Humans are exposed to radiation through the environment and in medical settings. To deal with radiation-induced damage, cells mount complex responses that rely on changes in gene expression. These gene expression responses differ greatly between individuals 1 and contribute to individual differences in response to radiation 2 . Here we identify regulators that influence expression levels of radiation-responsive genes. We treated radiation-induced changes in gene expression as quantitative phenotypes 3,4 , and conducted genetic linkage and association studies to map their regulators. For more than 1,200 of these phenotypes there was significant evidence of linkage to specific chromosomal regions. Nearly all of the regulators act in trans to influence the expression of their target genes; there are very few cis-acting regulators. Some of the transacting regulators are transcription factors, but others are genes that were not known to have a regulatory function in radiation response. These results have implications for our basic and clinical understanding of how human cells respond to radiation.In the past 20 years there has been a large increase in the use of radiation in medical diagnostic procedures and treatment protocols. Radiation is genotoxic and induces DNA damage in human cells. To ensure genomic integrity, cells mount complex responses that depend on changes in gene expression. It has long been known that individuals vary in their sensitivity to radiation. This individual variability is also observed at the gene expression level 1 . We and others have used genetic studies to identify chromosomal regions and genetic variants that influence expression levels of many genes in human cells at the baseline 5-9 .Here we extend our analysis by genetic mapping of regulatory elements that influence radiation-induced changes in gene expression.We used microarrays to measure the expression levels of genes in irradiated immortalized B cells from members of 15 Centre d'Étude du Polymorphisme Humain (CEPH) UtahCorrespondence and requests for materials should be addressed to V.G.C. (vcheung@mail.med.upenn.edu). Full Methods and any associated references are available in the online version of the paper at www.nature.com/nature.Supplementary Information is linked to the online version of the paper at www.nature.com/nature. Author InformationThe microarray data are deposited in the GEO database under accession number GSE12626. Reprints and permissions information is available at www.nature.com/reprints. 10 . Data were collected for cells at baseline and at 2 and 6 h after exposure to 10 Gy of ionizing radiation. Of the 10,174 genes on the microarrays that are expressed in immortalized B cells, we focused on 3,280 'ionizing-radiation-responsive' genes that showed at least a 1.5-fold change in gene expression levels at 2 h and/or 6 h after irradiation relative to the baseline. For each of these 3,280 genes we calculated the ratio of expression level at 2 h after irradiation relative to the expression level at the bas...

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Background Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS. Methods We used, for the first time, an inhalant CBC treatment as a potential therapeutic target in a murine model of ARDS-like symptoms. ARDS was induced by intranasal administration of Poly(I:C), a synthetic mismatched double-stranded RNA, into the C57BL/6 mice (6–10 male mice/group, including sham, placebo, and CBC treated), three once-daily doses followed by a daily dose of inhalant CBC or placebo for the period of 8 days starting the first dose 2 h after the second Poly(I:C) treatment. We employed histologic, immunohistochemistry, and flow cytometry methods to assess the findings. Statistical analysis was performed by using one way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test to determine the differences among the means of all experimental groups and to establish significance (p < 0.05) among all groups. Results Our data showed that CBC was able to reverse the hypoxia (increasing blood O2 saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance. Conclusion Our findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research.

Orbital emphysema refers to the infiltration of air or gas within the orbital soft tissue space. It is most commonly associated with a history of trauma or orbital wall fracture. [1][2][3] However, other mechanisms have been reported including infection, pulmonary barotrauma, and iatrogenic factors such as dental surgery. 4 Signs and symptoms include proptosis, crepitus, and diplopia presenting acutely or over the course of days to weeks. 5,6 Although orbital emphysema typically follows a benign course and is self-limiting, in severe cases, it can cause vision loss and require immediate intervention to prevent complications associated with orbital compartment syndrome. 2,7 Herein, we present a case report of bilateral orbital emphysema in a single individual after chest tube placement for spontaneous pneumothorax. This case illustrates the potential for dramatic complications of such a procedure

Iatrogenic orbital emphysema from chest tube insertion is a rare but potentially serious complication due to potential optic neuropathy from orbital compartment syndrome. Herein, we present a rare case of orbital emphysema in the setting of pneumothorax and chest tube insertion.