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Objectives Lower limb deformities in children need careful orthopedic evaluation to distinguish physiological forms from pathological ones. X-linked hypophosphatemia (XLH) is a rare hereditary condition caused by PHEX gene mutations where tibial varum can be the first sign. Case presentation We report a family presenting with severe tibial varum, harbouring a rare PHEX intron mutation, c.1586+6T>C. This is the first clinical description available in literature for this variant. Despite the previous prediction of a mild phenotype in functional study, our patients showed important bone deformities, rickets and impaired growth since infancy followed by severe bone pain, hearing loss and reduced life quality in adulthood. Burosumab therapy improved biochemical and radiological findings in children and ameliorated quality of life in adults. Conclusions This case demonstrated c.1586+6T>C causes a severe XLH phenotype, responsive to Burosumab. Familial genetic screening, enlarged to intronic region analysis, when XLH is suspected, allows precocious diagnosis to start timely the appropriate treatment.

ObjectiveTo investigate monoaminergic network abnormalities in patients with multiple sclerosis (MS) according to their fatigue and depressive status through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on resting state (RS) functional MRI (fMRI).MethodsIn this prospective study, 213 patients with MS (mean age=40.6±12.5 years; 94/119 men/women; 153 relapsing-remitting; 60 progressive) and 62 healthy controls (HCs, mean age=39.0±10.4 years; 30/32 men/women) underwent neurological, fatigue, depression and RS fMRI assessment. Patterns of dopamine, norepinephrine-related and serotonin-related RS functional connectivity (FC) were derived by ICA, constrained to PET atlases for dopamine, norepinephrine and serotonin transporters, obtained in HCs’ brain.ResultsCompared with HCs, patients with MS showed abnormalities in all three explored monoaminergic networks, mostly with decreased RS FC within PET-guided monoaminergic networks in frontal regions and subcortical areas including the cerebellum and thalamus, and increased RS FC in temporo-parieto-occipital cortical areas, including bilateral precunei.MS-related fatigue was associated with decreased RS FC within the PET-guided dopamine network in the left thalamus and left cerebellum, and with increased RS FC within the PET-guided serotonin network in the left middle occipital gyrus. MS-related depression was associated with more distributed abnormalities involving the three explored monoaminergic networks, resulting in overall reduced RS FC in the frontal lobe, limbic areas and the precuneus.ConclusionsPatients with MS present diffuse dysregulation in the monoaminergic networks. Specific alterations in these networks were associated with fatigue and depression, providing a pathological marker for these bothersome symptoms and putative targets for their treatment.

Objective We aim to evaluate 3-year effects of ocrelizumab (humanized anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS)) on lymphocytes, neutrophils and immunoglobulins: (1) when compared with pre-infusion assessment; (2) over the course of treatment; and (3) possible clinical correlates of the observed immunological modifications. Methods This real-world observational cohort study has been conducted on prospectively collected data from 78 MS patients (mean age 47.8 ± 10.5 years; females 48.7%) commencing on ocrelizumab from 2018, with mean follow-up of 36.5 ± 6.8 months. Clinical data and blood samples were collected every three months. Total lymphocyte count and subpopulations were assessed on peripheral blood using flow cytometry. Serum immunoglobulins were evaluated with nephelometry. Results When compared with pre-infusion values, we observed reduction of total, CD19 and CD20 lymphocyte counts; however, after the first infusion, their levels remained substantially stable. Over time we observed a progressive reduction of CD8 lymphocytes, while no changes were observed for CD4, CD27, CD3CD27, and CD19CD27. After the first infusion, we observed reduction in IgG, which further decreased during the follow-up. Higher probability of EDSS progression was associated with reduced modulation of CD8 lymphocytes. Interpretation Ocrelizumab affects both humoral and cellular immune responses. Disability progression over the follow-up was associated with lower CD8 cytotoxic T-lymphocyte reduction. Changes in humoral response are immediate and sustained, while modulation of cellular immunity occurs progressively through regular re-treatment, and is related to clinical stability.

We aimed to investigate abnormal time-varying functional connectivity (FC) for thalamic sub-regions in multiple sclerosis (MS) and their clinical, cognitive and MRI correlates. Eighty-nine MS patients (49 relapsing-remitting [RR] MS; 40 progressive [P] MS) and 53 matched healthy controls underwent neurological, neuropsychological and resting state fMRI assessment. Time-varying connectivity (TVC) was quantified using sliding-window seed-voxel correlation analysis. Standard deviation of FC across windows was taken as measure of TVC, while mean connectivity across windows expressed static FC. MS patients showed reduced TVC vs controls between most of thalamic sub-regions and fronto-temporo-occipital regions. At the same time, they showed increased static FC between all thalamic sub-regions and structurally connected cortico-subcortical regions. TVC reduction was mainly driven by RRMS; while PMS exhibited a variable pattern of TVC abnormalities, characterized by reduced TVC between frontal/motor thalamic seeds and default-mode network areas and increased TVC vs controls/RRMS between posterior thalamic sub-regions and occipito-temporo-insular cortices, associated with severity of clinical disability. Compared with controls, both cognitively preserved and impaired patients showed reduced TVC between anterior thalamic sub-regions and frontal cortex. Cognitively impaired patients also showed increased TVC of the right postcentral thalamic sub-region with the cingulate cortex and postcentral gyrus vs both controls and cognitively preserved patients. Divergent patterns of TVC thalamic abnormalities were found between RRMS and PMS patients. TVC reduction in RRMS may represent the attempt of thalamic network to keep with stable connections. Conversely, increased TVC of posterior thalamic sub-regions characterized PMS and cognitively impaired MS, possibly reflecting maladaptive mechanisms.

Functional neurological disorder (FND) is frequently encountered in clinical practice but commonly misdiagnosed, which might lead to higher direct costs for the health care system. The investigators analyzed the direct costs associated with the diagnosis of FND compared with costs associated with other neurological conditions and explored possible cost trends related to the clinical and demographic features of FND.Consecutive patients attending a general neurology clinic were recruited and underwent a structured assessment aimed to collect information pertaining to their demographic and clinical characteristics, as well as data regarding their prior diagnostic processes (e.g., the number of consulted specialists, number and type of investigations, emergency department visits, etc.). The costs were hence calculated and compared between the study groups.A total of 155 consecutive patients were recruited; of these, 18.6% had FND, 55.84% had one or more other neurological disorder (OND), and 27.10% presented with comorbid FND and OND. The total prediagnostic costs (in euros [€]) were higher in the FND group compared with the OND group (median=€289, interquartile range [IQR] €385 vs. median=€98, IQR €216; Mann-Whitney U=879.5, p=0.04). There was a higher diagnostic delay in the FND group compared with the OND group (median=48 months, IQR 60 months vs. median=12 months, IQR 6 months; Mann-Whitney U=162.00, p0.01). Diagnostic delay significantly correlated with the total costs in the entire study sample (Spearman's ρ=0.25, p=0.003) but more strongly in the FND group (Spearman's ρ=0.81, p0.001). In the FND group, higher numbers of investigations and costs were associated with the presence of a physiological or psychological trigger and multiple symptoms.Delayed diagnosis of FND significantly affects health care system costs, and raising awareness about FND to improve the diagnostic process and outcomes is necessary.

Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p&nbsp

Moving masses are of interest in many applications of structural dynamics, soliciting in the last decades a vast debate in the scientific literature. However, despite the attention devoted to the subject, to the best of the authors’ knowledge, there is a lack of analysis about the fate of a movable mass when it rolls or slips with friction on a structure. With the aim of elucidating the dynamics of the simplest paradigm of this system and to investigate its asymptotic response, we make reference to a two-degree-of-freedom model made of an elastically vibrating carriage surmounted by a spherical mass, facing the problem both theoretically and experimentally. In case of linear systems, the analytical solutions and the laboratory tests performed on ad hoc constructed prototypes highlighted a counterintuitive asymptotic dynamics, here called binary: in the absence of friction at the interface of the bodies’ system, the mass holds its initial position or, if nonzero damping acts, at the end of the motion it is in a position that exactly recovers the initial relative distance carriage–sphere. While the first result might be somewhat obvious, the second appears rather surprising. Such a binary behaviour is also confirmed for a Duffing-like system, equipped with cubic springs, while it can be lost when non-smooth friction phenomena occur, as well as in the case of elastic springs restraining the motion of the sphere. The obtained analytical results and the numerical findings, also confirmed by experimental evidences, contribute to the basic understanding of the role played by the damping parameters governing the systems’ dynamics with respect to its asymptotic behaviour and could pave the way for designing active or passive vibration controllers of interest in engineering.

A modern digital seismic network, with many stations optimally distributed on the earthquake causative seismic zone, enables detection of very low magnitude earthquakes and determination of their source parameters. It is essential to associate to such kind of networks procedures to analyze the huge amount of continuously recorded data for monitoring the space-time-magnitude evolution of natural and/or induced seismicity. Hence, the demand for near-real-time, automated data collection and analysis procedures for assisting seismic network operators in carrying out microearthquake monitoring is growing. In response to this need, we designed a computational software platform, TREMOR, for fast and reliable detection and characterization of seismicity recorded by a dense local seismic network. TREMOR integrates different open-source seismological algorithms for earthquake signal detection, location, and source characterizations in a fully automatic workflow. We applied the platform in play-back mode to the continuous waveform data recorded during 1 month at the Japanese Hi-net seismic network in the Nagano region (Japan) and compared the resulting catalog with the Japan Meteorological Agency bulletin in terms of number of detections, location pattern and magnitudes. The results show that the completeness magnitude of the new seismic catalog decreased by 0.35 units of the local magnitude scale and consequently the number of events increased by about 60% with respect to the available catalog. Moreover, the fault plane solutions resulted coherent with the stress regime of the region, and the Vp/Vs ratio well delineated the main structural features of the area. According to our results, TREMOR has shown to be a valid tool for investigating and studying earthquakes, especially to identify and monitor natural or induced micro-seismicity.

Do homestays benefit host communities, perpetuate neocolonial relationships, or both? While the St. Lawrence Kenya-Semester Program (KSP) has centered homestays as an essential component of experiential learning and community engagement since 1972, this article flips the script and places homestay families at the center of knowledge production on study abroad. Drawn from 15 years of homestay experiences in Nyeri and Kericho counties, we situate this program as an important case study to analyze host community perceptions of the benefits and challenges of homestays for rural agricultural Kenyan communities and the implications this has for study abroad assessment and community engagement. Abstract in Swahili Je, mpango wa wanafunzi wa kigeni kuishi kwenye nyumba za wenyeji husaidia jamii husika au hushadidia mahusiano ya kikoloni mamboleo ama yote mawili? Programu ya Chuo Kikuu cha St. Lawrence ya Kenya (KSP) imeuwekea uzito mpango wa wanafunzi kuishi kwa jamii wenyeji kama kipengele muhimu katika ujifunzaji wao wa kitajriba na mtagusano wao na jamii kutoka mwaka 1972. Ingawaje, makala haya yamebadilisha mtazamo na kuziona familia zinazohusika katika programu hii kama vituo muhimu vya uzalishaji wa maarifa katika masomo ya ughaibuni. Tukizingatia tajriba ya miaka 15 ya KSP kupeleka wanafunzi kuishi na jamii katika kaunti za Nyeri na Kericho, tunaitazama hii programu kama kifani muhimu cha kuchanganua mitazamo ya jamii wenyeji kuhusu faida na changamoto za wanafunzi kuishi na familia za wakulima vijijini na pia katika kutahini programu za masomo ya ughaibuni na mtagusano wa kijamii.

Background Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC). The guidelines have recognized various approaches, depending on the tumor stage and other risk factors such as histotype and lymphovascular positivity. Much more debate has centered around the boundary within which these treatments should be considered. Indeed, these are methods to be reserved for ECC, but tumor size may represent the most significant limitation. In particular, there is no consensus on the strategy to be adopted in the case of ECC ≥ 2 cm. Therefore, this systematic review was to collect the literature evidence regarding the management of these patients. Methods Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the Pubmed and Scopus databases was conducted in April 2022, from the date of the first publication. We made no limitation on the country. We included all studies containing data on disease-free survival, overall survival, recurrence rate (RR), or complete response rate (CRR) to chemotherapy. Results Twenty-six studies fulfilled the inclusion criteria, and 691 patients were analyzed regarding FST. Surgery-based FST showed an RR of between 0 and 42.9%, which drops to 12.9% after excluding the vaginal or minimally invasive approaches. Furthermore, papers regarding FST based on the neoadjuvant chemotherapy (NACT) approach showed a CRR of between 21.4 and 84.5%, and an RR of between 0 and 22.2% Conclusion This paper focused on the significant heterogeneity present in the clinical management of FST of ECC ≥ 2 cm. Nevertheless, from an oncological point of view, approaches limited to the minimally invasive or vaginal techniques showed the highest RR. Vice versa, the lack of standardization of NACT schemes and the wealth of confounders to be attributed to the histological features of the tumor make it difficult, if not impossible, to set a standard of treatment.

Purpose: The aim of this study was to evaluate the prevalence of bowel/bladder dysfunction in multiple sclerosis (MS) and its associations with cognitive impairment.Methods: We prospectively enrolled 150 MS patients. Patients were administered the Symbol Digit Modality Test (SDMT), the Neurogenic Bowel Dysfunction Score (NBDS), and the Actionable Bladder Symptom Screening Tool (ABSST). The associations between bowel/bladder dysfunction and cognitive function were assessed through hierarchical regression models using the SDMT and clinicodemographic features as independent variables and NBDS and ABSST scores as dependent variables.Results: The prevalence of bowel/bladder deficits was 44.7%, with 26 patients (17.3%) suffering from bowel deficits and 60 patients (40%) from bladder deficits. The total NBDS and ABSST scores were correlated with the SDMT (β=-0.10, P

Objectives: Here, we aim at describing the pattern of care, survival outcome and prognostic factors of ABC patients (pts) receiving third-line chemotherapy. Methods: Institutional registries across three academic medical centers were retrospectively reviewed. Kaplan–Meier estimators were used to calculate survival, the log-rank test to make comparisons, and the Cox proportional hazard models to assess the progostic impact of variables. Results: Among 101 pts included in the analysis. 68 (67.3%), 19 (18.8%) and 14 (13.8%) had intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, respectively. Atotal of 63 (62.3%) pts received monochemotherapy, while 38 (37.6%) were treated with adoublet. The median OS and PFS were 5 and 3 months, respectively. Disease control rate was achieved in 23 (22.7%) pts, with 2 (2%) partial responses. Grade 3–4 treatment-related adverse events were reported in 22 (21.7%) pts. At multivariate analysis, ECOG PS (p

Recent evidence has shown the existence of a CNS ‘waste clearance’ system, defined as the glymphatic system. Glymphatic abnormalities have been described in several neurodegenerative conditions, including Alzheimer’s and Parkinson’s disease. Glymphatic function has not been thoroughly explored in multiple sclerosis, where neurodegenerative processes are intermingled with inflammatory processes. We aimed to investigate glymphatic system function in multiple sclerosis and to evaluate its association with clinical disability, disease course, demyelination and neurodegeneration, quantified using different MRI techniques. In this retrospective study, we enrolled 71 multiple sclerosis patients (49 relapsing-remitting and 22 progressive multiple sclerosis) and 32 age- and sex-matched healthy control subjects. All subjects underwent neurological and MRI assessment including high-resolution T1, T2 and double inversion recovery sequences, diffusion and susceptibility weighted imaging. We calculated the diffusion along perivascular space index, a proxy for glymphatic function, cortical and deep grey matter volume, white and cortical grey matter lesion volume and normal-appearing white matter microstructural damage. Multiple sclerosis patients showed an overall lower diffusion along perivascular space index versus healthy controls (estimated mean difference: −0.09, P = 0.01). Both relapsing-remitting and progressive multiple sclerosis patients had lower diffusion along perivascular space index versus healthy controls (estimated mean difference: −0.06, P = 0.04 for relapsing-remitting and −0.19, P = 0.001 for progressive multiple sclerosis patients). Progressive multiple sclerosis patients showed lower diffusion along perivascular space index versus relapsing-remitting multiple sclerosis patients (estimated mean difference: −0.09, P = 0.03). In multiple sclerosis patients, lower diffusion along perivascular space index was associated with more severe clinical disability (r = −0.45, P = 0.001) and longer disease duration (r = −0.37, P = 0.002). Interestingly, we detected a negative association between diffusion along perivascular space index and disease duration in the first 4.13 years of the disease course (r = −0.38, P = 0.04) without any association thereafter (up to 34 years of disease duration). Lower diffusion along perivascular space index was associated with higher white (r = −0.36, P = 0.003) and cortical (r = −0.41, P = 0.001) lesion volume, more severe cortical (r = 0.30, P = 0.007) and deep (r = 0.42, P = 0.001) grey matter atrophy, reduced fractional anisotropy (r = 0.42, P = 0.001) and increased mean diffusivity (r = −0.45, P = 0.001) in the normal-appearing white matter. Our results suggest that the glymphatic system is impaired in multiple sclerosis, especially in progressive stages. Impaired glymphatic function was associated with measures of both demyelination and neurodegeneration and reflects a more severe clinical disability. These findings suggest that glymphatic impairment may be a pathological mechanism underpinning multiple sclerosis. The dynamic interplay with other pathological substrates of the disease deserves further investigation.

The group represents the social element in which every individual can experience them-selves after the achievement of the main stages of the neuro-psychomotor development, particularly in the affective-relational, neuropsychological and cognitive areas, and is thus identified as a fundamental device to support rehabilitation therapy. Early in a child’s development, social skills begin to maturate and their development path-way merges with different groups with a specific architecture which modifies and increases these skills over time. As a result, it is necessary to identify the process that leads from the exclusive belonging to the family-group to the need to prioritize comparison with peers to finally arrive at the interdependent social groups in the collectivity/community. Each group has distinct characteristics that move from its social dimension to the cross-sectional com-ponent of its matrix, where individuals’ desires and beliefs are based. The group’s evolution will allow the initial dimensional plan to be expanded, resulting in participants sharing inten-tions and goals. The group is a powerful tool at the therapist's disposal who is capable of monitoring variables that can quickly change the intra/interpersonal dynamics of patients undergoing treatment. The groupal therapy underlies clear rules within it, which ensure the observance of normative and setting parameters and the identification of the parameters of effectiveness to assess its progress.

OBJECTIVE To investigate risk factors, clinical features, and prognostic indicators in guinea pigs with urolithiasis. ANIMALS 158 guinea pigs with urolithiasis. PROCEDURES Medical records of an exotics animal specialty service were searched, identifying guinea pigs with urolithiasis. Signalment, clinical data, and outcomes were recorded. Variables of interest were analyzed for statistical associations with outcome. RESULTS Overall, 54.4% (86/158) of animals survived to discharge. Median survival time was 177 days. Females (53.2%; 84/158) were more common than males (46.8%; 74/158). Males were presented younger (mean age, 3.64 years) than females (4.41 years). In 81 of 154 (52.5%) cases, animals were presented with primary urinary concerns, while 73 (47.5%) presented for nonurinary primary concerns. Females more commonly presented with distal urinary tract urolithiasis (63/84; 75%) but fared better overall with a longer median survival time (1,149 days) than males (59 days). Surgical intervention was not a risk factor for nonsurvival; however, increased age (> 4.1 years), male sex, anorexia, weight loss, and lower rectal temperature (< 37.2 °C) on presentation were associated with nonsurvival. Reoccurrence was noted in 13.9% (22/158) of cases, at an average of 284 days. CLINICAL RELEVANCE Urolithiasis should always be considered a differential diagnosis for any unwell guinea pig. In particular, distal urinary tract urolithiasis should be considered in females. A poorer prognosis was associated with older, male guinea pigs, and those displaying anorexia, weight loss, and hypothermia. The need for surgical intervention should not confer a poorer outcome. Further studies are needed to determine specific risk factors and identify possible preventative measures.

The merging of micellar and photoredox catalysis represents a key issue to promote “in water” photochemical transformations. A photomicellar catalyzed synthesis of amides from N-methyl-N-alkyl aromatic amines and both aliphatic and aromatic isocyanides is herein presented. The mild reaction conditions enabled a wide substrate scope and a good functional groups tolerance, as further shown in the late-stage functionalization of complex bioactive scaffolds. Furthermore, solution 1D and 2D NMR experiments performed, for the first time, in the presence of paramagnetic probes enabled the study of the reaction environment at the atomic level along with the localization of the photocatalyst with respect to the micelles, thus providing experimental data to drive the identification of optimum photocatalyst/surfactant pairing.

This paper is focused on the detection and resolution of Unmanned Aerial Vehicles (UAVs) via a multi-channel phased-array radar with emphasis on the challenging situation where multiple targets are unresolved in the range-Doppler domain and closely spaced in angle. An adaptive processor is devised which, after triggering a detection in a given range-Doppler cell, implements a binary decision about the presence of a single or multiple targets. In the former situation, the plain monopulse algorithm is used to estimate the target azimuth whereas, in the latter case, a super-resolution technique is activated to get the angular parameters of the UAVs. The performance of the signal processor is assessed both on simulated and on measured data (endowed by ground-truth) collected by a 12-channel phased-array radar operating in the C-band. The results highlight the capabilities of the architecture to detect the presence of targets, to discriminate the single from the multiple targets scenario, and to resolve the UAVs in angle domain when they are unresolved in range and Doppler.

Antioxidant supplementation has been proposed as a new strategy to improve the long-term preservation of semen. The aim of this study was to evaluate the effect of Maca supplementation of semen extender on quality-related canine semen parameters during cooling. Ejaculates from nine dogs were cooled for 7 days in the absence (control group) or in the presence of 10, 20 and 50 μL/mL of an aqueous extract of Maca. Sperm were evaluated for sperm viability, motility, DNA fragmentation and lipid peroxidation after 3 h, 24 h, 4 days and 7 days of storage. The addition of 10 μL/mL of Maca preserved sperm DNA and plasma membrane integrity at 3 h and increased sperm curvilinear velocity after 24 h. Treatment with 20 and 50 μL/mL of Maca increased the percentage of hyperactivated sperm after 3 h. Moreover, semen treated with 20 μL/mL of Maca decreased lipid peroxidation at 24 h. A significant reduction of sperm DNA and plasma membrane integrity as well as of kinetics parameters between 3 and 24 h of refrigerated storage with the higher concentration tested was observed. Although Maca was not able to protect canine semen with extended refrigeration storage time, it increased hyperactivation and preserved DNA integrity in short-term storage.

Whilst there is a consensus that aerosol particles and primary biological aerosol particles (PBAPs) play an important role in regulating the global climate, with aerosols-PBAPs research increasing lately in Brazil, information summarizing the available knowledge is limited. Here, we present a systematic review of research published during the last 35-years on aerosols-PBAPs in Brazil. A total of 212 studies encompassing 474 cases met the selection criteria. The Amazon rainforest was the most studied biome represented by 72% of cases, followed by the Atlantic Forest with 18%. Studies focusing on the Amazon rainforest mostly studied climate-related issues and aerosol physics, with less than 5% examining the biological identity of aerosols, whereas outside the Amazon rainforest this number reached 16%. In addition, more than half of the cases within Amazon (55%) were held at seven sampling sites only, but conclusions were mainly extrapolated to the entire biome. On the other hand, research beyond Amazon has mostly addressed temporal and biological characterization of PBAPs, and not only is it scattered, but also scarce. Regarding sampling effort, most cases (72%) have had less than 100 days of sampling, and 60% of them spanned less than half a year of study, confining research to one or two seasons at the most. Consequently, while research from different countries that conduce their studies within Brazil and scientific fields are focusing on the same area, inconsistences are slowing the progress of this research topic. We argue that scientists from different fields of research (e.g., biologists, physicists) and countries should work together to produce more detailed and complete assessments of aerosols-PBAPs in the country as a whole, particularly on regards to their biological identity, given their importance to global climate regulation.

The current socio-economic and political scenario is posing serious challenges to energy usage, mobility, residential and industrial activities, which may impact local emission patterns, fossil fuel vs alternative fuels usage and air quality in unknown ways. On top of this, winter 2022-23 is being exceptionally warm across the European continent.The investigation of the interactions between air quality, meteorological factors and emissions sources at high spatio-temporal resolution plays a crucial role to detect areas and periods characterized by critical conditions, especially in complex urban environments. Data at such fine resolution can today be obtained through dense low-cost sensor networks integrating sparse official air quality stations. This research aims to assess meteorological forcing, emission proxies (i.e., population density, CO2 local enhancement, land-use) and particulate matter concentrations (PMs) for the last three winter seasons (2020-2023) characterized by contrasting conditions. The study was focused on the Lucca plain (central Italy), an area characterized by heterogeneous emission sources and classified among the most polluted in the region. Sixteen low-cost stations (“AirQino”), equipped with high-frequency sensors to detect PM10, PM2.5, air-temperature, relative humidity (RH), and CO2 concentration were installed on an area spanning approximately 10 x 20 km. Local land use surrounding the measurement stations was obtained from the Corine Land Cover. Mixing Layer Height (Hmix) and wind data were obtained from a WRF-CALMET coupled model. Population density was computed with demographic data from the Global Human Settlement database. For CO2 data, the nocturnal enhancement normalized by wind speed with respect the minimum midday values was used as an emission proxy (ΔCO2). Population density and land use including fractions of residential, industrial, and agricultural areas were computed in a 1-km radius surrounding each station.Preliminary comparisons between winter 2021/2022 and 2022/23 were performed to assess the effects of energy crisis and climatic conditions on air-quality. Different multivariate regression models were developed to investigate the inference between Hmix, air-temperature, RH, ΔCO2, population density, land use and PMs concentrations.Most recent analysis shows a consistent and robust positive air temperature anomaly in November-December 2022 vs 2021 (+ 1.25 °C). CO2 enhancements were on average 20% lower (-19.0 to +3.7 ppm in 2022 vs 2021 respectively) suggesting a relevant emission reduction occurring at the landscape scale. However, these reductions did not always translate into PM10 and PM2.5 reductions and air quality improvements. Among the 16 stations, 11 exhibited a decrease in PM2.5 concentration (-21.60 % on average) and only 9 in PM10 (-21.55 % on average). The locations where air quality did not improve or was even worse this year are characterized by the lowest population density and lowest presence of residential neighborhoods, being mostly in rural or rural/industrial contexts. This suggests that alternative fuels such as wood biomass are likely replacing natural gas in peri-urban areas for domestic heating, generating a negative impact on air quality that could be much worst when usual lower temperature conditions will be met. A complete multivariate analysis to confirm these patterns will be presented.

A Pre–deployment calibration and a field validation of two low-cost (LC) stations equipped with O3 and NO2 metal oxide sensors were addressed. Pre–deployment calibration was performed after developing and implementing a comprehensive calibration framework including several supervised learning models, such as univariate linear and non–linear algorithms, as well as multiple linear and non–linear algorithms. Univariate linear models included linear and robust regression, while univariate non–linear models included support vector machine, random forest, and gradient boosting. Multiple models consisted of both parametric and non-parametric algorithms. Internal temperature, relative humidity and gaseous interference compounds proved to be the most suitable predictors for multiple models, as they helped effectively mitigate the impact of environmental conditions and pollutant cross-sensitivity on sensor accuracy. A feature analysis, implementing Dominance analysis, feature permutations and, SHapley Additive exPlanations method, was also performed to provide further insight into the role played by each individual predictor and its impact on sensor performances. This study demonstrated that while multiple random forest (MRF) returned higher accuracy than multiple linear regression (MLR), it did not accurately represent physical models beyond the Pre–deployment calibration dataset, so that a linear approach may overall be a more suitable solution. Furthermore, as well as being less computationally demanding and generally more suitable for non-experts, parametric models such as MLR have a defined equation that also includes a few parameters, which allows easy adjustments for possible changes over time. Thus, drift correction or periodic automatable recalibration operations can be easily scheduled, which is particularly relevant for NO2 and O3 metal oxide sensors: as demonstrated in this study, they performed well with the same linear model form, but required unique parameter values due to inter-sensor variability.

The lung is the human organ mainly affected by the severe coronavirus disease (COVID-19) caused by the novel coronavirus SARS-CoV-2. In this pathology, the dynamic lung function and the respiratory mechanics are compromised, leading to the development of the ARDS (acute respiratory distress syndrome). The resulting damage is the progressive reduction of gas exchange and death in the most critical patients. For these reasons, it is important to study and analyze how this virus adversely affects lung dynamics. The main objective of the present paper proposes a modeling method of SARS-CoV-2 virus particles spread in the 23rd generation of lung tree and the mechanical estimation of how a severe stage of COVID-19 characterized by pulmonary fibrosis affects the alveolar sac expansion and hence the breathing capability of the sick person. In this context, the dynamic analysis of the influence of SARS-CoV-2 spread on human lung under real conditions has been shown by means of a numerical approach. Therefore, a multiphase three-dimensional computational fluid dynamics (CFD) study is performed to estimate the COVID-19 virus particles dispersion throughout a simplified model of the 23rd generation of the bronchial tree, at the alveolar region. Then, a fully coupled fluid-structure interaction (FSI) with the mesh morphing technique and solid displacement characteristics are used to obtain and evaluate a realistic wall displacement during the expansion of the alveolar sac. A comparison is made between a healthy and a diseased lung. These phases are studied under cyclic steady-state conditions The novelties of this analysis are: first, the innovative CFD method proposed in order to model the particles spread inside the alveolar region, and second the evaluation of how the presence of Sars-Cov-2 can affect the mechanical properties of the alveolar sac and damage the lung function of a sick person at an advanced stage of infection, such as a person affected by pulmonary fibrosis.

Flame synthesis of Carbon NanoParticle (CNP) films is gaining strong interest for novel industrial applications because of the easy tuning of the operating conditions that enables accurate control of the chemical and physical properties of the produced CNPs. This work proposes a novelty in the synthesis of CNP films, namely the possibility of applying electric fields in flame to trigger electrophoretic deposition phenomena. In this way, it is possible to add another degree of freedom to the harvesting process and potentially modify the properties of the CNP films, without changing the operating flame conditions. To investigate the physical mechanisms governing the thermo-electrophoretic deposition of CNPs, a numerical model to simulate the particle dynamics close to the collecting substrate has been developed, and experiments have been carried out to provide highly controlled test conditions that can be used to support model validation. The experimental results consist of Atomic Force Microscopy (AFM) measurements to determine the number of particles deposited after a controlled harvesting condition as a function of the applied electrophoretic force, imposed on the substrate by means of a DC voltage varied from 0 to -3kV. The AFM shows that the amount of deposited material increases up to six times when passing from an uncharged to the -3kV charged case. The model predictions are highly consistent with the AFM measurements and pointed out that the electric field in flame significantly alters the CNP deposition velocities and impact angles, which are likely to affect the properties of the film.

Objective The Fist-Palm Test (FiPaT) is a novel non-verbal task to be used at the patient’s bedside for a cognitive functions screening. The aims of this study are to analyze (I) the qualitative and quantitative performance features at FiPaT, (II) the psychometric characteristics of FiPaT, and (III) the correlation between FiPat and traditional cognitive assessments in subjects with normal cognition (NC), Mild Cognitive Impairment-single domain (MCI-sd), and Mild Cognitive Impairment-multiple domain (MCI-md). Methods One hundred-thirteen subjects (53M/60F), with a mean age of 66.28 ± 7.22 years and 11.08 ± 4.93 years of education, were recruited and underwent a complete neuropsychological battery and FiPaT. Results We found 68 subjects with NC, 31 with MCI-sd, and 14 with MCI-md and a high reliability of the FiPaT (alpha =0.762). The number of FiPaT errors correlated with age and all neuropsychological tests, except for the memory recall test. Subjects with MCI had greater FiPaT errors than subjects with NC. The FiPaT, used with the MOCA test, predicted the presence of MCI, with a variance of 44%. Conclusion The FiPaT is an acceptable and reliable non-verbal test, able to screen for global cognitive status, attention, and executive functions, and to predict the MCI. Future studies will validate this initial findings as well as the discriminatory role of the FiPaT in detecting specific types of cognitive impairment.

Background: Depressive symptoms are common in Alzheimer’s disease (AD) patients and are associated with an increased functional decline. Selective serotonin reuptake inhibitor antidepressants showed a limited efficacy. Objective: The purpose of this work was to evaluate if a higher brain cholinergic stimulation induced by the association between the acetylcholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate has any effect on depression in AD patients. Methods: Patients were selected among those recruited in the ASCOMALVA (association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in AD) trial. Depressive symptoms were investigated in 90 AD patients through the neuropsychiatric inventory at baseline and after 3, 6, 9, 12, 18, and 24 months of treatment. Patients were randomized in a group association therapy (45 subjects) receiving donepezil 10 mg plus choline alphoscerate 1,200 mg/day, and a group monotherapy (45 subjects) receiving donepezil 10 mg/day plus placebo. Based on the results of the MMSE at the recruitment patients were divided into 3 groups: severely impaired (score

Bile-duct cancers (BDC) are a group of solid tumors arising from the biliary tree. Despite their classification as rare cancers, the incidence of BDC is increasing worldwide. Poor prognosis is a common feature of this type of cancer and is mainly determined by the following factors: late diagnosis, lack of effective therapeutic approaches, and resistance to conventional treatments. In the past few years, next-generation sequencing technologies has allowed us to study the genome, exome, and transcriptome of BDC deeper, revealing a previously underestimated class of RNA: the noncoding RNA (ncRNA). MicroRNAs (miRNAs) are small ncRNAs that play an important regulatory role in gene expression. The aberrant expression of miRNAs and their pivotal role as oncogenes or tumor suppressors in biliary carcinogenesis has been widely described in BDC. Due to their ability to regulate multiple gene networks, miRNAs are involved in all cancer hallmarks, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing/accessing vasculature, activating invasion and metastasis, reprogramming cellular metabolism, and avoiding immune destruction. Their use as diagnostic, prognostic, and predictive biomarkers has been widely explored in several human cancers, including BDC. Furthermore, miRNA-based therapeutic strategies are currently the subject of numerous clinical trials that are providing evidence of their efficacy as potent anticancer agents. In this review, we will provide a detailed update of miRNAs affecting BDC, discussing their regulatory function in processes underlying the molecular pathology of BDC. Finally, an overview of their potential use as biomarkers or therapeutic tools in BDC will be further addressed.

Objectives: Deficits in facial emotion recognition and Theory of Mind are frequent in patients with epilepsy. Although this evidence, studies on pediatric age are few and the relation between these abilities and other cognitive domain remains to be better elucidated. The purpose of our study is to evaluate facial emotion recognition and Theory of Mind in children and adolescents with focal epilepsy, and correlate them with intelligence and executive functions. Materials and methods: Our work is a cross-sectional observational study. Sixty-two children and adolescents aged between 7-16 years diagnosed by focal epilepsy and 32 sex/age-matched controls were recruited. All participants were administered a standardized battery tests to assess social cognition (NEPSY-II), executive functions (EpiTrack Junior) and cognitive non-verbal level (Raven Progressive Matrices). Results: Emotion recognition mean score was significantly lower in the epilepsy group than in the controls to Student's t-test (p

The absorption of SO2 in electrified water sprays, either when the polluted gas is treated as is or when the gas is exposed to a corona source to ionize the SO2 was evaluated. An electrified spray with a charge-to-mass ratio of 50 ΜC/kg enabled the absorption rate of droplets to double, regardless of their polarities. Corona charging gave rise to an increase in the SO2 depletion rate over the scrubber wall, while negligible effects appeared on the actual droplets absorption rate. These findings suggested that faster absorption rates mostly, though not uniquely, depend on the modifications on the morphological and interfacial properties of the sprayed droplets induced by the free electric charge imposed on their surface. Conversely, the absorption rates were negligibly affected by the electrical interactions between droplets (either charged or uncharged) and the SO2 ions/radicals originating from the corona source.

The pharmacodynamic and pharmacokinetic properties of bioactive peptides can be modulated by introducing conformational constraints such as intramolecular macrocyclizations, which can involve either the backbone and/or side chains. Herein, we aimed at increasing the α-helicity content of temporin L, an isoform of an intriguing class of linear antimicrobial peptides (AMPs), endowed with a wide antimicrobial spectrum, by the employment of diverse side-chain tethering strategies, including lactam, 1,4-substituted [1,2,3]-triazole, hydrocarbon, and disulfide linkers. Our approach resulted in a library of cyclic temporin L analogues that were biologically assessed for their antimicrobial, cytotoxic, and antibiofilm activities, leading to the development of the first-in-class cyclic peptide related to this AMP family. Our results allowed us to expand the knowledge regarding the relationship between the α-helical character of temporin derivatives and their biological activity, paving the way for the development of improved antibiotic cyclic AMP analogues.

Pivotal trials showed the effectiveness of the monoclonal antibody ocrelizumab in relapsing and progressive multiple sclerosis (MS). However, data on everyday practice in MS patients and markers of treatment effectiveness are scarce. We aimed to collect real-world data from ocrelizumab-treated MS patients, relapsing-remitting (RR) and progressive MS patients (PMS), including active secondary progressive MS (aSPMS) and primary progressive MS (PPMS) patients, and to explore potential prognostic factors of clinical outcome. Patients were enrolled at MS centres in the Campania region, Italy. We collected clinic-demographic features retrospectively one year before ocrelizumab start (T−1), at ocrelizumab start (T0), and after one year from ocrelizumab start (T1). We explored possible clinical markers of treatment effectiveness in those patients receiving ocrelizumab treatment for at least one year using multilevel-mixed models. We included a total of 383 MS patients (89 RRMS and 294 PMS; 205 females, mean age: 45.8 ± 11.2, disease duration: 12.7 ± 11.6 years). Patients had a mean follow-up of 12.4 ± 8.2 months, and 217 patients completed one-year ocrelizumab treatment. Overall, EDSS increased from T−1 to T0 (coeff. = 0.30, 95% coefficient interval [CI] = 0.19–0.41, p < 0.001) without a further change between T0 and T1 (p = 0.61). RRMS patients did not show an EDSS change between T−1 and T0 nor between T0 and T1. Conversely, PMS patients showed EDSS increase from T−1 to T0 (coeff. = 0.34, 95% CI = 0.22–0.45, p < 0.001) without a further change between T0 and T1 (p = 0.21). PMS patients with a time from conversion shorter than 2 years showed increased EDSS from T−1 to T0 (coeff. = 0.63, 95% CI = 0.18–1.08, p = 0.006) without a further change between T0 and T1 (p = 0.94), whereas PMS patients with a time from conversion longer than 2 years showed increased EDSS from T0 to T1 (coeff. = 0.30, 95% CI = 0.11–0.49, p = 0.002). Naïve patients showed an EDSS decrease between T0 and T1 (coeff. = −0.30, 95% CI = −0.50–−0.09, p = 0.004). In conclusion, our study highlighted that early ocrelizumab treatment is effective in modifying the disability accrual in MS patients.

The objective of our study was to evaluate the impact of the COVID-19 pandemic on the emotional and behavioral symptoms in minors with neuropsychiatric disorders and on parental stress through a standardized neuropsychological assessment, comparing the data collected before the pandemic with those collected during the lock-down. Another goal of our study was to analyze the relationship between parental stress and behavioral/emotional symptoms in children. Our study was conducted on 383 families of patients who had already been referred at the Child Neuropsychiatry Unit of the University Hospital of Salerno for different neuropsychiatric conditions. All the parents completed two neuropsychological standardized questionnaires for the assessment of parental stress (PSI—Parenting Stress Index-Short Form) and the emotional/behavioral problems of their children (Child Behaviour CheckList). The data collected during the pandemic were compared with those collected from questionnaires administered during the six months preceding the pandemic, as is our usual clinical practice. The comparison between the mean scores of PSI and CBCL before and after the pandemic showed a statistically significant increase in all subscales analyzed in the total sample. The correlation analysis showed significant positive relationship between the subscale Total Stress of PSI and the subscales Total Problems and Internalizing Problems of CBCL. Our study suggested that the COVID-19 pandemic and the corresponding measures adopted led to an increase in internalizing and externalizing symptoms in children and adolescents with neuropsychiatric disorder. Similarly, parental stress increased during COVID-19 and ahigher level of stress in parents can be related to the internalizing symptoms of their children.

BACKGROUND: Bigorexia or muscle dysmorphia (MD) is a subtype of body dysmorphic disorder, and it is characterized by an excessive dissatisfaction with body size and muscularity. Orthorexia nervosa (ON) is an obsessive focus on healthy eating and emotional distress related to food choices that are perceived as unhealthy. MD and ON are considered two emerging psychiatric disorders. METHODS: The aim of this study was to evaluate the prevalence of traits of ON and MD between amateurs and professional athletes who practice bodybuilding. The secondary endpoint of the study is to identify the anabolic steroid abuse among the athletes. To this end we have administered a dichotomic questionnaire to 60 young men: 30 amateur bodybuilders (ABBs) and 30 professional bodybuilders (PBBs). RESULTS: Scores compatible with a full-blown MD disorder have been found in 100% of subjects of PBB group and in 83% of ABB group. Afull-blown ON has been detected in 87% of BBPs and 40% of BBAs and a risk for ON in 10% of BBPs and in 37% of BBAs. CONCLUSIONS: This study shows a high co-occurrence of MD and ON among the bodybuilders suggesting a link between eating disorders and body dysmorphic disorders.

Indoor positioning of objects and people is becoming of great importance in the Internet of Things (IoT), in-home automation, and navigation in malls, airports, or very large buildings. Positioning is determined by multiple distance measurements between reference points and sensors. Distance measurement uses the time of flight of an ultrasonic signal traveling from an emitter to receiving sensors. This requires close synchronization between the emitter and the sensors and a sharp time resolution of the time of arrival (TOA) of the ultrasonic signal. Usually, TOA is detected using cross-correlation processing requiring significant computational resources at the sensors level. In this work, the synchronization is done using the RFID standard protocol features. The TOA detection is performed firstly by training off-line a Machine Learning model using as input the peaks indexes of the ultrasonic signal received and the output of a cross-correlation-based positioning system, as ground-truth. In a second phase, the positioning is evaluated and tested on-board using the previously trained model on a microcontroller. The system architecture is presented and experimental results on the positioning accuracy are shown accordingly. Results show a mean positioning error below 25 cm in 95% of the positionings in a typical room.

Fragile X syndrome (FXS) is a genetic syndrome with intellectual disability due to the loss of expression of the FMR1 gene located on chromosome X (Xq27.3). This mutation can suppress the fragile X mental retardation protein (FMRP) with an impact on synaptic functioning and neuronal plasticity. Among associated sign and symptoms of this genetic condition, sleep disturbances have been already described, but few polysomnographic reports in pediatric age have been reported. This multicenter case-control study is aimed at assessing the sleep macrostructure and at analyzing the presence of EEG abnormalities in a cohort of FXS children. We enrolled children with FXS and, as controls, children with typical development. All subjects underwent at least 1 overnight polysomnographic recording (PSG). All recorded data obtained from patients and controls were compared. In children with FXS, all PSG-recorded parameters resulted pathological values compared to those obtained from controls, and in FXS children only, we recorded interictal epileptiform discharges (IEDs), as diffuse or focal spikes and sharp waves, usually singles or in brief runs with intermittent or occasional incidence. A possible link between IEDs and alterations in the circadian sleep-wake cycle may suggest a common dysregulation of the balance between inhibitory and excitatory pathways in these patients. The alteration in sleep pattern in children with FXS may negatively impact the neuropsychological and behavioral functioning, adding increasing burn of the disease on the overall management of these patients. In this regard, treating physicians have to early detect sleep disturbances in their patients for tailored management, in order to prevent adjunctive comorbidities.

Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. Objectives: To compare diagnostic performances of two different data-driven SPMS definitions. Methods: Data-driven SPMS definitions based on a version of Lorscheider’s algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist’s definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). Results: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). Conclusion: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist’s definition and the global accuracy of DDA seems to be higher than the EXPAND definition.

The peptide hormone relaxin (RLX), also available as clinical-grade recombinant protein (serelaxin), holds great promise as a cardiovascular and anti-fibrotic agent but is limited by the pharmacokinetic issues common to all peptide drugs. In this study, by a computational modelling chemistry approach, we have synthesized and tested a set of low molecular weight peptides based on the putative receptor-binding domain of the B chain of human H1 RLX isoform, with the objective to obtain RLX analogues with improved pharmacokinetic features. Some of them were stabilized to induce the appropriate 3-D conformation by intra-chain tri-azolic staples, which should theoretically enhance their resistance to digestive enzymes making them suited for oral administration. Despite these favourable premises, none of these H1 peptides, either linear or stapled, revealed a sufficient affinity to the specific RLX receptor RXFP1. Moreover, none of them was endowed with any RLX-like biological effects in RXFP1-expressing THP-1 human monocytic cells and mouse NIH-3T3-derived myofibroblasts in in vitro culture, in terms of significantly relevant cAMP elevation and ERK1/2 phosphorylation, which represent two major signal transduction events downstream RXFP1 activation. This was at variance with authentic serelaxin, which induced a clear-cut, significant activation of both these classical RLX signaling pathways. Albeit negative, the results of this study offer additional information about the structural requirements that new peptide therapeutics shall possess to effectively behave as RXFP1 agonists and RLX analogues.

This study investigates longitudinal changes in health-related quality of life (HRQoL) in early-onset multiple sclerosis (MS) patients and explores the impact of disease activity (relapses) on such changes. People with MS (PwMS) onset between 12 and 25 years of age were followed longitudinally. At baseline and at year 4, patients were asked to fill the Paediatric Quality of life inventory (PedsQL). Demographic and clinical features were collected at both time points. Longitudinal within-group comparison of HRQoL total score and sub-scores was performed via paired samples t-test. The effect of relapses on the HRQoL changes over time was explored via linear mixed-effects analysis. No longitudinal changes were observed in the overall PedsQL score, nor in the physical, school and psychological functioning. An increase in the social functioning subscale (p < 0.001) and a decrease in the emotional subscale (p = 0.006) were observed. The change in social functioning, but not the one in the emotional subscale, was affected by the occurrence of relapses (p = 0.044). In conclusion, stimulating the patients to accept their emotional responses to health-related limitations, while preserving their social and relational resources seems key to the preservation of an adequate QoL over time in juvenile-onset MS.

PRISMA (PRecursore IperSpettrale della Missione Applicativa) is a demonstrative spaceborne mission, fully deployed by the Italian Space Agency (ASI). To support the calibration/validation activities of the PRISMA hyperspectral mission, ASI and the National Research Council (CNR) started in 2019 the PRISCAV project (Scientific CAL/VAL of PRISMA mission). The main objective of PRISCAV is the comprehensive characterization of the performances of the PRISMA payload in orbit in different operational scenarios and the verification of the durability in time of the performances. To this end, PRISCAV created a network of 12 instrumented sites showing different land-use and surface settings (Snow; Sea; Inland and Coastal Water; Forest and Cropland) to obtain independent and traceable in-situ and airborne Fiducial Reference Measurements (FRM) simultaneous to PRISMA acquisitions in order to assess the required performance of sensor, data products, and processors at the different levels (i.e. Top-of-Atmosphere Level 1 Radiances and Bottom-of-Atmosphere Level 2 Reflectance standard products). Moreover, on some of these sites, simultaneous PRISMA and airborne AVIRISNG acquisitions were made coupling remote sensing with in-situ observations to support new mission development and in particular the Copernicus Hyperspectral Imaging Mission for the Environment (CHIME). Recent updates on CAL/VAL activities and on AVIRSNG campaigns are presented in this contribution.

Background The AHNAK2 gene encodes a large nucleoprotein expressed in several tissues, including brain, squamous epithelia, smooth muscle, and neuropil. Its role in calcium signaling has been suggested and to date, clear evidence about its involvement in the pathogenesis of clinical disorders is still lacking. Methods Here, we report a female 24-year-old patient diagnosed with a cardio-facio-cutaneous-like phenotype (CFC-like), characterized by epilepsy, psychomotor development delay, atopic dermatitis, congenital heart disease, hypotonia, and facial dysmorphism, who is compound heterozygote for two missense mutations in the AHNAK2 gene detected by exome sequencing. Results This patient had no detectable variant in any of the genes known to be associated with the cardio-facio-cutaneous syndrome. Moreover, the mode of inheritance does not appear to be autosomal dominant, as it is in typical CFC syndrome. We have performed in silico assessment of mutation severity separately for each missense mutation, but this analysis excludes a severe effect on protein function. Protein structure predictions indicate the mutations are located in flexible regions possibly involved in molecular interactions. Conclusion We discuss an alternative interpretation on the potential involvement of the two missense mutations in the AHNAK2 gene on the expression of CFC-like phenotype in this patient based on inter-allelic complementation. publishedVersion

Aims We aim to provide real-world evidence on the use of ocrelizumab for treating multiple sclerosis (MS), with specific regard to prescription pattern, adherence, persistence, healthcare resource utilization and related costs, also in relation to other disease-modifying treatments (DMTs). Methods We included 2495 people with MS from the Campania Region (South Italy) who received first or switch DMT prescription from Jan 2018 to Dec 2020, and with at least 6-month follow-up. We collected hospital discharge records, drug prescriptions, and related costs, and calculated persistence (time from first prescription to discontinuation or switch to other DMT), adherence (proportion of days covered (PDC)), annualized hospitalization rate (AHR) for MS-related hospital admissions, and DMT costs. Results Ocrelizumab was the most commonly prescribed DMT (n = 399; age = 45.74 ± 10.98 years; females = 224), after dimethyl fumarate (n = 588) and fingolimod (n = 401); 26% patients treated with ocrelizumab were naïve. When compared with ocrelizumab, the risk of discontinuation was higher for other highly active DMTs (HR = 3.78; p = 0.01), and low/medium efficacy DMTs (HR = 7.59; p p = 0.31), but higher for low/medium efficacy DMTs (Coeff = 0.09; p p = 0.51), and low/medium efficacy DMTs (Coeff = 0.01; p = 0.55). When compared with ocrelizumab, DMT monthly costs were higher for other highly active DMTs (Coeff = 92.30; p p Discussion Ocrelizumab was among the most frequently prescribed DMTs, with 26% prescriptions to treatment-naïve patients, suggesting its relevance in addressing unmet clinical needs (e.g., first approved treatment for primary progressive MS). Ocrelizumab was associated with the highest persistence, confirming its favorable benefit-risk profile. Costs for ocrelizumab were lower than those associated to similarly effective DMTs, in absence of changes in healthcare resource utilization.