Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains

Funding Information: The work was funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health grants U19AI111276 and U01AI065663 to R.R.R., R.D., J.J.E. and P.S., and NIAID training grant T32AI125185 to A.L. The study sponsors were not involved in the study design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Publisher Copyright: © 2022, The Author(s).Mechanisms underlying variability in transmission of Mycobacterium tuberculosis strains remain undefined. By characterizing high and low transmission strains of M.tuberculosis in mice, we show here that high transmission M.tuberculosis strain induce rapid IL-1R-dependent alveolar macrophage migration from the alveolar space into the interstitium and that this action is key to subsequent temporal events of early dissemination of bacteria to the lymph nodes, Th1 priming, granulomatous response and bacterial control. In contrast, IL-1R-dependent alveolar macrophage migration and early dissemination of bacteria to lymph nodes is significantly impeded in infection with low transmission M.tuberculosis strain; these events promote the development of Th17 immunity, fostering neutrophilic inflammation and increased bacterial replication. Our results suggest that by inducing granulomas with the potential to develop into cavitary lesions that aids bacterial escape into the airways, high transmission M.tuberculosis strain is poised for greater transmissibility. These findings implicate bacterial heterogeneity as an important modifier of TB disease manifestations and transmission.publishersversionpublishe

Variants of ST8SIA1 Are Associated with Risk of Developing Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system of unknown etiology with both genetic and environmental factors playing a role in susceptibility. To date, the HLA DR15/DQ6 haplotype within the major histocompatibility complex on chromosome 6p, is the strongest genetic risk factor associated with MS susceptibility. Additional alleles of IL7 and IL2 have been identified as risk factors for MS with small effect. Here we present two independent studies supporting an allelic association of MS with polymorphisms in the ST8SIA1 gene, located on chromosome 12p12 and encoding ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1. The initial association was made in a single three-generation family where a single-nucleotide polymorphism (SNP) rs4762896, was segregating together with HLA DR15/DQ6 in MS patients. A study of 274 family trios ( affected child and both unaffected parents) from Australia validated the association of ST8SIA1 in individuals with MS, showing transmission disequilibrium of the paternal alleles for three additional SNPs, namely rs704219, rs2041906, and rs1558793, with p = 0.001, p = 0.01 and p = 0.01 respectively. These findings implicate ST8SIA1 as a possible novel susceptibility gene for MS

Project #37: Management Guidelines for Patients with COVID-19: Rapid Cycle Improvement

Project’s purpose is to rapidly devise, continually improve, educate, and implement a live and changing COVID-19 management guideline based upon emerging best available evidence. This project also aims to optimize the care of patients with COVID-19 and improve patient outcomes.https://scholarlycommons.henryford.com/qualityexpo2022/1004/thumbnail.jp

Metastatic medulloblastoma at diagnosis

Medulloblastoma is an aggressive tumor of the brain. It is the most common and the most malignant embryonal tumor of the pediatric central nervous system and a rare tumor of adults. We are reporting a rare presentation of adult classic subtype of medulloblastoma which was central in location with metastases in the suprasellar region at the time of diagnosis

Adult primary pleomorphic leiomyosarcoma of forearm with axillary lymph node metastasis: A case report and literature review

A rare case of advanced pleomorphic leiomyosarcoma of forearm with axillary lymph node metastasis in a young adult, diagnosed with the aid of immunohistochemistry and electron microscopic examinations together with a review of the literature are reported. The primary tumor involved the extensor and flexor aspect of forearm without bone involvement and metastasized to the axillary lymph nodes. Patient showed poor treatment outcome with adjuvant chemoradiotherapy following incomplete surgery

Metastatic medulloblastoma at diagnosis

Medulloblastoma is an aggressive tumor of the brain. It is the most common and the most malignant embryonal tumor of the pediatric central nervous system and a rare tumor of adults. We are reporting a rare presentation of adult classic subtype of medulloblastoma which was central in location with metastases in the suprasellar region at the time of diagnosis

Metastatic medulloblastoma at diagnosis

Medulloblastoma is an aggressive tumor of the brain. It is the most common and the most malignant embryonal tumor of the pediatric central nervous system and a rare tumor of adults. We are reporting a rare presentation of adult classic subtype of medulloblastoma which was central in location with metastases in the suprasellar region at the time of diagnosis

Prognostics of Cyclin-D1 expression with chemoradiation response in patients of locally advanced oral squamous cell carcinoma

Objective: Cyclin-D1 has been strongly implicated in cell cycle proliferation particularly in the G1/S checkpoint in the cell cycle, and prognosis in many human malignancies. The present study evaluates its prognostic significance with chemoradiation response in patients of locally advanced oral squamous cell carcinoma (OSCC). Materials and Methods: A total of 97 OSCC patients (females = 19 and males = 78), aged 20-67 years and stage III/IV were recruited. Treatment response was assessed according to World Health Organization criteria. Cyclin-D1 expression in tumor tissue was estimated by immunohistochemical method and quantified as percentage positive nuclei. Results: The Cyclin-D1 expression showed significant (P < 0.01 or P < 0.001) association with tumor size, lymph node status, and clinical stage. After chemoradiation, there were 53.6% complete response (CR) and 34.0% partial response (PR) in primary tumor, and 49.5% CR and 39.2% PR in lymph node; giving an overall response rate of 85.6%. Further, the mean Cyclin-D1 expression showed significant (P < 0.05 or P < 0.001) and inverse association with chemoradiation responses (tumor size, lymph node status and overall treatment response). The 2-year progression-free and overall survival (OS) was 95.89% and 83.31% respectively. Multivariate Cox regression analysis found site of primary tumor, clinical stage, and Cyclin-D1 expression the significant (P < 0.05 or P < 0.01) and independent prognostic markers of OS and among these Cyclin-D1 expression showed the worst prognosis. The high Cyclin-D1 expression (>50%) also showed significantly lower survival in OSCC patients when compared with those had low (<10%) and moderate expressions (10-50%) (Logrank test: χ2 = 44.42, P < 0.001). Conclusion: The high Cyclin-D1 expression may serve as a poor prognostic marker in OSCC