Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction.

This study was directed to deepen the effects of nutrient shortage on BCR/Ablprotein expression and signaling in chronic myeloid leukemia (CML) cells. The backbone of the study was cell culture in medium lacking glucose, the consumption of which we had previously shown to drive BCR/Ablprotein suppression, and glutamine, the other main nutrient besides glucose. In this context, we focused on the role of lactate, the main by-product of glucose metabolism under conditions of rapid cell growth, in particular as a modulator of the maintenance of CML stem/progenitor cell potential, a crucial determinant of disease course and relapse of disease. The results obtained indicated that lactate is a powerful surrogate of glucose to prevent the suppression of BCR/Abl signaling and is therefore capable to maintain BCR/Abl-dependent CML stem/progenitor cell potential. A number of metabolism-related functional and phenotypical features of CML cells were also determined. Among these, we focused on the effect of lactate on oxygen consumption rate, the dependence of this effect on the cell surface lactate carrier MCT-1, and the relationship of the lactate effect to pyruvate and to the activity of mitochondrial pyruvate carrier.

A Human Bone Marrow 3D Model to Investigate the Dynamics and Interactions Between Resident Cells in Physiological or Tumoral Contexts.

The medullary niche is a complex ecosystem that is essential to maintain homeostasis for resident cells. Indeed, the bone marrow, which includes a complex extracellular matrix and various cell types, such as mesenchymal stem cells, osteoblasts, and endothelial cells, is deeply involved in hematopoietic stem cell regulation through direct cell-cell interactions, as well as cytokine production. To closely mimic this in vivo structure and conduct experiments reflecting the responses of the human bone marrow, several 3D models have been created based on biomaterials, relying primarily on primary stromal cells. Here, a protocol is described to obtain a minimal and standardized system that is easy to set up and provides features of bone marrow-like structure, which combines different cell populations including endothelial cells, and reflects the heterogeneity of in vivo bone marrow tissue. This 3D bone marrow-like structure-assembled using calcium phosphate-based particles and human cell lines, representative of the bone marrow microenvironment-allows the monitoring of a wide variety of biological processes by combining or replacing different primary cell populations within the system. The final 3D structures can then either be harvested for image analysis after fixation, paraffin-embedding, and histological/immunohistochemical staining for cell localization within the system, or dissociated to collect each cellular component for molecular or functional characterization.

New frontiers in e-health. Policies and the Doctor@Home case study. / La frontiera delle cure a distanza. Assetto normativo ed il caso Doctor@Home.

INTRODUCTION: In recent years, and even more following the need for social distancing generated by the global COVID-19 pandemic, e-health has become an increasingly widespread reality in clinical practice, especially for those clinicians operating in the front-line, like nurses. Its growing importance has been followed by increasing attention both by the literature as well as in the generation of specific rules aimed at regulating the phenomenon. METHODS: A regulatory review of the literature aims to outline the current regulatory framework relating to telemedicine. Telemedicine, especially in a pandemic context, calls for regulation that runs parallel to the rapid evolution of the phenomenon itself. The paper traces the European, Italian, and Regional legislation, focusing then on a practical experience of telemedicine, called Doctor @ Home, active at the IRCCS National Cancer Center in Aviano (Italy). DISCUSSION: First, the need for regulatory harmonization emerges. Secondly, the potential of co-production and co-learning processes for healthcare professionals and patients arises to adapt to the outpatient needs of patients in a post-pandemic "new normal," exploiting the new technological tools made available by the National Health Service.

Glutamine Availability Controls BCR/Abl Protein Expression and Functional Phenotype of Chronic Myeloid Leukemia Cells Endowed with Stem/Progenitor Cell Potential.

This study was directed to characterize the role of glutamine in the modulation of the response of chronic myeloid leukemia (CML) cells to low oxygen, a main condition of hematopoietic stem cell niches of bone marrow. Cells were incubated in atmosphere at 0.2% oxygen in the absence or the presence of glutamine. The absence of glutamine markedly delayed glucose consumption, which had previously been shown to drive the suppression of BCR/Abl oncoprotein (but not of the fusion oncogene BCR/abl) in low oxygen. Glutamine availability thus emerged as a key regulator of the balance between the pools of BCR/Abl protein-expressing and -negative CML cells endowed with stem/progenitor cell potential and capable to stand extremely low oxygen. These findings were confirmed by the effects of the inhibitors of glucose or glutamine metabolism. The BCR/Abl-negative cell phenotype is the best candidate to sustain the treatment-resistant minimal residual disease (MRD) of CML because these cells are devoid of the molecular target of the BCR/Abl-active tyrosine kinase inhibitors (TKi) used for CML therapy. Therefore, the treatments capable of interfering with glutamine action may result in the reduction in the BCR/Abl-negative cell subset sustaining MRD and in the concomitant rescue of the TKi sensitivity of CML stem cell potential. The data obtained with glutaminase inhibitors seem to confirm this perspective.

Peer education for medical students on health promotion and clinical risk management.

CONTEXT: Health promotion (HP) and clinical risk management (CRM) topics are seldom discussed during medical school lessons. Peer-assisted learning (PAL) has long occurred informally in medical education, and interest in this method has recently grown, as it is considered a valuable technique for both tutors and tutees. AIMS: The aim was to evaluate the impact of HP and CRM PAL intervention on medical students' (tutees) knowledge level. SETTINGS AND DESIGN: A PAL intervention has been implemented at Udine University medical school during 2017. It was composed of lectures and practical activities conducted by ten near-peer tutors. METHODS: The effectiveness has been evaluated by giving tutees: (1) a knowledge multiple-choice questionnaire, before and after the intervention; (2) a satisfaction questionnaire; and evaluating (3) tutees' group assignments. STATISTICAL ANALYSIS USED: We performed descriptive analysis; then McNemar, Wilcoxon signed rank, Wilcoxon Mann-Whitney, and t-tests were applied. RESULTS: The number of students addressed by PAL intervention was 62. Difference in total correct answers among pre- and post-intervention questionnaires showed a statistically significant improvement (P < 0.0001), both when analyzing it globally and by area (HP/CRM). Students' satisfaction for CRM was greater than for HP area (P = 0.0041). CONCLUSIONS: This educational intervention based on PAL showed its effectiveness producing a statistically significant improvement in students' knowledge. Our findings confirm that PAL could be a feasible method for HP and CRM topics.

Functional Decline in Residents Living in Nursing Homes: A Systematic Review of the Literature.

OBJECTIVES: To describe the functional dependence progression over time in older people living in nursing homes (NHs). DESIGN: A systematic review of the literature was performed. Studies involving individuals 65 years and older living in NHs, describing their functional decline, improvement or stability in activities of daily living (ADLs), were eligible. The search strategy was applied in MedLine, Cochrane, CINAHL, and SCOPUS databases; aimed at identifying an unbiased and complete list of studies, searching by hand was also performed. The methodological quality of the 27 studies included was assessed. RESULTS: Functional trajectories were documented mainly through multicenter study design including sample size ranging from 2 to 9336 NHs, from 1983 to 2011 throughout a single or multiple follow-ups (>20). The average rate of decline was expressed in different metrics and periods of time: from 3 months with a decline of -0.13 points of 28, to 6 months (-1.78 points of 2829) to 1.85 years (-0.5 points of 6). Eating and toileting were the most documented ADLs and the decline is approximately 0.4 points and 0.2 to 0.4 points of 5 a year, respectively. Among the covariates, individual factors, such as cognitive status, were mainly considered, whereas only 13 studies considered facility-level factors. CONCLUSIONS: Findings report the slow functional decline mainly in women living in US NHs, in years when residents were admitted with a low or medium degree of functional dependence. Considering that in recent years residents have been admitted to NHs with higher-level functional dependence, studies measuring each single ADL, using standardized instruments capable of capturing the signs of decline, stability, or improvement are strongly recommended. Among the covariates, evaluation of both individual and facility-level factors, which may affect functional decline, is also suggested.