ABSTRACT
The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibit more severe SARS-CoV-2 disease similar to hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and non-human primates, mRNA-1273- mediated immunity was non-sterilizing and coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high resolution analysis which is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a two-dose schedule and provides insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
ABSTRACT
BACKGROUND: Six-min walk test (6MWT), a simple functional capacity evaluation tool used globally to determine the prognosis and effectiveness of any therapeutic/medical intervention. However, variability in reference equations derived from western population (due to racial and ethnicity variations) hinders from adequate use of 6MWT clinically. Further, there are no valid Indian studies that predict reference values for 6-min walk distance (6MWD) in healthy Indian normal. OBJECTIVE: We aimed for framing individualized reference equations for 6MWT in healthy Indian population. MATERIALS AND METHODS: Anthropometric variables (age, weight, height, and body mass index (BMI)) and 6-min walk in a 30 m corridor were evaluated in 125 subjects (67 females) in a cross-sectional trial. RESULTS: 6MWD significantly correlated with age (r = -0.29), height (r = 0.393), weight (r = 0.08), and BMI (r = -0.17). The gender specific reference equations for healthy Indian individuals were: (1) Males: 561.022 - (2.507 × age [years]) + (1.505 × weight [kg]) - (0.055 × height [cm]). R (2) = 0.288. (2) Indian females: 30.325 - (0.809 × age [years]) - (2.074 × weight [kg]) + (4.235 × height [cm]). R (2) = 0.272. Though the equations possess a small coefficient of determination and larger standard error estimate, the former applicability to Indian population is justified. CONCLUSION: These reference equations are probably most appropriate for evaluating the walked capacity of Indian patients with chronic diseases.
ABSTRACT
Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and an aggressive malignancy with poor outcome. This tumor can co-express epithelial, neural, and mesenchymal markers. The molecular hallmark of DSRCT is the EWS-WT1 fusion protein. Despite the diversities in treatment modality, the best results have been seen with radical surgery and adjuvant or neoadjuvant chemotherapy.
Subject(s)
Abdominal Neoplasms/therapy , Desmoplastic Small Round Cell Tumor/therapy , Abdominal Neoplasms/genetics , Abdominal Neoplasms/mortality , Abdominal Neoplasms/pathology , Antibodies, Monoclonal/therapeutic use , Chemotherapy, Adjuvant , Chemotherapy, Cancer, Regional Perfusion , Desmoplastic Small Round Cell Tumor/genetics , Desmoplastic Small Round Cell Tumor/mortality , Desmoplastic Small Round Cell Tumor/pathology , Humans , Hyperthermia, Induced , Immunohistochemistry , Neoplasm Recurrence, Local , Neoplasm Staging , Oncogene Proteins, Fusion/genetics , Radiotherapy, Adjuvant , Tomography, X-Ray Computed , Translocation, GeneticABSTRACT
A 66-year-old man presented with acute respiratory distress due to a tracheal tumor involving the posterior wall of the upper trachea, with nearly complete airway obstruction. Partial debulking of the tumor's endoluminal component, via rigid bronchoscopy and yttrium-aluminum-perovskite laser, allowed timely and effective airway restoration. The diagnosis was benign tracheal glomus tumor. Two weeks later, elective tracheal sleeve resection with end-to-end anastomosis allowed complete resection of the lesion. No tumor recurrence was found at 21-month follow-up. We describe the multidisciplinary management of this extremely rare tracheal tumor, and review its features.
