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The Effect of Collagen Scaffold Structural Properties on Dental Pulp Stem Cells Viability and Survival
No full textDental pulp stem cells (DPSCs) seeded on a Collagen type I (Col I) scaffold has failed to produce dentine-like tissue in vivo. Therefore, an innovative approach is required to generate an optimal environment for these cells, enabling successful dental pulp regeneration. In response, we designed a variety of porous, cross-linked matrices composed of Col I, Collagen III (Col III), Collagen IV (Col IV), and Hyaluronic Acid ( HyA) to mimic the dental pulp extracellular matrix. Consequently, this study's primary objective was to investigate the biological response of DPSCs under different collagen concentrations within these scaffolds. The first task was to identify the optimal concentration of Col I, Col III and Col IV matrices that would facilitate viability and survival of DPSCs within 2D and 3D environments. Our observations revealed that a layer consisting solely of Col I (5μl/ml) or a combination of Col III and Col I (5μl/ml) is the ideal, low-toxic 2D environment for DPSCs viability and survival. Moreover, DPSCs gave the highest metabolic rate on 3D matrices composed of Col III (50 μl/ml) and Col I (5μl/ml) and on pure Collagen III (100 μl/ml). Moreover, DPSCs had well-organized architecture resembling connective-like tissue on a Col IV scaffold. Next, fabricated Col I scaffold with a stiffness of about 1kPa and an average pore size of 120μm supported DPSCs viability and survival. We used a softer HyA/Col IV scaffold as a control. DPSCs loaded on Col I scaffold showed significantly higher metabolicrate indicating that scaffold’s mechanical properties and increased stiffness determined better cellular viability. In conclusion, the higher stiffness of Col I scaffolds significantly enhanced the viability and survival of DPSCs. An increased concentration of Col III in scaffolds resulted in a better viability of DPSCs than pure Col I scaffold within the 3D environment. The scaffolds made of Col I and III and pure Col III may be a superior material to a traditional Col I matrix for enhancing DPSCs activity and survival. Col IV can be used to guide DPSCs polarization within matrix.</p
Right and left living donor nephrectomy and operative approach: a systematic review and meta-analysis of donor and recipient outcomes
No full textIntroduction: The left kidney is preferable in living donor nephrectomy (LDN). We aimed to investigate the safety and efficacy of right versus left LDN in both donor and recipients. A subgroup analysis of outcomes based on operative approach was also performed.
Methods: A systematic review and meta-analysis was performed as per PRISMA guidelines. Outcomes of interest were extracted from included studies and analysed.
Results: There were 31 studies included with 79,912 transplants. Left LDN was performed in 84.1 % of cases and right LDN in 15.9 %. Right LDN was associated with reduced EBL (P = 0.010), intra-operative complications (P = 0.030) and operative time (P = 0.006), but higher rates of conversion to open surgery (1.4 % vs 0.9 %). However, right living donor renal transplantation (LDRT) had higher rates of delayed graft function (5.4 % vs 4.2 %, P
Conclusion: Right LDRT has higher rates of delayed graft function and graft loss compared to left LDRT. Minimally-invasive surgical approaches potentially offer improved outcomes but further large-scale randomised controlled trials studies are required to confirm this finding.</p
Health care utilization and the associated costs attributable to cardiovascular disease in Ireland: a cross-sectional study
No full textBackground: Cardiovascular disease (CVD) is the leading cause of mortality and disability globally. We examined healthcare service utilization and costs attributable to CVD in Ireland in the period before the introduction of a major healthcare reform in 2016.Methods: Secondary analysis of data from 8113 participants of the first wave of The Irish Longitudinal Study on Ageing. Cardiovascular disease was defined as having a self-reported doctor's diagnosis of myocardial infarction, angina, heart failure, stroke, atrial fibrillation, or transient ischaemic attack. Participants self-reported the utilization of healthcare services in the year preceding the interview. Negative binomial regression with average marginal effects (AMEs) was used to estimate the incremental number of general practitioner (GP) and outpatient department (OPD) visits, accident and emergency department attendances and hospitalizations in population with CVD relative to population without CVD. We calculated the corresponding costs at individual and population levels, by gender and age groups.Results: The prevalence of CVD was 18.2% (95% CI: 17.3, 19.0) Participants with CVD reported higher utilization of all healthcare services. In adjusted models, having CVD was associated with incremental 1.19 [95% confidence interval (CI): 0.99, 1.39] GP and 0.79 (95% CI: 0.65, 0.93) OPD visits. There were twice as many incremental hospitalizations in males with CVD compared to females with CVD [AME (95% CI): 0.20 (0.16, 0.23) vs. 0.10 (0.07, 0.14)]. The incremental cost of healthcare service use in population with CVD was an estimated €352.2 million (95% CI: €272.8, €431.7), 93% of which was due to use of secondary care services.Conclusion: We identified substantially increased use of healthcare services attributable to CVD in Ireland. Continued efforts aimed at CVD primary prevention and management are required.</p
Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine
No full textMacrophages play a crucial role in immune responses and undergo metabolic reprogramming to fulfill their functions. The tetramerization of the glycolytic enzyme pyruvate kinase M2 (PKM2) induces the production of the anti-inflammatory cytokine interleukin (IL)-10 in vivo, but the underlying mechanism remains elusive. Here, we report that PKM2 activation with the pharmacological agent TEPP-46 increases IL-10 production in LPS-activated macrophages by metabolic reprogramming, leading to the production and release of ATP from glycolysis. The effect of TEPP-46 is abolished in PKM2-deficient macrophages. Extracellular ATP is converted into adenosine by ectonucleotidases that activate adenosine receptor A2a (A2aR) to enhance IL-10 production. Interestingly, IL-10 production induced by PKM2 activation is associated with improved mitochondrial health. Our results identify adenosine derived from glycolytic ATP as a driver of IL-10 production, highlighting the role of tetrameric PKM2 in regulating glycolysis to promote IL-10 production. </p
Potentials of presepsin as a novel sepsis biomarker in critically ill adults: correlation analysis with the current diagnostic markers
No full textBackground: Sepsis is a major cause of patient death in intensive care units (ICUs). Rapid diagnosis of sepsis assists in optimizing treatments and improves outcomes. Several biomarkers are employed to aid in the diagnosis, prognostication, severity grading, and sub-type discrimination of severe septic infections (SSIs), including current diagnostic parameters, hemostatic measures, and specific organ dysfunction markers.Methods: This study involved 129 critically ill adults categorized into three groups: sepsis (Se = 48), pneumonia (Pn = 48), and Se/Pn (33). Concentrations of five plasma markers (IL-6, IL-8, TREM1, uPAR, and presepsin) were compared with 13 well-established measures of SSI in critically ill patients. These measures were heart rate (HR), white blood count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lactate plasma concentrations, and measures of hemostasis status (platelets count (PLT), fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT), international normalization ratio (INR) and D-dimer). Plasma bilirubin and creatinine served as indicators of liver and kidney dysfunction, respectively.Results: Promising roles for these biomarkers were found. The best results were for presepsin, which scored 10/13, followed by IL-6 and IL-8 (each scored 7/13), and the worst were for TREM-1 and uPAR (scored 3/13). Presepsin, IL-6, and IL-8 discriminated between the SSI sub-types, whilst only presepsin correlated with bilirubin and creatinine. uPAR was positive for kidney dysfunction, and TREM-1 was the only indicator of artificial ventilation (AV).Conclusions: Presepsin is an important potential biomarker in SSIs. However, further work is needed to define this marker's diagnostic and prognostic cutoff values.</p
Green synthesis of metal nanoparticles using <i>Cinnamomum</i>-based extracts and their applications
No full textIntroduction: Nanotechnology is the science that deals with matter on the nanoscale, with sizes ranging from 1 to 100 nm. It involves designing, synthesising, characterising and applying these nanoscale materials. Nanoparticles (NPs) are known for their high surface-area to volume-ratio, surface charge density, low melting point, and distinguishably good optical/electrical properties. NPs exhibit an excellent drug delivery system, an effective contrast agent for vascular imaging, and effective antimicrobial activity. The biological synthesis of NPs is a simple, cost-effective, and environmentally friendly technique. This bottom-up technique utilises organisms' enzymes/bio-compounds and a plant extract as capping and reducing agents. Cinnamomum species are known for their intrinsic antimicrobial, antidiabetic, antioxidant, anti-inflammatory, anticancer, and neuroprotective properties. This review summarises articles that greenly synthesised NPs using Cinnamomum species' extracts, describing their methodologies, characterisation of the nanoparticles and their medical applications.Methods: A literature search has been conducted on databases PubMed, ScienceDirect, and Frontier on the green synthesis of metal nanoparticles (MNPs) using Cinnamomum-based extracts. Various articles reported the methodology of utilising Cinnamomum species' extracts as reducing and capping agents. Only original lab articles were considered.Results: Various types of MNPs have been successfully synthesised. The most common Cinnamomum species utilised as extracts is Cinnamomum tamala. The most common applications tested were the MNPs' antibacterial, antiviral, antifungal, antidiabetic and anticancerous activity. MNPs also had a role in treating mice-induced polycystic ovarian syndrome and Parkinson-like neurodegenerative diseases.Conclusion: Cinnamomum species have been successfully utilised in the green synthesis of various MNPs. Silver and Gold NPs were the most reported. These MNPs proved their efficacy in multiple fields of medicine and biology, especially their antibacterial, antiviral and antifungal activity. Notably, the newly synthesised NPs showed promising results in treating polycystic ovarian syndrome in rats.</p
Key considerations for a prostate cancer mRNA vaccine
No full textProstate cancer has the second highest cancer mortality rate in the UK in males. Early prostate cancer is typically asymptomatic, with diagnosis at a locally advanced or metastatic stage. In addition, the inherent heterogeneity of prostate cancer tumours differs significantly in terms of genetic, molecular, and histological features. The successful treatment of prostate cancer is therefore exceedingly challenging. Immunotherapies, particularly therapeutic vaccines, have been widely used in preclinical and clinical studies to treat various cancers. Sipuleucel-T was the first cancer vaccine approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), ushering in a new era of immunotherapy. In this review, the latest immunotherapy strategies for prostate cancer are considered with key tumour-associated antigens (TAA) and tumour-specific antigens (TSA) highlighted. The key components of mRNA vaccines include in vitro transcription, stability, and immunogenicity. Finally, strategies to circumvent in vivo mRNA degradation and approaches to optimise in vitro transcription (IVT) process are also discussed.</p
Identifying components of an enhanced recovery pathway for primary cleft palate repair: a scoping review
No full textObjective: This study aims to map the existing sources of evidence on perioperative care and recovery strategies for primary cleft palate repair, to identify elements that should be included in an enhanced recovery pathway (ERP), and to identify gaps in current knowledge.Design: Scoping review.Setting: ERPs are evidence-based, patient-centered, multimodal, perioperative care pathways designed to reduce surgical stress and improve postoperative outcomes and are increasingly being reported in the cleft lip and palate literature.Interventions: PubMed, Embase, Cochrane, and Scopus databases were searched. Results were uploaded to Covidence systematic review software. Studies were included for analysis if they described strategies or elements for enhanced recovery following primary cleft palate repair.Main outcome measures: ERP elements and outcome measures were recorded and collated.Results: Forty-seven studies were included. Frequently reported topics included anesthesia, peri-operative analgesia, and parent education. There was a dearth of evidence about peri-operative nursing care. Based on the extracted data, we propose that the following elements be included in any ERP for primary cleft palate repair: preoperative parent/caregiver education; minimization of preoperative fasting time; preoperative analgesia; local anesthetic nerve blocks; perioperative antibiotics and ondansetron; postoperative non-opioid analgesia; early postoperative oral feeding and discharge planning.Conclusions: The findings provide the framework to develop an institutional ERP for primary cleft palate repair. The positive contribution of consistent nursing care to enhanced recovery is obvious but under-investigated in the literature to date. The impact of ERPs on parent-reported outcomes also warrants further investigation.</p
Return to play following clavicular fracture – a systematic review and meta analysis
No full textBackground: Clavicular fractures are common injuries in athletes, constituting up to 10% of all sport-related fractures. The location and severity of these fractures influence treatment decisions, which can range from conservative to operative management. Concerns exist regarding complications and delayed return to play (RTP), particularly for displaced midshaft and lateral fractures. Despite numerous studies on RTP following clavicle fractures, there is a lack of recent systematic reviews presenting comprehensive data on RTP rates and influencing factors. This systematic review aims to provide an overview of RTP in athletes following clavicle fractures, including an examination of fracture type, location, and management strategies.Methods: This systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, identified 33 clinical studies through searches in PubMed, EMBASE, Cochrane, CINAHL, Web of Science, and Scopus databases. Two independent reviewers conducted study selection, data extraction, and quality assessment, with discrepancies resolved by a third reviewer. Studies reporting on RTP after clavicular fractures, published in English, were included.Results: The review included studies involving a total of 1087 patients, reflecting a range of fracture characteristics and patient demographics. Overall, the RTP rate was 91%, with 86% of athletes returning to the same level of play. Rates varied based on the fracture location, with medial fractures showing the highest RTP (100%) and lateral fractures the lowest (78%). Operative and nonoperative management demonstrated similar RTP rates (92% vs. 91%), but operatively managed patients had higher rates of RTP to the preinjury level (92% vs. 78%). The mean time to RTP was 3.1 months for operatively managed fractures and 3.9 months for those managed nonoperatively.Conclusion: High rates of RTP are seen for athletes managed both operatively and nonoperatively following a clavicular fracture. Effective management of lateral clavicular fractures remains an ongoing challenge. Patients with high functional demands need careful consideration to optimise RTP outcomes. While operative management may offer superior RTP to the preinjury level, the decision should consider potential complications and patient preferences. Standardized reporting of RTP outcomes is essential for future research to facilitate comparison and optimize management strategies.Level of evidence: Level III Systematic Review- Meta-Analysis</p
Applying advanced psychometric approaches yields differential randomized trial effect sizes: secondary analysis of individual participant data from antidepressant studies using the Hamilton rating scale for depression
No full textObjectives: As multiple sophisticated techniques are used to evaluate psychometric scales, in theory reducing error and enhancing the measurement of patient-reported outcomes, we aimed to determine whether applying different psychometric analyses would demonstrate important differences in treatment effects.Study design and setting: We conducted a secondary analysis of individual participant data (IPD) from 20 antidepressant treatment trials obtained from Vivli.org (n = 6843). Pooled item-level data from the Hamilton Rating Scale for Depression (HRSD-17) were analyzed using confirmatory factory analysis (CFA), item response theory (IRT), and network analysis (NA). Multilevel models were used to analyze differences in trial effects at approximately 8 weeks (range 4-12 weeks) post-treatment commencement, with standardized mean differences calculated as Cohen's d. The effect size outcomes for the original total depression scores were compared with psychometrically informed outcomes based on abbreviated and weighted depression scores.Results: Several items performed poorly during psychometric analyses and were eliminated, resulting in different models being obtained for each approach. Treatment effects were modified as follows per psychometric approach: 10.4%-14.9% increase for CFA, 0%-2.9% increase for IRT, and 14.9%-16.4% reduction for NA.Conclusion: Psychometric analyses differentially moderate effect size outcomes depending on the method used. In a 20-trial sample, factor analytic approaches increased treatment effect sizes relative to the original outcomes, NA decreased them, and IRT results reflected original trial outcomes.Plain language summary: This study aimed to determine if using advanced psychometrics methods would inform any clinically or statistically important differences in clinical trial outcomes when compared to original findings. We applied factor analysis (FA), item response theory (IRT), and network analysis (NA) to the most commonly used measure of depression in clinical settings - the Hamilton Rating Scale for Depression (HRSD) - to identify and remove nonperforming survey items and calculate weighted item scores. We found that the efficacy reported in trials increased when using FA to removed items, but decreased when using NA. There was almost no change in efficacy when using IRT. Using weighted scores based on respective models offered no additional utility in terms of increasing or decreasing efficacy outcomes.</p