Changes in morphology of white blood cells on peripheral smear in COVID-19 infection

Background: COVID-19 is an infectious disease caused by a newly discovered coronavirus, and has spread around the world in a deadly pandemic. The first case of COVID-19 was reported from Wuhan, China in December 2019. This is also called as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of its homology with SARS virus. The most common hematological manifestation of coronavirus is lymphopenia which is due to depletion of lymphocytes by coronavirus infection. Other manifestations are neutrophilia and mild thrombocytopenia. Literature is full of quantitative hematological parameters but the researches on morphology of white blood cells is still ongoing. We at our institute done study on 60 confirmed positive cases of COVID-19, and analyzed those peripheral smears in terms of morphology of white blood cells.Methods: The study was done using peripheral smear staining with methylene blue stain and was screened for various changes in white blood cells in peripheral smear.Results: Changes in the white blood cells were examined in the peripheral smear and findings were made in the tabular form.Conclusions: To conclude that all these changes are due to the virus infecting them or are secondary to pathogenesis of COVID disease, needs to be evaluated by larger studies

Probiotics as an adjuvant treatment for recurrent aphthous ulcer: A randomized clinical trial

Background: The most common ulcer in adults, recurrent aphthous ulcers affect roughly 25% of them. The purpose of this study was to see how beneficial probiotics are at treating it. Materials and Procedures: 160 people in total were split into two groups. Bacillus coagulans (Sporolac) and Tetracycline capsules 250 mg (Tetrastar) were given twice daily to 80 patients in Group 1 for 7 days. In Group 2, 80 patients received just Tetracycline capsules 250 mg (Tetrastar) twice a day for 7 days. At the beginning, fourth, and seventh days of the ulcer, discomfort, size, and average duration were recorded. In order to compare the parameters between the two groups, the Mann-Whitney U test was performed. Results: Over the course of just four days, all of the metrics for the Probiotic group dropped substantially. Conclusion: RAS can be treated and managed with probiotics as adjuvant therapy

Open Access Open Access Solitary Fibrous Tumor in the Maxillary Sinus Treated By Caldwell Luc Surgery

The patient was a 45 years old man who came with chief complaints of gradual onset Progressive left nasal obstruction since one year. Patient had history of septoplasty operation done in same hospital 2 years back. Patient had history of recurrent common cold but no history of epistaxis. His Medical history was insignificant. On anterior rhinoscopic examination, well-circumscribed mass was seen filling the left nasal cavity which probably aroused from the middle meatus Abstract Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually arises from the pleura. Also known as benign fibrous mesothelioma or submesothelial fibroma, it is one of the different types of mesothelial tumor. SFT was first described in 1931 as a primary spindle cell tumor of the pleura. There are some cases reported in the world extrapluraly. Here we describe an SFT that arose from the left maxillary sinus and extended to the nasal cavity. The tumor was removed by cald wel approach for enbloc resection. The majority of these tumors originate in the pleura, but SFTs can also be derived from other serosal membranes. Due to its mesenchymal origin there are extrapleural sites of origin of SFT such as the meninges, orbit, peritoneum, pelvis, adrenal glands, liver, and urogenital system. SFTs of the nasal cavity and paranasal sinuses are extremely rare, with only 24 cases reported in the English literature to date. The main treatment for SFT is complete surgical excision. Herein, we describe an SFT that arose from the left maxillary sinus and extended to the nasal cavity that was successfully treated by Caldwell Luc surgery

Cryo-EM structure of a transthyretin-derived amyloid fibril from a patient with hereditary ATTR amyloidosis

ATTR amyloidosis is one of the worldwide most abundant forms of systemic amyloidosis. The disease is caused by the misfolding of transthyretin protein and the formation of amyloid deposits at different sites within the body. Here, we present a 2.97 angstrom cryo electron microscopy structure of a fibril purified from the tissue of a patient with hereditary Val30Met ATTR amyloidosis. The fibril consists of a single protofilament that is formed from an N-terminal and a C-terminal fragment of transthyretin. Our structure provides insights into the mechanism of misfolding and implies the formation of an early fibril state from unfolded transthyretin molecules, which upon proteolysis converts into mature ATTR amyloid fibrils

Defining the Magnetic Resonance Features of Renal Lesions and Their Response to Everolimus in a Transgenic Mouse Model of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an inherited genetic disorder characterized by mutations in TSC1 or TSC2 class of tumor suppressers which impact several organs including the kidney. The renal manifestations are usually in the form of angiomyolipoma (AML, in 80% of the cases) and cystadenomas. mTOR inhibitors such as rapamycin and everolimus have shown efficacy in reducing the renal tumor burden. Early treatment prevents the progression of AML; however, the tumors regrow upon cessation of therapy implying a lifelong need for monitoring and management of this morbid disease. There is a critical need for development of imaging strategies to monitor response to therapy and progression of disease which will also facilitate development of newer targeted therapy. In this study we evaluated the potential of multiparametric 1H magnetic resonance imaging (mpMRI) to monitor tumor response to therapy in a preclinical model of TSC, the transgenic mouse A/J Tsc2+/- . We found 2-dimensional T2-weighted sequence with 0.5 mm slice thickness to be optimal for detecting renal lesions as small as 0.016 mm3. Baseline characterization of lesions with MRI to assess physiological parameters such as cellularity and perfusion is critical for distinguishing between cystic and solid lesions. Everolimus treatment for three weeks maintained tumor growth at 36% from baseline, while control tumors displayed steady growth and were 70% larger than baseline at the end of therapy. Apparent diffusion coefficient, T1 values and normalized T2 intensity changes were also indictive of response to treatment. Our results indicate that standardization and implementation of improved MR imaging protocols will significantly enhance the utility of mpMRI in determining the severity and composition of renal lesions for better treatment planning

55 Mn-based fiducial markers for rapid and automated RF coil localization for hyperpolarized 13 C MRI.

PurposeTo use fiducial markers containing manganese 55 to rapidly localize carbon 13 (13 C) RF coils for correcting images for B1 variation.MethodsHollow high-density polyethylene spheres were filled with 3M sodium permanganate and affixed to a rectangular 13 C-tuned RF coil. The relative positions of the markers and coil conductors were mapped using CT. Marker positions were measured by MRI using a series of 1D projections and automated peak detection. Once the coil location was determined, coil sensitivity was estimated using a quasi-static calculation. Simulations were performed to determine the minimum number of projections required for robust localization. Phantom experiments were used to confirm the accuracy of marker localization as well as the calculated coil sensitivity. Finally, in vivo validation was performed using hyperpolarized 13 C pyruvate in a rat model.ResultsIn simulations, our algorithm was accurate in determining marker positions when at least 6 projections were used (RMSE 1.4 ± 0.9 mm). These estimates were verified in phantom experiments, where markers locations were determined with an RMS accuracy of 1.3 mm. A minimum SNR of 4 was required for automated detection to perform accurately. Computed coil sensitivity had a median error of 17% when taken over the entire measured area and 5.7% over a central region. In a rat, correction for nonuniform reception and flip angle was able to normalize the signals arising from asymmetrically positioned kidneys.ConclusionManganese 55 fiducial markers are an inexpensive and reliable method for rapidly localizing 13 C RF coils and correcting 13 C images for B1 variation without user intervention

Metabolite-Specific Echo Planar Imaging for Preclinical Studies with Hyperpolarized 13C-Pyruvate MRI

Metabolite-specific echo-planar imaging (EPI) sequences with spectral-spatial (spsp) excitation are commonly used in clinical hyperpolarized [1-13C]pyruvate studies because of their speed, efficiency, and flexibility. In contrast, preclinical systems typically rely on slower spectroscopic methods, such as chemical shift imaging (CSI). In this study, a 2D spspEPI sequence was developed for use on a preclinical 3T Bruker system and tested on in vivo mice experiments with patient-derived xenograft renal cell carcinoma (RCC) or prostate cancer tissues implanted in the kidney or liver. Compared to spspEPI sequences, CSI were found to have a broader point spread function via simulations and exhibited signal bleeding between vasculature and tumors in vivo. Parameters for the spspEPI sequence were optimized using simulations and verified with in vivo data. The expected lactate SNR and pharmacokinetic modeling accuracy increased with lower pyruvate flip angles (less than 15°), intermediate lactate flip angles (25° to 40°), and temporal resolution of 3 s. Overall SNR was also higher with coarser spatial resolution (4 mm isotropic vs. 2 mm isotropic). Pharmacokinetic modelling used to fit kPL maps showed results consistent with the previous literature and across different sequences and tumor xenografts. This work describes and justifies the pulse design and parameter choices for preclinical spspEPI hyperpolarized 13C-pyruvate studies and shows superior image quality to CSI

Multiparametric Magnetic Resonance Imaging and Metabolic Characterization of Patient-Derived Xenograft Models of Clear Cell Renal Cell Carcinoma

Patient-derived xenografts (PDX) are high-fidelity cancer models typically credentialled by genomics, transcriptomics and proteomics. Characterization of metabolic reprogramming, a hallmark of cancer, is less frequent. Dysregulated metabolism is a key feature of clear cell renal cell carcinoma (ccRCC) and authentic preclinical models are needed to evaluate novel imaging and therapeutic approaches targeting metabolism. We characterized 5 PDX from high-grade or metastatic ccRCC by multiparametric magnetic resonance imaging (MRI) and steady state metabolic profiling and flux analysis. Similar to MRI of clinical ccRCC, T2-weighted images of orthotopic tumors of most PDX were homogeneous. The increased hyperintense (cystic) areas observed in one PDX mimicked the cystic phenotype typical of some RCC. The negligible hypointense (necrotic) areas of PDX grown under the highly vascularized renal capsule are beneficial for preclinical studies. Mean apparent diffusion coefficient (ADC) values were equivalent to those of ccRCC in human patients. Hyperpolarized (HP) [1-13C]pyruvate MRI of PDX showed high glycolytic activity typical of high-grade primary and metastatic ccRCC with considerable intra- and inter-tumoral variability, as has been observed in clinical HP MRI of ccRCC. Comparison of steady state metabolite concentrations and metabolic flux in [U-13C]glucose-labeled tumors highlighted the distinctive phenotypes of two PDX with elevated levels of numerous metabolites and increased fractional enrichment of lactate and/or glutamate, capturing the metabolic heterogeneity of glycolysis and the TCA cycle in clinical ccRCC. Culturing PDX cells and reimplanting to generate xenografts (XEN), or passaging PDX in vivo, altered some imaging and metabolic characteristics while transcription remained like that of the original PDX. These findings show that PDX are realistic models of ccRCC for imaging and metabolic studies but that the plasticity of metabolism must be considered when manipulating PDX for preclinical studies