The Role of Transport Infrastructures in determining Technical Efficiency in R&D activity of Italian regions. A double-bootstrapped DEA procedure

We measure technical efficiency in R&D of Italian regions with the aim of understanding whether the variation in transport infrastructure endowment across regions might be the cause of efficiency disparities. We use a semi-parametric method where in the first step we estimate bootstrapped efficiency scores through DEA. In the second step, efficiency scores are explained in a bootstrapped truncated regression using transport infrastructure variables as non-discretionary inputs. We find that well-developed transport infrastructures seriously improve R&D efficiency by facilitating connections and, thus, knowledge transfer

Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS Production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

Acute modulation of brain connectivity in Parkinson disease after automatic mechanical peripheral stimulation: A pilot study

The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease.Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre- and post-effective AMPS and pre- and post-sham condition were obtained and first entered in respective one-sample t-test analyses, to evaluate the mean effect of condition.Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-test analysis to rule out sub-threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79).Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration.This study provides Class II evidence that automatic mechanical peripheral stimulation is effective in modulating brain functional connectivity of patients with Parkinson Disease at rest.Clinical Trials.gov NCT01815281

Performance of a non-contact infrared thermometer in healthy newborns

OBJECTIVE: To evaluate the performance of a non-contact infrared thermometer (NCIT) in comparison with digital axillary thermometer (DAT) and infrared tympanic thermometers (ITT) in a population of healthy at term and preterm newborns nursed in incubators. SETTING: 1 level III maternity hospital, and its intensive neonatal care unit. PARTICIPANTS: 119 healthy at term newborns and 70 preterm newborns nursed in incubators were consecutively enrolled. Exclusion criteria were unstable/critical conditions, polymalformative congenital syndromes and severe congenital syndromes. INTERVENTIONS: Body temperature readings were prospectively collected. Each participant underwent bilateral axillary temperature measurement with DAT, bilateral tympanic measurement with ITT and mid-forehead temperature measurements using NCIT. PRIMARY OUTCOME MEASURES: Degree of agreement between methods was evaluated by the Bland and Altman method. RESULTS: 714 measurements in 119 healthy at term newborns and 420 measurements in 70 preterm newborns nursed in incubators were performed. Clinical reproducibility of NCIT was 0.0455°C for infants in incubators and 0.0861°C for infants outside an incubator. Bias was 0.029°C for infants in incubators and <0.0001°C for infants outside an incubator. Zero outliers were recorded. The mean difference between methods was good both for newborns at term (0.12°C for NCIT vs DAT and 0.02°C for NCIT vs ITT) and preterm newborns in incubators (0.10°C for NCIT vs DAT and 0.14°C for NCIT vs ITT). Limits of agreement were 0.99 to −0.75 and 0.78 to −0.75 in at term newborns and were particularly satisfactory in preterm newborns in incubators (95% CI: 0.48 to −0.27 and 0.68 to −0.40). CONCLUSIONS: Our results with Bland and Altman analysis demonstrate that NCIT is a very promising tool, especially in preterm newborns nursed in incubators. Trial registration: The study was approved by the Careggi University Hospital Ethics Committee (07/2011)

α7 Nicotinic Acetylcholine Receptors May Improve Schwann Cell Regenerating Potential via Metabotropic Signaling Pathways

Background: Schwann cells (SCs) are glial cells involved in peripheral axon myelination. SCs also play a strategic role after peripheral nerve injury, regulating local inflammation and axon regeneration. Our previous studies demonstrated the presence of cholinergic receptors in SCs. In particular, the α7 nicotinic acetylcholine receptors (nAChRs) are expressed in SCs after peripheral axotomy, suggesting their involvement in the regulation of SC-regenerating properties. To clarify the role that α7 nAChRs may play after peripheral axon damage, in this study we investigated the signal transduction pathways triggered by receptor activation and the effects produced by their activation. Methods: Both ionotropic and metabotropic cholinergic signaling were analyzed by calcium imaging and Western blot analysis, respectively, following α7 nAChR activation. In addition, the expression of c-Jun and α7 nAChRs was evaluated by immunocytochemistry and Western blot analysis. Finally, the cell migration was studied by a wound healing assay. Results: Activation of α7 nAChRs, activated by the selective partial agonist ICH3, did not induce calcium mobilization but positively modulated the PI3K/AKT/mTORC1 axis. Activation of the mTORC1 complex was also supported by the up-regulated expression of its specific p-p70 S6KThr389 target. Moreover, up-regulation of p-AMPKThr172, a negative regulator of myelination, was also observed concomitantly to an increased nuclear accumulation of the transcription factor c-Jun. Cell migration and morphology analyses proved that α7 nAChR activation also promotes SC migration. Conclusions: Our data demonstrate that α7 nAChRs, expressed by SCs only after peripheral axon damage and/or in an inflammatory microenvironment, contribute to improve the SCs regenerating properties. Indeed, α7 nAChR stimulation leads to an upregulation of c-Jun expression and promotes Schwann cell migration by non-canonical pathways involving the mTORC1 activity

Ranolazine attenuates trastuzumab-induced heart dysfunction by modulating ROS production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

Early and long-term outcomes of carotid stenting and carotid endarterectomy in women

Background: The role of carotid revascularization in women remains intensely debated because of the lower benefit and higher perioperative risks concerning the male counterpart. Carotid artery endarterectomy (CEA) and stenting (CAS) represent the two most valuable stroke prevention techniques due to large vessel disease. This study investigates the early and late outcomes in female sex in a real-world everyday clinical practice.Methods: Data were retrospectively analyzed from a single-center database prospectively compiled. A total of 234 procedures, both symptomatic and asymptomatic, were identified (98 CEAs and 136 CASs). Perioperative risks of death, cerebral ischemic events, and local complications were analyzed and compared between the two groups. Long-term outcomes were evaluated in overall survival, freedom from ipsilateral stroke/transient ischemic attack, and freedom from restenosis (&gt;50%) and reintervention.Results: Women who underwent CAS and CEA did not differ in perioperative ischemic cerebral events (2.2 vs. 0%, p = 0.26) and death (0.8 vs. 0%, p = 1). Other perioperative and 30-day outcomes were similarly distributed within the two groups. Kaplan-Meier curves between CAS and CEA groups highlighted no statistical differences at 6 years in overall survival (77.4 vs. 77.1%, p = 0.47) of ipsilateral stroke/transient ischemic attack (94.1 vs. 92.9%, p = 0.9). Conversely, significant differences were showed in 6 years freedom from restenosis (93.1 vs. 83.3%, p = 0.03) and reinterventions (97.7 vs. 87.8%, p = 0.015).Conclusion: Our results revealed that both CEA and CAS have acceptable perioperative risk in women. Long-term outcomes highlighted favorable indications for both procedures, especially for CAS, which seemed to be an excellent alternative to CEA in female patients when performed by well-trained operators

Implementing energy transition and SDGs targets throughout energy community schemes

Citizens are expected to play a great role in the future global energy transition, being able to give a decisive contribution to limit global warming to 1.5 degrees Celsius and avoid the worst consequences. Empowering citizens is crucial and assigning them the role of prosumers in the new energy market is necessary to ensure a sustainable and fair pathway to the low-carbon energy transition. Creating energy communities (ECs) can also engage citizens by providing flexibility and ancillary services, reducing losses and curtailments in the grid. It also yields environmental and social benefits, activating virtuous circles in the local economy aligned with the SDGs of Agenda 2030. We illustrate the experience of an EC implementation, using GECO-Green Energy COmmunity project, as a case study. In particular, the in-depth qualitative analysis of the project from a social and technical perspective is provided. The GECO Project is active in the districts of Pilastro and Roveri, Bologna, Italy, being implemented by a consortium including the Energy and Sustainable Development Agency (AESS), the National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA) and the University of Bologna (UniBo). Our findings show the potential interconnections among the development of an ECs and SDGs, especially goals 7, 11, 12 and 13. Placing ECs and prosumers at the centre of the international debate may deliver a more sustainable paradigm in the energy sector, in line with the climate change needs and community approaches