Low-energy Pulsed Electromagnetic Field Therapy Reduces Pain in Fibromyalgia: A Randomized Single-blind Controlled Pilot Study.

Objectives: Fibromyalgia symptoms have a significant impact on the quality of life and respond poorly to medications. It has been hypothesized that the use of low-energy pulsed electromagnetic field (PEMF) induces neuroprotective effects that may interfere with pain perception. We explored the efficacy of PEMF in patients affected by fibromyalgia. Methods: Twenty-one females (median age 59 years, interquartile range [IQR] 16.5) affected by fibromyalgia were randomized to receive pulsed electromagnetic field-triple energy pain treatment (PEMF-TEPT) or placebo at T0 and at 4 weeks and 8 weeks. Fibromyalgia impact questionnaire (FIQ), widespread pain index (WPI), visual analog score (VAS) pain, symptom severity (SS) scale, and short form 36 (SF-36) health survey questionnaire have been evaluated. Results: Patients in the PEMF-TEPT group had a significantly higher reduction of WPI compared to placebo (mean difference -12.90 ± standard deviation [SD] 5.32 vs. -1.91 ± 4.55, difference in difference [DD] of -10.99; P < 0.001), of SS score (-4.10 ± 4.85 vs. -2.00 ± 2.32; DD = -2.1; P < 0.05), of VAS pain (-48 ± 30.75 vs. -16.82 ± 23.69; DD = -31.18; P < 0.01). They also reported a higher improvement of FIQ and SF-36, albeit not reaching statistical significance. Conclusion: In our pilot controlled study, PEMF-TEPT appeared to be safe and improved fibromyalgia symptoms.

Frequency, characteristics and prognostic impact of hospital readmissions in elderly patients with heart failure: A population study from 2013 to 2017 in Liguria, Northern Italy.

BACKGROUND: Hospital readmissions are a key determinant of prognosis in elderly patients with heart failure (HF). We investigated their frequency, predictors and prognostic impact using a large administrative database from Liguria, the oldest region of Italy. METHODS: Patients aged ≥18 years with at least one hospitalization with HF and being prescribed a diuretic medication between January 2013 and December 2017 were included in the analysis. Their demographics and Charlson comorbidity index (CCI) were collected. Patients were grouped by number of readmissions, and negative binomial and Cox proportional hazard models were used to explore independent predictors of readmissions and mortality, respectively. RESULTS: There were 207,130 hospital admissions from 35,316 patients (mean age 81.6 years, 43.7% ≥85 years of age, 47.2% male, mean CCI 1.7, overall mortality 52.8%). About a quarter of patients (8.878, 25.1%) had more than eight readmissions during follow-up, for a total of 108.146 admissions (52.2% of admissions). Male gender, lower educational level and higher CCI were independently associated with increased number of readmissions and increased mortality. There was an independent inverse relationship between number of admissions and survival, with patients hospitalized 8 or more times displaying a 3-fold increase in mortality, and a significant interaction between older age and readmissions on mortality. CONCLUSION: A quarter of older comorbid HF patients contributed to more than half of HF hospital readmissions recorded over a 5-year period in Liguria, with a dismal impact on prognosis. Aging societies should pay greater attention to this matter and personalized disease-management programs should be implemented.

Analysis of the impacts of COVID-19 on selected categories of goods passing through the ports of Genoa and Savona, Italy.

The COVID-19 pandemic has had strong economic repercussions on the industrial fabric of many countries around the world, with different degrees of impact depending on the level of severity with which the pandemic hit these countries. Italy has suffered a significant impact on its economy and export volumes have dropped dramatically for some product categories. The objective of this research is to understand how the pandemic has affected some selected logistics flows (i.e., fruit, automotive and machinery) transiting through the ports of Genoa and Savona, and to highlight the mitigation strategies that have been implemented during the pandemic period. The research was carried out analyzing customs and port data, as well as with the support of interviews and focus groups with experts of the Ligurian port sector. Finally, some policy indications are outlined with the aim of increasing the resilience of the supply chains analyzed in this research. These indications should help supply chains to be efficient and effective in forwarding flows of goods to/from ports even in the occurrence of unforeseen high-impact events.

Frequent use of emergency departments and chronic conditions in ageing societies: a retrospective analysis based in Italy.

BACKGROUND: Most western countries are facing relevant demographic changes, and the percentage of older people is destined to rise in the next decades. This fact is likely to affect the sustainability of healthcare systems significantly, mainly due to the connected issue of chronicity. METHODS: In this paper, using an extensive and comprehensive administrative dataset, we analyse the phenomenon of frequent use of emergency departments (ED) in the oldest region in Europe (i.e. Liguria) over 4 years (2013-2016). Two alternative approaches are used to define categories of ED users based on the intensity and frequency of accesses and splitting patients into different age groups. RESULTS: Results allow identifying clinical and socio-demographic risk-factors connected to different levels of ED utilisation and highlight the influential role played by chronic conditions (particularly mental disorders, respiratory diseases) and by multiple chronic conditions. CONCLUSIONS: The study aims at representing an informative tool to support policy-makers in setting proper policies addressed, on the one side, towards the potentially preventable frequent users and, on the other, towards those accessing due to complex medical conditions. The results can help in building a warning system to help general practitioners in the identification of potential frequent users and to develop preventive policies.

Speeding up the clinical pathways by accessing emergency departments.

Inappropriate emergency admissions create overcrowding and may reduce the quality of emergency care. In Italy, overcrowding is further exacerbated by patients who use emergency admissions as a shortcut to avoid the general practitioner (GP) gateway. In this paper, we investigate access to emergency departments (EDs) by patients with non-severe medical conditions and their willingness to wait. Population data for ED accesses in Liguria (an Italian administrative region) in 2016 were used to estimate the number of strategic accesses and waiting time elasticities of low-severity patients. Our results show that the practice of using EDs to skip gatekeeping is a serious problem. The percentage of patients who engage in such practice vary from 8.7 to 9.9% of non-urgent patients; they generally prefer to access more specialized hospitals, especially during weekdays, when GPs are available, but hospitals run at full capacity. Strategic patients are usually much younger than average. From a policy point of view, our results show that long waits may discourage "genuine" patients rather than strategic ones. It is necessary to develop a system to improve access to patients mainly requiring specialist care, along with enhancing the management of diagnostic examinations through primary care.

Cerebral toxoplasmosis in a cat with feline leukemia and feline infectious peritonitis viral infections.

A diarrheic young cat died after neurological involvement. Biochemistry pointed to feline infectious peritonitis (FIP). The final diagnosis was severe multifocal meningoencephalitis due to Toxoplasma gondii. The presence of the parasite in the brain was confirmed using immunohistochemical staining. Concomitant feline leukemia virus (FeLV) and FIP were possible contributors to the clinical, fatal outcome.

Toxoplasmose cérébrale chez un chat atteint des infections virales de leucémie féline et de péritonite infectieuse féline. Un jeune chat diarrhéique est mort après des symptômes neurologiques. La biochimie a signalé une péritonite infectieuse féline (FIP). Le diagnostic final a été une méningo-encéphalite multifocale grave causée par Toxoplasma gondii. La présence du parasite dans le cerveau a été confirmée à l'aide de la coloration immunohistochimique. La présence concomitante du virus de la leucémie féline (FeLV) et de la FIP sont des facteurs possibles ayant contribué au résultat clinique mortel.(Traduit par Isabelle Vallières).

miRNA expression profile of bone marrow resident cells from children with neuroblastoma is not significantly different from that of healthy children.

The miRNA expression profiles of bone marrow resident cells from children with neuroblastoma were compared to that of healthy children. No significant difference was found between localized and metastatic neuroblastoma, or between children with neuroblastoma and healthy children. By considering the fold change we identified six miRNAs over-expressed by more than 150 fold in neuroblastoma. Validation confirmed miR-221 over-expression in BM resident cells from children with neuroblastoma, regardless of localized or metastatic disease. MiR-221 over-expression was unlikely derived from neuroblastoma primary tumors or from bone marrow-infiltrating metastatic cells, since neuroblastoma cells expressed lower or similar amount of miR-221 than BM cells, respectively. To get insight on the genes potentially regulated by miR-221 we merged the list of miR-221 potential targets with the genes under-expressed by BM resident cells from children with neuroblastoma, as compared with healthy children. In silico analysis demonstrated that none of the miR-221 target genes belonged to heme biosynthetic processes found altered in children with neuroblastoma, whereas two genes associated with mitochondria. However, the encoded proteins were not under-expressed in children with neuroblastoma, making unlikely that altered erythrocyte maturation in children with neuroblastoma was mediated by miR-221. In conclusion, miRNA expression profiles of BM resident cells from children with localized and metastatic neuroblastoma were similar to that of BM resident cells from healthy children. Moreover, miRNAs expressed by neuroblastoma primary tumors or by BM-infiltrating NB cells do not appear to be involved in mediating the functional defect of erythrocyte maturation recently observed in children with neuroblastoma.

Altered erythropoiesis and decreased number of erythrocytes in children with neuroblastoma.

Neuroblastoma (NB) is a pediatric tumor presenting at diagnosis either as localized or metastatic disease, which mainly involves the bone marrow (BM). The physical occupancy of BM space by metastatic NB cells has been held responsible for impairment of BM function. Here, we investigated whether localized or metastatic NB may alter hematopoietic lineages' maturation and release of mature cells in the periphery, through gene expression profiling, analysis of BM smears, cell blood count and flow cytometry analysis. Gene ontology and disease-associated analysis of the genes significantly under-expressed in BM resident cells from children with localized and metastatic NB, as compared to healthy children, indicated anemia, blood group antigens, and heme and porphyrin biosynthesis as major functional annotation clusters. Accordingly, in children with NB there was a selective impairment of erythrocyte maturation at the ortho-chromic stage that resulted in reduced erythrocyte count in the periphery, regardless of the presence of metastatic cells in the BM. By considering all NB patients, low erythrocyte count at diagnosis associated with worse survival. Moreover, in the subset of metastatic patients, low erythrocyte count, hemoglobin and hematocrit and high red cell distribution width at follow-up also associated with worse outcome. These observations provide an alternative model to the tenet that infiltrating cells inhibit BM functions due to physical occupancy of space and may open a new area of research in NB to understand the mechanism(s) responsible for such selective impairment.

Circulating miR-200c is up-regulated in paediatric patients with familial hypercholesterolaemia and correlates with miR-33a/b levels: implication of a ZEB1-dependent mechanism.

Hypercholesterolaemia provokes reactive oxygen species (ROS) increase and is a major risk factor for cardiovascular disease (CVD) development. We previously showed that circulating miR-33a/b expression levels were up-regulated in children with familial hypercholesterolaemia (FH). miR-33a/b control cholesterol homoeostasis and recently miR-33b has been demonstrated to directly target the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1). The latter acts in a negative feedback loop with the miR-200 family. Our previous studies showed that the ROS-dependent miR-200c up-regulation induces endothelial dysfunction and provokes a ZEB1-dependent apoptosis and senescence. In the present study, we aimed to verify whether circulating miR-200c was induced in FH children, and whether a correlation existed with miR-33a/b Total RNA was extracted from plasma of 28 FH children and 25 age-matched healthy subjects (HS) and miR-200c levels were measured. We found that miR-200c was up-regulated in FH compared with HS (4.00 ± 0.48-fold increase, P<0.05) and exhibited a positive correlation with miR-33a/b. miR-200c did not correlate with plasma lipids, but correlated with C-reactive protein (CRP) plasma levels and glycaemia (GLI). Ordinary least squares (OLS) regression analysis revealed that miR-200c was significantly affected by GLI and by miR-33a (P<0.01; P<0.001 respectively). Moreover, we found that miR-33 overexpression, in different cell lines, decreased ZEB1 expression and up-regulated both the intracellular and the extracellular miR-200c expression levels. In conclusion, circulating miR-200c is up-regulated in FH, probably due to oxidative stress and inflammation and via a miR-33a/b-ZEB1-dependent mechanism. The present study could provide the first evidence to point to the use of miR-33a/b and miR-200c, as early biomarkers of CVD, in paediatric FH.

Circulating miR-33a and miR-33b are up-regulated in familial hypercholesterolaemia in paediatric age.

Hypercholesterolaemia is one of the major causes of CVD (cardiovascular disease). It is associated with enhanced oxidative stress, leading to increased lipid peroxidation which in turn determines endothelial dysfunction and susceptibility to coronary vasoconstriction and atherosclerosis. Different miRNAs are involved in the pathogenesis of CVD and play an important role in inflammatory process control, therefore, together with atherogenic factors, they can stimulate atherosclerotic degeneration of the vessel walls of arteries. miR-33a and miR-33b play a pivotal role in a variety of biological processes including cholesterol homoeostasis, HDL (high-density lipoprotein)-cholesterol formation, fatty acid oxidation and insulin signalling. Our study aimed to determine whether circulating miR-33a and miR-33b expression was altered in familial hypercholesterolaemic children. Total RNA was extracted from plasma, and miR-33a and miR-33b were measured by quantitative real-time PCR. We found that miR-33a and miR-33b were significantly up-regulated in the plasma of 28 hypercholesterolaemic children compared with 25 healthy subjects (4.49±0.27-fold increase, P<0.001, and 3.21±0.39-fold increase, P<0.05 respectively), and for both miRNAs, a positive correlation with total cholesterol, LDL (low-density lipoprotein)-cholesterol, LDL-cholesterol/HDL-cholesterol ratio, apolipoprotein B, CRP (C-reactive protein) and glycaemia was found. OLS (ordinary least squares) regression analysis revealed that miR-33a was significantly affected by the presence of FH (familial hypercholesterolaemia), glycaemia and CRP (P<0.001, P<0.05 and P<0.05 respectively). The same analysis showed that miR-33b was significantly related to FH and CRP (P<0.05 and P<0.05 respectively). Although it is only explorative, the present study could be the first to point to the use of miR-33a and miR-33b as early biomarkers for cholesterol levels in childhood, once validated in independent larger cohorts.

Characterization of the Pall Celeris system as a point-of-care device for therapeutic angiogenesis.

BACKGROUND AIMS: The Pall Celeris system is a filtration-based point-of-care device designed to obtain a high concentrate of peripheral blood total nucleated cells (PB-TNCs). We have characterized the Pall Celeris-derived TNCs for their in vitro and in vivo angiogenic potency. METHODS: PB-TNCs isolated from healthy donors were characterized through the use of flow cytometry and functional assays, aiming to assess migratory capacity, ability to form capillary-like structures, endothelial trans-differentiation and paracrine factor secretion. In a hind limb ischemia mouse model, we evaluated perfusion immediately and 7 days after surgery, along with capillary, arteriole and regenerative fiber density and local bio-distribution. RESULTS: Human PB-TNCs isolated by use of the Pall Celeris filtration system were shown to secrete a panel of angiogenic factors and migrate in response to vascular endothelial growth factor and stromal-derived factor-1 stimuli. Moreover, after injection in a mouse model of hind limb ischemia, PB-TNCs induced neovascularization by increasing capillary, arteriole and regenerative fiber numbers, with human cells detected in murine tissue up to 7 days after ischemia. CONCLUSIONS: The Pall Celeris system may represent a novel, effective and reliable point-of-care device to obtain a PB-derived cell product with adequate potency for therapeutic angiogenesis.

Deregulation of focal adhesion pathway mediated by miR-659-3p is implicated in bone marrow infiltration of stage M neuroblastoma patients.

To get insights on the metastatic process of human neuroblastoma (NB), the miRNA expression profile of bone marrow (BM)-infiltrating cells has been determined and compared to that of primary tumors.Twenty-two BM-infiltrating cells, 22 primary tumors, and 4 paired samples from patients with metastatic NB aged > 12 months were analyzed for the expression of 670 miRNAs by stem-loop RT-qPCR. The miRNAs whose expression was significantly different were subjected to selection criteria, and 20 selected miRNAs were tested in 10 additional BM-infiltrating cells and primary tumors. Among the miRNAs confirmed to be differentially expressed, miR-659-3p was further analyzed. Transfection of miR-659-3p mimic and inhibitor demonstrated the specific suppression and over-expression, respectively, of the miR-659-3p target gene CNOT1, a regulator of transcription of genes containing AU-rich element (ARE) sequence. Among the ARE-containing genes, miR-659-3p mimic and inhibitor specifically modified the expression of AKT3, BCL2, CYR61 and THSB2, belonging to the focal adhesion pathway. Most importantly, in BM-infiltrating cells CNOT1 expression was significantly higher, and that of AKT3, BCL2, THSB2 and CYR61 was significantly lower than in primary tumors. Thus, our study suggests a role of the focal adhesion pathway, regulated by miR-659-3p through CNOT1, in the human NB metastatic process.

The Robustness and Effectiveness of the Triage System at Times of Overcrowding and the Extra Costs due to Inappropriate Use of Emergency Departments.

BACKGROUND: Overcrowding is one of the most harmful problems for Emergency Department (ED) management and the correct estimation of time resource absorption by each type of patient plays a strategic role in dealing with overcrowding and correctly programming ED activity. OBJECTIVE: We aimed to investigate how overcrowding may affect urgent patients' waiting times (i.e., the robustness of the triage patient priority system) and to evaluate the extra costs due to inappropriate use of EDs. METHODS: Data referring to 54,254 patients who accessed the ED of a major Italian hospital in 2011 were analyzed to study patient flows and overcrowding. To define an average per-patient cost, according to the severity of his or her health condition, the 2010 profit and loss account of the aforementioned hospital was studied and the time devoted by physicians to each type of patient was estimated by means of a self-reported survey. RESULTS: Empirical findings confirm a positive correlation between overcrowding and the time a patient has to wait before receiving treatment. This effect is relevant only for non-urgent patients who are responsible for the overcrowding itself. However, urgent patients' waiting times do not increase in the presence of overcrowding, confirming that the triage priority system is robust against the overcrowding situation. The analysis estimates, using 2010 data, that the actual per patient cost incurred by the hospital when treating white-coded patients is, on average, 36.54 euros; a green code costs 93.17, yellow 170.62, and red 227.62. It emerges that 4% of all the personnel costs are attributable to white color-code assistance, 67% to green codes, 23% to yellow codes, and the remaining 6% to red codes. CONCLUSION: The implementation of effective policies intended to improve both efficiency and quality in providing emergency health services has to deal with the systemic problem of inappropriate use of EDs. Policy-makers should be aware of the fact that there is a considerable portion of ED demand for assistance that is inappropriate and that oversizing EDs with respect to the true, appropriate, urgent patients' demands, could bring about a further and undesirable rise in inappropriate assistance demands and, therefore, an increase in ED costs that are not consistent with their objectives.

Patient profile modulates cardiac c-kit(+) progenitor cell availability and amplification potential.

Human c-kit(+) cardiac progenitor cells (CPCs) are multipotent and may be used for cardiac repair. The effect of cardiovascular risk factors and medications on CPCs isolation efficiency, c-kit stem cell marker expression, and ex vivo proliferative potential is unknown and was examined in the present work. Cells from human right atrial appendages (n = 50) were expanded in culture; after ∼16 days (T0), it was established the percentage of CPCs and c-kit protein mean fluorescence intensity (MFI) by fluorescence activated cell sorting (FACS). Thereafter, CPCs were isolated by high throughput sorting; after culturing for 4 passages CPCs-derived cells were re-analyzed to assess c-kit(+) cell percentage and enrichment vs T0. The association between 19 demographic and clinical variables to CPCs number and MFI at T0, and CPCs enrichment at P4, was determined by multiple linear regression analysis with stepwise selection procedure. The results revealed that (1) at T0, the number of isolated CPCs directly correlated to ß-blocker treatment; (2) at T0, c-kit protein expression directly correlated to pulmonary hypertension (PH); (3) at P4, CPC's enrichment inversely correlated to smoke, atrial fibrillation (AF), a history of myocardial infarction, whereas it directly correlated to PH and statins. Patient clinical profile and medications differently modulate CPCs isolation and amplification potential ex vivo. These results may provide new insights for the understanding of cardiac homeostasis and suggest both limitations and possible enhancing strategies for the therapeutic use of cardiac-resident progenitor cells.