MiR206 and 423-3p Are Differently Modulated in Fast and Slow-Progressing Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a rare neuromuscular disease with a wide disease progression. Despite several efforts to develop efficient biomarkers, many concerns about the available ones still need to be addressed. MicroRNA (miR) are non-coding RNAs that can modulate molecular circuits and are involved in ALS pathogenic mechanisms. 22 fast and 23 slow-progressing-defined ALS patients were recruited. ALSFRS-R, strength, respiratory function, nerve conduction studies, and creatine kinase were evaluated at the baseline and after 6 months of follow-up. The mean monthly reduction of the previous variables (progression index - PI) was calculated. MiR206, 133a-3p, 151a-5p, 199a-5p, and 423-3p were dosed. The univariate analysis showed an independent reduction of miR206 and an increase of miR423-3p in patients with a slow slope of ALSFRS-R and weakness, respectively. MiR206 and 423-3p are differently modulated in fast and slow-progressing ALS patients, suggesting a role for microRNAs in prognosis and therapeutic target.

Decreased fertility in female mice lacking urokinase plasminogen activator.

It is well established that mouse ovarian granulosa cells secrete urokinase plasminogen activator (uPA) under gonadotropin stimulation. The synthesis and secretion of the enzyme correlate well with the time of follicular rupture in vivo. Moreover, uPA is secreted by the trophoblast at the time of implantation. In the present study, we have analyzed whether the absence of uPA could influence follicular growth, ovulation, and embryo implantation. Our data show fewer preantral follicles in uPA-/- ovaries but no decrease in hormonally induced ovulation. However, we observed a significant decrease in the number of implanted embryos in uPA-/- animals and, therefore, a lower number of pups per family. Adding uPA to the epithelial and stromal uterine cell culture medium strongly upregulates the expression of prostaglandin-endoperoxide synthase 2 (Ptgs2), the enzyme required for prostaglandin production and embryo implantation. The uPA inhibitor amiloride abrogated this increase.

Wheel Running Adversely Affects Disease Onset and Neuromuscular Interplay in Amyotrophic Lateral Sclerosis Slow Progression Mouse Model.

BACKGROUND: Physical activity in Amyotrophic Lateral Sclerosis (ALS) plays a controversial role. In some epidemiological studies, both recreational or professional sport exercise has been associated to an increased risk for ALS but the mechanisms underlying the effects of exercise have not been fully elucidated in either patients or animal models. METHODS: To better reproduce the influence of this environmental factor in the pathogenesis of ALS, we exposed SOD1G93A low-copy male mice to multiple exercise sessions at asymptomatic and pre-symptomatic disease stages in an automated home-cage running-wheel system for about 3 months. RESULTS: Repeated voluntary running negatively influenced disease progression by anticipating disease onset, impairing neuromuscular transmission, worsening neuromuscular decline, and exacerbating muscle atrophy. Muscle fibers and neuromuscular junctions (NMJ) as well as key molecular players of the nerve-muscle circuit were similarly affected. CONCLUSION: It thus appears that excessive physical activity can be detrimental in predisposed individuals and these findings could model the increased risk of developing ALS in predisposed and specific professional athletes.

[Construction and implementation of an experimental instrument for assessing and monitoring oncological pain to use in professional nursing care]. / Costruzione e sperimentazione di uno strumento per la valutazione e monitoraggio del dolore oncologico in ospedale, e rilievo del suo impatto sulla relazione con il paziente.

In this study the construction and experimentation of an instrument for assessing and monitoring oncological pain is described with the aim of controlling pain in at least 90% of cases, training the nurses involved to acquire the competencies necessary. The study was observational and based on a questionnaire filled in on admission and updated daily . The patient population consisted of 97 patients with lung cancer admitted to the San Camillo Hospital of Rome during the last 3 months of 2010. On discharge pain was absent in 31,5%, mild in 59,3%, moderate in 3,7% and severe in 5,5%. The incidence of breakthrough pain was 6.8%. The percentage of patients without pain at discharge was judged satisfactory and, when added to the percentage of mild pain, brought the total number of patients in whom the quality of life improved to 90.8%.