Effect of biofilm removal from the occlusal tooth surfaces on fluorescence measurements. A clinical study

Aim: Early diagnosis and monitoring of caries lesions are the most important issues of primary and secondary prevention policies.The intraoral VistaCamiX(DurrDental, Bietigheim‐Bissingen,Germany) uses the fluorescence phenomenon for a non‐invasive, quantitative caries diagnosis. In order to make a precise evaluation the tooth surface must be completely cleaned and without biofilm. The current study aimed to evaluate the effects of biofilm removal, using air‐polishing device (Combi,MectronSpA) with glycine, on fluorescence VistaCam iX camera quantitative measurements of caries. Methods: Patients with complete permanent dentition without any kind of restorative treatments in the lateral and posterior section of upper and lower dental arches were enrolled. The occlusal surfaces of molars and premolars were photographed using the fluorescence terminal Proof of the intraoral camera VistaCam iX before and after air polishing glycine procedures, registering the highest value gained for each occlusal surface. Results:133cuspidate permanent teeth of patients aged between 13 and 25 were analyzed. Descriptive analysis showed an average of 0.82 (SD=0.65; Min=0.00; Max=1.80; Median=1.20) and of 0.93 (SD=0.60; Min=0.00; Max=1.70; Median=1.20) for values before and after treatment, respectively.The scores assigned by VistaCam iX Proof fluorescence based camera to the occlusal surfaces, after the air‐polishing treatment, are averagely higher than those before treatment, especially in the diagnosis of initial tooth decay. Conclusion: Biofilm removal with glycine air‐polishing improves the VistaCam camera accuracy in recognizing healthy tissue from the decayed one, due to the fact that air-polishing treatment increases the decayed tissue reaction to the fluorescence

The controversy on chronic cerebrospinal venous insufficiency

The objective of this review is to analyze the actual scientific controversy on chronic cerebrospinal venous insufficiency (CCSVI) and its association with both neurodegenerative disorders and multiple sclerosis (MS). We revised all published studies on prevalence of CCSVI in MS patients, including ultrasound and catheter venography series. Furthermore, we take into consideration other publications dealing with the pathophysiologic consequences of CCSVI in the brain, as well as ecent data characterizing the pathology of the venous wall in course of CCSVI. Finally, safety and pilot data on effectiveness of endovascular CCSVI treatment were further updated. Studies of prevalence show a big variability in prevalence of CCSVI in MS patients assessed by established ultrasonographic criteria. This could be related to high operator dependency of ultrasound. However, 12 studies, by the means of more objective catheter venography, show a prevalence >90% of CCSVI in MS. Global hypo-hypoperfusion of the brain, and reduced cerebral spinal fluid dynamics in MS was shown to be related to CCSVI. Postmortem studies and histology corroborate the 2009 International Union of Phlebology (UIP) Consensus decision to insert CCSVI among venous malformations. Finally, safety of balloon angioplasty of the extracranial veins was certainly demonstrated, while prospective data on the potential effectiveness of endovascular treatment of CCSVI support to increase the level of evidence by proceeding with a randomized control trial (RCT). Taking into account the current epidemiological data, including studies on catheter venography, the autoptic findings, and the relationship between CCSVI and both hypo-perfusion and cerebro-spinal fluid flow, we conclude that CCSVI can be definitively inserted among the medical entities. Research is still inconclusive in elucidating the CCSVI role in the pathogenesis of neurological disorders. The controversy between the vascular and the neurological community is due to the great variability in prevalence of CCSVI in MS patients by the means of venous ultrasound assessment. More reproducible and objective CCSVI assessment is warranted. Finally, current RCT may elucidate the role of CCSVI endovascular treatment

A seasonal periodicity in relapses of multiple sclerosis? A single-center, population-based, preliminary study conducted in Bologna, Italy

Fabrizio Salvi, Ilaria Bartolomei, Angelo Lorusso, and Elena Barbarossa are with the Department of Neuroscience, Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy -- Michael H. Smolensky is with the Department of Biomedical Engineering, the University of Texas at Austin, USA -- Ann Maria Malagoni, Paolo Zamboni, and Roberto Manfredini are with the Vascular Diseases Center, University of Ferrara, Italy -- Roberto Manfredini is with the Department of Internal Medicine, Hospital of the Delta, Azienda Unità Sanitaria Locale, Ferrara, Italy and the Department of Clinical and Experimental Medicine, Clinica Medica and Vascular Diseases Center, University of Ferrara, ItalyBackground: Temporal, i.e., 24-hour, weekly, and seasonal patterns in the occurrence of acute cardiovascular and cerebrovascular events are well documented; however, little is known about temporal, especially seasonal, variation in multiple sclerosis (MS) and its relapses. This study investigated, by means of a validated chronobiological method, whether severe relapses of MS, ones requiring medical specialty consultation, display seasonal differences, and whether they are linked with seasonal differences in local meteorological variables. Results: We considered 96 consecutive patients with severe MS relapse (29 men, 67 women, mean age 38.5 ± 8.8 years), referred to the Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy, between January 1, 2007 and December 31, 2008. Overall, we analyzed 164 relapses (56 in men, 108 in women; 115 in patients aged < 40 years, 49 in patients ≥40 years). Relapses were more frequent in May and June (12.2% each) and the least frequent in September (3.7%). Chronobiological analysis showed a biphasic pattern (major peak in May-June, secondary peak in November-December, p = 0.030). Analysis of monthly mean meteorological data showed a significant seasonal pattern in ambient temperature (peak in July, p < 0.001), relative humidity (peak in January, p < 0.001), and wind speed (peak in June, p = 0.011). Conclusions: In this Italian setting we found a biphasic pattern, peaks in spring and autumn, in severe MS relapses requiring medical consultation by doctors of the MS specialty center apparently unrelated to meteorological variables. Confirmations of the findings on larger multi-center populations residing in different climatic conditions are needed to further explore the potential seasonality of MS relapses and associated environmental triggers.Biomedical [email protected]

Cardiac amyloidosis: the great pretender

Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic “red flags” (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition

Frequency of Parkinson’s Disease Genes and Role of PARK2 in Amyotrophic Lateral Sclerosis: An NGS Study

Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) patients show a higher prevalence of Lewy body disease than the general population. Additionally, parkinsonian features were found in about 30% of ALS patients. We aimed to explore the frequency of Parkinson’s disease (PD)-causative genes in ALS patients, compared to AD and healthy controls (HCs). We used next-generation sequencing multigene panels by analyzing SNCA, LRRK2, PINK1, PARK2, PARK7, SYNJ1, CHCHD2, PLA2G6, GCH1, ATP13A2, DNAJC6 and FBXO genes. GBA gene, a risk factor for PD, was also analyzed. In total, 130 ALS and 100 AD patients were investigated. PD-related genes were found to be altered in 26.2% of ALS, 20% of AD patients and 19.2% of HCs. Autosomal recessive genes were significantly more involved in ALS as compared to AD and HCs (p = 0.021). PARK2 variants were more frequent in ALS than in AD and HCs, although not significantly. However, the p.Arg402Cys variant was increased in ALS than in HCs (p = 0.025). This finding is consistent with current literature, as parkin levels were found to be decreased in ALS animal models and patients. Our results confirm the possible role of PD-related genes as risk modifier in ALS pathogenesis

Neurological involvement in Ile68Leu (p.Ile88Leu) ATTR amyloidosis: not only a cardiogenic mutation

Ile68Leu transthyretin-related amyloidosis (ATTR) is known as a mainly or exclusively cardiogenic variant. We hypothesized that an accurate specialized neurological evaluation could reveal a consistent frequency of mixed phenotypes.Forty-six consecutive subjects with transthyretin (TTR) Ile68Leu (p.Ile88Leu) mutation (29 patients and 17 unaffected carriers) underwent an in-depth cardiac and neurologic evaluation at a single center.All 29 patients showed cardiac involvement. In 20 (69%) cases, it was associated with neurological abnormalities (i.e. a mixed phenotype): 10 (35% of the total) had signs and symptoms of neuropathy, 5 (17%) had abnormalities at the neurologic specialist examination but without symptoms, and 5 (17%) had abnormal nerve conduction study only. None of the asymptomatic carriers showed neurological abnormalities or cardiac involvement. The Neuropathy Impairment Score was5 in seven patients at baseline, and became5 in six more patients during follow-up. The probability of experiencing a major adverse cardiac event (MACE) during follow-up was higher in the mixed than cardiologic phenotype (At least two-thirds of patients with Ile68Leu ATTR and amyloidotic cardiomyopathy show an associated - definite or probable - neurologic impairment of variable degree if accurately evaluated in a neurologic setting. This proportion can rise during follow-up. The mixed phenotype carries a worse prognosis compared to the exclusively cardiologic one. These observations show that more patients could be eligible for treatment with gene silencers than currently indicated and highlight the need for an in-depth and continuous multidisciplinary evaluation of Ile68Leu ATTR patients

C6orf10 low-frequency and rare variants in italian multiple sclerosis patients

In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value <= 5 x 10(-6)). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) <= 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs 16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 x 10(-7) and p < 1 x 10(-20)). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3' region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS.In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value ≤ 5 × 10−6). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) ≤ 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 × 10−7 and p < 1 × 10−20). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3′ region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS

Carpal tunnel syndrome in cardiac amyloidosis: implications for early diagnosis and prognostic role across the spectrum of aetiologies

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