A Cardiovascular Risk Score for Use in Occupational Medicine

Cardiovascular disease is one of the most frequent causes of long-term sickness absence from work. The study aims to develop and validate a score to assess the 10-year risk of unsuitability for work accounting for the cardiovascular risk. The score can be considered as a prevention tool that would improve the cardiovascular risk assessment during health surveillance visits under the assumption that a high cardiovascular risk might also translate into high risk of unsuitability for work. A total of 11,079 Italian workers were examined, as part of their scheduled occupational health surveillance. Cox proportional hazards regression models were employed to derive risk equations for assessing the 10-year risk of a diagnosis of unsuitability for work. Two scores were developed: the CROMA score (Cardiovascular Risk in Occupational Medicine) included age, sex, smoking status, blood pressure (systolic and diastolic), body mass index, height, diagnosis of hypertension, diabetes, ischemic heart disease, mental disorders and prescription of antidiabetic and antihypertensive medications. The CROMB score was the same as CROMA score except for the inclusion of only variables statistically significant at the 0.05 level. For both scores, the expected risk of unsuitability for work was higher for workers in the highest risk class, as compared with the lowest. Moreover results showed a positive association between most of cardiovascular risk factors and the risk of unsuitability for work. The CROMA score demonstrated better calibration than the CROMB score (11.624 (p-value: 0.235)). Moreover, the CROMA score, in comparison with existing CVD risk scores, showed the best goodness of fit and discrimination

MiR-24 induces chemotherapy resistance and hypoxic advantage in breast cancer

Breast cancer remains one of the leading causes of cancer mortality among women. It has been proved that the onset of cancer depends on a very small pool of tumor cells with a phenotype similar to that of normal adult stem cells. Cancer stem cells (CSC) possess self-renewal and multilineage differentiation potential as well as a robust ability to sustain tumorigenesis. Evidence suggests that CSCs contribute to chemotherapy resistance and to survival under hypoxic conditions. Interestingly, hypoxia in turn regulates self-renewal in CSCs and these effects may be primarily mediated by hypoxic inducible factors (HIFs). Recently, microRNAs (miRNAs) have emerged as critical players in the maintenance of pluripotency and self-renewal in normal and cancer stem cells. Here, we demonstrate that miR-24 is upregulated in breast CSCs and that its overexpression increases the number of mammospheres and the expression of stem cell markers. MiR-24 also induces apoptosis resistance through the regulation of BimL expression. Moreover, we identify a new miR-24 target, FIH1, which promotes HIFα degradation: miR-24 increases under hypoxic conditions, causing downregulation of FIH1 and upregulation of HIF1α. In conclusion, miR-24 hampers chemotherapy-induced apoptosis in breast CSCs and increases cell resistance to hypoxic conditions through an FIH1−HIFα pathway

RYK promotes the stemness of glioblastoma cells via the WNT/ \u3b2-catenin pathway

Glioblastoma multiforme (GBM) is characterized by a strong self-renewal potential and a poor differentiation state. Since receptor-like tyrosine kinase (RYK) activates the WNT/\u3b2-catenin pathway essential for cancer stem cell maintenance, we evaluated its contribution in conferring stemness to GBM cells. Here, we report that Ryk (related-to-receptor tyrosine kinase), an atypical tyrosine kinase receptor, is upregulated in samples from GBM patients as well as in GSCs. Ryk overexpression confers stemness properties to GBM cells through the modulation of the canonical Wnt signaling and by promoting the activation of pluripotency-related transcription factor circuitry and neurosphere formation ability. In contrast, siRNA-mediated knockdown of Ryk expression suppresses this stem-like phenotype. Rescue experiments reveal that stemness-promoting activity of Ryk is attributable, at least in part, to \u3b2-catenin stabilization. Furthermore, Ryk overexpression improves cell motility and anchorage independent cell growth. Taken together, our findings demonstrate that Ryk promotes stem cell-like and tumorigenic features to glioma cells its essential for the maintenance of GSCs and could be a target of novel therapies

miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down-regulation of NRAS

Glioblastoma is the most common primary brain tumor in adults; with a survival rate of 12 months from diagnosis. However, a small subgroup of patients, termed long-term survivors (LTS), has a survival rate longer then 12–14 months. There is thus increasing interest in the identification of molecular signatures predicting glioblastoma prognosis and in how to improve the therapeutic approach. Here, we report miR-340 as prognostic tumor-suppressor microRNA for glioblastoma. We analyzed microRNA expression in > 500 glioblastoma patients and found that although miR-340 is strongly down-regulated in glioblastoma overall, it is up-regulated in LTS patients compared to short-term survivors (STS). Indeed, miR-340 expression predicted better prognosis in glioblastoma patients. Coherently, overexpression of miR-340 in glioblastoma cells was found to produce a tumor-suppressive activity. We identified NRAS mRNA as a critical, direct target of miR-340: in fact, miR-340 negatively influenced multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways. Thus, we demonstrate that expression of miR-340 in glioblastoma is responsible for a strong tumor-suppressive effect in LTS patients by down-regulating NRAS. miR-340 may thus represent a novel marker for glioblastoma diagnosis and prognosis, and may be developed into a tool to improve treatment of glioblastoma

A Cardiovascular Risk Score for Use in Occupational Medicine

Cardiovascular disease is one of the most frequent causes of long-term sickness absence from work. The study aims to develop and validate a score to assess the 10-year risk of unsuitability for work accounting for the cardiovascular risk. The score can be considered as a prevention tool that would improve the cardiovascular risk assessment during health surveillance visits under the assumption that a high cardiovascular risk might also translate into high risk of unsuitability for work. A total of 11,079 Italian workers were examined, as part of their scheduled occupational health surveillance. Cox proportional hazards regression models were employed to derive risk equations for assessing the 10-year risk of a diagnosis of unsuitability for work. Two scores were developed: the CROMA score (Cardiovascular Risk in Occupational Medicine) included age, sex, smoking status, blood pressure (systolic and diastolic), body mass index, height, diagnosis of hypertension, diabetes, ischemic heart disease, mental disorders and prescription of antidiabetic and antihypertensive medications. The CROMB score was the same as CROMA score except for the inclusion of only variables statistically significant at the 0.05 level. For both scores, the expected risk of unsuitability for work was higher for workers in the highest risk class, as compared with the lowest. Moreover results showed a positive association between most of cardiovascular risk factors and the risk of unsuitability for work. The CROMA score demonstrated better calibration than the CROMB score (11.624 (p-value: 0.235)). Moreover, the CROMA score, in comparison with existing CVD risk scores, showed the best goodness of fit and discrimination

The Role of Exo-miRNAs in Cancer: A Focus on Therapeutic and Diagnostic Applications

Exosomes are extracellular vesicles released into biological fluids where they act as carriers of various molecules, including proteins, lipids, and RNAs, between cells, modulating or perturbing specific physiological processes. Recently, it has been suggested that tumoral cells release excessive amounts of exosomes that, through their cargo, promote tumor progression, stimulating growth, angiogenesis, metastasis, insensitivity to chemotherapy, and immune evasion. Increasing evidence highlights exosomal microRNAs (exo-miRNAs) as important players in tumorigenesis. MicroRNA (miRNA) are a class of small non-coding RNA able to regulate gene expression, targeting multiple mRNAs and inducing translational repression and/or mRNA degradation. Exo-miRNAs are highly stable and easily detectable in biological fluids, and for these reasons, miRNAs are potential cancer biomarkers useful diagnostically and prognostically. Furthermore, since exosomes are natural delivery systems between cells, they can be appropriately modified to carry therapeutic miRNAs to specific recipient cells. Here we summarize the main functions of exo-miRNAs and their possible role for diagnostic and therapeutic applications

Persistence, adherence, healthcare resource utilization and costs for ocrelizumab in the real-world of the Campania Region of Italy

We aim to provide real-world evidence on the use of ocrelizumab for treating multiple sclerosis (MS), with specific regard to prescription pattern, adherence, persistence, healthcare resource utilization and related costs, also in relation to other disease-modifying treatments (DMTs)

The independent contribution of brain, spinal cord and gadolinium MRI in treatment decision in multiple sclerosis: A population-based retrospective study

Spinal cord and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) can provide additional information to brain MRI to determine prognosis of multiple sclerosis (MS). However, the real-world impact of routine use of brain MRI with spinal cord and/or Gd sequences is unknown. Our aim was to evaluate the effect of brain, spinal cord and Gd MRI on treatment decisions in MS