Cholesterol metabolism is altered in Rett syndrome: A study on plasma and primary cultured fibroblasts derived from patients

Rett (RTT) syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation-dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR), sterol regulatory element binding proteins (SREBPs), low density lipoprotein receptor (LDLr) and scavenger receptor B-1 (SRB-1) was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology

Diferencias en la conciliación de la vida laboral y personal y la satisfacción laboral en españoles e italianos: presencial vs teletrabajo

Objetivo: Investigar en qué medida las modalidades de trabajo "presencial" y "teletrabajo" influyen en los constructos de Satisfacción Laboral y Conciliación de la Vida Laboral y Personal para hipotetizar una distribución ideal dentro de una organización. Metodología: Se administró un cuestionario a una muestra de trabajadores españoles e italianos, diferenciados en presenciales y teletrabajadores, para investigar la Satisfacción Laboral y el nivel de desequilibrio percibido entre el trabajo y la vida personal. Resultados: El modo de trabajo y la nacionalidad no muestran un efecto significativo en el constructo Equilibrio Trabajo-Vida, mientras que sí muestran un impacto (aunque mínimo) en la Satisfacción Laboral. Conclusiones: Se puede afirmar que los dos constructos de Conciliación de la Vida Laboral y Personal y Satisfacción Laboral no parecen estar directamente relacionados con la forma en que se desempeña el trabajo y, en consecuencia, no es posible hipotetizar una distribución ideal dentro de una empresa en este momento sin tener en cuenta otras variables.Objective: To investigate the extent to which "presential" and "teleworking" work modes influence the constructs of Job Satisfaction and Work-Life Balance in order to hypothesise an ideal distribution within an organisation. Methodology: A questionnaire was administered to a sample of Spanish and Italian workers, differentiated into presential and teleworkers, to investigate Job Satisfaction and the level of perceived imbalance between work and personal life. Results: Mode of work and nationality do not show a significant effect on the Work-Life Balance construct whereas they do show an impact (albeit minimal) on Job Satisfaction. Conclusions: It is possible to state that the two constructs of Work-Life Balance and Job Satisfaction do not appear to be directly related to the way one performs one's job and, consequently, it is not possible to hypothesise an ideal distribution within a company at the moment without taking other variables into account

La Stima dei Moduli Elastici delle Murature Secondo le Norme Tecniche: il Confronto con la Sperimentazione

Nel presente lavoro viene proposto uno studio sperimentale per la caratterizzazione meccanica di diverse tipologie di muratura. Vengono in particolare valutati i moduli elastici longitudinali e tangenziali che come è noto condizionano la risposta di sistemi murari sotto carichi laterali. I valori sperimentali sono confrontati con quelli stimabili per mezzo dei modelli proposti dalle normative tecniche italiana (DM 14/01/2008) e europea (Eurocodice 6). Lo studio prende spunto dalla questio posta dalla norma americana (MSJC 2008) che, pur proponendo l’uso di tali modelli, riconosce la poca sperimentazione eseguita a supporto della loro validazione. La campagna sperimentale ha incluso prove di compressione sui componenti (malte e blocchi), prove di compressione diagonale e prove di compressione ordinaria (in direzione ortogonale ai letti di malta) su porzioni di muratura. I risultati conseguiti hanno consentito la valutazione diretta dei moduli elastici e successivamente di ottenere le grandezze meccaniche necessarie per l’utilizzo dei succitati modelli normativi

Modelling failure analysis of RC frame structures with masonry infills under sudden column losses

Abstract Robustness of structures is fundamental to limit progressive collapse of buildings in case of accidental loss of columns due to explosions, impacts or materials deterioration. Modelling of progressive collapse response of reinforced concrete (RC) frame structures needs considering extreme geometric and mechanical nonlinearities. Moreover, in the case of infilled frames the collapse mechanism becomes more complex because of the frame-infill interaction. This paper presents a numerical study aimed at proposing: a) an appropriate fiber-section modeling methodology for reinforced concrete frames under large displacement progressive collapse events; b) a new multi-strut fiber macro-element model to account for the influence of masonry infills in the progressive collapse response. Proposed numerical models are developed using the OpenSees software platform. The predictive capacity of the proposed methodology is widely validated in the paper through comparisons with experimental test results and refined numerical simulation pushdown test results. Results show that the new equivalent-strut modeling approach can be suitably employed as a simple assessment method when numerical simulation of progressive collapse scenarios is needed for bare and infilled reinforced concrete frames

Measles Immunization Status of Health Care Workers: A Cross-Sectional Study Exploring Factors Associated with Lack of Immunization According to the Health Belief Model

Suboptimal levels of measles vaccination coverage make Italy a country where the circulation of the virus is still endemic. In the past decade, several nosocomial outbreaks of measles occurred in Italy that rapidly spread the infection among large numbers of hospitalized patients and susceptible healthcare workers (HCWs). A cross-sectional study was conducted at the University Hospital of Palermo (Italy) to estimate the rate of HCWs immunization and to investigate the factors associated with lack of immunization. The attitude to the immunization practice was evaluated by exploring the Health Belief Model. Overall, 118 HCWs were enrolled, with a mean age of 31 years and 59.3% male. About half of the sample (45.8%, n = 54) was found not to be immunized against measles. Multivariable analysis showed that the factors directly associated with the non-immunization status against measles were female sex (OR = 3.70, p = 0.056), being an HCW different from a physician (OR = 10.27, p = 0.015), having a high perception of barriers to vaccination (OR = 5.13, p = 0.047), not being immunized for other exanthematous diseases such as chickenpox (OR = 9.93, p = 0.003), mumps (OR = 33.64, p < 0.001) and rubella (OR = 10.12, p= 0.002). There is a need to contrast the low adherence of HCWs to measles vaccination by identifying effective strategies to increase immunization coverage and limiting the risk of further nosocomial measles outbreaks

MMP-2, MMP-9 and activin A blood levels in patients with breast cancer or prostate cancer metastatic to the bone.

Background: The clinical significance of the circulating levels of activin A and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) was investigated in patients with breast cancer (BC) or prostate cancer (PC) with (M1) or without (M0) bone metastasis. Patients and Methods: MMP-2, MMP-9 and activin A blood concentrations were measured by enzyme immunoassays in 79 cancer patients and in 57 healthy blood donors (HS) who served as a control group. The diagnostic accuracy of these molecules to discriminate between M0 and M1 patients was evaluated by the receiver operating characteristic curve (ROC) and compared to that of tumor markers CA15.3 or prostate-specific antigen (PSA). Results: Activin A and MMP-2 were significantly increased in BC and PC patients as compared to sex-matched HS while MMP-9 levels were more elevated only in the PC patients. Interestingly, in the PC patients, activin A levels were significantly higher than those measured in the BC patients. In this latter group, activin A and CA15.3 but not MMP-2 or MMP-9 were increased in the M1 patients as compared to M0 patients. Furthermore, a significant relationship was also highlighted between activin A concentration and the number of bone metastases and tumor grade, between MMP-9 and tumor grade, and between MMP-2 and CA15.3. ROC curve analysis showed a good diagnostic accuracy for activin A and CA15.3 but a poor accuracy for MMP-2 and MMP-9 in discriminating between M0 and M1 patients. However, CA15.3 retained the best diagnostic accuracy in this respect. In the PC group, only activin A and PSA levels were significantly increased in the M1 patients as compared to the M0 patients. A similar although not statistically significant trend was noted for MMP-9. Interestingly, a significant correlation was observed between PSA and activin A and MMP-9, and between Activin A and Gleason score and the number of skeletal metastases. ROC curve analysis showed a good diagnostic accuracy for activin A, MMP-9 and PSA and a poor diagnostic accuracy for MMP-2 in detecting M1 patients. However, PSA showed the highest diagnostic accuracy. Conclusion: Activin A, MMP-2 and MMP-9 may be regarded as possible therapeutic targets in the treatment of metastatic bone disease. However, their usefulness as additional markers of bone metastasis remains to be better define

Definition of seismic vulnerability maps for civil protection systems: The case of lampedusa Island

The opportunity to locate and quantify the major criticalities associated to natural catastrophic events on a territory allows to plan adequate strategies and interventions by civil protection bodies involved in local and international emergencies. Seismic risk depends, most of all, on the vulnerability of buildings belonging to the urban areas. For this reason, the definition, by a deep analysis of the territory, of instruments identifying and locating vulnerability, largely favours the activities of institutions appointed to safeguard the safety of citizens. This paper proposes a procedure for the definition of vulnerability maps in terms of vulnerability indexes and critical peak ground accelerations for mid-small urban centres belonging to Mediterranean areas. The procedure, tested on the city centre of the Island of Lampedusa, is based on a preliminary historical investigation of the urban area and of the main formal and technological features of buildings involved. Moreover, the vulnerability of the constructions is evaluated by fast assessment methods (filling of evaluation forms). The vulnerability model, allowing the definition of the fragility curves, is calibrated on the basis of the results of an identification process of prototype buildings, selected to be adequately representative. Their characterizations have been provided using the results of an experimental dynamic investigation to develop high representative numerical model. Critical PGA values have been determined by pushover analyses. The results presented provided an unambiguous representation of the major criticalities with respect to seismic vulnerability and risk, of the city centre of the island, being a suitable tool for planning and handling of emergencies

Preparation of drug-loaded small unilamellar liposomes and evaluation of their potential for the treatment of chronic respiratory diseases

The aim of the present investigation was to evaluate the influence of liposome formulation on the ability of vesicles to penetrate a pathological mucus model obtained from COPD affected patients in order to assess the potential of such vesicles for the treatment of chronic respiratory diseases by inhalation. Therefore, Small Unilamellar Liposomes (PLAIN-LIPOSOMEs), Pluronic® F127- surface modified liposomes (PF-LIPOSOMEs) and PEG 2000PE-surface modified liposomes (PEG-LIPOSOMEs) were prepared using the micelle-to-vesicle transition (MVT) method and beclomethasone dipropionate (BDP) as model drug. The obtained liposomes showed diameters in the range of 40-65 nm, PDI values between 0.25-0.30 and surface electric charge essentially close to zero. The encapsulation efficiency was found to be dependent on the BDP/lipid ratio used and, furthermore, BDP-loaded liposomes were stable in size both at 37°C and at 4°C. All liposomes were not cytotoxic on H441 cell line as assessed by the MTT assay. The liposome uptake was evaluated through a cytofluorimetric assay that showed a non-significant reduction in the internalization of PEG-LIPOSOMEs as compared with PLAIN-LIPOSOMEs. The penetration studies of mucus from COPD patients showed that the PEG-LIPOSOMEs were the most mucuspenetrating vesicles after 27 hours. In addition, PEG- and PF-LIPOSOMEs did not cause any effect on bronchoalveolar lavage fluid proteins after aerosol administration in the mouse. The results highlight that PEG-LIPOSOMEs show the most interesting features in terms of penetration through the pathologic sputum, uptake by airway epithelial cells and safety profile

Combination therapy with aliskiren versus ramipril or losartan added to conventional therapy in patients with type 2 diabetes mellitus, uncontrolled hypertension and microalbuminuria.

Hypothesis/Introduction: The aim of this study was to assess the antihypertensive efficacy and safety of aliskiren versus ramipril or losartan in hypertensive patients with type 2 diabetes mellitus, microalbuminuria and uncontrolled hypertension, despite the use of optimal conventional antihypertensive therapy. Materials and methods: In this open-label active comparator study, 126 patients were randomly assigned to receive 24 weeks of additional therapy with aliskiren (Group A) or either losartan or ramipril (Group B), according to whether a patient was already treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, respectively. Results: After 24 weeks, both treatment groups experienced a significant reduction of systolic blood pressure (−11.37% and −8.47%, respectively; both p <0.001 vs . baseline) and diastolic blood pressure levels (−10.67% and −9.28%, respectively; both p <0.001 vs . baseline), with a greater reduction of mean systolic values in Group A compared with Group B ( p <0.001). Furthermore, after six months microalbuminuria was significantly decreased in both treatment groups (−67.62% and −49.1%, respectively; both p <0.001), with a reduction rate in Group A significantly higher than in Group B ( p <0.001). Conclusions: The addition of aliskiren to optimal conventional therapy provided a higher reduction of blood pressure and urinary albumin excretion when compared with the addition of losartan or ramipril

Enhancing a Transition to a Circular Economy in the Water Sector: The EU Project WIDER UPTAKE

Wastewater treatment plants (WWTPs) require an urgent transition from a linear to a circular economy operation/design concept with a consequent resource recovery and more sustainable waste management. Natural resources have to be preserved, and wastes have to become an opportunity for recovering resources and materials (water reuse, energy, sludge reuse). However, the transition toward a circular economy is a complex and long process due to the existence of technical, economic, social and regulatory barriers. These existing barriers are critical challenges for a modern and sustainable WWTP concept. The recovery of resources must be considered a strategic target from the earliest process-design phase. In this context, the European Union’s Horizon 2020 project “Achieving wider uptake of water-smart solutions—WIDER UPTAKE” aims to overcome the existing barriers (technological, regulatory, organizational, social and economic) toward the transition from a linear to a circular economy model for WWTPs. This study is aimed at increasing the awareness of the existing barriers to a circular economy and summarizes the key contributions of the WIDER UPTAKE project in terms of water reuse, sludge reuse and nutrient recovery