Cardiovascular autonomic function and MCI in Parkinson's disease

Introduction: dysautonomic dysfunction and cognitive impairment represent the most disabling non-motor features of Parkinson's Disease (PD). Recent evidences suggest the association between Orthostatic Hypotension (OH) and PD-Dementia. However, little is known on the interactions between cardiovascular dysautonomia and Mild Cognitive Impairment (MCI). We aimed to evaluate the association between cardiovascular dysautonomia and MCI in patients with PD. Methods: non-demented PD patients belonging to the PACOS cohort underwent a comprehensive instrumental neurovegetative assessment including the study of both parasympathetic and sympathetic function (30:15 ratio, Expiratory-Inspiratory ratio [E-I] and presence of Orthostatic Hypotension [OH]). Diagnosis of MCI was made according to the MDS criteria level II. Results: we enrolled 185 PD patients of whom 102 (55.1%) were men, mean age was 64.6 ± 9.7 years, mean disease duration of 5.6 ± 5.5 years with a mean UPDRS-ME score of 31.7 ± 10.9. MCI was diagnosed in 79 (42.7%) patients. OH was recorded in 52 (28.1%) patients, altered 30:15 ratio was recorded in 39 (24.1%) patients and an altered E-I ratio was found in 24 (19.1%) patients. Presence of MCI was associated with an altered 30:15 ratio (adjOR 2.83; 95%CI 1.25–6.40) but not with an altered E-I ratio, while OH was associated only with the amnestic MCI subgroup (OR 2.43; 95% CI 1.05–5.06). Conclusion: in our study sample, MCI was mainly associated with parasympathetic dysfunction in PD

18 Ne diproton decay

Two proton radioactivity studies have been performed on excited states of 18 Ne produced, among other fragments, by 20 Ne projectile fragmentation and excited via Coulomb excitation on a Pb target. Every incoming ion was tagged before interacting with the lead target on an event by event basis in order to discriminate the secondary reactions according to the projectile. Decay of 18 Ne levels has been studied by complete kinematical reconstruction. In spite of the low statistics a couple of events looks very promising for two proton correlated emission

Variations in Atmospheric CO2CO_2 Mixing Ratios across a Boston, MA Urban to Rural Gradient

Urban areas are directly or indirectly responsible for the majority of anthropogenic $CO_2$ emissions. In this study, we characterize observed atmospheric $CO_2$ mixing ratios and estimated $CO_2$ fluxes at three sites across an urban-to-rural gradient in Boston, MA, USA. $CO_2$ is a well-mixed greenhouse gas, but we found significant differences across this gradient in how, where, and when it was exchanged. Total anthropogenic emissions were estimated from an emissions inventory and ranged from $1.5 to 37.3 mg·C·ha^{-1}·yr^{-1}$ between rural Harvard Forest and urban Boston. Despite this large increase in anthropogenic emissions, the mean annual difference in atmospheric $CO_2$ between sites was approximately 5% $(20.6 \pm 0.4 ppm)$. The influence of vegetation was also visible across the gradient. Green-up occurred near day of year 126, 136, and 141 in Boston, Worcester and Harvard Forest, respectively, highlighting differences in growing season length. In Boston, gross primary production—estimated by scaling productivity by canopy cover—was ~75% lower than at Harvard Forest, yet still constituted a significant local flux of $3.8 mg·C·ha^{-1}·yr^{-1}$. In order to reduce greenhouse gas emissions, we must improve our understanding of the space-time variations and underlying drivers of urban carbon fluxes.Engineering and Applied Science

Past, present and future of radioactive ion beams produced In-Flight at LNS

The FRIBs@LNS facility produces Radioactive Ion Beams (RIBs) at intermediate energies, by projectile fragmentation. The possibility of using the produced RIBs as secondary beams in nuclear physics experiments by applying the tagging technique, i.e. the identification, event-by-event, in charge, mass and energy of each ion of the RIBs cocktail selected by the fragment separator, before it interacts with the secondary target, has been demonstrated. In 2010 an upgrade of the facility has been performed. Status and perspectives of the FRIBs@LNS facility are discussed

Immune-checkpoint inhibitors from cancer to COVID‑19: A promising avenue for the treatment of patients with COVID‑19

The severe acute respiratory syndrome associated coronavirus‑2 (SARS‑CoV‑2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID‑19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off‑label for the treatment of COVID‑19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune‑checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death‑1 (PD‑1)/PD ligand-1 (PD‑L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID‑19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T‑cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti‑tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T‑cell exhaustion, which is also observed following SARS‑CoV‑2 infection. Importantly, when treated with anti‑PD‑1 and anti‑PD‑L1 antibodies, they restore their T‑cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti‑PD‑1 antibody administration to both cancer and non‑cancer individuals affected by COVID‑19. The results may prove the hypothesis that restoring exhausted T‑cells may be a winning strategy to beat SARS‑CoV‑2 infection

Current molecular and clinical insights into uveal melanoma (Review)

Uveal melanoma (UM) represents the most prominent primary eye cancer in adults. With an incidence of approximately 5 cases per million individuals annually in the United States, UM could be considered a relatively rare cancer. The 90.95% of UM cases arise from the choroid. Diagnosis is based mainly on a clinical examination and ancillary tests, with ocular ultrasonography being of greatest value. Differential diagnosis can prove challenging in the case of indeterminate choroidal lesions and, sometimes, monitoring for documented growth may be the proper approach. Fine needle aspiration biopsy tends to be performed with a prognostic purpose, often in combination with radiotherapy. Gene expression profiling has allowed for the grading of UMs into two classes, which feature different metastatic risks. Patients with UM require a specialized multidisciplinary management. Primary tumor treatment can be either enucleation or globe preserving. Usually, enucleation is reserved for larger tumors, while radiotherapy is preferred for small/medium melanomas. The prognosis is unfavorable due to the high mortality rate and high tendency to metastasize. Following the development of metastatic disease, the mortality rate increases to 80% within one year, due to both the absence of an effective treatment and the aggressiveness of the condition. Novel molecular studies have allowed for a better understanding of the genetic and epigenetic mechanisms involved in UM biological activity, which differs compared to skin melanomas. The most commonly mutated genes are GNAQ, GNA11 and BAP1. Research in this field could help to identify effective diagnostic and prognostic biomarkers, as well as novel therapeutic targets

Wind tunnel testing of the DeepWind demonstrator in design and tilted operating conditions

The DeepWind Project aims at investigating the feasibility of a new floating vertical-axis wind turbine (VAWT) concept, whose purpose is to exploit wind resources at deep-water offshore sites.The results of an extensive experimental campaign on the DeepWind reduced scale demonstrator are here presented for different wind speeds and rotor angular velocities, including also skewed flow operation due to a tilted rotor arrangement. To accomplish this, after being instrumented to measure aerodynamic power and thrust (both in streamwise and transversal directions), a troposkien three-bladed rotor was installed on a high precision test bench, whose axis was suitable to be inclined up to 15° with respect to the design (i.e. upright) operating condition.The experiments were performed at the large scale, high speed wind tunnel of the Politecnico di Milano (Italy), using a "free jet" (open channel) configuration. The velocity field in the wake of the rotor was also fully characterized by means of an instrumented traversing system, to investigate the flow distribution downstream of the test section.Special care is taken in the description of the experimental set-up and of the measured data, so that the present results can be used as a benchmark for the validation of simulation models

GRP78 Mediates Cell Growth and Invasiveness in Endometrial Cancer.

Abstract Recent studies have indicated that endoplasmic reticulum stress, the unfolded protein response activation and altered GRP78 expression can play an important role in a variety of tumors development and progression. Very recently we reported for the first time that GRP78 is increased in endometrial tumors. However, whether GRP78 could play a role in the growth and/or invasiveness of endometrial cancer cells is still unknown. Here we report that the silencing of GRP78 expression affects both cell growth and invasiveness of Ishikawa and AN3CA cells, analyzed by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell migration assay, respectively. At variance with Ishikawa cells, AN3CA cells showed, besides an endoplasmic reticulum, also a plasma membrane GRP78 localization, evidenced by both immunofluorescence and cell membrane biotinylation experiments. Intriguingly, flow cytometry experiments showed that the treatment with a specific antibody targeting GRP78 C-terminal domain caused apoptosis in AN3CA but not in Ishikawa cells. Induction of apoptosis in AN3CA cells was not mediated by the p53 pathway activation but was rather associated to reduced AKT phosphorylation. Interestingly, immunofluorescence analysis evidenced that endometrioid adenocarcinoma tissues displayed, similarly to AN3CA cells, also a GRP78 plasma membrane localization. These data suggest that GRP78 and its plasma membrane localization, might play a role in endometrial cancer development and progression and might constitute a novel target for the treatment of endometrial cancer

Performance and midspan wake measurements on a H-Darrieus in controlled conditions

Performance and wake measurements on a H-Darrieus vertical axis wind turbine are discussed on the basis of an extensive experimental campaign performed at the large scale, high speed wind tunnel of the Politecnico di Milano (IT). The paper proposes a combined mechanical and fluid-dynamic investigation by virtue of an advanced measurement system that allows to reconstruct both phase-resolved thrust and torque acting on the machine and the phase-resolved multi-dimensional velocity field in the wake. The aerodynamic torque is presented as a function of the azimuthal angle of revolution, while the velocity field in the wake is fully characterized by means of a point to point detailed measurement on the midspan plane, where the influence of both blade support struts and tip vortices is negligible. Particular care is taken in the description of the experimental setup as well as in the presentation of the measurements. The here proposed achievements can be considered as a benchmark for the validation of several classes of computational tools