Marked Elevation Research Articles

Investigation of the embryo-toxicity of the antiviral drug “Ribavirin” in Wistar rats during different gestation periods

ABSTRACT Ribavirin (1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a water-soluble, guanosine nucleoside analog that mimics other purines, including inosine and adenosine. The current study was designed to assess the embryotoxic effect of ribavirin and investigate its teratogenic effect on the placental and fetal liver tissues. In this study, 18 pregnant Wistar rats (165–185 g) 11–13 weeks old were orally administrated ribavirin at a dosage of 82.3 mg/kg at intervals of the organogenesis period (5th −13th) gestation day and fetal developmental period (13th −19th) gestation day. At gestation day 20, the pregnant rats were postmortem, and their fetuses were examined via morphological, histopathological investigations, biochemical analysis, and DNA damage evaluation. The results showed that ribavirin increased the incidence of abortion during the organogenesis period and caused a marked decrease in corrected body weight, uterus, and placenta weight of dams during the fetal developmental period: ribavirin-induced intra-uterine growth retardation, fetal morphological abnormalities, and decreased number of implants/litter. In addition, ribavirin produced histopathological alterations of the placenta and fetal liver tissue, marked elevation of malonaldehyde level, a significant decrease in the activity of antioxidants, and triggered DNA damage. In conclusion, we found that ribavirin has an embryotoxic effect via the generation of free radicals that cause placental DNA damage and altered placental function that affects normal embryo/fetal development.

Marked elevations in lung and plasma ceramide in COVID-19 linked to microvascular injury.

The pathogenesis of the marked pulmonary microvasculature injury, a distinguishing feature of COVID-19 acute respiratory distress syndrome (COVID-ARDS), remains unclear. Implicated in the pathophysiology of diverse diseases characterized by endothelial damage, including ARDS and ischemic cardiovascular disease, ceramide and in particular palmitoyl ceramide (C16:0-ceramide) may be involved in the microvascular injury in COVID-19. Using deidentified plasma and lung samples from COVID-19 patients, ceramide profiling by mass spectrometry was performed. Compared with healthy individuals, a specific 3-fold C16:0-ceramide elevation in COVID-19 patient plasma was identified. Compared with age-matched controls, autopsied lungs of individuals succumbing to COVID-ARDS displayed a massive 9-fold C16:0-ceramide elevation and exhibited a previously unrecognized microvascular ceramide-staining pattern and markedly enhanced apoptosis. In COVID-19 plasma and lungs, the C16-ceramide/C24-ceramide ratios were increased and reversed, respectively, consistent with increased risk of vascular injury. Indeed, exposure of primary human lung microvascular endothelial cell monolayers to C16:0-ceramide-rich plasma lipid extracts from COVID-19, but not healthy, individuals led to a significant decrease in endothelial barrier function. This effect was phenocopied by spiking healthy plasma lipid extracts with synthetic C16:0-ceramide and was inhibited by treatment with ceramide-neutralizing monoclonal antibody or single-chain variable fragment. These results indicate that C16:0-ceramide may be implicated in the vascular injury associated with COVID-19.

P450 ADVANCED ATRIOVENTRICULAR BLOCK AT LOOP RECORDER MONITORING IN A YOUNG PATIENT WITH BRUGADA SYNDROME AND CONDUCTION ABNORMALITIES: CAUSE OF SYNCOPE OR INCIDENTAL FINDING?

Abstract A 32–year–old man healthy man presented to the emergency department because of remittent fever. His past medical history, physical examination and chest X–ray were unremarkable except for a body temperature of 39 Celsius degrees. Laboratory exams showed a marked elevation of transaminases, cholestasis markers and C–reactive protein, while an abdomen ultrasound revealed hepatomegaly and diffuse hyperechogenicity of the liver. He was diagnosed with acute hepatitis and admitted to the Gastroenterology Unit. Due to the persistent hyperpyrexia despite antipyretics and antibiotics, he was successfully treated with intravenous diclofenac, resulting in temporary remission of fever. First electrocardiogram during apyrexia showed sinus rhythm, first–degree atrioventricular block (PR interval 240 milliseconds), and non–specific intraventricular conduction delay. In the following days, liver and cholestasis markers improved, but he underwent two syncopal episodes without prodromes, the former while he was walking and the latter during meal. A new electrocardiogram revealed a type 1 Brugada pattern. At the time of its recording, however, his body temperature was 38.6 Celsius degrees. He was then admitted to the Cardiology Unit for monitoring and further investigations. 2D–echocardiogram and cardiac magnetic resonance imaging were unremarkable. Telemetry monitoring showed nocturnal episodes of marked sinus bradycardia (up to 35 beats per minute), but no ventricular arrhythmias were documented. He also underwent an invasive electrophysiological study with programmed ventricular stimulation, but again no ventricular arrhythmias were induced. Recording of His bundle electrogram, however, revealed the prolongation of both AH and HV interval (190 and 76 milliseconds respectively). Given the syncopal episodes, an implantable cardioverter defibrillator implantation was proposed, but the patient refused, so he underwent an implantable loop recorder implantation. After three months, at remote monitoring, a nocturnal episode of complete atrioventricular block with a pause of 15 seconds was recorded, thus he was again admitted to the Cardiology Unit. This time he was apyretic, but his electrocardiogram showed a spontaneous type 1 Brugada pattern with “high arrhythmic risk” features as first–degree atrioventricular block and a prominent S wave in lead I. He then underwent a successful implantable cardioverter defibrillator implantation with still an uneventful follow up.

Multiplex tandem mass spectrometry enzymatic activity assay for the screening and diagnosis of Mucolipidosis type II and III

Mucolipidosis type II and III (MLII/III) is caused by defects in the mannose-6-phosphate system, which is essential to target most of the lysosomal hydrolases to the lysosome. MLII/III patients present with marked elevations in the activities of most lysosomal enzymes in plasma, but their profiles in dried blood spots (DBS) have not been well described. In the current study, we measured the activities of 12 lysosomal enzymes in DBS, among which acid sphingomyelinase, iduronate-2-sulfatase, and alpha-N-acetylglucosaminidase were significantly elevated in MLII/III patients when compared to random newborns. This sets the stage for using DBS to diagnose MLII/III. Furthermore, given an increasing number of lysosomal storage disorders are being included in the recommended uniform screening panel, our results also indicate that population-based newborn screening for MLII/III can be implemented with minimal efforts.

Initial 24-h perfusion index of ICU admission is associated with acute kidney injury in perioperative critically ill patients: A retrospective cohort analysis

BackgroundThe relationship between perfusion index (PI) and organ dysfunction in patients in the intensive care unit (ICU) is not clear. This study aimed to explore the relationship between PI and renal function in the perioperative critical care setting and evaluate the predictive efficiency of PI on patients with acute kidney injury (AKI) in the ICU. MethodsThis retrospective analysis involved 12,979 patients who had undergone an operation and were admitted to the ICU in Peking Union Medical College Hospital from January 2014 to December 2019. The distribution of average PI in the first 24 h after ICU admission and its correlation with AKI was calculated by Cox regression. Receiver operating characteristic (ROC) curves were generated to compare the ability of PI, mean arterial pressure (MAP), creatinine, blood urea nitrogen (BUN), and central venous pressure (CVP) to discriminate AKI in the first 48 h in all perioperative critically ill patients. ResultsAverage PI in the first 24 h served as an independent protective factor of AKI (Odds ratio [OR]=0.786, 95% confidence interval [CI]: 0.704–0.873, P <0.0001). With a decrease in PI by one unit, the incidence of AKI increased 1.74 times. Among the variables explored for the prediction of AKI (PI, MAP, creatine, BUN, and CVP), PI yielded the highest area under the ROC curve, with a sensitivity of 64.34% and specificity of 70.14%. A cut-off value of PI ≤2.12 could be used to predict AKI according to the Youden index. Moreover, patients in the low PI group (PI ≤2.12) exhibited a marked creatine elevation at 24–48 h with a slower decrease compared with those in the high PI group (PI >2.12). ConclusionsAs a local blood flow indicator, the initial 24-h average PI for perioperative critically ill patients can predict AKI during their first 120 h in the ICU.

Etiologies and Outcomes of Transaminase Elevation > 1000IU/L: A Systematic Review and Meta-Analysis.

Among liver injury causes, few result in marked elevation of liver enzymes to a level > 1,000 international units per liter (IU/L). This review summarizes common etiologies of marked transaminase elevation and associated prognostic factors. We performed a comprehensive search on PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through December 2022 using MOOSE guidelines for studies reporting frequency of etiologies of marked transaminase elevation. We used a proportion meta-analysis to pool frequencies with corresponding 95% confidence interval (CI). I2 was used to adjudicate heterogeneity. We used CMA software for statistical analysis. Seven relevant studies (n = 1608 patients) were included. The pooled frequency of ischemic hepatitis was 51% (95% CI 42-60%, I2 = 91%), viral hepatitis was 13.1% (95% CI 9.7-17.6%, I2 = 80%), toxins or drug-induced liver injury (DILI) was 13% (95% CI 8-18%, I2 = 85%), and pancreaticobiliary-related injury was 7.8% (95% CI 4.4-13.6%, I2 = 89%). Mortality was significantly higher in ischemic hepatitis versus other causes of marked transaminase elevation, with an odds ratio of 21 (95% CI 9.9-44.8, P value < 0.0001, I2 = 64% Q 11.1). This is the first meta-analysis to examine etiologies of marked transaminase elevation > 1000IU/L. Liver ischemia is the most common cause, while other causes include DILI or toxins, viral hepatitis, and biliary pathologies. We found biliary pathologies to be the fourth most common cause. This is clinically relevant as it has been traditionally linked to a cholestatic pattern of liver injury. Being aware of this presentation may help prevent delayed or missed diagnoses and unnecessary testing.

Feline leishmaniosis with focus on ocular manifestation: a case report

BackgroundIn Europe, feline leishmaniosis is commonly caused by Leishmaniainfantum. There is little knowledge regarding pathogenesis, ocular manifestations and long-term follow-ups in cats with leishmaniosis.FindingsA 6-year-old female, spayed European Shorthair cat was imported from Spain to Germany 2 years prior to its first clinical presentation. The cat showed lethargy, weight loss, ulcerative lesions on the front limbs and high-grade chronic uveitis. The diagnosis of L. infantum infection was based on the cytological finding of amastigotes in skin lesions, positive qPCR of EDTA-blood and positive PCR of a cyto-brush sample from the conjunctiva. Supportive findings included positive serology by IFAT, serum protein capillary electrophoresis with peaks in alpha2- and gamma-globulin sections and marked elevation of SAA. Enucleation had to be performed on day 288 on both eyes because of blindness, glaucoma and high-grade uveitis. Histologically, high numbers of Leishmania spp. amastigotes were found in histiocytes. IFAT and PCR were positive in the aqueous humor in both eyes, respectively. Feline leukemia virus antigen and feline immunodeficiency virus antibody testings were positive. Hematological and biochemical results revealed mild leukocytosis with lymphocytosis, monocytosis and eosinopenia as well as marked elevation of SAA and hyperglobulinemia. The cat was treated with allopurinol, responded well and was still alive at follow-up on day 288 after first presentation. However, enucleation was necessary because of refractory glaucoma and uveitis. ConclusionFor the first time, ocular evidence of Leishmania IgG antibodies was demonstrated in the aqueous humor of both eyes in cats. There is limited knowledge about the pathogenesis, treatment options and outcomes in cats infected with L. infantum. This case report supports the hypothesis that immunosuppression increases the risk of clinical signs of leishmaniasis in cats. Alpha2- and gamma-globulin peaks in serum protein capillary electrophoresis are supportive criteria for the diagnosis of L. infantum infection. SAA is valuable for monitoring. Regarding ophthalmology, uveitis and glaucoma may have a poor prognosis. Graphical abstract

Obesity Is Associated with Changes in Laboratory Biomarkers in Chilean Patients Hospitalized with COVID-19.

It is reported that patients with obesity are more frequently hospitalized for COVID-19, and evidence exists that obesity is a risk factor, regardless of other comorbidities. The objective of this study was to evaluate the association of obesity with changes in laboratory biomarkers in hospitalized Chilean patients. A total of 202 hospitalized patients (71 with obesity and 131 without obesity) with a diagnosis of COVID-19 were included in the study. Demographic, clinical, and laboratory (days 1, 3, 7, 15) data were obtained. We performed a statistical analysis, assuming significance with a value of p < 0.05. Significant differences in chronic respiratory pathology are observed between patients with and without obesity. The inflammatory markers CPR, ferritin, NLR, and PLR are elevated during the evaluated period, while changes in leukocyte populations are present on day 1 (eosinophils) and day 3 (lymphocytes). Finally, a persistent elevation of D-dimer level is observed, presenting significant differences on day 7 between patients with and without obesity. Obesity had a positive correlation with admission to the critical patient unit, invasive mechanical ventilation, and length of hospital stay. Patients with obesity hospitalized for COVID-19 present marked elevations of inflammatory and hemostasis parameters, with a correlation between obesity, changes in laboratory biomarkers, and the risk of adverse clinical outcomes also observed.

Exposure to hypoxia during embryonic development affects blood flow patterns and heart rate in juvenile American alligators during digestion

The developmental environment can alter an organism's phenotype through epigenetic mechanisms. We incubated eggs from American alligators in 10% O2 (hypoxia) to investigate the functional plasticity of blood flow patterns in response to feeding later in life. Digestion is associated with marked elevations of metabolism, and we therefore used the feeding-induced stimulation of tissue O2 demand to determine whether there are lasting effects of developmental hypoxia on the cardiovascular response to digestion later in life. In all animals studied, digestion elicited tachycardia and an elevation of blood flow in the right aorta, left aorta, and the pulmonary artery, whereas flows in the carotid and subclavian artery did not change. We found that heart rate and systemic blood flow remained elevated for a longer time period in juvenile alligators that had been incubated in hypoxia; we also found that the pulmonary blood flow was elevated at 24, 36, and 48 h. Collectively, our findings demonstrate that exposure to hypoxia during incubation has lasting effects on the hemodynamics of juvenile alligators 4 years after hatching.

PO-04-103 WIDE COMPLEX TACHYCARDIA IN ACUTE ANTI-NMDA RECEPTOR ENCEPHALITIS

NA NA NA A 20-year-old male with no known past medical history presented with two months of episodic right-sided weakness. An extensive workup was notable for a lumbar puncture that was positive for antibodies to the N-methyl-D-aspartate (NMDA) receptor, confirming anti-NMDA receptor (NMDAR) encephalitis. Baseline cardiac workup included a transthoracic echocardiogram (TTE) that showed left ventricular (LV) hypokinesis with borderline ejection fraction (EF 52%), and an ECG showing sinus tachycardia (Figure-A). While admitted, the patient developed shock, necessitating intubation and vasopressors. Serial ECGs while in shock showed sinus tachycardia, a prolonged QTc, and broad sail-like T wave in V1 (similar to type 1 Brugada pattern), with ST elevations in aVR and diffuse ST depressions inferolaterally (Figure-B). Serial troponins were minimally elevated (0.11 ug/L) and TTE showed no regional wall motion abnormalities, so invasive coronary angiography was not pursued. During progressive shock, the patient developed a wide complex tachycardia (WCT, Figure-C), that was thought to most likely be LV outflow tract ventricular tachycardia. The patient became hemodynamically unstable with the WCT, necessitating amiodarone, lidocaine, and ultimately five cardioversions. Repeat TTE showed severe biventricular dysfunction, and the patient needed veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Ultimately, the patient’s biventricular function recovered, and he was able to be decannulated from VA-ECMO. He was managed with intravenous immunoglobulin, steroids and rituximab for his anti-NMDAR encephalitis. Cardiac arrhythmias are a known complication of anti-NMDAR encephalitis in up to one-third of patients. To the best of our knowledge, this is the first case of anti-NDMAR encephalitis associated with diffuse ST elevations suggestive of ischemia. Models suggest NMDA receptor-mediated signaling in the nervous system can alter the vagal outflow to the heart, leading to sinus brady/tachycardia. Other explanations for ECG changes in our patient include focal myocarditis/vasospasm. This is an unusual case of marked ST elevation and sustained VT in anti-NMDAR encephalitis. Pathogenesis and management of arrhythmias related to this condition warrant further study.

The role of circulatory chemokines in sepsis-induced myopathy in mice

BACKGROUND: Sepsis is a condition of life-threatening organ dysfunction caused by a dysregulated host response to infection and carries a high risk of mortality. A rapidly growing number of “sepsis survivors” experience persistent and severe skeletal muscle weakness and atrophy (i.e., sepsis-induced myopathy). The myopathy is triggered by the interaction of circulating pathogens, inflammatory factors (e.g., cytokines and chemokines), and myofibers. Currently, there are no treatments for sepsis-induced myopathy partially due to a lack of therapeutic targets. Chemokines are peptides that possess chemo attractant properties and are released by immune cells during infection insult. Circulating levels of chemokines in septic patients are known to be high. However, the role these chemokines play in context of sepsis-induced myopathy is currently unknown. Our goal in this study was to identify the role of circulating chemokines on sepsis-induced myopathy. METHODS: We induced sepsis via cecal ligation and puncture (CLP) or sham control surgeries in a group of young adults (5 mo) male C57BL6 mice. Seven days after surgery, serum was collected from sham and CLP mice. The serum samples were pooled for cell culture experiments. In a subset of healthy mice, we isolated primary myoblasts. The myoblasts were co-cultured in conditioned media containing pooled serum samples collected from sham and CLP mice. We performed a multiplex assay to identify the levels of chemokines on the pooled serum samples. We measured myoblast proliferation, myotube area, and fusion index. In follow-up experiments, we exposed C2C12 myotubes to a selected group of chemokine peptides previously identified in serum samples. RESULTS: Exposure to septic serum attenuated the proliferative capacity of healthy myoblasts by 46% (p &lt; 0.05). In addition, myoblasts exposed to septic serum did not differentiate into healthy myotubes. Multiplex analyses of pooled sham and septic serum revealed a marked elevation of the following chemokines: CXCL-1 (healthy = 173.4 ± 0.1, septic = 69,630 ± 13,732 pg/ml), CXCL-2 (healthy = 1,078 ± 0.1, septic = 3,907 ± 259 pg/ml), CXCL-10 (healthy = 366 ± 0.1, septic = 3,961 ± 293 pg/ml), CCL-2 (healthy = 276 ± 0.1, septic = 1672 ± 362 pg/ml). Exposure of mature C2C12 myotubes to the chemokine peptides for 24 h increased the mRNA expression of atrophy-related genes ( FOXO1, GABARAP, BNIP3, TRIM63, MAP11A3B, FOXO32, FOXO30). CONCLUSION: Circulating chemokines play a regulatory role in sepsis-induced myopathy via attenuation of the proliferative capacity of myoblasts and by altering myotube morphology and the expression of atrophy related genes. Chemokines are potential therapeutic targets to treat sepsis-induced myopathy. Funded by NIH R21AG072011-03 to OL This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Aqueous Leaf Extract of Vernonia amygdalina on High-Fat Diet-Induced Injury in the Heart and Aorta of the Adult Wistar Rat

The aim of this study was to investigate the effects of aqueous leaf extract of Vernonia amygdalina in Wistar rats fed with high-fat diet. 30 adult Wistar rats weighing between 250g and 280g were randomly assigned into 5 groups of 6 rats per group. Group A rats were placed on rat food and water only. Group B rats received 1000mg/kg body weight / day (BWT/D) of margarine. Group C rats received 300mg/kg BWT/D of V. amygdalina. Group D rats received 1000mg/kg BWT/D of margarine and 150mg/kg BWT/D of V. amygdalina. Group E rats received 1000mg/kg BWT/D of margarine and 300mg/kg BWT/D of V. amygdalina. The dosages were given for 56days via orogastric method. The biochemical outcome showed that Group B revealed decrease in high density lipoprotein (HDL) and marked elevation in the total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), and superoxide dismutase (SOD) levels when compared with the other groups. Histologcally, Group B showed moderate stenosis, perivascular fibrosis, asymmetrical vascular hypertrophy and mild intimal erosion while Group A, C, D and E revealed normal myocardium and vascular architecture. In conclusion, the aqueous leaf extract of Vernonia amygdalina have antihyperlipidemic and antioxidant properties against margarine-induced injury in the heart and aorta of Wistar rats.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk: a single-center study.

Lipid lowering effects and safety of evolocumab in Chinese patients at very high cardiovascular risk: a single-center study.

Toxicities of polystyrene microplastics (MPs) and hexabromocyclododecane (HBCD), alone or in combination, to the hepatopancreas of the whiteleg shrimp, Litopenaeus vannamei

The hepatopancreas is one of the largest organs playing crucial roles in metabolism and detoxification in crustacean invertebrates. Although toxicities have been increasingly documented for the two ubiquitous pollutants, hexabromocyclododecane (HBCD) and microplastics (MPs), in model animals, little is known about their impacts on the hepatopancreas of crustaceans. To fill this knowledge gap, the effects of MPs and HBCD, alone or in combination, on the hepatopancreas were evaluated in a commercially important crustacean species (the whiteleg shrimp) by histological observation as well as quantification of hepatic lesion-, metabolism-, and detoxification-related parameters. In addition, to reveal potential mechanisms underlying the hepatoxicity observed, the accumulation of HBCD in the shrimp and the status of oxidative stress were also investigated. Our results demonstrated that exposure of the whiteleg shrimp to MPs and HBCD for 4 weeks resulted in evident histological injury in the hepatopancreas and marked elevation in hepatic lesion markers (alanine aminotransferase and aspartate aminotransferase) in the hemolymph. Moreover, both metabolism (activity of phosphofructokinase, contents of lactic acid and adenosine triphosphate, and expression of metabolism-related genes) and detoxification (contents of cytochrome P450, UDP-glucuronosyltransferase, and glutathione, activity of glutathione S-transferase, and expression of detoxification-related genes) were found to be disrupted by the pollutants tested. In addition, exposure to MPs and HBCD also led to alterations in the contents and/or activities of antioxidant enzymes and resulted in oxidative damage to the hepatopancreas (indicated by marked elevation in malondialdehyde content). Furthermore, a significant amount of HBCD accumulated in shrimp treated with HBCD-containing seawater. The data also illustrated that HBCD-MP coexposure was more toxic than single exposure to these pollutants. These findings suggest that MPs and HBCD may exert hepatotoxic impacts on whiteleg shrimp by accumulating in vivo and inducing oxidative stress, which could pose a severe threat to the health of this important crustacean species.

Pulmonary Vascular Phenotypes of Prematurity: The Path to Precision Medicine

Pulmonary hypertension (PH) is associated with significant morbidities and high mortality in preterm infants, yet mechanisms contributing to the pathogenesis of PH, the impact of early pulmonary vascular disease (PVD) on the risk for BPD, the role for PH-targeted drug therapies, and long-term pulmonary vascular sequelae remain poorly understood. PVD is not a homogeneous disease, rather, PVD in the setting of prematurity includes various phenotypes as based on underlying pathophysiology, the severity of associated PH, the timing of disease onset, its contribution to hemodynamic and respiratory status, late outcomes, and other features. As with term newborns, severe hypoxemia with acute respiratory failure (HRF) in preterm infants can be due to marked elevation of pulmonary artery pressure with extrapulmonary shunt, traditionally referred to as persistent pulmonary hypertension of the newborn (PPHN). Transient and less severe levels of PH can also be observed during the early transition after birth without evidence of severe HRF, representing physiologic PH or delayed pulmonary vascular transition in preterm infants. Importantly, echocardiographic evidence of early PH has been strongly associated with the subsequent development of bronchopulmonary dysplasia (BPD), late PH, and chronic respiratory disease during infancy and early childhood. Late PH beyond the first postnatal months in preterm in neonates with established BPD is further associated with poor outcomes, especially as related to BPD severity. In addition, echocardiographic signs of PVD can further persist throughout childhood and may lead to chronic PH of variable severity and cardiac maldevelopment in prematurely born young adults. This review discusses the importance of characterizing diverse pulmonary vascular phenotypes in preterm infants to better guide clinical care and research, and to enhance the development of more precise therapeutic strategies to optimize early and late outcomes of preterm infants.

The diagnostic value of sST2 for myocardial fibrosis in idiopathic inflammatory myopathies in subclinical stage of cardiac involvement.

Myocardial fibrosis occurs in the early subclinical stage of cardiac involvement in idiopathic inflammatory myopathies (IIMs). Soluble suppression of tumorigenicity 2 (sST2) is known to have an immunomodulatory impact during autoimmune disease development. The current study investigated the diagnostic value of sST2 for myocardial fibrosis during early stage of cardiac involvement in IIM. A total of 44 IIM patients with normal heart function and 32 age- and gender-matched healthy controls (HCs) were enrolled. Serum sST2 levels were measured by ELISA and cardiac magnetic resonance (CMR) parameters for myocardial fibrosis [native T1, extracellular volume (ECV), late-gadolinium enhancement (LGE)] and oedema (T2 values) were analysed. IIM patients had significantly higher sST2 levels than HCs [67.5 ng/ml (s.d. 30.4)] vs 14.4 (5.5), P < 0.001] and levels correlated positively with diffuse myocardial fibrosis parameters, native T1 (r = 0.531, P = 0.000), ECV (r = 0.371, P = 0.013) and focal myocardial fibrosis index and LGE (r = 0.339, P = 0.024) by Spearman's correlation analysis. sST2 was an independent predictive factor for diffuse and focal myocardial fibrosis after adjustment for age, gender, BMI and ESR. Risk increased ≈15.4% for diffuse [odds ratio (OR) 1.154 (95% CI 1.021, 1.305), P = 0.022] and 3.8% for focal [OR 1.038 (95% CI 1.006, 1.072), P = 0.020] myocardial fibrosis per unit increase of sST2. Cut-off values for diagnosing diffuse and focal myocardial fibrosis were sST2 ≥51.3 ng/ml [area under the curve (AUC) = 0.942, sensitivity = 85.7%, specificity = 98.9%, P < 0.001] and 53.3 ng/ml (AUC = 0.753, sensitivity = 87.5%, specificity = 58.3%, P < 0.01), respectively. sST2 showed a marked elevation during the subclinical stage of cardiac involvement in IIM and has potential as a biomarker for predicting diffuse and focal myocardial fibrosis in IIM.

Hyperuricemia in a patient with Waldenström’s Macroglobulinemia: An innocent bystander?

Background: Paraproteins often cause factitious biochemical measurements by forming opaque precipitates with the test reagents and interfering with various automated assays. These interferences may be difficult to anticipate as they are intermittent and patient-specific. Increased IgM has been shown to result in the underestimation of uric acid levels and pseudo-hypouricemia; however, there are no reported cases of pseudo-hyperuricemia in the setting of paraproteinemia. Case presentation: We present a case of Waldenström’s Macroglobulinemia (WM), resulting in a marked elevation of the uric acid level in the absence of tumor lysis syndrome (TLS). On evaluation, it was noted that the elevation in the uric acid levels was spurious, potentially due to high IgM levels resulting in increased serum viscosity. Identifying actual and pseudo-abnormal laboratory results is critical to guide further workup and conserve scarce healthcare resources. The absence of other concomitant laboratory abnormalities and clinical symptoms should raise a suspicion of factitious results. In addition to uric acid, many other assays are affected by paraproteinemia, commonly including electrolytes, lipids, glucose, and liver function tests.

Design of high-monounsaturated fatty acid soybean seed oil using GmPDCTs knockout via a CRISPR-Cas9 system.

Design of high-monounsaturated fatty acid soybean seed oil using GmPDCTs knockout via a CRISPR-Cas9 system.

Wischnewski Spots in a Case of Hyperosmolar Hyperglycemic State.

Wischnewski spots were first described as a common finding in gastric mucosa of decedents exposed to hypothermic environmental conditions. In recent literature, they were also reported in cases of diabetic ketoacidosis, pancreatitis, and fatal burns. Although Wischnewski spots are not specific to cases of hypothermia, we present a case that further supports this contention. We report a case of a middle-aged woman with type 2 diabetes who died of complications of hyperosmolar hyperglycemic state. Although there were no features of hypothermia, she presented with Wischnewski spots in the gastric mucosa. On histology, the gastric mucosa contained brown-black pigmentations with no neutrophilic infiltration. Biochemical analysis from vitreous humor and femoral blood showed marked elevation of glucose levels, low concentration of ketone bodies, pseudohyponatremia, and prerenal azotemia. The autopsy findings in this case discussion shed light to the possible genesis and pathophysiology of Wischnewski spots and highlight an additional differential diagnosis for these lesions.

Bee Pollen and Probiotics' Potential to Protect and Treat Intestinal Permeability in Propionic Acid-Induced Rodent Model of Autism.

Rodent models may help investigations on the possible link between autism spectrum disorder (ASD) and gut microbiota since autistic patients frequently manifested gastrointestinal troubles as co-morbidities. Thirty young male rats were divided into five groups: Group 1 serves as control; Group 2, bee pollen and probiotic-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism; Group 4 and Group 5, the protective and therapeutic groups were given bee pollen and probiotic combination treatment either before or after the neurotoxic dose of PPA, respectively. Serum occludin, zonulin, lipid peroxides (MDA), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPX), catalase, and gut microbial composition were assessed in all investigated groups. Recorded data clearly indicated the marked elevation in serum occludin (1.23 ± 0.15 ng/mL) and zonulin (1.91 ± 0.13 ng/mL) levels as potent biomarkers of leaky gut in the PPA- treated rats while both were normalized to bee pollen/probiotic-treated rats. Similarly, the high significant decrease in catalase (3.55 ± 0.34 U/dL), GSH (39.68 ± 3.72 µg/mL), GST (29.85 ± 2.18 U/mL), and GPX (13.39 ± 1.54 U/mL) concomitant with a highly significant increase in MDA (3.41 ± 0.12 µmoles/mL) as a marker of oxidative stress was also observed in PPA-treated animals. Interestingly, combined bee pollen/probiotic treatments demonstrated remarkable amelioration of the five studied oxidative stress variables as well as the fecal microbial composition. Overall, our findings demonstrated a new approach to the beneficial use of bee pollen and probiotic combination as a therapeutic intervention strategy to relieve neurotoxic effects of PPA, a short-chain fatty acid linked to the pathoetiology of autism.