Hematological profiles of COVID-19 patients at the Ratlam district,Madhya Pradesh State,India

It is of interest to compare the hematological profile (using Complete blood count) of COVID patients admitted in ICU, private ward, and isolation ward with varying severity. This data will help predict the severity of infection at peripheries and rural areas.  Detailed history and CBC was performed for all the cases. Different ratios and indexes such as systemic inflammatory index (SII), Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) were assessed. A total of 862 cases with a mean age of 49.9 ±17.4 years were enrolled. Hemoglobin level, lymphocyte (count per liter and percentage) were significantly lower in patients admitted in ICU as compared to patients admitted in the isolation ward and private ward (p <0.05). However, TLC, neutrophils, platelet count were higher in patients admitted to ICU (p <0.05). The Various ratios such as SII, NLR, and PLR showed significantly higher value in cases admitted in ICU (p <0.05). The TLC, neutrophil count, neutrophil percentage, SII, NLR, and PLR were significant predictors of severe disease (admission in ICU) with high diagnostic accuracy. We show that complete blood count method is a simple, readily available, rapid, and inexpensive tool that can be utilized for diagnosis and can predicting the severity of COVID 19 where RTPCR or trained staff is not available. Thus, NLR (%), SII, PLR, and TLC can predict severe illness with high accuracy.     

Stochastic acquisition of Qa1 receptors during the development of fetal NK cells in vitro accounts in part but not in whole for the ability of these cells to distinguish between class I-sufficient and class I-deficient targets.

Fetal mouse NK cells are grossly deficient in the expression of Ly49 molecules yet show a limited ability to distinguish between wild-type and MHC class I-deficient target cells. In this paper we report that during their development in vitro from immature thymic progenitors, a proportion of C57BL/6 fetal NK cells acquires receptors for a soluble form of the nonclassical class I molecule Qa1b associated with the Qdm peptide, but not for soluble forms of the classical class I molecules Kb and Db. The acquisition of these Qa1 receptors occurs in a stochastic manner that is strictly controlled by cytokines, and in particular is strongly inhibited by IL-4. All fetal NK clones tested, including those that lack detectable Qa1 receptors, express mRNA for CD94 and for both inhibitory and noninhibitory members of the NKG2 family. Fetal NK cells lacking receptors for Qa1 (and also for classical class I molecules) cannot distinguish between wild-type and class I-deficient blasts but, surprisingly, distinguish efficiently between certain wild-type and class I-deficient tumor cells. A variant line that lacks several members of the NKG2 family kills both types of tumor cell equally well, suggesting the existence of NKG2-containing inhibitory receptors that recognize as yet undefined nonclassical class I molecules of restricted distribution.     

Extreme Divergence of Wolbachia Tropism for the Stem-Cell-Niche in the Drosophila Testis

Microbial tropism, the infection of specific cells and tissues by a microorganism, is a fundamental aspect of host-microbe interactions. The intracellular bacteria Wolbachia have a peculiar tropism for the stem cell niches in the Drosophila ovary, the microenvironments that support the cells producing the eggs. The molecular underpinnings of Wolbachia stem cell niche tropism are unknown. We have previously shown that the patterns of tropism in the ovary show a high degree of conservation across the Wolbachia lineage, with closely related Wolbachia strains usually displaying the same pattern of stem cell niche tropism. It has also been shown that tropism to these structures in the ovary facilitates both vertical and horizontal transmission, providing a strong selective pressure towards evolutionary conservation of tropism. Here we show great disparity in the evolutionary conservation and underlying mechanisms of stem cell niche tropism between male and female gonads. In contrast to females, niche tropism in the male testis is not pervasive, present in only 45% of niches analyzed. The patterns of niche tropism in the testis are not evolutionarily maintained across the Wolbachia lineage, unlike what was shown in the females. Furthermore, hub tropism does not correlate with cytoplasmic incompatibility, a Wolbachia-driven phenotype imprinted during spermatogenesis. Towards identifying the molecular mechanism of hub tropism, we performed hybrid analyses of Wolbachia strains in non-native hosts. These results indicate that both Wolbachia and host derived factors play a role in the targeting of the stem cell niche in the testis. Surprisingly, even closely related Wolbachia strains in Drosophila melanogaster, derived from a single ancestor only 8,000 years ago, have significantly different tropisms to the hub, highlighting that stem cell niche tropism is rapidly diverging in males. These findings provide a powerful system to investigate the mechanisms and evolution of microbial tissue tropism.     

PET imaging a MPTP-induced mouse model of Parkinson's disease using the fluoropropyl-dihydrotetrabenazine analog [18F]-DTBZ (AV-133)

Parkinson's disease (PD) is characterized by the loss of dopamine-producing neurons in the nigrostriatal system. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in PD. We applied a quantitative non-invasive PET imaging technique to follow this degeneration process in an MPTP-induced mouse model of PD. The VMAT2 ligand (18)F-DTBZ (AV-133) was used as a radioactive tracer in our imaging experiments to monitor the changes of the dopaminergic system. Intraperitoneal administrations of MPTP (a neurotoxin) were delivered to mice at regular intervals to induce lesions consistent with PD. Our results indicate a significant decline in the levels of striatal dopamine and its metabolites (DOPAC and HVA) following MPTP treatment as determined by HPLC method. Images obtained by positron emission tomography revealed uptake of (18)F-DTBZ analog in the mouse striatum. However, reduction in radioligand binding was evident in the striatum of MPTP lesioned animals as compared with the control group. Immunohistochemical analysis further confirmed PET imaging results and indicated the progressive loss of dopaminergic neurons in treated animals compared with the control counterparts. In conclusion, our findings suggest that MPTP induced PD in mouse model is appropriate to follow the degeneration of dopaminergic system and that (18)F-DTBZ analog is a potentially sensitive radiotracer that can used to diagnose changes associated with PD by PET imaging modality.     

A patient death attributable to implant-related primary anaplastic large cell lymphoma of the breast

Implant-related primary anaplastic large cell lymphoma (ALCL) of the breast is a rare clinical entity. With increasing attention being paid to this disease, most cases reported to date in the literature have demonstrated indolent clinical courses responsive to explantation, capsulectomy, chemotherapy, and/or radiotherapy. The authors describe a case of bilateral implant-related primary ALCL of the breast that proved refractory to both standard and aggressive interventions, ultimately resulting in patient death secondary to disease progression. The authors situate this case in the context of the current state of knowledge regarding implant-related primary ALCL of the breast and suggest that this entity is generally, but not universally, indolent in nature. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.     

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs

The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans.