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Pin-supported (PS) walls represent a possible solution for the seismic retrofit of existing reinforced concrete (RC) buildings, enabling linearization of the frame deformation along its height and consequently inhibiting soft storey collapse mechanisms. The effectiveness of this rehabilitation technology is strongly related to the characteristics of the existing frames, especially to the vertical distribution of the frame storey lateral stiffness. Since a larger 1st storey lateral stiffness may lead to a detrimental structural response of the retrofitted system, an alternative solution obtained from removing the connecting link between the 1st floor of the existing building and the pin-supported wall is investigated in this paper. An analytical method is proposed to derive the distribution of the internal actions in a dual 2D RC frame-PS wall system without the link at the 1st floor level, considering both a linear and nonlinear behaviour of the frame. It emerges that some parameters describing the structure type can provide straightforward information on the suitability of this solution in the seismic retrofit of existing RC buildings. As a result, a simplified procedure has been derived to preliminarily define the retrofit system configuration and evaluate the maximum demand in the PS wall. Such a procedure is finally applied with reference to a frame representing a RC building and finite element model analyses are carried out for validation purposes.

The decarbonization of the construction sector, which is one of the most impactful sectors worldwide, requires a significant paradigm shift from a linear economy to a circular, future-proofed and sustainable economy. In this transition, the role of designers and structural engineers becomes pivotal, and new design objectives and principles inspired by Life Cycle Thinking (LCT) should be defined and included from the early stages of the design process to allow for a truly sustainable renovation of the built environment. In this paper, an overview of LCT-based objectives and principles is provided, critically analyzing the current state of the art of sustainability and circularity in the construction sector. The effectiveness of applying such design principles from the early stages of the design of retrofit interventions is then demonstrated with reference to a case study building. Four seismic retrofit alternatives made of timber, steel and concrete, conceived according to either LCT principles or traditional, were designed and compared to a demolition and reconstruction scenario on the basis of five common environmental impact indicators. The indicators were calculated adopting simplified LCA analyses based on Environmental Product Declarations (EPDs), considering the product and End of Life stages of the building. The results of the comparative analyses confirm that LCT-based retrofit solutions are less impactful than both the traditional seismic retrofit interventions and the demolition and reconstruction scenario.

The seismic retrofit of the existing building heritage represents an urgent issue to be faced and innovative solutions which allow to overcome renovation barriers are needed. In this scenario, pin-supported (PS) walls represent an eligible solution, enabling linearization of the deformation of the frame along its height and inhibiting soft storey collapse mechanisms. The PS wall can be connected to the existing building from outside, thereby avoiding disruption to occupants or their relocation, which are acknowledged as the main barriers to the renovation nowadays. Suitability of PS wall solutions in the seismic retrofit of the existing building stock has been investigated herein, particularly in the case of existing reinforced concrete (RC) buildings, preliminarily focusing on 2D RC frames. The paper shows the weaknesses and strengths of the PS wall solution in relation to the specific features of the considered buildings. An analytical closed-form formulation is proposed and applied as a preliminary tool to evaluate the load distribution in the existing frame and in the PS wall after the retrofit considering the first mode of vibration of the retrofitted system. The results show that, in some conditions, the application of PS walls may be detrimental to the structural response. Along with the evaluation of the effectiveness of the retrofit solution, the proposed formulation allows a preliminary design of the retrofit system. Finally, a series of finite element model analyses have been carried out for validation purposes showing a good agreement between the proposed analytical formulation and the numerical results.

A growing attention has been paid to the deep renovation of RC buildings, particularly focusing on their structural vulnerability and on the development of retrofit strategies; however, the issue of the in-plane diaphragm action and the capacity of existing floors has rarely been addressed. Although floor capacity does not seem critical for the seismic capacity of existing structures, commonly affected by greater vulnerabilities, it may become critical when an additional lateral force resisting system is introduced. This paper investigates the in-plane capacity of beam and hollow-clay-block floor system, typical of the European post-WWII RC buildings. Considering the diaphragm action as associated with an in-plane tied-arch mechanism developing within the floor thickness, the main failure mechanisms are discussed, and some simplified equations are provided to preliminary estimate the maximum capacity of floors. Experimental and numerical analyses are than carried out to validate the simplified analytical model. The relevant influence of possible staircase openings on the in-plane load paths and on diaphragm flexibility and capacity are also considered. Finally, the influence of the floor capacity on the seismic vulnerability assessment and in the conceptual design of a seismic retrofit intervention is discussed. This preliminary study shows that only some of the beam-and-block floor systems have a reliable in-plane capacity, while other typologies cannot serve as floor diaphragms. When the diaphragm action can be relied upon, the diaphragms often exhibit a fairly stiff behaviour up to a brittle failure, which is commonly associated with the ultimate capacity at the tied-arch supports.

Background: This study identified risk factors and postoperative indicators for recurrent lumbar disc herniations (rLDH) following microdiscectomy. Methods: We retrospectively reviewed the 1-year recurrence rate for LDH in 209 consecutive patients undergoing microdiscectomy (2013–2018). Results: Utilizing a multivariate analysis, higher body mass index (BMI) and postsurgery Oswestry disability index (ODI) were significantly associated with an increased risk of rLDH. Conclusion: Elevated postsurgery ODI and higher BMI were significantly associated with increased risk of rLDH.

Mammalian sirtuins are involved in the control of metabolism and life-span regulation. Here, we link the mitochondrial sirtuin SIRT4 with cellular senescence, skin aging, and mitochondrial dysfunction. SIRT4 expression significantly increased in human dermal fibroblasts undergoing replicative or stress-induced senescence triggered by UVB or gamma-irradiation. In-vivo, SIRT4 mRNA levels were upregulated in photoaged vs. non-photoaged human skin. Interestingly, in all models of cellular senescence and in photoaged skin, upregulation of SIRT4 expression was associated with decreased levels of miR-15b. The latter was causally linked to increased SIRT4 expression because miR-15b targets a functional binding site in the SIRT4 gene and transfection of oligonucleotides mimicking miR-15b function prevented SIRT4 upregulation in senescent cells. Importantly, increased SIRT4 negatively impacted on mitochondrial functions and contributed to the development of a senescent phenotype. Accordingly, we observed that inhibition of miR-15b, in a SIRT4-dependent manner, increased generation of mitochondrial reactive oxygen species, decreased mitochondrial membrane potential, and modulated mRNA levels of nuclear encoded mitochondrial genes and components of the senescence-associated secretory phenotype (SASP). Thus, miR-15b is a negative regulator of stress-induced SIRT4 expression thereby counteracting senescence associated mitochondrial dysfunction and regulating the SASP and possibly organ aging, such as photoaging of human skin.

The identification of eosinophils by flow cytometry is difficult because most of the surface antigens expressed by eosinophils are shared with neutrophils. Some methods have been proposed, generally based on differential light scatter properties, enhanced autofluorescence, lack of CD16 or selective positivity of CD52. Such methods, however, show several limitations. In the present study we report a novel method based on the analysis of glycosylphosphatidylinositol (GPI)-linked molecules. The combination of CD157 and FLAER was used, since FLAER recognizes all GPI-linked molecules, while CD157 is absent on the membrane of eosinophils and expressed by neutrophils. Peripheral blood samples from normal subjects and patients with variable percentages of eosinophils (n = 31), and without any evidence for circulating immature myeloid cells, were stained with the combination of FLAER-Alexa Fluor and CD157-PE. A FascCanto II cytometer was used. Granulocytes were gated after CD33 staining and eosinophils were identified as CD157(-)/FLAER(+) events. Neutrophils were identified as CD157(+)/FLAER(+) events. The percentages of eosinophils detected by this method showed a very significant correlation both with automated counting and with manual counting (r = 0.981 and 0.989, respectively). Sorting assays were carried out by a S3 Cell Sorter: cytospins obtained from CD157(-)/FLAER(+) events consisted of 100% eosinophils, while samples from CD157(+)/FLAER(+) events were represented only by neutrophils. In conclusion, this method shows high sensitivity and specificity in order to distinguish eosinophils from neutrophils by flow cytometry. However, since CD157 is gradually up-regulated throughout bone marrow myeloid maturation, our method cannot be applied to cases characterized by immature myeloid cells.

Central nervous system (CNS) involvement in multiple myeloma (MM) is uncommon. Among its possible presentations, leptomeningeal involvement of MM, also termed central nervous system myelomatosis (CNS-MM) is rare and is characterized by the presence of neoplastic plasma cells in the cerebrospinal fluid (CSF). So far, 187 cases of CNS-MM have been reported : the great majority of them were diagnosed by cytological assays and flow cytometry was used in only eight cases. We describe a case of CNS-MM in a 62-year-old woman, previously treated with chemotherapy (VTD) and autologous peripheral blood hematopoietic stem cell transplantation for stage IIIB IgG-λ MM. After achieving a very good partial response, the patient showed progression of disease, with an extramedullary localization. During administration of second-line therapy, the patient showed severe neurological symptoms. MRI resulted negative. Diagnosis of CNS-MM was made by multiparameter flow cytometry, which showed the presence of CD56(+) plasma cells in a CSF sample, in the absence of plasma cell leukemia. In this paper we also present a review of the eight previous cases of CNS-MM diagnosed by flow cytometry. We found that the application of flow cytometry in cases of MM with neurological symptoms allows a rapid diagnosis of CNS-MM and provides useful information about plasma cell phenotype (including CD56 expression). Some cases of CNS-MM are characterized by normal MRI. In addition, some evidences deriving from the review of literature suggest that CSF monitoring by flow cytometry in such cases might be used to evaluate the efficacy of drugs capable of crossing the blood-brain barrier.

A patient with normocytic anemia and marked and persistent reticulocytosis is presented. Causes responsible for blood loss and hemolytic diseases were excluded and, after bone marrow examination, myelodysplastic syndrome (refractory anemia) was diagnosed. In vitro reticulocyte survival studies suggested that reticulocytosis was a consequence of delayed maturation of the reticulocytes. Pseudoreticulocytosis may be an unusual presentation of myelodysplastic syndromes, because only 4 patients with such a finding have previously been reported.

Kaposi's sarcoma (KS) shows a distinct geographical and ethnic distribution. The variable K1 gene serves to differentiate the KSHV subtypes A–E, M, N, and Q. Phylogenetic characterization of 19 classical and epidemic German KS specimens revealed the Eurasian KSHV subtypes C (n = 13, including 6 classical KS) and A (n = 6), while 27 Cuban specimens showed a variety of different subtypes (A: n = 16, 4 being A5; C: n = 8; B: n = 2; and the new subtype E: n = 1). Three pairs of isolates from KS patients and peripheral blood mononuclear cells (PBMC) of their sexual partners without KS were studied for the first time and found identical, strongly arguing for sexual transmission of KSHV in this unique cohort. The unique ethnic background of the Cuban population may explain the variety of different KSHV strains.

Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin.

Recombinant human erythropoietin (Epo) is used to prevent and treat tumor-related anemia and improve quality of life in cancer patients. Recent evidence suggested that Epo may adversely affect the survival of selected cancer patients by promoting tumor growth, inhibition of apoptosis, and induction of migration. Epo unfolds its effect on the Epo receptor (EpoR). We show--to the best of our knowledge for the first time--significantly increased EpoR expression in clinical melanoma metastases and primary melanomas in comparison with different sets of nevi by quantitative real-time reverse transcriptase-PCR, immunohistochemistry, and western blot analysis. When assessing the functionality of the EpoR-signaling pathway, recombinant human Epo led to the phosphorylation of JAK-2, signal transducers and activators of transcription 3 (STAT3), and ERK1/2 in several of the melanoma cell lines that were analyzed. Besides, Epo counteracted cisplatin-induced cell death in BLM and MV3 cells. Finally, Epo promoted cell migration of MV3 cells, whereas inhibition of the JAK/STAT and ERK1/2 pathways reduced Epo-mediated migration. In summary, we show the overexpression of functional EpoR expression in about half of the analyzed clinical melanoma metastasis specimens and show anti-apoptotic as well as pro-migratory effects of Epo, which is of importance for the treatment of anemia in advanced melanoma.

The modifications in the concentration of circulating myoglobin have been studied by means of a radioimmunoassay in 15 cancer patients undergoing polychemotherapy including adriamycin. In 8 patients significant increases in myoglobin levels were found after injection of low doses of the drug (25-50 mg/m2). Moreover, a disturbance of the normal biorhythm of the protein was evident in 12 patients. Creatine kinase-MB was evaluated by means of a radioimmunoassay, but there was no relation between an increase in the isoenzyme and an increase in myoglobin. No ECG modifications were detected. These data indicate that the measurement of myoglobin may offer an indication of myocardial or skeletal muscle damage caused by adriamycin.