RadioLab project: knowledge of radon gas in Italy.

RadioLab is an Italian project, addressed to school-age people, and designed for the dissemination of scientific culture on the theme of environmental radioactivity, with particular regards to the importance of knowledge of radon gas exposure. The project is a nationwide initiative promoted by the National Institute of Nuclear Physics- INFN. First tool used by the project, and of immediate impact to assess the public awareness on radon, is the administration of the survey "do you know the radon gas?". In the survey, together with the knowledge of radon and of its sources, information on personal, cultural and territorial details regarding the interviewees are also taken. Reasonably, the survey invests not only young people, but also their relatives, school workers and, gradually, the public. The survey is administrated during exhibitions or outreach events devoted to schools, but also open to the public. The survey is in dual form: printed and online. The online mode clearly leads RadioLab project even outside the school environment. Based on the results of the survey, several statistical analyses have been performed and many conclusions are drawn about the knowledge of the population on the radon risk. The RadioLab benefit and the requirement to carry on the project goals, spreading awareness of environmental radioactivity from radon, emerge. The dataset involves all twenty Italian regions and consists of 28,612 entries covering the 5-year period 2018-2022.

De novo Absence Status Epilepticus in a pediatric cohort: Electroclinical pattern in a multicenter Italian patients cohort.

PURPOSE: Absence Status epilepticus (AS) is a form of Non Convulsive Status Epilepticus defined as a prolonged, generalized and non-convulsive seizure, with an altered content of consciousness. We aim to describe a group of healthy children, who presented recurrent and unprovoked de novo AS as the only manifestation of their epilepsy, with an excellent response to antiepileptic drugs. METHOD: We retrospectively reviewed the electroclinical and genetic features of 13 pediatric patients, referring to our epilepsy centers from 2005 to 2019, on the following criteria: (1) regular psychomotor development, (2) one or more unprovoked AS as the only epileptic manifestation, (3) normal blood testing, (4) normal neuroimaging, (5) EEG recording, (6) available follow-up (1-14 years). RESULTS: Patients are 7 females and 6 males, aged 7-22, with a mean age at AS onset of 9,3 years. All of them started an antiepileptic therapy, with an excellent response to Valproic Acid (VPA) or Ethosuximide (ETS). 5 patients did not start the therapy immediately after the first AS and they presented recurrent AS (from 2 to 4 episodes). 10 of them performed aCGH, karyotype, NGS panel or Whole Exome Sequencing. CONCLUSIONS: We suggest that de novo AS may be a well-defined age-related and self-limited epilepsy syndrome, with a good prognosis and excellent response to therapy, but it comes with a high risk of relapsing if not adequately treated with antiepileptic drugs.

Production of fermented chestnut purees by lactic acid bacteria.

The objective of this study was to develop a new chestnut-based puree, in order to seasonally adjust the offer and use the surplus of undersized production, providing, at the same time, a response to the growing demand for healthy and environmentally friendly products. Broken dried chestnuts have been employed to prepare purees to be fermented with six different strains of Lactobacillus (Lb.) rhamnosus and Lactobacillus casei. The fermented purees were characterized by a technological and sensorial point of view, while the employed strains were tested for their probiotic potential. Conventional in vitro tests have indicated the six lactobacilli strains as promising probiotic candidates; moreover, being the strains able to grow and to survive in chestnut puree at a population level higher than 8 log10 CFU/mL along 40 days of storage at 4 °C, the bases for the production of a new food, lactose-free and with reduced fat content, have been laid.

Coronary artery disease, cerebral non-fatal ischemic stroke in retinal vein occlusion: an 8-yr follow-up.

Forty-five consecutive subjects (26M, 19F; mean age 54 ± 14 yrs) with a diagnosed retinal vein occlusion (RVO), were followed-up for 8 yrs. As many as 145 sex-age- and blood pressure-matched individuals (78M, 67F; mean age 54.4 ± 13.5 yrs), that did not experience any vascular event, served as controls. At the time of the RVO, controls and subjects did not differ as to hypercholesterolemia, hypertrigliceridemia, diabetes mellitus, smoking habits, inherited/acquired thrombophilia. At the follow-up completion, they differed as to statin consumption (p = 0.016). During the 8-yrs follow-up, in the control population, 11 out of 145 (7.6%) subjects had experienced a major vascular event (8 coronary artery disease; 3 cerebral non-fatal ischemic stroke). In contrast, of the 45 subjects with a history of RVO, as many as 10 (22.2%) had experienced a major vascular event: 4 coronary artery disease; 4 cerebral non-fatal ischemic stroke; 2 cardiovascular + cerebrovascular event (p = 0.012). A prolonged antiplatelet treatment, prior to the major vascular event, was found in 5/45 cases (11.1%) vs 23/145 (15.9%) controls (p = 0.63). In contrast, a long-lasting administration of anti-hypertensive drugs, to achieve a control of blood pressure, was found in 83.4% of controls and only in 46.7% of cases (p < 0.0001). In conclusion, in a 8-yr follow-up, coronary artery disease and/or non-fatal ischemic stroke were more common in subjects with a history of RVO than in a large setting of subjects comparable for cardiovascular risk factors. These data also argue for RVO as a vascular disease in which aggressive anti-hypertensive therapy to prevent stroke and/or myocardial infarction is needed.

Abnormally high prevalence of major components of the metabolic syndrome in subjects with early-onset idiopathic venous thromboembolism.

BACKGROUND: Although patients with idiopathic VTE are at higher than normal risk of asymptomatic atherosclerosis and of cardiovascular events, the impact of cardiovascular risk factors on VTE is poorly understood. OBJECTIVE: To assess the prevalence of the metabolic syndrome and of its components in patients with early-onset idiopathic VTE. METHODS: As many as 323 patients referred to our Thrombosis Ward for a recent (<6-months) early-onset idiopathic venous thromboembolism (VTE), were compared with 868 gender- and age-matched subjects, in whom a history of venous thrombosis had been excluded, referred during the same period time to our Ward. All had undergone a clinical assessment for smoking habits and for the presence of the components of the metabolic syndrome. RESULTS: The metabolic syndrome was detected in 76/323 cases (23.5%) and in 81/868 controls (9.3%) (p<0.001; OR:2.990; 95%C.I.:2.119-4.217). Smoking was more common in patients with idiopathic VTE than in controls. In addition to the metabolic syndrome as a whole, its major individual determinants (arterial hypertension, impaired fasting glucose plasma levels, abdominal obesity, hypertriglyceridemia, low HDL-cholesterol) significantly correlated with idiopathic VTE (p always <0.05). The prevalence of thrombotic events was lower in females than in males (p=0.000; OR:2.217), the latter being most often hypertensives, smokers, hypertriglyceridemics, carriers of a metabolic syndrome and of impaired fasting glucose than females. In a multivariate analysis, arterial hypertension, impaired fasting glucose, abdominal obesity, and hypercholesterolemia independently predicted idiopathic venous events. CONCLUSIONS: Both metabolic syndrome as a whole and its major components individually considered, independently predict early-onset idiopathic VTE.

Pontocerebellar hypoplasia: clinical, pathologic, and genetic studies.

BACKGROUND: Mutations in genes encoding subunits of the tRNA-splicing endonuclease (TSEN) complex were identified in patients with pontocerebellar hypoplasia 2 (PCH2) and pontocerebellar hypoplasia 4 (PCH4). OBJECTIVE: We report molecular genetic findings in 12 Italian patients with clinical and MRI findings compatible with PCH2 and PCH4. METHODS: We retrospectively selected a cohort of 12 children from 9 Italian families with MRI of hypoplastic pontocerebellar structures and clinical manifestations suggesting either PCH2 or PCH4 and submitted them to direct sequencing of the genes encoding the 4 subunits of the TSEN complex, namely TSEN54, TSEN34, TSEN15, and TSEN2. RESULTS: In a cohort of 12 children, we detected the common p.A307S mutation in TSEN54 in 9/12 available patients from nine unrelated families. We also detected a novel c.1170_1183del (p. V390fs39X) in compound heterozygosity with the common p.A307S in a child with a severe PCH4 phenotype. In another severely affected patient, the second mutant allele was not identified. Two sibs without mutations in the TSEN complex were unlinked to the PCH3 locus. In addition to typical clinical and neuroradiologic features of PCH2, both children were affected by a tubulopathy resembling Bartter syndrome. CONCLUSIONS: We confirm that the common p.A307S mutation in TSEN54 is responsible for most of the patients with a PCH2 phenotype. The presence of a heterozygous in/del variant correlates with a more severe phenotype as PCH4. In addition, we describe a new clinical form of PCH in 2 sibs with clinical and MRI features of PCH2.

Dorsal brain stem syndrome: MR imaging location of brain stem tegmental lesions in neonates with oral motor dysfunction.

The anatomic extent of brain stem damage may provide information about clinical outcome and prognosis in children with hypoxic-ischemic encephalopathy and oral motor dysfunction. The aim of this study was to retrospectively characterize the location and extent of brain stem lesions in children with oral motor dysfunction. From January 2005 to August 2009, 43 infants hospitalized at our institution were included in the study because of a history of hypoxic-ischemic events. Of this group, 14 patients showed oral motor dysfunction and brain stem tegmental lesions detected at MR imaging. MR imaging showed hypoxic-ischemic lesions in supra- and infratentorial areas. Six of 14 patients revealed only infratentorial lesions. Focal symmetric lesions of the tegmental brain stem were always present. The lesions appeared hyperintense on T2-weighted images and hypointense on IR images. We found a strong association (P < .0001) between oral motor dysfunction and infratentorial lesions on MR imaging. Oral motor dysfunction was associated with brain stem tegmental lesions in posthypoxic-ischemic infants. The MR imaging examination should be directed to the brain stem, especially when a condition of prolonged gavage feeding is necessary in infants.

Longer-acting factor VIII to overcome limitations in haemophilia management: the PEGylated liposomes formulation issue.

Injected factor VIII (FVIII), the current treatment for haemophilia A, leads to major improvements in the quality of life and life expectancy of individuals with this disorder. However, because injected FVIII has a short half-life in vivo, this strategy has major limitations for highly demanding regimens (e.g. prophylaxis, immune tolerance induction, surgery). Newer formulations of longer-acting FVIII are presently under investigation. The use of low molecular weight polyethylene glycol (PEG)-containing liposomes as carriers for recombinant FVIII (rFVIII) results in the prolongation of haemostatic efficacy. Data from preclinical experiments in mice, early clinical evaluations, and pharmacokinetics and pharmacodynamics results indicate that an rFVIII pegylated liposomal formulation may provide potential clinical benefit to patients with severe haemophilia A by prolonging the protection from bleeding. In light of this potential clinical benefit, a multicentre, randomized, active-controlled, non-inferiority phase II trial with two parallel treatment arms and equal randomization after stratification for the presence or absence of target joints in patients and for ages >/=18 years vs. <18 years is currently being conducted. The study will test the hypothesis that rFVIII-Lip once-weekly prophylaxis is not inferior to rFVIII-water for injection thrice-weekly prophylaxis. A total of 250 patients will be enrolled with severe haemophilia A (<1% FVIII) on on-demand or secondary prophylaxis treatment and with documented bleeds or injections during the 6 months before study entry. Sixty-four centres in 14 different countries are involved in the study; recruitment is underway. In Italy, six centres have already included 15 patients (no screening failure). Eight of these patients have completed the run-in phase and have begun the home treatment. No unexpected serious adverse events have been reported thus far. Data emerging from this phase II study will help collect relevant data to overcome current limitations in haemophilia management by employing treatment with longer-acting rFVIII.

Cost of care of haemophilia with inhibitors.

In Western countries, the treatment of patients with inhibitors is presently the most challenging and serious issue in haemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the healthcare of patients in this setting. Being designed to address questions of resource allocation and effectiveness, decision models are the golden standard to reliably assess the overall economic implications of haemophilia with inhibitors in terms of mortality, bleeding-related morbidity, and severity of arthropathy. However, presently, most data analyses stem from retrospective short-term evaluations, that only allow for the analysis of direct health costs. In the setting of chronic diseases, the cost-utility analysis, that takes into account the beneficial effects of a given treatment/healthcare intervention in terms of health-related quality of life, is likely to be the most appropriate approach. To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long-term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low-responding/high responding inhibitors) to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost-utility analysis in the treatment of haemophiliacs with inhibitors.

T lymphocyte subsets of the umbilical cord blood of dogs / Subpopulações de linfócitos t no sangue de cordão umbilical de cães

The hematological parameters red blood cells (RBC) and total white blood cells (WBC) counts, hematocrit, hemoglobin concentration, and RBC indexes (median corpuscular volume and median corpuscular hemoglobin concentration) were determined and T CD5+ lymphocytes and CD4+ and CD8+ subpopulations of the umbilical cord blood (UCB) of dogs were quantified by the cytofluorimetric technique. Nine adult Beagles, from two do five-year old, were used as control. The umbilical cord blood (UCB) was collected from 20 neonate dogs. The method for the UCB collection was adequate to obtain sufficient quantity of blood for the accomplishment of the hematological analyses and lymphocyte quantification. Cytoscopic preparations of the UCB suggested high erythropoietic activity. There was no difference for the global leukocyte and lymphocyte counts between the groups. UCB T lymphocyte counts were lower than those obtained for adult dogs. The proportion of CD4:CD8 showed a great dominance of T CD4+ cells over T CD8+ lymphocytes in UCB.

Determinaram-se os valores hematológicos da contagem de hemácias, contagem total de leucócitos, hematócrito, concentração de hemoglobina e os índices hematimétricos (volume corpuscular médio e concentração de hemoglobina corpuscular média) e quantificaram-se os linfócitos T CD5+ e as subpopulações CD4+ e CD8+ do sangue do cordão umbilical (SCU) de cães por meio da técnica de citometria de fluxo. Nove cães adultos, da raça Beagle, foram utilizados como controle. O SCU foi colhido de 20 cães neonatos, a termo. O método de colheita de SCU utilizado proporcionou quantidade suficiente de sangue para realização das análises hematológicas e quantificação de linfócitos. As preparações citoscópicas do SCU sugeriram elevada atividade eritropoética. Não houve diferença nas contagens globais de leucócitos e linfócitos entre os grupos. A contagem de linfócitos T no SCU foi mais baixa que a obtida em animais adultos. A proporção CD4:CD8 obtida demonstrou a grande dominância das células T CD4+ sobre os linfócitos T CD8+ no SCU canino.

Inclusive K(S);(0)K(S);(0) resonance production in ep collisions at HERA.

Inclusive K_{S};{0}K_{S};{0} production in ep collisions at the DESY ep collider HERA was studied with the ZEUS detector using an integrated luminosity of 0.5 fb;{-1}. Enhancements in the mass spectrum were observed and are attributed to the production of f_{2}(1270)/a_{2};{0}(1320), f_{2};{'}(1525) and f_{0}(1710). Masses and widths were obtained using a fit which takes into account theoretical predictions based on SU(3) symmetry arguments, and are consistent with the Particle Data Group values. The f_{0}(1710) state, which has a mass consistent with a glueball candidate, was observed with a statistical significance of 5 standard deviations. However, if this state is the same as that seen in gammagamma-->K_{S};{0}K_{S};{0}, it is unlikely to be a pure glueball state.

Infantile ascending hereditary spastic paralysis (IAHSP): clinical features in 11 families.

OBJECTIVE: To report clinical, neuroradiologic, neurophysiologic, and genetic findings on 16 patients from 11 unrelated families with a remarkable uniform phenotype characterized by infantile ascending hereditary spastic paralysis (IAHSP). METHODS: Sixteen patients from 11 families, originating from North Africa and Europe, who presented severe spastic paralysis and ascending progression were studied. RESULTS: Spastic paraplegia started in the first 2 years of life in most patients and extended to the upper limbs by the end of the first decade. The disease progressed to tetraplegia, anarthria, dysphagia, and slow eye movements in the second decade. The clinical course showed a long survival and preservation of intellectual skills. Clinical, neuroradiologic, and neurophysiologic findings were consistent with a relatively selective early involvement of the corticospinal and corticobulbar pathways. No signs of lower motor neuron involvement were observed, whereas motor evoked potentials demonstrated predominant involvement of the upper motor neurons. MRI was normal in young patients but showed brain cortical atrophy in the oldest, predominant in the motor areas, and T2-weighted bilateral hyperintense signals in the posterior arm of the internal capsule. The ALS2 gene, recently found mutated in consanguineous Arabic families with either an ALS2 phenotype or a juvenile-onset primary lateral sclerosis, was analyzed. Alsin mutations were found in only 4 of the 10 families, whereas haplotype analysis excluded the ALS2 locus in one family. CONCLUSIONS: The syndrome of IAHSP is genetically heterogeneous, and no clinical sign can help to distinguish patients with and without Alsin mutations.

Video/EEG aspects of early-infantile epileptic encephalopathy with suppression-bursts (Ohtahara syndrome).

Early-infantile epileptic encephalopathy (EIEE) with suppression-bursts is a severe neonatal epileptic encephalopathy. The etiology is multiple, with cerebral malformations as the more frequent. We review the clinical and video/EEG aspects of eight infants with EIEE. These infants, aged between 4 and 70 days at the time of video/EEG recordings, were studied in relation to their clinical and video/EEG characteristics, evolution, persistence of suppression-burst pattern and etiology. Seven of the eight infants showed an ictal clinical sign correlated to the burst of the suppression-burst pattern, four of whom died within 11 months of age. The other three are alive. One, now aged 4 years, underwent surgery for hemimegalencephaly and is seizure-free, with good neurological outcome. One, now aged 9 months, was pyridoxine-dependent and she is seizure-free, and with normal neurological evolution under pyridoxine therapy. One, now aged 3 years and 9 months, is seizure-free, but with severe neurological and cognitive impairment. The only child who did not show a clinical ictal correlation of burst is also alive, now aged 3 years and 9 months, with drug-resistant epilepsy, and severe neurological and cognitive deficits. With regard to the etiology, three showed structural abnormalities, two more showed some signs of prenatal origin of neurological disease, and three had metabolic etiology. Our study confirms that EIEE is a severe age-dependent early epileptic encephalopathy. The etiology is mostly malformative. The prognosis is poor regarding motor and cognitive development, seizures, as well as life expectancies. The presence of an ictal burst of the suppression-burst pattern usually correlates with a negative outcome.

Clinical and molecular findings in hyperornithinemia-hyperammonemia-homocitrullinuria syndrome.

The authors report the clinical and molecular findings in eight patients with hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome. The most consistent neurologic finding was spastic paraparesis, seen in five of the eight patients. However, all showed signs of pyramidal tract involvement. A broad spectrum of pathogenetic mutations (including missense, nonsense, splice site, insertion, and deletions) were identified in the ORNT1 gene.

Neurofibromatosis type 1 presenting with hand dystonia.

Neurofibromatosis type 1 is frequently associated with increased intensity T2-weighted magnetic resonance imaging (MRI) brain abnormalities, called "unidentified bright objects." Unidentified bright objects are generally held to be benign and tend to decrease in size during adulthood. We describe a case of neurofibromatosis type 1 with a similar thalamic and subthalamic MRI abnormality associated with contralateral hand dystonia. Over a 2-year follow-up, the lesions showed a reduction in size apparently correlated with a reduction in symptoms.

Respiratory chain defects in hereditary spastic paraplegias.

Hereditary Spastic Paraplegias (HSPs) are heterogeneous neurodegenerative disorders whose etiopathogenesis is still unclear. The identification of pathogenic mutations in a gene (SPG7) encoding a mitochondrial metalloprotease suggested that oxidative phosphorylation (OXPHOS) alterations might underlie HSP in a subgroup of patients. We performed clinical, morphological, biochemical, and molecular genetic studies in six HSP patients and in six sporadic patients to investigate OXPHOS in muscle biopsies. Complicated and pure forms were included in our study. Morphological alterations of the type seen in OXPHOS-related disorders were found in three patients. Five patients showed an isolated defect of complex I activity. No mutations in the SPG7 gene were detected. Our results suggest that OXPHOS defects in HSP patients are more common than previously believed.

Ataxia, deafness, leukodystrophy: inherited disorder of the white matter in three related patients.

The authors report three related patients, two girls and a boy, presenting a distinctive clinical phenotype characterized by early-onset, slowly progressive ataxia. Subsequently these patients experienced sensorineural deafness, resulting in complete hearing loss by the age of 12 years, and exhibited leukodystrophy on brain MRI. There was no mental deterioration. An extensive neurometabolic assessment failed to detect any anomalies in the three patients. The patients originated from a large consanguineous family in southern Italy (Calabria), with a pedigree that was traced back five generations. The disease's pattern of transmission suggests an autosomal recessive trait.

Neurophysiologic follow-up of long-term dietary treatment in adult-onset adrenoleukodystrophy.

OBJECTIVE: To monitor the effects of dietary treatment in adult-onset adrenoleukodystrophy (ALD) by means of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs). BACKGROUND: SEPs and MEPs have proved useful in revealing signs of progressively severe, central dying-back axonopathy in early stages of adult-onset ALD. METHODS: Eight patients with adult-onset ALD underwent clinical examination, brain and spine MRI, and SEP and MEP studies before and after 3 years of Lorenzo's oil dietary therapy. RESULTS: Before treatment, brain MRI was normal in five patients. Three of these patients had pure spinal SEP abnormalities and in the remaining two patients SEPs showed signs of involvement of both the spinal and cerebral somatosensory tracts. After treatment, the three patients with pure spinal abnormalities showed clinical and neurophysiologic worsening, whereas the two patients with a more advanced stage of disease (exhibited by SEPs) showed substantially unchanged clinical and neurophysiologic features. The patients with abnormal brain MRI at the onset of treatment showed clinical and neurophysiologic worsening. CONCLUSIONS: Lorenzo's oil therapy had no effect on patients with evidence of inflammatory brain lesions. Moreover, in patients without clear signs of inflammatory damage, this treatment does not modify significantly the natural course of the disease. However, because effective treatments should begin before the onset of severe neurologic symptoms, SEPs and MEPs should be considered to evaluate the effectiveness of other experimental treatments in the patient with a negative brain MRI.