Marked efficacy of Rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced anti-ganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the efficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Marked efficacy of rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced antiganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the eficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Estimates of non-genetic effects for measures of hunting performance in short-haired and rough-haired Italian hound

The aim of this work was to estimate the effects of eight non-genetic factors (sex, type of coat, pigmentation, type of the trial, the number of the judges in the jury, the location where the competition took place, the subjectivity of the judge and the breeders) on the assessment of seven hunting traits (morphology, the breed style, search, approach, find, pursuit and voice) for the short-haired and rough-haired Italian Hound. The data consisted of 3172 field trial records between the years 2016 and 2017. The Mann–Whitney test and Kruskal–Wallis test showed that each factor was statistically significant for some traits: the sex of the dogs was statistically significant only for the evaluation of the morphology the type of coat for breed style, search, approach, find and voice; the pigmentation for all traits excluding approach; the number of judges for morphology, approach and find; the type of trial for all traits excluding voice. Spearman's ρ (rho) correlation showed that high phenotypic correlations were between morphology, breed style and search. These traits showed low to moderate correlations with the other traits except breed style and search vs. pursuit. Furthermore, principal component analysis for the factor judge, location and breeders showed that among the seven traits assessed during the trials, the morphology and the breed style had the highest loading on the final score. Our results suggest that the effect of all the non-genetic factors analysed must be taken into account by the judges during the evaluation of the dogs.Highlights We evaluated the effects of eight non-genetic factors on the assessment of seven hunting traits for the Italian Hound. All the non-genetic factors had influence on some of the hunting traits considered. Principal component analysis showed that the highest loading for morphology and breed style are on location, judge and breeder. High phenotypic correlations were between morphology, breed style, search and pursuit

FirstLife. A geo-social network to support participation in urban design

FirstLife (http://www.firstlife.org/) is a civic social network, developed by the “Social Computing” research group of the Department of Computer Science, University of Turin. It is a civic media, since it explicitly conceives users as active players in the production of social knowledge to innovate and renovate the city. It offers a geo-referenced representation of crowdsourced data, by using a map-based interface where users can add places, events, news and stories as well as starting discussions about interested areas of change. Users can create open and public groups linked to a place in order to promote collaboration between citizens and strengthen social cohesion in the real world. First Life has been involved in an ongoing project “Riscopri Risorse” that will be presented as case study. The project is structured in four phases throughout two years to progressively activate the local communities of six municipalities in the province of Turin in micro-regeneration actions. The first phase, from September 2016 to November 2017, involved over 70 classes of 30 schools ranging from primary to high schools, with about 60 teachers, a group of public officers in each city, two trainers and facilitators of the University of Turin and four members of the promoter charity. During this phase, the methodology to integrate of a digital mapping tool in the regeneration process has been co-designed with teachers and facilitators in order to define use patterns based on the platform functionalities and common guidelines to map public spaces and commons and analyse these places. From November 2016 to January 2017, each school developed a proposal for a selection of public spaces in each municipality, with a final validation by the municipal technical officers, and a final selection of one place to be collaboratively regenerated. The project will continue from March 2017 to June 2018 documenting the regeneration process through the platform, and opening the participation to families and new local actors operating in the project areas

Hypogonadism in DM1 and its relationship to erectile dysfunction

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case-control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2)

Targeting of PDGF-C/NRP-1 autocrine loop as a new strategy for counteracting the invasiveness of melanoma resistant to braf inhibitors

: Melanoma resistance to BRAF inhibitors (BRAFi) is often accompanied by a switch from a proliferative to an invasive phenotype. Therefore, the identification of signaling molecules involved in the development of metastatic properties by resistant melanoma cells is of primary importance. We have previously demonstrated that activation of neuropilin-1 (NRP-1) by platelet-derived growth factor (PDGF)-C confers melanoma cells with an invasive behavior similar to that of BRAFi resistant tumors. Aims of the present study were to evaluate the role of PDGF-C/NRP-1 autocrine loop in the acquisition of an invasive and BRAFi-resistant phenotype by melanoma cells and the effect of its inhibition on drug resistance and extracellular matrix (ECM) invasion. Furthermore, we investigated whether PDGF-C serum levels were differentially modulated by drug treatment in metastatic melanoma patients responsive or refractory to BRAFi as single agents or in combination with MEK inhibitors (MEKi). The results indicated that human melanoma cells resistant to BRAFi express higher levels of PDGF-C and NRP-1 as compared to their susceptible counterparts. Overexpression occurs early during development of drug resistance and contributes to the invasive properties of resistant cells. Accordingly, silencing of NRP-1 or PDGF-C reduces tumor cell invasiveness. Analysis of PDGF-C in the serum collected from patients treated with BRAFi or BRAFi+MEKi, showed that in responders PDGF-C levels decrease after treatment and raise again at tumor progression. Conversely, in non-responders treatment does not affect PDGF-C serum levels. Thus, blockade of NRP-1 activation by PDGF-C might represent a new therapeutic approach to counteract the invasiveness of BRAFi-resistant melanoma

health related quality of life in myotonic dystrophy type 1 and its relationship with cognitive and emotional functioning

Objective: To evaluate the health-related quality of life in myotonic dystrophy type 1 and its relationships with clinical, genetic, neuropsychological and emotional factors. Design: Case-control study of a continuous series of patients with myotonic dystrophy type 1. Patients and methods: Twenty patients, and 20 age-, sex- and education-matched healthy controls underwent the MOS 36Item Short-Form Health Survey (SF-36), an extensive neuropsychological battery and emotional functioning tests. Results: Patients' SF-36 mean scores were lower than those of controls in all dimensions. The neuropsychological study showed a significant impairment in visuospatial and verba