A growing body of evidence suggests a role of proteolytic enzymes in the development of diabetic nephropathy. Cathepsin C (CatC) is a well-known regulator of inflammatory responses, but its involvement in podocyte and renal injury remains obscure. We used Zucker rats, a genetic model of metabolic syndrome and insulin resistance, to determine the presence, quantity, and activity of CatC in the urine. In addition to the animal study, we used two cellular models, immortalized human podocytes and primary rat podocytes, to determine mRNA and protein expression levels via RT-PCR, Western blot, and confocal microscopy, and to evaluate CatC activity. The role of CatC was analyzed in CatC-depleted podocytes using siRNA and glycolytic flux parameters were obtained from extracellular acidification rate (ECAR) measurements. In functional analyses, podocyte and glomerular permeability to albumin was determined. We found that podocytes express and secrete CatC, and a hyperglycemic environment increases CatC levels and activity. Both high glucose and non-specific activator of CatC phorbol 12-myristate 13-acetate (PMA) diminished nephrin, cofilin, and GLUT4 levels and induced cytoskeletal rearrangements, increasing albumin permeability in podocytes. These negative effects were completely reversed in CatC-depleted podocytes. Moreover, PMA, but not high glucose, increased glycolytic flux in podocytes. Finally, we demonstrated that CatC expression and activity are increased in the urine of diabetic Zucker rats. We propose a novel mechanism of podocyte injury in diabetes, providing deeper insight into the role of CatC in podocyte biology. Dermal fibroblasts seem critical for epidermal maturation and differentiation and recent work demonstrated that diseased fibroblasts may drive pathophysiological processes. Nevertheless, still very little is known about the actual crosstalk between epidermal keratinocytes and dermal fibroblasts and the impact of dermal fibroblasts on epidermal maturation and differentiation. Aiming for a more fundamental understanding of the impact of the cellular crosstalk between keratinocytes and fibroblasts on the skin homeostasis, we generated full-thickness skin equivalents with and without fibroblasts and subsequently analysed them for the expression of skin differentiation markers, their barrier function, skin lipid content and epidermal cell signalling. FLT3 inhibitor Skin equivalents without fibroblasts consistently showed an impaired differentiation and dysregulated expression of skin barrier and tight junction proteins, increased skin permeability, and a decreased skin lipid/protein ratio. Most interestingly, impaired Ras/Raf/ERK/MEK signalling was evident in skin equivalents without fibroblasts. Our data clearly indicate that the epidermal-dermal crosstalk between keratinocytes and fibroblasts is critical for adequate skin differentiation and that fibroblasts orchestrate epidermal differentiation processes. V.AIM The aim of this study was to investigate the factors involved in healing failure in a population of patients with diabetic foot ulcers (DFU) after one year of follow-up. METHODS One hundred and forty-four patients were treated for DFU in a tertiary-care center and had a regular follow-up for one year. Laboratory measurements and clinical assessments, including long-term diabetes complications and risk factors for DFU, were collected at baseline and patients were divided in two groups according to the outcome [Healed group (H, n = 91), and Not Healed group (NH, n = 53)]. RESULTS Compared with H group, NH group had significant higher levels of urinary albumin excretion [H vs NH, median (IQR), 23.5 (10.1, 41.1) vs 26.4 (20.8, 141.1), P = 0.032] and significantly increased prevalence of diabetic kidney disease (DKD) (22% vs 40%, P = 0.038) and Charcot Arthropathy (3% vs 16%, P = 0.025). No differences among the other long-term complications of diabetes, risk factors for DFU or clinical features were found. The multiple logistic regression analysis identified DKD and Charcot Arthropathy as negative predictors of healing. CONCLUSIONS In a population of people with type 2 diabetes with DFU treated in a tertiary-care center, DKD and Charcot Arthropathy were related to poor healing within one year-follow-up. AIMS Hypoglycemia is one of the most important complications associated with Ramadan fasting in people with type 2 diabetes. LixiRam (NCT02941367) was the first randomized trial comparing safety and efficacy of lixisenatide + basal insulin (BI) vs. sulphonylurea + BI in people with type 2 diabetes who fast during Ramadan. This post hoc analysis focuses on the LixiRam study population from India. METHODS Adults with type 2 diabetes insufficiently controlled with sulphonylurea + BI ± another oral anti-hyperglycemic drug were randomized 11 to receive lixisenatide + BI or to continue sulphonylurea + BI treatment. RESULTS In total, 150 participants were randomized in India. One participant (1.3%) with lixisenatide + BI vs. 5 participants (6.8%) with sulphonylurea + BI experienced ≥1 documented symptomatic hypoglycemic event during the Ramadan fast (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.02-1.93). Incidence of any hypoglycemia was numerically lower with lixisenatide + BI vs. sulphonylurea + BI during Ramadan fasting (1.3% [1/75] vs. 14.7% [11/75], respectively; OR 0.09; 95% CI 0.01-0.69). No new safety signals were identified. CONCLUSIONS A combination of lixisenatide prandial GLP1-RA + BI may be a suitable treatment option for people with type 2 diabetes who elect to fast during Ramadan. Clinical Trial Registry clinicaltrials.gov (NCT02941367). BACKGROUND Evidence suggests that better cognitive functioning is associated with better mobility in older age. It is unknown whether older adults with better cognitive function are more resilient to mobility decline after a fall. METHODS Participants from the Monongahela Youghiogheny Healthy Aging Team (MYHAT) study were followed annually for up to 9 years for incident falls. We examined one-year (mean 1.0 year, SD 0.1) change in mobility pre- to post-fall using the Timed Up and Go (TUG) in relation to pre-fall cognition (executive function, attention, memory, and visuospatial function) among incident fallers (n = 598, mean age 79.1, SD = 7.0). Linear regression models tested the association of cognition with change in TUG. Interaction terms were tested to explore if age, sex, body mass index, physical activity, depressive symptoms, or visual acuity modified the associations of cognition and mobility among fallers. The association between cognition and one-year change in TUG was also tested in a comparison sample of non-fallers (n = 442, mean age 76.