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The human action observation network (AON) encompasses brain areas consistently engaged when we observe other's actions. Although the core nodes of the AON are present from childhood, it is not known to what extent they are sensitive to different action features during development. Because social cognitive abilities continue to mature during adolescence, the AON response to socially-oriented actions, but not to object-related actions, may differ in adolescents and adults. To test this hypothesis, we scanned with functional magnetic resonance imaging (fMRI) male and female typically-developing teenagers (n= 28; 13 females) and adults (n= 25; 14 females) while they passively watched videos of manual actions varying along two dimensions: sociality (i.e., directed toward another person or not) and transitivity (i.e., involving an object or not). We found that action observation recruited the same fronto-parietal and occipito-temporal regions in adults and adolescents. The modulation of voxel-wise activity according to the social or transitive nature of the action was similar in both groups of participants. Multivariate pattern analysis, however, revealed that decoding accuracies in intraparietal sulcus (IPS)/superior parietal lobe (SPL) for both sociality and transitivity were lower for adolescents compared with adults. In addition, in the lateral occipital temporal cortex (LOTC), generalization of decoding across the orthogonal dimension was lower for sociality only in adolescents. These findings indicate that the representation of the content of others' actions, and in particular their social dimension, in the adolescent AON is still not as robust as in adults.SIGNIFICANCE STATEMENTThe activity of the action observation network (AON) in the human brain is modulated according to the purpose of the observed action, in particular the extent to which it involves interaction with an object or with another person. How this conceptual representation of actions is implemented during development is largely unknown. Here, using multivoxel pattern analysis (MVPA) of functional magnetic resonance imaging (fMRI) data, we discovered that, while the action observation network is in place in adolescence, the fine-grain organization of its posterior regions is less robust than in adults to decode the abstract social dimensions of an action. This finding highlights the late maturation of social processing in the human brain.

Deep-seated Gravitational Slope Deformations (DsGSDs) are widespread phenomena across alpine arch. Despite the slow evolution, long-lasting deformation trend of these huge phenomena can represent a relevant geo-hazard, variably affecting human settlements and infrastructures. Given the complexity and spatial heterogeneity of these phenomena, DsGSDs behavior can feature distinct deformation sectors, highlighted by distinctive morpho-structural lineaments. To assess the internal variability in terms of kinematics, deformation trends and style of activity of a deep-seated phenomenon, a local scale analysis is needed. Notoriously, spaceborne radar interferometry have proven to be suitable to characterize ground deformation displacement of very-slow phenomena as DsGSDs, although DInSAR techniques application remain challenging, especially in mountain areas due to complex topography, abundant vegetation and snow cover. In this study, a methodology for the characterization of DsGSDs, exploiting Sentinel-1 dataset on both ascending and descending orbits, is proposed. The Sentinel-1 images are processed with the multi-resolution Component extrAction and sElection SAR- Detector (CAESAR -D), which allows increasing the monitored area density via a spatially variable multilook. Subsequently, operating in a GIS environment, a post-processing and a dedicated analysis of the obtained measured points is implemented. Morpho-structural domains were mainly defined on the basis of geomorphological criteria, leveraging on DEM derivative products (e.g., slope, aspect and hillshade), orthophoto analysis and taking in account the information available in the Italian Landslide Inventory (IFFI). For each recognized domain, firstly, an analysis on the PSs coverage was performed in order to identify the proper distribution and density of the SAR-derived measurement points for a correct definition of the state of activity. Then, we operated filtering the available SAR datasets from possible anomalous values mainly related to the slope orientation to the satellite line of sight (LOS), in order to obtain suitable dataset for the ground deformation analysis. Finally, the filtered measured points were interpolated with the Inverse Distance Weighting (IDW) technique, with the aim of produce diverse ground deformation maps depending on the orientation of the analyzed phenomenon. The combination of ascending and descending geometries allowed to obtain east-west and vertical components of velocity. The projection on the VLOS along the slope allowed to partially reduce the limitation of the topography on SAR sensitivity. This allowed us to analyze the displacement pattern of DsGSDs in more reliable way. We tested the procedure on two variably oriented DsGSDs phenomena, located in the alpine region Aosta Valley, the Croix de Fana DsGSD, mainly north-south oriented, and the Valtournenche DsGSD, mainly east-west oriented. The variations of the kinematic behavior between the morpho-structural sectors is detected, also considering any other phenomenon as secondary landslide or talus, superimposed on the DsGSD. Overall, the implemented methodology allows to a rapid and low-cost generation of ground deformation maps able to spatially analyze and characterize the morpho-structural domains of DsGSDs, providing an effective tool suitable for the definition of DsGSDs impact on the diverse anthropic elements and a proper land use planning in mountainous territories. This research was carried out in the framework of the ASI contract n. 2021-10-U.0 CUP F65F21000630005 MEFISTO

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Cytokine-induced killer lymphocytes (CIK) are a promising alternative to conventional donor lymphocyte infusion (DLI), following allogeneic haematopoietic cell transplantation (HCT), due to their intrinsic anti-tumour activity and reduced risk of graft-versus-host disease (GVHD). We explored the feasibility, anti-leukaemic activity and alloreactive risk of CIK generated from full-donor chimaeric (fc) patients and genetically redirected by a chimeric antigen receptor (CAR) (fcCAR.CIK) against the leukaemic target CD44v6. fcCAR.CIK were successfully ex-vivo expanded from leukaemic patients in complete remission after HCT confirming their intense preclinical anti-leukaemic activity without enhancing the alloreactivity across human leukocyte antigen (HLA) barriers. Our study provides translational bases to support clinical studies with fcCAR.CIK, a sort of biological bridge between the autologous and allogeneic sources, as alternative DLI following HCT.

Nell’articolo sono delineate le caratteristiche sociolinguistiche dell’Italiano della Svizzera italiana e presentati i risultati di un questionario, raccolto al Dipartimento formazione e apprendimento della SUPSI, sulla percezione dei termini scolastici regionalmente marcati in un gruppo di docenti in formazione per l’insegnamento nella scuola elementare. Si tratta dei primi risultati del progetto Repertorio lessicale dei regionalismi d’uso scolastico della Svizzera italiana, nato dalla collaborazione tra il Dipartimento formazione e apprendimento della SUPSI e l’Osservatorio linguistico della Svizzera italiana. Il progetto si pone come obiettivo la valorizzazione dell’ISIt in contesto scolastico, superando atteggiamenti di sanzione o di condanna fondati spesso su una visione pregiudizievole dei registri e delle varietà linguistiche.

Contains fulltext : 291244.pdf (Publisher’s version ) (Open Access) Neuralgic amyotrophy (NA), also referred to as idiopathic brachial plexitis and Parsonage-Turner syndrome, is a peripheral nerve disorder characterized by acute severe shoulder pain followed by progressive upper limb weakness and muscle atrophy. While NA is incompletely understood and often difficult to diagnose, early recognition may prevent unnecessary tests and interventions and, in some situations, allow for prompt treatment, which can potentially minimize adverse long-term sequalae. High-resolution ultrasound (HRUS) has become a valuable tool in the diagnosis and evaluation of NA. Pathologic HRUS findings can be grouped into four categories: nerve swelling, swelling with incomplete constriction, swelling with complete constriction, and fascicular entwinement, which may represent a continuum of pathologic processes. Certain ultrasound findings may help predict the likelihood of spontaneous recovery with conservative management versus the need for surgical intervention. We recommend relying heavily on history and physical examination to determine which nerves are clinically affected and should therefore be assessed by HRUS. The nerves most frequently affected by NA are the suprascapular, long thoracic, median and anterior interosseous nerve (AIN) branch, radial and posterior interosseous nerve (PIN) branch, axillary, spinal accessory, and musculocutaneous. When distal upper limb nerves are affected (AIN, PIN, superficial radial nerve), the lesion is almost always located in their respective fascicles within the parent nerve, proximal to its branching point. The purpose of this review is to describe a reproducible, standardized, ultrasonographic approach for evaluating suspected NA, and to share reliable techniques and clinical considerations when imaging commonly affected nerves. 01 januari 2023

Anion supply in prepartum rations affects the mineral metabolism in primiparous cows. The objective of this study was to evaluate the effect of calcium chloride and dietary calcium sulfate in prepartum heifers’ rations on the composition of colostrum, fat and protein milk content, and total milk production during 305 days of lactation. Forty five Holstein heifers were assigned to three groups (15 per group) 21 days before calving. The heifers received a partially mixed ration (PMR) plus 2.5 kg/cow/day of wheat middlings (CP= 18.5%, neutral detergent fiber= 36.7%). Mineral salts with a dietary cation-anion difference (DCAD) of +200 mEq/kg of dry matter (DM) were added in the control group (TCon); calcium chloride was added in one of the experimental groups (TCICa), and calcium sulfate was added in the other experimental group (TSoCa), both with DCAD= +30 mEq/kg of DM. After calving, they were fed on commercial feed, corn silage, and alfalfa grazing. The content of fat, protein, calcium, phosphorus, and magnesium in the colostrum was not different among the treatments (p0.05). TClCa cows produced a greater average of milk (kg/day), fat and protein corrected milk (kg/day), fat (kg/day), and net energy of lactation (Mcal/day). The TClCa group had higher milk production, and fat (kg) and protein (kg) content than TCon (p0.05), with intermediate values for TSoCa. The supply of calcium chloride in the prepartum of heifers produced differences in milk production and composition during the 305 days of lactation.

PURPOSE To determine the relative efficacy of intravenous therapy for postconcussive headaches in a pediatric population, as compared to oral therapy. METHODS Pediatric patients treated for postconcussive headaches at an outpatient infusion clinic from 2016 to 2018 were selected for inclusion in the study. Of the 95 patients who were treated in clinic, 53 patients were selected for a retrospective chart review. Clinic visits before and after infusions were reviewed to determine changes in headache score (HA), symptom severity score (SSS), and self-reported symptom relief. An age-matched and SSS-matched group served as a control. The control group received only oral therapy for their headaches. The infusion consisted of parenteral ketorolac, compazine, diphenhydramine, and a normal saline bolus (20 mg/kg). RESULTS Following infusion therapy, overall mean HA and SSS scores were both reduced (p

Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first-line CHT. TL was measured by southern blot at each CHT cycle and after 1 year from CHT completion. Median age was 59 yrs (range 22-77). Median number of CHT cycles was 6 (range 3-6). The majority of patients (79%, n = 27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1 year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p 0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre-treatment evaluation. Stratifying the analysis by gender and age only young women (51 years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients.

Su quali principi si regge oggi la didattica dell’italiano come lingua prima? Quali sono i contenuti imprescindibili della disciplina? Come si differenzia l’insegnamento linguistico a seconda dell’età degli allievi? E quali sono i nodi dell’italiano di oggi cui prestare maggiore attenzione in classe? A queste e ad altre domande il volume fornisce risposte puntuali, affrontando in modo mirato le modalità di insegnamento delle diverse abilità linguistiche (leggere, scrivere, ascoltare e parlare), della riflessione sulla lingua, della testualità e del lessico, in una prospettiva che contempla tutti gli ordini di scolarità e sempre tesa a coniugare la dimensione teorica generale con la pratica applicativa. I singoli argomenti sono approfonditi con costante riferimento alle esigenze dell’insegnante di italiano: i contenuti linguistici che deve conoscere, le modalità di programmazione, le strategie di insegnamento in aula e la valutazione dei risultati ottenuti.

In recent years, human dihydroorotate dehydrogenase inhibitors have been associated with acute myelogenous leukemia as well as studied as potent host targeting antivirals. Starting from MEDS433 (IC

The global availability of Sentinel-2 data and the widespread coverage of free-cost and high-resolution images nowadays give opportunities to map, at low-cost, shallow landslides triggered by extreme events (e.g. rainfall, earthquake). A rapid and low-cost shallow landslides mapping could improve damages estimations, susceptibility models or land management. This work presents a semi-automatic methodology to map potential landslides (PL) using Sentinel-2 images, and it is the first step toward more detailed mapping. We create a GIS-based and user-friendly methodology to extract PL based on pre- post- event NDVI variation and geomorphological filtering. The semi-automatic inventory was compared with benchmark landslides inventory drawn on high-resolution images. We also used the Google Earth Engine scripts to extract the NDVI time series and make a multi-temporal analysis. We apply this to two study areas in NW Italy hatted in 2016 and 2019 by extreme rainfall events. The results show that the semi-automatic mapping based on Sentinel-2 allows detecting the majority of shallow landslides larger than satellite ground pixel (100 m2). PL density and distribution well match with the benchmark. However, the false positives (30 % to 50 % of cases) are challenging to filter, especially when they correspond to river bank erosions or cultivated land.

Prevention programs like Nurse-Family Partnership® (NFP) must enroll and retain clients of the intended population to maximize program impact. NFP is an evidence-based nurse home visitation program shown in randomized trials to improve maternal and child health and life course outcomes for first-time parents experiencing economic adversity, particularly for mothers with limited psychological resources. The purpose of this study was to understand enrollment and engagement experiences of mothers with previous live births referred to NFP in a formative study of the program for this population, but did not enroll or dropped out before program graduation. We used a grounded theory approach and purposively selected three NFP sites with variation in enrollment rates. We conducted telephone interviews with 23 mothers who were either referred to NFP and declined enrollment or former clients who dropped out before graduation. All interviews were conducted in English, recorded, transcribed, and validated. We developed an iterative codebook with multiple coders to analyze our data in NVivo11 and wrote thematic memos to synthesize data across study sites. Mothers described experiencing overlapping risk factors including physical and behavioral health conditions, child welfare involvement, and housing insecurity. Mothers from all sites discussed how they were referred to the NFP program, their experience of the enrollment process, reasons for enrolling or not enrolling, and reasons for dropping out after initial enrollment. Key themes that influenced mothers’ decision-making were: perceptions of program value, not needing the program, their living situation or being too busy as a deterrence, and past experiences including a distrust of health care. Reasons for attrition were related to no longer needing the service, being assigned a new nurse, being too tired postpartum, and moving out of the service area. One way to support home visiting nurses in family enrollment and engagement is to build their professional capacity to implement trauma-informed strategies given mothers’ life experiences.

Nurse home visitors in Nurse-Family Partnership® (NFP) work with mothers experiencing social and economic adversities to improve their and their children's health. Collaboration between nurse home visitors and primary care providers (PCPs: healthcare providers and social workers embedded within obstetrics, paediatrics and family medicine practices) can improve service delivery for families experiencing the greatest adversities. However, little is known about how and to what extent PCPs collaborate with home visiting nurses. We conducted a single exploratory case study between April 2019 and February 2020 to better understand how PCPs collaborate with home visiting nurses to meet family needs in one NFP site, purposefully selected for strong collaboration. We conducted in-depth qualitative interviews with 22 PCPs, including 5 nurses, 7 physicians, 7 social workers and 3 non-direct care professionals, including patient navigator and hospital executives. Interviews were recorded, transcribed, validated and coded inductively. Codes were grouped into broader categories and thematic memos across provider role were written to triangulate perspectives. Healthcare providers interacted with home visiting nurses mainly during the referral process, while social workers provided more specific examples of service co-ordination. In this case study, we saw mutual awareness, co-operation and collaboration to serve families with high needs. Even in this case, purposefully selected to represent strong collaboration, there were opportunities to enhance co-ordination to improve the health and social needs of young families experiencing adversity.

Rockfalls are a major hazard in mountain areas. They can endanger human settlements and infrastructures, and, every year, cause multiple damage and victims. An investigation of those areas more susceptible to rockfall represents a key approach to improve the analysis and management of rockfall impact and consequences. The proposed procedure involves the study of occurred rockfall databases and thematic maps to compute a susceptibility map, by the employment of Analytical Hierarchic Process. The computation is focused on the road network of Aosta Valley Region (northwestern Italy) and its proximity. The model results highlight the importance of morphometric factors on the investigated phenomena. The outcomes of the analysis were also validated by comparing rockfall databases with the receiver operating characteristic curve, in order to confirm their reliability. The results of the procedure are a starting point for a detailed planning action in order to manage the hazard related to these phenomena.

The connection with acute myelogenous leukemia (AML) of dihydroorotate dehydrogenase (hDHODH), a key enzyme in pyrimidine biosynthesis, has attracted significant interest from pharma as a possible AML therapeutic target. We recently discovered compound 1, a potent hDHODH inhibitor (IC50 = 1.2 nM), able to induce myeloid differentiation in AML cell lines (THP1) in the low nM range (EC50 = 32.8 nM) superior to brequinar's phase I/II clinical trial (EC50 = 265 nM). Herein, we investigate the 1 drug-like properties observing good metabolic stability and no toxic profile when administered at doses of 10 and 25 mg/kg every 3 days for 5 weeks (Balb/c mice). Moreover, in order to identify a backup compound, we investigate the SAR of this class of compounds. Inside the series, 17 is characterized by higher potency in inducing myeloid differentiation (EC50 = 17.3 nM), strong proapoptotic properties (EC50 = 20.2 nM), and low cytotoxicity toward non-AML cells (EC30(Jurkat) > 100 μM).

Defective proprioceptive integration may play a role in the pathophysiology of motor symptoms in Parkinson's disease (PD). Dysfunction related to proprioceptively-evoked postural reactions in PD patients is still a controversial issue, with only a limited number of studies to date and mostly discordant results. The aims of the present study were (1) to determine whether or not the proprioceptive defect in PD underlies postural impairment and (2) whether or not deep brain stimulation of the subthalamic nucleus (STN-DBS) affects proprioceptive integration. We examined proprioceptive integration during a postural task in 13 PD patients and 12 age-matched control subjects, using a muscle-tendon vibration paradigm. Analysis of the center of pressure displacement and kinematic data indicates a greater degree of postural destabilization and a reduced ability to maintain a vertical orientation in PD. We found a significant positive effect of STN-DBS on these postural features. Our findings indicate that Parkinson patients, even in the absence of any clinical evidence of instability, falls, or freezing, use proprioceptive information for postural control less efficiently than healthy subjects. Furthermore, STN-DBS was found to improve proprioceptive integration, with positive impacts on postural orientation and balance.

Additional file 1: Supplementary data.

Host immune homeostasis as an independent prognostic indicator has been inadequately evaluated in aggressive non-Hodgkin’s lymphomas (NHL). The present study addresses the prognostic significance in aggressive NHLs of the immunologic profile evaluated by pretreatment serum levels of immunoglobulins (Ig) and lymphocyte-monocyte ratio (LMR). In this series of 90 patients with aggressive lymphoma, the median level for IgG was 1,024mg/dl (range 436–2236), and for LMR was 2.2 (range 0.2–13.8). CR rate was higher with IgG levels ≥1,024mg/dL (91% vs 77% p=0.059). LMR ≤ 2.2 was associated with lower 1-year PFS (73% vs. 92%, p 0.016). Patients with good/very good R-IPI showed a reduced PFS if IgG or LMR was low, while patients with poor R-IPI did better if LMR or IgG levels were high. We combined both parameters with the R-IPI and produced a four-risk prognostic score showing one-year PFS of 95% (95% CI 68%–99%), 100% (95% CI 100%–100%), 73% (95% CI 52%–86%), and 59% (95% CI 31%–79%), in patients with zero, one, two and three risk factors, respectively. The results indicate for the first time the value of baseline serum Ig levels in the prognostic assessment of aggressive lymphoma.

Sensorimotor adaptation involves the recalibration of the mapping between motor command and sensory feedback in response to movement errors. Although adaptation operates within individual movements on a trial-to-trial basis, it can also undergo learning when adaptive responses improve over the course of many trials. Brain oscillatory activities related to these “adaptation” and “learning” processes remain unclear. The main reason for this is that previous studies principally focused on the beta band, which confined the outcome message to trial-to-trial adaptation. To provide a wider understanding of adaptive learning, we decoded visuomotor tasks with constant, random or no perturbation from EEG recordings in different bandwidths and brain regions using a multiple kernel learning approach. These different experimental tasks were intended to separate trial-to-trial adaptation from the formation of the new visuomotor mapping across trials. We found changes in EEG power in the post-movement period during the course of the visuomotor-constant rotation task, in particular an increased (i) theta power in prefrontal region, (ii) beta power in supplementary motor area, and (iii) gamma power in motor regions. Classifying the visuomotor task with constant rotation versus those with random or no rotation, we were able to relate power changes in beta band mainly to trial-to-trial adaptation to error while changes in theta band would relate rather to the learning of the new mapping. Altogether, this suggested that there is a tight relationship between modulation of the synchronization of low (theta) and higher (essentially beta) frequency oscillations in prefrontal and sensorimotor regions, respectively, and adaptive learning.

Introduction Neurofibromatosis type 1 (NF1) is considered a model of neurodevelopmental disorder because of the high frequency of learning deficits, especially developmental coordination disorder. In neurodevelopmental disorder, Nicolson and Fawcett formulated the hypothesis of an impaired procedural learning system that has its origins in cortico-subcortical circuits. Our aim was to investigate the relationship between cortico-striatal connectivity and procedural perceptual-motor learning performance and motor skills in NF1 children. Methods Seventeen NF1 and 18 typically developing children aged between 8 and 12 years old participated in the study. All were right-handed and did not present intellectual or attention deficits. In all children, procedural perceptual-motor learning was assessed using a bimanual visuo-spatial serial reaction time task (SRTT) and motor skills using the Movement Assessment Battery for Children (M-ABC). All participants underwent a resting-state functional MRI session. We used a seed-based approach to explore cortico-striatal connectivity in somatomotor and frontoparietal networks. A comparison between the groups’ striato-cortical connectivity and correlations between connectivity and learning (SRTT) and motor skills (M-ABC) were performed. Results At the behavioral level, SRTT scores are not significantly different in NF1 children compared to controls. However, M-ABC scores are significantly impaired within 9 patients (scores below the 15th percentile). At the cerebral level, NF1 children present a higher connectivity in the cortico-striatal regions mapping onto the right angular gyrus compared to controls. We found that the higher the connectivity values between these regions, differentiating NF1 and controls, the lower the M-ABC scores in the whole sample. No correlation was found for the SRTT scores. Conclusion NF1 children present atypical hyperconnectivity in cortico-striatal connections. The relationship with motor skills could suggest a sensorimotor dysfunction already found in children with developmental coordination disorder. These abnormalities are not linked to procedural perceptual-motor learning assessed by SRTT.

Introduction NF1 children have cognitive disorders, especially in executive functions, visuospatial, and language domains, the pathophysiological mechanisms of which are still poorly understood. Materials and methods A correlation study was performed from neuropsychological assessments and brain MRIs of 38 NF1 patients and 42 controls, all right-handed, aged 8–12 years and matched in age and gender. The most discriminating neuropsychological tests were selected to assess their visuospatial, metaphonological and visuospatial working memory abilities. The MRI analyses focused on the presence and location of Unidentified Bright Objects (UBOs) (1), volume analysis (2) and diffusion analysis (fractional anisotropy and mean diffusivity) (3) of the regions of interest including subcortical structures and posterior fossa, as well as shape analysis of subcortical structures (4). The level of attention, intelligence quotient, age and gender of the patients were taken into account in the statistical analysis. Then, we studied how diffusion and volumes parameters were associated with neuropsychological characteristics in NF1 children. Results NF1 children present different brain imaging characteristics compared to the control such as (1) UBOs in 68%, (2) enlarged total intracranial volume, involving all subcortical structures, especially thalamus, (3) increased MD and decreased FA in thalamus, corpus callosum and hippocampus. These alterations are diffuse, without shape involvement. In NF1 group, brain microstructure is all the more altered that volumes are enlarged. However, we fail to find a link between these brain characteristics and neurocognitive scores. Conclusion While NF1 patients have obvious pathological brain characteristics, the neuronal substrates of their cognitive deficits are still not fully understood, perhaps due to complex and multiple pathophysiological mechanisms underlying this disorder, as suggested by the heterogeneity observed in our study. However, our results are compatible with an interpretation of NF1 as a diffuse white matter disease.

Secondary acute myeloid leukemia (sAML) poorly responds to conventional treatments and allogeneic stem cell transplantation (HSCT). We evaluated toxicity and efficacy of CPX-351 in 71 elderly patients (median age 66 years) with sAML enrolled in the Italian Named (Compassionate) Use Program. Sixty days treatment-related mortality was 7% (5/71). The response rate at the end of treatment was: CR/CRi in 50/71 patients (70.4%), PR in 6/71 (8.5%), and NR in 10/71 (19.7%). After a median follow-up of 11 months relapse was observed in 10/50 patients (20%) and 12 months cumulative incidence of relapse (CIR) was 23.6%. Median duration of response was not reached. In competing risk analysis, CIR was reduced when HSCT was performed in first CR (12 months CIR of 5% and 37.4%, respectively, for patients receiving (=20) or not (=30) HSCT, p = 0.012). Twelve-months OS was 68.6% (median not reached). In landmark analysis, HSCT in CR1 was the only significant predictor of longer survival (12 months OS of 100 and 70.5%, for patients undergoing or not HSCT in CR1, respectively, p = 0.011). In conclusion, we extend to a real-life setting, the notion that CPX is an effective regimen for high risk AML patients and may improve the results of HSCT.

In recent years, Cinque Terre National Park, one of the most famous UNESCO sites in Italy, experienced a significant increase in tourist visits. This unique landscape is the result of the rough morphology of a small coastal basin with a very steep slope and a long-term human impact, mainly represented by anthropic terraces. This setting promotes the activation of numerous geo-hydrological instabilities, primarily related to heavy rainfall events that often affect this area. Currently, the main challenge for the administrators of Cinque Terre National Park is the correct maintenance of this environment along with the functional management of the hiking trail to ensure the safety of tourists. The definition of a methodology for effective management is mandatory for the sustainable administration of this unique site. We implement a new codified procedure based on the combined use of the Operative Monography and the Survey Form, focusing on the &ldquo, Sentiero Verde-Azzurro&rdquo, trail, for a proper description of the known landslides affecting the trail and the identification of damage and/or landslides activated by critical meteorological events. This guarantees effective geo-hydrological risk management, which is also applicable to other similar sites in a unique environmental and cultural heritage site such as Cinque Terre Park.

Perceiving and extracting information from others rely on functional Perception Action Coupling. Because motor experiences influence the strength of the perception action coupling, we explored the duality between vision and proprioceptive information about the self and others in body perception using a sequential same-different visual task from 6 to 7 years old to adults. Using a same-different matching task combined with congruent or incongruent action execution, this study explored in 30 children (M ± SD: 9.2 ± 1.5; 16♀), 33 adolescents (M ± SD: 14.7 ± 1.5; 16♀) and 28 adults (M ± SD: 29.5 ± 6.5; 12♀) how the congruence of the perception action coupling could influence the body representation building in memorizing and discriminating other's postures. The first result revealed better performances to perceive other's body postural changes compared to objects' shapes modifications as early as 6-7 years old. Nevertheless, this ability needs a long time to mature as reflected by the lower performances in children compared to older groups, i.e. adolescents and young adults. In addition, executing a congruent action during the encoding phase increased the RT, reflecting involvement of additional cognitive processes of self-other correspondence, without improving the performance accuracy, due to a slow maturation of multimodal body representations. On the other hand, executing an incongruent action during the encoding phase revealed an interference effect to perceive others' posture, demonstrated by the decrease of performance accuracy. As we initially hypothesized, the strength of perception action coupling appears to be modulated by age. Indeed, the interference effect had a greater impact in adolescents involved in a different judgment of two body postures. Therefore, the assessment of the perception action coupling may predict the body representation maturity in typical development or internal body representation dysfunction in neurodevelopmental disorders.

Background:. Resident cosmetic clinics (RCCs) are the training modality of choice among both residents and faculty and are a mainstay at most residency programs.1–4 Despite this, knowledge of RCCs among plastic surgery consumers remains untested. We hypothesize that the public would be aware of and receptive to RCCs. Methods:. Participants with prior cosmetic procedures or interest in future cosmetic procedures were recruited using Amazon Mechanical Turk and asked to complete a survey in September 2020. First, prior awareness of RCCs was assessed. After a brief description of RCCs, perceptions of safety and preferences for care were assessed. Results:. After screening for quality, 815 responses were included. Forty-five percent of consumers were aware of RCCs. Seventy-six percent of consumers believed that RCCs were just as safe as attending clinics and 65% were comfortable receiving care from fourth-year residents or higher. Belief in RCC safety was associated with 4.8 times higher odds of feeling comfortable receiving care at an RCC [95% confidence interval (3.3–7.1), P < 0.001]. When given a hypothetical choice between residents and attendings in two scenarios, 46% of consumers chose residents for abdominoplasty and 60% chose residents for Botox injections. Belief in RCC safety was associated with choosing a resident or being indifferent in both scenarios. Conclusions:. Consumer preference regarding RCCs has largely been untested. This study shows that belief in RCC safety influences consumers’ perceived comfort with receiving care at an RCC. This knowledge can help guide RCC practice and maximize learning opportunities for surgeons-in-training.

Introduction FLT3 receptor gene has been reported to be mutated in about 30% of AML, with two different kinds of mutations identified: in-frame duplications within the juxtamembrane region (FLT3-ITD) and point mutations in the tyrosine kinase domain (FLT3-TKD). In term of prognosis, the proper role of these mutations is still debated. Moreover, FLT3 mutations are often subjected to clonal evolution, thus how to properly monitor FLT3 mutated clones, evaluate minimal residual disease, manage FLT3 inhibitors (FLT3i) are only some of the open issues. FLAM is an observational study involving FLT3 positive AMLs to gain clinical and molecular data useful to ameliorate real-life physicians' management of this disease. Here we report the results of a preliminary analysis of the retrospective phase of the study. Methods The retrospective phase of FLAM multi-center observational study enrolled each AML patient treated in 33 participating Italian centers detected to carry a FLT3 mutation since 2012. Clinical and molecular data were collected in accordance with GCP and Helsinki declaration in electronic case report forms. Results At data cut-off , 1st of July 2020, 289 patients with FLT3 mutation at diagnosis were enrolled in the retrospective phase of FLAM study, being evaluable in this analysis, with a median age at diagnosis of 62 years (min-max: 18-94) and a M:F ratio of 141/148 (Patients' characteristics are summarized in table 1). 29 out 289 (10 %) patients had a low risk AML, 190/289 (65,7 %) had an intermediate risk AML and 27/289 (9,3 %) patients had a high risk AML, according to ELN 2017 risk stratification or ELN 2010 in case of allelic ratio unavailability (43 patients had no available ELN risk at baseline). A more frequent association between FLT3-ITD and normal karyotype and between FLT3-TKD mutation and other cytogenetic alterations not conferring a favorable/adverse risk has been observed (p = 0.045). Among the study population, 255/289 (88 %) patients carried a FLT3-ITD, 32/289 (11 %) a FLT3-TKD point mutation and 2/289 (1 %) patients both mutations. Capillary electrophoresis has been the technical method used to investigate FLT3-ITD in 163 of 226 (72 %) patients with information on the method used, while Sanger Sequencing in 47 out of 226 (21 %) patients and Next generation sequencing (NGS) in 16 out of 226 (7 %) patients. Overall, NGS has been adopted to investigate FLT3 gene status in 18 out of 259 patients (7 %). FLT3-ITD allelic ratio was available in 62 of 257 (24 %) ITD patients and was greater than or equal to 0.5 in 35/62 (56 %) patients. During patients' follow-up, 19/289 (7 %) patients affected by a FLT3 positive AML at diagnosis underwent a disease clonal evolution with a FLT3 negative AML progression or relapse. Regarding treatment options in FLT3-AML, in our cohort FLT3i were administered as first-line of therapy in only 36/289 (13 %) patients, always in a combination, of which in 26/36 (72.2 %) with intensive chemotherapy. As expected, intensive chemotherapy represented the induction regimen in the majority of the patients (211/289, 73 %). On the other hand, FLT3i were administered as rescue therapy in 62/171 (36 %) cases (47/62 single-agent and in 15/62 in combination) and as re-induction therapy in 22/80 (28 %) cases (10/22 single-agent and 12/22 in combination). Overall, a FLT3i has been administered as single-agent 81 times, of which Gilteritinib was the most frequently used (56/81, 69,1 %), followed by quizartinib (18/81, 22,2 %). Among the 52 documented combinations of a FLT3i with other drugs, particularly noteworthy is the administration of Sorafenib, in 20/52 (39 %) cases in this real-life study. Lastly, nine out of 289 (3 %) patients received a FLT3i as maintenance therapy after HSCT. Data regarding the correlation among the different regimens, with a special focus on FLT3i, other molecular features and response/survival are currently under analysis. Conclusions These data coming from a preliminary analysis portray the state of a large multi-center retrospective cohort of FLT3-positive AML patients treated in Italy between 2012 and 2020, including interesting insights regarding technical methods used to characterize the disease and the therapeutic scenario in which FLT3 inhibitors have been developed. Further safety and effectiveness data may reveal beneficial to ameliorate physicians' real-life clinical practice. Acknowledgements: work supported by Daiichi-Sankyo. Disclosures Martelli: Amgen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Rigolin:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Fracchiolla:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Speakers Bureau; ABBVIE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Speakers Bureau. Bocchia:Incyte: Honoraria; CELGENE: Honoraria. Todisco:Jannsen, Abbvie, Jazz: Membership on an entity's Board of Directors or advisory committees. Papayannidis:Abbvie, Janssen, Novartis, Amgen, Pfizer: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. OffLabel Disclosure: Sorafenib is a registered drug for the treatment of hepatocellular carcinoma. Due to its multi-targeted tirosine kinase inhibitor effect it demonstrated efficacy in FLT3-AML when administered as an off-label prescription.

Background Tibialis anterior (TA) tendinosis is rarely reported on in the literature. It is seen in patients older than 45 and causes weakness in dorsiflexion. This paper aims to describe surgical treatment and clinical outcomes. Methods Between 2015 and 2018, nine patients (six females, three males) with severe TA tendinosis with no tear (2), partial (1), or complete (6) underwent operative treatment. Patients underwent debridement and direct repair without augmentation, direct repair with fiber tape augmentation, tibialis posterior tendon (PTT) transfer, or tibialis anterior tendon (TAT) augmentation with a tendon autograft (n = 4). Autografts consisted of extensor digitalis longus (EDL) tendon, plantaris tendon, or both. Results Mean postoperative follow-up was 21.3 (range 8–31) months. All patients had a concomitant gastrocnemius recession, and three had hindfoot arthrodesis. Preoperative dorsiflexion strength was 0/5 for all and improved to 5/5 postoperatively in seven. The only current smoker developed wound dehiscence 2 weeks postoperatively and healed by 4. One developed marginal skin necrosis 3 weeks postoperatively and was treated successfully with casting. Conclusion Surgery reestablished function in individuals with TA tendinosis and allowed high level of satisfaction. Direct repair is possible. If the tendon gap is too large an autograft of EDL and plantaris tendon can be utilized. Level of evidence: Level III Retrospective Comparative Study

Chronic myeloid leukemia (CML) is caused by BCRABL1 in a cell with the biological potential, intrinsic or acquired, to cause leukemia. This cell is commonly termed the CML leukemia stem cell (LSC). In humans a CML LSC is operationally-defined by ≥1 in vitro or in vivo assays of human leukemia cells transferred to immune-deficient mice. Results of these assays are sometimes discordant. There is also the unproved assumption that biological features of a CML LSC are stable. These considerations make accurate and precise identification of a CML LSC difficult or impossible. In this review, we consider biological features of CML LSCs defined by these assays. We also consider whether CML LSCs are susceptible to targeting by tyrosine kinase inhibitors (TKIs) and other drugs, and whether elimination of CML LSCs is needed to achieve therapy-free remission or cure CML.

The shallow landslides assessment is a hard task in territories featuring composite influence of natural and anthropic factors. In Liguria region (northwestern Italy), the landscape presents widespread human intervention prevalently represented by terraces. The assessment of predisposing factors in such landscape deserve a multidisciplinary approach. We implemented a classification methodology based on the Analytical Hierarchy Process. In GIS environment we overlaid several layers: (i) slope, (ii) land use, (iii) lithology, and (iv) aspect. Slope and aspect have been computed on a filtered (based on TPI) high-resolution DTM with the removal of terraces, in order to obtain the pristine slope pattern. Each spatial data was then reclassified according to the weighting procedures thus producing a landslide susceptibility map. This methodology represents a starting point for the correct assessment of shallow landslides occurrence, capable to generate a map, taking in account of the peculiar features of this extremely man-made territory.

Hyperextension-distraction type injury of the thoracolumbar spine is an unstable fracture pattern that generally necessitates surgical stabilization by posterior instrumentation. Care must be taken when positioning these patients from supine to prone due to the unstable nature of their injury. The study objectives were (1) to describe a novel modification of the Jackson table turn technique, which may be safer and more effective than the conventional log-roll method and traditional Jackson table technique for positioning patients with hyperextension-distraction injuries of the thoracolumbar spine from supine to prone in the operating room and (2) to present two cases in which this technique was successfully performed. Two patients were carefully positioned from supine to prone by our modification of the Jackson table turn technique, which utilizes a Wilson frame sandwiched between two flat-top Jackson frames. Case 1: a 65-year-old female presented status-post motor vehicle collision with a T9–T10 extension-distraction injury, requiring T7–T12 posterior spinal instrumented fusion (PSIF). Case 2: a 72-year-old female presented status-post motor vehicle collision with a T9–T10 extension-distraction injury and an unstable L1 burst fracture, requiring T7–L2 PSIF. Both patients remained hemodynamically stable and neurologically intact throughout positioning and postoperatively. This technique is safe and effective for positioning patients with hyperextension-distraction type injuries of the thoracolumbar spine from supine to prone in the operating room and may be superior to conventional methods. These slides can be retrieved under Electronic Supplementary Material.

Prevention programs like Nurse-Family Partnership® (NFP) must enroll and retain clients of the intended population to maximize program impact. NFP is an evidence-based nurse home visitation program shown in randomized trials to improve maternal and child health and life course outcomes for first-time parents experiencing economic adversity, particularly for mothers with limited psychological resources. The purpose of this study was to understand enrollment and engagement experiences of mothers with previous live births referred to NFP in a formative study of the program for this population, but did not enroll or dropped out before program graduation. We used a grounded theory approach and purposively selected three NFP sites with variation in enrollment rates. We conducted telephone interviews with 23 mothers who were either referred to NFP and declined enrollment or former clients who dropped out before graduation. All interviews were conducted in English, recorded, transcribed, and validated. We developed an iterative codebook with multiple coders to analyze our data in NVivo11 and wrote thematic memos to synthesize data across study sites. Mothers described experiencing overlapping risk factors including physical and behavioral health conditions, child welfare involvement, and housing insecurity. Mothers from all sites discussed how they were referred to the NFP program, their experience of the enrollment process, reasons for enrolling or not enrolling, and reasons for dropping out after initial enrollment. Key themes that influenced mothers' decision-making were: perceptions of program value, not needing the program, their living situation or being too busy as a deterrence, and past experiences including a distrust of health care. Reasons for attrition were related to no longer needing the service, being assigned a new nurse, being too tired postpartum, and moving out of the service area. One way to support home visiting nurses in family enrollment and engagement is to build their professional capacity to implement trauma-informed strategies given mothers' life experiences.

The connection with acute myelogenous leukemia (AML) of dihydroorotate dehydrogenase (hDHODH), a key enzyme in pyrimidine biosynthesis, has attracted significant interest from pharma as a possible AML therapeutic target. We recently discovered compound 1, a potent hDHODH inhibitor (IC50 = 1.2 nM), able to induce myeloid differentiation in AML cell lines (THP1) in the low nM range (EC50 = 32.8 nM) superior to brequinar’s phase I/II clinical trial (EC50 = 265 nM). Herein, we investigate the 1 drug-like properties observing good metabolic stability and no toxic profile when administered at doses of 10 and 25 mg/kg every 3 days for 5 weeks (Balb/c mice). Moreover, in order to identify a backup compound, we investigate the SAR of this class of compounds. Inside the series, 17 is characterized by higher potency in inducing myeloid differentiation (EC50 = 17.3 nM), strong proapoptotic properties (EC50 = 20.2 nM), and low cytotoxicity toward non-AML cells (EC30(Jurkat) > 100 μM).

Prende l’avvio, con questo fascicolo, DIDIT. Didattica dell’italiano. Studi applicati di lingua e letteratura, una nuova rivista scientifica nata dalla collaborazione tra il Centro competenze didattica dell’italiano lingua di scolarizzazione del Dipartimento formazione e apprendimento della Scuola universitaria professionale della Svizzera italiana e l’Alta scuola pedagogica dei Grigioni. Alla rivista partecipano quindi due istituzioni universitarie che si occupano della formazione degli insegnanti del Ticino e dei Grigioni, i due cantoni svizzeri in cui l’italiano è lingua ufficiale (nei Grigioni accanto al tedesco e al romancio): un contesto del tutto particolare, che vede l’italiano insieme lingua di scolarizzazione e lingua prima (in Ticino e nel Grigioni italiano), lingua seconda (in Ticino) e lingua straniera nella scuola dell’obbligo (nella parte tedesca del Canton Grigioni). In una realtà così peculiare dal punto di vista linguistico e culturale, DIDIT intende offrire uno strumento di ricerca e aggiornamento rivolto a chi opera, per ragioni di studio o di lavoro, nell’ambito della didattica dell’italiano come lingua prima, come lingua seconda o come lingua straniera. Vista la particolare situazione linguistica del Canton Grigioni, del limitrofo Alto Adige e tenuto conto delle diverse altre lingue presenti sul territorio grigionese e ticinese accanto alle lingue ufficiali, la nuova rivista prende in considerazione anche la ricerca sulla didattica del plurilinguismo. In questo senso la rivista si presenta come luogo di scambio scientifico privilegiato e unico nel panorama delle pubblicazioni scientifiche presenti sul territorio nazionale svizzero e come uno dei pochi strumenti a livello internazionale che prendono in esame l’italiano nei diversi contesti di insegnamento; l’obiettivo sul medio-lungo termine è di configurarsi come un punto di riferimento nel campo degli studi sulla didattica dell’italiano e del plurilinguismo, caratterizzati dal costante connubio tra dimensione teorica e dimensione applicativa. DIDIT è divisa in tre sezioni: Studi e ricerche, Esperienze didattiche e Recensioni e segnalazioni. La prima, affidata alla penna di studiose e studiosi di chiara fama nel settore della didattica della lingua e della letteratura italiana (in questo primo numero Maria G. Lo Duca e Giuliana Fiorentino e, per la tematica del plurilinguismo, Ruth Videsott), accoglie approfondimenti teorici su temi afferenti agli ambiti didattici sopra ricordati. La seconda è dedicata a esempi di applicazioni e percorsi didattici, affidati a studiose e studiosi, ricercatrici e ricercatori, docenti attive e attivi nella scuola di ogni ordine e grado (in questo numero Livia Radici Tavernese, Daniele Dell’Agnola, Stefania Crameri e Daniela Kappler). La terza presenta, infine, recensioni di libri e studi che possono contribuire all’innovazione didattica nelle discipline di riferimento e a segnalazioni di opere – come albi illustrati, poesie, raccolte di racconti e romanzi – rivolte a lettori di diverse fasce di età. Tenuto conto dei contesti minoritari con cui si vede confrontato l’italiano in Svizzera, la rivista ambisce a diventare anche uno strumento per il sostegno e la promozione della lingua italiana in questo contesto nazionale, e non solo. In tal senso, si propone di estendere il proprio orizzonte agli studi sulla didattica dell’italiano in un’accezione ampia, che accolga prospettive plurali e sguardi capaci di spaziare dalla teoria all’applicazione pratica, avendo sempre come obiettivo di fondo un aggiornamento costante sulle strategie, sui metodi, sulle ricerche volte a migliorare e a innovare l’insegnamento dell’italiano. In tal modo la rivista garantisce lo scambio e la comunicazione tra il mondo della ricerca e quello della scuola, a livello nazionale e internazionale: attraverso la scelta dei temi, degli ambiti di ricerca e di riflessione, DIDIT vuole così rispondere alle sfide didattiche e teoriche poste alla disciplina e stimolare il dibattito scientifico e pubblico.

Simple Summary Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors. CML LSCs have many features in common with hematopoietic stem cells (HSCs) and selectively targeting this population and sparing HSCs is of paramount importance. Targeted therapy by liposome via reducing side effects, controlled release, and versatile surface modifications is an effective way for the treatment of different cancers including leukemia. Here for the first time, we designed a liposome conjugated with Begelomab (anti-CD26) loaded with venetoclax to selectively target CD26+ CML LSCs/progenitor cells and to increase treatment outcome in CML patients. We proved that after antigen binding and drug release, the CD26+ LSCs/progenitor cells could be eliminated without any side effect on CD26− cells. Abstract CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26− cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients.