The high frequency of spontaneous micronuclei observed in lymphocytes of systemic sclerosis patients: preliminary results

Objective: aim of the study is to assess the presence of spontaneous chromosome damage in patients affected by limited (lSSc) or diffuse (dSSc) Systemic Slerosis, using the micronucleus (MN) assay. Methods: we evaluated MN frequency in cultured peripheral lymphocytes of 18 SSc and in a group of 20 healthy controls. Patients were also classified as ACA+, Scl70+, FAN+ according to the presence of the specific anti-nuclear antibodies. We also explored the hypothesis that the extent of cytogenetic alteration might be related to the severity of the pathological condition and/or to the immunological profile. Results: compared to controls, the patient group as a whole showed significantly higher MN frequencies (10.8±4.5 vs. 27.8±13.7, p<0.001). No correlation was found between spontaneous chromosome damage and severity of the disease, being MN frequency 33.1±17.0 and 19.8±2.7 in lSSc and dSSc, respectively. Interestingly, ACA+ subjects displayed the highest MN frequency (36.9±15.0), as compared to patients with different antibody pattern (Scl70+, FAN+; 19.7±8.2). Conclusions: our results confirm the presence of chromosomal damage in circulating lymphocytes of SSc patients and would suggest a key role of antibodies to the centromere in determining the observed cytogenetic anomalies

The high frequency of spontaneous micronuclei observed in lymphocytes of systemic sclerosis patients: preliminary results.

OBJECTIVE: Aim of the study is to assess the presence of spontaneous chromosome damage in patients affected by limited (lSSc) or diffuse (dSSc) Systemic Slerosis, using the micronucleus (MN) assay.METHODS: We evaluated MN frequency in cultured peripheral lymphocytes of 18 SSc and in a group of 20 healthy controls. Patients were also classified as ACA+, Scl70+, FAN+ according to the presence of the specific anti-nuclear antibodies. We also explored the hypothesis that the extent of cytogenetic alteration might be related to the severity of the pathological condition and/or to the immunological profile.RESULTS: Compared to controls, the patient group as a whole showed significantly higher MN frequencies (10.8+/-4.5 vs. 27.8+/-13.7, p&lt;0.001). No correlation was found between spontaneous chromosome damage and severity of the disease, being MN frequency 33.1+/-17.0 and 19.8+/-2.7 in lSSc and dSSc, respectively. Interestingly, ACA+ subjects displayed the highest MN frequency (36.9+/-15.0), as compared to patients with different antibody pattern (Scl70+, FAN+; 19.7+/-8.2).CONCLUSIONS: Our results confirm the presence of chromosomal damage in circulating lymphocytes of SSc patients and would suggest a key role of antibodies to the centromere in determining the observed cytogenetic anomalies

Chromosome aberrations, valued as frequency of spontaneous micronuclei, in subjects with suspected presclerodermic Raynaud's phenomenon

OBJECTIVE: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with suspected presclerodermic Raynaud's phenomenon (RP), by means of molecular cytogenetic analysis.METHODS: We studied 20 suspected presclerodermic RP, 20 idiopathic RP and 25 healthy subjects. As marker of chromosome alteration we used the micronucleus assay. All subjects were also classified as ANA-, ACA+ or Scl70+. To identify the mechanism of MN formation, a MN fluorescence in situ hybridisation (FISH) analysis using a pancentromeric DNA probe was also performed.RESULTS: Suspected presclerodermic RP subjects, showed significantly higher MN frequencies than idiopathic RP and controls (39+/-15.2 vs 10+/-2.1 and 9.8+/-3.5 respectively p&lt;0.0001). Interestingly, subjects with idiopathic RP displayed MN frequency comparable to that of controls. Furthermore, ACA+ subjects showed the highest MN frequencies (44+/-8.1) as compared to subjects with different antibody pattern (26+/-7.1).CONCLUSIONS: Our results show the presence of higher levels of chromosomal damage in circulating lymphocytes of suspected presclerodermic RP. They also would suggest a key role of anti-centromere antibody in determining the observed cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contribute to the formation of MN observed in suspected presclerodermic RP

Long-Term Remission Achieved by Ponatinib and Donor Lymphocytes Infusion in a Ph+ Acute Lymphoblastic Leukemia Patient in Molecular Relapse After Allogenic Stem Cell Transplant and Dasatinib: A Case Report

Currently, the prognosis of Ph+ acute lymphoblastic leukemia (Ph+ ALL) patients relapsing after an allogenic hematopoietic stem cell transplantation (allo-SCT) remains poor, with few therapeutic options available. Here we present the case of a 32 years old patient with dasatinib-resistant post-transplant molecular relapse of ALL, who received, as second-line therapy, the combination of ponatinib and donor lymphocyte infusion (DLI). The therapy was safe and the patient achieved a sustained minimal residual disease negative disease, still ongoing after 22 months, which was accompanied by several changes in the immune populations distribution within the bone marrow (i.e., the increase in the CD8/CD4 lymphocytes ratio). Our report provides evidence of the efficacy of the third generation TKI inhibitor ponatinib in combination with DLI as second line therapy for Ph+ ALL relapsing after an allo-SCT

Anomalie cromosomiche, valutate come frequenza di micronuclei spontanei, in soggetti con fenomeno di Raynaud sospetto presclerodermico [Chromosome aberrations, valued as frequency of spontaneous micronuclei, in subjects with suspected presclerodermic Raynaud's phenomenon]

Objective: To evaluate the prevalence of spontaneous chromosome damage in cultured peripheral lymphocytes of subjects with suspected presclerodermic Raynaud’s phenomenon (RP), by means of molecular cytogenetic analysis. Methods: We studied 20 suspected presclerodermic RP, 20 idiopathic RP and 25 healthy subjects. As marker of chromosome alteration we used the micronucleus assay. All subjects were also classified as ANA-, ACA+ or Scl70+. To identify the mechanism of MN formation, a MN fluorescence in situ hybridisation (FISH) analysis using a pancentromeric DNA probe was also performed. Results: Suspected presclerodermic RP subjects, showed significantly higher MN frequencies than idiopathic RP and controls (39±15.2 vs 10±2.1 and 9.8±3.5 respectively p<0.0001). Interestingly, subjects with idiopathic RP displayed MN frequency comparable to that of controls. Furthermore, ACA+ subjects showed the highest MN frequencies (44±8.1) as compared to subjects with different antibody pattern (26±7.1). Conclusions: Our results show the presence of higher levels of chromosomal damage in circulating lymphocytes of suspected presclerodermic RP. They also would suggest a key role of anti-centromere antibody in determining the observed cytogenetic anomalies. FISH analysis indicated that both aneuploidogenic and clastogenic events contribute to the formation of MN observed in suspected presclerodermic RP

The Effects of \u3cem\u3eTithonia diversifolia\u3c/em\u3e on Dairy Cow Performance

Southeast, South and Central West are the main milk producing regions in the Brazil. Especially in the states of Minas Gerais, Goias and Sao Paulo, the tropical climate is very characteristic, with hot and rainy summers, and dry winters. Dry winters in these states are characterized by scarcity of pasture herbage mass, which directly influence the volume of milk produced. The high volume of milk produced in summer and low volume of milk produced in winter (i.e. seasonality of production which is about 20% of total milk volume) directly affects dairy farmers by reducing its revenue during dry winters due to a drop in milk yield. In addition, it increases the production costs by offering additional roughage supplements to the cattle (sugarcane fresh plus urea, corn silage or sorghum silage), or by feeding more concentrates and/or greater labour costs. Research evaluating the potential of the Tithonia diversifolia in improving milk yield and quality is extremely limited. This research project seeks to develop tools to understand the potential impact on milk composition and cow performance and to evaluate the significance of its outcomes and to aid in the ongoing development of innovative approaches. The aim of this study is to determine the effects of replacing up to 9.1% of sugarcane fresh and up to 6.3% of concentrates (DM basis) with Tithonia diversifolia fresh fed to lactating dairy cows. It is hypothesized that the initial replacement of a portion of the sugarcane fresh and concentrates (corn grain and soybean meal) with the Tithonia diversifolia fresh would not reduce dairy cow performance

Parenting Science Gang : radical co-creation of research projects led by parents of young children

Background Parents are increasingly searching online for information supported by research but can find it difficult to identify results relevant to their own experiences. More troublingly, a number of studies indicate that parenting information found online often can be misleading or wrong. The goal of the Parenting Science Gang (PSG) project was to use the power of the Internet to help parents ask questions they wanted to have answered by scientific research and to feel confident in assessing research evidence. Methods By using Facebook to recruit groups and facilitate interactions, PSG was able to engage fully the target public of parents of young children in the radical co-production of scientific studies, while not creating an undue burden on time or restricting participants due to disability, financial status or location. By giving parents true partnership and control of creation of projects, PSG ensured that the chosen questions were ones that were of most relevance and interest to them. Results This paper presents a summary of eight projects, with three in more detail, designed and implemented by PSG Facebook groups in collaboration with experts. Most projects had health related themes, often prompted by dissatisfaction with treatment of parents by health professionals or by feelings of being marginalised by pregnancy and motherhood, as well as by the lack of evidence for their questions and concerns. The PSG approach meant that these frustrations were channelled into actions. All eight of the PSG groups engaged in meaningful interactions with experts and co-produced studies with the groups defining the questions of interest. Conclusions This radically user-led design meant that the PSG staff and the collaborating experts had to live with a high degree of uncertainty. Nevertheless, PSG achieved its goal of academically productive, truly co-produced projects, but as important were the positive effects it had on many of the participants, both parents and experts. At the point of writing this paper, PSG projects have led to outputs including at least eight papers published, in press or in preparation, seven conference presentations, testimony to the Infant Feeding All-Party Parliamentary Group, and with more to come