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Introduction The detection in mild cognitive impairment (MCI) of metabolic alterations suggestive of depression and/or of evolution to dementia. Material and methods Sixty-nine MCI patients underwent clinical and imaging evaluation including position emission tomography/computed tomography with fluorodeoxy-glucose (FDG-PET/CT). Results The metabolism mean values in parietal, temporal and pre-cuneus areas were lower in subjects who evolved to dementia, and in frontal and in anterior cingulate areas in depressed subjects. Abnormal metabolism values were higher in the frontal and parietal lobes, and in the precuneus in subjects who evolved to dementia independently from depression. Conclusions In MCI FDG-PET/CT abnormality patterns suggest the presence of depression or the evolution to dementia.

High voltage transmission lines are crucial infrastructure that are demanded to supply an increasing request of electric energy. In the design and operations stages, sag represents a key parameter which must respect specific constraints. Therefore, sag continuous monitoring is becoming essential to guarantee the correct functioning of the line and to optimize the current flow. Different solutions have been proposed in literature, but they are still lacking efficiency and reliability to be used during operations. In this work, a simple and efficient method, based on conductor parabolic approximation, is developed and used to compute the sag through the measurement of the conductor slope in proximity of the span extremities. The angular measurements are obtained using wireless sensors equipped with MEMS accelerometers developed by authors and employed for HVTL conductor vibration monitoring. The proposed method and its implementation in the monitoring system was tested in a laboratory environment on a real conductor. The values of sag at different tensile loads have been obtained and compared to the measured ones, with satisfactory results according to the accelerometer resolution. The solution developed therefore represents a complete and innovative tool to be adopted in the field to monitor, in real time, both the sag and the level of vibration due to the wind action, allowing to increase the performance reliability of HVTL.

Bridges are strategic infrastructures which are subject to degradation during their lifetime. Therefore, structural health monitoring is becoming an essential tool in this field to drive maintenance activities. Conventional vibration monitoring systems relying on wired sensors present several limitations for continuous monitoring projects on a huge number of structures. In this work, a smart wireless monitoring system is developed for bridge modal identification with the aim of providing an alternative tool to wired sensors in this field. The main peculiarities of the designed wireless accelerometers are the low cost, the ease of installation on the structure, and the long-term autonomy granted by the use of energy harvesting techniques. To assess their measurement performance, some prototypes were installed for a field test on a railway bridge and significant data were acquired. Through the processing of the collected data, bridge main natural frequencies were estimated, and their values were in good agreement with the reference ones obtained with a conventional system. The assessment of the developed solution paves the way to the instrumentation of many bridges with the aim of performing continuous monitoring activities using simple diagnostic indicators, such as the variation of frequencies in time.

Abstract d-Serine acts as a co-agonist of N-methyl-d-aspartate receptors (NMDAR) which appear overactivated in AD, while d-aspartate is a modulatory molecule acting on NMDAR as a second agonist. The aim of this work is to clarify whether the levels of these d-amino acids in serum are deregulated in AD, with the final goal to identify novel and precocious biomarkers in AD. Serum levels of l- and d-enantiomers of serine and aspartate were determined by HPLC using a pre-column derivatization procedure and a selective enzymatic degradation. Experimental data obtained from age-matched healthy subjects (HS) and AD patients were statistically evaluated by considering age, gender, and disease progression, and compared. Minor changes were apparent in the serum l- and d-aspartate levels in AD patients compared to HS. A positive correlation for the d-serine level and age was apparent in the AD cohort. Notably, the serum d-serine level and the d-/total serine ratio significantly increased with the progression of the disease. Gender seems to have a minor effect on the levels of all analytes tested. This work proposes that the serum d-serine level and d-/total serine ratio values as novel and valuable biomarkers for the progression of AD: the latter parameter allows to discriminate CDR 2 and CDR 1 patients from healthy (CDR 0) individuals.

Alzheimer’s Disease is the most common cause in the world of progressive cognitive decline. Although many modifiable and non-modifiable risk factors have been proposed, in recent years, neuroinflammation has been hypothesized to be an important contributing factor of Alzheimer’s Disease pathogenesis. Neuroinflammation can occur through the combined action of the Central Nervous System resident immune cells and adaptive peripheral immune system. In the past years, immunotherapies for neurodegenerative diseases have focused wrongly on targeting protein aggregates Aβ plaques and NFT treatment. The role of both innate and adaptive immune cells has not been fully clarified, but several data suggest that immune system dysregulation plays a key role in neuroinflammation. Recent studies have focused especially on the role of the adaptive immune system and have shown that inflammatory markers are characterized by increased CD4+ Teff cells’ activities and reduced circulating CD4+ Treg cells. In this review, we discuss the key role of both innate and adaptive immune systems in the degeneration and regeneration mechanisms in the pathogenesis of Alzheimer’s Disease, with a focus on how the crosstalk between these two systems is able to sustain brain homeostasis or shift it to a neurodegenerative condition.

In a world accelerating the energy transition towards renewable sources, high voltage transmission lines represent strategic infrastructure for power delivery. Being slender and low-damped structures, HVTL conductors are affected by wind-induced vibrations that can lead to severe fatigue issues in conductors and other components. Vibration monitoring could represent a key activity to assess the safety level of the line and perform condition-based maintenance activities. This work proposes an innovative approach based on the knowledge of the physical phenomena and smart technological devices. A wireless monitoring system based on MEMS accelerometers and energy harvesting techniques has been designed to measure the fymax parameter in the field, which represents a fatigue indicator useful to identify the different wind-induced phenomena and assess the conductors’ strain level. A field test on a Canadian transmission line was used in the check of the efficiency of the system and collection of significant data. Vibrations due to vortex shedding were identified with a maximum value of fymax = 50 m/s, while subspan oscillation and galloping were not observed. We show the novel method can detect the different wind-induced phenomena and pave the way to the development of suitable software able to compute a conductor’s residual fatigue life.

Several studies focused on the role of vitamin D (vitD) in pain chronification. This study focused on vitD level and pain chronification and extension in headache disorders. Eighty patients with primary headache underwent neurological examination, laboratory exams, including serum calcifediol 25(OH)D, and headache features assessment along with three questionnaires investigating depression, anxiety, and allodynia. The 86.8% of the population had migraine (48% episodic and 52% chronic). The 44.1% of patients had extracranial pain, and 47.6% suffered from allodynia. A vitD deficit, namely a serum 25(OH)D level

Abstract Objectives Excessive daytime sleepiness (EDS) affects a large percentage of Parkinson's disease (PD) patients, and it is enhanced by dopamine agonist drugs. Currently, there is no treatment of choice for EDS in PD. Our aim was to check the clinical impression that some patients who were given selegiline, a selective inhibitor of monoamine oxidase B, experienced an improvement in their daytime somnolence. Methods In the present study, we retrospectively identified 45 Parkinson's disease patients (21 females and 24 males) among those referred to the PD Center in Varese that (a) showed excessive daytime sleepiness, usually developed after the introduction of a dopamine agonist, (b) were given selegiline 10 mg to improve their treatment schedule independently of excessive sleepiness, and (c) in whom the Epworth Sleepiness Scale (ESS) and the Parkinson's Disease Sleep Scale (PDSS) scores were available both before and 3 months after the introduction of selegiline. Results We compared the corresponding scores (ESS, PDSS, and UPDRS III) evaluated before and 3 months after the introduction of selegiline by the nonparametric Mann–Whitney U test: The differences showed a statistically significant improvement of somnolence but no change in the UPDRS III scores. Conclusion Despite some limitations, our data suggest that selegiline may be a valuable add‐on therapy in PD patients to reduce their daytime somnolence.

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment.

Rotary transformers are adopted to transfer energy from primary to secondary in situations in which the two sides are in relative rotation. These devices are cylindrical transformers with two cores and the corresponding winding separated by an air gap. Their employment became quite convenient with the availability of power electronics, allowing the operation of electrical systems at relatively high frequencies. In particular, this paper proposes the design of a light and efficient transformer which can be used in applications involving large shafts. Moreover, a sliced arrangement for the magnetic core is proposed together with the experimental validation of this solution on a reduced-size prototype.

In the context of the fourth revolution in healthcare technologies, leveraging monitoring and personalization across different domains becomes a key factor for providing useful services to maintain and promote well-being. This is even more crucial for older people, with aging being a complex multi-dimensional and multi-factorial process which can lead to frailty. The NESTORE project was recently funded by the EU Commission with the aim of supporting healthy older people to sustain their well-being and capacity to live independently. It is based on a multi-dimensional model of the healthy aging process that covers physical activity, nutrition, cognition, and social activity. NESTORE is based on the paradigm of the human-in-the-loop cyber-physical system that, exploiting the availability of Internet of Things technologies combined with analytics in the cloud, provides a virtual coaching system to support healthy aging. This work describes the design of the NESTORE methodology and its IoT architecture. We first model the end-user under several domains, then we present the NESTORE system that, analyzing relevant key-markers, provides coaching activities and personalized feedback to the user. Finally, we describe the validation strategy to assess the effectiveness of NESTORE as a coaching platform for healthy aging.

During the COVID-19 outbreak, the Neurology and Stroke Unit (SU) of the hospital of Varese had to serve as a cerebrovascular hub, meaning that the referral area for the unit doubled. The number of beds in the SU was increased from 4 to 8. We took advantage of the temporary suspension of the out-patient clinic and reshaped our activity to guarantee the 24/7 availability of recombinant tissue Plasminogen Activator (rtPA) intravenous therapy (IVT) in the SU, and to ensure we were able to admit patients to the SU as soon as they completed endovascular treatment (EVT). In 42 days, 46 stroke patients were admitted to our hospital, and 34.7% of them underwent IVT and/or EVT, which means that we treated 0.38 patients per day; in the baseline period from 2016 to 2018, these same figures had been 23.5% and 0.23, respectively. The mean values of the door-to-first CT/MRI and the door-to-groin puncture, but not of the onset-to-door and the door-to-needle periods were slightly but significantly longer than those observed in the baseline period in 276 patients. On an individual basis, only one patient exceeded the door-to-groin puncture time limit computed from the baseline period by about 10 min. None of the patients had a major complication following the procedures. None of the patients was or became SARS-CoV2 positive. In conclusion, we were able to manage the new hub-and-spoke system safely and without significant delays. The reshaping of the SU was made possible by the significant reduction of out-patient activity. The consequences of this reduction are still unknown but eventually, this emergency will suggest ways to reconsider the management and the allocation of health system resources.

Synthetic microbial consortia have been increasingly utilized in biotechnology and experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, though, a quantitative understanding of the conditions that make this possible, and of the trade-offs due to the concurrent growth of multiple species, is still limited. In this work, we contribute to filling this gap by the investigation of a known prototypical synthetic consortium. A first E. coli strain, producing a heterologous protein, is sided by a second E. coli strain engineered to scavenge toxic byproducts, thus favoring the growth of the producer at the expense of diverting part of the resources to the growth of the cleaner. The simplicity of the consortium is ideal to perform an in depth-analysis and draw conclusions of more general interest. We develop a coarse-grained mathematical model that quantitatively accounts for literature data from different key growth phenotypes. Based on this, assuming growth in chemostat, we first investigate the conditions enabling stable coexistence of both strains and the effect of the metabolic load due to heterologous protein production. In these conditions, we establish when and to what extent the consortium outperforms the producer alone in terms of productivity. Finally, we show in chemostat as well as in a fed-batch scenario that gain in productivity comes at the price of a reduced yield, reflecting at the level of the consortium resource allocation trade-offs that are well-known for individual species.

Nowadays, railway freight transportation is becoming more and more crucial since it represents the best alternative to road transport in terms of sustainability, pollution, and impact on the environment and on public health. Upgrading the potentiality of this kind of transportation, it would be possible to avoid delays in goods deliveries due to road accidents, traffic jams, and other situation occurring on roads. A key factor in this framework is therefore represented by monitoring and maintenance of the train components. Implementing a real time monitoring of the main components and a predictive maintenance approach, it would be possible to avoid unexpected breakdowns and consequently unavailability of wagons for unscheduled repair activities. As highlighted in recent statistical analysis, one of the elements more critical in case of failure is represented by the brake system. In this view, a real time monitoring of pressure values in some specific points of the system would provide significant information on its health status. In addition, since the braking actions are related to the load present on the convoy, thanks to this kind of monitoring, it would be possible to appreciate the different behavior of the system in case of loaded and unloaded trains. This paper presented an innovative wireless monitoring system to perform brake system diagnostics. A low-power system architecture, in terms of energy harvesting and wireless communication, was developed due to the difficulty in applying a wired monitoring system to a freight convoy. The developed system allows acquiring brake pressure data in critical points in order to verify the correct behavior of the brake system. Experimental results collected during a five-month field test were provided to validate the approach.

Abstract Background Proteins within the cytoplasmic membrane display distinct localization patterns and arrangements. While multiple models exist describing the dynamics of membrane proteins, to date, there have been few systematic studies, particularly in bacteria, to evaluate how protein size, number of transmembrane domains, and temperature affect their diffusion, and if conserved localization patterns exist. Results We have used fluorescence microscopy, single-molecule tracking (SMT), and computer-aided visualization methods to obtain a better understanding of the three-dimensional organization of bacterial membrane proteins, using the model bacterium Bacillus subtilis. First, we carried out a systematic study of the localization of over 200 B. subtilis membrane proteins, tagged with monomeric mVenus-YFP at their original gene locus. Their subcellular localization could be discriminated in polar, septal, patchy, and punctate patterns. Almost 20% of membrane proteins specifically localized to the cell poles, and a vast majority of all proteins localized in distinct structures, which we term microdomains. Dynamics were analyzed for selected membrane proteins, using SMT. Diffusion coefficients of the analyzed transmembrane proteins did not correlate with protein molecular weight, but correlated inversely with the number of transmembrane helices, i.e., transmembrane radius. We observed that temperature can strongly influence diffusion on the membrane, in that upon growth temperature upshift, diffusion coefficients of membrane proteins increased and still correlated inversely to the number of transmembrane domains, following the Saffman–Delbrück relation. Conclusions The vast majority of membrane proteins localized to distinct multimeric assemblies. Diffusion of membrane proteins can be suitably described by discriminating diffusion coefficients into two protein populations, one mobile and one immobile, the latter likely constituting microdomains. Our results show there is high heterogeneity and yet structural order in the cell membrane, and provide a roadmap for our understanding of membrane organization in prokaryotes.

Abstract Background Parkinson’s disease (PD) affects an estimated 7 to 10 million people worldwide, and only symptomatic treatments are presently available to relieve the consequences of brain dopaminergic neurons loss. Neuronal degeneration in PD is the consequence of neuroinflammation in turn influenced by peripheral adaptive immunity, with CD4+ T lymphocytes playing a key role. CD4+ T cells may however acquire proinflammatory phenotypes, such as T helper (Th) 1 and Th17, as well as anti-inflammatory phenotypes, such as Th2 and the T regulatory (Treg) one, and to what extent the different CD4+ T cell subsets are imbalanced and their functions dysregulated in PD remains largely an unresolved issue. Methods We performed two cross-sectional studies in antiparkinson drug-treated and drug-naïve PD patients, and in age- and sex-matched healthy subjects. In the first one, we examined circulating Th1, Th2, Th17, and in the second one circulating Treg. Number and frequency of CD4+ T cell subsets in peripheral blood were assessed by flow cytometry and their functions were studied in ex vivo assays. In both studies, complete clinical assessment, blood count and lineage-specific transcription factors mRNA levels in CD4+ T cells were independently assessed and thereafter compared for their consistency. Results PD patients have reduced circulating CD4+ T lymphocytes, due to reduced Th2, Th17, and Treg. Naïve CD4+ T cells from peripheral blood of PD patients preferentially differentiate towards the Th1 lineage. Production of interferon-γ and tumor necrosis factor-α by CD4+ T cells from PD patients is increased and maintained in the presence of homologous Treg. This Th1-biased immune signature occurs in both drug-naïve patients and in patients on dopaminergic drugs, suggesting that current antiparkinson drugs do not affect peripheral adaptive immunity. Conclusions The complex phenotypic and functional profile of CD4+ T cell subsets in PD patients strengthen the evidence that peripheral adaptive immunity is involved in PD, and represents a target for the preclinical and clinical assessment of novel immunomodulating therapeutics.

This paper proposes a model-based two-degree-of-freedom (2DOF) speed control for a medium voltage (MV) variable speed drive (VSD) connected to a centrifugal compressor (CC) train. Torsional mode excitations in the drive shaft due to converter switching behaviour are considered. An effective description of the harmonics transfer is proposed. The tuning strategy aims to optimize the tracking behaviour of the step and ramp command, taking care of critical speed excitations. The stability of the closed-loop dynamics against time delay and drive parameter variations are studied by means of Nyquist diagrams and time-domain simulations. A descriptive method for the process damping behaviour is proposed. The control strategy is evaluated through simulations as well as an experimental setup, based on a hardware in the loop (HIL) in a master–slave configuration.

Abstract Background Chronic immune sensory polyradiculopathy (CISP) identifies a progressive acquired peripheral dysimmune neuropathy recognized as a chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant. We describe a young woman with a thirteen-year history of CISP with a belated variable response to intravenous immunoglobulin (IVIG) and an almost erratic anticipation of symptoms between IVIG cycles. The association of IVIG and corticosteroids, immunosuppressants, plasmapheresis, did not lead to clinical improvement and was characterized by significant side effects. We evaluated a combined clinical and somatosensory evoked potentials (SSEPs) approach aimed to identify possible predictive parameters concerning the effect and duration of each IVIG administration. Neurologic disability was evaluated using INCAT - Overall Disability Sum Score (INCAT-ODSS). Case presentation A 30-year-old woman presented on 2004 for the subacute onset of asymmetric paresthesias in the lower limbs over the previous six months. The symptoms had been relapsing-remitting during the first four months, followed by a slow progression, resulting in limbs ataxia and a progressive gait disturbance requiring Canadian crutches. Motor and sensory nerve conduction studies and electromyographic evaluation were into normal limits. Median SSEPs were normal, while tibial SSEPs were characterised by the bilateral absence of both lumbar and cortical responses. Cerebrospinal fluid detected an increased protein concentration, while spinal MRI showed a pronounced thickening of the sacral nerve roots, together with a tube-shaped enlargement. These findings led to the diagnosis of CISP and the patient was treated with IVIG reaching a stable remission over the following 9 years. In early 2014, the patient began to show a variable response to treatment with erratic anticipation of sensory disturbances, and a more pronounced walking disability: corticosteroids, plasmapheresis, mycophenolate mofetil and cyclophosphamide were uneffective and burdened by relevant side effects. To better assess the response to IVIG in terms of time-effect, consistency and duration, we have combined a scheduled clinical and SSEPs evaluation during and after each IVIG cycle. Conclusions The correlation between the neurophysiological data and the INCAT-ODSS scores has allowed the modulation of IVIG cycles with a significant reduction of the clinical fluctuations and disability. SSEPs may therefore represent an useful and recommended additional aid for the treatment schedule of this rare clinical form.

Smart monitoring systems are currently gaining more attention and are being employed in several technological areas. These devices are particularly appreciated in the structural field, where the collected data are used with purposes of real time alarm generation and remaining fatigue life estimation. Furthermore, monitoring systems allow one to take advantage of predictive maintenance logics that are nowadays essential tools for mechanical and civil structures. In this context, a smart wireless node has been designed and developed. The sensor node main tasks are to carry out accelerometric measurements, to process data on-board, and to send wirelessly synthetic information. A deep analysis of the design stage is carried out, both in terms of hardware and software development. A key role is played by energy harvesting integrated in the device, which represents a peculiar feature and it is thanks to this solution and to the adoption of low power components that the node is essentially autonomous from an energy point of view. Some prototypes have been assembled and tested in a laboratory in order to check the design features. Finally, a field test on a real structure under extreme weather conditions has been performed in order to assess the accuracy and reliability of the sensors.

Marco Mauri, Simona Corbetta, Cristina Pianezzola, Elena Ambrosoni, Giulio Riboldazzi, Giorgio BonoUnit of Neurology, Dept of Clinical Medicine, Ospedale di Circolo – University of Insubria, Varese, ItalyAbstract: Mild parkinsonian signs (MPS) may be found among patients presenting with mild cognitive impairment (MCI), but few data are available about the relation of these signs with the prospective risk for dementia. Our retrospective investigation considered a case-series of 119 MCI subjects followed over a three-year period: their baseline clinical picture has been analyzed in search of correlation between the cognito-motor profile and the final diagnosis. The population included 66 patients with amnesic MCI and 53 with an involvement of other cognitive areas (nonamnesic MCI). MPS were detected in 22 subjects (18.5%). At the first observation, MPS cases showed an higher frequency of nonamnesic MCI and more pronounced deficits at the Trail Making Test (p

Sigma factors control global switches of the genetic expression program in bacteria. Different sigma factors compete for binding to a limited pool of RNA polymerase (RNAP) core enzymes, providing a mechanism for cross-talk between genes or gene classes via the sharing of expression machinery. To analyze the contribution of sigma factor competition to global changes in gene expression, we develop a theoretical model that describes binding between sigma factors and core RNAP, transcription, non-specific binding to DNA and the modulation of the availability of the molecular components. The model is validated by comparison with in vitro competition experiments, with which excellent agreement is found. Transcription is affected via the modulation of the concentrations of the different types of holoenzymes, so saturated promoters are only weakly affected by sigma factor competition. However, in case of overlapping promoters or promoters recognized by two types of sigma factors, we find that even saturated promoters are strongly affected. Active transcription effectively lowers the affinity between the sigma factor driving it and the core RNAP, resulting in complex cross-talk effects. Sigma factor competition is not strongly affected by non-specific binding of core RNAPs, sigma factors and holoenzymes to DNA. Finally, we analyze the role of increased core RNAP availability upon the shut-down of ribosomal RNA transcription during the stringent response. We find that passive up-regulation of alternative sigma-dependent transcription is not only possible, but also displays hypersensitivity based on the sigma factor competition. Our theoretical analysis thus provides support for a significant role of passive control during that global switch of the gene expression program.