Post Injections Research Articles

α-Synuclein aggregation decreases cortico-amygdala connectivity and impairs social behavior in mice

Abnormal accumulation of insoluble α-synuclein (α-Syn) inclusions in neurons, neurites, and glial cells is the defining neuropathology of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Accumulation of α-Syn inclusions in the amygdala has been well-documented in post-mortem studies of PD and DLB brains, as well as preclinical animal models of these conditions. Though α-Syn pathology is closely associated with neurodegeneration, there is a poor correlation between neuronal loss in the amygdala and the clinical features of PD and DLB. Moreover, functional interaction between the cerebral cortex and the amygdala is critical to regulating emotion, motivation, and social behaviors. The cortico-amygdala functional interaction is likely to be disrupted by the development of α-Syn pathology in the brain. Thus, we hypothesize that neuronal α-Syn inclusions disrupt cortical modulation of the amygdala circuits and are sufficient to drive social behavioral deficits. In the present work, we designed a series of longitudinal studies to rigorously measure the time courses of neurodegeneration, functional impairment of cortico-amygdala connectivity, and development of amygdala-dependent social behavioral deficits to test this hypothesis. We injected α-Syn preformed fibrils (PFFs) into the dorsal striatum to induce α-Syn aggregation in the amygdala and the medial prefrontal cortex (mPFC) of C57BL6 mice of both sexes, followed by a detailed analysis of temporal development of α-Syn pathology, synaptic deficits, and neuronal loss in the amygdala, as well as behavioral deficits at 3–12 months post injections. Development of α-Syn inclusions caused losses of cortical axon terminals and cell death in the basolateral amygdala (BLA) at 6- and 12-months post injections, respectively. At a relatively early stage of 3 months post injections, the connection strength of the mPFC-BLA synapse was decreased in PFFs-injection mice compared to controls. Meanwhile, the PFFs-injected mice showed impaired social interaction behavior, which was rescued by chemogenetic stimulation of mPFC-BLA connections. Altogether, we presented a series of evidence to delineate circuit events in the amygdala associated with the accumulation of α-Syn inclusions in the mouse brain, highlighting that functional impairment of the amygdala is sufficient to cause social behavior deficits. The present work further suggests that early circuit modulation could be an effective approach to alleviate symptoms associated with α-Syn pathology, necessitating studies of functional consequences of α-Syn aggregation.

Investigating the potential of a higher reactivity fuel to achieve faster heat-up of aftertreatment systems

Shortening the aftertreatment system heat-up period will be crucial to meet upcoming emissions regulations, which mandate significant reductions in tail-pipe emissions for on-road heavy-duty vehicles. This work studies the impact of increasing fuel reactivity on the combustion of post injections during the expansion stroke. The work demonstrates an operating strategy using a blend of di-butyl ether (a potential low-carbon biofuel component) and #2 diesel that achieves higher exhaust enthalpy, while maintaining similar engine-out emissions (NOx and combustion efficiency) in comparison to the baseline #2 diesel fuel (cetane number 41). On average, a 12% increase in exhaust enthalpy was observed for the blend (cetane number 60) relative to the baseline fuel. The ability to operate the higher reactivity fuel at a more retarded post-injection timing, where combustion with #2 diesel was found to be more unstable, and less complete was key to achieving higher exhaust enthalpy. However, a small fuel penalty (∼ 3%–5%) was also associated with the higher reactivity fuel with this operating strategy. The formation of fuel lean regions, due to the long ignition delays at late injection conditions, was predicted to be the leading contributor to the increased emissions of products of partial combustion. Chemical kinetic simulations using surrogates for the fuels used in the experiments, demonstrated the ability of a higher cetane fuel to outperform the baseline fuel under fuel lean conditions with equivalence ratios less than 0.7.

The use of platelet rich plasma in the treatment of degenerative joint disease in cats: an exploratory case series.

To evaluate the effectiveness of intra-articular autologous Platelet Rich Plasma (PRP) in managing Degenerative Joint Disease (DJD) in cats. Prospective pilot clinical trial. Six domestic cats with clinically and radiographically diagnosed DJD received intra-articular injections of autologous PRP. Clinical assessments pre and post intra-articular injections were conducted using the Feline Musculoskeletal Pain Index (FMPI, owner assessed) and Visual Analog Scale (VAS, clinician assessed) at baseline, Day 14, Day 28, and Day 42-45. Significant improvements were noted in both FMPI and VAS scores at the end of the study period, indicating enhanced joint function and reduced pain. The study suggests the potential of PRP therapy as a safe and effective treatment for feline DJD, warranting further research with larger cohorts and longer follow-up to establish comprehensive treatment guidelines.

Effectiveness of Intracameral Tissue Plasminogen (r-tPA) Activator in Resolution of Fibrinous Reaction in Refractory Toxic Anterior Segment Syndrome (TASS)

Purpose: To evaluate the effectiveness of tissue plasminogen activator (r-tPA) in resistant toxic anterior segment syndrome (TASS) after Phacoemulsification. Study Design: Quasi experimental. Place and Duration of Study: Khyber Teaching Hospital, Peshawar from August 2021 to August 2023. Methods: Forty-six patients (46 eyes) with an anterior chamber fibrin reaction after cataract surgery were treated with intra-cameral injection of t-PA (30µg/0.1cc) following failure to respond to conventional treatment with intensive topical and subconjunctival steroids. Outcome measures were best corrected visual acuity (BCVA), clearance/recurrence of the fibrin reaction and complications. Results: Intra-cameral t-PA was injected2 to 6 weeks post Phacoemulsification in TASS cases. Mean post-operative injection time was 18.5± 10.2 days. After 1st day post injection, we observed total abolition of fibrinous exudate in 36(78.2%) cases and subtotal resolution in 10 (21.7%) cases. After 6 weeks the TASS was completely settled in 43(93.4%)cases. Mean BCVA improved from 0.59 ± 0.40 log MAR pre-injection to 0.38 ± 0.40 log MAR at 6th week post-injection (p=0.07). There was no statistically significant difference in BCVA and rate of fibrinolysis between the two groups after post r-tPA injections. Intra-cameral r-tPA was not associated with adverse effects like raised IOP or endophthalmitis. Conclusion: Intra-cameral t-PA injection (30µg/0.1cc)appears to be a safe and effective treatment option for resolving anterior chamber fibrin reaction refractory to conventional steroid therapy following cataract surgery.

Role of BoNT-A in patient with post COVID-19 spasticity, assessed by H-reflex

Background. COVID-19 is a pandemic disease due to viral infection. It spread throughout the world, and the association of COVID-19 with neuroendocrine system is a well-known fact especially while the connection between the endocrine and immune system neuroinflammation play a crucial role in pathophysiology. Therapeutic indication of Botulinum-neurotoxin-A (BoNT-A) is used in the treatment of focal post-stroke spasticity (PSS) and in re-habilitation which is regarded as a safe and effective type of treatment. Objective. To assess spasticity after COVID-19 infection. Methods. Thirty patients diagnosed as post-COVID-19 stroke spasticity were enrolled, their age ranged from (30-60 years). They had focal spasticity of lower extremities. BoNT-A was given in day 0 and 4 weeks later, in the gastrocnemius and soleus muscle. H-reflex was recorded from soleus muscles at 1st presentation and 4 weeks after injection of BoNT-A. Muscle power was assessed by Medical Research Council scale (MRC) and MAS. Results. The amplitude and latency of H-reflex record from soleus muscles and the H/M ratio showed a statistically significant difference between pre- and post-therapy with BoNT-A injection in cases with post COVID-19 spasticity. There was a significant increase in MRC scale but, MAS scale showed a significant reduction after injection of BoNT-A. Conclusion. Post COVID spasticity is a well-known complication after COVID-19 infection, there was clinical improvement in PSS post BoNT-A injections, which was assessed clinically by MAS and MRC scale, neurophysiological the H-reflex was correlated negatively regarding latency, while there was no correlation regarding H-reflex amplitude or Hmax/Mmax ratio and MAS.

Disease quiescence in endophthalmitis patients treated with anti-VEGF injections for retinal pathologies

BackgroundThe most feared complication of intravitreal injections is the development of endophthalmitis, which could lead to irreversible visual loss. The aim of this study was to characterize the clinical profiles, causative pathogens, and clinical outcome of patients post-endophthalmitis.MethodsRetrospective, single center case series study. Clinical records, causative pathogens and management of all cases of endophthalmitis post intravitreal anti-vascular endothelial growth factor (VEGF) injections recorded between January 1st, 2006 and May 30th, 2022; were retrieved. The visual and anatomic changes prior to the episode of endophthalmitis and up to 2 years post-treatment were compared.ResultsEleven post-injection endophthalmitis eyes of 10 patients (n = 3 females; 30%) were recruited at mean age of 64.5 ± 20.4 years. The median last recorded BCVA, up to 3 months prior to the episode of endophthalmitis was 60 (Interquartile range (IQR) 55–75) ETDRS letters. Then, it dropped to 30 (IQR 0-57.5), 35 (IQR 0-52.5) and 35 (IQR 0-57.5) ETDRS letters at presentation, 6- and 12-months follow-up; respectively (p = 0.027, p = 0.017 and p = 0.012). However, at 24 months, the median BCVA returned to similar baseline values prior to the episode of endophthalmitis; BCVA 50 (IQR 0–60) ETDRS letters, p = 0.062. Interestingly, two eyes with neovascular age-related macular degeneration (NVAMD), 1 with myopic choroidal neovascularization (CNV) and 1 with retinal vein occlusion (RVO), experienced disease quiescence and did not require additional anti-VEGF injections up to 2 years of follow-up.ConclusionThis study demonstrates long-term recovery of vision loss due to endophthalmitis post anti-VEGF injections, regained up to 2 years later. It also indicates that disease quiescence post endophthalmitis may not only occur in eyes treated for NVAMD, but also with myopic CNV and RVO.

Are brake response times altered post CT-guided cervical spine nerve root injections?

To assess if brake response times are altered pre and post CT-guided cervical spine nerve root injections. Brake response times were assessed before and after CT-guided cervical spine nerve root injections in a cohort of patients. The average of 3 brake response times was recorded before and 30 min after injection. Statistical analysis was performed using GraphPad. A paired Student t-test was used to compare the times before and after the injections. Forty patients were included in this study. The mean age was 55 years. There were 17 male and 23 female patients. There was no significant difference in the mean pre and post CT-guided cervical spine nerve root injection brake response times; 0.94 s (range 0.4-1.2 s) and 0.93 s (range 0.5-1.25 s), respectively (P = .77). Brake response time did not significantly differ pre and 30 min post CT-guided cervical spine nerve root injections. To the authors' best knowledge, there are no current studies assessing brake response times post CT-guided cervical spine nerve root injections. While driving safety cannot be proven by a single metric, it is a useful study in demonstrating that this is not inhibited in a cohort of patients.

Adipose Tissue Stem Cells for Knee Arthritis and Cartilage Lesions: A Three-Year Follow Up.

The purpose of this research article is to evaluate the efficacy and the safety of injections of stromal vascular fraction (SVF), obtained with mini-lipoaspiration of fat tissue for knee osteoarthritis and cartilage lesions. Between January 2018 and February 2021, a total of 76 patients (45 females and 31 males, mean age 64 years; range 53-75 years, body mass index [BMI] no more than 30%, with symptomatic primary osteoarthritis of the knee, without previous arthroscopic intervention) underwent a local tumescent lipoaspiration procedure of 60-80cc of fat tissue from the abdomen. SVF was obtained after centrifugation according to the AdiPrep® Adipose Transfer System (Harvest-Terumo, Plymouth, Massachusetts) technique. The final product was checked with flow cytometry for absolute numbers, vitality, and the cluster of differentiation (CD) population. It was injected intraarticularly into the patients knees. Patients were divided in two groups: Group 1 had patients with knee osteoarthritis Kellgren-Lawrence grade early 4 and Group 2 with osteoarthritis K-L grade 2-3. The International Knee Documentation Committee (IKCD) and Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaires were used to evaluate clinical effects and measure patient's subjective assessment of pain, joint mobility, and physical disability before the injections. They were repeated at six months, one year, two years, and three years post injections. Knee cartilage lesions patients were divided in two subgroups: Group A (11 patients with OA K-L grade 2-3 and Outerbridge cartilage lesions grade 2-3) and Group B (7 patients with OA K-L grade early 4 and cartilage lesions Outerbridge grade late 3 to early 4) were estimated with quantitive analysis of magnetic resonance imaging (MRI) at one, two, and three years post injections. The average IKDC score in Group 1 was 45.9, 63.2, 62.4, 60, and 52. The KOOS score of the same group was 53, 79, 72, 69, and 62 at the end of the third year. At baseline, the average total IKDC score in Group 2 was 48.3, at 6 months 78.2, at one year 77, at two years 70.4, and at three years 61. The KOOS score of this group was 57, 84, 86, 79, and 69 at three years, respectively. For the patients with cartilage lesions, Group A presented lesser volume mean numbers of the lesion: 74% at the end of the first year post injection, 61% at the second, and 52% at the end of the third year with two out of seven patients in the group. The rest had no significant difference. Lesser volume mean number of the lesions in Group B was 85-88%, 70%, and 61% at the end of the third year in 5 out of 11 patients in the group. The rest had no significant difference. Adipose-derivedSVF, injected intraarticularly in arthritic knees, seems to provide good to excellent clinical results for three years and radiological results for cartilage lesions for two years post injections. All patients were satisfied with this treatment with reduction in pain and better joint mobility, especially after two to three months and up to three years. No serious side effects or complications were reported.

Catalyst-heating operation in compression-ignition engines: A comprehensive understanding using large eddy simulations

Catalyst-heating operation in compression-ignition engines is critical to ensure rapid light-off of exhaust catalysts during cold-start. This is typically achieved by using late post injections for increased exhaust enthalpy, where retardability is constrained mainly by emissions due to inactivity of the oxidation catalyst at these conditions. Comprehensive understanding of formation mechanism of pollutant emissions is needed to optimize engine performance and minimize tailpipe harmful emissions. In this study, a computational fluid dynamics model of a medium-duty compression-ignition engine is developed and validated against with catalyst-heating operation experimental data using large eddy simulations. The engine is fueled with a full boiling-range diesel fuel and uses an optimized five-injections strategy that consists of two pilots, one main, and two post injections. Results show that, significant amounts of unburned hydrocarbons (UHCs) and oxygenated UHCs (OUHC) are formed by the pilot injections, which may persist until exhaust valve opening. UHCs accumulate mainly in the outer-upper part of the cylinder guided by the piston lip, in the inner-bowl due to the bowl geometry, near the injector nozzle by the fuel from the end-phase of injection, and in the space between spray plumes transported by the swirl motion. The main injection exhibits a short ignition delay and rapidly consumes most of UHC and OUHC, except for the central part of the chamber near the injector nozzle. The 1st post injection counteracts the expansion effect on temperature, plays a key role in increasing the exhaust enthalpy and reducing the harmful emissions by promoting combustion associated with the 2nd post injection. The fuel delivered by the 2nd post injection penetrates through the flame of the 1st post injection, creating cool flame clouds beyond the flame that eventually transition to a diffusion flame. Finally, a unique phenomenological model is proposed to better visualize the interactions of post injections.

Distance and near vision changes after intravitreal anti-vascular endothelial growth factor injection in eyes with center-involving diabetic macular edema.

To elucidate distance and near vision changes after intravitreal injections in center-involving diabetic macular edema (CIDME) in phakic and pseudophakic groups. A retrospective study was done on 148 eyes (72 phakic and 76 pseudophakic) with center-involving DME. All eyes were treated with intravitreal anti-vascular endothelial growth factor (VEGF) injection. All patients underwent distance best-corrected visual acuity (BCVA) testing, near BCVA testing, dilated fundus examination, and optical coherence tomography (OCT) at baseline and follow-up visits. Eyes that could not improve after the first injection were given 2nd, 3rd, and more injections in the subsequent visits. On follow-up, post injections in the phakic group (n = 72), there were 65 eyes (90.3%) with stable/improved near vision and 59 eyes (81.9%) with stable/improved distance vision, whereas in the pseudophakic group (n = 76), 63 eyes (82.9%) and 60 eyes (78.9%), respectively. Both in phakic and pseudophakic eyes, 7.7%-13% of the cohort showed only near vision improvement. In DME, besides the changes in distance vision, there are also changes in near vision. These changes should be taken into account while determining the response to anti-VEGF in DME treatment.

Enhanced mitotic arrest and chromosome resolution for cytogenetic analysis in the eastern mosquitofish, Gambusia holbrooki

Maximising the number of cells arrested at metaphase and their resolution is fundamentally important for molecular cytogenetic investigations, particularly in fish, which typically yield low mitotic index and have highly condensed chromosomes. To overcome these limitations, fish were injected with a mitotic stimulator (the yeast, Saccharomyces cerevisiae) to improve the mitotic index, and the intercalating agent ethidium bromide to produce elongated chromosomes. Specifically, adults were injected with activated yeast and then Colcemid (0.025 µg/µl solution, 10 µl per 1 g of body weight) at 24–96 h post yeast injections, followed by chromosome preparations from multiple tissues. Results showed that gill tissue had the highest number of dividing cells at 72 h post yeast exposure with no significant (p > 0.05) differences between the sexes. Nonetheless, sex-specific differences in the mitotic index were observed in spleen, kidney, and liver, which may be attributed to sex-specific differences in immune responses. For elongation of mitotic chromosomes, individuals (both sexes) were first injected with activated yeast and after 48 h with ethidium bromide (2 or 4 µg/ml) and Colcemid (0.05 µg/µl solution, 10 µl per 1 g of body weight). Following which, animals were sampled at three time points (1, 4 and 8 h) for chromosome preparations. The results show that the optimum elongation of metaphase chromosomes of males and females was achieved by using 2 µg/ml and 4 µg/ml, respectively, for 1 h. Interestingly, the average mitotic chromosome length (μm) of males and females post-ethidium bromide exposure was significantly different (p < 0.05) for both concentrations, except at 1 h exposure for 2 µg/ml EtBr. Such differences can be attributed to overall chromosomal condensation differences between sexes. Regardless, the increased mitotic index and chromosome resolution could benefit cytogenetic studies in other fish species.

Platelet-rich plasma is similar to platelet-rich plasma plus hyaluronic acid for the treatment of knee osteoarthritis at 2 years: a randomized controlled trial

IntroductionAutologous platelet-rich plasma (PRP) and hyaluronic acid (HA) are common treatments for knee osteoarthritis (OA). Several studies have demonstrated PRP as a safe and effective treatment for OA and, in some studies, produces a better outcome than HA. ObjectiveThe primary objective of this study was to determine if HA injected with PRP would improve the efficacy of treatment of symptomatic knee OA compared to PRP alone. We hypothesized that the addition of HA would improve the efficacy of (PRP). MethodsA total of 64 participants with Kellgren-Lawrence (KL) Grades 1 to 4 knee OA were randomized into 2 groups and scheduled to receive 3-injections. Group 1 [PRP] received injections of PRP. Group 2 [HA+PRP] received the same treatment, with an additional HA injection for the first 2 injections. Both groups were blindfolded for the first 2 injections. To evaluate the efficacy of the regimen, participants completed patient reported outcome measures (PROMs). PROMs were completed prior to injections and at 1, 3, 6, 12, 18, and 24 months after the final injection. ResultsParticipants in both groups felt pain consistent with standard-of-care HA injection regimens with no difference in perceived pain. No infections or complications were observed. All PROM scores demonstrated improvement over baseline from 1-24 months post injections. There were no statistically significant differences between the groups. ConclusionsFor the treatment of OA, PRP alone or PRP concomitantly with HA performed similarly out to 24 months. PRP in combination with HA was not superior to PRP alone.

Formation of CH2O and UHC emissions during catalyst-heating operation in compression ignition engines: High-speed FID and mid-IR extinction diagnostics

To comply with increasingly stringent pollutant emissions regulations, catalyst-heating operation in diesel engines is critical to achieving rapid light-off of exhaust aftertreatment catalysts during the first minutes of cold start. Current approaches to catalyst-heating operation typically involve one or more late post injections to retard combustion phasing and increase exhaust gas temperatures. The ability to retard post injection timings while maintaining acceptable pollutant emissions levels is pivotal for improved catalyst-heating operations. This experimental study aims to provide further insight into unburned hydrocarbons (UHC) and formaldehyde (CH2O) formation under catalyst-heating operation.In this study, high-speed laser extinction based measurements of CH2O are demonstrated in an optically accessible exhaust runner, and high-speed UHC measurements are also performed using a fast flame ionization detector analyzer during catalyst-heating operation. Time-resolved CH2O and UHC emission measurements are used to analyze the effect of each injection event in a five-injection strategy (two pilots, one main and two posts) on the pollutant emissions. The first pilot injection generates a significant amount of UHC unevenly distributed in the chamber, with UHC trapped primarily in the upper-cylinder and inside-the-bowl regions. The fuel delivered with the second pilot injection partially burns the unburned fuel from the first pilot injection particularly in inner-bowl region, creating short-chain hydrocarbons corresponding to formation of CH2O. UHC is dramatically reduced in the presence of the main injection, reinforcing the hypothesis by showing large CH2O emission during intermediate and later exhaust process. The first post injection produces UHC and CH2O in the upper-cylinder area due to over-mixing, which is further promoted by the second post injection, while these post-injections do not substantially affect near-bowl emissions.

Efficacy and Safety of Suprachoroidal Triamcinolone Acetonide in Cases of Resistant Diabetic Macular Edema

Background and Aim: Patients with diabetes are at risk of losing their vision due to diabetic macular edema (DME). Symptoms of diabetic macular edema occur as fluid leaks from retinal vessels into the surrounding neural retina due to hypoglycemia-induced damage to the blood-retina barrier. The current study aimed to assess the safety and efficacy of suprachoroidal triamcinolone acetonide in resistant diabetic macular edema cases. Patients and Methods: This interventional case series was carried out on 32 diabetic macular edema cases in the Department of Ophthalmology, Hayatabad Medical Complex, Peshawar during the period from April 2019 to September 2019. All the patients above 16 years of age with Type-1 DM or Type-2 DM were enrolled in this study. Intraocular Pressure (IOP), Baseline Best Corrected Visual Acuity (BCVA), and Central Subfield Thickness (CST) were determined and recorded. Post-SCTA follow-up was done in one and three months. During follow-up, the measured clinical factors were noted and analyzed in SPSS version 26. Results: Of the total 32 diabetic macular edema cases, 15 (46.9%) were male and 17 (53.1%) were females. The overall mean age was 48.64 ± 8.72 years. The frequency of prior injections received were 6.2 with maximum 12 and minimum four. CST pre-injection mean value was 612.8 ± 198.3 um and CST post-injection mean value at one and three months was 308.6± 62.6 um and 302.72± 58.64 um respectively. Statistical significance was found in pre and post one-month CST injections. The BCVA pre-injection and post-injection mean value at one and three months was 0.8 ± 0.19 and 0.49 ± 0.29 and 0.39 ± 0.20 respectively. At the one and three months post injection, there was statistical significance for both pre and post injection CST. A mean IOP of 12.32 mmHg was recorded pre-injection. Previously, 14.82 mmHg and 14.48 mmHg of intraocular pressure were recorded respectively after one and three months of injection. Conclusion: The present study found that Triamcinolone Acetonide (TA) was administered for anatomical and functional improvement. OCT macular thickness can be improved and refractory diabetic macular edema can be reduced using SCT. Keywords: Resistant diabetic macular edema, Efficacy, Suprachoroidal Triamcinolone

PMON79 Supraphysiologic vasopressin-induced receptor desensitization; a case report

Abstract Background Arginine vasopressin (AVP) is a nonapeptide released from the neurohypophysis in response to increases in plasma osmolality, hypovolemia, hypotension, and angiotensin II. V2 receptors, expressed on the basolateral membrane of the renal collecting ducts coupled to the adenylyl cyclase-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway. PKA increases the synthesis and shuttling of aquaporin 2 water channel containing vesicles (AQMCV) from cytoplasmic vesicles to the luminal surface of the renal collecting ducts (and inhibits the endocytosis of the vesicles), where they are inserted into the apical cell membrane. As a result, AVP increases free water reabsorption from the filtrate and decreases serum osmolality. There are different protocols for CDI management in post neurosurgical patient, including IV or SQ injections as well as continuous vasopressin drip. Here we discussed a case where prolonged IV drip could probably have caused loss of response to IV DDAVP injections. Case Patient is a 46-year-old male admitted with AMS with imaging revealed ruptured anterior communicating artery aneurysm associated with subarachnoid and intra parenchymal hemorrhage. The patient underwent emergent aneurysm coiling and EVD placed. The patient was subsequently started on heparin infusion due to a large frontal lobe clot which was found on cerebral angiogram. The next day, the patient developed acute diabetes insipidus with hypernatremia and polyuria. Repeat head CT demonstrated increased cerebral edema around the frontal clot. The patient underwent right frontal craniotomy for clot evacuation. He patient was subsequently started on vasopressin infusion (ranging from 0.5-6 units/hour) by neurosurgery team for urinary output less than 200 mL/hour. ​Urinary output and sodium level improved and remained stable on infusion. When endocrinology attempted transition to DDAVP IV injections patient responded with severe polyuria to initial 0.5 mcg injection. Eventually patient required 1 mcg IV every 4 hours dosing to maintain normal urine output and required a slow wean off to the standard dose of 0.5 mcg every 8 hours over 14 days. Discussion we are presenting a case of CDI associated to SAH who was started on IV infusion of vasopressin, required slow weaning. phenomenon called for slow re-sensitization of the receptors with gradual decreasing of DDAVP dosing. Animal studies have shown that V1 and V2 receptors levels are sensitive to hormone-induced downregulation of hormone receptors. Hypervasopressinemia in rats whose blood vasopressin concentration was experimentally elevated by IV infusion to extraphysiologic levels caused significant desensitization of kidney vasopressin receptors. In another study, IM injection of DDAVP to rats led to a total loss of kidney V receptors. Thus, it is likely that administration of high dose DDAVP IV in this patient induced downregulation of kidney V2 receptors. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PMON79 Supraphysiologic Vasopressin-Induced Receptor Desensitization: A Case Report

Abstract Background Arginine vasopressin (AVP) is a nonapeptide released from the neurohypophysis in response to increases in plasma osmolality, hypovolemia, hypotension, and angiotensin II. V2 receptors, expressed on the basolateral membrane of the renal collecting ducts coupled to the adenylyl cyclase-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway. PKA increases the synthesis and shuttling of aquaporin 2 water channel containing vesicles (AQMCV) from cytoplasmic vesicles to the luminal surface of the renal collecting ducts (and inhibits the endocytosis of the vesicles), where they are inserted into the apical cell membrane. As a result, AVP increases free water reabsorption from the filtrate and decreases serum osmolality. There are different protocols for CDI management in post neurosurgical patient, including IV or SQ injections as well as continuous vasopressin drip. Here we discussed a case where prolonged IV drip could probably have caused loss of response to IV DDAVP injections. Case Patient is a 46-year-old male admitted with AMS with imaging revealed ruptured anterior communicating artery aneurysm associated with subarachnoid and intra parenchymal hemorrhage. The patient underwent emergent aneurysm coiling and EVD placed. The patient was subsequently started on heparin infusion due to a large frontal lobe clot which was found on cerebral angiogram. The next day, the patient developed acute diabetes insipidus with hypernatremia and polyuria. Repeat head CT demonstrated increased cerebral edema around the frontal clot. The patient underwent right frontal craniotomy for clot evacuation. He patient was subsequently started on vasopressin infusion (ranging from 0.5-6 units/hour) by neurosurgery team for urinary output less than 200 mL/hour. ​Urinary output and sodium level improved and remained stable on infusion. When endocrinology attempted transition to DDAVP IV injections patient responded with severe polyuria to initial 0.5 mcg injection. Eventually patient required 1 mcg IV every 4 hours dosing to maintain normal urine output and required a slow wean off to the standard dose of 0.5 mcg every 8 hours over 14 days. Discussion we are presenting a case of CDI associated to SAH who was started on IV infusion of vasopressin, required slow weaning. phenomenon called for slow re-sensitization of the receptors with gradual decreasing of DDAVP dosing. Animal studies have shown that V1 and V2 receptors levels are sensitive to hormone-induced downregulation of hormone receptors. Hypervasopressinemia in rats whose blood vasopressin concentration was experimentally elevated by IV infusion to extraphysiologic levels caused significant desensitization of kidney vasopressin receptors. In another study, IM injection of DDAVP to rats led to a total loss of kidney V receptors. Thus, it is likely that administration of high dose DDAVP IV in this patient induced downregulation of kidney V2 receptors. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Prediction of split injection strategy assisted diesel engine combustion, performance and emission characteristics fuelled waste frying oil methyl ester through central composite design

The objective of this study is to use response surface methodology to forecast the performance, combustion, and emission characteristics of an advanced injection strategy-assisted diesel engine running on waste frying oil methyl ester. The experiment was carried out on a diesel engine using a high-pressure fuel injection system. The main injection timing ranges varied from 16 to 24 °CA bTDC, whereas the post-injection ranges from −6 °CA bTDC to 6 °CA aTDC. The injection quantity for the main and post injections quantity varied from 70 % to 90 %, 10 % to 30 %, and the injection pressure is set at 500 bar. Experiments were carried out using a design matrix developed by the design of experiments. At 100 % load, B100-90 %-10 % obtained the highest BTE of 33.87 % and the lowest fuel consumption of 0.268 kg/kW-hr. At the main injection timing of 22 °CA and post-injection timing of −4 °CA, D100-80 %-20 % achieved the lowest unburned hydrocarbon, Smoke emission of 13 ppm, and 1.613 FSN respectively. The point prediction approach was used to forecast the combustion and emission parameters of a diesel engine, and the predicted results were in good agreement with the experimental results. Furthermore, when compared to advance injection timing for biodiesel fuel, retarded injection timing reduces nitric oxide emission. The Split injection strategy is one of the most effective techniques to reduce soot and NO × emissions while maintaining diesel engine efficiency.

Abstract 938: Characterization of a murine pancreatic ductal adenocarcinoma (PDAC) model with tamoxifen inducible pancreas-specific blockade of transforming growth factor-β (TGF-β) signaling with KrasG12D expression

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a five-year overall survival of less than 10%. The lack of effective therapeutic strategies for PDAC necessitates the development of models to better understand the disease. Transforming growth factor-β (TGFβ)-SMAD4 signaling plays a critical role in PDAC development with more than half of all patients either have mutated SMAD4 (loss of function) or altered type II TGF TGFβ -receptor (Tgfbr2) gene. Here we present a murine model of PDAC with Tamoxifen induced conditional deletion of the TGFβ-receptor 2 (Tgfbr2) gene and expression of an activating KrasG12D mutation in pancreatic acinar cells. LSL-KrasG12D/+; Tgfbriifl/fl; Ptf1a-CreER mice were generated by crossing Ptf1aCre-ERTM mice with LSL-KrasG12D mice in which expression of KrasG12D is restrained by a lox-stop-lox cassette until Cre activation by tamoxifen injection. These mice were then bred with Tgfbr2fl/fl mice with loxP sites flanking exon 4 of the Tgfbr2 allele to block TGFβ-SMAD4 signaling. 18Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography was performed to detect tumors and measure their metabolic volumes and standard uptake values over time. This model showed a latency of approximately 16-20 weeks following 5 i.p. injections of tamoxifen (~75 mg/kg in corn oil). Follow-up on the survival of the mice post tamoxifen injections showed the median survival of 252 days in male and 234 days in female mice. Histological evaluation showed multifocal nodules of neoplasia composed of tubules and acini with cuboidal to polygonal cells. Carcinoma cells were positive for cytokeratin 19 and for mucins identified by Alcian blue staining, both confirming the ductal phenotype of these tumors. Picrosirius red staining demonstrated dense stromal desmoplasia which recapitulates human disease. Flow cytometric evolution of the immune microenvironment was also done to evaluate the infiltration of immune cells. Additional characterization of our novel mouse model of pancreatic cancer is underway to understand PDAC progression and develop effective therapeutic approaches. Citation Format: Sanjay Pandey, Brett Bell, Claudia G. Chavez, Wade Koba, Talicia Savage, Patrik Asp, Indranil Basu, Chandan Guha. Characterization of a murine pancreatic ductal adenocarcinoma (PDAC) model with tamoxifen inducible pancreas-specific blockade of transforming growth factor-β (TGF-β) signaling with KrasG12D expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 938.

Hydraulic characterization of a second-generation common rail injector operating under solo and split injection strategies

In modern compression ignition engines, complex fuel injection strategies are adopted in order to enable a clean and efficient combustion process and an effective combustion noise control algorithm. Multi-injection strategies inject fuel into the combustion chamber several times (e.g. pilot, main, and post injections) during each combustion cycle, while split-injection approach further divides the main injection into different shots, with very short dwell time. Split injection may help to enhance air entrainment into the spray core where the fuel droplets are highly dense and mixing quality is poor. These advanced injection techniques lead to complex hydraulic behaviors including injection instability and eventually affecting fuel metering accuracy, hence detailed investigations are required. Understanding hydraulic characteristics especially during peculiar events like start/end of injection and accurately quantifying the actual injection volume, injection rate, and pressure variations in different locations of the injection system in each single activation of a complex strategy are key targets. In this work, the hydraulic behavior of a second generation common-rail solenoid injector operating under split-injection strategy has been experimentally investigated in terms of injection rate and injected volume. An extensive experiment has been conducted in this study using a state-of-the-art injection system operating on a hydraulic test bench equipped with a Zeuch-method type injection analyzer. It is found that although the standard of deviation of injection rates and injected volume is quite small for isolated injection events, the shot-to-shot deviation for split-injection mode can be significantly higher depending mainly on dwell time, fuel quantity ratio between the two shots and injection pressure level, as an effect of both pressure perturbations in the feeding line and in the injector caused by close actuations, eventually joined to inertial phenomena of the injector needle. The present paper reports an analysis methodology for the quantitative evaluation of systematic inter-cycle deviations, in the effort towards a deeper exploitation of the potential benefits offered by advanced injection strategies.

Effect of Fuel Cetane Number on the Performance of Catalyst-Heating Operation in a Medium-duty Diesel Engine

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;To comply with increasingly stringent pollutant emissions regulations, diesel engine operation in a catalyst-heating mode is critical to achieve rapid light-off of exhaust aftertreatment catalysts during the first minutes of cold starting. Current approaches to catalyst-heating operation typically involve one or more late post injections to retard combustion phasing and increase exhaust temperatures. The ability to retard post injection timing(s) while maintaining acceptable pollutant emissions levels is pivotal for improved catalyst-heating calibrations. Higher fuel cetane number has been reported to enable later post injections with increased exhaust heat and decreased pollutant emissions, but the mechanism is not well understood. The purpose of this experimental and numerical simulation study is to provide further insight into the ways in which fuel cetane number affects combustion and pollutant formation in a medium-duty diesel engine.&lt;/div&gt;&lt;div class="htmlview paragraph"&gt;Three full boiling-range diesel fuels with cetane numbers of approximately 45, 50, and 55 are employed in this study with a well-controlled set of calibrations employing a five-injection strategy. The two post injections are block-shifted to increasingly retarded timings, and the effects on exhaust heat and pollutant emissions are quantified for each fuel. For a given injection strategy calibration, increasing cetane number enables increased exhaust temperature and decreased hydrocarbon and carbon monoxide emissions for a fixed load. The increase in exhaust temperature is attributed to an increased fueling requirement to compensate for additional wall heat losses caused by earlier, more robust pilot combustion with the more reactive fuels. Formaldehyde is predicted to form in the fuel-lean periphery of the first pilot injection spray and can persist until exhaust valve opening in the absence of direct interactions with subsequent injections. Unreacted fuel-air mixture in the fuel-rich interior of the first-pilot spray is likely too cool for any significant reactions, and can persist until exhaust valve opening in the absence of turbulence/chemistry interactions and/or direct heating through interactions with subsequent injections.&lt;/div&gt;&lt;/div&gt;