Drug Injection Research Articles

Use of esketamine for tracheoscopic drug injection: a randomized controlled trial

BackgroundSufentanil may induce hypotensive bradycardia and other adverse reactions in elderly patients during anesthesia, while esketamine exhibits sedative and analgesic effects with minimal impact on respiration and circulation. The objective of this study was to investigate the impact of these two anesthetics on vital signs in patients undergoing bronchoscopy and lavage under general anesthesia.MethodThis study was a randomized controlled trial with a parallel design. A total of 100 patients aged ≥60 years with ASAI or II who were undergoing bronchoscopy and lavage were randomly assigned to two groups: group A (esketamine, n = 50) and group B (sufentanil, n = 50). During anesthesia induction, both groups received intravenous infusion of propofol at a dose of 1.5 mL/kg and atracurium. In group A, esketamine at a dose of 0.3 mg/kg was injected; in group B, sufentanil at a dose of 0.2 μg/kg was injected intravenously. Subsequently, a laryngeal mask was inserted and connected to an anesthesia machine for mechanical ventilation. Anesthesia maintenance involved continuous intravenous infusion of propofol at a dose of 3 mL/kg. The mean arterial pressure (MAP), heart rate (HR), and blood oxygen saturation (SpO2) were recorded at various time points: before anesthesia injection (T0), after laryngeal mask insertion (T1), 5 min after the operation started (T2), 15 min after the operation started (T3), and before the end of the operation (T4). Additionally, the recovery time was recorded.ResultsThe blood pressure of patients in the esketamine group exhibited higher levels compared to those in the sufentanil group at multiple time points during the operation, while maintaining a more stable intraoperative blood pressure and shorter postoperative recovery time than that observed in the sufentanil group. The blood pressure and heart rate of patients in the esketamine group exhibited significant fluctuations after laryngeal mask implantation compared to pre-anesthesia induction, with a statistically significant increase observed. Conversely, no significant changes were observed in the sufentanil group. The heart rate and oxygen saturation showed no significant differences between the two groups, nor did the amount of propofol administered during the procedure.ConclusionThe utilization of esketamine during the induction phase of bronchoscopy and lavage under general anesthesia can enhance hemodynamic stability and reduce the occurrence of hypotension, thereby facilitating postoperative anesthetic recovery.

Joint Injection or Aspiration before Total Knee Arthroplasty: Does it Increase the Risk of Periprosthetic Joint Infection?

Background Injections are a common preoperative treatment for patients who eventually undergo total knee arthroplasty (TKA). However, recent studies have shown a relationship between preoperative injections and adverse outcomes following surgery. The purpose of this study was to characterize the type of intra-articular procedure patients receive in the acute period prior to surgery and determine their association with postoperative periprosthetic joint infection (PJI) Methods An observational cohort study was conducted using the Merative MarketScan databases. Patients who underwent primary TKA between April 1, 2019, and July 4, 2021, were included in the study. Patients were grouped according to the type of intra-articular procedure they received in the 90-day period prior to TKA: (i) intra-articular hyaluronic (IA-HA), (ii) intra-articular corticosteroid (IA-CS), (iii) aspiration, and (iv) no drug injections or aspirations. The primary outcome was the postoperative 180-day PJI rate. Results 43,219 patients were included in the study. 11.8% of patients were found to have received at least one injection or aspiration in the 90 days prior to their TKA. The most common injection performed was IA-CS (78.3%), followed by aspiration (13.0%) and IA-HA (8.7%). No image guidance was performed for 92.3% of injections, with most being administered between 61-90 days before surgery (93.6%). 180-day PJI rates were similar between patients with and without injections (OR 1.11, p=.569). Neither drug type nor image guidance had an effect on overall postoperative PJI rate. Conclusion Injections performed prior to TKA do not increase the risk of developing postoperative.

Prevalence, Reasons, and Prevention for Drug Related Death After Release from Prisons: A Systematic Review and Meta-analysis

Context: Drug-related mortality is a major concern in public and global health discussions. Objectives: Therefore, the aim of this study was to investigate the prevalence, causes, and prevention of death after individuals are released from prison. Methods: This study was conducted systematically using MeSH keywords with no language or time restrictions. PubMed, Scopus, and Web of Science databases were extensively searched for observational studies from 1980/1/1 to 2023/12/30, following the PRISMA checklist. Fourteen research studies were ultimately included in the systematic review process. The CRD code is CRD42024571756. Results: The two-week period following release, with an 18% prevalence, was identified as the time when most overdose deaths occurred. The leading causes of death included prior heroin use, previous experiences with drug withdrawal, drug injection, and sedative use within six months before death. Compared to other unnatural causes of death, there was an increased risk of fatal drug overdose for individuals who died within the first two months of release. Men had higher death rates from all causes compared to women. Most studies reported that substance abuse treatment during imprisonment and providing take-home naloxone for emergencies protected against mortality from all causes. Conclusions: In conclusion, evidence from these systematic investigations highlights the urgent need for targeted interventions to address substance use disorders and overdose prevention among individuals recently released from prison. Efforts to bridge the gap between incarceration and community reintegration should prioritize comprehensive substance abuse treatment programs to reduce the heightened risk of mortality in this vulnerable population.

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.

Examining the health status of patients with COVID-19 hospitalized in Hajar(S) Shahrekord Medical Education Center after discharge

Background and aims: The emergence of some medium—and long-term outcomes following the acute phase of the disease, known as "long COVID-19," poses a challenge to medical science. This study aimed to determine the health status of COVID-19 patients after discharge. Methods: This is a descriptive-analytical cross-sectional study. The research population included all COVID-19 patients hospitalized at Hajar Educational and Medical Center in Shahrekord over three months. The data collection tool was a questionnaire assessing the health status of patients six weeks after discharge. Data analysis was performed using SPSS23 software and descriptive and analytical statistical tests, including Fisher’s exact test and independent t-test. Results: The total number of hospitalized patients was 160. Among them, 21 patients had died, and 72 patients either did not respond to the phone call or provided unreliable information. Ultimately, data were collected from 67 patients. In examining the complications of COVID-19, 34.4% of the study samples reported weakness and fatigue, 13.4% cough, 8.9% dyspnea, and 1.4% skin complications. A significant correlation was observed between the gender variable with dyspnea and cough variable (P=0.001) and between the gender variable with weakness and lethargy variable (P=0.05). In the correlation analysis between the variables of hypertension, diabetes, lung diseases, overweight, brain diseases, and remdesivir drug injection, a significant relationship was observed with COVID complications. Conclusion: The COVID-19 pandemic is not over, and many sufferers suffer from prolonged covid. Gender and underlying diseases are some of the most important underlying factors in the long-term COVID-19. Creating post-COVID care systems for these patients is highly needed and recommended.

Repeated treatment with VEGF receptor inhibitors induces phenotypic changes in endothelial cells and pericytes in the rat retina

Abnormal ocular angiogenesis is a major cause of visual impairment and vision loss in neovascularization-related diseases. Currently, anti-vascular endothelial growth factor (VEGF) drugs are used to treat ocular neovascularization, but repeated injections are needed to maintain their therapeutic effects. However, repeated injection of anti-VEGF drugs may affect the retinal blood vessel phenotype and diminish therapeutic effects. In this study, we aimed to investigate the phenotypic changes in endothelial cells and pericytes caused by the repeated interruption of the VEGF receptor signaling pathway in neonatal rats. KRN633 (10 mg/kg), a VEGF receptor tyrosine kinase inhibitor, was subcutaneously administered on postnatal day (P)-7 and P8 (first round), P14 and P15 (second round), and P21 and P22 (third round). The rat eyes were collected on P7, P9, P14, P16, P21, P23, P28, and P35. Using retinal flat-mount specimens stained with specific markers for vascular endothelial cells, basement membranes, and pericytes, the arteriolar tortuosity, capillary area density, and distribution of pericytes were evaluated. Significant loss of capillaries was observed the day after the first round of KRN633 treatment, after which aggressive angiogenesis occurred, leading to the formation of tortuous arterioles. Rats that completed second and third rounds of KRN633 treatment showed more severe abnormalities in the retinal vasculature than those that only completed first round treatment. Repeated treatment with KRN633 decreased the anti-angiogenic effects but increased the immunoreactivity of α-smooth muscle actin in the pericytes on veins and capillaries. α-Smooth muscle actin expression was inversely correlated to anti-angiogenic effects. Overall, these results revealed that repeated interruption of VEGF receptor signaling pathway altered the phenotypes of endothelial cells and pericytes and induced anti-VEGF drug resistance. Therefore, careful follow-up is necessary when using anti-VEGF drugs to treat abnormal angiogenesis-associated ocular diseases.

Epidural Analgesia for Palliative Pain Management for A Patient with An Advanced Stage Prostate Cancer: A Case Report

Introduction: Patients with advanced-stage cancer should be able to stay at home with their families without suffering from pain. This case report aims to discuss challenges in pain management of a patient with bone metastasis of prostate cancer who received epidural analgesia at home. Challenges were related to the patients, health professionals, and system. Understanding each factor will bring insights to develop a workable pain management program in the palliative setting. Case Presentation: A 66-year-old male was diagnosed with left sacroiliac joint pain due to metastatic prostate cancer. After a three-year history of prostate cancer and ineffective chemotherapy, the patient complained of pain in the left hip that did not improve with conventional medications (paracetamol, tramadol, and Morphine Sustained Release/MST). In response, the consideration of an epidural implant emerged as a potential solution, offering the prospect of home-based care and autonomous medication administration through an epidural continuous block with intermittent drug injection. Conclusions: This case highlights home-based interventional pain management for cancer, addressing challenges at the patient, health professional, and system level. Overcoming these challenges requires a multidisciplinary approach and robust institutional policies. The insights gained offer valuable lessons for hospitals aiming to enhance the competence of pain and palliative care teams and establish comprehensive support systems in hospital and home settings.

HIV and hepatitis C virus infection and co-infection among trans women in San Francisco, 2020.

Transgender women (hereafter "trans women") face social marginalization, stigma, and discrimination and experience a high burden of HIV. More recently, trans women have been identified as having a high risk for hepatitis C (HCV) infection. The interaction between these two diseases and the risks for HIV/HCV co-infection among trans women are understudied. To characterize epidemiological, behavioral, and socio-structural interactions between HIV and HCV infections among trans women. This cross-sectional study examined data from a community-based survey of trans women in San Francisco recruited through respondent-driven sampling (RDS) in 2019/2020. Face-to-face interviews collected data on demographics, medical history, drug injection practices, sexual behavior, and socio-structural factors (e.g., poverty, housing insecurity, incarceration, social support). HIV and HCV antibodies were detected using oral fluid rapid tests and prior diagnosis and treatment were collected by self-report. Blood specimens were collected to confirm antibodies using ELISA. Multinomial logistic regression analysis characterized factors associated with HIV infection alone, HCV infection alone, and HIV/HCV co-infection compared to neither infection. Among 201 trans women recruited, HIV prevalence was 42.3%; HCV infection by history or current seroprevalence was 28.9%; evidence for both HIV and HCV infection was present for 18.9%. Two-thirds of trans women (67.2%) had been incarcerated; 30.8% had ever injected drugs. History of injection drug use and receiving emotional support from family were factors found in common for HIV infection, HCV infection, and HIV/HCV co-infection compared to no infection. Having a sexual partner who injects drugs was associated with HIV infection alone. Not lacking care due to cost and older age were associated with co-infection. Older age was also associated with HCV infection. Of trans women with HIV infection, 91.8% had accessed HIV care, whereas only 62% with HCV had accessed some form of care. Our study found high levels of HIV, HCV, and HIV/HCV co-infection among trans women in San Francisco. We found common associations between HIV and HCV through injection practices and emotional support, but having a sexual partner who injects drugs was not associated with HCV infection alone or co-infection. We note a substantial gap in the treatment of HCV for trans women, including those in HIV care, that needs to be urgently addressed.

Metabolic Shift and Hyperosmolarity Underlie Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is both a poorly understood and devastating disease. Here, we analyze the physico-chemical forces at stake, including osmolarity, redox shift, and pressure due to inflammation. Hyperosmolarity plays a key role in diseases of the anterior segment of the eye such as glaucoma, cataracts or dry eyes, and corneal ulceration. However, its role in macular degeneration has been largely overlooked. Hyperosmolarity is responsible for metabolic shifts such as aerobic glycolysis which increases lactate secretion by Muller cells. Increased osmolarity will also cause neoangiogenesis and cell death. Because of its unique energetic demands, the macula is very sensitive to metabolic shifts. As a proof of concept, subretinal injection of drugs increasing hyperosmolarity such as polyethylene glycol causes neoangiogenesis and drusen-like structures in rodents. The link between AMD and hyperosmolarity is reinforced by the fact that treatments aiming to restore mitochondrial activity, such as lipoic acid and/or methylene blue, have been experimentally shown to be effective. We suggest that metabolic shift, inflammation, and hyperosmolarity are hallmarks in the pathogenesis and treatment of AMD.

Natural pachypodol integrated, lung targeted and inhaled lipid nanomedicine ameliorates acute lung injury via anti-inflammation and repairing lung barrier

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1β, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic.

Multifunctional injectable microspheres for osteoarthritis therapy via spatiotemporally modulating macrophage polarization and inflammation

Local injection of anti-inflammatory drugs for osteoarthritis emerged as a promising administration in the clinic, and sustained-release dosage forms have great potential for future therapeutic applications. Controlling the response of patients only in the acute inflammatory phase is currently the focus of therapeutic interventions. To relieve acute pain in patients and to improve the long-term prognosis effect of osteoarthritis treatment, we designed a two-pronged approach in this research: an injectable double-layer microsphere containing a “nonsteroidal anti-inflammatory drug - macrophage polarizing factor” was constructed. The results indicated that microspheres could regulate the intra-articular environment by inhibiting local inflammatory cytokine production, promoting macrophage polarization to the M2-phenotype, and increasing the expression of cartilage repair factors. Polymers chosen could govern the biocompatibility of microspheres and control the release sequence of the two drugs. Injection of microspheres into the degenerative articular cavity of rats leads to suppressed inflammation and well-promoted cartilage regeneration.

Foreign body pulmonary vessel embolism and granulomatosis in intravenous drug abuse: An autopsy study.

The abuse of illicit drugs causes a myriad of systemic complications. Intravenous (IV) injection of such drugs poses various additional threats, primarily due to the use of excipient materials in them. Pulmonary artery embolism with foreign material and granulomatosis may be encountered in the lungs on histopathological examination in such cases. In this study, we aimed to analyze the histopathological findings in lungs in postmortem specimens with suspected IV drug abuse. This was a retrospective study of 5 years in which 15 cases of known or suspected history of drug abuse were assessed. The clinical details were compiled, and the hematoxylin and eosin (H and E)-stained microscopic slides were retrieved from the archives for reviewing the histopathological features in lungs submitted for postmortem analysis. All the cases were male, aged 21 to 36 years (median: 27 years). Gross examination revealed edematous lungs in four cases (26.6%). On microscopic examination of the lungs, all the cases (100%) showed the presence of basophilic irregular structures to rod-like pale crystalline refractile material, which was accompanied by a granulomatous reaction in the lumen of the pulmonary arteries. Four of these cases (26.6%) showed birefringence on polarizing microscopy. The use of illicit drugs is becoming widespread, especially among young individuals. IV drug abuse increases the rate of morbidity and mortality by affecting primarily the pulmonary vasculature, particularly pulmonary arteries. An acquaintance with the various patterns of pulmonary involvement in IV drug abuse is essential to arrive at an accurate pathological diagnosis and provide a possible cause of death in such cases.

Harm Reduction in Peer-Assisted Telemedicine for Hepatitis C: Secondary Outcomes of a Randomized Controlled Trial.

Hepatitis C (HCV) treatment for people who use drugs (PWUD) decreases injection drug use and injection equipment sharing. We examined changes in injection drug use and injection equipment sharing following HCV treatment in a randomized trial comparing peer-assisted telemedicine for HCV treatment (TeleHCV) versus peer-assisted usual care in rural PWUD. We hypothesize that TeleHCV reduces risky behaviors and peers facilitate this change. We used mixed-effects logistic regression to describe participant-level (n = 203) associations between both injection drug use and injection equipment sharing and randomized groups, frequency of peer contact, HCV treatment initiation, HCV cure, and time. Risky behaviors were surveyed at baseline and 12 and 36 weeks after HCV treatment completion. Injection drug use declined more over time in TeleHCV participants vs. control at 12 weeks (adjusted odds ratio [aOR] = 0.42, 95% CI 0.20-0.87, p = 0.02) and 36 weeks (aOR = 0.48, 95% CI 0.21-1.08, p = 0.076). Injection drug use decreased more with a greater number of peer interactions, with reductions among participants in the 3rd quartile exceeding those in the 1st quartile of peer interactions at 12 weeks (aOR = 0.75, 95% CI 0.57-0.99, p = 0.04). Similarly, injection equipment sharing decreased over time, with reductions among participants in the 3rd quartile exceeding those in the 1st quartile of peer interactions at 36 weeks (aOR = 0.08, 95% CI 0.01-0.97, p = 0.047). Peer-assisted telemedicine for HCV treatment decreases injection drug use and injection equipment sharing; peers contribute to this effect.

Perceived Naturalness Biases Objective Behavior in Both Trivial and Meaningful Contexts

Research shows that perceived naturalness can bias beliefs about the positivity of items such as food, human talent, and vaccines. Yet, this research focuses on self-reports, which leaves open the implications it has for behavior. In four studies ( N = 492), we tested if perceived naturalness impacts trivial and meaningful behaviors. Participants were asked to consume a purported natural/synthetic performance drink (Study 1), test a purported natural/synthetic drug that would be injected (Study 2), eat chocolate containing a purported natural/synthetic cocoa described as causing stomach discomfort (Study 3), or choose a sticker purportedly made with natural/synthetic ink (Study 4). A significant majority of participants (66%–84%) chose and followed through with the natural versus synthetic option. Perceived naturalness guided behavior in contexts involving little (sticker choice) to substantial (drug injection) potential consequences. Self-reports can weakly predict behaviors, but the results revealed that perceived naturalness biases self-reports and behaviors in a similar fashion.

Self-Reported Illicitly Manufactured Fentanyl Use and Associated Health and Substance Use Risks in the United States, 2022

Objective Illicitly manufactured fentanyl (IMF) has emerged as a catalyst of the recent drug epidemic in the United States. To devise more targeted and effective prevention and treatment strategies, it is crucial to understand the demographics of the population who consumes IMF and their health and associated substance use risks. Therefore, this study explores the sociodemographic characteristics, health diagnoses, and drug injection practices of individuals reporting IMF use. Methods Data were derived from the 2022 National Survey on Drug Use Health, based on a nationally representative sample of non-institutionalized individuals aged 12 and older in the United States. Focusing on 306 adults who reported ever using IMF, we examined their sociodemographic characteristics, health diagnoses, and substance-related behaviors in comparison to adults with a drug use disorder who did not report IMF use, using logistic regression analyses. Results The majority of U.S. adults reporting IMF use were aged 35–64, male, non-Hispanic White, with a high school education or lower, never married, and had an annual household income below $40,000. Compared to adults with a drug use disorder who did not report IMF use, they were more likely to report heart conditions (AOR = 2.67, 95% CI = 1.29–5.54) and Hepatitis B or C (AOR = 8.35, 95% CI = 4.05–17.02). Nearly half of this group had an opioid use disorder (OUD) in the past year, and 65.7% (95% CI = 56.7–74.8) reported a history of injecting drugs. Conclusions To effectively curb the current drug epidemic, incorporating effective treatment for OUD and harm reduction strategies is crucial.

Amitriptyline nanoparticle repositioning prolongs the anti-allodynic effect of enhanced microglia targeting.

Aim: Amitriptyline (AMI) has been used to treat neuropathic pain. However, the clinical outcomes remain unsatisfactory, presumably due to a limited understanding of the underlying molecular mechanisms. Here, we investigated a drug repositioning strategy using a low-dose of AMI encapsulated in poly (D, L lactic-co-glycolic acid) (PLGA) nanoparticles (AMI NPs) for neuropathic pain, since PLGA nanoparticles are known to enhance delivery to microglia.Methods: We evaluated the anti-allodynic effects of AMI and AMI NPs on neuropathic pain by assessing behaviors and inflammatory responses in a rat model of spinal nerve ligation (SNL). While the anti-allodynic effect of AMI (30μg) drug injection on SNL-induced neuropathic pain persisted for 12h, AMI NPs significantly alleviated mechanical allodynia for 3days.Results: Histological and cytokine analyses showed AMI NPs facilitated the reduction of microglial activation and pro-inflammatory mediators in the spinal dorsal horn. This study suggests that AMI NPs can provide a sustained anti-allodynic effect by enhancing the targeting of microglia and regulating the release of pro-inflammatory cytokines from activated microglia.Conclusion: Our findings suggest that the use of microglial-targeted NPs continuously releasing AMI (2μg) as a drug repositioning strategy offers long-term anti-allodynic effects.

Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Learning meaningful representation of single-neuron morphology via large-scale pre-training.

Single-neuron morphology, the study of the structure, form, and shape of a group of specialized cells in the nervous system, is of vital importance to define the type of neurons, assess changes in neuronal development and aging and determine the effects of brain disorders and treatments. Despite the recent surge in the amount of available neuron morphology reconstructions due to advancements in microscopy imaging, existing computational and deep learning methods for modeling neuron morphology have been limited in both scale and accuracy. In this paper, we propose MorphRep, a model for learning meaningful representation of neuron morphology pre-trained with over 250 000 existing neuron morphology data. By encoding the neuron morphology into graph-structured data, using graph transformers for feature encoding and enforcing the consistency between multiple augmented views of neuron morphology, MorphRep achieves the state of the art performance on widely used benchmarking datasets. Meanwhile, MorphRep can accurately characterize the neuron morphology space across neuron morphometrics, fine-grained cell types, brain regions and ages. Furthermore, MorphRep can be applied to distinguish neurons under a wide range of conditions, including genetic perturbation, drug injection, environment change and disease. In summary, MorphRep provides an effective strategy to embed and represent neuron morphology and can be a valuable tool in integrating cell morphology into single-cell multiomics analysis. The codebase has been deposited in https://github.com/YaxuanLi-cn/MorphRep.

Pharmacokinetics of Injectable Meloxicam and Buprenorphine in the Naked Mole-Rat (Heterocephalus glaber).

Unique characteristics of the naked mole-rat (NMR) have made it increasingly popular as a laboratory animal model. These rodents are used to study many fields of research including longevity and aging, cancer, circadian rhythm, pain, and metabolism. Currently, the analgesic dosing regimens used in the NMR mirror those used in other rodent species. However, there is no pharmacokinetic (PK) data supporting the use of injectable analgesics in the NMR. Therefore, we conducted 2 independent PK studies to evaluate 2 commonly used analgesics in the NMR: meloxicam (2 mg/kg SC) and buprenorphine (0.1 mg/kg SC). In each study, blood was collected at 8 time points after subcutaneous injection of meloxicam or buprenorphine (0 [predose], 0.25, 0.5, 1, 2, 4, 8, and 24 h). Three NMRs were used per time point for a total of 24 animals per PK study. Plasma concentrations of meloxicam were highest between 0.5 and 1 h postinjection. Levels remained above the extrapolated dog and cat therapeutic threshold levels (390 to 911 ng/mL) for at least 24 h. Plasma concentrations of buprenorphine were highest between 0.25 and 0.5 h postinjection. Levels remained above the human therapeutic threshold (1 ng/mL) for up to 21 h. No skin reactions were seen in association with injection of either drug. In summary, these data support dosing meloxicam (2 mg/kg SC) once every 24 h and buprenorphine (0.1 mg/kg SC) once every 8 to 12 h in the NMR. Further studies should be performed to evaluate the clinical efficacy of these drugs by correlating plasma concentrations with postoperative pain assessments.

Visualisation and quantification of subcutaneous injections of different volumes, viscosities and injection rates: An ex-vivo micro-CT study

The effects of subcutaneous (SC) injection parameters such as drug formulation volume, viscosity and injection rate on therapeutic performance and tolerability have not been established for any drug product. In this study four groups of SC injections were performed on fresh ex vivo minipig abdominal tissue samples, varying volume (0.5-1 mL), viscosity (1-11 cP) and rate (0.02-0.1 mL/s). Micro-CT provided high resolution (50 micron) imaging of the SC tissues before and after injection, enabling a detailed 3D visualisation and analysis of how both injection parameters and tissue microstructure influence spatial distribution of injectables. We found that volume was the only significant factor for spatial distribution of injectate within our design space, and there were no significant factors for tissue backpressure. Variability within test groups was typically greater than differences between group means. Accordingly, whilst the higher viscosity formulations consistently exhibited reduced spatial distribution, the sample size was not large enough to establish confidence in this result. Comparing our findings to clinical evidence, we conclude that injection site and depth are more likely to influence PK and bioavailability than volume, viscosity and rate within our experimental space.