Clinical Demands Research Articles

Using a simplified version of Shaughnessy's guideline trustworthiness tool (G-TRUST) to help clinicians choose the most relevant guidelines for their practice

Reliance on trusted secondary sources, such as clinical practice guidelines, has emerged as a pragmatic solution for evidence-based practice. This editorial underscores the necessity of adapting medical education to equip clinicians with skills aligned with practical clinical demands and introduces a streamlined version of Shaughnessy's G-TRUST tool tailored for swift guideline assessment in clinical settings.

Navigating challenges and shaping futures through mental health nursing in the United Kingdom.

WHAT IS KNOWN ON THE SUBJECT?: Mental health nurses in the UK play a critical role in providing care, advocating for patients and navigating the complexities associated with mental health challenges. Acknowledging and supporting the efforts of mental health nurses is essential for advancing mental health care, promoting inclusivity and fostering community resilience amidst ongoing challenges within existing health care organisations. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Highlights the integral role of mental health nurses in the UK's health system as both care providers and advocates, underpinning the importance of addressing the growing demand for mental health services Introduces innovative digital tools like the 'Hub of Hope' and the potential of social prescribing as effective strategies for improving access to mental health care and support. Emphasises the need for enhanced support and recognition of mental health nurses to ensure the sustainable advancement of mental health services and the well-being of communities. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses should integrate innovative digital tools like the 'Hub of Hope' into their practice to improve signposting and access to mental health resources for individuals in need. There is a critical need for ongoing education and support for mental health nurses within practice settings to maintain their well-being and enhance their ability to provide holistic care despite increasing clinical demands. Advocacy for increased investment in mental health resources and support for research activities lead by mental health nurses is essential to address current service gaps and promote the development of more effective interventions.

Deep learning-based diagnosis and survival prediction of patients with renal cell carcinoma from primary whole slide images

There is an urgent clinical demand to explore novel diagnostic and prognostic biomarkers for renal cell carcinoma (RCC). We proposed deep learning-based artificial intelligence strategies. The study included 1752 whole slide images from multiple centres. Based on the pixel-level of RCC segmentation, the diagnosis diagnostic model achieved an area under the receiver operating characteristic curve (AUC) of 0.977 (95% CI 0.969-0.984) in the external validation cohort. In addition, our diagnostic model exhibited excellent performance in the differential diagnosis of RCC from renal oncocytoma, which achieved an AUC of 0.951 (0.922-0.972). The graderisk for the recognition of high-grade tumour achieved AUCs of 0.840 (0.805-0.871) in the Cancer Genome Atlas (TCGA) cohort, 0.857 (0.813-0.894) in the Shanghai General Hospital (General) cohort, and 0.894 (0.842-0.933) in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort, for the recognition of high-grade tumour. The OSrisk for predicting 5-year survival status achieved an AUC of 0.784 (0.746-0.819) in the TCGA cohort, which was further verified in the independent general cohort and the CPTAC cohort, with AUCs of 0.774 (0.723-0.820) and 0.702 (0.632-0.765), respectively. Moreover, the competing-risk nomogram (CRN) showed its potential to be a prognostic indicator, with a hazard ratio (HR) of 5.664 (3.893-8.239, p<0.0001), outperforming other traditional clinical prognostic indicators. Kaplan-Meier survival analysis further illustrated that our CRN could significantly distinguish patients with high survival risk. Deep learning-based artificial intelligence could be a useful tool for clinicians to diagnose and predict the prognosis of RCC patients, thus improving the process of individualised treatment.

Chronological adaptive polyoxometalate-based hydrogel for diabetic chronic wounds through synchronous bacterial ferroptosis death and immunomodulation

Chronic wounds are a serious complication for diabetic patients, causing substantial inconvenience and significant economic burden to patients, due to their characteristics of sequential development encountering bacterial infections, excessive reactive oxygen species (ROS)-induced inflammation and M1 macrophage accumulation. Herein, we developed a chronological adaptive Fe-based polyoxometalate on hyaluronic acid (Fe-POM@HA) hydrogel for diabetic chronic wounds, whose capacity can be strengthened by synergistic the acid-activated and glutathione-enhanced NIR-II photothermal therapy and achieving spatiotemporal selective and adaptive inhibition of bacterial infection. During the bacteria-infection slightly acidic stage, Fe-POM catalyzes endogenous H2O2 for ROS generation inducing bacterial ferroptosis, suppressing glutathione peroxidase activity, and promoting lipid peroxidation to disrupt the bacterial biofilm. As the wound transitions to neutral inflammation stage, Fe-POM with Fe2+/Mo5+ mixed valences can simultaneously alleviate oxidative stress and overcome the hypoxia microenvironment by continuously scavenging excessive ROS for endogenous H2O2 cyclic accumulation and O2 sustainable replenishment. Importantly, the Fe-POM@HA hydrogel could further promote wound angiogenesis at the new tissue proliferation stage through the immunomodulation of macrophage polarization and inflammatory factor expression. Therefore, Fe-POM@HA hydrogel provides a promising chronologically adaptive protocol for the repair and regeneration of chronic cutaneous wounds addressing complex clinical demands.

Dynamic Cross-Linking, Self-Healing, Antibacterial Hydrogel for Regenerating Irregular Cranial Bone Defects.

Given the widespread clinical demand, addressing irregular cranial bone defects poses a significant challenge following surgical procedures and traumatic events. In situ-formed injectable hydrogels are attractive for irregular bone defects due to their ease of administration and the ability to incorporate ceramics, ions, and proteins into the hydrogel. In this study, a multifunctional hydrogel composed of oxidized sodium alginate (OSA)-grafted dopamine (DO), carboxymethyl chitosan (CMCS), calcium ions (Ca2+), nanohydroxyapatite (nHA), and magnesium oxide (MgO) (DOCMCHM) was prepared to address irregular cranial bone defects via dynamic Schiff base and chelation reactions. DOCMCHM hydrogel exhibits strong adhesion to wet tissues, self-healing properties, and antibacterial characteristics. Biological evaluations indicate that DOCMCHM hydrogel has good biocompatibility, in vivo degradability, and the ability to promote cell proliferation. Importantly, DOCMCHM hydrogel, containing MgO, promotes the expression of osteogenic protein markers COL-1, OCN, and RUNX2, and stimulates the formation of new blood vessels by upregulating CD31. This study could provide meaningful insights into ion therapy for the repair of cranial bone defects.

Impact of Medical Trainees on Efficiency and Productivity in the Emergency Department: Systematic Review and Narrative Synthesis.

Effective medical education must balance clinical service demands for institutions and learning needs of trainees. The question of whether these are competing demands or can serve complementary roles has profound impacts on graduate medical education, ranging from funding decisions to the willingness of community-based hospitals and physicians to include learners at their clinical sites. Our objective in this article was to systematically review the evidence on the impact of medical trainees on productivity and efficiency in the emergency department (ED). We queried PubMed, Embase, Scopus, and Web of Science from earliest available dates to March 2023. We identified all studies evaluating the impact of medical students and/or residents in the ED on commonly used productivity and efficiency metrics. Only studies in EDs in the United States were included. No additional filters were used. We assessed the risk of bias of included studies using the Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) tool. Certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Study findings were combined in a narrative synthesis and reported according to PRISMA guidelines. The literature search yielded 3,390 unique articles for abstract screening. Eighty-one abstracts were identified as relevant to our PICO question (population, intervention, control, and outcomes), 76 of which had retrievable full-text articles and the themes of which were discussed in a narrative synthesis. We selected 13 of the full-text articles for final inclusion in a systematic review. Studies were roughly split between observational (6) and quasi-experimental (7) designs. The majority of studies (11) were single-site studies. Only two studies could be graded as low risk of bias per the ROBINS-I tool. Low-GRADE evidence suggests that students and residents decrease ED efficiency by a statistically small effect size of debatable clinical importance. Residents provide a moderate boost to ED productivity. Students do not produce a statistically or clinically significant impact on ED productivity. Residents increase emergency department relative value units revenue by $26.30 an hour, while students have no impact. Both types of learners decrease efficiency.

The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: A promising therapeutic compound against the cytokine storm.

The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-γ induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF-α & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NFκB using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF-α and IFN-γ, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 μM, 95% CI = 7.4 to 10.4 μM) was comparable to that of paracetamol (IC50 = 7.73 μM, 95% CI = 6.14 to 9.73 μM). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NFκB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

RGD and (−)-epigallocatechin-3-gallate modification enhanced biostability, bioactive and biofunctionality of acellular porcine cornea stroma crosslinked with oxidized dextran

The cornea is the main refractive element of the eye. Corneal transplantation is the foremost choice for addressing severe corneal diseases or trauma; however, corneal donors are difficult to meet the large clinical demand. Despite the clinical adoption of acellular porcine corneas stroma (APCS), their utility is limited by complications, such as post-implantation swelling, suture loosening, and rapid degradation. In this study, the APCS was crosslinked with oxidized dextran (ODEX) to enhance their biostability and preserve their original optical properties. Furthermore, to meet clinical indications in different pathological environments, it was double-modified with Arg-Gly-Asp (RGD) and (−)-epigallocatechin-3-gallate (EGCG) to prepare an artificial bio-cornea (OD-RE-APCS) with good bioactivity and biofunctionality. The results suggest that OD-RE-APCS effectively improves the mechanical, swelling, and degradation properties of APCS, enhances the adhesion, proliferation, and migration of corneal epithelial cells, and has anti-inflammatory, anti-oxidant and anti-angiogenic functions, which makes it a promising artificial bio-cornea.

P-112 Magnetic resonance spectroscopy at the micro scale (Micro-MRS) for non-invasively assessing individual mammalian embryos’ metabolism

Abstract Study question Can Micro-Magnetic Resonance Spectroscopy (micro-MRS) reveal the metabolic fingerprint of mammalian pre-implantation embryo? Summary answer Our research demonstrates that rapid, non-invasive analysis of embryos using Micro-Magnetic Resonance Spectroscopy (micro-MRS) can effectively uncover the significance of embryonic metabolites during development. What is known already Non-invasive selection of optimal embryos for transfer is a crucial challenge in assisted reproduction for both humans and animals. Magnetic Resonance Spectroscopy (MRS) emerges as a promising solution due to its chemical sensitivity and non-invasive nature. Despite its effectiveness in analysing large organisms, MRS faces obstacles in small sample handling and sensitivity, particularly with embryos, limiting its clinical and research applications. Our study overcomes these challenges using innovative microchip-based MRS sensors. This approach enabled successful MRS at the embryo scale, revealing metabolic biomarker linked to developmental potential in pre-implantation bovine embryos and opening new possibilities in assisted reproduction technology. Study design, size, duration Multiple MRS measuring sessions were conducted on two distinct embryo cohorts. The first cohort involved naturally arrested IVP embryos at early (8-cell) and late (morula/blastocyst) stages, establishing metabolic biomarkers in mammalian pre-implantation embryos. The second cohort involved 8-cell embryos which were further cultured over 10 days post-MRS with imaging at specific intervals (3 hours post-thawing, days 5, 8, and 10). This step was crucial to back-correlate biomarkers with in-vitro development based on bright field microscopy. Participants/materials, setting, methods Both studies involved vitrified samples that were subjected to a 50-minute MRS measurement following a 3-hour post-warming culture period. Single bovine embryo analysis was performed using our 1nL micro-MRS probe. Pre-implantation bovine embryos were obtained through IVF (n = 32 samples for cohort one and, n = 61 for cohort two). Post-MRS, the embryos were cultured in equilibrated IVC medium in a humidified incubator with 5% CO2 and 6% O2 at 38 °C. Statistical significance was set at p &amp;lt; 0.05. Main results and the role of chance Micro-Magnetic Resonance Spectroscopy (Micro-MRS) was utilized to identify metabolic markers in single bovine embryos, providing insights into their pre-implantation developmental stages. The spectroscopy data revealed distinct peak regions in the spectra of both cohorts, indicative of essential life-supporting fatty acids. Notably, up to six lipid markers were identified in the first cohort, five of which displayed statistically significant differences (p &amp;lt; 0.05). However, the majority of these biomarkers in the first cohort did not show significant expression differences in the groups of embryos assigned to the second cohort. An exception was noted in the case of the Principal Lipid Component (PLC) marker, which was significantly less prevalent in the arrested embryos than in those progressing to the blastocyst stage (p = 0.0016). Further data analysis based on AI-classification algorithms revealed up to 80% precision in predicting the development to the blastocyst stage solely based on their metabolic profiles at the 8-cell stage. Limitations, reasons for caution Magnetic Resonance Spectroscopy (MRS) shows promise for clinical and research use, requiring reliable signal detection from cellular components. While suitable for research, clinical deployment demands further safety assessments and protocol refinement. Additionally, larger sample sizes and data on post-MRS implantation and pregnancy rates are needed to validate AI-classification algorithms. Wider implications of the findings Micro-Magnetic Resonance Spectroscopy (Micro-MRS) holds potential as a reliable and non-invasive method for embryo screening prior to transfer. This innovative tool can shed light on the role of embryonic metabolites during development making Micro-MRS a key instrument in advancing both embryology research and human assisted reproduction techniques. Trial registration number not applicable

P-333 Combining deep shotgun metagenomic sequencing and culturomics for in-depth characterization of a potential endometrial microbiome

Abstract Study question Does the endometrium host a microbiome, and if so, are these taxa distinct from the vaginal/cervical microbiome? Summary answer Multifaceted analysis of endometrial tissue reveals no distinct microbial taxa compared to the vaginal/cervical samples, questioning whether detected microbiota are endometrium-related or result from cross-contamination. What is known already Recent studies suggest a role for the endometrial microbiota in reproductive health, yet the existence of an endometrial microbiome and its specific bacterial taxa remain enigmatic. The female reproductive tract, with a bacterial abundance gradient, is predominantly Lactobacillus-dominated in the lower region. Inconsistent findings on Lactobacillus dominance in endometrial samples are often ascribed to cross-contamination and methodological constraints, highlighting the need for precise methodologies in studying the low-biomass endometrial environment. Study design, size, duration Fifteen women, undergoing a diagnostic hysteroscopy and endometrial biopsy, as part of the subfertility work-up, were included in this study. Microbiota profiles of endometrial biopsies were compared to paired vaginal and cervical swabs from nine patients using 16S amplicon sequencing. Furthermore, the microbial composition of six additional endometrium biopsies was characterized using both a culturomics-based approach and deep metagenomic sequencing. Participants/materials, setting, methods Endometrial biopsies (n = 15) were taken with a sterile Pipelle de Cornier and snap-frozen in liquid nitrogen, followed by -80 °C storage and 16S amplicon sequencing (n = 9) targeting the V4-region or deep shotgun metagenomic sequencing (n = 6) (Prebiomics, Italy). Simultaneously, in nine women, paired cervical and vaginal swabs (Copan Diagnostics, Italy) were taken and preserved in eNAT medium. In six participants, an additional endometrial biopsy was collected and stored in Amies medium for immediate culturomics. Main results and the role of chance We observed a high similarity in the microbial composition of endometrial biopsies, cervical, and vaginal samples using 16 amplicon sequencing, but also some taxa were only found in the endometrial samples. Notably, the presence of Gemmobacter, a waterborne genus, was only found in endometrial biopsies and could be a source of contamination from water used during hysteroscopy to flush the uterus. Most endometrial microbiome profiles were Lactobacillus dominated, with exceptions observed in three patients. No significant differences for alpha diversity measures (richness and evenness) of the microbiota composition were observed between the different niches. For the first time we applied both culturomics and deep shotgun metagenomic sequencing for the characterization of the microbial composition in the same endometrial biopsies. Commonly identified genera using both techniques include Lactobacillus, Prevotella, Bifidobacterium, Anaerococcus, and Cuticubacterium. Remarkably, at the species level, the two approaches revealed almost no overlapping species within each biopsy, underscoring the importance of combining multiple methodologies in examining low-biomass niches like the endometrium. Limitations, reasons for caution A limitation of this study is the low-biomass nature of endometrial biopsies which are prone to cross-contamination with the lower female reproductive tract. This challenges downstream analysis, as it becomes difficult to distinguish between a relevant microbiological signal and contaminating noise. Wider implications of the findings This study emphasizes the need to consider a multifaceted microbiome approach when exploring low-biomass environments, like the endometrium. The critical consideration of potential cross-contamination by the lower female reproductive tract and its implications for downstream analysis is paramount in clinical microbiology research and demands meticulous handling. Trial registration number not applicable

Flipping the script: A multiyear assessment and comparison of flipped classroom versus traditional didactic teaching at two academic institutions

Rationale and objectivesHistorically radiology resident education has taken the form of workstation and didactic teaching. Due to increasing clinical demand and administrative burden for academic radiologists, the need for more efficient and effective teaching has increased. Flipped classroom teaching, where trainees independently learn material prior to interactive teaching sessions with faculty, is a possible alternative. While the use of flipped teaching in radiology has been studied in the medical student setting, its use in the radiology residency setting has been less published. Materials and methodsAt two academic institutions (University of Washington and Northwestern), exam scores from five PGY-2 Core rotations were collected. Flipped teaching was used for one rotation at the University of Washington (FR). The influence of teaching method, rotation, and institution on exam score was examined. Resident surveys were also collected to understand perceptions of flipped classroom teaching. ResultsAt the University of Washington, the mean exam score for the flipped rotation was significantly higher than the majority of other rotations utilizing traditional teaching (p<0.05). Between the University of Washington and Northwestern, there was no difference in exam scores when comparing comparable rotations. Among residents at the University of Washington, the flipped teaching rotation was perceived as more educationally valuable than traditional teaching rotations. ConclusionFlipped classroom teaching is at least as effective as the traditional teaching model and associated with better performance on standardized exams at one institution. Among residents, flipped learning is also associated with higher perceived educational value.

Eating Disorder and Other Psychiatric Hospitalizations in New Zealand During the COVID-19 Pandemic.

An unprecedented rise in eating disorder presentations has been documented in several countries during the COVID-19 pandemic. We explored this phenomenon by analyzing nationwide psychiatric admissions over 5 years, controlling for demographic variables. We retrospectively analyzed all hospitalizations in New Zealand with a primary psychiatric diagnosis from 2017 to 2021, using Poisson regression to calculate admission rates by diagnosis, before and during the pandemic. Using Fisher's exact test and Poisson modeling, national data were validated against a manually collected sample of eating disorder admissions. Eating disorder admissions rose significantly during the pandemic (RR 1.48, p < 0.0001), while other diagnoses remained unchanged or decreased slightly. Anorexia nervosa in 10 to 19-year-old females drove increases, with persistent elevations noted in the 10-14 age group. Pandemic-associated increases were more striking for Māori (RR 2.55), the indigenous Polynesian population, compared with non-Māori (RR 1.43). Eating disorder hospital presentations increased during the COVID-19 pandemic, while other psychiatric presentations to hospital remained relatively unchanged. Possible drivers include disrupted routines, barriers to healthcare access, altered social networks, and increased social media use. Clinical services require additional resources to manage the increased disease burden, especially in vulnerable pediatric and indigenous populations. Ongoing monitoring will be required to establish the time-course of pandemic-related clinical demand.

Addressing Burnout and Enhancing Well-Being Among Academic Physicians: A Call for Future Research and Organizational Support.

Description Burnout among academic physicians, who navigate multiple roles beyond the clinical environment, is a pressing issue. However, the factors driving burnout among academic physicians are not fully understood. Prior research has revealed differences in burnout dimensions between clinical and basic science faculty, but the impact of balancing research, education, and clinical demands on academic physicians is still unclear. This knowledge gap negatively affects the clinical, translational science, research, and medical education workforces and has particular implications for minoritized and marginalized groups working in academic medical centers. Creating a culture of well-being has been vital in addressing burnout. Further research is needed to explore the unique experiences and demands of academic physicians- particularly those from minoritized and marginalized backgrounds-and to develop effective strategies to promote well-being as they balance diverse roles and contexts. This commentary highlights gaps in understanding burnout among academic physicians and proposes guidelines for future research as well as strategies to improve well-being at academic medical centers.

Decision support strategies for bedside nursing clinical reasoning: A scoping review protocol

The aim of this scoping review is to map the evidence on self-instructed bedside decision strategies applied by nurses to support clinical reasoning. The ability to perform solid clinical reasoning is essential for providing healthcare with favourable patient outcomes. Accordingly, nurses should play an active role in developing clinical reasoning skills. Bedside support strategies are intended to be pragmatic, invaluable, and easy-to-apply resources to restructure cognitive processes when the clinical demands are complex. This review will consider studies that focus on bedside decision strategies, context-suitable, and practical to apply, self-instructed by nurses aimed to support nursing clinical reasoning. Studies focused on educational content, clinical case-specific studies, and studies related to software applications development or artificial intelligence will be excluded. The methodology will follow the JBI recommendations for scoping reviews. All published and unpublished sources of relevant evidence will be considered. Studies published in Portuguese, English, Spanish or Swedish will be included, without geographical or cultural limitations. Duplicates will be removed, and two independent reviewers will screen the abstracts and appraise the full text of the selected studies, based on the inclusion criteria. The results of the study selection will be summarized in a flowchart adapted from Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The overview of datasets will be presented in a narrative summary to provide a description of the existing evidence.

Hydrogel-Based 3D Bioprinting Technology for Articular Cartilage Regenerative Engineering.

Articular cartilage is an avascular tissue with very limited capacity of self-regeneration. Trauma or injury-related defects, inflammation, or aging in articular cartilage can induce progressive degenerative joint diseases such as osteoarthritis. There are significant clinical demands for the development of effective therapeutic approaches to promote articular cartilage repair or regeneration. The current treatment modalities used for the repair of cartilage lesions mainly include cell-based therapy, small molecules, surgical approaches, and tissue engineering. However, these approaches remain unsatisfactory. With the advent of three-dimensional (3D) bioprinting technology, tissue engineering provides an opportunity to repair articular cartilage defects or degeneration through the construction of organized, living structures composed of biomaterials, chondrogenic cells, and bioactive factors. The bioprinted cartilage-like structures can mimic native articular cartilage, as opposed to traditional approaches, by allowing excellent control of chondrogenic cell distribution and the modulation of biomechanical and biochemical properties with high precision. This review focuses on various hydrogels, including natural and synthetic hydrogels, and their current developments as bioinks in 3D bioprinting for cartilage tissue engineering. In addition, the challenges and prospects of these hydrogels in cartilage tissue engineering applications are also discussed.

Human Acellular Collagen Matrices-Clinical Opportunities in Tissue Replacement.

The field of regenerative medicine is increasingly in need of effective and biocompatible materials for tissue engineering. Human acellular dermal matrix (hADM)-derived collagen matrices stand out as a particularly promising candidate. Their ability to preserve structural integrity, coupled with exceptional biocompatibility, positions them as a viable choice for tissue replacement. However, their clinical application has been largely confined to serving as scaffolds. This study aims to expand the horizon of clinical uses for collagen sheets by exploring the diverse cutting-edge clinical demands. This review illustrates the clinical utilizations of collagen sheets beyond traditional roles, such as covering skin defects or acting solely as scaffolds. In particular, the potential of Epiflex®, a commercially available and immediately clinically usable allogeneic membrane, will be evaluated. Collagen sheets have demonstrated efficacy in bone reconstruction, where they can substitute the induced Masquelet membrane in a single-stage procedure, proving to be clinically effective and safe. The application of these membranes allow the reconstruction of substantial tissue defects, without requiring extensive plastic reconstructive surgery. Additionally, they are found to be apt for addressing osteochondritis dissecans lesions and for ligament reconstruction in the carpus. The compelling clinical examples showcased in this study affirm that the applications of human ADM extend significantly beyond its initial use for skin defect treatments. hADM has proven to be highly successful and well-tolerated in managing various etiologies of bone and soft tissue defects, enhancing patient care outcomes. In particular, the application from the shelf reduces the need for additional surgery or donor site defects.

Biomaterials Design for Human Body Repair

The global clinical demand for biomaterials is constantly increasing due to the aging population [...]

Full operating parameter recording as an essential component of the reproducibility of laser-tissue interaction and treatments.

The number and diversity of published peer-reviewed studies in the discipline of laser dentistry have grown considerably during the past 10 years. Within primary research, the development of protocols to guide and formulate clinical practice demands precision and ease of reproducibility. Errors in data acquisition and management may become amplified as the applied randomized clinical trials (RCTs) forge new levels of clinical diversity and predictability in the use of laser photonic energy in both ablative (surgical) and sub-ablative (photobiomodulation (PBM) or photodynamic therapy (PDT)) applications. A comprehensive range of empirical and computational operating parameters must be included in published studies to facilitate the uniformity of powerand time-related values of laser irradiation. Choosing the correct "tissue irradiation parameters" is difficult and depends on the pathology and symptoms, the surface area to be treated, laser wavelength, the thermal relaxation time of each targeted tissue, and controlling penetration depth of the light into tissues. Therefore, to allow the reproducibility of the results, it is recommended that authors mention with the greatest care and clarity the irradiation parameters used in their study. This paper outlines the concerns felt regarding the general shortfalls and proposes a minimum range of laser operating parameters that should be represented in future peer-reviewed publications.

Bowtie Nanoantenna LSPR Biosensor for Early Prediction of Preeclampsia.

The concentration of the placental circulating factor in early pregnancy is often extremely low, and the traditional prediction method cannot meet the clinical demand for early detection preeclampsia in high-risk gravida. It is of prime importance to seek an ultra-sensitive early prediction method. In this study, finite-different time-domain (FDTD) and Discrete Dipole Approximation (DDA) simulation, and electron beam lithography (EBL) methods were used to develop a bowtie nanoantenna (BNA) with the best field enhancement and maximum coupling efficiency. Bio-modification of the placental circulating factor (sFlt-1, PLGF) to the noble nanoparticles based on the amino coupling method were explored. A BNA LSPR biosensor which can specifically identify the placental circulating factor in preeclampsia was constructed. The BNA LSPR biosensor can detect serum placental circulating factors without toxic labeling. Serum sFlt-1 extinction signal (Δλmax) in the preeclampsia group was higher than that in the normal pregnancy group (14.37 ± 2.56 nm vs. 4.21 ± 1.36 nm), p = 0.008, while the serum PLGF extinction signal in the preeclampsia group was lower than that in the normal pregnancy group (5.36 ± 3.15 nm vs. 11.47 ± 4.92 nm), p = 0.013. The LSPR biosensor detection results were linearly consistent with the ELISA kit. LSPR biosensor based on BNA can identify the serum placental circulating factor of preeclampsia with high sensitivity, without toxic labeling and with simple operation, and it is expected to be an early detection method for preeclampsia.