From Companion Diagnostics to Theranostics:A New Avenue for Alzheimer's Disease?

The recent literature signals a growing paradigm shift toward integrating therapeutics and diagnostics rather than developing and deploying them separately. In this gradual move toward more effective and personalized medications, companion diagnostics are an intermediate stage. The next step may be "theranostics", in which single chemical entities are developed to deliver therapy and diagnosis simultaneously. This strategy has been successfully exploited in oncology and is now emerging as a possibility for Alzheimer's disease, where its feasibility has caught the attention of researchers from industry and academia. Medicinal chemists do not yet completely understand the nuances of theranostic action and consequently have not yet developed universally validated strategies for developing theranostic clinical applications against Alzheimer's disease. However, given the emerging indications of the potentially enormous benefits that theranostics may bring to the fight against this devastating disease, further rigorous research is warranted

A Systematic Literature Review of User Experience Evaluation Scales for Human-Robot Collaboration

In the last decade, the field of Human-Robot Collaboration (HRC) has received much attention from both research institutions and industries. Robot technologies are in fact deployed in many different areas (e.g., industrial processes, people assistance) to support an effective collaboration between humans and robots. In this transdisciplinary context, User eXperience (UX) has inevitably to be considered to achieve an effective HRC, namely to allow the robots to better respond to the users’ needs and thus improve the interaction quality. The present paper reviews the evaluation scales used in HRC scenarios, focusing on the application context and evaluated aspects. In particular, a systematic review was conducted based on the following questions: (RQ1) which evaluation scales are adopted within the HRI scenario with collaborative tasks?, and (RQ2) how the UX and user satisfaction are assessed?. The records analysis highlighted that the UX aspects are not sufficiently examined in the current HRC design practice, particularly in the industrial field. This is most likely due to a lack of standardized scales. To respond to this recognized need, a set of dimensions to be considered in a new UX evaluation scale were proposed

UX Evaluation of a Tractor Cabin Digital Twin Using Mixed Reality

Understanding user experience (UX) is essential to design engaging and attractive products, so nowadays has emerged an increasingly interest in user- centred design approach; in this perspective, digital technologies such as Virtual Reality (VR) and Mixed Reality (MR) could help designers and engineers to create a digital prototype through which the user feedback can be considered during the product design stage. This research aims at creating an interactive Digital Twin (DT) using MR to enable a tractor driving simulation and involve real users to carry out an early UX evaluation, with the scope to validate the design of the control dashboard through a transdisciplinary approach. MR combines virtual simulation with real physical hardware devices which the user can interact with and have control through both visual and tactile feedback. The result is a MR simulator that combines virtual contents and physical controls, capable of reproducing a plowing activity close to reality. The principles of UX design was applied to this research for a continuous and dynamic UX evaluation during the project development

Ultrasonographic Investigation of Human Fetus Responses to Maternal Communicative and Non-communicative Stimuli

During pregnancy fetuses are responsive to the external environment, specifically to maternal stimulation. During this period, brain circuits develop to prepare neonates to respond appropriately. The detailed behavioral analysis of fetus’ mouth movements in response to mothers’ speech may reveal important aspects of their sensorimotor and affective skills; however, to date, no studies have investigated this response. Given that newborns at birth are capable of responding with matched behaviors to the social signals emitted by the caregiver, we hypothesize that such precocious responses could emerge in the prenatal period by exploiting infants’ sensitivity to their mother’s voice. By means of a two-dimensional (2D) ultrasonography, we assessed whether fetuses at 25 weeks of gestation, showed a congruent mouth motor response to maternal acoustic stimulation. Mothers were asked to provide different stimuli, each characterized by a different acoustic output (e.g. chewing, yawning, nursery rhymes, etc.) and we recorded the behavioral responses of 29 fetuses. We found that, when mothers sang the syllable LA in a nursery rhyme, fetuses significantly increased mouth openings. Other stimuli provided by the mother did not produce other significant changes in fetus’ behavior. This finding suggests that fetuses are sensitive only to specific maternal vocalizations (LA) and that fetal matched responses are rudimentary signs of early mirroring behaviors that become functional in the postnatal period. In conclusion, fetuses seem to be predisposed to respond selectively to specific maternal stimuli. We propose that such responses may play a role in the development of behavioral and emotional attunement with their mothers long before birth

Macro- And Microvascular Functions In Cystic Fibrosis Adults Without Cardiovascular Risk Factors: A Case-Control Study.

Increasing survival from cystic fibrosis show untypical systems involvement, such as cardiocirculatory. In particular, the presence of CFTR in smooth muscle and endothelial cells, systemic inflammation and oxidative stress could explain vascular alterations in these patients. We aimed at noninvasely evaluating macro- and microvascular dysfunction in cystic fibrosis adults without cardiovascular risk factors. Twenty-twoadults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors. All people underwent blood pressure measurement, microvascular function assessment by EndoPAT-2000 device (calculating RH-PAT index) and macrovascular evaluation by pulse wave velocity (PWV). RH-PAT index was significantly lower in patients than in controls (1.74±0.59 vs 2.33±0.34; p<0.001). Thirteen patients of 22 had a value inferior to the threshold of 1.67 (59.1%), while no controls had (p<0.001). Carotid-femoral PWV did not differ between the two groups (5.2±1.5 m/s vs 5.4±1.1; p=0.9), while brachial-ankle one did (11.0±2.2 m/s vs 10.1±0.8 m/s; p=0.04).Adults patients affected by cystic fibrosis show peripheral endothelial dysfunction, which is the first alteration in atherosclerotic phenomenon. Moreover, arterial stiffness measured by PWV unclearly seems to differ respect of healthy people, perhaps because PWV alterations are typical of above 50 years old people. It is unclear what prognostic role of future developing of atherosclerotic disease these findings could be, but it seems evident that cystic fibrosis directly affects cardiovascular system itself

Type 1 neurofibromatosis complicated by pulmonary artery hypertension : a case report

We describe the case of a patient with neurofibromatosis type 1 (NF1) complicated by severe pulmonary aterial hypertension (PAH) ; only seven cases have been reported on this association so far, and PAH seems to be related to the vascular involvement of neurofibromatosis. The histology of our patient’s lung tissue showed thickening of arteries and veins by medial and/or intimal hypertrophy and fibrosis. In order to exclude a familiar PAH, the analysis of the bone morphogenetic protein receptor 2 gene was carried out, but no mutations were found. On the basis of histological findings and of the results of genetic study we believe that PAH was a complication of NF1 in our patient and we suggest to screen patients with NF1 for the presence of PAH by means of trans-thoracic echocardiogram

Discovery of sustainable drugs for neglected tropical diseases: cashew nutshell liquid (CNSL)-based hybrids target mitochondrial function and ATP production in Trypanosoma brucei.

In a search for effective and sustainable treatments for trypanosomiasis, we developed a library of hybrid compounds by merging the structural features of a previously synthesized quinone hit (4) with those of long‐chain phenolic constituents from cashew nut shell liquid (CNSL). CNSL is an agro‐waste product from cashew nut processing factories with great potential as a precursor for the production of drugs. The synthesized compounds were tested against Trypanosoma brucei brucei, including three multi‐drug resistant strains (B48, ISMR1, and aqp2/aqp3‐KO), T. congolense, and a human cell line (HFF). The most potent activity was found against T. b. brucei, the causative agent of African trypanosomiasis. Shorter‐chain derivatives were more active than the starting hit in parasite growth inhibition, displaying rapid trypanocidal activity with low micromolar EC50 values, but no discernable toxicity on human cell lines. Preliminary studies probing their mode of action on trypanosomes showed depletion of cellular ATP, followed by the depolarization of the mitochondrial membrane and ultrastructural damage to the mitochondrion. This was accompanied by the production of high levels of reactive oxygen species. We envisage that such hybrid compounds, obtained from renewable and inexpensive material, might be promising bio‐based, sustainable hits for anti‐trypanosomatid drug discovery

A PM10 chemically characterised nation-wide dataset for Italy. Geographical influence on urban air pollution and source apportionment

: Urban textures of the Italian cities are peculiarly shaped by the local geography generating similarities among cities placed in different regions but comparable topographical districts. This suggested the following scientific question: can such different topographies generate significant differences on the PM10 chemical composition at Italian urban sites that share similar geography despite being in different regions? To investigate whether such communalities can be found and are applicable at Country-scale, we propose here a novel methodological approach. A dataset comprising season-averages of PM10 mass concentration and chemical composition data was built, covering the decade 2005-2016 and referring to urban sites only (21 cities). Statistical analyses, estimation of missing data, identification of latent clusters and source apportionment modelling by Positive Matrix Factorization (PMF) were performed on this unique dataset. The first original result is the demonstration that a dataset with atypical time resolution can be successfully exploited as an input matrix for PMF obtaining Country-scale representative chemical profiles, whose physical consistency has been assessed by different tests of modelling performance. Secondly, this dataset can be considered a reference repository of season averages of chemical species over the Italian territory and the chemical profiles obtained by PMF for urban Italian agglomerations could contribute to emission repositories. These findings indicate that our approach is powerful, and it could be further employed with datasets typically available in the air pollution monitoring networks