Marked Signs Research Articles

MODL-11. COMPARISON OF HUMAN & MURINE PA/PXA CHARACTERISTICS

Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Despite recent advances in the molecular characterization of this heterogeneous set of tumors, the separation of specific tumor types is still not fully established. Pilocytic astrocytoma (PA; WHO grade I) and pleomorphic xanthoastrocytoma (PXA; WHO grade II) are two pLGG types that can be difficult to distinguish based on histology alone. Even though their clinical course is different, they are often grouped as ‘pLGG’ in clinical trials (and therefore treated similarly). Based on a cohort of 89 human pediatric tumor samples, we show that PAs and PXAs have clearly distinct methylation and transcriptome profiles. The difference in gene expression is mainly caused by cell cycle- and development-associated genes, suggesting a key difference in the regulatory circuits involved in tumor growth. In addition to BRAF V600E, we found NTRK fusions and a previously unknown EGFR:BRAF fusion as mutually exclusive driving events in PXAs. Both tumor types show marked signs of immune cell infiltration, but with significant qualitative differences, which might represent therapeutic vulnerabilities. To pave the way for further research on PA and PXA, we developed corresponding mouse models using the virus-based RCAS system, which allows introduction of an oncogenic driver into immunocompetent mice for molecular and preclinical research. The murine tumors do not only histologically resemble their human counterparts but also show a similar growth behavior. Expression analysis revealed that the murine PXAs have a stronger gene signature of proliferation and immune cell infiltration compared to PAs.

Pengaruh Latihan Multiball Terhadap Keterampilan Smash Forehand Tenis Meja Pada Club Pade Angen Mataram Tahun 2020

The focus of the problem in this study is that this research is motivated by the low accuracy of the forehand smash. Table tennis at Club Pade Angen Mataram in 2020. The research objectives to be achieved based on the predetermined problem formulation are as follows: To find out the effect of multiball training on the smash forehand table tennis skills at Club Pade Angen Mataram in 2020. The research design in use is an experimental research "One-Group Pretest-posttest Design". This experiment still has external variables that influence the formation of the dependent variable. So the experimental results which are the dependent variable (bound) are not merely influenced by the independent variable (free). Table Tennis Forehand Drive Accuracy Instrument To make it easier to understand below is a picture of a table marking sign of two targets on the right side of the testicle, namely the area of 30cm x 30cm, both of which are 60cm x 60cm. . Table Sampling technique using a population study of 12 players. Based on data analysis, getting the t-count obtained a value of 10.30 then the t-table with degrees of magnitude N - 1 = 11 at a significant level of 5% shows a number that is 1.796. This result means that the t-count> t-table, namely (3.995> 1.796) or in other words the t-count obtained is greater than the limit of the rejection of the null hypothesis (Ho), it is necessary that the t-value is equal to or greater than the t value. -table.

Pengaruh Latihan Multiball Terhadap Keterampilan Smash Forehand Tenis Meja Pada Club Pade Angen Mataram Tahun 2020

The focus of the problem in this study is that this research is motivated by the low accuracy of the forehand smash. Table tennis at Club Pade Angen Mataram in 2020. The research objectives to be achieved based on the predetermined problem formulation are as follows: To find out the effect of multiball training on the smash forehand table tennis skills at Club Pade Angen Mataram in 2020. The research design in use is an experimental research "One-Group Pretest-posttest Design". This experiment still has external variables that influence the formation of the dependent variable. So the experimental results which are the dependent variable (bound) are not merely influenced by the independent variable (free). Table Tennis Forehand Drive Accuracy Instrument To make it easier to understand below is a picture of a table marking sign of two targets on the right side of the testicle, namely the area of 30cm x 30cm, both of which are 60cm x 60cm. . Table Sampling technique using a population study of 12 players. Based on data analysis, getting the t-count obtained a value of 10.30 then the t-table with degrees of magnitude N - 1 = 11 at a significant level of 5% shows a number that is 1.796. This result means that the t-count> t-table, namely (3.995> 1.796) or in other words the t-count obtained is greater than the limit of the rejection of the null hypothesis (Ho), it is necessary that the t-value is equal to or greater than the t value. -table.

The Jarisch-Herxheimer reaction associated with doxycycline in a patient with Lyme arthritis.

ObjectivesThe objective of this article was to present the clinical peculiarity of the Jarisch-Herxheimer reaction (JHR) during antibiotic treatment of Lyme arthritis.Material and methodsCase study presentation as a basis for discussion, literature search of PubMed database particularly in the subject of combination of the JHR and Lyme borreliosis using the combination of words “Jarisch-Herxheimer reaction” and “Lyme borreliosis”, “Lyme arthritis”, “antibiotic treatment”, “generalized inflammation”, “cytokine production”, “children”, “increasing awareness”; discussion of the problem based on a clinical case and cited articles.ResultsThe authors present a case of Lyme arthritis in a 13-year-old boy, as well as a discussion of clinical features of this complication of Lyme disease treatment as the Jarisch-Herxheimer reaction. On the 7th day of doxycycline treatment the patient’s condition deteriorated: a low-grade fever occurred, and severe arthralgias with intense hip, ankle and cervical spine pain and myalgias developed. Erythrocyte sedimentation rate and C-reactive protein were elevated. The Jarisch-Herxheimer reaction was diagnosed. This complication was characterized by severity, long duration and marked signs of inflammation.ConclusionsIn the reviewed literature the Jarisch-Herxheimer reaction in patients with Lyme borreliosis is described more often in adults, with mild course and short duration of the disease. Based on the presented clinical picture this severe complication may also be associated with long duration and marked signs of inflammation. The authors suggest that informing health professionals about occurrence of the Jarisch-Herxheimer reaction should help physicians to distinguish it from allergic reactions or other conditions and improve treatment outcomes.

Dynamics of indicators of C-reactive protein and procalcitonin in the oral fluid of patients with plastic oroantral communication

Relevance. The most frequent complication in surgeries of tooth extraction on the upper jaw is perforation of the upper jaw sinus. Plastic surgery is necessary to eliminate the appeared communication. Prior to this, the dentist-surgeon should be sure of absence of chronic polyposes process in the sinus. At present the usual roentgenogram of the paranasal sinus is often proved to be not informative, while taking computer tomography is often not available in many cases either. The biochemical methods of studies of oral fluid is of possible concern in diagnostics of chronic inflammatory processes in the sinus. Purpose . To study the dynamics of indicators of C-reactive protein and procalcitonin in the mixed saliva of patients with plastic oroantral communication caused by tooth extraction. Materials and methods . There were studied the indicators of two inflammation markers (C-reactive protein and procalcitonin) in 62 patients of the age from 20 to 45 with oroantral communications. The patients were studied with the help of cone beam computer tomography either and after that they were divided into 2 groups. The first group included patients without x-ray signs of chronic sinus inflammation. The second group was formed by patients with marked signs of chronic inflammation of the maxillary sinus mucosa. There was studied the level of C-reactive protein and procalcitonin in the oral fluid of 23 volunteers (control group). The studies were started 2-3 days after the tooth extraction. Results. It was determined that before the operation the level of markers was statistically essentially increased in comparison with the control group in all patients with oroantral communications. In the first group C-reactive protein was increased 2,7 times, procalcitonin – 2,4 times. In the second group accordingly 3,1 and 3,3 times. By the 3rd day after the operation the concentration of markers increased more. However in the first group the C-reactive protein increased 3,3 times if compared with the control group and procalcitonin -3,6 times. In the second group – 8,6 and 8,4 times accordingly. By the seventh day after the operation the concentration of the inflammation markers decreased statistically essentially, but while in the 1st group it approached to the norm level, the second group revealed C-reactive protein staying 4,5 times higher than normal and procalcitonin was 4,7 times higher. Conclusion . The indicators of C-reactive protein and procalcitonin in the oral fluid of patients with oroantral communications are the markers of high sensitivity of the acute inflammation and they can be used either for the verification of the diagnosis or for the monitoring of the disease dynamics in post-operative period.

Exchanging dietary fat source with extra virgin olive oil does not prevent progression of diet-induced non-alcoholic fatty liver disease and insulin resistance.

Dietary fat is discussed to be critical in the development of non-alcoholic fatty liver disease. Here, we assess the effect of exchanging dietary fat source from butterfat to extra virgin olive oil on the progression of an already existing diet-induced non-alcoholic fatty liver disease in mice. Female C57BL/6J mice were fed a liquid butterfat-, fructose- and cholesterol-rich diet (BFC, 25E% from butterfat) or control diet (C, 12%E from soybean oil) for 13 weeks. In week 9, fat sources of some BFC- and C-fed mice were switched either to 25E% or 12E% olive oil (OFC and CO). Glucose and insulin tolerance tests were performed, and markers of liver damage and glucose metabolism were assessed. After 6 weeks of feeding, BFC-fed mice had developed marked signs of insulin resistance, which progressed to week 12 being not affected by the exchange of fat sources. Liver damage was similar between BFC- and OFC-fed mice. Markers of lipid metabolism and lipid peroxidation in liver and of insulin signaling in liver and muscle were also similarly altered in BFC- and OFC-fed mice. Taken together, our data suggest that exchanging butterfat with extra virgin olive oil has no effect on the progression of non-alcoholic fatty liver disease and glucose tolerance in mice.

Toxicological Profile of the Pain-Relieving Antioxidant Compound Thioctic Acid in Its Racemic and Enantiomeric Forms.

Thioctic acid is a multipotent antioxidant compound existing as dextrorotatory (+), eutomer and naturally occurring and levorotatory (−). It has been proven to help fight many pathologies and is sold as racemate. In agreement with studies claiming a greater biopotency of the eutomer compared to the levorotatory compound, we recently preclinically and clinically showed that (+) thioctic acid is a pain-reliever as effective as double-dosed racemate. We investigated acute and subchronical toxicity of (+/−) thioctic acid, (−) thioctic acid, (+) thioctic acid and (+) salt thioctic acid on Sprague–Dawley rats. For acute toxicity, compounds were administered intraperitoneally (i.p.) with a single-injection at 125, 240, 360, 480 µmol/kg, then rodents were tested for motorial coordination and minimum lethal dose (LDmin). A subtoxic dose (360 µmol/kg) was administered i.p. for 15 days and we finally evaluated motorial impairment, glycemia, organ toxicity, and apoptosis state. Acutely administered, the highest doses of all thioctic acid compounds negatively affected motorial ability and (−) thioctic acid LDmin resulted higher than the others. Subchronic administrations caused overall body weight loss, motorial impairment, mass loss in some organs. (+/−) and (−) thioctic acid injections enhanced caspase-3 activity in some organs, (−) enantiomer-treated animals displayed more marked organ toxicity signs. Together with our previous study on the biologic role of enantiomers, these data suggest a therapeutic use of (+) enantiomer-based formulations, thus lowering dose and toxicity without affecting the positive effects brought by the drug.

Management plan of a paediatric outpatient department during the SARS-CoV-2 epidemic.

With the novel coronavirus (2019-nCoV) infection outbreak and spread, serious cases of infection and neonatal infection have been reported. Moreover, children show milder cases and a better prognosis than adults. The outpatient Department of Paediatrics has played a crucial role in the prevention and control of novel coronavirus (2019-nCoV) infection in children. Based on previous experience and existing diagnosis and treatment guidelines, we present the relevant strategies of this particular paediatric outpatient department when responding to the epidemic. Conclusion: Concurrently, we hope that this article can act as a reference in the fight against SARS-CoV-2 infection. Further modifications will be made in the future with the increase in clinical experience and changes in the disease. This article is protected by copyright. All rights reserved.

Study of Kyasanur forest disease viremia, antibody kinetics, and virus infection in target organs of Macaca radiata

The present manuscript deals with experimental infections of bonnet macaques (Macaca radiata) to study disease progression for better insights into the Kyasanur Forest Disease (KFD) pathogenesis and transmission. Experimentally, 10 monkeys were inoculated with KFD virus (KFDV) (high or low dose) and were regularly monitored and sampled for various body fluids and tissues at preset time points. We found that only 2 out of the 10 animals showed marked clinical signs becoming moribund, both in the low dose group, even though viremia, virus shedding in the secretions and excretions were evident in all inoculated monkeys. Anti-KFDV immunoglobulin (Ig)M antibody response was observed around a week after inoculation and anti-KFDV IgG antibody response after two weeks. Anaemia, leucopenia, thrombocytopenia, monocytosis, increase in average clotting time, and reduction in the serum protein levels were evident. The virus could be re-isolated from the skin during the viremic period. The persistence of viral RNA in the gastrointestinal tract and lymph nodes was seen up to 53 and 81 days respectively. Neuro-invasion was observed only in moribund macaques. Re-challenge with the virus after 21 days of initial inoculation in a monkey did not result in virus shedding or immune response boosting.

“Cerebellar Challenge” for Adolescents at Risk of School Failure: Evaluation of a School-Based “Whole Person” Intervention

Forty adolescents at risk of school failure, including 18 with a diagnosis of dyslexia, were assessed on measures of physical, cognitive and affective wellbeing. Overall both groups of participants showed marked signs of anxiety together with at risk performance on a range of cognitive and physical measures, with the dyslexic participants significantly more adversely affected on almost all measures. Half of the participants then undertook an 8 week internet-based ‘cerebellar challenge’ programme within their school environment, with the remainder having equivalent time in the existing ‘School Support as Usual’ (SSAU) activities. Compared with their initial performance, and with the SSAU group, the intervention group showed significant improvement on measures of motor performance, declarative learning, procedural learning, and mental health, both for those with dyslexia and those without. The findings are interpreted in terms of increased self-efficacy and improvements in cerebellar and hippocampal function. Given its scaleability, the intervention may prove valuable for many adolescents at risk of school failure.

Mindfulness in the foreign language classroom: Influence on academic achievement and awareness

Incorporating mindfulness into education has been linked to improving academic, social and emotional learning. This article describes an investigation of the implementation of meditative practices in a foreign language setting (German). Two classes underwent distinct varieties of meditation: The count-to-ten method and the guided meditation approach, whereas a third class served as a comparison group by not partaking in meditative activities. Meditative practices were implemented for a period of one year and data were collected on students’ academic achievement, measures of mindfulness, and evaluations of their perspectives on meditative practices. Results revealed that classes in the treatment conditions showed marked signs of academic achievement and increased awareness relative to the comparison group. Differences were revealed between the two meditation methods in terms of distinct aspects of mindfulness as measured by the five-facet mindfulness questionnaire (FFMQ). In addition, students showed a positive disposition towards meditative practices in general, which was measured by a new developed instrument: the five spheres of meditation experience survey (FSMES). Results suggest that meditative practices may play a role in designing and developing novel pedagogical practices.

Small size vehicle application with lane tracking capability via CHEVP algorithm

Humans are living things that make mistakes. Failure of drivers while driving can cause life, cost, organ loss. Some accidents may remain traumatic in people's memory and adversely affect their future lives. Traffic rules have been developed to prevent such accidents. Traffic is formally organized in many jurisdictions, with marked lanes, junctions, intersections, interchanges, traffic signals, or signs. Rules of the road and driving etiquette are the general practices and procedures that road users are required to follow. Thanks to these guides placed on the roads, drivers can go on the road in harmony. Despite all these precautions, there are many traffic accidents caused by the driver's carelessness, sleeplessness and tiredness. In today's technology, it is possible to utilize methods of processing images from cameras located in the vehicle to minimize driver-induced accidents. In this study, a prototype system was established in order to use the technologies used in autonomous vehicles and to teach these technologies. Camera and computer are placed on a battery-powered vehicle. Using the OpenCV library, lane tracking is performed successfully using the Canny/Hough Estimation of Vanishing Points (CHEVP) method. The developed system is suitable for the use and development of image processing technologies that are used in autonomous vehicle technology. The system is tested in real-time on a designed runway. From the real-time experimental studies, high-performance results were obtained.

Lipid droplet utilization by the mouse embryo

High numbers of lipid droplets (LDs) in mammalian eggs are stored and maintained throughout embryo development without marked signs of their utilization. It was previously demonstrated in large domestic mammals that removing lipids from the zygote does not influence post-implantation development in terms of the rate of delivered offspring. Previously studied pig and cow eggs contain considerable amounts of LDs, while mice have a very low level of ooplasmic lipids, which allows to more precisely analyze any effect of lipid removal on developmental dynamics in vitro. We wanted to know if lipid fraction removal would influence the dynamics of preimplantation development of mouse embryos. To do this, mouse zygotes were mechanically delipidated and their progression to the blastocyst stage was evaluated in vitro. Part of blastocysts were transferred to pseudopregnant females for development to term, and then offspring health parameters were evaluated. Our experiments showed no effects of lipid removal on the rate and timing of mouse embryo development. Furthermore, there were no differences in post-natal characteristics of offspring developed from delipidated and non-delipidated embryos. In conclusion, normal developmental progression of dilapidated embryos indicates that LDs are largely unutilized during preimplantation stages. The apparent dispensability of the LDs fraction throughout preimplantation development prompts questions about their so far uncovered role in mammalian embryo. Based on our preliminary observation of the ultrastructure of diapaused blastocysts from mouse and sheep, we speculate that LDs are utilized by the embryo during delayed implantation, i.e., while waiting for the maternal receptivity signal before implantation.

Isolation and pharmacological characterization of α-Elapitoxin-Na1a, a novel short-chain postsynaptic neurotoxin from the venom of the Chinese Cobra (Naja atra)

The Chinese Cobra (Naja atra) is an elapid snake of major medical importance in southern China. Although previous studies have shown that postsynaptic neurotoxins account for 11–23% of N. atra venom, envenomed patients do not display marked signs of neurotoxicity. We have previously shown that the lack of clinical neurotoxicity following snake envenoming by some species with ‘neurotoxic’ venoms may be related to the high prevalence of short-chain postsynaptic neurotoxins in these venoms. In this study, we describe the isolation and characterization of α-Elapitoxin-Na1a (α-EPTX-Na1a; 6949 Da), a short-chain postsynaptic neurotoxin, which accounts for approximately 9% of N. atra crude venom. α-EPTX-Na1a (30–300 nM) produced concentration-dependent inhibition of indirect-twitches, with a t90 value of 17 ± 2 min at 300 nM, and abolished contractile responses to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The prior addition of either Chinese N. atra monovalent antivenom (0.3 U/ml) or Australian polyvalent snake antivenom (2.4 U/ml), prevented the in vitro neurotoxic effects of α-EPTX-Na1a (30 nM). Addition of each of these antivenoms at the t90 time point partially reversed the in vitro neurotoxicity caused by α-EPTX-Na1a (30 nM). The inhibition of indirect twitches by α-EPTX-Na1a (30 nM) was not reversed by repeatedly washing the tissue. α-EPTX-Na1a displayed pseudo-irreversible antagonism of concentration-response curves to carbachol with a pA2 value of 8.21. De novo protein sequencing of α-EPTX-Na1a revealed a typical short-chain postsynaptic neurotoxin profile of 62 amino acids which shared >98% amino acid sequence similarity with short-chain postsynaptic neurotoxins from other Naja species. When compared to short-chain neurotoxins isolated from cobras in China, α-EPTX-Na1a contained novel residues K47Q (i.e. lysine to glutamine), N48T (i.e. asparagine to threonine) and G49A (i.e. glycine to alanine). In conclusion, α-EPTX-Na1a is a potent, pseudo-irreversible, short-chain neurotoxin. The high prevalence of α-EPTX-Na1a in Chinese N. atra venom is likely to explain the mild neurotoxicity experienced by envenomed patients.

Anaphylactic Shock Due to Atracurium in a Patient Underwent General Anesthesia

BACKGROUND: Anaphylaxis is a systemic hypersensitivity reaction marked by life-threatening, rapid onset of the airway, breathing, and circulation problems. Despite its rare incidence, without proper treatment, it may cause fatality.
 CASE REPORT: In this report, we present a 19-year-old female with an infected ovarian cyst, who was scheduled for gynecologic laparotomy. In pre-operative assessment, she was classified as an American Society of Anesthesiologist (ASA) one patient without any history of drug or food allergy. Hemodynamic changes occurred on anesthesia induction after the administration ofatracurium, a muscle relaxant agent. Marked clinical signs were wheezed-bronchospasm, dyspnea, hypersalivation, desaturation, tachycardia, hypotension, and systemic erythema. She was diagnosed with anaphylactic shock. We provided 100% oxygenation, fluid resuscitation, epinephrine, and supportive therapy by anaphylaxis guidelines. Respiratory and cardiovascular functions stabilized 2 h post-resuscitation. The surgery was canceled, and she was observed in ICU for 24 h.
 CONCLUSION: Timely diagnosis and early resuscitation are key factors determining the outcome of an anaphylactic reaction.

Histological Variants Induced by Gamma Irradiation in the Alimentary Tract of Callosbruchus maculatus (Coleoptera: Bruchidae)

This study had been conducted to evaluate the histological alternations induced by gamma irradiation in the alimentary tract of the 4th instar larvae of cowpea beetle Callosbruchus maculates (cowpea weevil). Using gamma rays at (0.25kGy, 0.50 kGy, 0.75 kGy, 1.0 and 1.5 kGy), and mortality was recorded at 48 and 96 hours after irradiation. The highest mortality 100% had been recorded at 1.5 kGy gamma irradiation, there wasn't any significance (P≥0.05) between irradiation at 1kGy and 1.5kGy but the significance was (P≤0.05) compared with other treatments. The lethal dose (LD50) of gamma irradiations at 48 and 96 hours were 0.4663 kGy and 0.4275kGy respectively; results revealed that the mortality augmented by increasing the radiation doses; indicated that the effectiveness of the application was dose-dependent. Histological variations triggered by irradiation showed obvious deformations, cytoplasmic vacuolization and apical degeneration of cells. Also, The tissues exhibited marked signs of lysis and necrosis of cells. Hence, gamma irradiation could be incorporated into the control strategy of C. maculatus as a physical control means for the reduction of loss caused by stored product insects.

The Antioxidant and Anti-Inflammatory Properties of Anacardium occidentale L. Cashew Nuts in a Mouse Model of Colitis.

Background: Anacardium occidentale L. is a tropical plant used for the treatment of inflammatory diseases. The goal of the present work was to investigate the anti-inflammatory and anti-oxidant potential of oral administration of cashew nuts (from Anacardium occidentale L.) in a mouse model of colitis. Methods: Induction of colitis was performed by intrarectally injection of dinitrobenzene sulfonic acid (DNBS). Cashew nuts were administered daily orally (100 mg/kg) in DNBS-injected mice. Results: Four days after DNBS, histological and macroscopic colon alterations as well as marked clinical signs and increased cytokine production were observed. Neutrophil infiltration, measured by myeloperoxidase (MPO) positive immunostaining, was correlated with up-regulation of adhesion molecules ICAM-1 and P-selectin in colons. Oxidative stress was detected with increased malondialdehyde (MDA) levels, nitrotyrosine, and poly ADP-ribose polymerase (PARP) positive staining in inflamed colons. Oral treatment with cashew nuts reduced histological, macroscopic damage, neutrophil infiltration, pro-inflammatory cytokines and MDA levels, as well as nitrotyrosine, PARP and ICAM-1, and P-selectin expressions. Colon inflammation could be related to nuclear factor (NF)-kB pathway activation and reduced manganese superoxide dismutase (MnSOD) antioxidant activity. Cashew nuts administration inhibited NF-kB and increased MnSOD antioxidant expressions. Conclusions: The results suggested that oral assumption of cashew nuts may be beneficial for the management of colitis.

Aging-related liver degeneration is associated with increased bacterial endotoxin and lipopolysaccharide binding protein levels.

Aging is a risk factor in the development of many diseases, including liver-related diseases. The two aims of the present study were 1) to determine how aging affects liver health in mice in the absence of any interventions and 2) if degenerations observed in relation to blood endotoxin levels are critical in aging-associated liver degeneration. Endotoxin levels and markers of liver damage, mitochondrial dysfunction, insulin resistance, and apoptosis as well as the Toll-like receptor 4 (Tlr-4) signaling cascade were studied in liver tissue and blood, respectively, of 3- and 24-mo-old male C57BL/6J mice. In a second set of experiments, 3- to 4-mo-old and 14-mo-old female lipopolysaccharide-binding protein (LBP)-/- mice and littermates fed standard chow, markers of liver damage, insulin resistance, and mitochondrial dysfunction were assessed. Plasma activity of aspartate aminotransferase and histological signs of hepatic inflammation and fibrosis were significantly higher in old C57BL/6J mice than in young animals. The number of neutrophils, CD8α-positive cells, and mRNA expression of markers of apoptosis were also significantly higher in livers of old C57BL/6J mice compared with young animals, being also associated with a significant induction of hepatic Tlr-4 and LBP expression as well as higher endotoxin levels in peripheral blood. Compared with age-matched littermates, LBP-/- mice display less signs of senescence in liver. Taken together, our data suggest that, despite being fed standard chow, old mice developed liver inflammation and beginning fibrosis and that bacterial endotoxin may play a critical role herein.NEW & NOTEWORTHY Old age in mice is associated with marked signs of liver degeneration, hepatic inflammation, and fibrosis. Aging-associated liver degeneration is associated with elevated bacterial endotoxin levels and an induction of lipopolysaccharide-binding protein (LBP) and Toll-like receptor 4-dependent signaling cascades in liver tissue. Furthermore, in old aged LBP-/- mice, markers of senescence seem to be lessened, supporting the hypothesis that bacterial endotoxin levels might be critical in aging-associated decline of liver.

Question Mark Sign and Transvaginal Ultrasound Uterine Tenderness for the Diagnosis of Adenomyosis: A Prospective Validation.

To evaluate the diagnostic accuracy of the classic ultrasound (US) signs of adenomyosis, the question mark sign and transvaginal ultrasound (TVUS) uterine tenderness, in the diagnosis of adenomyosis. This was a prospective study including 78 patients waiting for hysterectomy for uterine benign diseases and undergoing preoperative US examinations to evaluate all criteria for US diagnosis of adenomyosis as reported by the consensus statement of the Morphological Uterus Sonographic Assessment group. A US diagnosis of adenomyosis was made in the presence of 2 or more Morphological Uterus Sonographic Assessment features. Moreover, the question mark sign and TVUS uterine tenderness were evaluated. Ultrasound features were compared with the histologic examination, which was considered the reference standard for the diagnosis of adenomyosis. The Cohen κ coefficient was used to measure the accordance between US and histologic results. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of each US feature were calculated. The prevalence of adenomyosis in the sample was 33.3%. The sensitivity, specificity, PPV, NPV, and accuracy of TVUS in the diagnosis of adenomyosis were 77%, 96%, 91%, 89%, and 90%, respectively. Myometrial heterogeneity was the most frequently encountered feature (100%) but showed low specificity (7%). The question mark sign and TVUS uterine tenderness showed sensitivity, specificity, PPV, NPV, and accuracy of 41%, 96%, 83%, 77%, and 69% and 69%, 65%, 66%, 81%, and 67%. The question mark sign and TVUS uterine tenderness are useful tools for the diagnosis of adenomyosis.

3′‐(4‐(Benzyloxy)phenyl)‐1′‐phenyl‐5‐(heteroaryl/aryl)‐3,4‐dihydro‐1′H,2H‐[3,4′‐bipyrazole]‐2‐carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies

Pyrazoline-linked carboxamide derivatives were designed, synthesized, and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer activity, and apoptotic and cardiomyopathy toxicity. Compounds 6m and 6n inhibit EGFR kinase at a concentration of 6.5 ± 2.91 and 3.65 ± 0.54 µM, respectively. Some of these compounds showed effects on proliferation, which were also then evaluated against four different human cancer cell lines, that is, MCF-7 (breast cancer), A549 (non-small-cell lung tumor), HCT-116 (colon cancer), and SiHa cells (cancerous tissues of the cervix uteri). The results showedthat certainsynthetic compounds showed significant inhibitor activity; compounds 6m and 6n were more cytotoxic than doxorubicin against A549 cancer cells, with IC50 values of 10.3 ± 1.07 and 4.6 ± 0.57 µM, respectively. Additionally, compounds 6m and 6n induced apoptosis in A549 cancer cells, as evidenced by 4',6-diamidino-2-phenylindole (DAPI) staining and phase-contrast microscopy. Potency to induce apoptosis by compound 6n was further confirmed by fluorescence-activated cell sorting using Annexin V-FITC and propidium iodide labeling. Compound 6n showed normal cardiomyocytes with no marked sign of pyknotic nuclei in cardiomyopathy and also normal histological appearance of the renal cortex when compared with that of control. Results of molecular docking studies suggested that compounds 6m and 6n can bind to the hinge region of the adenosine triphosphate-binding site of EGFR kinase, like the standard drug erlotinib. Therefore, the present study suggests that compounds 6m and 6n have potent in vitro antitumor activities against the human non-small-cell lung tumor cell line A549, which can be further explored in other cancer cell lines and in animal studies.