Post-translational modification of the membrane type 1 matrix metalloproteinase (MT1-MMP) cytoplasmic tail impacts ovarian cancer multicellular aggregate dynamics.

Membrane type 1 matrix metalloproteinase (MT1-MMP, MMP-14) is a transmembrane collagenase highly expressed in metastatic ovarian cancer and correlates with poor survival. Accumulating evidence shows that the cytoplasmic tail of MT1-MMP is subjected to phosphorylation, and this post-translational modification regulates enzymatic activity at the cell surface. To investigate the potential role of MT1-MMP cytoplasmic residue Thr567 phosphorylation in regulation of metastasis-associated behaviors, ovarian cancer cells that express low endogenous levels of MT1-MMP were engineered to express wild-type MT1-MMP, a phosphomimetic mutant (T567E), or a phosphodeficient mutant (T567A). Results show that Thr567 modulation influences behavior of both individual cells and multicellular aggregates (MCAs). The acquisition of either wild-type or mutant MT1-MMP expression results in altered cohesion of epithelial sheets and the formation of more compact MCAs relative to parental cells. Cells expressing MT1-MMP-T567E phosphomimetic mutants exhibit enhanced cell migration. Furthermore, MCAs formed from MT1-MMP-T567E-expressing cells adhere avidly to both intact ex vivo peritoneal explants and three-dimensional collagen gels. Interaction of these MCAs with peritoneal mesothelium disrupts mesothelial integrity, exposing the submesothelial collagen matrix on which MT1-MMP-T567E MCAs rapidly disperse. Together, these findings suggest that post-translational regulation of the Thr567 in the MT1-MMP cytoplasmic tail may function as a regulatory mechanism to impact ovarian cancer metastatic success.

Association of depression and COVID-induced PTSD with cognitive symptoms after COVID-19 illness.

OBJECTIVE: Many patients recovering from COVID-19 report persistent psychological and cognitive symptoms months after viral clearance. We examined the association of depression and COVID-induced PTSD with cognitive symptoms following COVID-19 illness. METHODS: Patients treated for COVID-19 between March 26 and May 27, 2020 were surveyed three months later. Cognitive symptoms were assessed by asking "Since your COVID-19 illness, do you now have more difficulty: 1) Remembering conversations a few days later? 2) Remembering where you placed familiar objects? 3) Finding the right words while speaking?" Patients endorsing at least one such complaint were coded positive for cognitive symptoms. Logistic regression was used to estimate the association of depression (PHQ-8 ≥ 10) and COVID-induced PTSD (PCL-5 ≥ 30) with cognitive symptoms, adjusting for demographic and clinical factors. RESULTS: Among 153 participants, 44.4% reported at least one cognitive symptom, 18.3% were depressed, and 23.5% had COVID-induced PTSD. Adjusting for covariates, depression (OR 5.15, 95% CI 1.30-20.35, p = 0.02) and COVID-induced PTSD (OR 3.67, 95% CI 1.13-11.89, p = 0.03) were significantly associated with cognitive symptoms; self-reported history of mental illness was also associated (OR 4.90, 95% CI 1.24-19.41, p = 0.02). CONCLUSIONS: Depression, COVID-induced PTSD, and prior mental illness were strongly associated with cognitive symptoms three months after acute COVID-19 illness.

Interventions to reduce short-wavelength ("blue") light exposure at night and their effects on sleep: A systematic review and meta-analysis.

The sleep-wake and circadian cycles are influenced by light, particularly in the short-wavelength portion of the visible spectrum. Most personal light-emitting electronic devices are enriched in this so-called "blue" light. Exposure to these devices in the evening can disturb sleep. Interventions to reduce short-wavelength light exposure before bedtime may reduce adverse effects on sleep. We conducted a systematic review and meta-analysis to examine the effect of wearing color-tinted lenses (e.g. orange or amber) in frames to filter short-wavelength light exposure to the eye before nocturnal sleep. Outcomes were self-reported or objective measures of nocturnal sleep. Relatively few (k = 12) studies have been done. Study findings were inconsistent, with some showing benefit and others showing no effect of intervention. Meta-analyses yielded a small-to-medium magnitude combined effect size for sleep efficiency (Hedge's g = 0.31; 95% CI: -0.05, 0.66; I2 = 38.16%; k = 7), and a small-to-medium combined effect size for total sleep time (Hedge's g = 0.32; 95% CI: 0.01, 0.63; I2 = 12.07%; k = 6). For self-report measures, meta-analysis yielded a large magnitude combined effects size for Pittsburgh Sleep Quality Index ratings (Hedge's g = -1.25; 95% CI: -2.39, -0.11; I2 = 36.35%; k = 3) and a medium combined effect size for total sleep time (Hedge's g = 0.51; 95% CI: 0.18, 0.84; I2 = 0%; k = 3), Overall, there is some, albeit mixed, evidence that this approach can improve sleep, particularly in individuals with insomnia, bipolar disorder, delayed sleep phase syndrome, or attention-deficit hyperactive disorder. Considering the ubiquitousness of short-wavelength-enriched light sources, future controlled studies to examine the efficacy of this approach to improve sleep are warranted. Systematic review registration: PROSPERO 2018 CRD42018105854.