Psychological Health, Sleep Quality, Behavior, and Internet Use Among People During the COVID-19 Pandemic: A Cross-Sectional Study.

Background: The COVID-19 pandemic has led to an increase in the risk of suicide, uncertainty, mental stress, terror, annoyance, weariness, financial issues, and frustration. We aim to determine the prevalence of insomnia, depressive and anxiety symptoms, and their associated factors among Libyan populations during the COVID-19 pandemic and the civil war. Methods: An online cross-sectional survey was conducted among the Libyan population between July 18 and August 23, 2020. The data collected included basic demographic characteristics, level of education, employment status, COVID-19-related questions, and questions about abuse and domestic violence. This study assessed the psychological status of participants who were screened for anxiety symptoms using the seven-item Generalized Anxiety Disorder scale (GAD-7). Depressive symptoms were also screened for using the two-item Patient Health Questionnaire (PHQ-2) and the Insomnia Severity Index (ISI). Binomial logistic regression was used to predict the probability of insomnia, anxiety and depressive symptoms. Results: A total of 10,296 responses were recorded. Among the participants, 4,756 (46.2%) obtained a cut-off score of ≥ 3 which indicated depressive symptoms. For anxiety, 1,952 participants (19%) obtained a cut-off score of ≥ 15, which indicated anxiety symptoms. For the ISI, the mean (SD) was 11.4 (6.1) for the following categories: no clinical insomnia (0-7) 3,132 (30.4%), sub-threshold insomnia (1-7) 3,747 (36.4%), moderate severity clinical insomnia (8-14) 2,929 (28.4%), and severe clinical insomnia (15-21) 488 (4.7%). Logistic regression analysis showed that depressive symptoms were statistically associated with age, marital status, education level, occupational category, financial problems during the COVID-19 pandemic, health status, having a COVID-19 infection, current health status, suicide ideation, abuse or domestic violence, and lockdown compliance (p < 0.05). The regression analysis revealed a statistically significant association between anxiety symptoms and age, education level, occupational status, financial problems during the COVID-19 pandemic, having a COVID-19 infection, health status, suicide ideation, abuse or domestic violence, and lockdown compliance (p < 0.05). The regression analysis revealed a statistically significant association between insomnia and all study variables with the exception of age, educational level, and occupational status (p < 0.05). Conclusion: Confronted with the COVID-19 outbreak, the Libyan population exhibited high levels of psychological stress manifested in the form of depressive and anxiety symptoms, while one-third of the Libyan population suffered from clinical insomnia. Policymakers need to promote effective measures to reduce mental health issues and improve people's quality of life during the civil war and the COVID-19 pandemic.

Subclonal Evolution of Cancer-Related Gene Mutations in p53 Immunopositive Patches in Human Skin.

Normal sun-exposed skin contains numerous epidermal patches that stain positive for p53 protein (p53 immunopositive patches, PIPs), which are considered potential early precursors of skin cancer. Although the TP53 gene is mutated in many PIPs, it is unclear whether PIPs contain any other cancer-related mutations. Here we report that PIPs, predominantly <3,000 p53 immunopositive cells in size, within normal chronically exposed skin contain mutations in multiple genes that are mutated in cutaneous squamous cell cancers. These mutations in the PIPs were not detected within the non-PIP epidermis of corresponding normal chronically exposed skin. Although some of these genetic alterations are clonal in the PIPs, many of the mutations are subclonal within these lesions. Similar mutations are seen in later precancers (actinic keratoses and Bowen's disease). Our results demonstrate that PIPs in chronically exposed skin contain multiple mutations in cancer-related genes. In addition, the results indicate that the clonal evolution of mutations that are seen within later precancerous lesions and in established malignancy can also occur in PIPs within normal human skin.

OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential.

PURPOSE: Cutaneous squamous cell carcinoma (cSCC) is the most common human cancer with metastatic potential. Despite T cells accumulating around cSCCs, these tumors continue to grow and persist. To investigate reasons for failure of T cells to mount a protective response in cSCC, we focused on regulatory T cells (Tregs) as this suppressive population is well represented among the infiltrating lymphocytes. EXPERIMENTAL DESIGN: Flow cytometry was conducted on cSCC lymphocytes and in vitro functional assays were performed using sorted tumoral T cells. Lymphocyte subsets in primary cSCCs were quantified immunohistochemically. RESULTS: FOXP3(+) Tregs were more frequent in cSCCs than in peripheral blood (P < 0.0001, n = 86 tumors). Tumoral Tregs suppressed proliferation of tumoral effector CD4(+) (P = 0.005, n = 10 tumors) and CD8(+) T cells (P = 0.043, n = 9 tumors) and inhibited IFNγ secretion by tumoral effector T cells (P = 0.0186, n = 11 tumors). The costimulatory molecule OX40 was expressed predominantly on tumoral Tregs (P < 0.0001, n = 15 tumors) and triggering OX40 with an agonist anti-OX40 antibody overcame the suppression exerted by Tregs, leading to increased tumoral effector CD4(+) lymphocyte proliferation (P = 0.0098, n = 10 tumors). Tregs and OX40(+) lymphocytes were more abundant in primary cSCCs that metastasized than in primary cSCCs that had not metastasized (n = 48 and n = 49 tumors, respectively). CONCLUSIONS: Tregs in cSCCs suppress effector T-cell responses and are associated with subsequent metastasis, suggesting a key role for Tregs in cSCC development and progression. OX40 agonism reversed the suppressive effects of Tregs in vitro, suggesting that targeting OX40 could benefit the subset of cSCC patients at high risk of metastasis. Clin Cancer Res; 22(16); 4236-48. ©2016 AACR.