A systematic review on drugs for synaptic plasticity in the treatment of dementia.

The aim of the present systematic review (SR) was to provide an overview of all published and unpublished clinical trials investigating the safety and efficacy of disease-modifying drugs targeting synaptic plasticity in dementia. Searches on CT.gov and EuCT identified 27 trials (4 phase-1, 1 phase-1/2, 18 phase-2, 1 phase-2/3, 1 phase-3, 1 phase-4, and 1 not reported). Twenty of them completed, and seven are currently active or enrolling. The structured bibliographic searches yielded 3585 records. A total of 12 studies were selected on Levetiracetam, Masitinib, Saracatinib, BI 40930, Bryostatin 1, PF-04447943 and Edonerpic drugs. We used RoB tool for quality analysis of randomized studies. Efficacy was assessed as a primary outcome in all studies except one and the main scale used was ADAS-Cog (7 studies), MMSE and CDR (4 studies). Safety and tolerability were reported in eleven studies. The incidence of SAEs was similar between treatment and placebo. At the moment, only one molecule reached phase-3. This could suggest that research on these drugs is still preliminary. Of all, three studies reported promising results on Levetiracetam, Bryostatin 1 and Masitinib.

Biological recognition of graphene nanoflakes.

The systematic study of nanoparticle-biological interactions requires particles to be reproducibly dispersed in relevant fluids along with further development in the identification of biologically relevant structural details at the materials-biology interface. Here, we develop a biocompatible long-term colloidally stable water dispersion of few-layered graphene nanoflakes in the biological exposure medium in which it will be studied. We also report the study of the orientation and functionality of key proteins of interest in the biolayer (corona) that are believed to mediate most of the early biological interactions. The evidence accumulated shows that graphene nanoflakes are rich in effective apolipoprotein A-I presentation, and we are able to map specific functional epitopes located in the C-terminal portion that are known to mediate the binding of high-density lipoprotein to binding sites in receptors that are abundant in the liver. This could suggest a way of connecting the materials' properties to the biological outcomes.

[5 days Cefaclor vs. 10 days amoxicillin/clavulanate in the treatment of childhood streptococcal pharyngitis. Data from a randomized clinical trial]. / Efficacia di Cefaclor 5 giorni vs. amoxicillina-acido clavulanico 10 giorni, nella terapia della faringotonsillite streptococcia del bambino. Risultati di uno studio clinico randomizzato.

AIM: The duration of therapy represents a fundamental aspect in the compliance to the therapy of child pathologies, such as pharyngotonsillitis, treated with oral therapy. Although penicillin and amoxicillin are the first choice antibiotics in the case of a child suffering from pharyngotonsillitis with the proven presence of Group A ß-hemolytic Streptococcus (GAS), the number of orally administered doses and 10 days of therapy, considerably lower the compliance. METHODS: An open phase IV randomized multicenter clinical trial was conducted in parallel groups, involving 49 family pediatrician (FP), distributed over the entire national territory, enrolling 435 children suffering from GAS-FT. 210 children received Cefaclor, 50 mg/kg/day, administered twice daily for five days, whilst 213 children received amoxicillin/clavulanate 40 mg/kg/day administered twice daily for 10 days. RESULTS: The results showed percentages of eradication of 88.4% for the Cefaclor group and 94.3% for the amoxicillin/clavulanate group, and a positive clinical judgement of 92.3% for the Cefaclor group and 96.6% for the amoxicillin/clavulanate group. The two arms of the study did not have any significant statistical differences, neither for the eradication, nor for the clinical judgement nor for the reduction of the Milano Score between the beginning and the end of treatment, with a P=0.042 for amoxicillin/clavulanate for eradication. CONCLUSION: This study confirms that the administration of Cefaclor for five days during GAS-FT has the same efficacy as a 10-day therapy with amoxicillin/clavulanate, with a clearly different compliance.

Universal varicella vaccination in the Sicilian paediatric population: rapid uptake of the vaccination programme and morbidity trends over five years.

Following the licensure of the Oka/Merck varicella vaccine in Italy in January 2003, the Sicilian health authorities launched a universal vaccination programme in all nine Local Health Units. A two-cohort vaccination strategy was adopted to minimise the shift of the mean age of varicella occurrence to older age groups, with the goal of vaccinating with one dose at least 80% of children in their second year of life and 50% of susceptible adolescents in their 12th year of life. Two studies were implemented in parallel to closely monitor vaccination coverage as well as varicella incidence.

CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

OBJECTIVE: To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations. METHODS: Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis. RESULTS: We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep. CONCLUSIONS: This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) are characterized by progressive lower extremity spasticity due to an axonal degeneration of motor and sensory neurons. We report a four-generation pedigree segregating an autosomal dominant phenotype for HSP and showing a linkage to the SPG10 locus, coding for Kinesin family member 5A. Subsequent to a denaturing high performance liquid chromatography (dHPLC) mutation screening we found a new missense mutation 838C>T (R280C) at an invariant arginine residue in a region involved in the microtubule binding activity.