Time Dependence of the Electron and Positron Components of the Cosmic Radiation Measured by the PAMELA Experiment between July 2006 and December 2015.

Cosmic-ray electrons and positrons are a unique probe of the propagation of cosmic rays as well as of the nature and distribution of particle sources in our Galaxy. Recent measurements of these particles are challenging our basic understanding of the mechanisms of production, acceleration, and propagation of cosmic rays. Particularly striking are the differences between the low energy results collected by the space-borne PAMELA and AMS-02 experiments and older measurements pointing to sign-charge dependence of the solar modulation of cosmic-ray spectra. The PAMELA experiment has been measuring the time variation of the positron and electron intensity at Earth from July 2006 to December 2015 covering the period for the minimum of solar cycle 23 (2006-2009) until the middle of the maximum of solar cycle 24, through the polarity reversal of the heliospheric magnetic field which took place between 2013 and 2014. The positron to electron ratio measured in this time period clearly shows a sign-charge dependence of the solar modulation introduced by particle drifts. These results provide the first clear and continuous observation of how drift effects on solar modulation have unfolded with time from solar minimum to solar maximum and their dependence on the particle rigidity and the cyclic polarity of the solar magnetic field.

New upper limit on strange quark matter abundance in cosmic rays with the PAMELA space experiment.

In this work we present results of a direct search for strange quark matter (SQM) in cosmic rays with the PAMELA space spectrometer. If this state of matter exists it may be present in cosmic rays as particles, called strangelets, having a high density and an anomalously high mass-to-charge (A/Z) ratio. A direct search in space is complementary to those from ground-based spectrometers. Furthermore, it has the advantage of being potentially capable of directly identifying these particles, without any assumption on their interaction model with Earth's atmosphere and the long-term stability in terrestrial and lunar rocks. In the rigidity range from 1.0 to ∼1.0×10^{3} GV, no such particles were found in the data collected by PAMELA between 2006 and 2009. An upper limit on the strangelet flux in cosmic rays was therefore set for particles with charge 1≤Z≤8 and mass 4≤A≤1.2×10^{5}. This limit as a function of mass and as a function of magnetic rigidity allows us to constrain models of SQM production and propagation in the Galaxy.

Label-free electrochemical biosensor for direct detection of Oncostatin M (OSM) inflammatory bowel diseases (IBD) biomarker in human serum.

Oncostatin M (OSM) is an interleukin-6 (IL-6) member family cytokine implicated in the pathogenesis of chronic diseases including inflammatory bowel disease (IBD). OSM is a novel diagnostic biomarker over-expressed in the serum of IBD patients. This paper reports on the first electrochemical OSM immunosensor, developed using a multistep fabrication process aimed at covalently immobilizing OSM antibodies on a mixed self-assembled monolayer coated gold working electrode. Cyclic voltammetry, atomic force microscopy (AFM), IR spectroscopy and optical characterizations were used to validate the sensor functionalization protocol. Electrochemical impedance spectroscopy (EIS) measurements were performed to assess the reliability of the immunosensor preparation and to verify the antibody-antigen complexes formation. The label-free immunosensor showed high sensitivity identifying OSM at clinically relevant concentrations (37-1000 pg mL-1) with low detection limit of 2.86 pg mL-1. Both sensitivity and selectivity of the proposed immunosensor were also demonstrated in human serum in the presence of interfering biomarkers, making it an innovative potential platform for the OSM biomarker detection in IBD patients' serum.

Cosmic-ray positron energy spectrum measured by PAMELA.

Precision measurements of the positron component in the cosmic radiation provide important information about the propagation of cosmic rays and the nature of particle sources in our Galaxy. The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray positron flux and fraction that extends previously published measurements up to 300 GeV in kinetic energy. The combined measurements of the cosmic-ray positron energy spectrum and fraction provide a unique tool to constrain interpretation models. During the recent solar minimum activity period from July 2006 to December 2009, approximately 24,500 positrons were observed. The results cannot be easily reconciled with purely secondary production, and additional sources of either astrophysical or exotic origin may be required.

CT and MRI diagnosis of silent sinus syndrome.

PURPOSE: The purpose of this study was to determine computed tomography (CT) and magnetic resonance (MR) findings of silent sinus syndrome (SSS) - a rare clinical entity with the constellation of progressive enophthalmos and hypoglobus, facial asymmetry and possible diplopia - due to otherwise asymptomatic maxillary sinus disease. MATERIALS AND METHODS: We reviewed the pre- and postoperative CT and MR images of six patients with a definitive diagnosis of SSS and compared the radiological and clinical findings with those reported in the literature. RESULTS: The CT and MR studies demonstrated in all cases the most characteristic imaging features of SSS reported in the literature. CONCLUSIONS: Both CT and MR imaging enable a diagnosis of SSS to be made, but CT provides a better depiction of all features of SSS necessary for diagnosis and differentiation from other sinus conditions, even in patients without a clinical suspicion of SSS.

Array-comparative genomic hybridization analysis in a cohort of 130 children with Autism Spectrum Disorders: A single Center Italian Study.

Introduction: utism spectrum disorder (ASD) is a heterogeneous clinical condition, and its genetic basis is widely confirmed. The chromosomal microarray analysis (CMA) is a first-line diagnostic test that identifies copy number variants (CNVs). Some of these genomic rearrangements are associated with ASD, but the meaning of most of them is still unknown. Materials and methods: We performed a comparative genome hybridization (array-CGH) analysis in 130 children with confirmed ASD. Genetic results were analyzed and compared to clinical phenotype. Results and discussion.: 61/130 children carry CNVs, 44 presenting variants of unknown significance (u-CNVs), and 17 with susceptibility-CNVs (c-CNVs). Clinical evaluation showed no differences in cognitive abilities, language and EEG abnormalities, ASD symptoms among CNVs group and other patients. Finally, we highlight the role of GPHN, IMMP2L and ZMYND11, as ASD susceptibility genes. Conclusions: Our findings underscore the importance of array-CGH in ASD children since new CNVs and emerging genes appear to be associated with different clinical pictures.

Sleep behavior of children with Autism Spectrum Disorder during the Covid-19 pandemic: A Parent survey.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a group of neurodevelopmental conditions characterized by social interaction and communication deficits and restricted, repetitive interests and behaviors (1). It is very common for children with ASD to present with several comorbidities, including sleep disorders. During the Covid-19 pandemic, children with ASD have been particularly at risk of adverse effects because of their difficulties in adapting to changes in daily habits and routines. METHODS AND AIM: Therefore, the aim of our study was to investigate sleep habits during the Covid-19 pandemic by administering the Child Sleep Habits Questionnaire (CSHQ) to parents. RESULTS: Twenty-five children of 28 (89.3%) had a score above 41 during the pandemic. Of these, 11 children also had clinically signifi-cant scores before the pandemic. DISCUSSION: Our data confirm that sleep disturbances have been very common in autistic children during the Covid-19 pandemic and suggest new considerations. In particular, in our clinical sample, sleep habits seemed to improve or not change significantly during the Covid-19 pandemic in a population with a high prevalence of cli-nically significant sleep disturbances. These data confirm that in this particular context, a supportive environment (family, parent training, tele-rehabilitation) is very important for autistic people and a predicta-ble routine can help prevent stress, anxiety, and behavioral problems.

What if sharing music as a language is the key to meeting halfway? Absolute pitch, pitch discrimination and Autism Spectrum Disorder.

BACKGROUND: Absolute pitch is the ability to identify a given note in the absence of a reference note. The prevalence of absolute pitch in autism is between 5% and 11% and autism involves notably enhanced abilities in pitch discrimination. OBJECTIVES: To summarize the evidence about the role and the meaning of these special skills in autism. METHODS: Systematic electronic database searches were conducted using Pubmed, Scopus, Psycinfo, and Web of Science. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRI-SMA) guideline was followed, and, after thorough screening by two independent reviewers, 17 articles remained eligible for inclusion in this study. RESULTS: We have two different groups of results. Eight case-control studies discuss pitch discrimination and autism. The second group included four case reports about autistic individuals with absolute pitch and five case-control studies. These results strongly suggest that music elicits special attention for children with autism, and taken together, this evidence supports a major frequency of AP in autistic children. CONCLUSION: Based on this evidence, future perspectives could include studies aiming to detect absolute pitch at an early age and to use this special skill to stimulate joint attention, as well as socio-communicative skills.

Quantitative ultrasound of the tongue: Echo intensity is a potential biomarker of bulbar dysfunction in amyotrophic lateral sclerosis.

OBJECTIVES: To learn if quantitative ultrasound (QUS) distinguishes the tongues of healthy participants and amyotrophic lateral sclerosis (ALS) patients by echo intensity (EI) and to evaluate if EI correlates with measures of bulbar function. METHODS: Ultrasound was performed along the midline of the anterior tongue surface in 16 ALS patients and 16 age-matched controls using a linear hockey stick 16-7 MHz transducer. A region of interest was manually drawn and then EI was determined for the upper 1/3 of the muscle. For patients, the ALS functional rating scale - revised (ALSFRS-R) was used to calculate bulbar sub-scores and the Iowa Oral Performance Instrument (IOPI) was used to measure tongue strength. RESULTS: EI was significantly higher in ALS patients than in healthy participants (49.8 versus 37.8 arbitrary units, p < 0.01). In the patient group, EI was negatively correlated with ALSFRS-R bulbar sub-score (RS = -0.65, p < 0.01). An inverse correlation between EI and tongue strength did not reach significance (RS = -0.34, p = 0.28). CONCLUSIONS: This study suggests that EI can differentiate healthy from diseased tongue muscle, and correlates with a standard functional measure in ALS patients. SIGNIFICANCE: Tongue EI may represent a novel biomarker for bulbar dysfunction in ALS.

Brain DSC MR Perfusion in Children: A Clinical Feasibility Study Using Different Technical Standards of Contrast Administration.

BACKGROUND AND PURPOSE: Dynamic susceptibility contrast MR perfusion imaging has limited results in children due to difficulties in reproducing technical standards derived from adults. This prospective, multicenter study aimed to determine DSC feasibility and quality in children using custom administration of a standard dose of gadolinium. MATERIALS AND METHODS: Eighty-three consecutive children with brain tumors underwent DSC perfusion with a standard dose of gadobutrol administered by an automated power injector. The location and size of intravenous catheters and gadobutrol volume and flow rates were reported, and local and/or systemic adverse effects were recorded. DSC was qualitatively evaluated by CBV maps and signal intensity-time curves and quantitatively by the percentage of signal drop and full width at half-maximum, and the data were compared with the standards reported for adults. Quantitative data were grouped by flow rate, and differences among groups were assessed by analysis of covariance and tested for statistical significance with a t test. RESULTS: No local or systemic adverse events were recorded independent of catheter location (63 arm, 14 hand, 6 foot), size (24-18 ga), and flow rates (1-5 mL/s). High-quality CBV maps and signal intensity-time curves were achieved in all patients, and quantitative evaluations were equal or superior to those reported for adults. No significant differences (P ≥ .05) were identified among the higher-flow-rate groups in the quantitative data. CONCLUSIONS: A custom administration of a standard dose of gadobutrol allows safe and high-quality DSC MR perfusion imaging in children.

Comprehensive analysis by liquid chromatography Q-Orbitrap mass spectrometry: Fast screening of peptides and organic molecules.

The number of substances nominally listed in the prohibited list of the World Anti-Doping Agency increases each year. Moreover, many of these substances do not have a single analytical target and must be monitored through different metabolites, artifacts, degradation products, or biomarkers. A new analytical method was developed and validated for the simultaneous analysis of peptides and organic molecules using a single sample preparation and LC-Q-HRMS detection. The simultaneous analysis of 450 target molecules was performed after cleanup on a mixed-mode solid-phase extraction cartridge, combined with untreated urine. The cleanup solvent and reconstitution solvent were the most important parameters for achieving a comprehensive sample preparation approach. A fast chromatographic run based on a multistep gradient was optimized under different flows; the detection of all substances without isomeric coelution was achieved in 11 minutes, and the chromatographic resolution was considered a critical parameter, even in high-resolution mass spectrometry detection. The mass spectrometer was set to operate by switching between positive and negative ionization mode for FULL-MS, all-ion fragmentation, and FULL-MS/MS2 . The suitable parameters for the curved linear trap (c-trap) conditions were determined and found to be the most important factors for the development of the method. Only FULL-MS/MS2 enables the detection of steroids and peptides at concentrations lower than the minimum required performance levels set by World Anti-Doping Agency (1 ng mL-1 ). The combination of the maximum injection time of the ions into the c-trap, multiplexing experiments, and loop count under optimized conditions enabled the method to be applied to over 10 000 samples in only 2 months during the 2016 Rio Summer Olympic and Paralympic Games. The procedure details all aspects, from sample preparation to mass spectrometry detection. FULL-MS data acquisition is performed in positive and negative ion mode simultaneously and can be applied to untargeted approaches.

Portal-systemic shunting in patients with fibrosis or cirrhosis due to chronic hepatitis C: the minimal model for measuring cholate clearances and shunt.

BACKGROUND: Measurement of portal inflow and portal-systemic shunt using cholate clearances could be useful in monitoring patients with liver disease. AIM: To examine relationships of cholate clearances and shunt to cirrhosis and varices and to define minimal sampling requirements. METHODS: Five hundred forty-eight studies were performed in 282 patients enrolled in the Hepatitis C Antiviral Long-term Treatment to prevent Cirrhosis (HALT-C) trial. Stable, non-radioactive isotopes of cholate were administered intravenously and orally, clearances (Cl(iv) and Cl(oral)) were calculated from [dose/area under curve (AUC)] and cholate shunt from [(AUC(oral):AUC(iv)) x (Dose(iv):Dose(oral)) x 100%]. RESULTS: Cholate Cl(oral) and cholate shunt correlated with prevalences of both cirrhosis and varices (P < 0.0001 for all). Peripheral venous sampling at 5, 20, 45, 60 and 90 min defined the minimal model. Linear regression of cholate shunt determined from five points within 90 min vs. the standard method of 14 points over 3 h yielded slope of 1.0 and intercept 0.5% (r(2) = 0.98, P < 0.0001). Results were identical in the 189 validation studies (slope 1.0, intercept 0.5%, r(2) = 0.99, P < 0.0001). CONCLUSIONS: Cholate Cl(oral) and cholate shunt may be useful in monitoring patients with liver disease. The 5-point model enhances application of cholate Cl(oral) and cholate shunt in the non-invasive assessment of the portal circulation.

T1 Signal Measurements in Pediatric Brain: Findings after Multiple Exposures to Gadobenate Dimeglumine for Imaging of Nonneurologic Disease.

BACKGROUND AND PURPOSE: Signal intensity increases possibly suggestive of gadolinium retention have recently been reported on unenhanced T1-weighted images of the pediatric brain following multiple exposures to gadolinium-based MR contrast agents. Our aim was to determine whether T1 signal changes suggestive of gadolinium deposition occur in the brains of pediatric nonneurologic patients after multiple exposures to gadobenate dimeglumine. MATERIALS AND METHODS: Thirty-four nonneurologic patients (group 1; 17 males/17 females; mean age, 7.18 years) who received between 5 and 15 injections (mean, 7.8 injections) of 0.05 mmol/kg of gadobenate during a mean of 2.24 years were compared with 24 control patients (group 2; 16 males/8 females; mean age, 8.78 years) who had never received gadolinium-based contrast agents. Exposure to gadobenate was for diagnosis and therapy monitoring. Five blinded readers independently determined the signal intensity at ROIs in the dentate nucleus, globus pallidus, pons, and thalamus on unenhanced T1-weighted spin-echo images from both groups. Unpaired t tests were used to compare signal-intensity values and dentate nucleus-pons and globus pallidus-thalamus signal-intensity ratios between groups 1 and 2. RESULTS: Mean signal-intensity values in the dentate nucleus, globus pallidus, pons, and thalamus of gadobenate-exposed patients ranged from 366.4 to 389.2, 360.5 to 392.9, 370.5 to 374.9, and 356.9 to 371.0, respectively. Corresponding values in gadolinium-based contrast agent-naïve subjects were not significantly different (P > .05). Similarly, no significant differences were noted by any reader for comparisons of the dentate nucleus-pons signal-intensity ratios. One reader noted a difference in the mean globus pallidus-thalamus signal-intensity ratios (1.06 ± 0.006 versus 1.02 ± 0.009, P = .002), but this reflected nonsignificantly higher T1 signal in the thalamus of control subjects. The number of exposures and the interval between the first and last exposures did not influence signal-intensity values. CONCLUSIONS: Signal-intensity increases potentially indicative of gadolinium deposition are not seen in pediatric nonneurologic patients after multiple exposures to low-dose gadobenate.

Euthyroid goitre and sleep apnea.

A number of predisposing factors (obesity, nasal obstruction, adenoidal hypertrophy, macroglossia, etc) have been related to obstructive sleep apnea syndrome (OSAS). In addition hypothyroidism and large goitres have been reported to be associated to OSAS, but this association has not been adequately studied. We describe an obese patient with euthyroid goitre associated with OSAS. The patient showed a body mass index (BMI) of 47 and a large neck with a circumference of 60 cm. The flow-volume curve demonstrated an expiratory plateau suggesting an intrathoracic upper airway obstruction. Arterial blood gas analysis results were: pH 7.39; PCO2 54.2 mmHg; P O2 47 mmHg. Nocturnal polisomnography showed an apnea/hypopnea index (AHI) of 31 episodes/hour. Upper airway collapse was overcome by a nasal continuous positive airway pressure (nCPAP) of 14 cmH2O. Weight loss obtained by a hypocaloric diet was not accompanied by any OSAS improvement. After thyroidectomy, a nCPAP of 4 cmH2O was sufficient to prevent upper airway closure. Discontinuation of nCPAP treatment for 4 consecutive nights did not determine worsening of sleep apnea symptoms, nor a worsening of overnight oxymetry. A new polysomnography carried out after 4 nights off nCPAP showed an AHI of 33 episodes/hour. OSAS should be suspected in patients with large goitres. Decisions regarding discontinuation of nCPAP treatment after thyroidectomy should be based on polisomnographic results.

Postoperative MR Imaging of Spontaneous Transdural Spinal Cord Herniation: Expected Findings and Complications.

BACKGROUND AND PURPOSE: Spontaneous transdural spinal cord herniation is no longer a rare cause of myelopathy. The high frequency of diagnoses has led to an increase in the number of surgical procedures. The purpose of this study was to describe the spectrum of postoperative MR imaging findings concerning spontaneous transdural spinal cord herniation and to provide a practical imaging approach for differentiating expected changes and complications after an operation. MATERIALS AND METHODS: We retrospectively reviewed MR images from 12 patients surgically treated for spontaneous transdural spinal cord herniation. Surgery comprised either dural defect enlargement or duraplasty procedures. Postoperative follow-ups included at least 3 (early, intermediate, late) MR imaging studies. MR images were analyzed with respect to 3 spinal compartments: intradural intramedullary, intradural extramedullary, and extradural. The meaning and reliability of changes detected on MR images were related to their radiologic and clinical evolution with time. RESULTS: Spinal cord realignment has been stable since the early study, whereas spinal cord signal and thickness evolved during the following scans. Most extramedullary and extradural changes gradually reduced in later MR images. Three patients treated with dural defect enlargements experienced the onset of new neurologic symptoms. In those patients, late MR images showed extradural fluid collection and the development of pial siderosis. CONCLUSIONS: Our findings demonstrate the spectrum of postoperative imaging findings in spontaneous transdural spinal cord herniation. Spinal cord thickness and signal intensity continued to evolve with time; most extramedullary postsurgical changes became stable. Changes observed in later images may be suggestive of complications.

Multiple oblique illumination and high-definition microscopy for breast fine-needle aspirates.

The ability of multiple oblique illumination (MOI) and high-definition microscopy (Edge R-400 3-D microscope) to improve resolution of cellular detail in the evaluation of cytopathological specimens of Pap smears and thyroid fine-needle aspirates (FNAs) has been demonstrated. However, previous experiments showed that the advantages of MOI and high-definition stereo microscopy were less certain for the breast FNAs. We hypothesized that these findings were due to the lack of sample thickness for the breast FNA specimens. To test this hypothesis, we analyzed breast FNA specimens that were significantly thicker (10.5 microm). The number of lights (1, 2, 3, 4) and the angle of light (+1.5, 0, -3) were varied independently, creating 12 groups. Three images at each combination of settings were digitally captured and analyzed to obtain a histogram. The coefficient of resolution (Cr) was calculated to mathematically evaluate the grayscale histograms for intensities (0-255), where Cr = [¿IM - IN¿ x (N)] (IM, median pixel intensity; IN, measured pixel intensity; and N, number of pixels at given intensity). Mean Cr values demonstrated that the angle of light obliquity was not a factor in altering the resolution and contrast (p = .9). However, there was a significant increase in resolution, as measured by mean Cr values, as the number of lights was successively reduced from four lights to one light. Thus, the thicker specimen did show that increases in resolution were a significant function of the number of lights utilized.

[Areas in Calabria with an elevated incidence of congenital hypothyroidism and iodine content of drinking water]. / Aree della Calabria con elevata incidenza di ipotiroidismo congenito e contenuto di iodio nelle acque potabili.

The screening of 128,442 newborns, carried out in our laboratory from 1/1/1991 to 31/12/1996, detected 51 cases of congenital hypothyroidism (CH). Due to a 98% coverage, the accurate regional map of CH distribution has been obtained. Two rural and/or mountainous areas showed high incidence, 1/1145 (area A) and 1/1193 (area B), respectively. The incidence of the remaining region is 1/4621, whereas the mean regional incidence is 1/2518. In order to verify a relationship between CH incidence and iodine deficiency, we analyzed the iodine concentration in drinkable water from 148 localities. The high incidence of CH in the A and B areas corresponds with a high percentage of water samples with iodine concentration < 2 micrograms/l (92% and 85% respectively). In 15 coastal localities with low CH incidence, iodine concentration was between 7 and 80 micrograms/l. For populations of the A and B areas showing dietary iodine deficiency due to local product diet, we suggest the iodine prophylaxis as soon as possible.

[Use of naltrexone in the treatment of opiate addicts. Efficacy and indications for type categories]. / L'utilizzo del naltrexone nella terapia delle tossicodipendenze da oppiacei. Efficacia ed indicazioni per categorie tipologiche.

Naltrexone is a pure narcotic antagonist with optimum pharmacologic properties for the long-term management of opiate addiction. The above study confirms the usefulness of naltrexone for the prevention of relapse in subjects who have been weaned from narcotics. However, the short follow up does not yet permit evaluation of its medium and long-term efficacy. The better course and outcome of treatment are significantly related to certain characteristics and types of addicts. It may be said that by assuring complete, albeit time-limited, remission the antagonist allows the addict to open a window through which to face the world, and offers the therapist the possibility to apply all the instruments at his disposal in an effective manner.

Review: putative roles for the macrophage migratory inhibitory factor at the maternal fetal interface.

Complex and dynamic networks of molecules participate in the essential interactions between maternal organism, placenta and fetus in a healthy and successful pregnancy. Macrophage migratory inhibitory factor (MIF) is one of several molecules produced at implantation sites; MIF is mostly expressed by trophoblast cells. This has led to expectations of MIF's relevance as a partner in the maternal/fetal dialog. MIF is known by its biological interactions and functional roles as an activator of innate immunity, regulating subsequent adaptive responses, which include inhibition of migration of mononuclear cells in vitro, antagonism of glucocorticoids, and regulation of expression of Toll-like receptor 4. Beyond roles in the inflammatory response, MIF can interfere with proliferative activities in different cell types, as well as with cell death pathways. This intriguing factor found at the human, porcine, ovine, bovine and rodent maternal-fetal interfaces is present in a time- and spatially-dependent manner, indicating regulatory roles in the process of embryo implantation, placental development, maintenance of pregnancy and birth. Here, we will review MIF participation in placental physiology, including new evidence for a dialog with uterine cells, and a potential role in protection of uterine decidual cells.