3,5-dicaffeoylquinic acid lowers 3T3-L1 mitotic clonal expansion and adipocyte differentiation by enhancing heme oxygenase-1 expression

Adipogenesis is a complex process in which cell commitment and mitotic clonal expansion (MCE) are in-sequence crucial events leading to terminal adipocyte differentiation. The molecules able to block some key signals in this cascade can hamper adipogenesis becoming promising agents to counteract hyperplasia and hypertrophy of adipose tissue. Mono- and di-caffeoylquinic acid isomers are biologically active polyphenols, displaying in vitro and in vivo antioxidant, hepatoprotective, anti-diabetic and anti-obesity properties. Among these isomers, 3,5-dicaffeoylquinic acid (DCQA) has been reported to inhibit lipid accumulation in adipose cells more successfully than others. Thus, we investigated DCQA effects and molecular mechanisms on 3T3-L1 pre-adipocytes induced to differentiate with a hormonal cocktail (MDI). Oil Red O incorporation assessed that DCQA pre-treatment inhibited lipid accumulation in 3T3-L1 cells induced to differentiate for 10 days. At this time, an increased phosphorylation of both AMP-activated kinase and acetyl-CoA carboxylase, as well as a strong decrease in fatty acid synthase protein level, were registered by immunoblotting, thereby suggesting that DCQA treatment can reduce fatty acid anabolism in 3T3-L1 adipocytes. Furthermore, BrdU incorporation assay, performed 48 h after hormonal stimulation, revealed that DCQA treatment was also able to hinder the 3T3-L1 cell proliferation during the MCE, which is an essential step in the adipogenic process. Thus, we focused our attention on early signals triggered by the differentiation stimuli. In the first hours after hormonal cocktail administration, the activation of ERK1/2 and Akt kinases, or CREB and STAT3 transcription factors, was not affected by DCQA pre-treatment. Whereas 24 h after MDI induction, DCQA pre-treated cells showed increased level of the transcription factor Nrf2, that induced the expression of the antioxidant enzyme heme oxygenase 1 (HO-1). In control samples, the expression level of HO-1 was reduced 24 h after MDI induction in comparison with the higher amount of HO-1 protein found at 2 h. The HO-1 decrease was functional by allowing reactive oxygen species to boost and allowing cell proliferation induction at the beginning of MCE phase. Instead, in DCQA-treated cells the HO-1 expression was maintained at high levels for a further 24 h; in fact, its expression decreased only 48 h after MDI stimulation. The longer period in which HO-1 expression remained high led to a delay of the MCE phase, with a subsequent inhibition of both C/EBP-α expression and adipocyte terminal differentiation. In conclusion, DCQA counteracting an excessive adipose tissue expansion may become an attractive option in obesity treatment

A wearable system for visual cueing gait rehabilitation in Parkinson's disease: a randomized non-inferiority trial

Background: Gait disturbances represent one of the most disabling features of Parkinson's disease (PD). Aim: The aim of this study was to evaluate the non-inferiority of a new wearable visual cueing system (Q-Walk) for gait rehabilitation in PD subjects, compared to traditional visual cues (stripes on the floor). Design: Open-label, monocentric, randomized controlled non-inferiority trial. Setting: Outpatients. Population: Patients affected by idiopathic PD without cognitive impairment, Hoehn and Yahr stage II-IV, Unified Parkinson's Disease Rating Scale motor section III ≥2, stable drug usage since at least 3 weeks. Methods: At the enrollment (T0), all subjects underwent a clinical/functional evaluation and the instrumental gait and postural analysis; then they were randomly assigned to the Study Group (SG) or Control Group (CG). Rehabilitation program consisted in 10 consecutive individual sessions (5 sessions/week for 2 consecutive weeks). Each session included 60 minutes of conventional physiotherapy plus 30 minutes of gait training by Q-Walk (SG) or by traditional visual cues (CG). Follow-up visits were scheduled at the end of the treatment (T1) and after 3 months (T2). Results: Fifty-two subjects were enrolled in the study, 26 in each group. The within-groups analysis showed a significant improvement in clinical scales and instrumental data at T1 and at T2, compared to baseline, in both groups. According to the between-group analysis, Q-Walk cueing system was not-inferior to the traditional cues for gait rehabilitation. The satisfaction questionnaire revealed that most subjects described the Q-Walk cueing system as simple, motivating and easily usable, possibly suitable for home use. Conclusions: Data showed that motor rehabilitation of PD subjects performed by means of the new wearable Q-Walk cueing system was feasible and as effective as traditional cues in improving gait parameters and balance. Clinical rehabilitation impact: Wearable devices can act as an additional rehabilitation strategy for long-term and continuous care, allowing patients to train intensively and extensively in household settings, favoring a tailor-made and personalized approach as well as remote monitoring

Intensive monitoring of conventional and surrogate quality parameters in a highly urbanized river affected by multiple combined sewer overflows

Abstract The paper reports results of four intensive campaigns carried out on the Seveso River (Milan metropolitan area, Italy) between 2014 and 2016, during intense precipitation events. Laboratory analyses were coupled with on-site, continuous measurements to assess the impact of pollutants on water quality based on both conventional and surrogate parameters. Laboratory data included total suspended solids, caffeine, total phosphorus and nitrogen, and their dissolved forms. Screening of trace metals (Cr, Cu, Pb, Ni, Cd) and PBDEs (polybromodiphenylethers) was carried out. Continuous measurements included water level, physico-chemical variables and turbidity. Nutrient concentrations were generally high (e.g. average total phosphorus > 1,000 μg/L) indicating strong sewage contributions. Among monitored pollutants Cr, Cu, Pb, and Cd concentrations were well correlated to TSS, turbidity and discharge, being bound mostly to suspended particulate matter. A different behavior was found for Ni, that showed an early peak occurring before the flow peak, as a result of first flush events. PBDEs correlated well to nutrient concentrations, showing the highest peaks soon after activation of the combined sewer overflows, likely because of its accumulation in sewers. In addition to showing the existing correlations between quality parameters, the paper highlights the importance of surrogate parameters as indicators of anthropic pollution inputs

Mobilization in early rehabilitation in intensive care unit patients with severe acquired brain injury: An observational study.

Objective: To determine whether early mobilization of patients with severe acquired brain injury, performed in the intensive/neurointensive care unit, influences functional outcome. Design: Prospective observational study. Setting: Fourteen centres in Italy. Subjects: A total of 103 consecutive patients with acquired brain injury. Methods: Clinical, neurological and functional data, including the Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), the Rancho Los Amigos Levels of Cognitive Functioning (LCF), Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome Scale (GOS), and Functional Independence Measure (FIM) were collected at admission and every 3–5 days until discharge from the intensive/neurointensive care unit. Patients were divided into mobilization and no mobilization groups, depending on whether they received mobilization. Data were analysed by intragroup and intergroup analysis using a multilevel regression model. Results: Sixty-eight patients were included in the mobilization group. At discharge, both groups showed significant improvements in GCS, DRS, LCF and ERBI scores. The mobilization group showed significantly better improvements in FIM cognitive, GOS and ERBI. The patients in the mobilization group stayed longer in the intensive care unit (p = 0.01) and were more likely to be discharged to intensive rehabilitation at a significantly higher rate (p = 0.002) than patients in the no mobilization group. No adverse events were reported in either group. Conclusion: Early mobilization appears to favour the clinical and functional recovery of patients with severe acquired brain injury in the intensive care unit

The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals: Evidence for Interaction With Obesity in Diabetic Patients

Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals

Stepwise analysis of MIR9 loci identifies miR-9-5p to be involved in Oestrogen regulated pathways in breast cancer patients

miR-9 was initially identified as an epigenetically regulated miRNA in tumours, but inconsistent findings have been reported so far. We analysed the expression of miR-9-5p, miR-9-3p, pri-miRs and MIR9 promoters methylation status in 131 breast cancer cases and 12 normal breast tissues (NBTs). The expression of both mature miRs was increased in tumours as compared to NBTs (P < 0.001) and negatively correlated with ER protein expression (P = 0.005 and P = 0.003, for miR-9-3p and miR-9-5p respectively). In addition, miR-9-5p showed a significant negative correlation with PgR (P = 0.002). Consistently, miR-9-5p and miR-9 3p were differentially expressed in the breast cancer subgroups identified by ER and PgR expression and HER2 amplification. No significant correlation between promoter methylation and pri-miRNAs expressions was found either in tumours or in NBTs. In the Luminal breast cancer subtype the expression of miR-9-5p was associated with a worse prognosis in both univariable and multivariable analyses. Ingenuity Pathway Analysis exploring the putative interactions among miR-9-5p/miR-9-3p, ER and PgR upstream and downstream regulators suggested a regulatory loop by which miR-9-5p but not miR-9-3p is induced by steroid hormone receptor and acts within hormone-receptor regulated pathways

Bartolomeo S: Evaluation of lung ultrasound for the diagnosis of pneumonia

Abstract Objectives: The aim of this study is to assess the ability of bedside lung ultrasound (US) to confirm clinical suspicion of pneumonia and the feasibility of its integration in common emergency department (ED) clinical practice. Methods: In this study we performed lung US in adult patients admitted in our ED with a suspected pneumonia.Subsequently, a chest radiograph (CXR) was carried out for each patient. A thoracic computed tomographic (CT) scan was made in patients with a positive lung US and a negative CXR. In patients with confirmed pneumonia, we performed a follow-up after 10 days to evaluate clinical conditions after antibiotic therapy. Results: We studied 49 patients: pneumonia was confirmed in 32 cases (65.3%). In this group we had 31 (96.9%) positive lung US and 24 (75%) positive CXR. In 8 (25%) cases, lung US was positive with a negative CXR. In this group, CT scan always confirmed the US results. In one case, US was negative and CXR positive. Follow-up turned out to be always consistent with the diagnosis. Conclusion: Considering that lung US is a bedside, reliable, rapid, and noninvasive technique, these results suggest it could have a significant role in the diagnostic workup of pneumonia in the ED, even if no sensitivity nor specificity can be inferred from this study because the real gold standard is CT, which could not be performed in all patients

Lung Ultrasound Diagnostic Accuracy in Neonatal Pneumothorax

Background. Pneumothorax (PTX) still remains a common cause of morbidity in critically ill and ventilated neonates. At the present time, lung ultrasound (LUS) is not included in the diagnostic work-up of PTX in newborns despite of excellent evidence of reliability in adults. The aim of this study was to compare LUS, chest X-ray (CXR), and chest transillumination (CTR) for PTX diagnosis in a group of neonates in which the presence of air in the pleural space was confirmed. Methods. In a 36-month period, 49 neonates with respiratory distress were enrolled in the study. Twenty-three had PTX requiring aspiration or chest drainage (birth weight 2120 ± 1640 grams; gestational age = 36 ± 5 weeks), and 26 were suffering from respiratory distress without PTX (birth weight 2120 ± 1640 grams; gestational age = 34 ± 5 weeks). Both groups had done LUS, CTR, and CXR. Results. LUS was consistent with PTX in all 23 patients requiring chest aspiration. In this group, CXR did not detect PTX in one patient while CTR did not detect it in 3 patients. Sensitivity and specificity in diagnosing PTX were therefore 1 for LUS, 0.96 and 1 for CXR, and 0.87 and 0.96 for CTR. Conclusions. Our results confirm that also in newborns LUS is at least as accurate as CXR in the diagnosis of PTX while CTR has a lower accuracy