ZOLEDRONIC ACID: A MISCHIEVOUS SUSPECT FOR LIVER INJURY

ABSTRACTA 47-year-old male diagnosed as adenocarcinoma of the lung and received 8 cycles of chemotherapy comprising intravenous administration ofcisplatin 125 mg, pemetrexed 850 mg along with zoledronic acid 4 mg. After the completion of the 8 cycle, the liver enzymes were found to bemarkedly elevated, evincing zoledronic acid as the cause for hepatotoxicity. The case details were taken from the patient's medical record along withthe biochemical test reports and radiographic images. The causal association was confirmed using Naranjo's algorithm and Roussel Uclaf CausalityAssessment Method (RUCAM). After the uneventful chemotherapy, patient's liver function tests (LFT) were abnormal. There was an elevation in theaspartate aminotransferase, alanine transaminase, alkaline phosphatase, and direct bilirubin. The causal relationship was established using Naranjo'salgorithm (score-6) and RUCAM (score-5), displayed a probable†and possible†association. Hartwig's severity scale and Thornton's preventabilityscale displayed the adverse drug reaction to being moderately severe and not preventable, respectively. The zoledronic acid was stopped and neverreadministered. The LFTs assumed normal after a span of 2 months. The mechanism underlying hepatotoxicity due to zoledronic acid remains elusive.Zoledronic acid can induce acute phase response mediated by active production of interleukin-6, tumor necrosis factor alpha, and pro-inflammatorycytokines from the T-cells and macrophages. Vigilant monitoring along with timely assessment and management can prevent the occurrence ofirreversible liver damage. Henceforth, we would like to report the rare incidence of drug induced hepatic damage due to zoledronic acid. Henceforth,we would like to report the rare incidence of drug induced hepatic damage due to zoledronic acid.Keywords: Bisphosphonate, Dechallenge, Hepatotoxicity, Rechallenge.t

Novel molecules and target genes for vegetative heat tolerance in wheat

To prevent yield losses caused by climate change it is important to identify naturally tolerant genotypes with traits and related pathways that can be targeted for crop improvement. Here we report on the characterization of contrasting vegetative heat tolerance in two UK bread wheat varieties. Under chronic heat stress, the heat-tolerant cultivar Cadenza produced an excessive number of tillers which translated into more spikes and higher grain yield compared to heat-sensitive Paragon. RNAseq and metabolomics analyses revealed a set of about 400 heat-responsive genes common to both genotypes. Only 71 genes showed a genotype x temperature interaction. As well as known heat-responsive genes such as HSPs, several genes that have not been previously linked to the heat response, particularly in wheat, have been identified, including several dehydrins, a number of ankyrin-repeat protein-encoding genes, and lipases. Over 5000 genotype-specific genes were identified, including photosynthesis-related genes which might explain the observed ability of Cadenza to maintain photosynthetic rate under heat stress. Contrary to primary metabolites, secondary metabolites showed a highly differentiated heat response and genotypic differences. These included e.g., benzoxazinoid (DIBOA, DIMBOA) but in particular phenylpropanoids and flavonoids with known radical scavenging capacity, which was assessed via the DPPH assay. The most highly heat-induced metabolite was (glycosylated) propanediol, which is widely used in industry as an anti-freeze. To our knowledge this is the first report on its response to stress in plants. The identified metabolites and candidate genes provide novel targets for the development of heat tolerant wheat

An integrative approach for a network based meta-analysis of viral RNAi screens.

BACKGROUND: Big data is becoming ubiquitous in biology, and poses significant challenges in data analysis and interpretation. RNAi screening has become a workhorse of functional genomics, and has been applied, for example, to identify host factors involved in infection for a panel of different viruses. However, the analysis of data resulting from such screens is difficult, with often low overlap between hit lists, even when comparing screens targeting the same virus. This makes it a major challenge to select interesting candidates for further detailed, mechanistic experimental characterization. RESULTS: To address this problem we propose an integrative bioinformatics pipeline that allows for a network based meta-analysis of viral high-throughput RNAi screens. Initially, we collate a human protein interaction network from various public repositories, which is then subjected to unsupervised clustering to determine functional modules. Modules that are significantly enriched with host dependency factors (HDFs) and/or host restriction factors (HRFs) are then filtered based on network topology and semantic similarity measures. Modules passing all these criteria are finally interpreted for their biological significance using enrichment analysis, and interesting candidate genes can be selected from the modules. CONCLUSIONS: We apply our approach to seven screens targeting three different viruses, and compare results with other published meta-analyses of viral RNAi screens. We recover key hit genes, and identify additional candidates from the screens. While we demonstrate the application of the approach using viral RNAi data, the method is generally applicable to identify underlying mechanisms from hit lists derived from high-throughput experimental data, and to select a small number of most promising genes for further mechanistic studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13015-015-0035-7) contains supplementary material, which is available to authorized users

Vital Staining- Pivotal Role in the Field of Pathology

A dye or stain is capable of penetrating the living cells or tissues and not inducing immediate degenerative changes. Vital stain means a stain that can be applied on a living cells without killing them. Thus these stains have been useful for both diagnostic and surgical techniques in a variety of medical specialities. As this technique is quite simple, easy to perform and cost effective, it can be useful in diagnosing any malignant changes occurring and also preventing them in a community level. Thus this vital staining can be used as an important tool in the field of diagnostic pathology. This article reviews about the various types of vital stains and its applications in the field of pathology.</p

Glandular odontogenic cyst: Report of an unusual bilateral occurrence

Glandular odontogenic cyst (GOC) is a recently recognized rare developmental odontogenic cyst having an aggressive behavior and accounting for 0.012% to 1.3% of all jaw cysts. GOC usually presents as a painless, slow-growing swelling that tends to affect the anterior part of the jaws. It chiefly occurs in the fourth and fifth decades of life and presents as an expansion of jaws with or without pain or paresthesia. Aggressive nature of the lesion has been reported, as supported by the fact that 25 to 55% of cases recur following curettage. So far only just over 113 cases of GOC have been reported in the literature. Here, we report a case of bilateral GOC in the posterior region of the maxilla, in a 29-year-old male patient, which is unique, being the first case of bilateral GOC to be reported in the literature

Mucormyc.osis of the Palatal tissues : Case Report

Mucormycosis is a serious infection caused by a opportunistic fungi. The most frequently affected are is the maxillofacial region. A case of mucormycosis of the palatal tissue in a female diabetic patient is reported

GET_PANGENES: calling pangenes from plant genome alignments confirms presence-absence variation.

Crop pangenomes made from individual cultivar assemblies promise easy access to conserved genes, but genome content variability and inconsistent identifiers hamper their exploration. To address this, we define pangenes, which summarize a species coding potential and link back to original annotations. The protocol get_pangenes performs whole genome alignments (WGA) to call syntenic gene models based on coordinate overlaps. A benchmark with small and large plant genomes shows that pangenes recapitulate phylogeny-based orthologies and produce complete soft-core gene sets. Moreover, WGAs support lift-over and help confirm gene presence-absence variation. Source code and documentation: https://github.com/Ensembl/plant-scripts

Additional file 1 of GET_PANGENES: calling pangenes from plant genome alignments confirms presence-absence variation

Additional file 1: Table S1. Other Whole Genome Alignment stats for minimap2 and GSAlign algorithms. Table S2. Summary of BUSCO completeness analyses of individual genomes that are part of datasets in this paper. Table S3. Collinear genes found between Arabidopsis thaliana and A. lyrata within 23 blocks of the Ancestral Crucifer Karyotype based on Whole Genome Alignments produced with minimap2 and GSAlign. Table S4. Excerpt from BED-like pangene matrix produced during the analysis of dataset rice3. Table S5. Summary of Whole Genome Alignment (WGA) evidence for the gene models in CDS cluster Horvu_MOREX_1H01G011400 resulting from the analysis of dataset barley20. Figure S1. Overlap ratio of collinear gene models in rice, wheat and barley. Figure S2. Dot plots of collinear gene models called in rice, wheat and barley genomes. Figure S3. Venn diagrams of pangene clusters based on minimap2 and GSAlign Whole Genome Alignments of the rice3 dataset. Figure S4. Sequence identity among sequences in rice3 pangene clusters based on minimap2 (left) and GSAlign (right). Figure S5. Example of pangene cluster where the cDNA sequences have a long local alignment but the encoded CDS sequences cannot be aligned. Figure S6. Examples of rice pangene clusters not matched by Ensembl Compara orthogroups. Figure S7. Example of pangene cluster where the encoded protein sequences do not share protein domains. Figure S8. Flowchart of script check_evidence.pl , which uses as input a cluster in FASTA format and precomputed collinearity evidence in TSV format. Figure S9. Partial deletion of locus HvFT3/Ppd-H2 in barley cultivar Igri. Figure S10. Genomic context of pangene cluster HORVU.MOREX.r3.2HG0166090 (cluster members indicated with green arrows), which corresponds to barley locus HvCEN. Figure S11. Multiple alignment of protein sequences of pangene cluster HORVU.MOREX.r3.2HG0184740, which corresponds to barley locus Vrs1. Figure S12. Multiple alignment of protein sequences of pangene cluster HORVU.MOREX.r3.3HG0311160, which corresponds to barley locus HvOS2. Figure S13. Genomic context of pangene cluster gene:HORVU.MOREX.r3.7HG0752640, an example with tandem copies (cluster members indicated with green arrows), which encode acidic proteins