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Osteosarcoma is one of the most common metastatic bone cancers, which results in significant morbidity and mortality. Unfolding of effectual therapeutic strategies against osteosarcoma is impeded because of the absence of adequate animal models, which can truly recapitulate disease biology of humans. Tissue engineering provides an opportunity to develop physiologically relevant, reproducible, and tunable in vitro platforms to investigate the interactions of osteosarcoma cells with its microenvironment. Adipose-derived stem cells (ASCs) are detected adjacent to osteosarcoma masses and are considered to have protumor effects. Hence, the present study focuses on investigating the role of reactive ASCs in formation of spheroids of osteosarcoma cells (Saos 2) within a three-dimensional (3D) niche, which is created using gellan gum (GG)–silk fibroin. By modifying the blending ratio of GG–silk, the optimum stiffness of the resultant hydrogels such as GG and GG75: S25 is obtained for cancer spheroid formation. This work indicates that the co-existence of cancer and stem cells can form a spheroid, the hallmark of cancer, only in particular microenvironment stiffness. The incorporation of fibrillar silk fibroin within the hydrophilic network of GG in GG75: S25 spongy-like hydrogels closely mimics the stiffness of commercially established cancer biomaterials (e.g., Matrigel, HyStem). The GG75: S25 hydrogel maintains the metabolically active construct for a longer time with elevated expression of osteopontin, osteocalcin, RUNX 2, and bone sialoprotein genes, the biomarkers of osteosarcoma, compared to GG. The GG75: S25 construct also exhibits intense alkaline phosphatase expression in immunohistochemistry compared to GG, indicating itspotentiality to serve as biomimetic niche to model osteosarcoma. Taken together, the GG–silk fibroin-blended spongy-like hydrogel is envisioned as an alternative low-cost platform for 3D cancer modeling.

Polycystic Ovary Syndrome (PCOS) is characterized by an extreme variety of phenotypes and controversial metabolic implications. Hepatic Steatosis (HS) and low-grade chronic inflammation (LGCI) might be common findings in PCOS. We conducted a cross-sectional study to evaluate the LGCI and HS in young women with PCOS according to their Body Mass index (BMI), Insulin Resistance (IR), and PCOS phenotypes. Sixty young premenopausal PCOS women and 20 age-matched controls participated. Primary outcome measures were the presence/severity of HS; LGCI index evaluated as spleen longitudinal diameter (SLD) by UltraSound, C-Reactive Protein (CRP) and Interleukin (IL)-6 levels; BMI and the Homeostasis Model Assessment (HoMA) of IR. The second outcome measures were testosterone, Sex Hormone-Binding Globulin (SHBG) levels, and Free Androgen Index (FAI). The presence of HS and LGCI was not significantly different between NW and O/O patients, while there were significant differences particularly when the PCOS-women were grouped according to IR or to PCOS phenotypes. At multiple regression adjusted for BMI, HoMA-IR and the spleen size were the major determinants of the severity of HS (ß= 0.36, p=0.007, and ß= 0.28, p=0.034, respectively). At multiple regression SLD represented the unique predictor of FAI (ß=0.32; p=0.018). In young women with PCOS, HS was detected independently from obesity and was well predicted not only by IR but also by spleen size, with variable expression of the liver-spleen axis across the different PCOS subtypes. A possible role of the spleen in determining LGCI also in women with PCOS is emphasized.

Psoriatic patients have an accumulation of metabolic syndrome (MS) and cardiovascular diseases (CVD), likely mediated by systemic inflammation, and exhibiting low circulating levels of insulin-like growth factor (IGF)-I, a marker of MS and CVD in the general population. The aim of this study is to determine the association of IGF-I and inflammation, and to assess the cardio-metabolic risk calculating the visceral adiposity index (VAI), in a group of psoriatic patients without MS. IGF-I, fibrinogen, C-reactive protein (CRP), and interleukin (IL)-6 levels were determined in 20 patients with moderate to severe psoriasis (age range 23–77 yrs) without MS, according to criteria of the National Cholesterol Education Program's Adult Panel III (ATP III), and 20 age- and BMI-matched controls. The standard deviation score (SDS) of IGF-I levels according to age (zSDS), the homeostasis model assessment of insulin resistance (HOMA-IR), the whole-body insulin sensitivity index (ISI), and VAI were also calculated. Psoriasis Area and Severity Index (PASI) mean value was 17.8±11. HDL cholesterol and IGF-I zSDS values were lower (p<0.001) and waist circumference (p<0.001), VAI, fibrinogen, and IL-6 (p<0.005) were higher compared with controls, while HOMA-IR and ISI were not statistically different. Lower IGF-I zSDS values were associated to higher values of BMI (p=0.04), waist circumference, VAI (p<0.001), PASI (p=0.011), or IL-6 (p<0.001). At the multivariate analysis PASI was the major determinant of IGF-I zSDS (p=0.016), accounting for 37% of its variability. In a subset of psoriatic patients without MS, chronic inflammation might be an important modulator of low IGF-I status, as a further possible mechanistic link between psoriasis and associated metabolic co-morbidities. The negative correlation between age-related IGF-I values and VAI suggest the involvement of adipocyte dysfunction in low IGF-I status more than MS per se. Further studies are needed to address whether these results are valid also for other psoriatic patients.

Seventy-five patients affected by chronic constipation were treated for 4 weeks with an Ispaghula Husk preparation (Fibrolax®), a bulk-forming laxative.Frequency, stool consistency, abdominal pain and signs of venous stasis improved after treatment. No important side-effect was recorded. Cholesterol, HDL-cholesterol and triglycerides did not show significant changes.

Denman Glacier, East Antarctica, holds an ice volume equivalent to a 1.5 m rise in global sea level. Using satellite radar interferometry from the COSMO‐SkyMed constellation, we detect a 5.4 ± 0.3 km grounding line retreat between 1996 and 2017–2018. A novel reconstruction of the glacier bed topography indicates that the retreat proceeds on the western flank along a previously unknown 5 km wide, 1,800 m deep trough, deepening to 3,400 m below sea level. On the eastern flank, the grounding line is stabilized by a 10 km wide ridge. At tidal frequencies, the grounding line extends over a several kilometer‐wide grounding zone, enabling warm ocean water to melt ice at critical locations for glacier stability. If warm, modified Circumpolar Deep Water reaches the sub‐ice‐shelf cavity and continues to melt ice at a rate exceeding balance conditions, the potential exists for Denman Glacier to retreat irreversibly into the deepest, marine‐based basin in Antarctica. Using satellite radar data from the Italian COSMO‐SkyMed constellation, we document the grounding line retreat of Denman Glacier, a major glacier in East Antarctica that holds an ice volume equivalent to a 1.5 m global sea level rise. The grounding line is retreating asymmetrically. On the eastern flank, the glacier is protected by a subglacial ridge. On the western flank, we find a deep and steep trough with a bed slope that makes the glacier conducive to rapid retreat. If warm water continues to induce high rates of ice melt near the glacier grounding zone, the potential exists for Denman Glacier to undergo a rapid and irreversible retreat, with major consequences for sea level rise. SAR observations of Denman Glacier grounding line, East Antarctica, reveal fast retreat of a glacier with a 1.5 m sea level rise equivalentDenman is retreating along a deep trough with a retrograde bed deepening up to 3.5 km below sea level, one of the deepest basin in AntarcticaWarm water intrusion in the sub‐ice shelf cavity and the retrograde bed topography makes Denman prone to marine instability in near future