Impact of 2021 European Academy of Neurology/Peripheral Nerve Society diagnostic criteria on diagnosis and therapy of chronic inflammatory demyelinating polyradiculoneuropathy variants.

BACKGROUND AND PURPOSE: There are different criteria for the diagnosis of different variants of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guidelines provide specific clinical criteria for each CIDP variant even if their therapeutical impact has not been investigated. METHODS: We applied the clinical criteria for CIDP variants of the 2021 EAN/PNS guidelines to 369 patients included in the Italian CIDP database who fulfilled the 2021 EAN/PNS electrodiagnostic criteria for CIDP. RESULTS: According to the 2021 EAN/PNS clinical criteria, 245 patients achieved a clinical diagnosis of typical CIDP or CIDP variant (66%). We identified 106 patients with typical CIDP (29%), 62 distal CIDP (17%), 28 multifocal or focal CIDP (7%), four sensory CIDP (1%), 27 sensory-predominant CIDP (7%), 10 motor CIDP (3%), and eight motor-predominant CIDP (2%). Patients with multifocal, distal, and sensory CIDP had milder impairment and symptoms. Patients with multifocal CIDP had less frequently reduced conduction velocity and prolonged F-wave latency and had lower levels of cerebrospinal fluid protein. Patients with distal CIDP more frequently had reduced distal compound muscle action potentials. Patients with motor CIDP did not improve after steroid therapy, whereas those with motor-predominant CIDP did. None of the patients with sensory CIDP responded to steroids, whereas most of those with sensory-predominant CIDP did. CONCLUSIONS: The 2021 EAN/PNS criteria for CIDP allow a better characterization of CIDP variants, permitting their distinction from typical CIDP and more appropriate treatment for patients.

Cytokines and chemokines in patients with chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: A systematic review.

Advances in the understanding of cytokines have revolutionized mechanistic treatments for chronic inflammatory and autoimmune diseases, as exemplified by rheumatoid arthritis. We conducted a systematic literature review on the role of cytokines and chemokines in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Ovid Medline, EMBASE and Web of Science were searched until August 31, 2022 for human studies investigating cytokines levels in CIDP or MMN. Fifty-five articles on 1061 CIDP patients and 86 MMN patients were included, with a median of 18 patients per study (range 3-71). Studies differed in the inclusion criteria, type of assay, manufacturer, control subjects, and tested biological material. Only a minority of studies reported data on disease activity. Interleukin (IL)-6, IL-17, CXCL10, and tumor necrosis factor alpha (TNF-α), were elevated in CIDP compared to controls in most of the studies. IL-6 and TNF-α levels are also correlated with disability. In MMN patients, IL-1Ra was elevated in the majority of the reports. While acknowledging the challenges in comparing studies and the various limitations of the studies, including small patient numbers, particularly in MMN, our review suggests that IL-6, IL-17, CXCL10, and TNF-α might play a role in CIDP pathogenesis. Larger studies are needed in MMN.

Regular assessment of serum vascular endothelial growth factor levels to monitor POEMS syndrome.

BACKGROUND: To investigate the utility of regular serum VEGF (sVEGF) levels assessment in the monitoring of POEMS syndrome. METHODS: We retrospectively reviewed data of 30 patients with POEMS syndrome whose sVEGF was tested regularly every 6 months. sVEGF levels after treatment were measured and correlated with disability (Overall Neuropathy Limitations Scale, ONLS), clinical impairment (measured with the modified Clinical Response Evaluation Scale, mCRES), and relapse-free survival. The ability of sVEGF to predict disease flares during remission and refractory disease was also analysed. RESULTS: Patients with normalised serum VEGF levels (< 1000 pg/ml) at 6 months showed prolonged relapse-free survival (at 3-year 94% for complete VEGF response, 57% partial, 0% none, p < 0.001) and greater later clinical improvement (median ΔmCRES complete VEGF response -5 vs partial -4, p = 0.019, and vs no VEGF response -2, p = 0.006). After remission, the sensitivity of 6-month sVEGF monitoring in predicting clinical relapse was 58% with a specificity of 100%. In patients refractory to treatment, the sensitivity in predicting further clinical worsening was 15%. In addition, in 25% of the patients in remission and 16% of those refractory to therapy, sVEGF levels only increased at the time of relapse. CONCLUSIONS: Regular sVEGF assessment is a valid biomarker in the prediction of disease reactivation in POEMS syndrome and was particularly useful during the phase of remission.

Longitudinal Feasibility of the Montreal Cognitive Assessment (MoCA) in Non-Demented ALS Patients.

INTRODUCTION: The present study aimed at testing the longitudinal feasibility of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented amyotrophic lateral sclerosis (ALS) patients. METHODS: N = 39 non-demented ALS patients were followed-up at a 5-to-10-month interval (M = 6.8; SD = 1.4) with the MoCA and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Practice effects, test-retest reliability, and predictive validity (against follow-up ECAS scores) were assessed. Reliable change indices (RCIs) were derived via a regression-based approach by accounting for retest interval and baseline confounders (i.e., demographics, disease duration, and severity and progression rate). RESULTS: At retest, 100% and 69.2% of patients completed the ECAS and the MoCA, respectively. Patients who could not complete the MoCA showed a slightly more severe and fast-progressing disease. The MoCA was not subject to practice effects (t[32] = -0.80; p = 0.429) and was reliable at retest (intra-class correlation = 0.82). Moreover, baseline MoCA scores predicted the ECAS at retest. RCIs were successfully derived - with baseline MoCA scores being the only significant predictor of retest performances (ps < 0.001). CONCLUSIONS: As long as motor disabilities do not undermine its applicability, the MoCA appears to be longitudinally feasible at a 5-to-10-month interval in non-demented ALS patients. However, ALS-specific screeners - such as the ECAS - should be preferred whenever possible.

Do Elite Basketball Players Maintain Peak External Demands throughout the Entire Game?

Consideration of workload intensity and peak demands across different periods of basketball games contributes to understanding the external physical requirements of elite basketball players. Therefore, the aim of this study was to investigate the average intensity and peak demands encountered by players throughout game quarters. PlayerLoad per minute and PlayerLoad at three different time samples (30 s, 1 min, and 3 min) were used as workload metrics. A total of 14 professional elite male basketball players were monitored during 30 official games to investigate this. A linear mixed model and Cohen's d were employed to identify significant differences and quantify the effect sizes among game quarters. The results showed a significant, moderate effect in PlayerLoad per minute between Q1 vs. Q4, and a small effect between Q2 and Q3 vs. Q4. Furthermore, a small to moderate decline was observed in external peak values for PlayerLoad across game quarters. Specifically,, a significant decrease was found for the 3 min time window between Q1 and other quarters. The findings from the present study suggest that professional basketball players tend to experience fatigue or reduced physical output as the game progresses.

Carotid free-floating thrombus stemming from carotid web: co-occurrence of two rare causes of ischemic stroke.

BACKGROUND: Carotid web (CaW) and carotid free-floating thrombus (CFFT) are rare yet critical causes of ischemic stroke in young adults. CASE PRESENTATION: A 54-year-old woman presented with a fluctuating right sensory-motor faciobrachial syndrome. A brain MRI scan revealed multiple small recent asynchronous cortico-subcortical ischemic foci in the vascular territory of the left internal carotid artery. A CT angiography identified a CFFT in the left internal carotid artery arising from an underlying CaW. The patient was treated with excellent clinical outcomes with carotid artery stenting and dual antiplatelet therapy. CONCLUSIONS: We provide a structured pathophysiological rationale connecting CaW and CFFT and highlight pivotal therapeutic implications. Further studies are needed to investigate this relationship and guide assessment and treatment.

Influence of game and quarter results on external peak demands during games in under-18 years, male basketball players.

To quantify and compare the external peak demands (PD) encountered according to game result (win vs. loss), quarter result (win vs. tie vs. loss), and quarter point difference (± difference in score) in under-18 years (U18), male basketball players. Thirteen basketball players had external load variables monitored across 9 games using local positioning system technology, including distance covered, distance covered in different intensity zones, accelerations, decelerations, and PlayerLoad™. PD were calculated across 30-s, 1-min, and 5-min time windows for each variable. Linear mixed models were used to compare PD for each variable according to game result (win vs. loss), quarter result (win vs tie vs loss), and quarter point difference (high vs. low). External PD were comparable between games that were won and lost for all variables and between quarters that were won and lost for most variables (p > 0.05, trivial-small effects). In contrast, players produced higher (p < 0.05, small effects) 1-min high-speed running distance and 5-min PlayerLoadTM in quarters that were won compared to quarters that were lost. Additionally, high quarter point differences (7.51 ± 3.75 points) elicited greater (p < 0.05, small effects) external PD (30-s PlayerLoadTM, 30-s and 5-min decelerations, and 1-min and 5-min high-speed running distance) than low quarter point differences (-2.47 ± 2.67 points). External PD remain consistent (trivial-small effects) regardless of game result, quarter result, and quarter point difference in U18, male basketball players. Accordingly, external PD attained during games may not be a key indicator of team success.

Lmo2 expression defines tumor cell identity during T-cell leukemogenesis.

The impact of LMO2 expression on cell lineage decisions during T-cell leukemogenesis remains largely elusive. Using genetic lineage tracing, we have explored the potential of LMO2 in dictating a T-cell malignant phenotype. We first initiated LMO2 expression in hematopoietic stem/progenitor cells and maintained its expression in all hematopoietic cells. These mice develop exclusively aggressive human-like T-ALL In order to uncover a potential exclusive reprogramming effect of LMO2 in murine hematopoietic stem/progenitor cells, we next showed that transient LMO2 expression is sufficient for oncogenic function and induction of T-ALL The resulting T-ALLs lacked LMO2 and its target-gene expression, and histologically, transcriptionally, and genetically similar to human LMO2-driven T-ALL We next found that during T-ALL development, secondary genomic alterations take place within the thymus. However, the permissiveness for development of T-ALL seems to be associated with wider windows of differentiation than previously appreciated. Restricted Cre-mediated activation of Lmo2 at different stages of B-cell development induces systematically and unexpectedly T-ALL that closely resembled those of their natural counterparts. Together, these results provide a novel paradigm for the generation of tumor T cells through reprogramming in vivo and could be relevant to improve the response of T-ALL to current therapies.

Comparison of the diagnostic accuracy of the 2021 EAN/PNS and 2010 EFNS/PNS diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVES: To compare the sensitivity and specificity of the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with those of the 2010 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS). METHODS: Sensitivity and specificity of the two sets of criteria were evaluated in 330 patients with CIDP and 166 axonal peripheral neuropathy controls. Comparison of the utility of nerve conduction studies with different number of nerves examined and of the sensitivity and specificity of the two criteria in typical CIDP and its variants were assessed. RESULTS: EFNS/PNS criteria had a sensitivity of 92% for possible CIDP and 85% for probable/definite CIDP, while the EAN/PNS criteria had a sensitivity of 83% for possible CIDP and 74% for CIDP. Using supportive criteria, the sensitivity of the EAN/PNS criteria for possible CIDP increased to 85% and that of CIDP to 77%, remaining lower than that of the EFNS/PNS criteria. Specificity of the EFNS/PNS criteria was 68% for possible CIDP and 84% for probable/definite CIDP, while the EAN/PNS criteria had a specificity of 88% for possible CIDP and 98% for CIDP. More extended studies increased the sensitivity of both sets of criteria by 4%-7% but reduced their specificity by 2%-3%. The EFNS/PNS criteria were more sensitive for the diagnosis of typical CIDP while the EAN/PNS criteria were more specific for the diagnosis of distal and sensory CIDP. CONCLUSIONS: In our population, the EAN/PNS criteria were more specific but less sensitive than the EFNS/PNS criteria. With the EAN/PNS criteria, more extended nerve conduction studies are recommended to obtain an acceptable sensitivity while maintaining a high specificity.

Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy.

INTRODUCTION: The association between a change in proteinuria over time and its impact on kidney prognosis has not been analysed in complement component 3 (C3) glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure. METHODS: This was a retrospective, multicentre observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modelling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure. RESULTS: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13-41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (hazard ratio 0.79; 95% confidence interval 0.56-0.97; P < 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up. CONCLUSIONS: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.

Frequency and clinical correlates of anti-nerve antibodies in a large population of CIDP patients included in the Italian database.

OBJECTIVE: To investigate the frequency and clinical correlates of anti-nerve autoantibodies in an unselected series of Italian patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) METHODS: Sera from 276 CIDP patients fulfilling the EFNS/PNS criteria and included in the Italian CIDP database were examined for the presence of anti-nerve autoantibodies. Results were correlated with the clinical data collected in the database. RESULTS: Anti-neurofascin155 (NF155) antibodies were found in 9/258 (3.5%) patients, anti-contactin1 (CNTN1) antibodies in 4/258 (1.6%) patients, and anti-contactin-associated protein1 (Caspr1) in 1/197 (0.5%) patients, while none had reactivity to gliomedin or neurofascin 186. Predominance of IgG4 isotype was present in 7of the 9 examined patients. Anti-NF155 patients more frequently had ataxia, tremor, and higher CSF protein levels than antibody-negative patients. Anti-CNTN1 patients more frequently had a GBS-like onset, pain, and ataxia and had more severe motor impairment at enrollment than antibody-negative patients. They more frequently received plasmapheresis, possibly reflecting a less satisfactory response to IVIg or steroids. IgM antibodies against one or more gangliosides were found in 6.5% of the patients (17/260) and were more frequently directed against GM1 (3.9%). They were frequently associated with a progressive course, with a multifocal sensorimotor phenotype and less frequent cranial nerve involvement and ataxia. CONCLUSIONS: Anti-paranodal and anti-ganglioside antibodies are infrequent in patients with CIDP but are associated with some typical clinical association supporting the hypothesis that CIDP might be a pathogenically heterogeneous syndrome possibly explaining the different clinical presentations.

Ecological Validity of the Montreal Cognitive Assessment in Non-Demented Parkinson's Disease Patients.

BACKGROUND: The ecological validity of performance-based cognitive screeners needs to be tested in order for them to be fully recommended for use within clinical practice and research. OBJECTIVES: The objective of this study was to examine, within an Italian cohort of non-demented Parkinson's disease (PD) patients, the ecological validity of the Montreal Cognitive Assessment (MoCA) by assessing its association with (1) functional independence (FI), (2) quality of life (QoL), and (3) behavioural-psychological (BP) outcomes. METHODS: Seventy-four non-demented PD patients were administered the MoCA and underwent motor functional - i.e., Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn-Yahr Scale (HY), and Schwab and England Scale (SES) -, behavioural and psychological - i.e., State- and Trait-Anxiety Inventory-Form Y (STAI-Y1/-Y2), Beck Depression Inventory (BDI), and Dimensional Apathy Scale (DAS) - and QoL evaluations - i.e., MOS 36-Item Short Form Health Survey (SF-36). Associations of interest against FI, QoL, and BP outcomes were tested via Bonferroni-corrected Pearson's/Spearman's correlations while covarying for demographics, disease duration as well as UPDRS-III, UPDRS-IV, and HY scores. Intake of psychotropic drugs was also covaried when assessing the association between the MoCA and BP/QoL measures. RESULTS: MoCA scores were significantly associated with the SES (rs(73) = 0.34; p = 0.005) and the DAS-Executive (r(67) = -0.47; p < 0.001), while not to other FI/BP outcomes and QoL measures. CONCLUSIONS: The MoCA is a valid estimate of daily life functional autonomy in non-demented PD patients, also reflecting apathetic features of a dysexecutive nature.

Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

The evolution of physical and technical performance parameters in the Chinese Soccer Super League.

Performance analysis in soccer has attained greater importance for coaching staff in order to gather and manage useful information (i.e., physical, technical, and tactical) of their teams during consecutive seasons. Accordingly, we examined the evolution of physical and technical performance parameters in the Chinese Soccer Super League (CSL). Data were collected from 1,429 CSL matches from the 2012 season to the 2017 season using the Amisco Pro (Amisco, Nice, France) system. Fourteen technical performance-related indicators and 11 physical performance-related indicators were analysed using a mixed linear model for repeated measures. Significant main effects of season were followed up using the Bonferroni correction (multiple comparisons). Although there were some irregularities, performance variables generally showed significant upward trends across the six seasons (p<0.05), resulting in significant increases from the 2012 season to the 2017 season in the total sprint distance (2,069.7±509.3 m vs. 2,272±493.6 m; p<0.001; effect size [ES]: 0.40), number of sprints (100.1±22.8 vs. 104.8±20.8, p<0.001; ES: 0.22), high-speed distance (2568.4±503.5 m vs. 2823.1±479.2 m; (p<0.001; ES: 0.52), and high-speed effort (187.5±36.1 to 204.7±33.7; p<0.001; ES: 0.49). Furthermore, there were ~23% more crosses (p<0.001; ES: 0.45), ~12% more shots on target (p<0.001; ES: 0.22), and ~11% more opponent penalty area entries (p<0.001; ES: 0.20) during the 2017 season than in the 2012 season. Coaches and sports scientists should be mindful of this evolution when preparing training sessions and recruiting new players, and even when predicting future trends in the Chinese Soccer Super League.

Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice.

CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 overexpression to promote B-cell lymphoma. Through transcriptional and epigenetic profiling of these B cells, we found that Crebbp inactivation was associated with broad transcriptional alterations, but no changes in the patterns of histone acetylation at the proximal regulatory regions of these genes. However, B cells with Crebbp inactivation showed high expression of Myc and patterns of altered histone acetylation that were localized to intragenic regions, enriched for Myc DNA binding motifs, and showed Myc binding. Through the analysis of CREBBP mutations from a large cohort of primary human FL and DLBCL, we show a significant difference in the spectrum of CREBBP mutations in these 2 diseases, with higher frequencies of nonsense/frameshift mutations in DLBCL compared with FL. Together, our data therefore provide important links between Crebbp inactivation and Bcl2 dependence and show a role for Crebbp inactivation in the induction of Myc expression. We suggest this may parallel the role of CREBBP frameshift/nonsense mutations in DLBCL that result in loss of the protein, but may contrast the role of missense mutations in the lysine acetyltransferase domain that are more frequently observed in FL and yield an inactive protein.

Clustering performances in the NBA according to players' anthropometric attributes and playing experience.

The aim of this study was: (i) to group basketball players into similar clusters based on a combination of anthropometric characteristics and playing experience; and (ii) explore the distribution of players (included starters and non-starters) from different levels of teams within the obtained clusters. The game-related statistics from 699 regular season balanced games were analyzed using a two-step cluster model and a discriminant analysis. The clustering process allowed identifying five different player profiles: Top height and weight (HW) with low experience, TopHW-LowE; Middle HW with middle experience, MiddleHW-MiddleE; Middle HW with top experience, MiddleHW-TopE; Low HW with low experience, LowHW-LowE; Low HW with middle experience, LowHW-MiddleE. Discriminant analysis showed that TopHW-LowE group was highlighted by two-point field goals made and missed, offensive and defensive rebounds, blocks, and personal fouls; whereas the LowHW-LowE group made fewest passes and touches. The players from weaker teams were mostly distributed in LowHW-LowE group, whereas players from stronger teams were mainly grouped in LowHW-MiddleE group; and players that participated in the finals were allocated in the MiddleHW-MiddleE group. These results provide alternative references for basketball staff concerning the process of evaluating performance.

Exploring the effects of substituting basketball players in high-level teams.

Substituting basketball players during competition is a key process to optimise collective performance. Available research on this topic is scarce, probably due to the difficulty in isolating these effects; thus, the aim of this study was to identify the temporal effects of substitutions in basketball (Spanish professional basketball league). The sample was composed of 1118 substitutions gathered from 21 basketball games. The analysed variables were coach-controlled (player and team's personal fouls, player in and player out roles, player's in and out minutes on-court and timeout situation); on-court (foul committed, free throws, 2- and 3-point field-goal effectiveness) and situational variables (scoreline, quality of opposition, game location and game quarter). The results showed positive scoring performances after the substitution for all the analyses. During the first quarter, there were significant effects for fouls committed, scoreline and game location after the substitution. The player's out personal fouls, free-throw effectiveness, player in, minutes on-court player in, timeout situation and 3-point field-goal effectiveness were significant during the second quarter. The team's personal fouls, game location, and scoreline were identified as important in the third quarter. The fourth quarter did not show significant effects on the independent variables. Current findings allow optimising coaches' plans and team management of on-court and bench players throughout the game.

Could Vitamin D Analogues Be Used to Target Leukemia Stem Cells?

Leukemic stem cells (LSCs) are defined as cells that possess the ability to self-renew and give rise to the differentiated cancer cells that comprise the tumor. These LSCs seem to show chemo-resistance and radio-resistance leading to the failure of conventional cancer therapies. Current therapies are directed at the fast growing tumor mass leaving the LSC fraction untouched. Eliminating LSCs, the root of cancer origin and recurrence, is considered to be a hopeful approach to improve survival or even to cure cancer patients. In order to achieve this, the characterization of LSCs is a prerequisite in order to develop LSC-based therapies to eliminate them. Here we review if vitamin D analogues may allow an avenue to target the LSCs.

Effects of CK2 inhibition in cultured fibroblasts from Type 1 Diabetic patients with or without nephropathy.

CK2 is a multifunctional, pleiotropic protein kinase involved in the regulation of cell proliferation and survival. Since fibroblasts from Type 1 Diabetes patients (T1DM) with Nephropathy exhibit increased proliferation, we studied cell viability, basal CK2 expression and activity, and response to specific CK2 inhibitors TBB (4,5,6,7-tetrabenzotriazole) and CX4945, in fibroblasts from T1DM patients either with (T1DM+) or without (T1DM-) Nephropathy, and from healthy controls (N). We tested expression and phosphorylation of CK2-specific molecular targets. In untreated fibroblasts from T1DM+, the cell viability was higher than in both N and T1DM-. CK2 inhibitors significantly reduced cell viability in all groups, but more promptly and with a larger effect in T1DM+. Differences in CK2-dependent phosphorylation sites were detected. In conclusion, our results unveil a higher dependence of T1DM+ cells on CK2 for their survival, despite a similar expression and a lower activity of this kinase compared with those of normal cells.