Evaluation of anti-nociceptive, anti-inflammatory and hepatoprotective effects of methanol extract of Mazus pumilus (Burm. f.) Steenis (Mazaceae) herb

Purpose: This study was designed to investigate the anti-nociceptive, anti-inflammatory and hepatoprotective activities of the methanol extract of Mazus pumilus (Mazaceae) herb. Methods: Anti-nociceptive activity was determined using hot plate, tail flick and acetic acid-induced writing methods. Carrageenan-induced rat paw edema (0.1 mL of 1 %) model was used for the assessment of anti-inflammatory activity. The methanol extract was administered orally at three different doses (150, 300 and 600 mg/kg) to three separate groups in all the experiments. Diclofenac sodium (50 mg/kg) was used as standard drug while control group received DMSO (1 %, 10 mL/kg). The hepatocurative effect of methanol extract of M. pumilus (400 mg/kg) was determined in isoniazid (50 mg/kg) and rifampicin (100 mg/kg) induced liver injury. Silymarin (100 mg/kg) was used as standard drug for comparison. The control group received distilled water (10 mL/kg). Preliminary phytochemical screening was also carried out. Results: The methanol extract of M. pumilus significantly (p < 0.05) augmented latency time and reduced the number of writhes in the pain models at all doses used for the assessment of antinociceptive actions. The anti-inflammatory activity of different doses of extract was evaluated by measuring the reduction in the size of the paw. A significant (p < 0.05) hepatocurative effect was observed when administered after anti-tuberculosis drugs. Histopathological analysis of the liver tissues also revealed restored hepatocellular architecture. Conclusion: The results demonstrate the anti-nociceptive, anti-inflammatory and hepatoprotective effects of the methanol extract of M. pumilus, thus substantiating the ethnomedical claims associated with the herb

Quantitative cardiac magnetic resonance T2 imaging offers ability to non-invasively predict acute allograft rejection in children

BACKGROUND: Monitoring for acute allograft rejection improves outcomes after cardiac transplantation. Endomyocardial biopsy is the gold standard test defining rejection, but carries risk and has limitations. Cardiac magnetic resonance T2 mapping may be able to predict rejection in adults, but has not been studied in children. Our aim was to evaluate T2 mapping in identifying paediatric cardiac transplant patients with acute rejection. METHODS: Eleven paediatric transplant patients presenting 18 times were prospectively enrolled for non-contrast cardiac magnetic resonance at 1.5 T followed by endomyocardial biopsy. Imaging included volumetry, flow, and T2 mapping. Regions of interest were manually selected on the T2 maps using the middle-third technique in the left ventricular septal and lateral wall in a short-axis and four-chamber slice. Mean and maximum T2 values were compared with Student\u27s t-tests analysis. RESULTS: Five cases of acute rejection were identified in three patients, including two cases of grade 2R on biopsy and three cases of negative biopsy treated for clinical symptoms attributed to rejection (new arrhythmia, decreased exercise capacity). A monotonic trend between increasing T2 values and higher biopsy grades was observed: grade 0R T2 53.4 ± 3 ms, grade 1R T2 54.5 ms ± 3 ms, grade 2R T2 61.3 ± 1 ms. The five rejection cases had significantly higher mean T2 values compared to cases without rejection (58.3 ± 4 ms versus 53 ± 2 ms, p = 0.001). CONCLUSIONS: Cardiac magnetic resonance with quantitative T2 mapping may offer a non-invasive method for screening paediatric cardiac transplant patients for acute allograft rejection. More data are needed to understand the relationship between T2 and rejection in children

Incident disease associations with mosaic chromosomal alterations on autosomes, X and Y chromosomes: insights from a phenome-wide association study in the UK Biobank.

BackgroundMosaic chromosomal alterations (mCAs) are large chromosomal gains, losses and copy-neutral losses of heterozygosity (LOH) in peripheral leukocytes. While many individuals with detectable mCAs have no notable adverse outcomes, mCA-associated gene dosage alterations as well as clonal expansion of mutated leukocyte clones could increase susceptibility to disease.ResultsWe performed a phenome-wide association study (PheWAS) using existing data from 482,396 UK Biobank (UKBB) participants to investigate potential associations between mCAs and incident disease. Of the 1290 ICD codes we examined, our adjusted analysis identified a total of 50 incident disease outcomes associated with mCAs at PheWAS significance levels. We observed striking differences in the diseases associated with each type of alteration, with autosomal mCAs most associated with increased hematologic malignancies, incident infections and possibly cancer therapy-related conditions. Alterations of chromosome X were associated with increased lymphoid leukemia risk and, mCAs of chromosome Y were linked to potential reduced metabolic disease risk.ConclusionsOur findings demonstrate that a wide range of diseases are potential sequelae of mCAs and highlight the critical importance of careful covariate adjustment in mCA disease association studies

Targeted long-read sequencing of the Ewing sarcoma 6p25.1 susceptibility locus identifies germline-somatic interactions with EWSR1-FLI1 binding

Ewing sarcoma (EwS) is a rare bone and soft tissue malignancy driven by chromosomal translocations encoding chimeric transcription factors, such as EWSR1-FLI1, that bind GGAA motifs forming novel enhancers that alter nearby expression. We propose that germline microsatellite variation at the 6p25.1 EwS susceptibility locus could impact downstream gene expression and EwS biology. We performed targeted long-read sequencing of EwS blood DNA to characterize variation and genomic features important for EWSR1-FLI1 binding. We identified 50 microsatellite alleles at 6p25.1 and observed that EwS-affected individuals had longer alleles (>135 bp) with more GGAA repeats. The 6p25.1 GGAA microsatellite showed chromatin features of an EWSR1-FLI1 enhancer and regulated expression of RREB1, a transcription factor associated with RAS/MAPK signaling. RREB1 knockdown reduced proliferation and clonogenic potential and reduced expression of cell cycle and DNA replication genes. Our integrative analysis at 6p25.1 details increased binding of longer GGAA microsatellite alleles with acquired EWSR-FLI1 to promote Ewing sarcomagenesis by RREB1-mediated proliferation

Ongoing strategies to improve antimicrobial utilization in hospitals across the Middle East and North Africa (MENA) : findings and implications

Antimicrobial resistance (AMR) is an increasing global concern, increasing costs, morbidity, and mortality. National action plans (NAPs) to minimize AMR are one of several global and national initiatives to slow down rising AMR rates. NAPs are also helping key stakeholders understand current antimicrobial utilization patterns and resistance rates. The Middle East is no exception with high AMR rates. Antibiotic point prevalence surveys (PPS) provide a better understanding of existing antimicrobial consumption trends in hospitals, and assist with the subsequent imple-mentation of antimicrobial stewardship programs (ASPs). These are important NAP activities. We examined current hospital consumption trends across the Middle East along with documented ASPs. A narrative assessment of 24 PPS studies in the Region found that, on average, more than 50% of in-patients received antibiotics, with Jordan having the highest rate at 98.1%. Published studies ranged in size from single to 18 hospitals. The most prescribed antibiotics were ceftriax-one, metronidazole, and penicillin. In addition, significant postoperative antibiotic prescribing lasting up to five days or longer was common to avoid surgical site infections. These findings have resulted in a variety of suggested short-, medium-, and long-term actions among key stakehold-ers, including governments and healthcare workers, to improve and sustain future antibiotic prescribing in order to decrease AMR throughout the Middle East

Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides—Where Are We Now

Peptide receptor radionuclide therapy (PRRT) has been one of the most successful and exciting examples of theranostics in nuclear medicine in recent decades and is now firmly embedded in many treatment algorithms for unresectable or metastatic neuroendocrine neoplasms (NENs) worldwide. It is widely considered to be an effective treatment for well- or moderately differentiated neoplasms, which express high levels of somatostatin receptors that can be selectively targeted. This review article outlines the scientific basis of PRRT in treatment of NENs and describes its discovery dating back to the early 1990s. Early treatments utilizing Indium-111, a γ-emitter, showed promise in reduction in tumor size and improvement in biochemistry, but were also met with high radiation doses and myelotoxic and nephrotoxic effects. Subsequently, stable conjugation of DOTA-peptides with β-emitting radionuclides, such as Yttrium-90 and Lutetium-177, served as a breakthrough for PRRT and studies highlighted their potential in eliciting progression-free survival and quality of life benefits. This article will also elaborate on the key trials which paved the way for its approval and will discuss therapeutic considerations, such as patient selection and administration technique, to optimize its use

Perfusion CT assessment of the colon and rectum : Feasibility of quantification of bowel wall perfusion and vascularization

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.The aim was to determine the feasibility of vascular quantification of the bowel wall for different anatomical segments of the colorectum. Following institutional ethical approval and informed consent, 39 patients with colorectal cancer underwent perfusion CT. Blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS) were assessed for different segments of the colorectum: ascending, transverse, descending colon, sigmoid, or rectum, that were distant from the tumor, and which were proven normal on contemporary colonoscopy, and subsequent imaging and clinical follow up. Mean (SD) for BF, BV, MTT and PS for the different anatomical colorectal segments were obtained and compared using a pooled t-test. Significance was at 5%. Assessment was not possible in 9 of 39 (23%) patients as the bowel wall was ≤5mm precluding quantitative analysis. Forty-four segments were evaluated in the remaining 30 patients. Mean BF was higher in the proximal than distal colon: 24.0 versus 17.8mL/min/100g tissue; p=0.009; BV, MTT and PS were not significantly different; BV: 3.46 versus 3.15mL/100g tissue, p=0.45; MTT: 15.1 versus 18.3s; p=0.10; PS: 6.84 versus 8.97mL/min/100 tissue, p=0.13, respectively. In conclusion, assessment of bowel wall perfusion may fail in 23% of patients. The colorectum demonstrates segmental differences in perfusion.Peer reviewe