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A theory of the Erigen’s differential nonlocal beams of (isotropic) elastic material is prospected independent of the original integral formulation. The beam problem is addressed within a $$C^{(0)}-$$ C ( 0 ) - continuous displacement framework admitting slope discontinuities of the deflected beam axis with the formation of bending hinges at every cross section where a transverse concentrated external force is applied, either a load or a reaction. Concepts sparsely known from the literature are in this paper used within a more general context, in which the beam is envisioned as a macro-beam whose microstructure is able to take on a size dependent initial curvature dictated by the loading and constraint conditions. Indeed, initial curvature seems to be an effective analytical tool to inject size effects into micro- and nano-beams. The proposed theory is applied to a set of benchmark beam problems showing that a softening behaviour is always predicted without the appearance of paradoxical situations. Comparisons with other theories are also presented.

Hypoxia-induced miR-210 is a crucial component of the tissue response to ischemia, stimulating angiogenesis and improving tissue regeneration. Previous analysis of miR-210 impact on the transcriptome in a mouse model of hindlimb ischemia showed that miR-210 regulated not only vascular regeneration functions, but also inflammation. To investigate this event, doxycycline-inducible miR-210 transgenic mice (Tg-210) and anti-miR-210 LNA-oligonucleotides were used. It was found that global miR-210 expression decreased inflammatory cells density and macrophages accumulation in the ischemic tissue. To dissect the underpinning cell mechanisms, Tg-210 mice were used in bone marrow (BM) transplantation experiments and chimeric mice underwent hindlimb ischemia. MiR-210 overexpression in the ischemic tissue was sufficient to increase capillary density and tissue repair, and to reduce inflammation in the presence of Wt-BM infiltrating cells. Conversely, when Tg-210-BM cells migrated in a Wt ischemic tissue, dysfunctional angiogenesis, inflammation, and impaired tissue repair, accompanied by fibrosis were observed. The fibrotic regions were positive for α-SMA, Vimentin, and Collagen V fibrotic markers and for phospho-Smad3, highlighting the activation of TGF-β1 pathway. Identification of Tg-210 cells by in situ hybridization showed that BM-derived cells contributed directly to fibrotic areas, where macrophages co-expressing fibrotic markers were observed. Cell cultures of Tg-210 BM-derived macrophages exhibited a pro-fibrotic phenotype and were enriched with myofibroblast-like cells, which expressed canonical fibrosis markers. Interestingly, inhibitors of TGF-β type-1-receptor completely abrogated this pro-fibrotic phenotype. In conclusion, a context-dependent regulation by miR-210 of the inflammatory response was identified. miR-210 expression in infiltrating macrophages is associated to improved angiogenesis and tissue repair when the ischemic recipient tissue also expresses high levels of miR-210. Conversely, when infiltrating an ischemic tissue with mismatched miR-210 levels, macrophages expressing high miR-210 levels display a pro-fibrotic phenotype, leading to impaired tissue repair, fibrosis, and dysfunctional angiogenesis.

A limit analysis numerical approach oriented to predict the peak/collapse load of human proximal femur, under two different loading conditions, is presented. A yield criterion of Tsai–Hu-type, expressed in principal stress space, is used to model the orthotropic bone tissues. A simplified human femur 3D model is envisaged to carry on numerical simulation of in-vitro tests borrowed from the relevant literature and to reproduce their findings. A critical discussion, together with possible future developments, is presented.

Critical limb ischemia is the most serious form of peripheral artery disease, characterized by severe functional consequences, difficult clinical management and reduced life expectancy. The goal of this study was to investigate the miR-210 role in the neo-angiogenic response after acute limb ischemia. Complementary approaches were used in a mouse model of hindlimb ischemia: miR-210 loss-of-function was obtained by administration of LNA-oligonucleotides anti-miR-210, for miR-210 gain-of-function, a doxycycline-inducible miR-210 transgenic mouse was used. We tested miR-210 ability to stimulate vascular regeneration following ischemia. We found that miR-210 was necessary and sufficient to stimulate blood perfusion recovery, as well as arteriolar and capillary density increase, in the ischemic muscle. To clarify the molecular events underpinning miR-210 pro-angiogenic action, the transcriptomic changes in ischemic muscles upon miR-210 blocking were analyzed. We found that miR-210 impacted the transcriptome significantly, regulating pathways and functions linked to vascular regeneration. In agreement with a pro-angiogenic role, miR-210 also improved cardiac function and left ventricular remodeling after myocardial infarction. Moreover, miR-210 blocking decreased capillary density in a Matrigel plug assay, indicating that miR-210 is necessary for angiogenesis independently of ischemia. Collectively, these data indicate that miR-210 plays a pivotal role in promoting vascular regeneration.

The aim of this study was to compare the perioperative and functional results between laparoscopic and robot-assisted simple prostatectomy (LSP and RASP) and Holmium laser enucleation of prostate (HoLEP) in prostate volumes ≥120 mL. The primary endpoint was to investigate and compare minimally invasive techniques in the management of large prostate gland volume, and the secondary endpoint was to evaluate the frequency and type of postoperative complications according to Clavien Dindo Classification.This multicenter study was conducted on male patients with LUTS associated with BPO candidates for surgical treatment. The surgery approach choice in relation to the prostatic volume ≥120 mL was HoLEP or minimally-invasive simple prostatectomy (LSP or RASP). All patients were prospectively randomized into three groups, according to a simple computed randomization: HoLEP, LSP and RASP groups. During the follow-up, all patients underwent postoperative control at 1, 3, 6, 12 and 24 months from the surgical procedure.One hundred ten male patients were randomized in three homogeneous groups: 36 in LSP, 32 in RASP and 42 in HoLEP group. During the follow-up (mean 26.15 months), despite the significant improvement compared to baseline results, no significant differences were shown, between the groups in terms of functional and perioperative outcomes. The only statistically significant data was reported for catheterization time, that resulted longer in the LSP group than RASP and HoLEP groups (P=0.002). Furthermore, MISP resulted in longer hospitalization, and lower rate of patients with new-onset irritative symptoms.This prospective randomized study is the first to compare extraperitoneal LSP, RASP and HoLEP in the treatment of LUTS secondary to benign prostatic hyperplasia for prostate volumes ≥120 mL. Our findings confirm the safety and efficacy of MISP, demonstrating its equivalence in functional outcomes and perioperative morbidity in comparison to HoLEP.

Introduction We previously demonstrated in mouse models of peripheral and heart ischemia that miR-210 is necessary and sufficient to stimulate blood perfusion recovery, as well as arteriolar and capillary density increase following ischemic damage. Aim To clarify the role of inflammatory cells in miR-210-induced angiogenesis. Methods and results In a mouse model of acute limb ischemia, miR-210 loss-of-function was obtained by administration of complementary anti-miR-210 LNA oligonucleotides (anti-210), while doxycycline-inducible miR-210 transgenic mice (Tg210) were used for gain-of-function experiments. Transcriptomic and gene ontology analysis in ischemic gastrocnemius muscles upon miR-210 blocking displayed an enrichment of categories related not only to angiogenesis, but also to inflammation, suggesting that miR-210 decrease prompted a pro-inflammatory and anti-regenerative response. Accordingly, immunofluorescence staining of ischemic muscles of anti-210 treated mice, showed an increased presence of granulocytes (Scr = 28±7, anti-210 = 108±17 cells/mm2, p Conclusions Collectively, these data show that a miR-210 enriched milieu was sufficient to improve angiogenesis after ischemia. Moreover, a context-dependent regulation by miR-210 of the inflammatory response and of fibrosis were identified. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Italian Ministry of health: Ricerca Corrente and 5X1000

Papillary renal cell carcinoma (PRCC) is a rare cancer and is the second most frequent histologic type among all renal cell carcinoma, accounting for up to 15%. A 72-year-old man underwent a right radical nephrectomy 7 years ago with final histopathology diagnosis of type 1 PRCC with negative surgical margins. Five years after surgery, computed tomography scan imaging showed the presence of multiple masses suspicious for node recurrences disease localized in the renal lodge, in the inter-aorto-caval space, at the iliac vessels bifurcation and right common iliac vessels. Patient underwent a robotic retroperitoneal lymphadenectomy. The histopathological examination confirmed the recurrence of type I papillary renal cancer in all the specimens. No further recurrences have been observed at 24-month follow-up after surgery. This report is the first describing a robot-assisted minimally invasive surgical excision for type I papillary renal cancer nodal and renal fossa recurrences.