BackgroundRadiotherapy for head and neck cancer results in severe and chronic salivary gland dysfunction in most individuals. This results in significant side effects including xerostomia, dysphagia, and malnutrition which are linked to significant reductions in patients' quality of life. Currently there are few xerostomia treatment approaches that provide long-term results without significant side effects. To address this problem we investigated the potential for post-therapeutic IGF-1 to reverse radiation-induced salivary gland dysfunction.MethodsFVB mice were treated with targeted head and neck radiation and significant reductions in salivary function were confirmed 3 days after treatment. On days 4-8 after radiation, one group of mice was injected intravenously with IGF-1 while a second group served as a vehicle control. Stimulated salivary flow rates were evaluated on days 30, 60, and 90 and histological analysis was performed on days 9, 30, 60, and 90.ResultsIrradiated animals receiving vehicle injections have 40-50% reductions in stimulated salivary flow rates throughout the entire time course. Mice receiving injections of IGF-1 have improved stimulated salivary flow rates 30 days after treatment. By days 60-90, IGF-1 injected mice have restored salivary flow rates to unirradiated control mice levels. Parotid tissue sections were stained for amylase as an indicator of functioning acinar cells and significant reductions in total amylase area are detected in irradiated animals compared to unirradiated groups on all days. Post-therapeutic injections of IGF-1 results in increased amylase-positive acinar cell area and improved amylase secretion. Irradiated mice receiving IGF-1 show similar proliferation indices as untreated mice suggesting a return to tissue homeostasis.ConclusionsPost-therapeutic IGF-1 treatment restores salivary gland function potentially through normalization of cell proliferation and improved expression of amylase. These findings could aid in the rational design of therapy protocols or drugs for the treatment of radiation-induced salivary gland dysfunction in patients who have completed their anti-cancer therapies.
CDC COVID-19 Response Team * Mitigation policies implemented by government authorities during January 1-June 30, 2020 were abstracted from media reports and government and United Nations websites and compiled by WHO. The CDC COVID-19 International Taskforce global mitigation database is a sub-set of the WHO public health and social measures database.
Purpose-Radiotherapy for head and neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available.Methods and materials-Mouse models were exposed to fractionated radiation and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated.Results-In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVB mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection of recombinant IGF-1 into FVB mice, which activates endogenous Akt, suppresses acute apoptosis and preserves salivary gland function following fractionated doses of radiation 30-90 days after treatment. FVB mice exposed to fractionated radiation have significantly lower levels of PCNA positive salivary acinar cells 90 days after treatment which correlates with a chronic loss of function. In contrast, FVB mice injected with IGF-1 prior to each radiation exhibit acinar cell proliferation rates similar to untreated controls.Conclusion-These studies suggest that activation of IGF-1 mediated pathways prior to head and neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.
Objectives To characterize the timing and trends of select mitigation policies, changes in community mobility, and COVID-19 epidemiology in Australia, Japan, Hong Kong, and Singapore. Study design and methods : Prospective abstraction of publicly available mitigation policies obtained from media reports and government websites. Data analyzed include seven kinds of mitigation policies (mass gathering restrictions, international travel restrictions, passenger screening, traveler isolation/quarantine, school closures, business closures, and domestic movement restrictions) implemented between January 1 and April 26, 2020, changes in selected measures of community mobility assessed by Google Community Mobility Reports data, and COVID-19 epidemiology in Australia, Japan, Hong Kong, and Singapore. Results During the study period, community mobility decreased in Australia, Japan, and Singapore; there was little change in Hong Kong. The largest declines in mobility were seen in places that enforced mitigation policies. Across settings, transit-associated mobility declined the most and workplace-associated mobility the least. Singapore experienced an increase in cases despite the presence of stay-at-home orders, as migrant workers living in dormitories faced challenges to safely quarantine. Conclusions Public policies may have different impacts on mobility and SARS-CoV-2 transmission. When enacting mitigation policies, decision makers should consider the possible impact of enforcement measures, the influence on transmission of factors other than movement restrictions, and the differential impact of mitigation policies on sub-populations.
Cannabis cultivation is an emerging industry within the United States. Organic dust derived in part from naturally occurring microorganisms is known to cause byssinosis in the hemp industry. In this pilot study, bacteria and fungi encountered by workers at an outdoor cannabis farm that utilized organic practices were elucidated by 16 S ribosomal RNA (rRNA) and Internal Transcribed Spacer (ITS) region sequencing, respectively. Area (n = 14) and personal air samples (n = 12) were collected during harvesting and processing activities. 16 S rRNA and ITS regions of extracted bacterial and fungal genomic DNA were amplified and sequenced using Sanger sequencing. Bacterial sequencing resolved 1,077 sequences that were clustered into 639 operational taxonomic units (OTUs) and predominantly placed in the phylum, Actinobacteria (46%). Personal air samples revealed higher bacterial and Actinobacteria diversity compared to outdoor area samples collected within the facility (p < 0.05). A high degree of dissimilarity between bacteria was identified within and between samples. Fungal sequences (n = 985) were identified and predominantly clustered in the phylum Ascomycota (53%). Of the 216 fungal OTUs elucidated, the cannabis plant pathogenic species, Botrytis cinerea, was the most prevalent and accounted for 34% of all fungal sequences. The relative abundance of B. cinerea was highest in personal air samples (59%) compared to area samples collected in the drying room (19%), greenhouse (18%), and outdoor environment (6%). There was 49% sample similarity between fungi identified within personal air samples, but higher dissimilarity coefficients were observed within and between greenhouse, drying room, and outdoor area air samples. The results of this pilot study suggest that the cannabis farm workers are potentially exposed to Actinobacteria as well as the cannabis plant pathogen, B. cinerea during harvesting, bud-stripping, and hand-trimming processes.
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