The Effects of ADAS on Driving Behavior: A Case Study.

The presence of numerous sensors inside modern vehicles leads to the development of new driving assistance tools, the real usefulness of which depends, however, on the environmental context. This study proposes a procedure capable of quantifying the effectiveness of some warnings produced by an On-Board Unit (OBU) inside the vehicle in a specific environmental context, even if limited only to the considered road. The experimentation was carried out by means of a driving simulator with a sample of young users with sufficiently homogeneous characteristics. The collected data were treated by ANOVA to highlight any differentiation between a traditional driving condition, without any instrumental support, and another involving the OBU was present. The results showed that only in relation to the investigated road, the OBU ensured the advantage of sending information of interest to the driver without invalidating their performance in terms of longitudinal and transverse acceleration, speeding, and steering angle. This research could be of interest to the infrastructure managers who, in case of inappropriate use of a road, could intensify active and passive safety devices for users' safety.

CCM3/SERPINI1 bidirectional promoter variants in patients with cerebral cavernous malformations: a molecular and functional study.

BACKGROUND: Cerebral cavernous malformations (CCMs) are vascular anomalies of the nervous system mostly located in the brain presenting sporadically or familial. Causes of familial forms are mutations in CCM1 (Krit1), CCM2 (MGC4607) and CCM3 (PDCD10) genes. Sporadic forms with no affected relative most often have only one lesion and no germ line mutations. However, a number of sporadic cases with multiple lesions have been reported and are indeed genetic cases with a de novo mutation or a mutation inherited from an asymptomatic parent. METHODS: Here, we performed an analysis of regulatory region of CCM genes in 60 sporadic patients, negative for mutations in coding region and intron-exon boundaries and large deletion/duplications in CCM genes by direct sequencing and MLPA. Among 5 variants identified in 851-bp region shared by CCM3 and SERPINI1 genes and acting as asymmetric bidirectional promoter, two polymorphisms c.-639 T > C/rs9853967 and c.-591 T > C/rs11714980 were selected. A case-control study was performed to analyze their possible relationships with sporadic CCMs. Promoter haplotypes activities on CCM3/SERPINI1 genes expression were tested by dual-luciferase assay. RESULTS: No variants were identified in CCM1 and CCM2 regulatory regions. In CCM3/SERPINI1 asymmetric bidirectional promoter 5 variants, 2 of them unknown and 3 corresponding to polymorphisms c.-639 T > C/rs9853967, c.-591 T > C/rs11714980 and c.-359G > A/rs9834676 were detected. While rs9853967 and rs11714980 polymorphisms fall in a critical regulatory fragment outside the minimal promoter in intergenic region, other variants had no effects on transcription factor binding according to RegRNA tool. Case-control study performed on 60 patients and 350 healthy controls showed frequencies of the mutated alleles significantly higher in the control group than in patients. Furthermore, the functional assay showed a significant reduction of CCM3 expression for C-C haplotype even more than for T-C and C-T haplotypes. In SERPINI1 direction, the reduction was not statistically significant. CONCLUSIONS: Our data indicated that rs9853967 and rs11714980 polymorphisms could be associated with a protective role in CCM disease.

Expression of sarcoglycans in the human cerebral cortex: an immunohistochemical and molecular study.

The sarcoglycan (SG) complex (SGC) is a subcomplex within the dystrophin-glycoprotein complex (DGC) and is composed of several transmembrane proteins (α, ß, δ, γ, ε and ζ). The DGC supplies a transmembranous connection between the subsarcolemmal cytoskeleton networks and the basal lamina in order to protect the lipid bilayer and to provide a scaffold for signaling molecules in all muscle cells. In addition to its role in muscle tissue, dystrophin and some DGC components are expressed in neurons and glia. Very little is known about the SG subunits in the central nervous system (CNS) and some data suggested the presence of ε and ζ subunits only. In fact, mutations in the ε-SG gene cause myoclonus-dystonia, indicating its importance for brain function. To determine the presence and localization of SGC in the human cerebral cortex, we performed an investigation using immunofluorescence, immunoblotting and reverse transcriptase polymerase chain reaction. The results showed that all SG subunits are expressed in the human cerebral cortex, particularly in large neurons but also in astrocytes. These data suggest that the SG subcomplex may be involved in the organization of CNS synapses.

[Neurologic inflammation and oral disease. An aetiopathogenic hypothesis]. / L'infiammazione neuro-mediata e le patologie della mucosa orale: un'ipotesi etiopatogetica.

The nervous system contributes to the pathophysiology of peripheral inflammation and a neurogenic component has been implicated in many inflammatory disease, including oral diseases. Neurogenic inflammation should be regarded as a protective mechanism wich forms the first line of defense and protects tissue integrity. However, prolonged noxius stimulation may result in the inflammatory response. This review focuses on the evidence suggesting that neuropeptides have a pivotal role in the complex cascade of chemical activity associated with oral diseases. The pathophysiology is complex and neuropeptides are not solely responsible for the initiation and progression of the disease. However, since neuropeptides and inflammatory modulators are released together during the inflammatory response, it will be impossible to assign a specific role to each until work with selective antagonists is completed.

Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations.

Cerebral cavernous malformations are vascular lesions that usually involve brain micro-vessels. They can occur both in a sporadic form and familial one. Causes of familial forms are mutations at three loci: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. Here, we describe a novel CCM3 missense mutation (c.422T>G) detected in two Greek brothers showing multiple lesions at magnetic resonance imaging; to date, only the youngest is symptomatic. Bioinformatics tools showed this novel variant causes a loss of function in Pdcd10 protein due to its localization in the eighth helix and, particularly, affects Leu141, a highly conserved amino acid. Roles of Pdcd10 in angiogenesis regulation and its association with early development of cerebral cavernous malformations were also considered.

Fish odor syndrome (trimethylaminuria) supporting the possible FMO3 down expression in childhood: a case report.

INTRODUCTION: Trimethylaminuria is a rare inherited disorder due to decreased metabolism of dietary-derived trimethylamine by flavin-containing monooxygenase 3. Several single nucleotide polymorphisms of the flavin-containing monooxygenase 3 gene have been described and result in an enzyme with decreased or abolished functional activity for trimethylamine N-oxygenation thus leading to trimethylaminuria. CASE PRESENTATION: Here we investigated an Italian family in which the proband was a 7-year-old girl with suspected trimethylaminuria, by flavin-containing monooxygenase 3 gene direct sequencing and urinary determination of trimethylamine and trimethylamine N-oxide. Genetic analysis found that, as with her parents and one of her two brothers, the proband carried three polymorphisms: c.472 G>A p. E158K (rs 2266782) in exon 4, c.627+10 C>G (IVS5+10G>C) (rs 2066534) and c.485-21 G>A (IVS4-22G>A) (rs 1920149) in intronic regions. CONCLUSIONS: Despite the same genotypic condition only the girl had symptoms attributable to the trimethylaminuria. The suspicion is that she has transient childhood trimethylaminuria. Therefore, we bring attention to the importance of genetic testing and eventual determination of urinary trimethylamine and trimethylamine N-oxide as instruments to offer to clinicians in the management of these pediatric patients.

Sporadic cerebral cavernous malformations: report of further mutations of CCM genes in 40 Italian patients.

Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities, affecting the central nervous system. CCMs can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1 (K-Rev interaction trapped 1 (KRIT1)), CCM2 (MGC4607), and CCM3 (PDCD10). CCMs occur as a single or multiple malformations that can lead to seizures, focal neurological deficits, hemorrhagic stroke, and headache. However, patients are frequently asymptomatic. In our previous mutation screening, performed in a cohort of 95 Italian patients, both sporadic and familial, we have identified several mutations in CCM genes, three of which in three distinct sporadic patients. In this study, representing further molecular screening of the three CCM genes, in a south Italian cohort of CCM patients enrolled by us in the last three years, we report the identification of other four new mutations in 40 sporadic patients with either single or multiple CCM.

Age dependent switching role of cyclin D1 in breast cancer.

BACKGROUND: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. The aim of this study was to better understand the molecular dynamics of ductal carcinomas with regard to proliferation and the ageing process. METHODS: 130 cases of ductal breast cancer in postmenopausal women, aged 52-96 in 3 age classes were selected. Tumoral tissues preserved in formaldehyde solution and subsequently embedded in paraffin were subjected to analysis Fluorescence in situ Hybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT- PCR) and immuno-histochemical tests. The molecular variables studied were estimated in relation to the patients' age. RESULTS: The results obtained suggest that the increment of the levels of cyclin D1 in intra-ductal breast tumors in older woman that we have examined is significantly associated with a lower proliferation rate. CONCLUSION: Cyclin D1, which characterizes tumor in young women as molecular director involved in strengthening tumoral proliferation mechanisms, may be seen as a potential blocking molecular switch in corresponding tumours in old women.

CCR5Δ32 Polymorphism Associated with a Slower Rate Disease Progression in a Cohort of RR-MS Sicilian Patients.

Multiple sclerosis (MS) disease is carried through inflammatory and degenerative stages. Based on clinical feaures, it can be subdivided into three groups: relapsing-remitting MS, secondary progressive MS, and primary progressive MS. Multiple sclerosis has a multifactorial etiology with an interplay of genetic predisposition, environmental factors, and autoimmune inflammatory mechanism in which play a key role CC-chemokines and its receptors. In this paper, we studied the frequency of CCR5 gene Δ32 allele in a cohort of Sicilian RR-MS patients comparing with general Sicilian population. Also, we evaluate the association between this commonly polymorphism and disability development and age of disease onset in the same cohort. Our results show that presence of CCR5Δ32 is significantly associated with expanded disability status scale score (EDSS) but not with age of disease onset.

Type I IFN signaling is crucial for host resistance against different species of pathogenic bacteria.

It is known that host cells can produce type I IFNs (IFN-alphabeta) after exposure to conserved bacterial products, but the functional consequences of such responses on the outcome of bacterial infections are incompletely understood. We show in this study that IFN-alphabeta signaling is crucial for host defenses against different bacteria, including group B streptococci (GBS), pneumococci, and Escherichia coli. In response to GBS challenge, most mice lacking either the IFN-alphabetaR or IFN-beta died from unrestrained bacteremia, whereas all wild-type controls survived. The effect of IFN-alphabetaR deficiency was marked, with mortality surpassing that seen in IFN-gammaR-deficient mice. Animals lacking both IFN-alphabetaR and IFN-gammaR displayed additive lethality, suggesting that the two IFN types have complementary and nonredundant roles in host defenses. Increased production of IFN-alphabeta was detected in macrophages after exposure to GBS. Moreover, in the absence of IFN-alphabeta signaling, a marked reduction in macrophage production of IFN-gamma, NO, and TNF-alpha was observed after stimulation with live bacteria or with purified LPS. Collectively, our data document a novel, fundamental function of IFN-alphabeta in boosting macrophage responses and host resistance against bacterial pathogens. These data may be useful to devise alternative strategies to treat bacterial infections.