A Preliminary Proposal for Quality Control Assessment and Harmonization of Leukocytes Morphology-Structural Parameters (Cell Population Data Parameters)

Background: The cell population data (CPD) measured by Sysmex XN-9000 can be used for screening many hematological and non-hematological disorders. Since little information is available on harmonization of CPD among different instrumentation and clinical laboratories, this study aimed at assessing the current degree of CPD harmonization between separate Sysmex XN modules allocated to the same laboratory.Methods: A total number of 78291 data were used for verification of within-run imprecision, analyzers harmonization, reference ranges and assessment of blood sample stability of CPD parameters, including results of daily quality control testing and those generated in samples collected from blood donors and healthy volunteers.Results: Within-run imprecision of CPD parameters ranged between 0.4 and 14.1%. Good agreement was found among five different XN-modules, especially when values were adjusted after calculation of instrument-specific alignment factors. The bias of all parameters remained always lower than the reference change values in samples stored for up to 8 hours, regardless of storage temperature.Conclusions: The imprecision of CPD parameters was acceptable, except for those reflecting the dispersion of cellular clusters. Due to the lack of reference control materials, we showed that the use of data generated on a large number of normal routine samples (i.e., a Moving Average population) may be a reliable approach for testing analyzers harmonization. Nevertheless, availability of both calibration and quality control materials for these parameters is highly advisable in the future. We finally showed that whole blood samples may be stable for up to 2-4 hours for most CPD parameters

regenerative medicine the blurred boundaries between life sciences and biotechnology towards a new inductive medicine of the third millennium

Not available

Regulator of G-protein signaling 5 (RGS5) protein: a novel marker of cancer vasculature elicited and sustained by the tumor’s proangiogenic microenvironment

We previously identified regulator of G-protein signaling 5 (RGS5) among several genes expressed by tumor-derived endothelial cells (EC). In this study, we provide the first in vivo/ex vivo evidence of RGS5 protein in the vasculature of ovarian carcinoma clinical specimens and its absence in human ovaries. Consistent with this, we show higher amounts of Rgs5 transcript in EC isolated from human cancers (as opposed to normal tissues) and demonstrate that expression is sustained by a milieu of factors typical of the proangiogenic tumor environment, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). Supporting these findings, we show elevated levels of Rgs5 mRNA in the stroma from strongly (as opposed to weakly) angiogenic ovarian carcinoma xenografts and accordingly, we also show more of the protein associated to the abnormal vasculature. RGS5 protein predominantly colocalizes with the endothelium expressing platelet/endothelial cell adhesion molecule-1 (PECAM-1/CD31) and to a much lesser extent with perivascular/mural cells expressing platelet-derived growth factor receptor-beta (PDGFR-β) or alpha smooth muscle actin (αSMA). To toughen the relevance of the findings, we demonstrate RGS5 in the blood vessels of other cancer models endowed with a proangiogenic environment, such as human melanoma and renal carcinoma xenografts; to the contrary, it was undetectable in the vasculature of normal mouse tissues. RGS5 expression by the cancer vasculature triggered and retained by the proangiogenic microenvironment supports its exploitation as a novel biomarker and opens the path to explore new possibilities of therapeutic intervention aimed at targeting tumor blood vessels

Building cooperation through health initiatives: an Arab and Israeli case study

<p>Abstract</p> <p>Background</p> <p>Ongoing conflict in the Middle East poses a major threat to health and security. A project screening Arab and Israeli newborns for hearing loss provided an opportunity to evaluate ways for building cooperation. The aims of this study were to: a) examine what attracted Israeli, Jordanian and Palestinian participants to the project, b) describe challenges they faced, and c) draw lessons learned for guiding cross-border health initiatives.</p> <p>Methods</p> <p>A case study method was used involving 12 key informants stratified by country (3 Israeli, 3 Jordanian, 3 Palestinian, 3 Canadian). In-depth interviews were tape-recorded, transcribed and analyzed using an inductive qualitative approach to derive key themes.</p> <p>Results</p> <p>Major reasons for getting involved included: concern over an important health problem, curiosity about neighbors and opportunities for professional advancement. Participants were attracted to prospects for opening the dialogue, building relationships and facilitating cooperation in the region. The political situation was a major challenge that delayed implementation of the project and placed participants under social pressure. Among lessons learned, fostering personal relationships was viewed as critical for success of this initiative.</p> <p>Conclusion</p> <p>Arab and Israeli health professionals were prepared to get involved for two types of reasons: a) Project Level: opportunity to address a significant health issue (e.g. congenital hearing loss) while enhancing their professional careers, and b) Meta Level: concern about taking positive steps for building cooperation in the region. We invite discussion about roles that health professionals can play in building "cooperation networks" for underpinning health security, conflict resolution and global health promotion.</p

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Reply to letter to the editor \u201ctDCS effect on cognitive performance in Parkinson's disease\u201d by Biundo et al

N/

The role of the motor system in action naming in patients with neurodegenerative extrapyramidal syndromes

Previous studies of patients with brain damage have suggested a close relationship between aphasia and movement disorders. Neurodegenerative extrapyramidal syndromes associated with cognitive impairment provide an interesting model for studying the neural substrates of cognitive and motor symptoms. In this review, we focused on studies investigating language production abilities in patients with Parkinson's disease (PD), Corticobasal Syndrome (CBS) and Progressive Supranuclear Palsy (PSP). According to some reports, these patients exhibit a reduction in performance in both action and object naming or verb production compared to healthy individuals. Furthermore, a disproportional impairment of action naming compared to object naming was systematically observed in patients with these disorders. The study of these clinical conditions offers the unique opportunity to examine the close link between linguistic features and motor characteristics of action. This particular pattern of language impairment may contribute to the debate on embodiment theory and on the involvement of the basal ganglia in language and in integrating language and movement. From a translational perspective, we suggest that language ability assessments are useful in the clinical work-up, along with neuropsychological and motor evaluations. Specific protocols should be developed in the near future to better characterize language deficits and to permit an early cognitive diagnosis. Moreover, the link between language deficits and motor impairment opens a new issue for treatment approaches. Treatment of one of these two symptoms may ameliorate the other, and treating both may produce a greater improvement in patients' global clinical conditions

Habitat features and distribution of <i>Salamandra salamandra</i> in underground springs

Subterranean habitats are among the less known terrestrial habitats, but can reveal an unexpected biodiversity, and can play an underestimated role for amphibians. The fire salamander <i>Salamandra salamandra</i> is sometimes found in underground environments, but the factors affecting its distribution in subterranean spaces remain substantially unexplored. We repeatedly surveyed some hypogeous springs, such as draining galleries and “bottini” in NW Italy, in order to evaluate the relationship between environmental features and distribution of <i>S. salamandra</i> in these underground springs. We performed visual encounter surveys to assess the occurrence of larvae, juveniles or adults in springs. We also recorded four habitat variables: easy of access, isolation, macrobenthos richness and forest cover of the surrounding landscape. We used generalized linear models to evaluate the relationships between habitat features and occurrence of larvae. We observed larvae of <i>S. salamandra</i> in 13 out of 22 springs; their presence was associated to springs with high easy of access and with relatively rich macrobenthos communities. In underground springs, larval development apparently required longer time than in nearby epigeous streams. Nevertheless, S. salamandra can attain metamorphosis in this environment. The occurrence of <i>S. salamandra</i> in underground environments was not accidental, but repeated in the time and interesting from an ecological point of view, confirming the high plasticity of the species