Inhibition of phosphoinositide 3-kinase/protein kinase B signaling hampers the vasopressin-dependent stimulation of myogenic differentiation

Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. The AVP system is impaired in several neuromuscular diseases, suggesting that AVP may act as a physiological factor in skeletal muscle. Since the Phosphoinositide 3-kinases/Protein Kinase B/mammalian Target Of Rapamycin (PI3K/Akt/mTOR) signaling plays a significant role in regulating muscle mass, we evaluated its role in the AVP myogenic effect. In L6 cells AKT1 expression was knocked down, and the AVP-dependent expression of mTOR and Forkhead box O3 (FoxO) was analyzed by Western blotting. The effect of the PI3K inhibitor LY294002 was evaluated by cellular and molecular techniques. Akt knockdown hampered the AVP-dependent mTOR expression while increased the levels of FoxO transcription factor. LY294002 treatment inhibited the AVP-dependent expression of Myocyte Enhancer Factor-2 (MEF2) and myogenin and prevented the nuclear translocation of MEF2. LY294002 also repressed the AVP-dependent nuclear export of histone deacetylase 4 (HDAC4) interfering with the formation of multifactorial complexes on the myogenin promoter. We demonstrate that the PI3K/Akt pathway is essential for the full myogenic effect of AVP and that, by targeting this pathway, one may highlight novel strategies to counteract muscle wasting in aging or neuromuscular disorders

Cockayne syndrome group A protein localizes at centrosomes during mitosis and regulates Cyclin B1 ubiquitination

Mutations in CSA and CSB proteins cause Cockayne syndrome, a rare genetic neurodevelopment disorder. Alongside their demonstrated roles in DNA repair and transcription, these two proteins have recently been discovered to regulate cytokinesis, the final stage of the cell division. This last finding allowed, for the first time, to highlight an extranuclear localization of CS proteins, beyond the one already known at mitochondria. In this study, we demonstrated an additional role for CSA protein being recruited at centrosomes in a strictly determined step of mitosis, which ranges from pro-metaphase until metaphase exit. Centrosomal CSA exerts its function in specifically targeting the pool of centrosomal Cyclin B1 for ubiquitination and proteasomal degradation. Interestingly, a lack of CSA recruitment at centrosomes does not affect Cyclin B1 centrosomal localization but, instead, it causes its lasting centrosomal permanence, thus inducing Caspase 3 activation and apoptosis. The discovery of this unveiled before CSA recruitment at centrosomes opens a new and promising scenario for the understanding of some of the complex and different clinical aspects of Cockayne Syndrom

Split spectrum: a multi-channel approach to elastic optical networking

This paper introduces Split Spectrum, which enhances elastic optical networking by splitting a bulk traffic demand into multiple channels, when a single-channel transmission is prohibited by distance or spectrum availability. We performed transmission simulations to determine the maximum reach as a function of modulation format (dual polarization BPSK, QPSK, 16QAM), baud-rate (from 5 to 28 GBd), and number of ROADMs, for a Nyquist WDM super-channel with subcarrier spacing equal to 1.2 x baud-rate. Performance evaluation on two representative topologies shows that, compared to the previously proposed elastic optical networking, Split Spectrum doubles the zero-blocking load and achieves 100% higher network spectral efficiency at zero-blocking loads as a result of extended transmission distance and efficient utilization of spectrum fragments. (C) 2012 Optical Society of Americ

Sex and Gender Differences in Ischemic Heart Disease: Endocrine Vascular Disease Approach (EVA) Study Design

Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study ( Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions

An energy saving solution applied to the final use of electrical and lighting systems of school buildings managed by Perugia Province

In this paper, a study and design of energy conservation actions and the obtention of Energy Efficiency Titles, according to the Italian Ministerial Decree 20th July 2004, applied to lighting and electrical systems in a school district managed by Perugia Province (Italy), is presented. Specifically, the analysis regarded the replacement of neon lamps with high efficiency ones, and the power factor correction of the electrical system with a lower value. The work was carried out through an energy audit of some school buildings. From the results of this energy audit, project solutions were developed and a technical and economical feasibility study was made. This study was then extended to the whole school building fleet managed by Perugia Province. The results of this work were validated by a commercial feasibility assessment through an ESCo

Wearable Robotics for Impaired Upper-Limb Assistance and Rehabilitation: State of the Art and Future Perspectives

Despite more than thirty-five years of research on wearable technologies to assist the upper-limb and a multitude of promising preliminary results, the goal of restoring pre-impairment quality of life of people with physical disabilities has not been fully reached yet. Whether it is for rehabilitation or for assistance, nowadays robotics is still only used in a few high-tech clinics and hospitals, limiting the access to a small amount of people. This work provides a description of the three major 'revolutions' occurred in the field (end-effector robots, rigid exoskeletons, and soft exosuits), reviewing forty-eight systems for the upper-limb (excluding hand-only devices) used in eighty-nine studies enrolling a clinical population before June 2022. The review critically discusses the state of the art, analyzes the different technologies, and compares the clinical outcomes, with the goal of determine new potential directions to follow

The impact of COVID-19 on shoulder and elbow trauma: an Italian survey

Background: Because of the rapid spread of COVID-19, on March 8, 2020 Italy became a “protected area”: people were told not to leave their homes unless it was essential. The aim of this study was to evaluate the activity of our trauma center, relative to shoulder and elbow, in the 30 days starting from March 8, 2020, the first day of restrictions in Italy, and to compare it with the same days of 2019 to weigh the impact of COVID-19 on shoulder and elbow trauma. Materials and methods: Patients managed in our trauma center between March 8, 2020, and April 8, 2020 (COVID period), for shoulder and elbow trauma were retrospectively included and compared to patients admitted in the same period of 2019 (no-COVID period). Clinical records of all participants were examined to obtain information regarding age, sex, mechanism of injury, and diagnosis. Results: During the no-COVID period, 133 patients were admitted for a shoulder or elbow trauma; in the COVID period, there were 47 patients (65% less first aid). In the no-COVID and COVID period, patients with shoulder contusion totaled 60 (14.78% of all; male [M]: 34; female [F]: 26; mean age 51.8 years, range 18-88) and 11 (12.09% of all contusions; M: 7, F: 4; mean age 43 years, range 24-60), respectively. In the no-COVID period, 27 fractures (9.34% of all fractures) involved the shoulder, whereas 18 fractures (8.69%) were registered in the COVID period. In the no-COVID period, 14 elbow fractures were treated (4.8% of all fractures), compared with 4 in the COVID period. In the no-COVID and COVID periods, 6 patients (M: 5, F: 1; mean age 42 years, range 21-64) and 2 patients (M: 1, F: 1; mean age 29.5 years, range 24-35) reported having a feeling of momentary post-traumatic shoulder instability, and 0 and 1 patients (M: 1, F: 0; age 56 years), respectively, reported similar symptoms at the elbow. Finally, first or recurrent dislocations in the no-COVID period were 10, and in the COVID period, 7; elbow dislocations in the no-COVID period were 2, and in the COVID period, there were 3. Conclusions: During the COVID period, we provided a reduced number of health services, especially for patients with low-energy trauma and for those who underwent sports and traffic accidents. However, during the COVID period, elderly subjects remain exposed to shoulder and elbow trauma due to low-energy (domestic) falls. The subsequent hospitalization of these patients has contributed to making it more difficult to manage the hospital wards that are partly occupied by COVID-19 patients

Feasibility study and design of a low-energy residential unit in Sagarmatha park for environmental impact reduction of high altitude buildings

The project presented in this paper is geographically set within Sagarmatha National Park, a wide area located on the Nepalese mountainside of Everest and declared as World Heritage Site since 1979. In recent years the park was the focus of several studies and initiatives, aimed at improving the management of its many-sided ecosystem, significantly influenced by climate change and increase of human activities and tourism, which occurred from the end of the 1970s, as well as by practices that are harmful both to human health and to our environment (e.g. burn up kerosene or animal excrements in order to obtain heat). Research work has focused on designing a residential unit that meets population needs, in terms of simplicity of realization, replicability, use of local materials, environmental compatibility and exploitation of available renewable energies. For this purpose a thorough analysis was conducted to identify the housing standard characteristic of reference context and Sherpa people, concerning indoor thermal comfort conditions, construction techniques, availability and skills of local workforce. Data necessary for the design phase were obtained through a collaboration with researchers of Ev-K2-CNR center, active at 5,050 meters a.s.l. in Nepal at the base of Mount Everest with a laboratory/observatory (known as the "Pyramid") for highaltitude meteorological studies since 1989. Climate conditions were registered by specific monitoring stations at certain times (2002-2008); during preliminary stage, these values were considered representative of the local context chosen for the project, that is Namche Bazar, a village located within the park, in a central point both from the logistic and altimetric/weather points of view. For the residential unit under investigation, two different constructive approaches were selected and compared: earthbags and straw bales. Both techniques have several advantages, in particular availability of raw material (jute bags, soil, straw), simplicity (e.g. earthbag constructions are realized using the ancient technique of pisé, combined with flexible bags or tubes), durability, insulation performance, costeffectiveness. Through a specific software for calculation of winter/summer thermal loads, different combinations of selections of structure and insulation were examined for both solutions, in order to achieve the optimum for the case study. Furthermore on the base of data monitored on site, a specific assessment was carried out to evaluate the potential of solar and wind resources. Aiming at entirely covering the heat and electric energy needs by exploiting renewable energy sources, various plant configurations were finally assumed. Every single choice was made to reduce human influence on land resources, such as timber, and to improve internal and external environmental quality