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Aflatoxins are the most common mycotoxin contaminant reported in food and feed. Aflatoxin B1, the most toxic among different aflatoxins, is known to cause hepatocellular carcinoma in animals. Aspergillus flavus and A. parasiticus are the main producers of aflatoxins and are widely distributed in tropical countries. Even though several robust strategies have been in use to control aflatoxin contamination, the control at the pre-harvest level is primitive and incompetent. Therefore, the aim of the study was to isolate and identify the non-aflatoxigenic A. flavus and to delineate the molecular mechanism for the loss of aflatoxin production by the non-aflatoxigenic isolates. Eighteen non-aflatoxigenic strains were isolated from various biological sources using cultural and analytical methods. Among the 18 isolates, 8 isolates produced sclerotia and 17 isolates had type I deletion in norB-cypA region. The isolates were confirmed as A. flavus using gene-specific PCR and sequencing of the ITS region. Later, aflatoxin gene-specific PCR revealed that the defect in one or more genes has led to non-aflatoxigenic phenotype. The strain R9 had maximum defect, and genes avnA and verB had the highest frequency of defect among the non-aflatoxigenic strains. Further, qRT-PCR confirmed that the non-aflatoxigenic strains had high frequency of defect or downregulation in the late pathway genes compared to early pathway genes. Thus, these non-aflatoxigenic strains can be the potential candidates for an effective and proficient strategy for the control of pre-harvest aflatoxin contamination.

Orbital infarction syndrome is an uncommon pathology with devastating consequences. It is frequently secondary to atherothrombotic phenomena in the internal carotid artery. We report a case of a 66-year-old male with uncontrolled diabetes and use of systemic steroids for COVID-19, who presented with a sudden loss of vision in the left eye, with total ophthalmoplegia and diffuse opacification of the retina. On imaging, he was found to have features of rhino-orbital cellulitis with ischemia of the orbital tissue secondary to isolated ophthalmic artery obstruction (OAO) with a patent internal carotid artery. KOH mount of deep nasal swab was confirmatory of mucor. This is the first reported case of orbital infarction syndrome in the setting of COVID-19.

Transcriptomic profiling of several drugs in cancer cell lines has been utilised to obtain drug-specific signatures and guided combination therapy to combat drug resistance and toxicity. Global metabolomics reflects changes due to altered activity of enzymes, environmental factors, etc. Integrating transcriptomics and metabolomics can provide genotype-phenotype correlation, providing meaningful insights into alterations in gene expression and its outcome to understand differential metabolism and guide therapy. This study uses a multi-omics approach to understand the global gene expression and metabolite changes induced by Disarib, a novel Bcl2-specific inhibitor in the Ehrlich adenocarcinoma (EAC) breast cancer mouse model. RNAseq analysis was performed on EAC mouse tumours treated with Disarib and compared to the controls. The expression of 6 oncogenes and 101 tumour suppressor genes interacting with Bcl2 and Bak were modulated upon Disarib treatment. Cancer hallmark pathways like DNA repair, Cell cycle, angiogenesis, and mitochondrial metabolism were downregulated, and programmed cell death platelet-related pathways were upregulated. Global metabolomic profiling using LC-MS revealed that Oncometabolites like carnitine, oleic acid, glycine, and arginine were elevated in tumour mice compared to normal and were downregulated upon Disarib treatment. Integrated transcriptomic and metabolomic profiles identified arginine metabolism, histidine, and purine metabolism to be altered upon Disarib treatment. Pro-angiogenic metabolites, arginine, palmitic acid, oleic acid, and myristoleic acid were downregulated in Disarib-treated mice. We further validated the effect of Disarib on angiogenesis by qRT-PCR analysis of genes in the VEGF pathway. Disarib treatment led to the downregulation of pro-angiogenic markers. Furthermore, the chorioallantoic membrane assay displayed a reduction in the formation of the number of secondary blood vessels upon Disarib treatment. Disarib reduces tumours by reducing oncometabolite and activating apoptosis and downregulating angiogenesis.

Background/aimTo evaluate the efficacy of intravitreal topotecan for refractory or recurrent vitreous seeds in retinoblastoma.MethodsIntravitreal injection of topotecan hydrochloride (30 µg/0.15 mL) was provided every 3 weeks by the safety enhanced technique.ResultsThe study included 17 consecutive patients with retinoblastoma with refractory or recurrent vitreous seeds. Five eyes (29%) belonged to International Classification of Retinoblastoma group C and 12 eyes (71%) belonged to group D. Primary treatment included triple drug intravenous chemotherapy for a mean of 10 cycles (median, 9 cycles; range, 6–18 cycles). Fifteen patients (88%) had undergone 56 periocular carboplatin injections with a mean of 4 injections (median, 3 injections; range, 1–8 injections), concurrent with intravenous chemotherapy. A total of 53 intravitreal topotecan injections were performed in 17 eyes of 17 consecutive patients with refractory or recurrent vitreous seeds with a mean of 3 injections (median, 3 injections; range, 2–6 injections). Complete regression of vitreous seeds was achieved in 17 of 17 eyes (100%). At a mean follow-up of 23.8 months (median, 24 months; range, 15.1–34.1 months), one eye (6%) with a recurrent retinal tumour needed enucleation, and the rest of the 16 eyes (94%) maintained complete regression. Final visual acuity could be reliably assessed in all 16 eyes (100%), of whom 12 eyes (75%) had visual acuity ≥20/200. None of the patients developed ocular or systemic complications.ConclusionThree-weekly intravitreal topotecan appears effective and safe in controlling focal or diffuse refractory or recurrent vitreous seeds in retinoblastoma.

Magnetic resonance imaging (MRI) is an eloquent, noninvasive, cross-sectional imaging modality that offers superior tissue characterization of orbital pathologies. The ophthalmologist needs to be aware of the advantages of MRI and its step-wise interpretation in liaison with a radiologist to optimize patient outcomes. In this review, we discuss the basic principles of MRI, some of the commonly used sequences and protocols, the anatomy of the orbit on MRI, and an approach to radiological interpretation.

In this article we focus on a systematic approach to assess common orbital lesions on magnetic resonance imaging (MRI). The identification of the probable compartment or structure of origin helps narrow the differential diagnosis of a lesion. Analyzing the morphology, appearance, and signal intensity on various sequences, the pattern, and degree of contrast enhancement are key to characterize lesions on MRI. Imaging features suggesting cellularity and vascularity can also be determined to help plan for biopsy or surgery of these lesions. MRI can also distinguish active from chronic disease in certain pathologies and aids in selecting appropriate medical management. MRI may thus serve as a diagnostic tool and help in guiding therapeutic strategies and posttreatment follow-up.

Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions in the genome of malaria vectors are implicated in adaptation. We report the genome assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome reported here with a L50 of 4, completes the trilogy of high-resolution genomes of strains with respect to a 16.5 Mbp 2R b genotype in An. stephensi known to be associated with adaptation to environmental heterogeneity. Unlike the reported genomes of two other strains, STE2 (2R+ b /2R b ) and UCI (2R b /2R b ), IndCh is found to be homozygous for the standard form (2R+ b /2R+ b ). Comparative genome analysis revealed base-level details of the breakpoints and allowed extraction of 22,650 segregating SNPs for typing this inversion in populations. Whole genome sequencing of 82 individual mosquitoes from diverse geographical locations reveal that one third of both wild and laboratory populations maintain the heterozygous genotype of 2R b . The large number of SNPs can be tailored to 1740 exonic SNPs enabling genotyping directly from transcriptome sequencing. The genome trilogy approach accelerated the study of fine structure and typing of an important inversion in An. stephensi , putting the genome resources for this understudied species on par with the extensively studied malaria vector, Anopheles gambiae . We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse geographical locations cluster with IndCh, pointing to significant convergence resulting from travel and commerce between cities, perhaps, contributing to the survival of the fittest strain.

Isolated cardiac sarcoidosis (ICS) accounts for 5%-10% of patients with sarcoidosis. It can involve atrioventricular node causing heart block, as well as the basal septum, papillary muscles, focal regions in the free wall, and the myocardium being more commonly involved. The diagnosis is achieved on magnetic resonance imaging (MRI) and endomyocardial biopsy. Recently, Fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (F-18 FDG PET) has been incorporated in the diagnosis as well as management algorithm. We describe an interesting case of ICS detected on F-18 FDG PET and MRI and discuss its role in the management of this rare presentation.

Purpose: The novel coronavirus SARS-CoV-2 (COVID-19) and the resultant nationwide lockdown and travel restrictions led to difficulty in providing timely and regular treatment to patients with childhood cancers such as retinoblastoma. This study is aimed at assessing the demography, clinical presentation, treatment strategies, and outcome of treatment defaulters due to the lockdown. Methods: Cross-sectional, observational study of retinoblastoma patients at a tertiary care ocular oncology center during the first wave of COVID-19 and the resulting nationwide lockdown. Results: Of the 476 eyes of 326 patients undergoing active management with a median age of 57 months (range: 4-214 months), 205 (63%) patients returned for follow-up after a mean delay of 45.8 ± 24.3 weeks (range: 8-80 weeks) and 121 (37%) were defaulters according to the data analyzed till June 30, 2021. Distance of residence was ≥1000 km for 148 patients (46%). In terms of need for active treatment, the number of emergent cases was 2 (<1%), 11 (3%) were urgent, and 313 (96%) were semi-urgent. International classification groups D (n = 107 eyes, 23%) and E (n = 173 eyes, 36%) were in majority, and 13 eyes (4%) and 4 eyes (1%) were at stages 3 and 4, respectively. Prior to lockdown, 86 eyes (18%) had active tumor, which remained unchanged (n = 26, 30%) or worsened (n = 49, 60%) after failure to follow-up. Vision (47%), eye (92%), and life salvage (98%) were achieved by individualized protocol-based management after the patients returned for further management. Five children succumbed to intracranial extension. Conclusion: The COVID-19-related nationwide lockdown has deprived retinoblastoma patients of optimal and timely management, leading to prolonged treatment interruptions, delays, permanent default, and death. It is of paramount importance for all the stakeholders to increase awareness, make necessary travel and logistic arrangements, and ensure continuity of care for children with retinoblastoma.

In the age of genomics-based crop improvement, a high-quality genome of a local landrace adapted to the local environmental conditions is critically important. Grain amaranths produce highly nutritional grains with a multitude of desirable properties including C4 photosynthesis highly sought-after in other crops. For improving the agronomic traits of grain amaranth and for the transfer of desirable traits to dicot crops, a reference genome of a local landrace is necessary. Toward this end, our lab had initiated sequencing the genome of (A.hyp_K_white) and had reported a draft genome in 2014. We selected this landrace because it is well adapted for cultivation in India during the last century and is currently a candidate for TILLING-based crop improvement. More recently, a high-quality chromosome-level assembly of (PI558499, Plainsman) was reported. Here, we report a chromosome-level assembly of A.hyp_K_white (AhKP) using low-coverage PacBio reads, contigs from the reported draft genome of A.hyp_K_white, raw HiC data and reference genome of Plainsman (A.hyp.V.2.1). The placement of A.hyp_K_white on the phylogenetic tree of grain amaranths of known accessions clearly suggests that A.hyp_K_white is genetically distal from Plainsman and is most closely related to the accession PI619259 from Nepal (Ramdana). Furthermore, the classification of another accession, Suvarna, adapted to the local environment and selected for yield and other desirable traits, is clearly . A classification based on hundreds of thousands of SNPs validated taxonomy-based classification for a majority of the accessions providing the opportunity for reclassification of a few.