Between barriers and inclusion. Multidisciplinary reflections on gender and disability

The European project RISEWISE offered a possible model for a multidisciplinary collaboration. During the four years, innovative goals were pursued for breaking down barriers ranging from creating spaces for dialogue and communication, to exchanging knowledge and experience between disciplines by bringing together academics and associations

Hematocrit: another important factor in systemic neonatal cardiovascular adaptation

Background: Global cardiovascular adaptation of normal healthy term newborns is rarely studied from a multiorgan and hematological point of view. Aims: To evaluate comprehensive neonatal cardiovascular adaptation during the first days of life with echocardiography and renal-cerebral echo color-Doppler and to correlate it with hematocrit (Ht) changes. Study design: A prospective observational study was conducted on 35 healthy term neonates with a mean ± SD gestational age and birth weight of 39.5 ± 1.1 weeks and 3,400 ± 330 g, respectively. All infants underwent serial echocardiograms at 15 ± 4 hours (day 1) and 72 ± 4 hours (day 3) of age. At the same time, cerebral and renal Doppler parameters were acquired and Ht was sampled. Results: The weight and Ht declined by 220 g (189-251) and 8.1% (6.7-9.5), respectively. Systolic and diastolic diameters of the right ventricle and diastolic left ventricle posterior wall thickness showed a reduction, while the diastolic diameter of the left ventricle showed a small increase. The Doppler cardiac evaluation showed an increase in the mitral E/A ratio and pulmonary acceleration time, a reduction of late transmitral flow peak velocity, aortic peak systolic velocity (PSV), aortic peak systolic pressure gradient, aortic velocity-time integral, aortic mean pressure gradient and pulmonary mean acceleration. We also found a reduction of cerebral resistance parameters and an increase in PSV, end-diastolic velocity, and time-averaged velocity. Other measured parameters remained unchanged. Conclusion: Systemic cardiovascular evaluation about changes in Ht is an essential approach to study newborns, especially during the first days of life when Ht shows a significant decrease. Knowledge of the laws of physics related to the effect of Ht changes on vascular parameters is another important factor in understanding the pathophysiology of neonatal disease states. Further studies are useful to help physicians make evidence-based decisions in the management of newborns in Neonatal Intensive Care Units (NICUs)

Small Angle Scattering and Zeta Potential of Liposomes Loaded with Octa(carboranyl)porphyrazine

In this work the physicochemical characterization of liposomes loaded with a newly synthesised carboranyl porphyrazine (H2HECASPz) is described. This molecule represents a potential drug for different anticancer therapies, such as Boron Neutron Capture Therapy, Photodynamic Therapy and Photothermal Therapy. Different loading methods and different lipid mixtures were tested. The corresponding loaded vectors were studied by Small Angle Scattering (SANS and SAXS), light scattering and zeta potential. The combined analysis of structural data at various length scales and the measurement of the surface charge allowed to obtain a detailed characterization of the investigated systems. The mechanisms underlying the onset of differences in relevant physicochemical parameters (size, polydispersity and charge) were also critically discussed

The karyotype of Nothoscordum arenarium Herter (Gilliesioideae, Alliaceae): A populational and cytomolecular analysis

The genus Nothoscordum Kunth comprises approximately 20 species native to South America. Karyologically, the genus is remarkable for its large chromosomes and Robertsonian translocations. Variation in chromosome number has been recorded in a few polyploid species and it is unknown among diploids. This study presents the chromosome number and morphology of 53 individuals of seven populations of N. arenarium Herter (2n = 10). In addition, karyotype analyses after C-banding, staining with CMA and DAPI, and in situ hybridization with 5S and 45S rDNA probes were performed in six individuals from one population. All individuals exhibited 2n = 10 (6M + 4A), except for one tetraploid (2n = 20, 12M + 8A) and one triploid (2n = 15, 9M + 6A) plant. C-banding revealed the presence of CMA+ /DAPI - heterochromatin in the short arm and in the proximal region of the long arm of all acrocentric chromosomes. The 45S rDNA sites co-localized with the CMA + regions of the acrocentrics short arms, while the 5S rDNA probe only hybridized with the subterminal region of a pair of metacentric chromosomes. A change in the pattern of CMA bands and rDNA sites was observed in only one individual bearing a reciprocal translocation involving the long arm of a metacentric and the long arm of an acrocentric chromosome. These data suggest that, despite isolated cases of polyploidy and translocation, the karyotype of N. arenarium is very stable and the karyotypic instability described for other species may be associated with their polyploid condition

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

The aims of this phase I study were to establish the maximum tolerated dose, safety profile and activity of liposomal daunorubicin, DaunoXome (NeXstar Pharmaceuticals), in the treatment of metastatic breast cancer. DaunoXome was administered intravenously over 2 h in 21 day cycles and doses were increased from 80 to 100, 120 and 150 mg m2. Sixteen patients were enrolled. A total of 70 cycles of DaunoXome were administered. The maximum tolerated dose was 120 mg m2, the dose-limiting toxicity being prolonged grade 4 neutropenia or neutropenic pyrexia necessitating dose reductions at 120 and 150 mg m2. Asymptomatic cardiotoxicity was observed in three patients: grade 1 in one treated with a cumulative dose of 800 mg m2 and grade 2 in two, one who received a cumulative dose of 960 mg m2 and the other a cumulative dose of 600 mg m2 with a previous neoadjuvant doxorubicin chemotherapy of 300 mg m2. Tumour response was evaluable in 15 patients, of whom two had objective responses, six had stable disease and seven had progressive disease. In conclusion, DaunoXome is associated with mild, manageable toxicities and has anti-tumour activity in metastatic breast cancer. The findings support further phase II evaluation of DaunoXome alone and in combination with other standard non-anthracycline cytotoxic or novel targeted agents. Although the dose-limiting toxicity for DaunoXome was febrile neutropenia at 120 mg m2, we would recommend this dose for further evaluation, as the febrile neutropenia occurred after four or more cycles in three of the four episodes seen, was short lived and uncomplicated

A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, ‘DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m−2 for Group A and 100 mg m−2 for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Anaerobes As Biofilms

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