The indirect effect of cognitive reserve on the relationship between age and cognition in pathological ageing: A cross-sectional retrospective study in an unselected and consecutively enrolled sample

Cognitive reserve (CR) allows individuals to maintain cognitive functionality even in the presence of pathologies. The compensation hypothesis suggests that CR plays an indirect role between age and cognitive decline, contrasting the negative effect of ageing on cognition. We test this hypothesis in an unselected and consecutively enrolled sample of memory clinic attendees (n = 134) who completed the CR Index questionnaire and three neuropsychological tests assessing global cognition (MMSE, FAB, CDT). Participants were divided into two groups based on standard diagnostic criteria (DSM-5): those who were cognitively impaired (n = 92) and those who were preserved (n = 42). A principal component analysis was used to extract a composite measure of global cognitive functioning from the three neuropsychological tests, and mediation analysis was used to examine the relationship between CR, age and global cognitive functioning in the two groups. Results revealed that: (i) age had a significant direct negative effect on the global cognitive score in both groups; (ii) the three socio-behavioural proxies of CR together suppress the direct negative relationship between age and global cognitive score in cognitively impaired patients but not in cognitively preserved participants. This study confirms the association between CR, age and cognition and allows us to validate its role in a population with cognitive impairment and extend findings to a low-to-middle educated population. These results hold important implications for public health and wellness promotion, emphasising the beneficial role of maintaining healthy and active physical, cognitive and social lifestyles

FPGA-based digital back-ends for the Sardinia Radio Telescope

The Sardinia Radio Telescope (SRT), located in San Basilio, about 35 km north of Cagliari, is the largest (64-m diameter) radio telescope in Italy. It is a general-purpose, fully-steerable radio telescope designed to operate in the 300 MHz - 116 GHz frequency range, which allows it to perform a wide variety of scientific studies. The advanced electronic digital platforms that are installed at SRT play a key role, in particular those based on FPGAs (Field Programmable Gate Array), both because of their processing capability and their reconfigurability. In this paper, we present an overview of the digital back-ends available at SRT, as well as the ones under development; it is important to underline that, for all of them, FPGAs are the beating heart

Reducing Effect of Saikosaponin A, an Active Ingredient of Bupleurum falcatum, on Intake of Highly Palatable Food in a Rat Model of Overeating

Recent lines of experimental evidence have indicated that saikosaponin A (SSA)—a bioactive ingredient of the medicinal plant, Bupleurum falcatum L.—potently and effectively reduced operant self-administration of chocolate and reinstatement of chocolate-seeking behavior in rats. The present study was designed to assess whether the protective properties of SSA on addictive-like, food-related behaviors generalize to a rat model of overeating of palatable food. To this end, rats were habituated to feed on a standard rat chow for 3 h/day; every 4 days, the 3-h chow-feeding session was followed by a 1-h availability of highly palatable, calorie-rich Danish butter cookies or Oreo chocolate cookies. Even though fed, rats consumed large amounts of cookies; intake of calories from cookies (consumed in 1 h) was even larger than that of calories from chow (consumed in 3 h). SSA (0, 0.25, 0.5, and 1 mg/kg, i.p.) was administered 10 min before cookie presentation. Treatment with SSA resulted in a dose-related decrease in intake of both butter and chocolate cookies. Administration of the cannabinoid CB1 receptor antagonist/inverse agonist, rimonabant (0, 0.3, 1, and 3 mg/kg, i.p.; tested as reference compound), produced a similar reduction in intake of butter cookies. These results (a) contribute to the set-up and validation of a rat model of overeating, characterized by the intake of large amounts of unnecessary calories and (b) provide an additional piece of evidence to the anorectic profile of SSA in rats

The Sardinia Radio Telescope . From a technological project to a radio observatory

Context. The Sardinia Radio Telescope (SRT) is the new 64 m dish operated by the Italian National Institute for Astrophysics (INAF). Its active surface, comprised of 1008 separate aluminium panels supported by electromechanical actuators, will allow us to observe at frequencies of up to 116 GHz. At the moment, three receivers, one per focal position, have been installed and tested: a 7-beam K-band receiver, a mono-feed C-band receiver, and a coaxial dual-feed L/P band receiver. The SRT was officially opened in September 2013, upon completion of its technical commissioning phase. In this paper, we provide an overview of the main science drivers for the SRT, describe the main outcomes from the scientific commissioning of the telescope, and discuss a set of observations demonstrating the scientific capabilities of the SRT. Aims: The scientific commissioning phase, carried out in the 2012-2015 period, proceeded in stages following the implementation and/or fine-tuning of advanced subsystems such as the active surface, the derotator, new releases of the acquisition software, etc. One of the main objectives of scientific commissioning was the identification of deficiencies in the instrumentation and/or in the telescope subsystems for further optimization. As a result, the overall telescope performance has been significantly improved. Methods: As part of the scientific commissioning activities, different observing modes were tested and validated, and the first astronomical observations were carried out to demonstrate the science capabilities of the SRT. In addition, we developed astronomer-oriented software tools to support future observers on site. In the following, we refer to the overall scientific commissioning and software development activities as astronomical validation. Results: The astronomical validation activities were prioritized based on technical readiness and scientific impact. The highest priority was to make the SRT available for joint observations as part of European networks. As a result, the SRT started to participate (in shared-risk mode) in European VLBI Network (EVN) and Large European Array for Pulsars (LEAP) observing sessions in early 2014. The validation of single-dish operations for the suite of SRT first light receivers and backends continued in the following year, and was concluded with the first call for shared-risk early-science observations issued at the end of 2015. As discussed in the paper, the SRT capabilities were tested (and optimized when possible) for several different observing modes: imaging, spectroscopy, pulsar timing, and transients

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p

A New Challenge for Radiologists: Radiomics in Breast Cancer

Introduction. Over the last decade, the field of medical imaging experienced an exponential growth, leading to the development of radiomics, with which innumerable quantitative features are obtained from digital medical images, providing a comprehensive characterization of the tumor. This review aims to assess the role of this emerging diagnostic tool in breast cancer, focusing on the ability of radiomics to predict malignancy, response to neoadjuvant chemotherapy, prognostic factors, molecular subtypes, and risk of recurrence. Evidence Acquisition. A literature search on PubMed and on Cochrane database websites to retrieve English-written systematic reviews, review articles, meta-analyses, and randomized clinical trials published from August 2013 up to July 2018 was carried out. Results. Twenty papers (19 retrospective and 1 prospective studies) conducted with different conventional imaging modalities were included. Discussion. The integration of quantitative information with clinical, histological, and genomic data could enable clinicians to provide personalized treatments for breast cancer patients. Current limitations of a routinely application of radiomics are represented by the limited knowledge of its basics concepts among radiologists and by the lack of efficient and standardized systems of feature extraction and data sharing

Suppressing effect of CMPPE, a new positive allosteric modulator of the GABAB receptor, on alcohol self-administration and reinstatement of alcohol seeking in rats

Positive allosteric modulators (PAMs) of the GABAB receptor constitute a class of pharmacological agents gaining increasing attention in the alcohol research field because of their ability to suppress several alcohol-related behaviors in rodents. CMPPE is a novel GABAB PAM, still limitedly characterized in vivo. It was therefore of interest to test its ability to affect operant, oral self-administration of alcohol and cueinduced reinstatement of alcohol seeking in alcohol-preferring rats. To this end, female Sardinian alcohol-preferring (sP) rats were trained to lever-respond for alcohol (15% v/v) under the fixed ratio (FR) 5 (FR5) schedule of reinforcement. Once lever-responding had stabilized, rats were exposed to test sessions (under the FR5 [Experiment 1] and progressive ratio [PR; Experiment 2] schedules of reinforcement) preceded by treatment with CMPPE (0, 2.5, 5, and 10 mg/kg; intraperitoneally [i.p.]). In Experiment 3, once lever-responding had stabilized, rats underwent an extinction responding phase and then a single reinstatement session during which lever-responding was resumed by the non-contingent presentation of a complex of alcohol-associated cues; CMPPE (0, 2.5, 5, and 10 mg/kg; i.p.) was administered before the reinstatement session. Selectivity of CMPPE actionwas assessed by evaluating the effect of CMPPE (0, 2.5, 5, and 10 mg/kg; i.p.) on self-administration of a chocolate solution in male Wistar rats (Experiment 4). In Experiments 1 and 2, treatment with 5 and 10 mg/kg CMPPE reduced lever-responding and breakpoint for alcohol. In Experiment 3, treatment with 5 and 10 mg/kg CMPPE suppressed reinstatement of alcohol seeking. In Experiment 4, no dose of CMPPE affected lever-responding for the chocolate solution. These results extend to CMPPE the ability of all previously tested GABAB PAMs to affect alcohol-motivated behaviors in rodents and confirm that these effects are a shared feature of the entire class of GABAB PAMs. This conclusion is of relevance in view of the forthcoming transition of GABAB PAMs to clinical testing

The GABAB receptor positive allosteric modulator COR659: In vitro metabolism, in vivo pharmacokinetics in rats, synthesis and pharmacological characterization of metabolically protected derivatives

We report an in vitro phase I metabolism study on COR659 (1), a 2-acylaminothiophene derivative able to suppress alcohol and chocolate self-administration in rats, likely via positive allosteric modulation of the GABAB receptor and antagonism/inverse agonism at the cannabinoid CB1 receptor. Given the identification of the methyl ester group at C-3 of the thiophene ring as a metabolic soft spot, we also report the chemical optimization project aimed to balance metabolic stability with in vitro and in vivo potency on a set of 3-substituted COR659 analogues. High performance liquid chromatography coupled to tandem and high resolution mass spectrometry was employed for the characterization of in vitro metabolism and in vivo pharmacokinetics of COR659 in rats. In vitro [35S]GTPγS binding assays on stimulated GABAB and CB1 receptors, in combination with alcohol and chocolate self-administration experiments in rats, were employed to assess the pharmacological profile of this novel set of analogues, using COR659 as reference compound. Eight metabolites of COR659 were discovered in liver microsomal incubates; two of them (M1, M2) were identified by comparison with synthetic reference standards. M2, oxidation product of methyl group at C-5 of the thiophene ring, was a major metabolite in vitro, but showed a low systemic exposure in vivo. M1, cleavage product of the methyl ester group at C-3, revealed in vitro an unusual mechanism of metabolism by a NADPH- dependent route and, in vivo, it maintained high and persistent levels in plasma, which could represent a po- tential pharmacokinetic and toxicological issue. In the novel set of COR659 analogues, those bearing branched alkyl substituents on the ester group, showed an improved in vitro metabolic stability (2–4), had an in vitro GABAB PAM (2–4) and/or CB1 partial agonist/ antagonist profile (2–3) and maintained the ability to reduce alcohol (2–4) and/or chocolate (4) self-adminis- tration in rats. Both PK and PD data ruled out any involvement of metabolite M1 in the in vivo potency of COR659 and 4. The present results, therefore, highlight the importance to design and synthesize novel compounds endowed with the dual activity profile and devoid of metabolic liabilities

Accidental parathyroidectomy as a risk factor for postoperative hypocalcemia in thyroid surgery

Introduction Hypocalcemia is the most common complication in thyroid surgery. The identification of risk factors is useful toavoid postoperative hypocalcemia and prolonged hospital stay in patients who underwent total thyroidectomy. The aim of this study was to evaluate the impact of accidental parathyroidectomy during thyroidectomy on the postoperative calcemic status of the patients. Materials and Methods Clinical and pathological data of 102 patients who underwent total thyroidectomy were reviewed. We compared postoperative serum calcium levels of 51 patients without accidental removal of the parathyroids (group A) with those of 51 patients with unintentional parathyroidectomy (group B). Furthermore, calcemic levels were stratified in relation to the number of parathyroids accidentally removed. Results Biochemical postoperative hypocalcemia was observed in 40 (39%) patients overall: eleven of them belonged to Group A and 29 to Group B. The mean value of postoperative calcemia was 8.5 mg/dL in group A and 7.9 mg/dL in Group B. Patients with one parathyroid excised presented hypocalcemia in 50% of cases, while biochemical hypocalcemia was observed in all patients with more than one gland excised. Conclusion Biochemical postoperative hypocalcemia was observed in 40 (39%) patients overall: eleven of them belonged to Group A and 29 to Group B. The mean value of postoperative calcemia was 8.5 mg/dL in group A and 7.9 mg/dL in Group B. Patients with one parathyroid excised presented hypocalcemia in 50% of cases, while biochemical hypocalcemia was observed in all patients with more than one gland excised.</br