In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy.

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The interactions between cancer cells and their microenvironment are crucial for malignant progression, as they modulate invasion-related activities. Tumor-associated macrophages are generally considered allies in the process of tumor progression in several types of cancer, although their role on gastric and colorectal carcinomas is still poorly understood. In this report, we studied the influence of primary human macrophages on gastric and colorectal cancer cells, considering invasion, motility/migration, proteolysis and activated intracellular signaling pathways. We demonstrated that macrophages stimulate cancer cell invasion, motility and migration, and that these effects depend on matrix metalloproteinase (MMP) activity and on the activation of epidermal growth factor receptor (EGFR) (at the residue Y(1086)), PLC-γ (phospholipase C-gamma) and Gab1 (GRB2-associated binding protein-1), as evidenced by siRNA (small interference RNA) experiments. Epidermal growth factor (EGF)-immunodepletion impaired macrophage-mediated cancer cell invasion and motility, suggesting that EGF is the pro-invasive and pro-motile factor produced by macrophages. Macrophages also induced gastric and colorectal cancer cell phosphorylation of Akt, c-Src and ERK1/2, and led to an increase of RhoA and Cdc42 activity. Interestingly, whereas macrophage-mediated cancer cell c-Src and ERK1/2 phosphorylation occurred downstream EGFR activation, Akt phosphorylation seems to be a parallel event, taking place in an EGFR-independent manner. The involvement of EGF, EGFR-downstream signaling partners and MMPs in macrophage-mediated invasion provides novel insights into the molecular crosstalk established between cancer cells and macrophages, opening new perspectives for the design of new and more efficient therapeutic strategies to counteract cancer cell invasion.

Aerial photographs have been systematically collected from as early as the 1930s, providing a unique resource to describe changes in vegetation and land cover over extended periods of time. However, their use is often limited by technical constraints, such as the lack of ground control information and precise camera parameters, which hamper an accurate orthorectification of the raw imagery. Here, we describe the historical aerial photographs orthorectification (HAPO) workflow, based on a conventional photogrammetric procedure (the direct linear transformation (DLT) Method), integrated as a geographic information systems (GIS) procedure, in order to perform the image orientation and orthorectification, thereby converting historical aerial imagery into high-definition historical orthoimages. HAPO implementation is illustrated with an application to a rugged landscape in Portugal, where we aimed to produce land-cover maps using an aerial photograph coverage from 1947, as part of a study on long-term socioecological dynamics. We show that HAPO produces highly accurate orthoimages and discuss the wider usefulness of our framework in long-term socioecological research.

Purpose COVID-19 associated hearing loss is still an ongoing matter of debate. No original studies exist on audiological effects of SARS-CoV-2 infection in hospitalized patients. The main objective was to determine whether SARS-CoV-2 may affect auditory function in clinically ill COVID-19 patients. Materials and Methods COVID-19 patients with moderate-severe disease and without prior history of hearing abnormalities were enrolled from a tertiary referral center, and matched with controls. Participants performed an audiometric evaluation, and thresholds were compared. Results 120 ears from 60 patients were enrolled. Patients with COVID-19 showed worse mean auditory thresholds starting from 1000 Hz through higher frequencies, when compared to controls ( 1000 Hz : 18.52 ± 5.49 dB HL in controls vs 25.36 ± 6.79 dB HL in COVID-19, p<0.001; 2000Hz : 17.50 ± 5.57 dB HL in controls vs 21.96 ± 7.05 dB HL in COVID-19, p=0.010; 3000Hz : 17.97 ± 8.07 dB HL in controls vs 25 ± 9.38 dB HL in COVID-19, p=0.003; 4000 Hz : 20.16 ± 10.12 dB HL in controls vs 29.55 ± 11.26 dB HL in COVID-19, p=0.001; 8000 Hz : 31.09 ± 12.75 dB HL in controls vs 40.71 ± 19.40 dB HL in COVID-19, p=0.030; Pure Tone Average : 20.42 ± 4.29 dB HL in controls vs 24.85 ± 5.62 dB HL in COVID-19, p=0.001). Statistical significance persisted after adjusting for confounders such as age, gender and various comorbidities (p<0.05). Conclusions SARS-CoV-2 may affect hearing in COVID-19 patients with moderate-severe disease. Results are in line with the previous suggested effects of COVID-19 on auditory system. This study is expected to encourage further research on this topic.