ObjectiveTo estimate the prevalence of depression in patients diagnosed with type 2 diabetes mellitus (T2DM), and to identify sociodemographic, clinical and psychological factors associated with depression in this population. Additionally, we examine the annual incidence rate of depression among patients with T2DM.MethodsWe performed a large prospective cohort study of patients with T2DM from the Madrid Diabetes Study. The first recruitment drive included 3443 patients. The second recruitment drive included 727 new patients. Data have been collected since 2007 (baseline visit) and annually during the follow-up period (since 2008).ResultsDepression was prevalent in 20.03% of patients (n=592; 95% CI 18.6% to 21.5%) and was associated with previous personal history of depression (OR 6.482; 95% CI 5.138 to 8.178), mental health status below mean (OR 1.423; 95% CI 1.452 to 2.577), neuropathy (OR 1.951; 95% CI 1.423 to 2.674), fair or poor self-reported health status (OR 1.509; 95% CI 1.209 to 1.882), treatment with oral antidiabetic agents plus insulin (OR 1.802; 95% CI 1.364 to 2.380), female gender (OR 1.333; 95% CI 1.009 to 1.761) and blood cholesterol level (OR 1.005; 95% CI 1.002 to 1.009). The variables inversely associated with depression were: being in employment (OR 0.595; 95% CI 0.397 to 0.894), low physical activity (OR 0.552; 95% CI 0.408 to 0.746), systolic blood pressure (OR 0.982; 95% CI 0.971 to 0.992) and social support (OR 0.978; 95% CI 0.963 to 0.993). In patients without depression at baseline, the incidence of depression after 1 year of follow-up was 1.20% (95% CI 1.11% to 2.81%).ConclusionsDepression is very prevalent among patients with T2DM and is associated with several key diabetes-related outcomes. Our results suggest that previous mental status, self-reported health status, gender and several diabetes-related complications are associated with differences in the degree of depression. These findings should alert practitioners to the importance of detecting depression in patients with T2DM.

The 'cancer cell fusion' theory is controversial due to the lack of methods available to identify hybrid cells and to follow the phenomenon in patients. However, it seems to be one of the best explanations for both the origin and metastasis of primary tumors. Herein, we co-cultured lung cancer stem cells with human monocytes and analyzed the dynamics and properties of tumor-hybrid cells (THC), as well as the molecular mechanisms beneath this fusion process by several techniques: electron-microscopy, karyotyping, CRISPR-Cas9, RNA-seq, immunostaining, signaling blockage, among others. Moreover, mice models were assessed for in vivo characterization of hybrids colonization and invasiveness. Then, the presence of THCs in bloodstream and samples from primary and metastatic lesions were detected by FACS and immunofluorescence protocols, and their correlations with TNM stages established. Our data indicate that the generation of THCs depends on the expression of CD36 on tumor stem cells and the oxidative state and polarization of monocytes, the latter being strongly influenced by microenvironmental fluctuations. Highly oxidized M2-like monocytes show the strongest affinity to fuse with tumor stem cells. THCs are able to proliferate, colonize and invade organs. THC-specific cell surface signature CD36 + CD14 + PANK + allows identifying them in matched primary tumor tissues and metastases as well as in bloodstream from patients with lung cancer, thus functioning as a biomarker. THCs levels in circulation correlate with TNM classification. Our results suggest that THCs are involved in both origin and spread of metastatic cells. Furthermore, they might set the bases for future therapies to avoid or eradicate lung cancer metastasis.

Sepsis, among other pathologies, is an endotoxin tolerance (ET)-related disease. On admission, we classified 48 patients with sepsis into 3 subgroups according to the ex vivo response to lipopolysaccharide. This response correlates with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the ET degree. Moreover, the ET-related classification determines the outcome of these patients. Programmed cell death-ligand 1 (PD-L1) expression on septic monocytes is also linked with ET status. In addition to the regulation of cytokine production, one of the hallmarks of ET that significantly affects patients with sepsis is T-cell proliferation impairment or a poor switch to the adaptive response. PD-L1/programmed cell death-1 (PD-1) blocking and knockdown assays on tolerant monocytes from both patients with sepsis and the in vitro model reverted the impaired adaptive response. Mechanistically, the transcription factor hypoxia-inducible factor-1α (HIF1α) has been translocated into the nucleus and drives PD-L1 expression during ET in human monocytes. This fact, together with patient classification according to the ex vivo lipopolysaccharide response, opens an interesting field of study and potential personalized clinical applications, not only for sepsis but also for all ET-associated pathologies.

This study has demonstrated that hand hygiene compliance in primary healthcare workers can be improved with a multimodal hand hygiene improvement strategy.