Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia

Mutations in the profilin 1 (PFN1) gene, encoding a protein regulating filamentous actin growth through its binding to monomeric G-actin, have been recently identified in familial amyotrophic lateral sclerosis (ALS). Functional studies performed on ALS-associated PFN1 mutants demonstrated aggregation propensity, alterations in growth cone, and cytoskeletal dynamics. Previous screening of PFN1 gene in sporadic ALS (SALS) cases led to the identification of the p.E117G mutation, which is likely to represent a less pathogenic variant according to both frequency data in control subjects and cases, and functional experiments. To determine the effective contribution of PFN1 mutations in SALS, we analyzed a large cohort of 1168 Italian SALS patients and also included 203 frontotemporal dementia (FTD) cases because of the great overlap between these 2 neurodegenerative diseases. We detected the p.E117G variant in 1 SALS patient and the novel synonymous change p.G15G in another patient, but none in a panel of 1512 control subjects. Our results suggest that PFN1 mutations in sporadic ALS and in FTD are rare, at least in the Italian population.     

Clinical phenotype, muscle MRI and muscle pathology of LGMD1F

Of the seven autosomal dominant genetically distinct forms of LGMD so far described, in only four the causative gene has been identified (LGMD1A-1D). We describe clinical, histopathological and muscle MRI features of a large Italo-Spanish kindred with LGMD1F presenting proximal-limb and axial muscle weakness. We obtained complete clinical data and graded the progression of the disease in 29 patients. Muscle MRI was performed in seven patients. Three muscle biopsies from two patients were investigated. Patients with age at onset in the early teens, had a more severe phenotype with a rapid disease course; adult onset patients presented a slow course. Muscle MRI showed prominent atrophy of lower limb muscles, involving especially the vastus lateralis. Widening the patients population resulted in the identification of previously unreported features, including dysphagia, arachnodactyly and respiratory insufficiency. Muscle biopsies showed diffuse fibre atrophy, which evolved with time, chronic myopathic changes, basophilic cytoplasmic areas, autophagosomes and accumulation of myofibrillar and cytoskeletal proteins. The LGMD1F is characterized by a selective involvement of limb muscles with respiratory impairment in advanced stages, and by different degrees of clinical progression. Novel clinical features emerged from the investigation of additional patients.     

Prevalence of ADHD in a sample of Italian students: A population-based study

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common diagnosis for children and adolescents, although the reported estimates for prevalence are extremely variable worldwide. In the present work we investigate the prevalence of ADHD in a sample of Italian students in a study divided in two phases. In Phase I, a total of 6183 schoolchildren (3178 males and 3005 females, aged range 5–15 years) were screened using the SDAI rating scale for teachers. In Phase II, the parents of children and adolescents who met high screen criteria according to SDAI (cut-off > 14; n = 471, 7.3%) were invited to complete a specific clinical-diagnostic assessment for ADHD with the help of an experienced clinician. Within the entire sample, 107 children dropped out and 12 had mental retardation, whereas 332 subjects (278 males and 54 females, age range 5–14 years) completed the Phase II of the study. One hundred ninety subjects (163 males and 27 females, male: female ratio 6:1, mean age 8 years) were diagnosed with ADHD, indicating a prevalence of 3%. ADHD subtypes included the following: combined (n = 108; 56.8%), inattentive (n = 48; 25.2%) and hyperactive/impulsive (n = 33; 17.3%).Our findings are in line with other reports of ADHD prevalence in the European Countries, and may contribute to underline the impact of this phenomenon in the population, and the need of achieving an improvement in the quality of the public health mental service for the prevention and treatment of ADHD.     

Prediction of community mental health service utilization by individual and ecological level socio-economic factors

Individuals with a more deprived socioeconomic status (SES) are more likely to have higher rates of psychiatric morbidity and use of psychiatric services. Such service use is also influenced by socioeconomic factors at the ecological level. The aim of this article is to investigate the influence of these variables on service utilization. All patients in contact with three Italian community psychiatric services (CPS) were included. Community and hospital contacts over 6 months were investigated. Socio-economic characteristics were described using a SES Index and two new Resources Accessibility Indexes. Low SES was found to be associated with more community service contacts. When other individual and ecological variables were controlled for, SES was negatively associated only with the number of home visits, which was about half the rate in deprived areas. An association between service utilization and the resources of the catchment area was also detected. The economic crisis in Europe is increasing inequality of access, so paying attention to SES characteristics at both the individual and the ecological levels is likely to become increasingly important in understanding patterns of psychiatric service utilization and planning care accordingly.     

TNF-related apoptosis-inducing ligand (TRAIL) in rheumatoid arthritis: what’s new?

TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein of the TNF superfamily that serves as an extracellular signal that triggers programmed cell death in tumor cells, without affecting normal cells. Recently, scientists have turned their attention to the emerging role of TRAIL in immune and autoimmune responses. TRAIL has been shown to down-regulate the self-antigens in autoimmune diseases, such as rheumatoid arthritis (RA) by exerting its apoptotic effect on activated T cells and synoviocytes and by its local anti-inflammatory effect. The impact of TRAIL molecular variants and agonistic monoclonal antibodies in the regulation of TRAIL activity in arthritis animal models strongly supports the idea of testing the role of TRAIL in humans, with the aim of developing new effective therapies that promote apoptosis of synoviocytes and/or infiltrating lymphocytes, by targeting TRAIL. The aim of this review is to summarize recent progress and current knowledge of TRAIL functions in RA.     

Marshall's vein persistence: a rare and occasional finding during pacemaker implantation

In adults the oblique vein of Marshall is usually absent or very thin, and it is hard to be found. In this case report we describe a case of persistence observed during pacemaker implantation.     

RETRACTED ARTICLE: Undertreatment of breast cancer in the elderly

Aims

The effect of undertreatment with adjuvant hormonal therapy, chemotherapy or radiation was studied in elderly women with breast cancer.

Methods

A prospectively maintained database was used to identify women undergoing potentially curative surgery between 1997 and 2011. The presentation, pathologic findings, treatment and outcomes of 449 women over 65 were compared to the findings in 1049 younger patients. Moreover, conventionally treated and undertreated elderly patients were identified and their characteristics and outcomes were compared.

Results

Both young and old patients presented most frequently with mammographic findings, but older patients presented more frequently with mammographic masses while younger patients presented more frequently with mammographic calcifications. Cancers of older patients were signicantly more favorable than cancers in younger patients with more infiltrating lobular, fewer ductal carcinoma in situ and more frequently estrogen receptor positive and fewer were poorly differentiated. Elderly patients had less axillary surgery, less adjuvant radiation therapy and more hormonal therapy. Fourty-six percent of the 449 elderly patients were undertreated by conventional criteria. Undertreated patients were more frequently in situ, better differentiated, smaller, and more often estrogen receptor positive. Forty-four percent of the undertreated patients died during follow-up without disease recurrence.

Conclusions

Despite undertreatment, local and distant disease-free survival was comparable to patients who were not undertreated.