Post Injection Research Articles

Intra-articular corticosteroid injections versus platelet-rich plasma as a treatment for cervical facetogenic pain: a randomized clinical trial

ObjectiveThe study’s primary objective was to compare the effectiveness of intra-articular platelet-rich plasma injections versus corticosteroid injections for the treatment of cervical facetogenic pain. Secondary aims were to compare self-rated...

Abstract 4126304: A Cardiac Targeting Peptide Linked to miRNA106a Targets and Suppresses Genes Known to Cause Heart Failure: Reversing Heart Failure at the Source

Background: About one in five adults at age 40 will develop heart failure (HF) during their lifetime. Risk factors for HF (e.g., hypertension, etc.) alter cardiomyocytes structure and function resulting in HF. At the cellular level, these changes consist of mis/over-expression of genes that regulate cardiac identity (e.g., CamK2d, PKC, etc). The current paradigm for treating HF is pharmacological intervention or surgery; however, with few exceptions, the condition worsens with time. We are proposing a paradigm-shift for treating HF from a drug-centric system to a molecular approach that would reverse hypertrophy and adverse remodeling. Methods: A cardiac targeting peptide (CTP) was generated and linked by disulfide bond to miRNA106a, which was then introduced into a HF mouse model to measure its ability to reverse multiple heart failure parameters. CTP-miRNA106a was also introduced into a human cardiac cell line, followed by multiple analyses including Western Blot, qPCR, FACS, immunofluorescence all used to identify mechanism(s) utilized by CTP-miRNA106a to reverse HF characteristics. Results: Bio-distribution studies showed CTP delivered its miRNA106a cargo specifically to the heart within 30 mins, followed by clearance of CTP from the heart to the kidneys and liver by 3-5hrs post systemic drug injection. MiRNA106a persisted in cardiomyocytes until day 7 (latest tested time-point). CTP-miRNA106a reversed Ang2/Iso induced hypertrophy in 90% of the experimental mice ( Fig1 ). We also identified two potential HF intracellular signaling mechanisms (PLCb1/PKC/IP3 and NfkB) targeted by CTP-miRNA106a that could benefit both types of HF, HFrEF and HFpEF. PLCβ1 is a direct target for miRNA106a while the Nfkb pathway is indirectly targeted by decreased Camk2d (an miRNA106a target) signaling to IκBα. NfkB activity is quelled by miRNA106a. Conclusions: Our approach utilizes the function of miRNA106a to downregulate genes involved in cardiac hypertrophy and inflammation through the PLCb1 and CamKIId/Nfkb pathways. Most importantly, using a CTP-miRNA106a, we show delivery of miRNA106a cargo is specific to cardiomyocytes both in vitro and in vivo and that once delivered, many HF parameters including hypertrophy are reversed.

Optimisation of Animal Handing and Timing of 2-deoxy-2-[18F]fluoro-D-glucose PET Tumour Imaging in Mice.

In humans, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) tumour-to-background contrast continues to increase long after a typical uptake period of 45 - 60min. Similar studies have not been performed in mice and the static imaging time point for most studies is arbitrarily set at 30 - 60min post-injection of [18F]FDG. Ideally, static PET imaging should be performed after the initial period of rapid uptake but this period has not been defined in mice, with previous dynamic studies in mice being limited to 60min. This study aimed to define the kinetics of [18F]FDG biodistribution over periods of 3 - 4h in different murine tumour models, both subcutaneous and autochthonous, and to further refine fasting and warming protocols used prior to imaging. Dynamic [18F]FDG PET-CT scans lasting 3 or 4h were performed with C57BL/6J and Balb/c nude mice bearing subcutaneous EL4 murine T-cell lymphoma and Colo205 human colorectal tumours, respectively, and with transgenic Eμ-Myc lymphoma mice. Prior to [18F]FDG injection, four combinations of different animal handling conditions were used: warming for 1h at 31°C; maintenance at room temperature (20 - 24°C), fasting for 6 - 10h and a fed state. Tumour mean standardised uptake value (SUVmean) peaked at 147 ± 48min post injection in subcutaneous tumours and 74 ± 31min in autochthonous Eμ-Myc lymphomas. The tumour-to-blood ratio (TBR) peaked at 171 ± 57 and 83 ± 33min in subcutaneous and autochthonous Eμ-Myc tumours, respectively. Fasting increased tumour [18F]FDG uptake and suppressed myocardial uptake in EL4 tumour-bearing mice. There was a good correlation between tumour SUVmean and Ki calculated using an input function (IDIF) derived from the inferior vena cava. Delayed static [18F]FDG-PET imaging (> 60min) in both autochthonous and subcutaneous tumours in improved tumour-to-background contrast and increased reproducibility.

Targeting c-MET for Endoscopic Detection of Dysplastic Lesions Within Barrett's Esophagus Using EMI-137 Fluorescence Imaging.

Esophageal cancer (EC) carries a poor prognosis with 5-year overall survival of less than 20%. Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). The aim of this study was to investigate the ability of EMI-137, a mesenchymal-epithelial transition factor (c-MET)-targeting optical imaging tracer, to detect dysplasia in BE. c-MET expression in human esophageal tissue was investigated using Gene Expression Omnibus (GEO) datasets, tissue microarrays and BE biopsies. EMI-137 was tested in a dual xenograft mouse model bearing OE33 (c-MET high expression) and FLO-1 (c-MET low expression) tumors. Fluorescence molecular endoscopy (FME) was performed in a mouse model of Barrett's-like metaplasia and dysplasia (L2-IL1β). Tumors and organs-of-interest were evaluated through ex vivo fluorescence imaging. MET mRNA expression analyses and c-MET immunostaining confirmed upregulation of c-MET in BE and EAC compared to normal epithelium. There was strong accumulation of EMI-137 in OE33 xenografts 3 h post injection decreasing by more than 50% on co-injection of a 10-fold molar excess of unlabeled EMI-137. The target-to background ratio (TBR) at 3 h p.i. for OE33 and FLO-1 tumors was 10.08 and 1.42, respectively. FME of L2-IL1β mice showed uptake of EMI-137 in dysplastic lesions within BE with a TBR of 1.9 in vivo, and greater than 2 in ex vivo fluorescence imaging. EMI-137 accumulates in dysplastic lesions within BE and in c-MET positive EAC. EMI-137 imaging has potential as a screening and surveillance tool for patients with BE and as a means to detecting dysplasia and EAC.

Safety and Efficiency of Anti-VEGF with Dexamethasone Intravitreal Implant for Non-Ischemic Retinal Vein Occlusion: A Prospective, Case-controlled, Cohort Study.

This study aimed to assess the efficacy and safety of anti-VEGF combined with dexamethasone implant for the retinal vein occlusion patients with macular edema. In this prospective, case-controlled, cohort clinical trial (Register ID: ChiCTR2400080048), patients with non-ischemic retinal vein occlusion were enrolled from the Sanmenxia Central Hospital from August 2020 to April 2023. The patients were randomized into two groups. All the patients received ranibizumab intravitreal injection in the first 3 consecutive months. For the ranibizumab group, anti-VEGF injections were as needed thereafter in case of recurrence of macular edema; For the combination group, the patients received an intravitreal dexamethasone implant injection at 15 days after the first ranibizumab injection. The primary outcome measurements were improvement in best corrected visual acuity (BCVA) and reduction in central macular thickness (CMT). The secondary outcomes were recurrence of macular edema, number of intravitreal injections, and injection interval. Safety profiles were also recorded. A total of 124 patients were included, of which 73 patients completed all follow-ups. Both the ranibizumab monotherapy and the combination therapy significantly improved BCVA at all time points, compared to the baseline. The combined group achieved more BCVA improvement in 3 months, 6 months, and 12 months, compared to the ranibizumab alone group. Compared to the baseline, both groups achieved significant reductions in CMT at all follow-ups. However, the combination group showed more CMT reduction at 1 week post injection, compared to the ranibizumab group. The combination group had a significantly longer injection interval, lower injection time, and recurrence of macular edema. Ocular hypertension was the most common adverse events. Lastly, intraocular pressure was all well controlled by 1-3 glaucoma medications without surgical intervention. The combination therapy could significantly improve the BCVA and reduce the CMT with a good safety profile.

Assessment of TIMI frame count pre- and post- intracoronary acetylcholine administration in patients with angina and non-obstructive coronary arteries (ANOCA)

Abstract Background Patients with Angina and unobstructed coronary arteries (ANOCA) represent a diagnostic challenge. Current ESC guidelines on the management of patients with chronic coronary syndrome recommend intracoronary spasm testing and coronary spasm represents a frequent diagnosis in such patients. Previous studies have shown that coronary artery flow assessments during acetylcholine testing frequently show non-uniform results. Purpose The aim of the present study was to assess changes in TIMI Frame Count (a quantitative method for the assessment of coronary artery flow) pre- and post- intracoronary acetylcholine testing in patients with ANOCA. Methods From 2007 to 2018, a total of 141 consecutive patients (51.8% female, mean age 61 ± 13.2 years) were included in the study. Among them, 63 patients (45%) presented with myocardial infarction with unobstructed coronary arteries, while 78 patients (55%) presented with stable angina and unobstructed coronaries. Following diagnostic angiography, all patients underwent intracoronary acetylcholine testing using a standardized protocol. TIMI frame count (TFC) was measured both for LAD and LCX before and after ACh injection, and post nitroglycerine injection. All counted frames were adjusted to a frame rate of 30 frames per second (fps). Furthermore, TFC of the LAD was divided by 1.7 to obtain the corrected TFC (cTFC). Results Of all 141 patients, coronary spasm was found in 98 patients (70%) during ACh testing (44% epicardial and 56% microvascular spasm). In the spasm cohort, the median cTFC in the LAD pre-ACh was 21.8 fps (quartiles: 16.3 – 30.0), decreased to 12.9 fps (8.8 - 19.2) post-ACh, and increased to 15.9 fps (10.6 - 21.3) post-nitro. The difference in the LAD between pre-ACh and post-ACh was statistically significant (p < 0.001). In the LCX the median TFC was 26.5 fps (15.0 – 40.5) pre-ACh, decreased to 16.0 fps (11.5 - 28.5) post-ACh and reached 24.0 fps (15.5 - 33.3) post-nitro. Again, this reduction from pre-ACh to post-ACh was statistically significant (p < 0.001). In the negative spasm cohort median cTFC for the LAD was 22.9 fps (16.0 – 18.2) pre-Ach, 15.3 fps (9.4 – 24.7) post-ACh and 15.8 fps (10.6 - 24.7) post-nitro, TFC for LCX was 24.0 fps (18.0 - 36.0) pre-ACh, 18.0 fps (12.0 – 33.0) post-ACh and 24.0 fps (12.0 – 34.0) post-nitro. The change in cTFC/TFC pre-ACh compared to post-ACh was statistically significant for both coronary arteries (LAD, p=0.012; LCX p=0.005, Table 1). Interestingly, in the spasm cohort 22% of LAD and 32% of LCX vessels showed higher TFC post-ACh compared to pre-ACh (Figure 1). Conclusions In patients with ANOCA and coronary spasm assessment of TIMI frame count reveals a hetereogeneous response. The majority of cases shows a decrease in TFC suggesting an increase in flow despite coronary spasm. This interesting finding allows speculations about the presence of coronary shunts.Figure 1

First‐in‐human orbital tumor surgery guided by near‐infrared II window fluorescence imaging: A feasibility study

AbstractPrecise resection of orbital tumors is a critically important but elusive issue. Fluorescence imaging in the near‐infrared II window (NIR‐II) holds the potential to provide the surgeons with real‐time identification for orbital tumors. Here, for the first time, we evaluated the feasibility and clinical value of NIR‐II fluorescence imaging in orbital tumor surgery. To establish the method of NIR‐II fluorescence imaging for orbital tumors, we developed a NIR‐II fluorescence imaging system and indocyanine green (ICG) served as the fluorescent contrast agent. Twenty‐two patients diagnosed with orbital tumors and scheduled for standard‐of‐care surgery were enrolled in this study. Time‐course NIR‐II fluorescence imaging of two patients with superficial orbital tumors showed the optimum imaging time was 2 h post injection of ICG. Fifteen patients were allocated for diagnostic test, which showed that both the in situ and ex vivo NIR‐II fluorescence imaging showed better sensitivity and specificity than the surgeon judgment. In the feasibility trial of the remaining five patients, the surgeon encountered 34 suspicious regions and surgical decisions were changed nine times due to NIR‐II fluorescence imaging. The resultant seven additional resections were justified by histopathology and the two conservative treatments did not result in recurrence. Based on these findings, we suggested that ICG‐based NIR‐II fluorescence imaging was feasible to guide precise resection of orbital tumors. A future randomized controlled trial with a larger cohort is encouraged to further verify the clinical value.

Synthesis and Evaluation of 68Ga- and 177Lu-Labeled [Pro14]bombesin(8-14) Derivatives for Detection and Radioligand Therapy of Gastrin-Releasing Peptide Receptor-Expressing Cancer.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of cancers and represents a promising target for diagnosis and therapy. However, the extremely high accumulation in the pancreas observed for most of the clinically evaluated GRPR-targeted radiopharmaceuticals could limit their applications. In this study, we synthesized one GRPR antagonist (ProBOMB5) and two GRPR agonists (LW02056 and LW02057) by replacing the 4-thiazolidinecarboxylic acid (Thz14) residue in our previously reported GRPR-targeted tracers with Pro14. The 68Ga and 177Lu labeling were conducted in HEPES (2 M, pH 5.0) buffer and acetate (0.1 M, pH 4.5) buffer, respectively, and the radiolabeled products were obtained in a 24-57% decay-corrected radiochemical yield and >92% radiochemical purity. The binding affinities (Ki) of Ga-ProBOMB5, Ga-LW02056, Ga-LW02057, and Lu-ProBOMB5 were measured via in vitro competition binding assays and were 12.2 ± 1.89, 14.7 ± 4.81, 13.8 ± 2.24, and 13.6 ± 0.25 nM, respectively. The PET imaging and ex vivo biodistribution studies were conducted in PC-3 tumor-bearing mice at 1 h post injection. [68Ga]Ga-ProBOMB5, [68Ga]Ga-LW02056, and [68Ga]Ga-LW02057 enabled clear tumor visualization in PET images. The tumor uptake values of [68Ga]Ga-ProBOMB5, [68Ga]Ga-LW02056, and [68Ga]Ga-LW02057 were 12.4 ± 1.35, 8.93 ± 1.96, and 7.64 ± 0.55%ID/g, respectively, and their average pancreas uptake values were minimal (0.60-1.37%ID/g). Longitudinal SPECT imaging and ex vivo biodistribution studies were also conducted for [177Lu]Lu-ProBOMB5 and clinically validated [177Lu]Lu-RM2. Despite comparable tumor uptake at 1 h post injection ([177Lu]Lu-ProBOMB5:8.09 ± 1.70%ID/g; [177Lu]Lu-RM2:7.73 ± 0.96%ID/g), a faster clearance from PC-3 tumor xenografts was observed for [177Lu]Lu-ProBOMB5, leading to a lower radiation-absorbed dose delivered to tumors. Our data demonstrate that [68Ga]Ga-ProBOMB5 is a promising tracer for clinical translation for detecting GRPR-expressing tumor lesions. However, further optimizations are needed for [177Lu]Lu-ProBOMB5 to prolong tumor retention for therapeutic applications.

Application of immunoinformatics to develop a novel and effective multiepitope chimeric vaccine against Variovorax durovernensis

Bloodstream infections pose a significant public health challenge caused by resistant bacteria such as Variovorax durovernensis, a recently reported Gram-negative bacterium, worsening the burden on healthcare systems. The design of a vaccine using chimeric peptides derived from a representative V. durovernensis strain holds significant promise for preventing disease onset. The current study aimed to employ reverse vaccinology (RV) approaches such as the retrieval of V. durovernensis proteomics data, removal of redundant proteins by CD-HIT, filtering of non-homologous proteins to humans and essential proteins, identification of outer membrane (OM) proteins by CELLO and PSORTb. Following these steps immunoinformatic approaches were applied, such as epitope prediction by IEDB, vaccine design using linkers and adjuvant and analysis of antigenicity, allergenicity, safety and stability. Among the 4208 nonredundant proteins, an OmpA family protein (A0A940EKP4) was designated a potential candidate for the development of a multiepitope vaccine construct. Upon analysis of OM protein, six immunodominant (B cell) epitopes were found on the basis of the chimeric construct following the prediction of CTL stands cytotoxic T lymphocyte and HTL stands helper T lymphocyte epitopes. To ensure comprehensive population coverage globally, the CTL and HTL coverage rates were 58.18 % and 46.56 %, respectively, and 77.23 % overall. By utilizing EAAAK, GPGPG, and AAY linkers, Cholera toxin B subunit adjuvants, and appropriate epitopes were smoothly incorporated into a chimeric vaccine effectively triggering both adaptive and innate immune responses. For example, the administered antigen showed a peak in counts on the fifthday post injection and then gradually declined until the fifteenth day. Elevated levels of several antibodies (IgG + IgM > 700,000; IgM > 600,000; IgG1 + IgG2; IgG1 > 500,000) were observed as decreased in the antigen concentration. Molecular dynamics simulations carried out via iMODS revealed strong correlations between residue pairs, highlighting the stability of the docked complex. The designed vaccine has promising potential in eliciting specific immunogenic responses, thereby facilitating future research for vaccine development against V. durovernensis.

Proposal of a Theoretically Feasible Method to Perform Perilymph Sampling in Clinical Settings

The ability to analyze perilymph could allow inner ear pathologies to be studied. However, today, perilymph sampling is only performed for research purposes because of the risk of negative outcomes such as hearing loss or balance disorders. This paper aims to analyze the current literature on perilymph sampling and propose a method to collect perilymph in clinical settings. The published literature on perilymph sampling and its analyses was screened, and the results were analyzed and discussed in this mini review. Also, articles that discussed microneedle technology were reviewed and included in the analysis of the data. Based on the results of this review, we would like to propose a feasible technique to perform perilymph sampling in clinical settings. A total of eight studies analyzing perilymph were identified; data on proteomic, metabolomic and miRNA features present within human perilymph were collected and described. Two articles describing the use and auditory outcomes post microneedle drug injection into the inner ear were identified. Based on the methods for perilymph sampling described in humans and the recent innovations introduced by the use of microneedles, we suggested a feasible method to collect perilymph in the outpatient setting. The analysis of perilymph undoubtedly represents a valid instrument to fully understand inner ear diseases. A combination of traditional and innovative techniques, such as gaining access to the round window through the transcanalar approach using micro-endoscopes and microneedles to perform sampling, might simplify the sampling procedure and make it practicable in a clinical setting.

Intravenous Bolus Injection of Fentanyl Triggers an Immediate Central and Upper Airway Obstructive Apnea via Activating Vagal Sensory Afferents.

Intravenous bolus (IVb) injection of fentanyl induces an immediate apnea, but the characteristics of the apnea and relevant mechanism remain unclear. Here, we tested whether IVb injection of fentanyl induced an immediate central and upper airway obstructive apnea associated with chest wall rigidity via activating vagal C-fibers (VCFs) and vagal afferent opioid receptors (ORs). Cardiorespiratory and electromyography of external and internal intercostal, thyroarytenoid and superior pharyngeal constrictor muscles (EMGEI, EMGII, EMGTA and EMGSPC) responses to IVb injection of fentanyl were recorded in anesthetized and spontaneously breathing rats with or without bilateral peri-vagal capsaicin treatment or intra-vagal microinjection of naloxone. Immunohistochemical approach was employed to define the presence of opioid mu-receptor (MOR) expression in vagal C-neurons and a patch clamp technique utilized to determine the evoked current responses of vagal C-neurons to fentanyl in vitro. Fentanyl induced an immediate apnea and subsequent respiratory depression. The apnea was characterized by cessation of EMGEI activity and augmentation of tonic discharges of EMGII, EMGTA, and EMGSPC, i.e., central expiratory apnea, laryngeal closure and pharyngeal constriction/collapse accompanied with chest wall rigidity. The apneic response was abolished by blockade of VCF signal conduction and largely attenuated by antagonism of vagal afferent ORs. The latter significantly alleviated the initial (within 5 min post injection), but not the later, respiratory depression. Vagal C-neurons expressed MORs and were activated by fentanyl. We conclude that IVb injection of fentanyl causes a VCF- and vagal afferent OR-mediated immediate central apnea, upper airway obstruction and chest wall rigidity.

Novel TSPO Ligand 2-Cl-MGV-1 Can Counteract Lipopolysaccharide Induced Inflammatory Response in Murine RAW264.7 Macrophage Cell Line and Lung Models.

We assessed the anti-inflammatory activity of the TSPO ligand 2-Cl-MGV-1. Lipopolysaccharide (LPS) was used to induce inflammatory response in a murine RAW264.7 macrophage model (LPS: 100 ng/mL) and a mouse model (C57BL/6) of lung inflammation (LPS: 5 mg/kg). In the macrophage model, the presence of 2-Cl-MGV-1 (25 µM) caused the LPS-induced elevation in nitrite levels to decrease by 70% (p < 0.0001) and interleukin (IL)-6 by 50% (p < 0.05). In the mouse model, 2-Cl-MGV-1, administered 30 min before, or co-administered with, an LPS injection, significantly inhibited the elevation in serum IL-5 levels (both by 65%; p < 0.001 and p < 0.01, respectively). 2-Cl-MGV-1 administration to mice 30 min before LPS injection and 1 h thereafter significantly inhibited the elevation in IL-1β serum levels (both by 63%, p < 0.005). IL-6 elevation was inhibited by 73% (p < 0.005) when 2-Cl-MGV-1 was administered 30 min before LPS, by 60% (p < 0.05) when co-administered with LPS, and by 64% (p < 0.05) when administered 1 h after LPS. All cytokine assessments were conducted 6 h post LPS injection. Histological analyses showed decreased leukocyte adherence in the lung tissue of the ligand-treated mice. 2-Cl-MGV-1 administration 30 min prior to exposure to LPS inhibited inflammation-induced open field immobility. The beneficial effect of 2-Cl-MGV-1 suggests its potential as a therapeutic option for inflammatory diseases.

Novel anti-CEA affibody for rapid tumor-targeting and molecular imaging diagnosis in mice bearing gastrointestinal cancer cell lines.

Gastrointestinal cancer is a common malignant tumor with a high incidence worldwide. Despite continuous improvements in diagnosis and treatment strategies, the overall prognosis of gastrointestinal tumors remains poor. Carcinoembryonic antigen (CEA) is highly expressed in various types of cancers, especially in gastrointestinal cancers, making it a potential target for therapeutic intervention. Therefore, the expression of CEA can be used as an indication of the existence of tumors, chosen as a target for molecular imaging diagnosis, and effectively utilized in the targeted therapy of gastrointestinal cancers. In this study, we report the selection and characterization of affibody molecules (ZCEA539, ZCEA546, and ZCEA919) specific to the CEA protein. Their ability to bind to recombinant and native CEA protein has been confirmed by surface plasmon resonance (SPR), immunofluorescence, and immunohistochemistry assays. Furthermore, Dylight755-labeled ZCEA affibody showed accumulation within the tumor site 1 h post injection and was continuously enhanced for 4 h. The Dylight755-labeled ZCEA affibody exhibited high tumor-targeting specificity in CEA+ xenograft-bearing mice and possesses promising characteristics for tumor-targeting imaging. Overall, our results suggest the potential use of ZCEA affibodies as fluorescent molecular imaging probes for detecting CEA expression in gastrointestinal cancer.

A novel approach of in-cylinder NOx control by inner selective non-catalytic reduction effect for high-pressure direct-injection ammonia engine

As an efficient hydrogen carrier and carbon-free fuel, ammonia shows great promise in realizing zero-carbon propulsions. However, challenges such as poor ignition stability, low combustion efficiency, and fuel-NOx emissions are yet to overcome. In this paper, the high-pressure direct-injection ammonia/diesel dual-fuel combustion mode (HPDF) with post injection strategy is proposed as a solution. The study reveals that HPDF combustion mode enables in-cylinder reduction of NOx, which is attributed to the selective non-catalytic reduction (SNCR) reaction. The results uncover that NH2, NH, and N radicals have a significant reducing effect on NO and NO2, while N2O serves as an important byproduct of the reduction reactions. Subsequently, the generated N2O can be further reduced to N2 through the involvement of O, H, and OH radicals. Building upon these findings, an innovative ammonia post injection method for reducing NOx emissions is explored. The post injection strategy effectively reduces the NOx emissions with only a minor decrease in indicated thermal efficiency, but an over-delayed post injection could also cause significant increase in N2O and unburned NH3 emissions. A post injection proportion of 20%-30% with appropriate post injection timing is found to achieve desired emission reduction. Overall, the HPDF combustion mode is a promising solution for ammonia engine, due to the high thermal efficiency and low nitrogen oxide emissions, as well as the ability to further reduce the NOx emissions through ammonia post injection strategy.

Correlation of perfusion index change and analgesic efficacy in transforaminal steroid injection for lumbosacral pain, a prospective observational study

Background and Aims: Low back pain is a common problem and a major burden to society. Transforaminal epidural steroid injection is one of the most effective treatment modalities for back pain. We aim to objectively quantify pain relief of lumbosacral radicular pain post transforaminal steroid injection by correlating perfusion index (PI), reflecting real-time peripheral blood flow change at the site of monitoring, controlled by sympathetic system with Numerical rate score (NRS) and SLRT improvement. Material and Methods: A prospective observational study, conducted at K.S Hegde Medical Academy, Mangaluru, from June 2021 to June 2022 as a time-bound study. After IEC clearance (IEC certificate number) for the procedure and study, patients undergoing transforaminal epidural steroid injection for lumbosacral radicular pain were enrolled, excluding those meeting the exclusion criteria. PI change and NRS score improvement were noted at 0, 5, 10, 15, and 30 minutes along with pre and post-procedure SLRT. Results were analyzed. Results: A total of 40 patients were analyzed. PI change at 30 minutes was 2.113 from a baseline of 0.217. Median NRS of 5, improved to 0 and the mean SLRT of 45.17 to 61.45 at the end of 30 minutes. All changes are statistically significant with P (&lt;0.01). correlation between the PI change with NRS is mild (-0.312). Conclusion: PI change ratio shows an overall improvement in pain levels objectively, in a non-invasive, easy, and reliable way. Simultaneous improvement in both NRS and SLRT is clinically significant but cannot predict a correlated quantitative measure of pain relief.

Drug-Loaded Mesoporous Polydopamine Nanoparticles in Chitosan Hydrogels Enable Myocardial Infarction Repair through ROS Scavenging and Inhibition of Apoptosis.

In this study, we synthesized mesoporous polydopamine nanoparticles (MPDA NPs) using an emulsion-induced interface assembly strategy and loaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic attraction to form EGCG@MPDA NPs. In the post myocardial infarction (MI) environment, these interventions specifically aimed to eliminate reactive oxygen species (ROS) and facilitate the repair of MI. We further combined them with a thermosensitive chitosan (CS) hydrogel to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel). Utilizing in vitro experiments, the EGCG@MPDA/CS hydrogel exhibited excellent ROS-scavenging ability of H9C2 cells under the oxidative stress environment and also could inhibit their apoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular ejection fraction (LVEF) in infarcted rat models post injection for 28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ± 0.78%, P < 0.05). In comparison to the PBS group, histological analysis revealed a substantial increase in left ventricular (LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58 ± 0.03 to 1.39 ± 1.11 mm, P < 0.05). This work presents a novel approach to enhance MI repair by employing the EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local oxidative stress by ROS and stimulates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.

Assessment of dual time point protocols to produce parametric Ki images in FDG PET/CT: A virtual clinical study.

This simulation study investigated the feasibility of generating Patlak Ki images using a dual time point (DTP-Ki) scan protocol involving two 3-min/bed routine static PET scans and, subsequently, assessed DTP-Ki performance for an optimal DTP scan time frame combination, against conventional Patlak Ki estimated from complete 0-93min dynamic PET data. Six realistic heterogeneous tumors of different characteristic spatiotemporal [18F]FDG uptake distributions for three noise levels commonly found in clinical studies and 20 noise realizations (N=360 samples) were produced by analytic simulations of the XCAT phantom. Subsequently, DTP-Ki images were generated by performing standard linear indirect Patlak analysis with t* -min (Patlakt* = 12) using a scaled population-based input function (sPBIF) model on 66 combinations of early and late 3-min/bed static whole-body PET reconstructed images. All DTP-Ki images were evaluated against respective DTP-Ki images estimated with Patlakt* = 12 and 0-93min individual input functions (iIFs) and against gold standard Ki images estimated with Patlakt* = 12, 0-93min iIFs and tissue time activity curves from all reconstructed WB passes 12-93min post injection. The optimal combination of early and late frames, in terms of attaining the highest correlation between DTP-Ki with sPBIF and gold standard Ki was also determined from a set of 66 different combinations of 2-min early and late frames. Moreover, the performance of DTP-Ki with sPBIF was compared against that of the retention index (RI) in terms of their correlation to the gold standard Ki. Finally, the feasibility and practicality of DTP protocol in the clinic were assessed through the analysis of nine patients. High correlations(>0.9) were observed between DTP-Ki values from sPBIF and those from iIFs for all evaluated DTP protocols while the mean AUC difference between sPBIF and iIFs was less than 10%. The percentage difference of mean values between DTP-Ki from sPBIF and from iIFs was less than 1%. DTP Ki from sPBIF exhibited significantly higher correlation with gold standard Ki, in contrast to RI, across all 66 DTP protocols (p<0.05 using the two-tailed t-test by Williams) with the highest correlation attained for the 50-53-min early + 90-93-min late scan time frames (optimal DTP protocol). Feasibility of generating Patlak Ki [18F] FDG images from an early and a late post injection 3-min/bed routine static scan using a population-based input function model was demonstrated and an optimal DTP scan protocol was determined. The results indicated high correlations between DTP-Ki and gold-standard Ki images that are significantly larger than those between RI and gold-standard Ki.

Allogenic Vertebral Body Adherent Mesenchymal Stromal Cells Promote Muscle Recovery in Diabetic Mouse Model of Limb Ischemia

Chronic limb threatening ischemia (CLTI) carries a significant risk for amputation especially in diabetic patients with poor options for revascularization. Phase I trials have demonstrated efficacy of allogeneic mesenchymal stromal cells (MSC) in treating diabetic CLTI. Vertebral bone adherent mesenchymal stromal cells (vBA-MSC) are derived from vertebral bodies of deceased organ donors which offer the distinct advantage of providing a 1,000x greater yield compared to that of living donor bone aspiration. This study describes the effects of intramuscular injection of allogenic vBA-MSC in promoting limb perfusion and muscle recovery in a diabetic CLTI mouse model. A CLTI mouse model was created through unilateral ligation of the femoral artery in male polygenic diabetic TALLYHO mice. Treated mice were injected with vBA-MSC into the gracilis muscle of the ischemic limb 7 days post ligation. Gastrocnemius or tibialis muscle was assessed post-mortem for fibrosis by collagen staining, capillary density via immunohistochemistry, and mRNA by quantitative real time PCR. Laser Doppler perfusion imaging and plantar flexion muscle testing were performed to quantify changes in limb perfusion and muscle function. Compared to vehicle control, treated mice demonstrated indicators of muscle recovery including decreased fibrosis, increased perfusion, muscle torque, and angiogenesis. PCR analysis of muscle obtained 7- and 30-days post vBA-MSC injection showed an upregulation in expression of MyoD1 (p = 0.03) and MyH3 (p = 0.008) mRNA representing muscle regeneration, VEGF-A (p = 0.002 ; p = 0.004) signifying angiogenesis as well as IL-10 (p < 0.001), T regulatory cell marker Foxp3 (p = 0.04), and M2-biased macrophage marker Mrc1 (CD206) (p = 0.02). These findings indicate human allogeneic vBA-MSC ameliorate ischemic muscle damage and rescue muscle function. These results in a murine model will enable further studies to develop potential therapies for diabetic CLTI patients.

Application of H2N-Fe3O4 Nanoparticles for Prostate Cancer Magnetic Resonance Imaging in an Animal Model.

This paper presents the efficacy of a contrast agent based on H2N-Fe3O4 nanoparticles for the detection of prostate cancer in an animal model using a preclinical 9.4 T MRI system. The relaxivities r1 and r2 of the nanoparticles were 6.31 mM-1s-1 and 8.33 mM-1s-1, respectively. Nanoparticles injected in a concentration of 2 mg Fe/mL decreased the tumor-relative T1 relaxation across all animals from 100 to 76 ± 26, 85 ± 27, 89 ± 20, and 97 ± 16 12 min 1 h, 2 h, and 24 h post injection, respectively. The corresponding T1 decrease in muscle tissues was 90 ± 20, 94 ± 23, 99 ± 12, and 99 ± 14. The relative T2 changes in the tumor were 82 ± 17, 89 ± 19, 97 ± 14, and 99 ± 8 12 min, 1 h, 2 h, and 24 h post injection, respectively, while, for muscle tissues, these values were 95 ± 11, 95 ± 8, 97 ± 6, and 95 ± 10 at the corresponding time points. The differences in the relative T1 and T2 were only significant 12 min after injection (p < 0.05), although a decrease was visible at each time point, but it was statistically insignificant (p > 0.05). The results showed the potential application of H2N-Fe3O4 nanoparticles as contrast agents for enhanced prostate cancer MRI.

Combination of high cetane diesel fuel and post injection mode in a diesel engine: A path towards lower exhaust emissions

The major objective of the presented work is to explore the effect of post injection (PI) strategy using neat diesel fuel (D100) blended with cetane number enhancer (CNE). The motive behind adding CNE in diesel fuel was to lower its self-ignition temperature and hence delay period subsequently. This can lead to more efficient combustion of post injected fuel which leads to lower incomplete combustion losses. The CNE used was Di-Tert-Butyl Peroxide (DTBP) which was blended with D100 in proportion of 1 % by volume. Initially experiments were conducted with D100 under various PI modes where variation of post injection timing (PIT) as well as post quantity (PQ) was considered. The experimental results showed that implementing PI resulted in lower smoke, unburned hydrocarbon (UHC), carbon monoxide (CO) and nitrogen oxides (NOx) emissions compared to single injection while affecting fuel consumption negatively. Then after similar experiments under various PI modes were repeated using blends of D100 and DTBP (D/DTBP) and results were compared with D100 case. It was found that addition of CNE in D100 resulted in more complete combustion of post fuel which further reduced CO and UHC emissions. The shorter delay period in case of D/DTBP blend compared to D100 case led to lower NOx emissions as well as higher smoke emissions. The obtained results revealed that PI mode with 3 mg PQ and 20° after top dead center (ATDC) PIT with D/DTBP blend offered 41.18 %, 17.55 %, 64 % and 62.5 % reduction in smoke, NOx, UHC and CO emissions respectively compared to single injection mode using D100 fuel.