Acute Damage Research Articles

Cardiac troponin elevation in intracerebral hemorrhage patients may rather reflect acute myocardial damage than acute myocardial infarction

Abstract Background Patients with acute ischemic stroke (AIS) and elevated cardiac troponin (cTn) have worse functional and mortality-related outcome. While elevated cTn is also frequently observed in patients with intracerebral hemorrhage (ICH), routine invasive coronary angiography should not be performed on these patients. Existing data on correlation of cTn elevation with patient outcome and the underlying causes in this specific patient group are sparse and largely heterogeneous. Purpose To investigate the clinical variables that predict cTn elevation in patients with ICH and the impact of cTn elevation on intrahospital mortality and functional outcome. Methods Our long-term Stroke Database was screened for ICH patients with high-sensitivity (hs) cTn measurement on admission (from 2015 onwards). Baseline characteristics, intrahospital mortality and functional outcome at discharge were compared between the groups with and without cTn elevation (hs-cTnI > vs. ≤0.045 µg/L). In addition, clinical variables with suspected significance for cTn elevation were analyzed for their predictive value. Results A total of 93/498 patients with ICH (18.7%; mean age 73±15 years, 53.8% females) were found to have a cTn elevation. Regarding etiology, 38.7% had an ICH occurring after AIS and 31.2% had a hypertensive ICH (each p=NS between groups). Patients with cTn elevation did not have a more pronounced cardiovascular risk profile and had a comparably low prevalence of coronary artery disease (CAD; 18.5%, p=NS). However, they were significantly less likely to be on oral anticoagulation at the time of the bleeding event (7.5 vs. 18.0%, p=0.013). CTn elevation had no negative impact on intrahospital mortality (21.5 vs. 20.5%, p=NS) or functional outcome at discharge (NIHSS score 10 (2; 26) vs. 9 (2; 22) points, mRS 5 (3; 5) vs. 5 (3; 5) points, each p=NS). Increasing NIHSS score on admission (p=0.021, OR 1.084 [1.012-1.160]), mRS ≥4 on admission (p=0.005, OR 2.207 [1.180-2.826]), infratentorial bleeding localization (p=0.034, OR 4.899 [1.132-21.207]) and aortic valve stenosis ≥ intermediate (p<0.001, OR 8.435 [2.429-29.294]) predicted cTn elevation. In contrast, severely impaired left ventricular function, CAD, atrial fibrillation, intraventricular hemorrhage or ICH occurring after AIS had no predictive value. Conclusions Almost one fifth of patients with ICH had an elevated cTn. Unlike in AIS, in ICH cTn elevation was not associated with a worse functional or mortality-related intrahospital outcome. In particular, severe functional impairment on admission, reflecting severe ICH, or infratentorial hemorrhage localization, thought to affect the autonomic nervous system, was predictive of concomitant myocardial cell damage. CAD was rare overall. This could indicate that the cTn elevation in connection with ICH is primarily related to acute myocardial damage along the brain-heart axis and less to myocardial infarction.

Protection of mice against cecal ligation and puncture-induced polymicrobial sepsis by a Fasciola hepatica helminth defence molecule.

Sepsis results from a dysregulated host immune response to infection and is responsible for ~11 million deaths each year. In the laboratory, many aspects of sepsis can be replicated using a cecal ligation and puncture (CLP) model, which is considered the most clinically relevant rodent model of sepsis. In the present study, histological and biomarker multiplex analyses revealed that the CLP model initiated a large-scale inflammatory response in mice by 24 h, with evidence of acute organ damage by 48-72 h. While many typical pro-inflammatory cytokine/chemokines were systemically elevated, a specific array including IL-10, eotaxin, MIP-1α, MIP-1β, MCP-1 and RANTES noticeably increased just prior to animals reaching the humane endpoint. Treatment of mice with 10 μg of a synthetic 68-amino acid peptide derived from an immunomodulatory molecule secreted by a parasitic worm of humans and livestock, Fasciola hepatica, termed Fasciola hepatica helminth defence molecule (FhHDM), potently suppressed the systemic inflammatory profile, protected mice against acute kidney injury, and improved survival between 48 and 72 h post-procedure. These results suggest that the anti-inflammatory parasite-derived FhHDM peptide has potential as a bio-therapeutic treatment for sepsis.

Cardiac autonomic changes after stroke

Abstract Introduction There is a highly complex and clinically important relationship between the cardiac and the nervous system, called the heart-brain axis [1]. Therefore, acute brain damage may lead to alterations in cardiac function due to changes in the autonomic nervous system[2,3]. Novel computerised biosignal analysis techniques and advanced biosignal assessment could provide a valuable tool to sensitively analyse cardiac autonomic function (CAF). CAF can be characterized by two complementary digital biomarkers, periodic repolariation dynamics (PRD) and deceleration capacity (DC). The aim of this study was to determine CAF by means of PRD and DC in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and to analyze them according to their relationship with specific cardiac (high-sensitive Troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro BNP)) and stroke (location, type, severity) characteristics. Methoden / Methods Between February 22, 2021, and May 5, 2023, 282 patients after an AIS or TIA were enrolled in the study. During the inpatient stay, all relevant parameters were recorded and stored in a database. To assess CAF, a 30-minute biosignal measurement was performed with a high resolution (1kHz) electrocardiogram (ECG). Cardiac autonomic biomarkers, PRD and DC, were calculated semiautomatically afterwards from patients. Results Fifteen ECGs were excluded due to poor recording quality. Consequently, data from 261 AIS and 21 TIA patients were analyzed. A total of 105 patients (37.2 %) had pathological PRD (≥ 5.75 deg2) and/or DC (≤ 2.5 ms), 78 patients (27.7 %) had pathological PRD, and 57 patients (20.2 %) had pathological DC. The median PRD was 3.13 deg2 and the median DC was 5.30 ms (see Figure). There were no significant differences in the distribution of PRD and DC between male and female patients (PRD p = 0.38, DC p = 0.30), and between AIS and TIA patients (PRD p = 0.13, DC p = 0.66). Patients with middle cerebral artery (MCA) infarction had significantly higher median PRD values (3.56 deg2 [IQR 1.51 - 6.59 ] vs. 2.81 deg2 [IQR 1.15 - 5.99], p = 0.047) and lower median DC values (4.66 ms [IQR 2.65 – 7.76] vs. 6.11 ms [IQR 3.15 – 10.61], p = 0.011) than patients with stroke located in another cerebral regions (see Figure). Patients with pathological PRD or DC had significantly higher hsTnT (13.50 ng/l [IQR 9.7 – 24.1] vs. 11.05 ng/l [ IQR 7.13 – 16.23], p < 0.001) and NT-pro BNP (269.00 ng/l [IQR 117.50 – 687.00] vs. 125.50 ng/l [IQR 57.00 – 288.25], p < 0.001) values. Conclusions The study showed that a considerable proportion, more than one third of all patients, had evidence of cardiac autonomic dysfunction after acute cerebral ischaemia. Of particular interest, PRD was higher and DC was lower in patients with MCA ischaemia, reflecting a potentially higher cardiac risk profile. Cardiac autonomic dysfunction was also associated with increased hsTnT and NT-proBNP levels.

Determination of proinflammatory cytokine levels to assess the reparative potential of tissues in ischemic damage and local correction with hyaluronic acid

The hypothesis of the study was the assumption that local correction of secondary alteration stops excessive inflammation activity and promotes early activation of reparative processes. Objective: in an animal experiment, to evaluate the dynamics in blood plasma of the concentration of circulating inflammatory cytokines in acute ischemic damage to soft tissues and after local action of a hyaluronic acid-based drug. In anesthetized Wistar rats, acute ischemic damage to the soft tissues of the thigh was simulated by mechanical compression with a vise for 7 hours. After removing the vise, the rats were divided into 2 groups of 32 individuals: control (without treatment) and experimental (3 hours after removing the vise, the drug was injected into the area bordering the compression zone with a sterile syringe based on hyaluronic acid “Hyalift-3.5”, diluted with 0.9% solution to the final concentration of the drug – 1.75%). The concentration of cytokines in blood plasma was determined, histological sections of soft tissues in the compression area were examined. An increase in the plasma concentration of proinflammatory cytokines (IL-1β, TNFα, IL-6) was revealed during the entire follow-up period (21 days), especially 7 days after the injury. To the greatest extent, these changes were observed in animals in the control group, which was manifested by a statistically significant increase in the concentration of IL-1β, TNFα and IL-6, relative to the values in intact rats: on average by 7.2; 3.7 and 5.3 times, respectively. In rats in the experimental group, local administration of a hyaluronic acid-based drug already in the early period after injury limited the severity of inflammation (an increased concentration of IL-10 was recorded in blood plasma). The sanogenetic role of local administration of hyaluronic acid in the wound process is mediated by the relief of inflammation in the early period of damage and is realized in increasing the reparative potential of tissues according to the variant of earlier and significant formation of musculoskeletal tissue regenerates.

A novel immunopharmacological biocompound

The publication is devoted to topical issues of experimental study of new biocompounds, based on the creation of a consortium of biological composite compounds – biological active substances (metabiotics) produced by strains 59T and 60T of saprophytic compounds of the genus Bacillus subtilis. These strains are very promising for the creation of hepatopicts, new medicinal substances, in the creation and development of a new pharmacological class of hepatoprotectors. Previous studies have shown the safety and hepatoprotective effect of biologically active drugs. It is worth noting that the very effective compounds are the produced biologically active substances – metabolites of bacterial origin, on the basis of which it seems appropriate to create a new class of drugs – metabiotics. The absence of vegetative probiotic cells in such compounds will reduce the additional immune load on the body. The combined use of these compounds provides a potentiated pharmacological effect. In this regard, it seemed appropriate, under the conditions of modeling toxic liver damage by carbon tetrachloride, to conduct an experimental assessment of the immunotropic effect of biologically active substances (BAS) on laboratory animals in order to confirm the effect on cellular factors of immunity. The purpose of the study was to study the effect of the combined use of dietary supplements produced by Bacillus subtilis microorganisms on indicators of cellular immunity in laboratory animals with toxic liver damage. Acute toxic hepatitis was reproduced in white laboratory rats with repeated intragastric administration of carbon tetrachloride. The comparison drug was a registered hepatoprotective drug – ursosan. The immunotropic effect was assessed using factors such as: phagocytic activity of macrophages and neutrophils (FA), NBT test, quantitative assessment of antibody-forming cells, T and B lymphocytes. As a result of the studies performed, reliable data were obtained on an increase in the number of T and B lymphocytes, antibody-forming cells, as well as an increase in FA, which confirms the activation of all parts of cellular immunity in conditions of acute toxic liver damage. The data obtained allow us to recommend the studied biocompound for the creation of new drug candidates of microbiological origin, hepatoprotective agents with immunotropic effects.

The Pathology and Blood Biochemistry of Juvenile Lates calcarifer on Diets Contaminated With Mycotoxins, Histamines and Rancid Fats-A Case Study.

Mycotoxins, originating from contaminated raw materials or suboptimal feed storage, are a growing concern in tropical aquaculture. Common fungi such as Aspergillus spp. and Fusarium spp. produce mycotoxins including aflatoxin, fumonisin, deoxynivalenol and zearalenone. High doses or prolonged exposure (weeks) to low doses of these mycotoxins (< 20 μg/kg) can depress growth, immunity, and cause mortality. This study investigated poor growth and low survival in juvenile Asian seabass, Lates calcarifer fed two different diets (FM40 and ABS3) for 5 weeks. Analysis of these diets revealed high peroxide values, multiple mycotoxins and high histamine levels. Fish fed the FM40 diet, which was contaminated with aflatoxin B1 (13.2 μg/kg), aflatoxin B2 (1.9 μg/kg), deoxynivalenol (29.5 μg/kg), alternariol (2.2 μg/kg), elevated peroxide value (45.91 mEq/kg), and histamine (129.51 mg/kg) developed mild bile duct hyperplasia, depressed total serum proteins (50.40 ± 10.06 g/L), markedly elevated blood potassium (8.2 ± 0.18 mmol/L), and heavy iron deposits in splenic melanomacrophage centres (Perl's stain) indicative of increased haemolysis. The presence of multiple cytotoxic mycotoxins in FM40 diet could explain the increased haemolysis and elevated blood potassium. In contrast, fish fed the ABS3 diet, which had high histamine levels (210.05 mg/kg), exhibited protein-losing nephropathy with multifocal fibrin plugs (Martius scarlet blue stain) indicating acute renal damage, and elevated blood calcium and phosphorus levels. Histamine is metabolised and excreted through the kidneys and known to induce renal arteriolar constriction, disrupt glomerular filtration barrier and increase permeability resulting in protein loss. This study shows that blood biochemistry and histopathology are useful diagnostic tools for assessing the impact of mycotoxins and histamines on fish health.

Mesenchymal Stem Cell Therapy Mitigates Acute and Chronic Lung Damages of Sulfur Mustard Analog Exposure

Sulfur mustard (SM) is an established chemical weapon that can result in severe damage to parts of the body. Currently, there are no effective treatments available for SM-caused damage. We aimed to investigate the therapeutic potential of adipose-derived mesenchymal stromal cells (AD-MSCs) and conditioned medium (CM-MSCs) in acute and chronic pulmonary mouse models caused by 2-chloroethyl ethyl sulfide (CEES), an SM analog. The mice were divided into 4 experimental groups:(1) CEES+AD-MSCs, (2) CEES+CM-MSCs, (3) CEES, and (4) control. The model observation time was divided into 7 days for the short and 6 months for the long term. AD-MSCs were injected into mice via intraperitoneal injection 24 hours after CEES exposure. The therapeutic effects of AD-MSCs on pulmonary tissue damage were assessed using a histopathologic assay, measuring the neutrophil count, and bronchial alveolar lavage fluid (BALF) protein level. The levels of inflammatory and anti-inflammatory cytokines were evaluated using the enzyme-linked immunosorbent assay as the outcomes of interest. Lung damage progression was reduced by AD-MSC treatment in mice after CEES injection into the peritoneum. The proportion of CD11b+F4/80+ macrophages in the peritoneum was significantly lowered by AD-MSC treatment following CEES exposure. AD-MSC administration also reduced the level of pro-inflammatory cytokines, BALF protein, and nitric oxide levels in the peritoneal cavity. By reducing inflammation and enhancing tissue healing, AD-MSCs and CM-MSC help prevent acute lung damage caused by CEES. The current study supports the use of a mouse model as a solid experimental foundation and indicates potential use for future cell treatment.

Diethylhexyl phthalate induces immune dysregulation and is an environmental immune disruptor

Diethylhexyl phthalate (DEHP) is the most abundant phthalate compound in the environment, and has been linked with multiple human diseases. The immune system is closely associated with the occurrence and progression of various diseases. However, minimal research has addressed the impact of DEHP on the immune system. In this study, single-cell RNA sequencing was performed using spleen tissue of mice to comprehensively determine alterations of the immune system in response to DEHP. The results showed that DEHP exposure reduced the absolute number of peripheral white blood cells (WBCs), including lymphocytes, monocytes, eosinophils, basophils, and neutrophils in mice. In addition, scRNA-seq analyses showed that inflammatory signaling and the expression of heat shock proteins (HSPs) were reduced in all peripheral immune cell populations. Furthermore, we established a mice cecal ligation and puncture (CLP) model, and showed that DEHP exacerbated sepsis-induced immunosuppression and organ damage. These results suggest that DEHP is an environmental immune disruptor that undermines the immune system, exacerbating acute infections and organ damage. Our findings offer a novel perspective on the hazards of DEHP to human health.

Role of Vitamin C on methotrexate-induced nephrotoxicity in psoriasis context: A preclinical assessment

Methotrexate (MTX) is the most prescribed drug for systemic treatment of psoriasis. However, its clinical use is limited by its nephrotoxicity, which antioxidants can attenuate. This study evaluates the impact of vitamin C (vitC), a well-known antioxidant, on nephrotoxicity induced by high MTX doses in the context of psoriasis. To achieve this purpose, the kidney injury triggered by acute MTX exposure was established in an imiquimod-induced psoriasis-like mouse model. Mice were randomly divided into six groups: group 1 (control); group 2 (Imiquimod, IMQ), group 3 (IMQ+vitC 175 mg/kg/day); group 4 (MTX 20 mg/kg i.p); group 5 (IMQ+MTX 20 mg/kg) and group 6 (IMQ+MTX 20 mg/kg + vitC 175 mg/kg/day). The effects of these treatments were determined by considering the evolution of IMQ-induced skin lesions and serum creatinine levels. Moreover, histopathological analysis, lipid peroxidation, oxidative stress, and TNF-α production were determined in kidney tissue. Results showed that vitC attenuates renal damage in the context of IMQ-induced psoriasis. However, the opposite occurs when administered with IMQ+MTX, worsening skin psoriasis lesions and exacerbating acute renal tubular necrosis and oxidative DNA damage. These results establish new clues about the MTX-induced nephrotoxicity in the psoriasis context and the putative protective effects of vitC. It suggests that vitC supplementation could help attenuate the renal damage promoted by the psoriatic pathological environment. However, it should be avoided in psoriasis patients with renal dysfunction treated with MTX.

Biochemical and Histopathological Analysis of Aqueous Extract of an Aphrodisiac Formulation against Acetaminophen Induce Hepatocyte Injuries in Wistar Rats

The aimed of this study was to examine the biochemical parameters and histopathological effects of aqueous extract of an aphrodisiac formulation against acetaminophen induce hepatocyte injuries in Wistar rats. Zainacin Dadin duniya (aphrodisiac herbs) extract was prepared by cold maceration. The animal study was done using 30 adult both male and female Wistar rats was grouped into 5 groups (n=6) and orally administered with five different treatments (saline, liver drug, acetaminophen, extract and extract/ acetaminophen) for the period of 28days. The blood is collected from each grouped rat for biochemical parameters test and all rats were later sacrificed for histologically processed investigation. The results showed that the oral administration of the acetaminophen in group 3 treated rats causes a significant (P&lt;0.05) increased in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), but, when administered with the extract in group 4 rats, there was a significantly (p&lt;0.05) decreased in the activities of ALT, AST and ALP. Significantly (p&lt;0.05) increased in the Kidney Function Markers (Creatinine, and Urea) and decreased in Glucose level in the group 3 rats treated with acetaminophen, when compared with the group 4 rats treated with the extract, there was a significant (p&lt;0.05) decreased in Creatinine, and Urea level and increased in the Glucose level. The serum total protein, Albumin, and Globulin significantly (p&lt;0.05) decreased in the group 3 rats treated with acetaminophen while the bilirubin increased significantly. While group 4 rats showed significant increase in the total protein, Albumin, and Globulin and decreased in the bilirubin levels. The Results of Histopathology findings revealed hepatic tissue with distorted hepatocytes, portal vein, and sinusoids accompanied with massive necrosis in the liver of the group 3 rats treated with acetaminophen. While the liver of the group 4 rats showed, hepatic tissue with preserved architecture composed of cords of normal hepatocytes, normal portal vein, and sinusoids. There are no features of acute or chronic damage. The histologically Results of the small intestines of the all five (5) grouped rats showed preserved layers of muscosa, submucosa, muscularis externa, and serosa. There are no features of acute or chronic toxicity. Conclusively, the prolonged oral consumption of acetaminophen in animals resulted in hepatocellular deleterious effects and may be of a similar hazard in humans. Overall, administration of the extract in rats has significant ameliorative effect on the rats; this may be of immense benefits in the management of hepatocytes, necrosis in the liver and its associated biomarkers complications. Improved liver functions as well as improved antioxidant status are beneficial in the management of chronic diseases such as liver failure.

The Ambivalent Role of miRNA-21 in Trauma and Acute Organ Injury

Since their initial recognition, miRNAs have been the subject of rising scientific interest. Especially in recent years, miRNAs have been recognized to play an important role in the mediation of various diseases, and further, their potential as biomarkers was recognized. Rising attention has also been given to miRNA-21, which has proven to play an ambivalent role as a biomarker. Responding to the demand for biomarkers in the trauma field, the present review summarizes the contrary roles of miRNA-21 in acute organ damage after trauma with a specific focus on the role of miRNA-21 in traumatic brain injury, spinal cord injury, cardiac damage, lung injury, and bone injury. This review is based on a PubMed literature search including the terms “miRNA-21” and “trauma”, “miRNA-21” and “severe injury”, and “miRNA-21” and “acute lung respiratory distress syndrome”. The present summary makes it clear that miRNA-21 has both beneficial and detrimental effects in various acute organ injuries, which precludes its utility as a biomarker but makes it intriguing for mechanistic investigations in the trauma field.

Clove Aqueous Extract Alleviates Acute Kidney Injury Induced by Folic Acid in Rats

Background: Acute Kidney Injury (AKI) is a common clinical disease that has a high incidence and mortality rate. Clove, a robust natural source of bioactive chemicals and rich in secondary metabolites, plays a wide range of biological roles. Aim: The present study aimed to assess the ameliorative efficacy of clove extract against acute renal damage induced by folic acid in rats. Methods: Gas Chromatography/Mass Spectrometry (GC/MS) was used to investigate the main components of clove extract. Folic acid, at a dose of 250 mg/kg, was delivered intraperitoneally to rats to induce AKI. Eighteen rats were divided into three groups: control, AKI, and AKI + clove extract (500 mg/kg). Results: The administration of clove extract significantly restored the levels of creatine, urea, uric acid, sodium, potassium, chloride, creatinine clearance, and microalbumin to nearly normal levels. Also, clove water extract inhibited oxidative stress by decreasing concentrations of Malondialdehyde (MDA) and Nitric Oxide (NO). Furthermore, clove extract elevated the levels of Glutathionereduced (GSH), Catalase (CAT), and Glutathione S-transferase (GST). Kidney section histology showed notable improvements after the administration of clove extract. Conclusion: The clove water extract has been found to contain many bioactive components possessing antioxidant and anti-inflammatory properties, effectively protecting against acute renal injury.

Mitochondria are absent from microglial processes performing surveillance, chemotaxis, and phagocytic engulfment.

Microglia continually surveil the brain allowing for rapid detection of tissue damage or infection. Microglial metabolism is linked to tissue homeostasis, yet how mitochondria are subcellularly partitioned in microglia and dynamically reorganize during surveillance, injury responses, and phagocytic engulfment in the intact brain are not known. Here, we performed intravital imaging of microglia mitochondria, revealing that microglial processes diverge, with some containing multiple mitochondria while others are completely void. Microglial processes that engage in minute-to-minute surveillance typically do not have mitochondria. Moreover, unlike process surveillance, mitochondrial motility does not change with animal anesthesia. Likewise, the processes that acutely chemoattract to a lesion site or initially engage with a neuron undergoing programmed cell death do not contain mitochondria. Rather, microglia mitochondria have a delayed arrival into the responding cell processes. Thus, there is subcellular heterogeneity of mitochondrial partitioning and asymmetry between mitochondrial localization and cell process motility or acute damage responses.

Macroscopic hematuria-associated severe acute kidney injury triggered by kidney stone formation in a patient with thin basement membrane and no history of microscopic hematuria.

Macroscopic hematuria (MH)-associated acute kidney injury (AKI) is a rare condition that causes acute tubular damage due to severe glomerular bleeding with MH. A 66-year-old Japanese woman with no significant past medical history was referred for severe kidney injury with oliguric MH. Her prior medical checkup results showed no occult blood in her urine. Seven days earlier, she had experienced transient severe acute right lumbar back pain. On admission, her serum urea nitrogen was 147mg/dL, serum creatinine (sCr) 18.3mg/dL, urinary red blood cells (RBCs) > 100/hpf, urinary protein 28.8g/gCr, with no hydronephrosis in either kidney, but two stones were found in the right kidney and right ureteropelvicjunction. At the start of her hemodialysis, the patient was treated with high-dose steroids because of suspected rapidly progressive glomerulonephritis. A renal biopsy of the left kidney showed acute tubular injury with massive RBC casts filling the tubular lumen. Glomerulitis was not detected, but electron microscopy revealed diffuse glomerular thin basement membrane (TBM). Despite immediate steroid discontinuation, the patient's renal function and MH improved, and she was weaned from hemodialysis. The stones resolved 2months after onset, but microscopic hematuria persisted for 7months post-onset. The sCr level was fixed at 1.1mg/dL 20months post-onset. This is the first report of MH-AKI in a TBM without the risk of MH-AKI development, such as bleeding tendency or iron overload. In this TBM, a colic attack of the renal urinary tract induced glomerular bleeding, and intolerance to hematuria may have caused severe tubular damage.

Deep Learning-Enhanced Paper-Based Vertical Flow Assay for High-Sensitivity Troponin Detection Using Nanoparticle Amplification.

Successful integration of point-of-care testing (POCT) into clinical settings requires improved assay sensitivity and precision to match laboratory standards. Here, we show how innovations in amplified biosensing, imaging, and data processing, coupled with deep learning, can help improve POCT. To demonstrate the performance of our approach, we present a rapid and cost-effective paper-based high-sensitivity vertical flow assay (hs-VFA) for quantitative measurement of cardiac troponin I (cTnI), a biomarker widely used for measuring acute cardiac damage and assessing cardiovascular risk. The hs-VFA includes a colorimetric paper-based sensor, a portable reader with time-lapse imaging, and computational algorithms for digital assay validation and outlier detection. Operating at the level of a rapid at-home test, the hs-VFA enabled the accurate quantification of cTnI using 50 μL of serum within 15 min per test and achieved a detection limit of 0.2 pg/mL, enabled by gold ion amplification chemistry and time-lapse imaging. It also achieved high precision with a coefficient of variation of <7% and a very large dynamic range, covering cTnI concentrations over 6 orders of magnitude, up to 100 ng/mL, satisfying clinical requirements. In blinded testing, this computational hs-VFA platform accurately quantified cTnI levels in patient samples and showed a strong correlation with the ground truth values obtained by a benchtop clinical analyzer. This nanoparticle amplification-based computational hs-VFA platform can democratize access to high-sensitivity point-of-care diagnostics and provide a cost-effective alternative to laboratory-based biomarker testing.

Assessment of Neutrophil Gelatinase Associated Lipocalin in Children with Acute Gastroenteritis and Dehydration to Identify Early Signs of Acute Kidney Injury

Background: Gastroenteritis often correlates with acute kidney injury (AKI) in children who are hospitalized. The primary diagnostic test for acute kidney injury (AKI) in modern times is serum creatinine (SCr), which increases in the presence of AKI and is eliminated by glomerular filtration. SCr is an unsuitable biomarker for renal sickness because it lacks specificity and a slow response to disease severity or treatment changes. NGAL, or neutrophil gelatinase-associated lipocalin, is a molecular weight of 25 kDa protein and forms a covalent bond with neutrophil gelatinase. Elevations in NGAL levels due to kidney injury have important predictive value and may forecast the onset of acute kidney injury (AKI) 24-72 hours before an increase in diagnostic serum creatinine (SCr) values. Aim and objectives: This study aims to determine whether plasma NGAL concentrations in mild, moderate, or severe dehydrated acute gastroenteritis patients may indicate acute kidney damage (AKI). The research will investigate whether acute renal injury and plasma NGAL concentrations are connected. Patients and methods: The cross-sectional design was employed in this study and included 80 patients who attended the pediatric gastrointestinal clinic at Babylon Children's Hospital. Between November 2022 and June 2023, all patients had gastroenteritis symptoms accompanied by different dehydration levels. Results: Patients with severe dehydration had considerable higher level of NGAL than those with mild to moderate dehydration (p&lt;0.001). There was a notable inverse relationship (p = 0.046) between the NGAL level and potassium but a considerable direct link (p&lt;0.001) between the NGAL level and creatinine. However, no significant correlation was seen between the NGAL level and urea (p = 0.404 and 0.062, respectively). The confidence range for the area under the curve (AUC) is 0.940 to 0.981, with a confidence level of 95%. The p-value is less than 0.001. The sensitivity is 88%. An accuracy of 88.4% has been attained. The NGAL cut-off point is 3.9832. Conclusion: An analysis of plasma neutrophil gelatinase-associated lipocalin (NGAL) in individuals with gastroenteritis and varied degrees of dehydration indicated a clear and direct link between the two parameters. Specifically, when dehydration worsened, the average NGAL value increased

In situ photocrosslinkable hydrogel treats radiation-induced skin injury by ROS elimination and inflammation regulation

The clinical management of radiation-induced skin injury (RSI) poses a significant challenge, primarily due to the acute damage caused by an overabundance of reactive oxygen species (ROS) and the ongoing inflammatory microenvironment. Here, we designed a dual-network hydrogel composed of 5 % (w/v) Pluronic F127 diacrylate and 2 % (w/v) hyaluronic acid methacryloyl, termed the FH hydrogel. To confer antioxidant and anti-inflammation properties to the hydrogel, we incorporated PVP-modified Prussian blue nanoparticles (PPBs) and resveratrol (Res) to form PHF@Res hydrogels. PHF@Res hydrogels not only exhibited multiple free radical scavenging activities (DPPH, ABTS), but also displayed multiple enzyme-like activities (POD-, catalase). Meanwhile, PHF@Res-2 hydrogels significantly suppressed intracellular ROS and promoted the migration of fibroblasts in a high-oxidative stress environment. Moreover, in the RSI mouse model, the PHF@Res-2 hydrogel regulated inflammatory factors and collagen deposition, significantly reduced epithelial hyperplasia, promoted limb regeneration and neovascularization, and accelerated wound healing, outperforming the commercial antiradiation formulation, Kangfuxin. The PHF@Res-2 hydrogel dressing shows great potential in accelerating wound healing in RSI, offering tremendous promise for clinical wound management and regeneration.

Role of aldosterone in various target organ damage in patients with hypertensive emergency: a cross-sectional study

BackgroundHypertensive emergency is a critical disease that causes multiple organ injuries. Although the renin-angiotensin-aldosterone system (RAS) is enormously activated in this disorder, whether the RAS contributes to the development of the organ damage has not been fully elucidated. This cross-sectional study was conducted to characterize the association between RAS and the organ damage in patients with hypertensive emergencies.MethodsWe enrolled 63 patients who visited our medical center with acute severe hypertension and multiple organ damage between 2012 and 2020. Hypertensive target organ damage was evaluated on admission, including severe kidney impairment (eGFR less than 30 mL/min/1.73 m2, SKI), severe retinopathy, concentric left ventricular hypertrophy (c-LVH), thrombotic microangiopathy (TMA), heart failure with reduced ejection fraction (HFrEF) and cerebrovascular disease. Then, whether each organ injury was associated with blood pressure or a plasma aldosterone concentration was analyzed.ResultsAmong 63 patients, 31, 37, 43 and 8 cases manifested SKI, severe retinopathy, c-LVH and ischemic stroke, respectively. All populations with the organ injuries except cerebral infarction had higher plasma aldosterone concentrations than the remaining subset but exhibited a variable difference in systolic or diastolic blood pressure. Twenty-two patients had a triad of SKI, severe retinopathy and c-LVH, among whom 5 patients manifested TMA. Furthermore, the number of the damaged organs was correlated with plasma aldosterone levels (Spearman’s coefficient = 0.50), with a strong association observed between plasma aldosterone (≥ 250 pg/mL) and 3 or more complications (odds ratio = 9.16 [95%CI: 2.76–30.35]).ConclusionIn patients with hypertensive emergencies, a higher aldosterone level not only contributed to the development of the organ damage but also was associated with the number of damaged organs in each patient.

Change in Nfkb/Nrf2/Bax Levels by High Monomeric Polyphenols Berries Extract (HMPBE) in Acute and Chronic Secondary Brain Damage.

High Monomeric Polyphenols Berries Extract (HMPBE) is a formula highly rich in polyphenols clinically proven to enhance learning and memory. It is currently used to enhances cognitive performance including accuracy, working memory and concentration. Here, we investigated for the first time the beneficial effects of HMPBE in a mouse model of acute and chronic traumatic brain injury (TBI). HMPBE, at the dose of 15 mg/kg was able to reduce histological alteration as well as inflammation and lipid peroxidation. HMPBE ameliorate TBI by improving Nrf-2 pathway, reducing Nf-kb nuclear translocation and apoptosis, and ameliorating behavioral alteration such as anxiety and depression. Moreover, in the chronic model of TBI, HMPBE administration restored the decline of Tyrosine Hydroxylase (TH) and dopamine transporter (DAT) and the accumulation of a-synuclein into the midbrain region. This finding correlates the beneficial effect of HMPBE administration with the onset of parkinsonism related to traumatic brain damage. The data may open a window for developing new support strategies to limit the neuroinflammation event of acute and chronic TBI.

7725 Could COVID-19 Be the Trigger for Type 1 Diabetes?

Abstract Disclosure: E. Ahsan: None. F.F. Foo: None. A. Ravin: None. M. Akula: None. K. Hu: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. Introduction: COVID-19 disrupts glucose homeostasis, which may result in hyperglycemia and new-onset diabetes mellitus. It has been hypothesized to be caused by an increased inflammatory response, increased insulin resistance, and a degree of acute viral pancreatic damage. A meta-analysis showed that the incidence of new-onset diabetes was found to be as high as 14.4% (95% CI: [5.9%-25.8%]). Here, we report a case of COVID-19-induced diabetes to spread awareness among healthcare providers and encourage early detection to prevent long-term complications. Clinical Case: A 54-year-old African American female with a past medical history of hyperlipidemia, obesity, and hypothyroidism presented to our endocrinology office for evaluation and management of diabetes mellitus (DM). She presented with symptoms of 66-pound weight loss, polydipsia, polyphagia, and polyuria. Her labs on diagnosis were significant for blood glucose of 550 mg/dl (70-100 mg/dl), hemoglobin A1c &amp;gt;15.5% (&amp;lt;5.7%), and bicarbonate 23 mmol/L (20-31 mmol/L). She started on insulin and then switched to semaglutide after six months. Her fasting glucose on the follow-up visit was 103 mg/dl, the anti-glutamic acid decarboxylase 65 (GAD-65) antibody was 8,558.9 units/ml (&amp;lt;5 units/ml), C peptide was 1.9 ng/ml (0.5-2ng/ml), and Islet Antigen-2 (IA-2) autoantibody was &amp;lt;7.5 U/ml (0-7.49 U/ml). Despite positive antibodies, her C-peptide suggested enough beta-cell function, and she was switched from insulin to semaglutide. The patient was diagnosed with autoimmune diabetes, which may be from the COVID-19 infection, and was educated about regular follow-up and new medications like teplizumab that may help prevent the progression to needing insulin. Clinical Lesson: The exact mechanism of new-onset COVID-19-induced diabetes is still unknown. However, multiple risk factors are theorized to play a role in COVID-induced DM. These include defects in insulin production and glucose clearance, obesity, stress hyperglycemia, insulin resistance, and steroid therapy. Our patient had a history of obesity but no history of diabetes, steroid use, or any personal or family history of autoimmune processes. Compared to COVID-19 patients with normoglycemia or hyperglycemia, patients with preexisting diabetes and newly diagnosed diabetes experienced more severe complications, such as shock, ARDS, acute kidney injury, hypoalbuminemia, and severe COVID-19 complications. Additional research is required to investigate the various pathophysiologies and treatment options, including new medications that may prevent the disease's further progression. Diabetes caused by COVID-19 should be treated cautiously, and prompt diagnosis and care are essential to preventing further complications. Presentation: 6/3/2024