Results From a Large,Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

ReProComet: a new in vitro method to assess DNA damage in mammalian sperm.

The increasing request of chemical safety assessment demands for the validation of alternative methods to reduce the resort to animal experimentation. Methods that evaluate reproductive toxicity are among those requiring the largest use of animals. Presently, no validated in vitro alternative exists for the assessment of reproductive toxicity. Mammalian sperm are sensitive targets of DNA-reactive chemicals, which form premutagenic adducts. Here, we propose a new method based on comet assay to detect DNA damage induced by potential germ cell mutagens in bull sperm available from assisted reproduction practices. In somatic cells, chemical-induced adducts can be revealed by comet assay that detects DNA breaks produced during adduct repair. Mature sperm, however, are devoid of repair enzymes, and adducts are processed only after fertilization. For this reason, comet assay is not sensitive to detect DNA lesions induced in sperm by most chemicals. To overcome such limitation, we developed a modified comet assay based on the addition of a protein extract from HeLa cells to agarose-embedded sperm on microscopic slides. To test the method, sperm were treated in vitro with methyl methanesulfonate (MMS) or melphalan (MLP) and comet assay was conducted both with and without protein supplementation. No effect of MMS or MLP was detected without protein supplementation; on the contrary, a clear-cut dose-dependent effect was measured after addition of the cell extract. These results represent a proof of concept of a novel in vitro mutagenicity test on sperm that could offer a promising approach to complement previously validated in vivo germ cell genotoxicity assays.     

Implications of remarriage and stepfamily formation for marriage education*

Couples in remarriages with stepchildren are a significant portion of the marriage population and have unique educational needs regarding aspects of couple functioning within the context of stepfamily development. From a review of the literature, we examine current curricula focused on these couples. Information is offered on implementation issues regarding recruitment, delivery context, facilitator and participant characteristics, and evaluation.     

Temporal lobe dual pathology in malignant migrating partial seizures in infancy.

A child had the characteristic clinical and EEG pattern of migrating partial seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and cortical-subcortical blurring.Seizures were drug-resistant, with recurring episodes of status epilepticus. The child developed microcephaly with arrest of psychomotor development. Focal brain lesions, in the context of migrating partial seizures, have not been previously reported.[Published with video sequences].     

Upregulation of basic fibroblast growth factor in smokers with chronic bronchitis.

The aim of the study was to investigate the expression of basic fibroblast growth factor (bFGF) and its receptor, fibroblast growth factor receptor (FGFR)-1, in the central airways of smokers with chronic bronchitis. The lobar bronchi from 17 subjects undergoing thoracotomy for solitary nodules were examined. All had a history of cigarette smoking, nine had symptoms of chronic bronchitis and airflow limitation, and eight were asymptomatic with normal lung function. Using immunohistochemical methods, bFGF and FGFR-1 expression in the total airway wall and the different airway compartments, i.e. bronchial glands, submucosal vessels and smooth muscle, was quantified. Moreover, to investigate the role of bFGF in angiogenesis, the number of submucosal vessels was quantified. Smokers with chronic bronchitis had an increased bFGF expression in the total airway wall compared with asymptomatic smokers, which was mainly due to bFGF upregulation in bronchial glands. By contrast, the expression of FGFR-1 and the number of submucosal vessels was similar in the two groups of subjects examined. In conclusion, smokers with chronic bronchitis have an increased expression of basic fibroblast growth factor in the central airways, which is mainly due to an increased expression in bronchial glands, suggesting the involvement of this growth factor in the pathogenesis of chronic bronchitis.     

Botulinum toxin and neuromotor rehabilitation: An integrated approach to idiopathic cervical dystonia.

Currently, the best treatment option for idiopathic cervical dystonia (ICD) is injection of botulinum toxin (BTX) into the affected muscles, whereas rehabilitative approaches have given disappointing results. We evaluated whether the association of an ad hoc rehabilitative program may improve the clinical efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty patients with ICD were randomly assigned to two different treatment groups: (1) BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2) BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at reinjection (284.5 vs. 325.5 units). In addition, they showed more marked reductions in their disability in activities of daily living (-9.7 vs. -4.85 points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A therapy with a specific program of physical therapy may improve ICD treatment outcome.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

Progressive knowledge loss: a longitudinal case study.

The evolution of the progressive loss of semantic knowledge of a patient, VZ, with lesions mainly affecting the infero-medial temporal lobes, was followed for two years. At the beginning of the study VZ's performance was mainly characterized by a category-specific deficit for living things and a modality-specific deficit for perceptual attribute knowledge. As time went on, VZ's disorder affected all categories by changing the relationship between category and attribute knowledge. Data show that dissociations may change in the course of progressive cognitive breakdown, depending on both degeneration stage and task demands. VZ's performance is discussed in the light of the most influential theoretical accounts. Methodological suggestions regarding longitudinal studies of degenerative patients are also put forward.