Background: A nasally applied cellulose powder is increasingly used in many countries as a remedy for allergic rhinitis. In 2009, a 4-week study in birch pollen-allergic children showed a reduction in nasal symptoms. The best effect occurred on days with lower pollen counts. The present study in grass pollen-allergic adults used the same basic design. Methods: In May 2013, a double-blind, placebo-controlled study was conducted in 108 patients with allergic rhinitis due to grass pollen (18-40 years of age). SMS on mobile phones were used as reminders of treatment and reporting of symptom scores. Results: We found significant reductions in severity scores for sneezing, runny nose, stuffy nose and symptoms from eyes and lower airways, both separately and together (all p < 0.001). Reflective opinion of effect and guess on treatment at follow-up visits (both p < 0.001) confirmed a high efficacy. No clinically significant adverse effects were reported. Conclusions: The product provided significant protection against all seasonal allergic rhinitis symptoms from both upper and lower airways during the grass pollen season in an adult population. The magnitude and scope of efficacy support the use of the product as an early choice in the treatment of allergic rhinitis.
Immunometabolism within the tumor microenvironment is an appealing target for precision therapy approaches in lung cancer. Interestingly, obesity confers an improved response to immune checkpoint inhibition in non-small cell lung cancer (NSCLC), suggesting intriguing relationships between systemic metabolism and the immunometabolic environment in lung tumors. We hypothesized that visceral fat and 18F-Fluorodeoxyglucose uptake influenced the tumor immunometabolic environment and that these bidirectional relationships differ in NSCLC subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). By integrating 18F-FDG PET/CT imaging, bulk and single-cell RNA-sequencing, and histology, we observed that LUSC had a greater dependence on glucose than LUAD. In LUAD tumors with high glucose uptake, glutaminase was downregulated, suggesting a tradeoff between glucose and glutamine metabolism, while in LUSC tumors with high glucose uptake, genes related to fatty acid and amino acid metabolism were also increased. We found that tumor-infiltrating T cells had the highest expression of glutaminase, ribosomal protein 37, and cystathionine gamma-lyase in NSCLC, highlighting the metabolic flexibility of this cell type. Further, we demonstrate that visceral adiposity, but not body mass index (BMI), was positively associated with tumor glucose uptake in LUAD and that patients with high BMI had favorable prognostic transcriptional profiles, while tumors of patients with high visceral fat had poor prognostic gene expression. We posit that metabolic adjunct therapy may be more successful in LUSC rather than LUAD due to LUAD’s metabolic flexibility and that visceral adiposity, not BMI alone, should be considered when developing precision medicine approaches for the treatment of NSCLC.
In this work, we present a particle-based SEIR epidemic simulator as a tool to assess the impact of different vaccination strategies on viral propagation and to model sterilizing and effective immunization outcomes. The simulator includes modules to support contact tracing of the interactions amongst individuals and epidemiological testing of the general population. The particles are distinguished by age to represent more accurately the infection and mortality rates. The tool can be calibrated by region of interest and for different vaccination strategies to enable locality-sensitive virus mitigation policy measures and resource allocation. Moreover, the vaccination policy can be simulated based on the prioritization of certain age groups or randomly vaccinating individuals across all age groups. The results based on the experience of the province of Lecco, Italy, indicate that the simulator can evaluate vaccination strategies in a way that incorporates local circumstances of viral propagation and demographic susceptibilities. Further, the simulator accounts for modeling the distinction between sterilizing immunization, where immunized people are no longer contagious, and effective immunization, where the individuals can transmit the virus even after getting immunized. The parametric simulation results showed that the sterilizing-age-based vaccination scenario results in the least number of deaths. Furthermore, it revealed that older people should be vaccinated first to decrease the overall mortality rate. Also, the results showed that as the vaccination rate increases, the mortality rate between the scenarios shrinks.
CPT1A is a rate-limiting enzyme in fatty acid oxidation and is upregulated in high-risk breast cancer. Obesity and menopausal status’ relationship with breast cancer prognosis is well established, but its connection with fatty acid metabolism is not. We utilized RNA sequencing data in the Xena Functional Genomics Explorer, to explore CPT1A’s effect on breast cancer patients’ survival probability. Using [18F]-fluorothymidine positron emission tomography-computed tomography images from The Cancer Imaging Archive, we segmented these analyses by obesity and menopausal status. In 1214 patients, higher CPT1A expression is associated with lower breast cancer survivability. We confirmed a previously observed protective relationship between obesity and breast cancer in pre-menopausal patients and supported this data using two-sided Pearson correlations. Taken together, these analyses using open-access databases bolster the potential role of CPT1A-dependent fatty acid metabolism as a pathogenic factor in breast cancer.
Background: The relationship between systemic metabolism, immune function, and lung cancer is complex and remains poorly defined. Seemingly paradoxically, overweight and obesity confer an improved response to immune checkpoint inhibition in non-small cell lung cancer (NSCLC); however, it is not known whether excess body weight or adiposity impacts the immunometabolic tumor microenvironment. Methods: Utilizing three complementary National Cancer Institute-funded open-source databases containing 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET-CT) images for tumor and tissue glucose uptake, adipose tissue and skeletal muscle mass, histology annotated with tumor infiltrating lymphocytes, and tumor RNA sequencing, we performed a retrospective cross-sectional analysis to examine phenotypic, metabolic, and genomic intersections of adiposity and tumor immune-metabolism in patients with lung adenocarcinoma (LUAD) versus squamous cell carcinoma (LUSC). Results: Our data reveal distinct immunometabolomic features of LUSC as compared to LUAD: despite unchanged stage between the two tumor types, visceral fat content was negatively correlated with both tumor glucose uptake and lymphocyte infiltration, and correlated with enrichment of gene expression in pathways involved in mitochondrial translation and function in tumors. LUSC showed greater gene expression pathways related to pyruvate, glucose, amino acid, and lipid metabolism based on 18F-FDG uptake compared with LUAD, suggesting deeper metabolic regulation within the LUSC tumor microenvironment. Conclusions: Several immunometabolomic characteristics of LUSC and LUAD differ, including tumor glucose uptake and the associated metabolic pathways in the tumor, as well as the impact of visceral adiposity on tumor metabolism. These data may highlight opportunities to advance mechanistically targeted precision medicine approaches by better understanding the interplay between metabolic, immunologic, and genomic factors in lung cancer treatment.
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