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This is the first study to describe the daytime evolution of respiratory parameters in mechanically ventilated COVID-19 patients. The data base refers to patients hospitalised in the intensive care unit (ICU) at Arequipa Hospital (Peru, 2335 m) in 2021. In both survivors (S) and non-survivors (NS) patients, a remarkable decrease in respiratory compliance was observed, revealing a proportional decrease in inflatable alveolar units. The S and NS patients were all hyperventilated and their SatO 2 was maintained at >90%. However, while S remained normocapnic, NS developed progressive hypercapnia. We compared the efficiency of O 2 uptake and CO 2 removal in the air blood barrier relying on a model allowing to partition between diffusion and perfusion limitations to gas exchange. The decrease in O 2 uptake was interpreted as diffusion limitation, while the impairment in CO 2 removal was modelled by progressive perfusion limitation. The latter correlated with the increase in positive end-expiratory pressure (PEEP) and plateau pressure (Pplat), leading to capillary compression, increased blood velocity, and considerable shortening of the air-blood contact time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Miserocchi, Rezoagli, Muñoz-Del-Carpio-Toia, Paricahua-Yucra, Zubieta-DeUrioste, Zubieta-Calleja and Beretta.)

Purpose: The diagnostic accuracy of Narrow Band Imaging (NBI) in the endoscopic surveillance of ulcerative colitis (UC) has been disappointing in most trials which used the Kudo classification. We aim to compare the performance of NBI in the lesion characterization of UC, when applied according to three different classifications (NICE, Kudo, Kudo-IBD)., Methods: In a prospective, real-life study, all visible lesions found during consecutive surveillance colonoscopies with NBI (Exera-II CV-180) for UC were classified as suspected or non-suspected for neoplasia according to the NICE, Kudo and Kudo-IBD criteria. The sensitivity (SE), specificity (SP), positive (+LR) and negative (-LR) likelihood ratios of the three classifications were calculated, using histology as the reference standard., Results: 394 lesions (mean size 6 mm, range 2-40 mm) from 84 patients were analysed. Twenty-one neoplastic (5%), 49 hyperplastic (12%), and 324 inflammatory (82%) lesions were found. The diagnostic accuracy of the NICE, Kudo and Kudo-IBD classifications were, respectively: SE 76%-71%-86%; SP 55-69%-79% (p < 0.05 Kudo-IBD vs. both Kudo and NICE); +LR 1.69-2.34-4.15 (p < 0.05 Kudo-IBD vs. both Kudo and NICE); -LR 0.43-0.41-0.18., Conclusion: The diagnostic accuracy of NBI in the differentiation of neoplastic and non-neoplastic lesions in UC is low if used with conventional classifications of the general population, but it is significantly better with the modified Kudo classification specific for UC., (© 2024. The Author(s).)

This study focuses on characterising two seasoned products, violino and bresaola, derived from grass-fed Bergamasca sheep monitored with a GPS system. The evaluation includes both nutritional and sensory aspects. Results reveal that both products boast a high protein content (approximately 40%) and a beneficial fatty acid profile, endorsing a healthy n-6/n-3 ratio (2.2), along with rumenic acid (92-184 mg/100 g) and branched-chain fatty acids (BCFAs) (237-621 mg/100 g). The sensory evaluation highlights distinctive ovine characteristics in aroma and flavour. Violino and bresaola from grass-fed Bergamasca sheep showcase positive attributes for human consumption. The study emphasises the potential for added value to seasoned products from Bergamasca sheep through a traceable, sustainable, and health-conscious supply chain.

Background and Aims: Mutations in FDXR gene, involved in mitochondrial pathway, cause a rare recessive neurological disorder with variable severity of phenotypes. The most common presentation includes optic and/or auditory neuropathy, variably associated to developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures. The review of clinical findings in previously described cases from literature reveals also a significant incidence of sensorimotor peripheral polyneuropathy (22.72%) and ataxia (43.18%). To date, 44 patients with FDXR mutations have been reported. We describe here on two new patients, siblings, who presented with a quite different phenotype compared to previously described patients., Methods: Clinical, neurophysiological, and genetic features of two siblings and a systematic literature review focused on the clinical spectrum of the disease are described., Results: Both patients presented with an acute-sub-acute onset of peripheral neuropathy and only in later stages of the disease developed the typical features of FDXR-associated disease., Interpretation: The peculiar clinical presentation at onset and the evolution of the disease in our patients and in some cases revised from the literature shed lights on a new possible phenotype of FDXR-associated disease: a peripheral neuropathy which can mimic an acute inflammatory disease., (© 2023. Fondazione Società Italiana di Neurologia.)

The emergence of large language models has led to the development of powerful tools such as ChatGPT that can produce text indistinguishable from human-generated work. With the increasing accessibility of such technology, students across the globe may utilize it to help with their school work-a possibility that has sparked ample discussion on the integrity of student evaluation processes in the age of artificial intelligence (AI). To date, it is unclear how such tools perform compared to students on university-level courses across various disciplines. Further, students' perspectives regarding the use of such tools in school work, and educators' perspectives on treating their use as plagiarism, remain unknown. Here, we compare the performance of the state-of-the-art tool, ChatGPT, against that of students on 32 university-level courses. We also assess the degree to which its use can be detected by two classifiers designed specifically for this purpose. Additionally, we conduct a global survey across five countries, as well as a more in-depth survey at the authors' institution, to discern students' and educators' perceptions of ChatGPT's use in school work. We find that ChatGPT's performance is comparable, if not superior, to that of students in a multitude of courses. Moreover, current AI-text classifiers cannot reliably detect ChatGPT's use in school work, due to both their propensity to classify human-written answers as AI-generated, as well as the relative ease with which AI-generated text can be edited to evade detection. Finally, there seems to be an emerging consensus among students to use the tool, and among educators to treat its use as plagiarism. Our findings offer insights that could guide policy discussions addressing the integration of artificial intelligence into educational frameworks., (© 2023. The Author(s).)

Purpose: This review recalls the principles developed over a century to describe trans-capillary fluid exchanges concerning in particular the lung during exercise, a specific condition where dyspnea is a leading symptom, the question being whether this symptom simply relates to fatigue or also implies some degree of lung edema., Method: Data from experimental models of lung edema are recalled aiming to: (1) describe how extravascular lung water is strictly controlled by "safety factors" in physiological conditions, (2) consider how waning of "safety factors" inevitably leads to development of lung edema, (3) correlate data from experimental models with data from exercising humans., Results: Exercise is a strong edemagenic condition as the increase in cardiac output leads to lung capillary recruitment, increase in capillary surface for fluid exchange and potential increase in capillary pressure. The physiological low microvascular permeability may be impaired by conditions causing damage to the interstitial matrix macromolecular assembly leading to alveolar edema and haemorrhage. These conditions include hypoxia, cyclic alveolar unfolding/folding during hyperventilation putting a tensile stress on septa, intensity and duration of exercise as well as inter-individual proneness to develop lung edema., Conclusion: Data from exercising humans showed inter-individual differences in the dispersion of the lung ventilation/perfusion ratio and increase in oxygen alveolar-capillary gradient. More recent data in humans support the hypothesis that greater vasoconstriction, pulmonary hypertension and slower kinetics of alveolar-capillary O2 equilibration relate with greater proneness to develop lung edema due higher inborn microvascular permeability possibly reflecting the morpho-functional features of the air-blood barrier., (© 2022. The Author(s).)

In Southern Italy, since 2013, there has been an ongoing Olive Quick Decline Syndrome (OQDS) outbreak, due to the bacterium Xylella fastidiosa, which has caused a dramatic impact from both socio-economic and environmental points of view. The main players involved in OQDS are represented by the insect vector, Philaenus spumarius, its host plants (olive trees and weeds) and the bacterium, X. fastidiosa. Current agronomic practices are mainly based on uprooting the sick olive trees and their surrounding ones, with later installment of olive cultivars more resistant to the bacterium infection. Unfortunately, both of these practices are having an undesirable impact on the environment (most of these olive trees were monumental ones) and on the economy. Based on a mathematical model expressed in terms of a nontrivial system of ordinary differential equations, our analysis has provided a clear picture of all possible steady states (feasible equilibria) and their stability properties, corresponding to a variety of different parameter scenarios; all of this has been illustrated by a set of computational experiments. A significant original contribution of this paper is the proof of the global asymptotic stability of each of the feasible equilibria under its existence assumptions, a fact that excludes multiple equilibria under the given conditions. It has emerged that the removal of a suitable amount of weed biomass (host plants of the juvenile stages of the insect vector of X. fastidiosa) from olive orchards and surrounding areas leads to the eradication of the epidemic, without requiring neither the removal nor the substitution of the existing olive trees., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The air blood barrier phenotype can be reasonably described by the ratio of lung capillary blood volume to the diffusion capacity of the alveolar membrane ( Vc/Dm ), which can be determined at rest in normoxia. The distribution of the Vc/Dm ratio in the population is normal; Vc/Dm shifts from ∼1, reflecting a higher number of alveoli of smaller radius, providing a high alveolar surface and a limited extension of the capillary network, to just opposite features on increasing Vc/Dm up to ∼6. We studied the kinetics of alveolar-capillary equilibration on exposure to edemagenic conditions (work at ∼60% maximum aerobic power) in hypoxia (HA) (P I O 2 90 mmHg), based on an estimate of time constant of equilibration (τ) and blood capillary transit time ( Tt ). A shunt-like effect was described for subjects having a high Vc/Dm ratio, reflecting a longer τ (>0.5 s) and a shorter Tt (<0.8 s) due to pulmonary vasoconstriction and a larger increase in cardiac output (>3-fold). The tendency to develop lung edema in edemagenic conditions (work in HA) was found to be directly proportional to the value of Vc/Dm as suggested by an estimate of the mechanical properties of the respiratory system with the forced frequency oscillation technique., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miserocchi, Beretta, Rivolta and Bartesaghi.)

Studies on the effects of school openings or closures during the Covid-19 pandemic seem to reach contrasting conclusions even in similar contexts. We aim at clarifying this controversy. A mathematical analysis of compartmental models with subpopulations has been conducted, starting from the SIR model, and progressively adding features modeling outbreaks or upsurge of variants, lockdowns, and vaccinations. We find that in all cases, the in-school transmission rates only affect the overall course of the pandemic above a certain context dependent threshold. We provide rigorous proofs and computations of the thresdhold through linearization. We then confirm our theoretical findings through simulations and the review of data-driven studies that exhibit an often unnoticed phase transition. Specific implications are: awareness about the threshold could inform choice of data collection, analysis and release, such as in-school transmission rates, and clarify the reason for divergent conclusions in similar studies; schools may remain open at any stage of the Covid-19 pandemic, including variants upsurge, given suitable containment rules; these rules would be extremely strict and hardly sustainable if only adults are vaccinated, making a compelling argument for vaccinating children whenever possible., (© 2022. The Author(s).)

Background: The use of robotic technologies in pediatric rehabilitation has seen a large increase, but with a lack of a comprehensive framework about their effectiveness., Objective: An Italian Consensus Conference has been promoted to develop recommendations on these technologies: definitions and classification criteria of devices, indications and limits of their use in neurological diseases, theoretical models, ethical and legal implications. In this paper, we present the results for the pediatric age., Methods: A systematic search on Cochrane Library, PEDro and PubMed was performed. Papers published up to March 1st, 2020, in English, were included and analyzed using the methodology of the Centre for Evidence-Based Medicine in Oxford, AMSTAR2 and PEDro scales for systematic reviews and RCT, respectively., Results: Some positives aspects emerged in the area of gait: an increased number of children reaching the stance, an improvement in walking distance, speed and endurance. Critical aspects include the heterogeneity of the studied cases, measurements and training protocols., Conclusion: Many studies demonstrate the benefits of robotic training in developmental age. However, it is necessary to increase the number of trials to achieve greater homogeneity between protocols and to confirm the effectiveness of pediatric robotic rehabilitation.

This review analyses the mechanisms by which lung fluid balance is strictly controlled in the air-blood barrier (ABB). Relatively large trans-endothelial and trans-epithelial Starling pressure gradients result in a minimal flow across the ABB thanks to low microvascular permeability aided by the macromolecular structure of the interstitial matrix. These edema safety factors are lost when the integrity of the interstitial matrix is damaged. The result is that small Starling pressure gradients, acting on a progressively expanding alveolar barrier with high permeability, generate a high transvascular flow that causes alveolar flooding in minutes. We modeled the trans-endothelial and trans-epithelial Starling pressure gradients under control conditions, as well as under increasing alveolar pressure (Palv) conditions of up to 25 cmH 2 O. We referred to the wet-to-dry weight (W/D) ratio, a specific index of lung water balance, to be correlated with the functional state of the interstitial structure. W/D averages ∼5 in control and might increase by up to ∼9 in severe edema, corresponding to ∼70% loss in the integrity of the native matrix. Factors buffering edemagenic conditions include: (i) an interstitial capacity for fluid accumulation located in the thick portion of ABB, (ii) the increase in interstitial pressure due to water binding by hyaluronan (the "safety factor" opposing the filtration gradient), and (iii) increased lymphatic flow. Inflammatory factors causing lung tissue damage include those of bacterial/viral and those of sterile nature. Production of reactive oxygen species (ROS) during hypoxia or hyperoxia, or excessive parenchymal stress/strain [lung overdistension caused by patient self-induced lung injury (P-SILI)] can all cause excessive inflammation. We discuss the heterogeneity of intrapulmonary distribution of W/D ratios. A W/D ∼6.5 has been identified as being critical for the transition to severe edema formation. Increasing Palv for W/D > 6.5, both trans-endothelial and trans-epithelial gradients favor filtration leading to alveolar flooding. Neither CT scan nor ultrasound can identify this initial level of lung fluid balance perturbation. A suggestion is put forward to identify a non-invasive tool to detect the earliest stages of perturbation of lung fluid balance before the condition becomes life-threatening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Beretta, Romanò, Sancini, Grotberg, Nieman and Miserocchi.)

This study examined the feasibility and acceptability of a telerehabilitation intervention during the COVID-19 pandemic in a sample of children and young adults with Acquired Brain Injury (ABI). Thirteen patients and/or their families agreed to participate in the speech and neuropsychological telerehabilitation sessions. The treatment was synchronous, patient centered and aimed at improving specific abilities. Sessions were held twice a week over a 10-week period. Two questionnaires were completed both by parents and therapists to assess feasibility and acceptability. Neither technical issues nor clinical obstacles were found. The quality of the therapeutic relationship played a key role in the intervention. Synchronous telerehabilitation provided several advantages both for patients and therapists. Moreover, the patient centered intervention eased the burden of the caregivers at a time of high stress. The real-time telerehabilitation treatments were deemed suitable for children and young adults with ABI. Further studies are needed to support the use of telerehabilitation as an integral part of their standard care., (Copyright © 2021 Maria Chiara Oprandi, Alessandra Bardoni, Luisa Corno, Agata Marchetti Guerrini, Luigi Molatore, Elena Beretta, Federica Locatelli, Sandra Strazzer, Geraldina Poggi.)

In pediatric acquired brain injury, heterogeneity of functional response to specific rehabilitation treatments is a key confound to medical decisions and outcome prediction. We aimed to identify patient subgroups sharing comparable trajectories, and to implement a method for the early prediction of the long-term recovery course from clinical condition at first discharge. 600 consecutive patients with acquired brain injury (7.4 years ± 5.2; 367 males; median GCS = 6) entered a standardized rehabilitation program. Functional Independent Measure scores were measured yearly, until year 7. We classified the functional trajectories in clusters, through a latent class model. We performed single-subject prediction of trajectory membership in cases unseen during model fitting. Four trajectory types were identified (post.prob. > 0.95): high-start fast ( N = 92), low-start fast ( N = 168), slow ( N = 130) and non-responders ( N = 210). Fast responders were older (chigh = 1.8; clow = 1.1) than non-responders and suffered shorter coma (chigh = -14.7; clow = -4.3). High-start fast-responders had shorter length of stay (c = -1.6), and slow responders had lower incidence of epilepsy (c = -1.4), than non-responders ( p < 0.001). Single-subject trajectory could be predicted with high accuracy at first discharge (accuracy = 0.80). In conclusion, we stratified patients based on the evolution of their response to a specific treatment program. Data at first discharge predicted the response over 7 years. This method enables early detection of the slow responders, who show poor post-acute functional gains, but achieve recovery comparable to fast responders by year 7. Further external validation in other rehabilitation programs is warranted.

Background: Stressful conditions during competitive golf putting may result in impaired performance, producing physiological changes. Nevertheless, simultaneous measurements of postural sway (PS), heart rate variability (HRV) and electrodermal activity (EDA) during a competitive golf putting have not yet been examined. This study aims at describing if changes in PS, HRV and EDA during golf putting, might affect the golfer's performance., Methods: Based on EGA-handicap, 40 amateur golfers were divided in 2 groups. They competed in an indoor round of golf putting. PS, EDA, HRV and putting performance (SCORE) were recorded at basal and during competition., Results: During the putting round, a significant increase in low-frequency power (LF) and decrease in high-frequency power (HF) was found in Group A, leading to an increased LF/HF ratio. The heart rate increased significantly more in Group A than in Group B, but the stress index (SI) remained lower in this group. EDA significantly increased in both groups, with no statistical difference between groups. No statistical difference in SCORE was observed., Conclusions: Despite the significant differences observed between the two groups, both at baseline and in response to competition, no variation of the studied variables was associated with a better putting performance.

Robot assisted gait training (RAGT) and virtual reality plus treadmill training (VRTT) are two technologies that can support locomotion rehabilitation in children and adolescents affected by acquired brain injury (ABI). The literature provides evidence of their effectiveness in this population. However, a comparison between these methods is not available. This study aims at comparing the effectiveness of RAGT and VRTT for the gait rehabilitation of children and adolescents suffering from ABI. This is a prospective cohort study with propensity score matching. Between October 2016 and September 2018, all patients undergoing an intensive gait rehabilitation treatment based on RAGT or VRTT were prospectively observed. To minimize selection bias associated with the study design, patients who underwent RAGT or VRTT were retrospectively matched for age, gender, time elapsed from injury, level of impairment, and motor impairment using propensity score in a matching ratio of 1:1. Outcome measures were Gross Motor Function Mesure-88 (GMFM-88), six-min walking test (6MWT), Gillette Functional Assessment Questionnaire (FAQ), and three-dimensional gait analysis (GA). The FAQ and the GMFM-88 had a statistically significant increase in both groups while the 6MWT improved in the RAGT group only. GA highlighted changes at the proximal level in the RAGT group, and at the distal district in the VRTT group. Although preliminary, this work suggests that RAGT and VRTT protocols foster different motor improvements, thus recommending to couple the two therapies in the paediatric population with ABI.

Purpose: Early de-tethering procedures are performed on spinal dysraphisms to prevent neuro-urological deterioration caused by growth. Partial lipoma removal may cause delayed deterioration by re-tethering, while complete removal may increase the risk of postoperative worsening. The present study evaluates the risk of postoperative deterioration and the protective potential of intraoperative neurophysiological monitoring (IOM), with a special reference to the conus lipomas treated with the radical approach., Methods: Forty toddlers (< 24 months) underwent complete perioperative neurological and urological assessment, including urodynamic study (UDS). The dysraphisms were subgrouped according to Pang's classification. IOM was applied in all patients: transcranial motor evoked potentials (tMep) combined with mapping were recorded in all cases while bulbocavernosus reflex (BCR) was evaluable just in 7 cases., Results: At preoperative evaluation, 11 children already had UDS impairment and 2 had motor disturbances before neurosurgery. At 1-month follow-up, preoperative motor disturbances were stable, 7/11 UDS alterations normalized, and the remaining 4 were stable. At 6-month follow-up, all motor deficits and 8/11 preoperative UDS alterations had improved. Unfortunately, 7 children with previously normal UDS experienced a new impairment after surgery: 2/7 normalized while 5/7 did not recover. This postoperative permanent urodynamic impairment occurred in 4 chaotic lipoma (CLchaos) and in one terminal myelocystocele (TMC) that means a surgical deterioration rate of 22% for the high risk cases., Conclusions: This small highly selected series confirms that early de-tethering may stop or revert the spontaneous neuro-urological deterioration: in fact, preoperative UDS impairment was frequent (27.5%) and improved in all the low surgical risk cases (limited dorsal myeloschisis, filar, transitional and dorsal lipomas). On the contrary, in CLchaos and TMC, early de-tethering was unable to revert preoperative UDS impairment, and radical surgery carried a high risk of new neuro-urological deterioration directly caused by the operation. In our experience, IOM had a protective role for motor functions, while it was less effective for the neuro-urological ones, probably due to the anesthesiology regimens applied. In conclusion, among the dysraphisms, CLchoas proved to be the worst enemy that often camouflages at MRI. Affording it without all possible IOM weapons carries a high risk to harm the patient.

We extend the classic approach (SIR) to a SEAIRD model with policy controls. A social planner's objective reflects the trade-off between mortality reduction and GDP, featuring its perception of the value of statistical life (PVSL). We introduce realistic and drastic limitations to the control available to it. Within this setup, we explore the results of various control policies. We notably describe the joint dynamics of infection and economy in different contexts with unique or multiple confinement episodes. Compared to other approaches, our contributions are: (i) to restrict the class of functions accessible to the social planner, and in particular to impose that they remain constant over some fixed periods; (ii) to impose implementation frictions, e.g. a lag in their implementation; (iii) to prove the existence of optimal strategies within this set of possible controls; iv) to exhibit a sudden change in optimal policy as the statistical value of life is raised, from laissez-faire to a sizeable lockdown level, indicating a possible reason for conflicting policy proposals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier B.V. All rights reserved.)

Objective: The minimum clinically important difference (MCID) is a standard way of measuring clinical relevance. The objective of this work was to establish the MCID for the 6-minute walking test (6minWT) and the Gross Motor Function Measure (GMFM-88) in pediatric gait disorders., Methods: A cohort, pretest-posttest study was conducted in a hospitalized care setting. A total of 182 patients with acquired brain injury (ABI) or cerebral palsy (CP) performed 20 robot-assisted gait training sessions complemented with 20 sessions of physical therapy over 4 weeks. Separate MCIDs were calculated using 5 distribution-based approaches, complemented with an anonymized survey completed by clinical professionals., Results: The MCID range for the 6minWT was 20-38 m in the ABI cohort, with subgroup ranges of 20-36 m for GMFCS I-II, 23-46 m for GMFCS III, and 24-46 m for GMFCS IV. MCIDs for the CP population were 6-23 m, with subgroup ranges of 4-28 m for GMFCS I-II, 9-19 m for GMFCS III, and 10-27 m for GMFCS IV. For GMFM-88 total score, MCID values were 1.1%-5.3% for the ABI cohort and 0.1%-3.0% for the CP population. For dimension "D" of the GMFM, MCID ranges were 2.3%-6.5% and 0.8%-5.2% for ABI and CP populations, respectively. For dimension "E," MCID ranges were 2.8%-6.5% and 0.3%-4.9% for ABI and CP cohorts, respectively. The survey showed a large interquartile range, but the results well mimicked the distribution-based methods., Conclusions: This study identified for the first time MCID ranges for 6minWT and GMFM-88 in pediatric patients with neurological impairments, offering useful insights for clinicians to evaluate the impact of treatments. Distribution-based methods should be used with caution: methods based on pre-post correlation may underestimate MCID when applied to patients with small improvements over the treatment period. Our results should be complemented with estimates obtained using consensus- and anchor-based approaches., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2020 Fabio Alexander Storm et al.)

Objective: To evaluate retrospectively the effect of robotic rehabilitation in a large group of children with motor impairment; an additional goal was to identify the effects in children with cerebral palsy (CP) and acquired brain injury (ABI) and with different levels of motor impairment according to the Gross Motor Function Classification System. Finally, we examined the effect of time elapsed from injury on children's functions., Design: A cohort, pretest-posttest retrospective study was conducted., Setting: Hospitalized care., Participants: A total of 182 children, 110 with ABI and 72 with CP and with Gross Motor Function Classification System (GMFCS) levels I-IV, were evaluated retrospectively., Interventions: Patients underwent a combined treatment of robot-assisted gait training and physical therapy., Main Outcome Measures: All the patients were evaluated before and after the training using the 6-minute walk test and the Gross Motor Function Measure. A linear mixed model with 3 fixed factors and 1 random factor was used to evaluate improvements., Results: The 6-minute walk test showed improvement in the whole group and in both ABI and CP. The Gross Motor Function Measure showed improvement in the whole group and in the patients with ABI but not in children with CP. The GMFCS analysis showed that all outcomes improved significantly in all classes within the ABI subgroup, whereas improvements were significant only for GMFCS III in children with CP., Conclusions: Children with motor impairment can benefit from a combination of robotic rehabilitation and physical therapy. Our data suggest positive results for the whole group and substantial differences between ABI and CP subgroups, with better results for children with ABI, that seem to be consistently related to time elapsed from injury., (Copyright © 2019 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: This study is aimed at better understanding the role of a wearable and silent ElectroMyoGraphy-based biofeedback on motor learning in children and adolescents with primary and secondary dystonia., Methods: A crossover study with a wash-out period of at least 1 week was designed; the device provides the patient with a vibration proportional to the activation of an impaired target muscle. The protocol consisted of two 5-day blocks during which subjects were trained and tested on a figure-8 writing task: their performances (at different levels of difficulty) were evaluated in terms of both kinematics and muscular activations on day 1 and day 5, while the other 3 days were purely used as training sessions. The training was performed with and without using the biofeedback device: the week of use was randomized. Data were collected on 14 subjects with primary and secondary (acquired) dystonia (age: 6-19 years)., Results: Results comparing kinematic-based and EMG-based outcome measures pre- and post-training showed learning due to practice for both subjects with primary and secondary dystonia. On top of said learning, an improvement in terms of inter-joint coordination and muscular pattern functionality was recorded only for secondary dystonia subjects, when trained with the aid of the EMG-based biofeedback device., Conclusions: Our results support the hypothesis that children and adolescents with primary dystonia in which there is intact sensory processing do not benefit from feedback augmentation, whereas children with secondary dystonia, in which sensory deficits are often present, exhibit a higher learning capacity when augmented movement-related sensory information is provided. This study represents a fundamental investigation to address the scarcity of noninvasive therapeutic interventions for young subjects with dystonia.

Aim: To assess changes in locomotion and balance in adolescents affected by ataxia secondary to acquired brain injury after a rehabilitation treatment with physiotherapy and the Gait Real-time Analysis Interactive Lab (GRAIL), an immersive virtual reality platform., Methods: 11 ataxic adolescents (16(5) years old, 4.7(6.7) years from injury) underwent 20 45-minute sessions with GRAIL plus 20 45-minute sessions of physiotherapy in one month. Patients were assessed before and after rehabilitation with functional scales and three-dimensional multiple-step gait analysis., Results: Results showed significant improvements in ataxia score assessed by the Scale for the Assessment and Rating of Ataxia, in dimension D and E of Gross Motor Function Measure, in walking endurance and in balance abilities. Moreover, the training fostered significant changes at hip, knee, and ankle joints, and the decrease of gait variability, toward healthy references., Interpretation: In spite of the pilot nature of the study, data suggest that training with immersive virtual reality and physiotherapy is a promising approach for ataxic gait rehabilitation, even in chronic conditions., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Elisabetta Peri et al.)

Oxygen diffusion across the air-blood barrier in the lung is commensurate with metabolic needs and ideally allows full equilibration between alveolar and blood partial oxygen pressures. We estimated the alveolo-capillary O 2 equilibration in 18 healthy subjects at sea level at rest and after exposure to increased O 2 demand, including work at sea level and on hypobaric hypoxia exposure at 3840 m (P A  ~ 50 mmHg). For each subject we estimated O 2 diffusion capacity (DO 2 ), pulmonary capillary blood volume (Vc) and cardiac output ([Formula: see text]). We derived blood capillary transit time [Formula: see text] and the time constant of the equilibration process ([Formula: see text], β being the slope of the hemoglobin dissociation curve). O 2 equilibration at the arterial end of the pulmonary capillary was defined as [Formula: see text]. L eq greately differed among subjects in the most demanding O 2 condition (work in hypoxia): lack of full equilibration was found to range from 5 to 42% of the alveolo-capillary PO 2 gradient at the venous end. The present analysis proves to be sensible enough to highlight inter-individual differences in alveolo-capillary equilibration among healthy subjects.

Background: In patients with moderate and severe paediatric traumatic brain injury (TBI), we investigated the presence and severity of white matter (WM) tract damage, cortical lobar and deep grey matter (GM) atrophies, their interplay and their correlation with outcome rating scales., Methods: Diffusion tensor (DT) and 3D T1-weighted MRI scans were obtained from 22 TBI children (13 boys; mean age at insult = 11.6 years; 72.7% in chronic condition) and 31 age-matched healthy children. Patients were tested with outcome rating scales and the Wechsler Intelligence Scale for Children (WISC). DT MRI indices were obtained from several supra- and infra-tentorial WM tracts. Cortical lobar and deep GM volumes were derived. Comparisons between patients and controls, and between patients in acute (<6 months from the event) vs. chronic (≥6 months) condition were performed., Results: Patients showed a widespread pattern of decreased WM FA and GM atrophy. Compared to acute, chronic patients showed severer atrophy in the right frontal lobe and reduced FA in the left inferior longitudinal fasciculus and corpus callosum (CC). Decreased axial diffusivity was observed in acute patients versus controls in the inferior fronto-occipital fasciculus and CC. Chronic patients showed increased axial diffusivity in the same structures. Uncinate fasciculus DT MRI abnormalities correlated with atrophy in the frontal and temporal lobes. Hippocampal atrophy correlated with reduced WISC scores, whereas putamen atrophy correlated with lower functional independence measure scores., Conclusions: The study isolated a distributed fronto-temporal network of structures particularly vulnerable to axonal damage and atrophy that may contribute to cognitive deficits following TBI., (© 2019 EAN.)

Severe Disorders of Consciousness (DoC) are generally caused by brain trauma, anoxia or stroke, and result in conditions ranging from coma to the confused-agitated state. Prognostic decision is difficult to achieve during the first year after injury, especially in the pediatric cases. Nevertheless, prognosis crucially informs rehabilitation decision and family expectations. We compared four multi-class machine learning classification approaches for the prognostic decision in pediatric DoC. We identified domains of a neurobehavioral assessment tool, Level of Cognitive Functioning Assessment Scale, mostly contributing to decision in a cohort of 124 cases. We showed the possibility to generalize to new admitted pediatric cases, thus paving the way for real employment of machine learning classifiers as an assistive tool to prognostic decision in clinics.

Harness hang syncope (HHS) is a risk that specifically affects safety of harness users in mountain climbing. Aims: To evaluate individual patterns of breathing resulting from deranged cardiovascular reflexes triggering a syncopal event when a mismatch between cerebral O 2 demand and supply is present. Results: Forty healthy participants [aged 39.1 (8.2) years] were enrolled in a motionless suspension test while hanging in harness. Respiratory gas exchange values were analyzed to assess the pattern of breathing (EpInW el , respiratory elastic power) and cardiovascular parameters were monitored (BP, blood pressure). Four participants experienced HHS after 30.0 (7.6) minutes, with an early manifestation of loss of control of both a sustainable EpInW el and BP, starting after 10-12 minutes. Among the other participants, two different reactions were observed during suspension: (1) group G1 tolerated 32.7 (11.4) minutes of suspension by a favorable adaptation of the EpInW el and BP parameters and (2) group G2 showed significantly shorter time of suspension 24.0 (10.4) minutes with unfavorable increase in EpInW el and BP. Conclusions: Greater resistance to HHS occurs in people developing less marked fluctuations of both respiratory and cardiovascular reflex responses. Conversely, wider fluctuations both in control of EpInW el and BP were observed in the event of decreased suspension tolerance or in syncopal events.

Background & Aims: Urolithiasis affects pediatric patients with severe acquired brain injury, in whom the role of several clinical variables and of the presence and composition of enteral nutrition has not been investigated., Methods: Retrospective chart review on 371 pediatric patients with severe acquired brain injury. We used an essential electronic database to check the association between stones and enteral feeding. We then picked at random paper clinical records until we collected 20 and 20 complete records for patients with/without stones, not matched. With that information, we tested the association of stones with: nutrition facts of enteral formulae (sodium, potassium, calcium, magnesium, phosphorus, proteins, vitamin C); bladder dysfunction, urinary infections, catheterisms, tracheostomy, gallstones, way of feeding; blood and urine exams before stones diagnosis; age, type and severity of injury; prior physical activity, relevant drugs., Results: All patients with stones were fed enterally. At univariate statistics they were older, weighed more, received bigger volumes of hydration and nutrition; they had worse GCS, more UTIs and they alone received catheterisms; their nutrition mixes were richer in sodium. In multivariate logistic regression for stone development, UTIs (OR 11.4, 95% C.I. 1.6-83.4) and higher sodium nutrition content (OR 7.5, 95% C.I. 1.6-34.3) were risk factors; higher GCS (OR 0.66, 95% C.I. 0.43-0.99) and higher calcium nutrition content (OR 0.14, 95% C.I. 0.03-0.73) were protective factors., Conclusions: Besides known risk factors for urolithiasis, including UTIs, catheterisms, worse neurological states, also enteral nutrition was a risk factor, particularly with higher sodium and lower calcium contents. Future studies should test the effect of different sodium/calcium nutrition contents on lithogenesis., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Abstract: Respiratory disorders may follow brain injury and may also occur because of comorbidities and drug use, especially central depressants or muscle relaxants. Sleep can precipitate respiratory disorders, thus polysomnography can be a powerful diagnostic tool. By revealing breathing patterns that identify specific sleep disorders, polysomnography may unmask adverse pharmacological effects, for instance connecting central depressant drugs with central sleep apneas. We describe the case of a pediatric patient in rehabilitation from brain injury who developed a central sleep apnea following a baclofen dose increase within the therapeutic range, while assuming an under-dosed benzodiazepine. Polysomnography identified a typical respiration pattern, previously observed in adults treated with baclofen and other central depressants. Baclofen tapering resolved the central sleep apnea. Polysomnography, and this specific pattern, may be proposed as diagnostic tools in patients with high dose baclofen that can be used to prevent potential respiratory disorders in children., (© 2019 American Academy of Sleep Medicine.)

Purpose: Intraoperative PTH testing (IOPTH) in treatment of primary hyperparathyroidism (PH) is debated. Some authors advise against IOPTH in patients with concordant preoperative imaging undergoing focused parathyroidectomy. This study aims to compare focused parathyroidectomy success rates with and without IOPTH in patients with concordant preoperative imaging., Methods: Retrospective cohort study involving 599 consecutive patients underwent surgery for PH from 2012 to 2017. Patients with discordant preoperative imaging were excluded. 426 patients underwent focused parathyroidectomy (214 patients without IOPTH and 212 with IOPTH) and were considered for the statistical analysis. In case of insufficient IOPTH decay (less than 50%), a bilateral exploration was carried out., Results: The IOPTH group and the non-IOPTH group were similar for demographics and preoperative PTH and calcaemia. 413 patients were cured and disease persistence rates between groups were not significantly different (p > 0.05)., Conclusions: Although further testing and randomized-controlled trials are required to validate our findings, our data show that IOPTH does not seem to improve the outcome in patients with concordant preoperative imaging undergoing focused parathyroidectomy.

Background: Children with cerebral palsy (CP) and acquired brain injury (ABI) often exhibit upper limb impairment, with repercussions in their daily activities. Robotic rehabilitation may promote their functional recovery, but evidence of its effectiveness is often based on qualitative functional scales. The primary aim of the present work was to assess movement precision, velocity, and smoothness using numerical indices from the endpoint trajectory of Armeo®Spring. Secondly, an investigation of the effectiveness of robotic rehabilitation in CP and ABI children was performed., Methods: Upper limb functional changes were evaluated in children with CP (N=21) or ABI (N=22) treated with Armeo®Spring (20 45-minute sessions over 4 weeks) using clinical scales and numerical indices computed from the exoskeleton trajectory., Results: Functional scales (i.e., QUEST and Melbourne) were sensitive to changes produced by the treatment for the whole study group and for the two etiology-based subgroups (improvements above Minimal Clinically Importance Difference). Significant improvement was also observed in terms of velocity, fluidity, and precision of the movement through the numerical indices of kinematic performance. Differences in the temporal evolution of the motor outcome were highlighted between the ABI and CP subgroups, pointing toward adopting different rehabilitative protocols in these two populations., Conclusions: Robot-assisted upper limb rehabilitation seems to be a promising tool to promote and assess rehabilitation in children affected by acquired and congenital brain diseases.

Purpose: The description of motor changes and clinical evolution of a pediatric cohort with acquired brain injury (ABI) over 5 years by the functional independence measure for children (WeeFIM)., Methods: We analyzed retrospective data from 496 patients (aged 0-18 years) with severe ABI admitted for rehabilitation. WeeFIM scores and disability rating scale (reference scale) were collected at admission, discharge and yearly, up to year 5., Results: Functional limitations gradually reduced after ABI, but children still had residual disabilities at the endpoint. Seventeen percent of patients demonstrated no improvement at WeeFIM. Gait analysis showed that decreased WeeFIM scores in the mobility domain are associated with slower and shorter steps, and increased step width, compensating for imbalance., Conclusions: Five years after ABI, improvement is still found in the mobility domain of WeeFIM. This work adds evidence that margin still exists at least until year 5 after injury for profitably continuing the rehabilitation effort.

Metformin is an antidiabetic drug; used to treat type II diabetes mellitus, metformin associated lactic acidosis has an incidence of 2-9 cases / 100,000 patients / year with high mortality (30%). We have had the case of a 75-year-old woman with metabolic acidosis as a result of metformin assumption, treated by renal replacement therapy (CRRT) with continuous veno-venous hemodiafiltration (CVVHDF)., Results: after a short treatment period there was a reduction in Lactates (from 16.8 mmol/L to 12.6 mmol/L) and a progressive improvement of acidosis. In 72 hours the recovery of diuresis and subsequent suspension of CRRT was achieved., Conclusion: CRRT, in addition to ensuring support for renal failure and volume correction, allowed a rapid recovery from metformin-associated lactic acidosis., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Parathyroid tumors deregulate microRNAs belonging to the two clusters on the chromosome 19, the C19MC and miR-371-373 clusters. Here, we report that the embryonic miR-372 is aberrantly expressed in half of parathyroid adenomas (PAds) in most of atypical adenomas and carcinomas ( n  = 15). Through in situ hybridization, we identified that miR-372-positive parathyroid tumor cells were scattered throughout the tumor parenchyma. In PAd-derived cells, ectopic miR-372 inhibited the expression of its targets CDKN1A /p21 and LATS2 at both mRNA and protein levels. Although the viability of parathyroid cells was not affected by miR-372 overexpression, the miRNA blunted camptothecin-induced apoptosis in primary PAd-derived cultures. miR-372 overexpression in parathyroid tumor cells increased parathormone ( PTH ) mRNA levels, and it positively correlated in vivo with circulating PTH levels. Conversely, the parathyroid-specific genes TBX1 and GCM2 were not affected by miR-372 mimic transfection. Finally, miR-372 dampened the Wnt pathway in parathyroid tumor cells through DKK1 upregulation. In conclusion, miR-372 is a novel mechanism exploited by a subset of parathyroid tumor cells to partially decrease sensitivity to apoptosis, to increase PTH synthesis and to deregulate Wnt signaling., (© 2018 Society for Endocrinology.)

Robotically-driven orthoses (RDO) are promising for treating gait impairment in children with hemiplegia after acquired brain injury (ABI). Despite this, existing literature on the employment of RDO in ABI is scanty, and cohorts' age spans throughout the adult age, with no specific focus on the developmental age. We aim to compare a treatment solely based on conventional physiotherapy (CP) with a program combining RDO training with CP, and to examine the effect of time following ABI on recovery. A prospective two-cohorts study was conducted in a rehabilitation hospital. Post-acute and chronic children with hemiplegia due to ABI underwent either: (i) 20 sessions of RDO plus 20 sessions of CP (n = 29), or (ii) 40 of CP (n = 12). Gross Motor Function Measures (GMFM), Functional Assessment Questionnaire (FAQ), 6 Minutes Walk Test and gait analysis (GA) parameters were recorded before and after training. Over all the patients in RDO + CP group, all GMFM domains and FAQ improved after RDO training (p < 0.05). The unaffected limb showed significantly decreased stance, increased step length and reduced anteroposterior center of pressure oscillation; the affected side increased the stride length. ROM hip and knee flex-extension increased bilaterally (p < 0.05 for all). RDO training during the acute/subacute post-injury phase increased motor functional abilities, cadence and velocity of gait (p < 0.05). We conclude that RDO imposes a proximal-to-distal differential effect on the lower limbs, with the hip joint being the most stimulated. RDO training fostered recovery, increasing the quality of gait on the unaffected side. Planning RDO early in the rehabilitation course of pediatric ABI is advantageous. RDO + CP may extend rehabilitation efficacy to the proximal segment of leg and to gait velocity., (Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Background: Laminoplasty and laminectomy are 2 common surgical procedures used in treating degenerative and neoplastic diseases of the spinal canal. Routinely used instruments, such as the Kerrison rongeur and high-speed drill, can result in potentially serious complications, such as dural injury and thermal and mechanical damage to neurovascular structures. We adopted piezoelectric bone surgery, which permits a selective cut of mineralized tissues, to perform posterior procedures on the thoracic spine, where the relationship between bone and the spinal cord is critical. The aim of this article was to evaluate the use of piezoelectric surgery for performing dorsal spine laminectomy and laminoplasty., Methods: The Mectron piezosurgery device was developed for cutting bone with microvibrations that are created by the piezoelectric effect. This instrument allows a safe and precise bone cut, and it is characterized by no heat generation, thus avoiding thermal injury to bone and soft tissues. We used this device to perform 8 laminoplasties for tumors of the dorsal spine and 2 laminectomies for thoracic spinal stenosis in 10 patients., Results: There were no procedure-related intraoperative complications, such as dural injury or damage to neural structures., Conclusions: The piezoelectric device showed excellent results in terms of safety and precise bone cutting properties when performing posterior surgical procedures in the dorsal spine, where thermal injury produced by the conventionally used drill may damage the spinal cord closer to bony elements., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this paper a conceptual mathematical model of malaria transmission proposed in a previous paper has been analyzed in a deeper detail. Among its key epidemiological features of this model, two-age-classes (child and adult) and asymptomatic carriers have been included. The extra mortality of mosquitoes due to the use of long-lasting treated mosquito nets (LLINs) and Indoor Residual Spraying (IRS) has been included too. By taking advantage of the natural double time scale of the parasite and the human populations, it has been possible to provide interesting threshold results. In particular it has been shown that key parameters can be identified such that below a threshold level, built on these parameters, the epidemic tends to extinction, while above another threshold level it tends to a nontrivial endemic state, for which an interval estimate has been provided. Numerical simulations confirm the analytical results., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Acquired brain injuries (ABIs) can lead to a wide range of impairments, including weakness or paralysis on one side of the body known as hemiplegia. In hemiplegic patients, the rehabilitation of the upper limb skills is crucial, because the recovery has an immediate impact on patient quality of life. For this reason, several treatments were developed to flank physical therapy (PT) and improve functional recovery of the upper limbs. Among them, Constraint-Induced Movement Therapy (CIMT) and robot-aided therapy have shown interesting potentialities in the rehabilitation of the hemiplegic upper limb. Nevertheless, there is a lack of quantitative evaluations of effectiveness in a standard clinical setting, especially in children, as well as a lack of direct comparative studies between these therapeutic techniques. In this study, a group of 18 children and adolescents with hemiplegia was enrolled and underwent intensive rehabilitation treatment including PT and CIMT or Armeo®Spring therapy. The effects of the treatments were assessed using clinical functional scales and upper limb kinematic analysis during horizontal and vertical motor tasks. Results showed CIMT to be the most effective in terms of improved functional scales, while PT seemed to be the most significant in terms of kinematic variations. Specifically, PT resulted to have positive influence on distal movements while CIMT conveyed more changes in the proximal kinematics. Armeo treatment delivered improvements mainly in the vertical motor task, showing trends of progresses of the movement efficiency and reduction of compensatory movements of the shoulder with respect to other treatments. Therefore, every treatment gave advantages in a specific and different upper limb district. Therefore, results of this preliminary study may be of help to define the best rehabilitation treatment for each patient, depending on the goal, and may thus support clinical decision.

Aim: To describe and evaluate the anaesthesiological regimen used in neurophysiologically monitored image-guided mini-invasive neurosurgery., Material and Methods: Twenty-four patients underwent elective surgery under general anaesthesia that was administered through Target Controlled Infusion (TCI) for effect-site concentration (Ce) of Propofol and Remifentanil, targeting the Bispectral Index (BIS) in the 40-60 intervals. The stimulating intensity of transcranial motor evoked potentials (tMEP), BIS, Propofol and Remifentanil Ce were collected at MEPs threshold (T) definition (respectively BIS@T, CeProp@T and CeRemi@T). Intraoperative seizure, explicit recall for intraoperative awareness and clinical motor status were assessed., Results: CeProp@T and CeRemi@T ranged respectively between 1.5-2.2 μg/ml (Median 1.6 μg/ml) and 3.5-18 ng/ml (Median 8 ng/ml) that were effective in keeping the BIS@T between 40 and 60 in all surgeries. tMEP thresholds ranged between 45 and 120 mA. There was no correlation between CeProp@T, CeRemi@T and tMEP, as well as between BIS@T and respectively tMEP, CeProp@T, CeRemi@T. None of patients had induced electrical seizure or explicit recalls. Motor scores were equal to preoperative values in 22/24 patients., Conclusion: BIS-guided general anaesthesia within a 40-60 interval, with low Ce of Propofol (≤2 μ/ml) and high analgesic regime allow reliable tMEP measurements, avoiding postoperative neurological impairment and major adverse outcomes, such as seizure and awareness.

Objective: To describe behavioural and adjustment problems in a group of 57 adolescents with severe traumatic brain injury (TBI) and compare them with a clinical group of peers with brain lesions of other origin (N = 33) and a control group of healthy adolescents (N = 48)., Methods: All subjects received an age-appropriate assessment, including the child behaviour checklist (CBCL) 4/18, the strengths and difficulties questionnaire (SDQ) and the vineland adaptive behaviour scales (VABS)., Results: Compared with healthy peers, adolescents with TBI presented with more marked behavioural problems on most CBCL scales (Internalization and Externalization domains were both affected) and on the SDQ Hyperactivity and Peer problems scales. They also showed a more impaired functioning in most VABS domains. Compared with adolescents with brain lesions of other aetiology, patients with TBI showed more conduct problems on the SDQ scale, but no significant differences were found on the CBCL scales. Regarding the VABS, patients with other lesions presented with the worst outcome in the Motor and Daily Living Skills domains., Conclusions: Adolescents with TBI are exposed at a very high risk to develop behavioural and psychological disturbances with the potential to severely affect their social re-entry. Further knowledge is needed to plan early and well-timed interventions.

The O 2 diffusion limitation across the air blood barrier (DO 2 and subcomponents Dm and Vc) was evaluated in 17 healthy participants exposed to hypobaric hypoxia (HA, 3840m, P I O 2 ∼90mmHg). A 10% decrease in alveolar volume (VA) in all participants suggested the development of sub-clinical interstitial lung edema. In >80% of participants DO 2 /VA increased, reflecting an individual strategy to cope with the hypoxia stimulus by remodulating Vc or Dm. Opposite changes in Dm/Vc ratio were observed and participants decreasing Vc showed reduced alveolar blood capillary transit time. The interplay between diffusion and perfusion (cardiac output) was estimated in order to investigate the individual adaptive response to hypoxia. It appears remarkable that despite individual differences in the adaptive response to HA, diffusion limitation did not exceed ∼11% of the alveolar-venous PO 2 gradient, revealing an admirable functional design of the air-blood barrier to defend the O 2 diffusion/perfusion function when facing hypobaric hypoxia corresponding to 50mmHg decreased P A O 2 ., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Transcription factors active in embryonic parathyroid cells can be maintained in adult parathyroids and be involved in tumorigenesis. TBX1, the candidate gene of 22q11.2-DiGeorge syndrome, which includes congenital hypoparathyroidism, is involved in parathyroid embryogenesis. The study aimed to investigate expression, function, and regulation of the parathyroid embryonic transcription factor TBX1 in human parathyroid adult normal and tumor tissues. TBX1 transcripts were detected in normal parathyroids and were deregulated in parathyroid tumors. Using immunohistochemistry, TBX1 protein was detected, mainly at the nuclear level, in a consistent proportion of cells in normal adult parathyroids, whereas TBX1 immunoreactivity was absent in fetal parathyroids. TBX1-expressing cells were markedly reduced in about a half of adenomas (PAds) and two-thirds of carcinomas and the proportion of TBX1-expressing cells negatively correlated with the serum albumin-corrected calcium levels in the analyzed tumors. Moreover, a subset of TBX1-expressing tumor cells coexpressed PTH. TBX1 silencing in HEK293 cells, expressing endogenous TBX1, increased the proportion of cells in the G0/G1 phase of cell cycle; concomitantly, CDKN1A/p21 and CDKN2A/p16 transcripts increased and ID1 mRNA levels decreased. TBX1 silencing exerted similar effects in PAd-derived cells, suggesting cell cycle arrest. Moreover, in PAd-derived cells GCM2 and PTH mRNA levels were unaffected by TBX1 deficiency, whereas it was associated with reduction of WNT5A, an antagonist of canonical WNT/β-catenin pathway. WNT/β-catenin activation by lithium chloride inhibited TBX1 expression levels both in HEK293 and PAd-derived cells. In conclusion, TBX1 is expressed in adult parathyroid cells and deregulated in parathyroid tumors, where TBX1 deficiency may potentially contribute to the low proliferative nature of parathyroid tumors.

Background: Secondary intracranial hypotension is a clinical syndrome associated with reduction of cerebrospinal fluid volume and dural continuity violation. The main symptoms are orthostatic headache associated with nausea, vomiting, diplopia, dizziness, and tinnitus. The treatment is usually nonspecific., Case Description: A 37-year-old woman developed secondary intracranial hypotension caused by lumbosacral iatrogenic dural ectasia following detethering surgery. An orthostatic headache was the mainstay of her clinical picture, and it was confirmed by intracranial pressure monitoring. Conservative treatment including spinal blood patch improved symptoms for a limited amount of time (<1 month). Altered compliance of the dural spinal sac was suspected. Therefore thecal sac remodeling by placing autologous fat at the level of the dural ectasia was performed, improving the symptoms for 2 years., Conclusion: Volumetric reduction of the epidural space may be considered as a valuable therapeutic option in case of intracranial hypotension that is unresponsive to medical treatments and spinal blood patch, as well as when an altered compliance of the dural sac is hypothesized., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The outcome of headache in a series of 135 operated CM1 is presented. Favorable results were obtained in 85% of atypical and 93% typical headache with the support of a multidisciplinary approach that restricted the indications for surgery.

Chiari type 1 Malformation (CM 1) is a structural defect consisting of a displacement of the cerebellar tonsils through the foramen magnum causing obstruction of cerebrospinal fluid (CSF) outflow. CM 1 has a variety of presentation with headache being the most common symptom. The evaluation and treatment of headache related to CM 1 are often difficult, because the pain in the occipital-suboccipital region or headache that is of cough-type suggests symptomatic CM 1, but patients suffering from CM 1 can also report migraine or tension-type headache. In 2015 we started a collaborative project in which our group of neurologists, neurosurgeons and neuroradiologists contribute to create a Chiari Special Outpatient Service; this was set up to provide a multidisciplinary evaluation, treatment and follow-up of patient suffering from CM 1. 201 patients (58 males, 143 females) suffering from CM 1 were multidisciplinary evaluated. Headache characteristics, clinical features, and treatment of patients are discussed. Further progress in multidisciplinary care of headache and CM 1 should be performed to define guidelines.

DLCO measured in hypoxia must be corrected due to the higher affinity (increase in coefficient θ) of CO with Hb. We propose an adjustment accounting for individual changes in the equation relating DLCO to subcomponents Dm (membrane diffusive capacity) and Vc (lung capillary volume): 1/DLCO=1/Dm+1/θVc. We adjusted the individual DLCO measured in hypoxia (HA, 3269m) by interpolating the 1/DLCO to the sea level (SL) 1/θ value. Nineteen healthy subjects were studied at SL and HA. Based on the proposed adjustment, DLCO increased in HA in 53% of subjects, reflecting the increase in Dm that largely overruled the decrease in Vc. We hypothesize that a decrease in Vc (buffering microvascular filtration) and the increase in Dm (possibly resulting from a decrease in thickness of the air-blood barrier) represent the anti-edemagenic adaptation of the lung to hypoxia exposure. The efficiency of this adaptation varied among subjects as DLCO did not change in 31% of subjects and decreased in 16%., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Acquired brain injury (ABI) may result in lifelong impairment of physical, cognitive, and psychosocial functions. Several rehabilitative treatments are often needed to support walking recovery, thus participants' engagement becomes a crucial aspect, especially when patients are children. In the last few years, traditional physiotherapy (PT) has been flanked by innovative technologies for rehabilitation in the fields of robotics and Virtual Reality (VR). Preliminary results have shown interesting perspectives in the use of a VR system, the GRAIL (Gait Real-time Analysis Interactive Lab), in improving walking abilities in a small group of children with ABI, although further insights are needed about its use as rehabilitative tool in the pediatric population., Objectives: To evaluate the efficacy of a rehabilitation treatment on a GRAIL system for the improvement of walking abilities, in a group of children suffering from ABI., Methods: 12 children with ABI (study group - SG; mean age = 12.1 ± 3.8 years old) underwent a 10-session treatment with the GRAIL, an instrumented multi-sensor platform based on immersive VR for gait training and rehabilitation in engaging VR environments. Before (T0) and at the end of the treatment (T1), the participants were assessed by means of functional scales (Gross Motor Function Measure (GMFM), Functional Assessment Questionnaire (FAQ), 6-Minute Walk Test (6minWT) and the 3D-Gait Analysis, over ground (OGA) and on GRAIL (GGA)., Results: All the participants completed the rehabilitative treatment. The functional evaluations showed an improvement in Gross Motor abilities (GMFM-88, p = 0.008), especially in standing (GMFM-D, p = 0.007) and walking (GMFM-E, p = 0.005), an increase of the endurance (6minWT, p = 0.002), and enhanced autonomy in daily life activities (FAQ, p = 0.025). OGA identified a significant decrease of the Gillette Gait Index for the impaired side and a general increase of symmetry. GGA showed improvements in spatiotemporal parameters and joints range of motion that moved towards normality and symmetry recovery., Conclusions: A 10-session treatment with GRAIL on children with ABI led to improvements in their walking abilities and enhanced their engagement during the training. This is desirable when long life impairments are faced and children's motor functions have to be regained and it supports the leading role that VR might have in the rehabilitation field.