigration to Europe that has challenged the healthcare system and especially the management of chronic conditions. Objective: The aims of this scoping review are to investigate the burden, prevalence, and associated factors of chronic musculoskeletal pain in immigrants from North Africa and the Middle East in Europe during the last decade. The intentions of the review are to inform healthcare policymakers, to identify gaps in the literature, and aid the planning of future research. Design: Online databases Medline, Embase, PubMed and Web of Science were used to identify epidemiological studies published from2012–2022 examining chronic pain in populations from North Africa and the Middle East with a migration background residing in Europe. Results: In total eleven studies were identified conducted in Norway (n = 3), Denmark (n = 3), Germany (n = 1), Austria (n = 1), Sweden (n = 1), and Switzerland (n = 1). Among the identified studies, eight studies were cross-sectional (n = 8), two were prospective cohort studies (n = 2) and one was a retrospective cohort study (n = 1). Data suggested that chronic pain is more prevalent, more widespread, and more severe in people with than without a migration background. Furthermore, immigrants who have resided in the destination country for a longer period experience a higher prevalence of chronic pain compared to those in the early phases of migration. The following factors were found to be associated with chronic pain in this population: female gender, lower education, financial hardship, being underweight or obese, time in transit during migration, experience of trauma, immigration status, anxiety, depression, and post-traumatic stress disorder. Conclusion: Several gaps in the literature were identified. Research is limited in terms of quantity and quality, does not reflect actual immigration trends, and does not account for immigration factors. Prospective cohort studies with long follow-ups would aid in improving prevention and management of chronic pain in populations with a migration background. In particular, they should reflect actual immigration trajectories, account for immigration factors, and have valid comparison groups in the countries of origin, transit and destination. Key points: • Chronic pain is more prevalent in populations with a migration background than without. • Immigrant women are a particularly susceptible group in developing chronic pain. • Length of stay, socio-economic class and mental health are other associated factors. • Current research does not reflect the magnitude and geography of the issue. [ABSTRACT FROM AUTHOR]

Background: Eimeria genus belongs to the apicomplexan parasite phylum and is responsible for coccidiosis, an intestinal disease with a major economic impact on poultry production. Eimeria tenella is one of the most virulent species in chickens. In a previous study, we showed a negative impact of caecal microbiota on the physiopathology of this infection. However, the mechanism by which microbiota leads to the physiopathology remained undetermined. Macrophages play a key role in inflammatory processes and their interaction with the microbiota during E. tenella infection have never been investigated. We therefore examined the impact of microbiota on macrophages during E. tenella infection. Macrophages were monitored in caecal tissues by immunofluorescence staining with KUL01 antibody in non-infected and infected germ-free and conventional chickens. Caecal cells were isolated, stained, analyzed and sorted to examine their gene expression using high-throughput qPCR. Results: We demonstrated that microbiota was essential for caecal macrophage recruitment in E. tenella infection. Furthermore, microbiota promoted a pro-inflammatory transcriptomic profile of macrophages characterized by increased gene expression of NOS2, ACOD1, PTGS2, TNFα, IL1β, IL6, IL8L1, IL8L2 and CCL20 in infected chickens. Administration of caecal microbiota from conventional chickens to germ-free infected chickens partially restored macrophage recruitment and response. Conclusions: Taken together, these results suggest that the microbiota enhances the physiopathology of this infection through macrophage recruitment and activation. Consequently, strategies involving modulation of the gut microbiota may lead to attenuation of the macrophage-mediated inflammatory response, thereby limiting the negative clinical outcome of the disease. [ABSTRACT FROM AUTHOR]

Background: Physiological and pathological cardiomyocyte hypertrophy are important pathophysiological processes of adult congenital heart disease-associated ventricular hypertrophy. Glutamic oxaloacetic transaminase (GOT) is a vital marker of myocardial injury. This study aimed to investigate the changes in GOT levels during physiological and pathological cardiomyocyte hypertrophy in rats. Methods: RNA-seq analysis and colorimetric methods were used to evaluate the changes in GOT mRNA and activity, respectively. GOT2 protein expression was detected by western blotting and immunofluorescence. Hematoxylin-eosin and wheat germ agglutinin methods were used to observe changes in rat cardiomyocyte morphology. Results: In juvenile rat hearts, GOT mRNA expression and activity, and GOT2 protein level increased with age-related physiological cardiomyocyte hypertrophy; however, GOT2 protein level was reduced in hypoxia-induced pathological cardiomyocyte hypertrophy. Conclusions: GOT2 may regulate physiological and pathological myocardial hypertrophy in rats. We speculated that the low GOT2 level contributed to the rapid occurrence of pathological cardiomyocyte hypertrophy, causing strong plasticity of right ventricular cardiomyocytes in the early postnatal period and heart failure in adulthood. [ABSTRACT FROM AUTHOR]

Background: No definitive treatment methods of curative for knee osteoarthritis (KOA). The combined therapies that into account both the biochemical and biomechanical may provide potential opportunities for treat KOA, and previous studies have demonstrated that the platelet-rich plasma of intra-articular injection (IAI-PRP) and exercise treatments afford more benefits than do their corresponding monotherapies. The absence of a specific exercise plan and detailed explanation renders the aforementioned study results questionable. Furthermore, Tai Chi (TC) with moderate-intensity, whole body movements and good adherence may prove to be more effective for treating KOA. However, few studies examined the effectiveness and safety of combined IAI-PRP and TC for KOA. Methods: This study protocol will be a placebo-controlled, assessor-blinded randomized trial involving 12-week intervention and 1-year follow-up. The stratified randomization will be used to randomly assign the 212 participants to four groups: group A (placebo IAI); group B (PRP IAI); group C (TC and placebo IAI); group D (TC and PRP IAI). Injection will be performed once a week, three consecutive times as a course, after a week of rest to continue the next course, a total of 3 courses (12 week). Additionally, the TC interventions will be carried out 3 days per week for a total of 12 weeks. The primary outcome measures will include the efficacy (Western Ontario and McMaster Universities Osteoarthritis Index), acceptability and safety of these interventions. The secondary outcome measures will include physical function (Timed Up and Go test), walking function (Gait Analysis), inflammatory factor levels (e.g., Interleukin-1 β, interleukin-6, vascular endothelial growth factor), quality of life (36-Item Short Form Health Survey), volume of patellofemoral cartilage and effusion-synovitis (MRI). Two-way of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. Discussion: This trial will be first one to propose an integrated scheme combing IAI-PRP and TC for treatment of KOA, based on the consideration of the biochemical and biomechanical pathogenesis of KOA. These results of the study will provide evidence with high quality for integrated IAI-PRP and TC to treatment KOA. Trial Registration Chinese Clinical Trial Registry ChiCTR2300067559. Registered on 11 January 2023. [ABSTRACT FROM AUTHOR]

Pathogenic germline variants in the DNA polymerase genes POLE and POLD1 cause polymerase proofreading-associated polyposis, a dominantly inherited disorder with increased risk of colorectal carcinomas and other tumors. POLE/POLD1 variants may result in high somatic mutation and neoantigen loads that confer susceptibility to immune checkpoint inhibitors (ICIs). To explore the role of POLE/POLD1 germline variants in glioma predisposition, whole-exome sequencing was applied to leukocyte DNA of glioma patients from 61 tumor families with at least one glioma case each. Rare heterozygous POLE/POLD1 missense variants predicted to be deleterious were identified in glioma patients from 10 (16%) families, co-segregating with the tumor phenotype in families with available DNA from several tumor patients. Glioblastoma patients carrying rare POLE variants had a mean overall survival of 21 months. Additionally, germline variants in POLD1, located at 19q13.33, were detected in 2/34 (6%) patients with 1p/19q-codeleted oligodendrogliomas, while POLE variants were identified in 2/4 (50%) glioblastoma patients with a spinal metastasis. In 13/15 (87%) gliomas from patients carrying POLE/POLD1 variants, features of defective polymerase proofreading, e.g. hypermutation, POLE/POLD1-associated mutational signatures, multinucleated cells, and increased intratumoral T cell response, were observed. In a CRISPR/Cas9-derived POLE-deficient LN-229 glioblastoma cell clone, a mutator phenotype and delayed S phase progression were detected compared to wildtype POLE cells. Our data provide evidence that rare POLE/POLD1 germline variants predispose to gliomas that may be susceptible to ICIs. Data compiled here suggest that glioma patients carrying POLE/POLD1 variants may be recognized by cutaneous manifestations, e.g. café-au-lait macules, and benefit from surveillance colonoscopy. [ABSTRACT FROM AUTHOR]

Background: For patients with Parkinson's disease (PwPD), promotion of habitual physical activity (PA) assists in the prevention of disease progression. Patients' health literacy (HL) is integral for meeting PA standards and turning it into a habit. This study evaluated the association between PA level and each HL domain in PwPD. Methods: Online web-based assessment instruments and self-administered questionnaires, including the PA Questionnaire (IPAQ) Short Form and the Functional, Communicative, and Critical Health Literacy (FCCHL) scale, were used to assess PA levels and health literacy domains of PwPD. Results: The mean age of PwPD (n = 114) was 65.9 (SD = 11.6) years; 59.6% female, and the mean duration of disease was 6.4 (SD = 5.1) years. Of participants, 47.4% met the recommended criteria for PA. When comparing each HL domain by PA level, participants with lower PA had significantly lower critical HL (p = 0.03). Logistic regression analysis revealed that PA level correlated with critical HL (OR = 2.46; 95% CI = 1.16–5.19; p = 0.02). Conclusions: Adherence to recommended PA standards was associated with critical HL, but not other HL domains. Proactive attitudes to critically evaluate and utilize as well as understand health information may positively influence the promotion of PA. [ABSTRACT FROM AUTHOR]

Background: Current health care demonstrates an insufficient provision and utilization of physical exercises despite their recommendation as a first-line treatment in clinical guidelines for patients with knee osteoarthritis (OA). Mobile health (m-health) technologies offer new opportunities to guide and monitor home-based exercise programs by using mobile devices and inertial sensors in combination with a digital application (app). This study will evaluate patient benefits resulting from the use of the specific digital health application re.flex for patients with knee OA. Methods: This monocentric, two-arm, randomized controlled parallel-group trial will evaluate the effectiveness of the app- and sensor-guided exercise program re.flex for patients with moderate-to-severe knee OA. We aim to recruit 200 participants via newspapers, newsletters and information events. Participants will be randomly allocated to the intervention group and the control group in a 1:1 ratio. Participants in the control group will not receive any study intervention or instruction for any change to their previous health care utilization. Despite this, they are allowed to make use of usual care provided by their treating physician. The intervention group comprises a 12-week home training program with three sessions per week in addition to usual care. Exercises will be guided and monitored by use of the training app (re.flex) and two accelerometers that are attached proximally and distally to the affected knee joint. Pre- and postmeasurements will take place at baseline (t0) and after 12 weeks (t1). Primary outcomes will be osteoarthritis-specific pain and physical function measured with the Knee Osteoarthritis Outcome Score (KOOS) subscales Pain and Function in daily living (ADL). Second, further self-reported health outcomes, a performance measurement, app logfiles and safety will be assessed. Intervention effects will be calculated by baseline-adjusted analysis of covariance (ANCOVA) using an intention-to-treat approach. Multiple imputation will be applied. Discussion: Re.flex can bridge part of the gap between recommendations for strengthening exercises in patients with knee OA and the insufficient actual care situation. This randomized controlled trial is designed to provide conclusions on the effectiveness of the health application re.flex for the population under study and will provide further insight into adherence rates and the safety of its use. Trial registration: The trial was registered on 20/01/2023 at www.drks.de (ID: DRKS00030932). [ABSTRACT FROM AUTHOR]

Background: Video consultations has been suggested to lower the threshold for child and adolescent mental healthcare treatment. This study explores how young people receiving child welfare services experience video consultations in child and adolescent mental healthcare. The study is part of a larger Norwegian study of access to health services for this target group. Methods: The study has a mixed methods design including qualitative interviews and a quantitative survey, with young people receiving child welfare services. The qualitative interviews included 10 participants aged 15–19. The survey included 232 participants aged 16–24 of which 36 reported having received video consultations in mental healthcare. The interviews were analysed using thematic analysis. The survey data was presented as frequencies to clarify the distribution of positive and negative perceptions of video consultation. Results: The results show that the participants experienced video consultations as more superficial and less binding, compared to in-person sessions. They raised concerns of the therapeutic relationship, however some found it easier to regulate closeness and distance. In the survey several reported that their relationship with the therapist got worse, and that it was much more difficult to talk on screen. Moreover, a large proportion (42%) claimed that video consultations did not fit their treatment needs overall. However, a minority of the participants found it easier to talk to the therapist on screen. Conclusions: The study reveals important weaknesses and disadvantages of online therapy as experienced by young people receiving child welfare services. It is particularly worrying that their criticism involves the relational aspects of treatment, as children receiving child welfare services often have relational experiences which make them particularly sensitive to challenges in relationships. This study shows that youth involvement in decision making of video consultations in therapy has been rare. Clinicians should be aware of these young people's doubts regarding the quality of video consultations in child and adolescent mental health care. Further studies should examine how user involvement can be incorporated in video consultations in therapy and how this could improve experiences and the quality of video consultations. [ABSTRACT FROM AUTHOR]

Background: Trauma related deaths remain a relevant public health problem, in particular in the younger male population. A significant number of these deaths occur prehospitally without transfer to a hospital. These patients, sometimes termed "the forgotten cohort", are usually not included in clinical registries, resulting in a lack of information about prehospitally trauma deaths. The aim of the present study was to compare patients who died prehospital with those who sustained life-threatening injuries in order to analyze and potentially improve prehospital strategies. Methods: This cohort study included all primary operations carried out by Switzerland's largest helicopter emergency medical service (HEMS) between January 1, 2011, and December 31, 2021. We included all adult trauma patients with life-threatening or fatal conditions. The outcome of this study is the vital status of the patient at the end of mission, i.e. fatal or life-threatening. Injury, rescue characteristics, and interventions of the forgotten trauma cohort, defined as patients with a fatal injury (NACA score of VII), were compared with life-threatening injuries (NACA score V and VI). Results: Of 110,331 HEMS missions, 5534 primary operations were finally analyzed, including 5191 (93.8%) life-threatening and 343 (6.2%) fatal injuries. More than two-thirds of patients (n = 3772, 68.2%) had a traumatic brain injury without a significant difference between the two groups (p > 0.05). Thoracic trauma (44.6% vs. 28.7%, p < 0.001) and abdominal trauma (22.2% vs. 16.1%, p = 0.004) were more frequent in fatal missions whereas pelvic trauma was similar between the two groups (13.4% vs. 12.9%, p = 0.788). Pneumothorax decompression rate (17.2% vs. 3.7%, p < 0.001) was higher in the forgotten cohort group and measures for bleeding control (15.2% vs. 42.7%, p < 0.001) and pelvic belt application (2.9% vs. 13.1% p < 0.001) were more common in the life-threating injury group. Conclusion: Chest decompression rates and measures for early hemorrhage control are areas for potential improvement in prehospital care. [ABSTRACT FROM AUTHOR]

Background: Lupus nephritis and lupus erythematosus tumidus (LET) are uncommon manifestations of systemic lupus erythematosus (SLE), and their coexistence as the initial presentation of SLE is exceedingly rare. Here, we report such a case, emphasizing the diagnostic challenges and therapeutic implications of this unusual association. Case report: A 38-year-old North African woman presented in Nephrology department with a history of lower extremity edema, fatigue, and weight loss of 3 kg in 4 weeks. Physical examination revealed LET lesions on the chest and the Neck. Laboratory investigations showed lymphopenia, low C3 and C4 complement levels, positive antinuclear antibodies, anti-dsDNA antibodies, and anti-SSA/Ro antibodies. Renal function tests showed normal serum creatinine and nephrotic proteinuria. Renal biopsy revealed Class V lupus nephritis. Skin biopsy confirmed the diagnosis of LET, with the presence of lymphohistiocytic infiltrates and dermal mucin. The patient was diagnosed with SLE based on the 2019 EULAR/ACR criteria and treated with prednisone (1 mg/kg/day) and hydroxychloroquine. She showed significant improvement in her cutaneous and renal symptoms at 6 and 12 months follow-up. Conclusion: The rarity of the coexistence of LET and lupus nephritis as the initial manifestation of SLE, especially in the North African population, underscores the need for further research to elucidate the immunopathogenic mechanisms and prognostic factors associated with this association. [ABSTRACT FROM AUTHOR]

Due to the limited accessibility of the in vivo situation, the scarcity of the human tissue, legal constraints, and ethical considerations, the underlying molecular mechanisms of disorders, such as preeclampsia, the pathological consequences of fetomaternal microchimerism, or infertility, are still not fully understood. And although substantial progress has already been made, the therapeutic strategies for reproductive system diseases are still facing limitations. In the recent years, it became more and more evident that stem cells are powerful tools for basic research in human reproduction and stem cell-based approaches moved into the center of endeavors to establish new clinical concepts. Multipotent fetal stem cells derived from the amniotic fluid, amniotic membrane, chorion leave, Wharton´s jelly, or placenta came to the fore because they are easy to acquire, are not associated with ethical concerns or covered by strict legal restrictions, and can be banked for autologous utilization later in life. Compared to adult stem cells, they exhibit a significantly higher differentiation potential and are much easier to propagate in vitro. Compared to pluripotent stem cells, they harbor less mutations, are not tumorigenic, and exhibit low immunogenicity. Studies on multipotent fetal stem cells can be invaluable to gain knowledge on the development of dysfunctional fetal cell types, to characterize the fetal stem cells migrating into the body of a pregnant woman in the context of fetomaternal microchimerism, and to obtain a more comprehensive picture of germ cell development in the course of in vitro differentiation experiments. The in vivo transplantation of fetal stem cells or their paracrine factors can mediate therapeutic effects in preeclampsia and can restore reproductive organ functions. Together with the use of fetal stem cell-derived gametes, such strategies could once help individuals, who do not develop functional gametes, to conceive genetically related children. Although there is still a long way to go, these developments regarding the usage of multipotent fetal stem cells in the clinic should continuously be accompanied by a wide and detailed ethical discussion. [ABSTRACT FROM AUTHOR]

Background: Kashin–Beck disease (KBD) is an endemic deformable bone and joint disease, which affects the quality of life (QOL) of patients. We conducted a cross-sectional study of the QOL of KBD patients by a new KBD quality of life (KBDQOL) questionnaire. Methods: A total of 252 KBD patients and 248 OA patients came from Northwest China, and 260 healthy people living in the same area as KBD and osteoarthritis (OA) patients served as the controls. KBDQOL questionnaire was used to evaluate the QOL of all objects. Results: The average scores for physical functions, activity limitations, support of society, mental health and general health were significantly lower in KBD patients than that in OA patients and healthy people except for economics. Monofactor analysis showed that age, height, weight status, education level and grade of KBD had a significant effect on KBDQOL score. Multivariate analysis showed that grade of KBD was the influencing factor of physical function score; gender, age, height, grade of KBD and duration of symptoms were the influencing factors of activity restriction score; age and grade of KBD were factors affecting the general health score. Conclusion: The QOL of KBD patients was significantly lower than that of OA patients and healthy people. The KBDQOL questionnaire may be a promising tool for assessing the QOL of KBD patients. [ABSTRACT FROM AUTHOR]

Background: Impairment of bulbar function in adult individuals with spinal muscular atrophy (SMA) usually is not assessed by established motor scores. Measurements of oral function including quantitative muscle and endurance tests are able to detect subtle changes. The aim of this study was to systematically evaluate the measurement of maximum bite force and endurance, maximum tongue pressure and endurance, as well as maximum mouth opening in adult individuals with SMA types 2 and 3. Methods: Data from oral function tests in 43 individuals were analyzed. Differences in oral function between individuals with different SMA types and numbers of SMN2 copies were tested. Spearman´s rho correlations among oral function measures themselves as well as with established clinical outcome scales were analyzed. Results: The absolute maximum measures of oral function (maximum bite force, maximum tongue pressure, maximum mouth opening) were able to discriminate between individuals with different SMA types, individuals with a different number of SMN2 copies and with different walking abilities. The pairwise correlations of the absolute maximum measures of oral function were fair to moderate in size; the same was true for their correlations with the established motor scores. All correlations assessing endurance measures of oral function were weaker and statistically insignificant. Conclusions: Among the oral function tests maximum tongue pressure and maximum mouth opening are particulary promising as clinical and sensitive outcome measures for clinical trials. Oral function tests may supplement existing motor scores, in particular concerning specific questions about bulbar function or in severely affected non-ambulatory individuals where mild (treatment-related) changes would otherwise remain undetected. Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/search/de/trial/DRKS00015842 [ABSTRACT FROM AUTHOR]

Background: Graph databases enable efficient storage of heterogeneous, highly-interlinked data, such as clinical data. Subsequently, researchers can extract relevant features from these datasets and apply machine learning for diagnosis, biomarker discovery, or understanding pathogenesis. Methods: To facilitate machine learning and save time for extracting data from the graph database, we developed and optimized Decision Tree Plug-in (DTP) containing 24 procedures to generate and evaluate decision trees directly in the graph database Neo4j on homogeneous and unconnected nodes. Results: Creation of the decision tree for three clinical datasets directly in the graph database from the nodes required between 0.059 and 0.099 s, while calculating the decision tree with the same algorithm in Java from CSV files took 0.085–0.112 s. Furthermore, our approach was faster than the standard decision tree implementations in R (0.62 s) and equal to Python (0.08 s), also using CSV files as input for small datasets. In addition, we have explored the strengths of DTP by evaluating a large dataset (approx. 250,000 instances) to predict patients with diabetes and compared the performance against algorithms generated by state-of-the-art packages in R and Python. By doing so, we have been able to show competitive results on the performance of Neo4j, in terms of quality of predictions as well as time efficiency. Furthermore, we could show that high body-mass index and high blood pressure are the main risk factors for diabetes. Conclusion: Overall, our work shows that integrating machine learning into graph databases saves time for additional processes as well as external memory, and could be applied to a variety of use cases, including clinical applications. This provides user with the advantages of high scalability, visualization and complex querying. [ABSTRACT FROM AUTHOR]

Background: Microbes typically live in communities where individuals can interact with each other in numerous ways. However, knowledge on the importance of these interactions is limited and derives mainly from studies using a limited number of species grown in coculture. Here, we manipulated soil microbial communities to assess the contribution of interactions between microorganisms for assembly of the soil microbiome. Results: By combining experimental removal (taxa depletion in the community) and coalescence (mixing of manipulated and control communities) approaches, we demonstrated that interactions between microorganisms can play a key role in determining their fitness during soil recolonization. The coalescence approach not only revealed the importance of density-dependent interactions in microbial community assembly but also allowed to restore partly or fully community diversity and soil functions. Microbial community manipulation resulted in shifts in both inorganic nitrogen pools and soil pH, which were related to the proportion of ammonia-oxidizing bacteria. Conclusions: Our work provides new insights into the understanding of the importance of microbial interactions in soil. Our top-down approach combining removal and coalescence manipulation also allowed linking community structure and ecosystem functions. Furthermore, these results highlight the potential of manipulating microbial communities for the restoration of soil ecosystems. 1hnKtMhPkxX_a_nwXw9y6K Video Abstract [ABSTRACT FROM AUTHOR]

Background: Selenium is an essential nutrient with antioxidant, anti-inflammatory, and immuno-regulatory properties. Studies have displayed that in critically ill patients, selenium supplementation may be a potentially promising adjunctive therapy. Objective: We aimed to present an overview of the effects of selenium supplementation in adult critically ill patients based on published systematic reviews and meta-analyses (SRMAs) of randomized controlled trials (RCTs). Methods: A literature search in three electronic databases, PubMed, Scopus, and Web of Science, was performed to find eligible SRMAs until July 2022. For each outcome, the risk ratios (RRs) or mean differences (MDs) and 95% confidence intervals (CIs) were recalculated using either random or fixed effect models. The methodological quality and quality of evidence of the SRMAs were assessed by applying "A Measurement Tool to Assess Systematic Reviews" (AMSTAR2) and Grading of Recommendations Assessment, Development, and Evaluation(GRADE) tools, respectively. Results: We included 17 meta-analyses containing 24 RCTs based on inclusion criteria. Selenium supplementation can reduce the incidence of mortality (RR: 0.83, 95% CI 0.71, 0.98, P = 0.024) and incidence of acute renal failure (RR: 0.67, 95% CI 0.46, 0.98, P: 0.038) significantly; however, the certainty of evidence was low. Moreover, with moderate to very low certainty of evidence, no significant effects were found for risk of infection (RR: 0.92, 95% CI 0.80, 1.05, P: 0.207), pneumonia (RR: 1.11, 95% CI 0.72, 1.72, P: 0.675), as well as the length of ICU (MD: 0.15, 95% CI − 1.75, 2.05, P: 0.876) and hospital stay (MD: − 0.51, 95% CI − 3.74, 2.72, P: 0.757) and days on ventilation (MD: − 0.98, 95% CI − 2.93, 0.98, P: 0.329). Conclusions: With low quality of evidence, the use of selenium supplementation could improve the risk of mortality and acute renal failure, but not other outcomes in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Plants are found in a large percentage of indoor environments, yet the potential for bacteria associated with indoor plant leaves and soil to colonize human skin remains unclear. We report results of experiments in a controlled climate chamber to characterize bacterial communities inhabiting the substrates and leaves of five indoor plant species, and quantify microbial transfer dynamics and residence times on human skin following simulated touch contact events. Controlled bacterial propagule transfer events with soil and leaf donors were applied to the arms of human occupants and repeatedly measured over a 24-h period using 16S rRNA gene amplicon sequencing. Results: Substrate samples had greater biomass and alpha diversity compared to leaves and baseline skin bacterial communities, as well as dissimilar taxonomic compositions. Despite these differences in donor community diversity and biomass, we observed repeatable patterns in the dynamics of transfer events. Recipient human skin bacterial communities increased in alpha diversity and became more similar to donor communities, an effect which, for soil contact only, persisted for at least 24 h. Washing with soap and water effectively returned communities to their pre-perturbed state, although some abundant soil taxa resisted removal through washing. Conclusions: This study represents an initial characterization of bacterial relationships between humans and indoor plants, which represent a potentially valuable element of biodiversity in the built environment. Although environmental microbiota are unlikely to permanently colonize skin following a single contact event, repeated or continuous exposures to indoor biodiversity may be increasingly relevant for the functioning and diversity of the human microbiome as urbanization continues. [ABSTRACT FROM AUTHOR]

Background: Uniportal video-assisted thoracoscopic surgery without drainage-tube placement has been demonstrated to be safe and feasible for select situations. The purpose of this study is to assess the demographic, baseline, and intraoperative characteristics of patients who developed residual pneumothorax after thoracic surgery without drainage-tube placement. Methods: We reviewed the records of all patients who underwent pulmonary wedge resection via uniportal video-assisted thoracoscopic surgery without drainage-tube placement between May 2019 and May 2022. The decision to omit chest-tube drainage was originally made on a case-by-case basis, using internal criteria. Postoperative chest radiography was performed on the day of surgery, on postoperative day 1, at the first outpatient visit, and at 1 month after surgery. Results: A total of 134 patients met the selection criteria; 23 (17.2%) had residual pneumothorax on chest radiography on postoperative day 1, and 5 (3.7%) had residual pneumothorax at the first outpatient visit. Only 1 patient (0.7%) had residual pneumothorax on chest radiography at 1 month after surgery; this patient did not require chest-tube insertion or any other intervention. The presence of partial pleural adhesions independently increased the risk for postoperative residual pneumothorax on chest radiography, whereas older patient age reduced the risk. Conclusions: Uniportal video-assisted thoracoscopic surgery for pulmonary wedge resection without drainage-tube placement is both safe and feasible for carefully selected patients. Most patients with residual pneumothorax in our study experienced spontaneous resolution, and none required reintervention. [ABSTRACT FROM AUTHOR]

Background: Lipoedema is a chronic disease in adipose tissue that almost exclusively affects women during periods of hormonal alterations. Its main symptoms include an abnormal accumulation of subcutaneous fat in the buttock, hips, and legs, which is associated with pain, swelling, and easy bruising. Herein, a grading in three stages is used to determine disease progression. Problematically, lipoedema manifestations are often confused with lifestyle-induced obesity, which is why the various health problems among affected women often remain unrecognized. Overall, research on lipoedema is scarce. As such, this study examined the health, health-related quality of life (HRQOL), and sense of coherence (SOC) among women with lipoedema.Methods: We conducted a national cross-sectional study using an online survey assessing sociodemographic data, lipoedema characteristics, symptom severity, comorbidities, HRQOL (RAND-36), and SOC (SOC-13). In total, 245 women with lipoedema, recruited from all Lipoedema Association groups in Sweden, participated. Data were compiled with descriptive statistics, and mean differences between groups were analysed by using parametric and non-parametric tests.Results: Moderate and severe leg heaviness, pain, numbness, cold skin, feeling cold, easy bruising, and sleep problems were found to occur in all lipoedema stages. Moreover, almost all participants reported having comorbidities. Worse physical health and most substantial limitations in daily life were reported among women with the most progressive lipoedema (i.e., stage 3). Social and emotional functioning and SOC were found to be, on the other hand, primarily related to respondents' sociodemographic data and their ages at lipoedema onset. Even though approximately 70% of the women had experienced lipoedema onset before age 30, only three (1.6%) had been diagnosed by a healthcare professional before that age.Conclusion: Having lipoedema is associated with several health problems and a lower HRQOL. In addition, the extent of delay in diagnosis within this sample indicates that many women with lipoedema are often underdiagnosed and are left without support from healthcare. These findings call for the need for greater attention on lipoedema. Moreover, further studies on how women with lipoedema manage their health and symptoms, as well as on their experiences of healthcare services and lipoedema treatments, are needed. [ABSTRACT FROM AUTHOR]

We identified here mechanism by which hAECs exert their anti-cancer effects. We showed that vaccination with live hAEC conferred effective protection against murine colon cancer and melanoma but not against breast cancer in an orthotopic cancer cell inoculation model. hAEC induced strong cross-reactive antibody response to CT26 cells, but not against B16F10 and 4T1 cells. Neither heterotopic injection of tumor cells in AEC-vaccinated mice nor vaccination with hAEC lysate conferred protection against melanoma or colon cancer. Nano-sized AEC-derived small-extracellular vesicles (sEV) (AD-sEV) induced apoptosis in CT26 cells and inhibited their proliferation. Co-administration of AD-sEV with tumor cells substantially inhibited tumor development and increased CTL responses in vaccinated mice. AD-sEV triggered the Warburg’s effect leading to Arginine consumption and cancer cell apoptosis. Our results clearly showed that it is AD-sEV but not the cross-reactive immune responses against tumor cells that mediate inhibitory effects of hAEC on cancer development. Our results highlight the potential anti-cancer effects of extracellular vesicles derived from hAEC.Highlights: Anti-cancer effects of hAEC depend on cancer type. Cross-reactive humoral responses do not mediate anti-cancer effects of hAEC. Anti-cancer effects of hAECs are mainly mediated by small-extracellular vesicles (sEV). hAEC-derived sEV (AD-sEV) trigger the Warburg’s effect leading to Arginine consumption and cancer cell apoptosis. AD-sEV substantially inhibits tumor development and increases survival and CTL responses. [ABSTRACT FROM AUTHOR]

In the present study, we explored multiple plasma factors to predict the outcomes of patients with AIS after IVT. Fifty AIS patients who received IVT with alteplase were recruited and divided into two groups according to their NIHSS scores. Serum from all subjects was collected to quantitatively analyze the levels of different plasma factors, IL-6, MMP-9, ADAMTS13, TNC, GSN and TRX, using Luminex assays or ELISA measurements. Compared with the levels assessed at the onset of AIS, the levels of MMP-9 (P < 0.001), ADAMTS13 (P < 0.001), and TRX (P < 0.001) significantly decreased after IVT. The level of IL-6 was significantly increased in the NIHSS > 5 group at admission (P < 0.001) compared to the NIHSS ≤ 5 group. AIS patients with a poor prognosis had lower levels of ADAMTS13 at 72 h post-IVT compared with patients with a good prognosis (P = 0.021). IL-6 also was notably higher in the poor outcome group (P = 0.012). After adjusting for confounders, ADAMTS13 at 72 h post-IVT was an independent protective factor for prognosis in AIS patients with an adjusted OR of 0.07 (P = 0.049), whereas IL-6 was an independent predictor of risk for AIS patients with an adjusted OR of 1.152 (P = 0.028). IVT decreased MMP-9, ADAMTS13, and TRX levels in the plasma of AIS patients. Patients with a NIHSS score of less than 5 exhibited lower IL-6 levels, indicating that increased levels of IL-6 correlated with AIS severity after IVT. Therefore, IL-6 and ADAMTS13 might be useful plasma markers to predict the prognosis in AIS patients at 90-days after IVT. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory skin disease. Tissue stem cells have exhibited a therapeutic effect on psoriatic mice. However, the therapeutic effect of topical administration of the secretome derived from tissue stem cells on psoriasis has not been reported. Methods: The secretome from human amniotic epithelial cells (AEC-SC) and human umbilical cord mesenchymal stem cells (UMSC-SC) was topically administrated on the back of imiquimod-induced psoriasis-like mice. Subsequently, we observed the skin lesions and skin inflammation of psoriasis-like mice. Next, we further analyzed the paracrine factors in AEC-SC and UMSC-SC by protein chips. Lastly, the effect of the crucial paracrine factor was investigated by imiquimod-induced psoriasis-like mice. Results: We found that AEC-SC had a better therapeutic effect on attenuating psoriasis-like skin lesions including skin scales, skin redness and skin thickness than UMSC-SC, and it had a better regulatory effect on keratinocyte hyperproliferation and altered differentiation. Thus, we focused on AEC-SC. Further study showed that AEC-SC reduced the infiltration of neutrophils and interleukin-17-producing T cells. Next, the analysis of AEC-SC with protein chip revealed that the levels of anti-inflammatory factor interleukin-1 receptor antagonist (IL-1ra) were much higher in AEC-SC compared to that in UMSC-SC. More importantly, the beneficial effect of AEC-SC on psoriasis-like skin lesions and skin inflammation of mice were significantly impaired when neutralizing with IL-1ra antibody, while the recombinant human IL-1ra showed a less protective effect than AEC-SC. Conclusions: The present study demonstrated that AEC-SC could efficiently ameliorate psoriasis-like skin lesions and skin inflammation and IL-1ra plays an essential role. Therefore, topical administration of AEC-SC may provide a novel strategy for treating psoriasis-like inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Background: Emerging pathogenic bacteria are an increasing threat to public health. Two recently described species of the genus Aliarcobacter, A. faecis and A. lanthieri, isolated from human or livestock feces, are closely related to Aliarcobacter zoonotic pathogens (A. cryaerophilus, A. skirrowii, and A. butzleri). In this study, comparative genomics analysis was carried out to examine the virulence-related, including virulence, antibiotic, and toxin (VAT) factors in the reference strains of A. faecis and A. lanthieri that may enable them to become potentially opportunistic zoonotic pathogens. Results: Our results showed that the genomes of the reference strains of both species have flagella genes (flaA, flaB, flgG, flhA, flhB, fliI, fliP, motA and cheY1) as motility and export apparatus, as well as genes encoding the Twin-arginine translocation (Tat) (tatA, tatB and tatC), type II (pulE and pulF) and III (fliF, fliN and ylqH) secretory pathways, allowing them to secrete proteins into the periplasm and host cells. Invasion and immune evasion genes (ciaB, iamA, mviN, pldA, irgA and fur2) are found in both species, while adherence genes (cadF and cj1349) are only found in A. lanthieri. Acid (clpB), heat (clpA and clpB), osmotic (mviN), and low-iron (irgA and fur2) stress resistance genes were observed in both species, although urease genes were not found in them. In addition, arcB, gyrA and gyrB were found in both species, mutations of which may mediate the resistance to quaternary ammonium compounds (QACs). Furthermore, 11 VAT genes including six virulence (cadF, ciaB, irgA, mviN, pldA, and tlyA), two antibiotic resistance [tet(O) and tet(W)] and three cytolethal distending toxin (cdtA, cdtB, and cdtC) genes were validated with the PCR assays. A. lanthieri tested positive for all 11 VAT genes. By contrast, A. faecis showed positive for ten genes except for cdtB because no PCR assay for this gene was available for this species. Conclusions: The identification of the virulence, antibiotic-resistance, and toxin genes in the genomes of A. faecis and A. lanthieri reference strains through comparative genomics analysis and PCR assays highlighted the potential zoonotic pathogenicity of these two species. However, it is necessary to extend this study to include more clinical and environmental strains to explore inter-species and strain-level genetic variations in virulence-related genes and assess their potential to be opportunistic pathogens for animals and humans. [ABSTRACT FROM AUTHOR]

Background: Data on mental health improvement after cardiac rehabilitation (CR) are contradictory. The aim was to examine the mental and psycho-social health of patients admitted to our rehabilitation center following hospital treatment for acute coronary syndrome, before and after multidisciplinary CR.Methods: Outcome was measured at admission and discharge by the 36-Item Short Form Survey (SF-36), the Symptom Checklist-90 Revised (SCL-90R), the Coping Strategy Questionnaire (CSQ) and the 6-min-walking distance test. The patients' health status was compared with norms of sex-, age- and comorbidity-matched data from the German general population. Score differences from norms were measured by standardized mean differences (SMDs); health changes were quantified by standardized effect sizes (ESs). Their importance for comprehensive assessment was quantified by explorative factor analysis.Results: Of n = 70 patients followed-up (male: 79%; mean age: 66.6 years), 79% had ≥ 3 comorbidities. At baseline, SF-36 Physical functioning (SMD = - 0.75), Role physical (- 0.90), Social functioning (SMD = - 0.44), and Role emotional (SMD = - 0.45) were significantly worse than the norm. After CR, almost all scores significantly improved by ES = 0.23 (SCL-90R Interpersonal sensitivity) to 1.04 (SF-36 Physical functioning). The strongest factor (up to 41.1% explained variance) for health state and change was the mental health domain, followed by function & pain (up to 26.3%).Conclusions: Normative deficits in physical and psycho-social health were reported at baseline. After CR, at follow-up, all scores, except phobia, showed significant improvement. The comprehensive measurement of bio-psycho-social health should not be limited to depression and anxiety but include, especially, the somatization and social participation dimensions. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has become in the spotlight regarding the serious early and late complications, including acute respiratory distress syndrome (ARDS), systemic inflammation, multi-organ failure and death. Although many preventive and therapeutic approaches have been suggested for ameliorating complications of COVID-19, emerging new resistant viral variants has called the efficacy of current therapeutic approaches into question. Besides, recent reports on the late and chronic complications of COVID-19, including organ fibrosis, emphasize a need for a multi-aspect therapeutic method that could control various COVID-19 consequences. Human amniotic epithelial cells (hAECs), a group of placenta-derived amniotic membrane resident stem cells, possess considerable therapeutic features that bring them up as a proposed therapeutic option for COVID-19. These cells display immunomodulatory effects in different organs that could reduce the adverse consequences of immune system hyper-reaction against SARS-CoV-2. Besides, hAECs would participate in alveolar fluid clearance, renin–angiotensin–aldosterone system regulation, and regeneration of damaged organs. hAECs could also prevent thrombotic events, which is a serious complication of COVID-19. This review focuses on the proposed early and late therapeutic mechanisms of hAECs and their exosomes to the injured organs. It also discusses the possible application of preconditioned and genetically modified hAECs as well as their promising role as a drug delivery system in COVID-19. Moreover, the recent advances in the pre-clinical and clinical application of hAECs and their exosomes as an optimistic therapeutic hope in COVID-19 have been reviewed. [ABSTRACT FROM AUTHOR]

There are over 15 disease-modifying drugs that have been approved over the last 20 years for the treatment of relapsing-remitting multiple sclerosis (MS), but there are limited treatment options available for progressive MS. The development of new drugs for the treatment of progressive MS remains challenging as the pathophysiology of progressive MS is poorly understood.The progressive phase of MS is dominated by neurodegeneration and a heightened innate immune response with trapped immune cells behind a closed blood-brain barrier in the central nervous system. Here we review microglia and border-associated macrophages, which include perivascular, meningeal, and choroid plexus macrophages, during the progressive phase of MS. These cells are vital and are largely the basis to define lesion types in MS. We will review the evidence that reactive microglia and macrophages upregulate pro-inflammatory genes and downregulate homeostatic genes, that may promote neurodegeneration in progressive MS. We will also review the factors that regulate microglia and macrophage function during progressive MS, as well as potential toxic functions of these cells. Disease-modifying drugs that solely target microglia and macrophage in progressive MS are lacking. The recent treatment successes for progressive MS include include B-cell depletion therapies and sphingosine-1-phosphate receptor modulators. We will describe several therapies being evaluated as a potential treatment option for progressive MS, such as immunomodulatory therapies that can target myeloid cells or as a potential neuroprotective agent. [ABSTRACT FROM AUTHOR]

Objective: To gain insight into the molecular mechanisms underlying the early stages of vocal fold extracellular matrix (ECM) remodeling after a mid-membranous injury resulting from the use of human amniotic epithelial cells (hAEC), as a novel regenerative medicine cell-based therapy. Methods: Vocal folds of six female, New Zealand White rabbits were bilaterally injured. Three rabbits had immediate bilateral direct injection of 1 × 106 hAEC in 100 µl of saline solution (hAEC) and three with 100 µl of saline solution (controls, CTR). Rabbits were euthanized 6 weeks after injury. Proteomic analyses (in-gel trypsin protein digestion, LC–MS/MS, protein identification using Proteome Discoverer and the Uniprot Oryctolagus cuniculus (Rabbit) proteome) and histological analyses were performed. Results: hAEC treatment significantly increased the expression of ECM proteins, elastin microfibril interface-located protein 1 (EMILIN-1) and myocilin that are primarily involved in elastogenesis of blood vessels and granulation tissue. A reactome pathway analysis showed increased activity of the anchoring fibril formation by collagen I and laminin, providing mechanical stability and activation of cell signaling pathways regulating cell function. hAEC increased the abundance of keratin 1 indicating accelerated induction of the differentiation programming of the basal epithelial cells and, thereby, improved barrier function. Lastly, upregulation of Rab GDP dissociation inhibitor indicates that hAEC activate the vesicle endocytic and exocytic pathways, supporting the exosome-mediated activation of cell–matrix and cell-to-cell interactions. Conclusions: This pilot study suggests that injection of hAEC into an injured rabbit vocal fold favorably alters ECM composition creating a microenvironment that accelerates differentiation of regenerated epithelium and promotes stabilization of new blood vessels indicative of accelerated and improved repair. [ABSTRACT FROM AUTHOR]

Background: There is an existing perception that obesity has a negative impact on complications following total knee arthroplasty (TKA). However, data on the impact of obesity levels on patient-reported outcomes (PROMs) is sparse. We investigated the association between different obesity classes with PROMs among patients who underwent TKA.Methods: We performed retrospective secondary analyses on data extracted from the total joint replacement data repository (Alberta, Canada) managed by the Alberta Bone and Joint Health Institute (ABJHI). Patients had WOMAC and EQ5D scores measured at baseline in addition to 3 and/or 12 months following TKA. Patients were stratified according to the World Health Organization (WHO) classification, into five body mass index (BMI) groups of normal, overweight, BMI class I, BMI class II, and BMI class III. The association between BMI and mean changes in WOMAC subscales (pain, function, and stiffness) and EQ-5D-5L index over the time intervals of baseline to 3 months and 3 to 12 months following TKA was assessed. Linear mixed-effects models were used, and the models were adjusted for age, sex, length of surgery, comorbidities, year of surgery, and geographical zone where the surgery was performed.Results: Mean age was 65.5 years (SD = 8.7). Postoperatively, there was a significant improvement (p < 0.001) in WOMAC subscales of patient-reported pain, function, and stiffness, as well as EQ-5D-5L regardless of BMI group. Although, patients in BMI class II and class III reported significantly improved pain 3 months after TKA compared to those with normal BMI, all BMI groups attained similar level of pain reduction at 12 months after TKA. The greatest improvement in all WOMAC subscales, as well as EQ5D index, occurred between baseline and 3 months (adjusted p < 0.0001).Conclusion: The findings indicate that patients reported improved pain, function, and stiffness across all BMI groups following TKA. Patients with BMI classified as obese reported similar benefits to those with BMI classified as normal weight. These results may help health care providers to discuss expectations regarding the TKA recovery in terms of pain, function, and quality of life improvements with their TKA candidates. [ABSTRACT FROM AUTHOR]

The amniotic membrane (Amnio-M) has various applications in regenerative medicine. It acts as a highly biocompatible natural scaffold and as a source of several types of stem cells and potent growth factors. It also serves as an effective nano-reservoir for drug delivery, thanks to its high entrapment properties. Over the past century, the use of the Amnio-M in the clinic has evolved from a simple sheet for topical applications for skin and corneal repair into more advanced forms, such as micronized dehydrated membrane, amniotic cytokine extract, and solubilized powder injections to regenerate muscles, cartilage, and tendons. This review highlights the development of the Amnio-M over the years and the implication of new and emerging nanotechnology to support expanding its use for tissue engineering and clinical applications. [ABSTRACT FROM AUTHOR]