Ultrasound diagnosis of lung herniation: The push-out sign

Lung ultrasound is an expanding field and is becoming a standard of care. Its various bedside applications have modified many diagnostic paths from the newborn to the geriatric patient. In this case report, we describe and show a new sign of the lung ultrasound semeiotics, the push-out sign

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

Comparing the impact of power supply voltage on CMOS-and FinFET-based SRAMs in the presence of resistive defects

CMOS technology scaling has reached its limit at the 22 nm technology node due to several factors including Process Variations (PV), increased leakage current, Random Dopant Fluctuation (RDF), and mainly the Short-Channel Effect (SCE). In order to continue the miniaturization process via technology down-scaling while preserving system reliability and performance, Fin Field-Effect Transistors (FinFETs) arise as an alternative to CMOS transistors. In parallel, Static Random-Access Memories (SRAMs) increasingly occupy great part of Systems-on-Chips’ (SoCs) silicon area, making their reliability an important issue. SRAMs are designed to reach densities at the limit of the manufacturing process, making this component susceptible to manufacturing defects, including the resistive ones. Such defects may cause dynamic faults during the circuits’ lifetime, an important cause of test escape. Thus, the identification of the proper faulty behavior taking different operating conditions into account is considered crucial to guarantee the development of more suitable test methodologies. In this context, a comparison between the behavior of a 22 nm CMOS-based and a 20 nm FinFET-based SRAM in the presence of resistive defects is carried out considering different power supply voltages. In more detail, the behavior of defective cells operating under different power supply voltages has been investigated performing SPICE simulations. Results show that the power supply voltage plays an important role in the faulty behavior of both CMOS- and FinFET-based SRAM cells in the presence of resistive defects but demonstrate to be more expressive when considering the FinFET-based memories. Studying different operating temperatures, the results show an expressively higher occurrence of dynamic faults in FinFET-based SRAMs when compared to CMOS technology

Choosing wisely in cardiology: Five proposals from the Italian Association for Cardiovascular Prevention and Rehabilitation

We do not always accomplish what is best for our patients. Is "more procedures, more drugs" a real synonym of good and always useful medicine? Probably not. Indeed, it has been highlighted that many tests and treatments, widely used in medical practice, do not bring benefits to patients, but they can be harmful. So, why do we keep performing them? Many reasons, surely one of the main is the constant fear of malpractice legal-medical consequences; this led to the development of a defensive medicine, no longer focused on the health of the patient. For this reason, the Italian Association of Cardiac Prevention and Rehabilitation (GICR-IACPR) joined an international project "Choosing Wisely", supported by the Slow Medicine Initiative, a network which states that "Less is more”. The purpose of "Choosing Wisely " project is to improve the quality and safety of health services through the reduction of practices that, according to available scientific knowledge, do not bring significant benefits to the patients, but can, on the contrary, expose them to risks. This GICR-IACPR paper proposes to avoid five widespread practices in cardiology, at risk for inappropriateness and lacking of clinical evidence of benefit: • Do not perform routine chest X-ray in patients entering rehabilitation programme after cardiac surgery • Do not perform Computed Tomography for coronary calcium score in patients at high cardiovascular risk • Do not perform Holter electrocardiographic monitoring in patients suffering from syncope, near syncope or dizziness, in whom a non-arrhythmic origin has been documented • Do not routinely prescribe proton pump inhibitors (PPI) for gastrointestinal bleeding prophylaxis in patient with single drug antiplatelet therapy in absence of additional risk factors. • Avoid routine use of infective endocarditis prophylaxis in mild to moderate native valve diseas

Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel

MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656-1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517-1.000) and 10-years (AUC: 0.804. 95%CI: 0.517-1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients

Time related variations in stem cell harvesting of umbilical cord blood

Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units

Hsa-miR155-5p up-regulation in Breast Cancer and its relevance for treatment with Poly [ADP-ribose] polymerase 1 (PARP-1) inhibitors

miR-155-5p is a well-known oncogenic microRNA, showing frequent overexpression in human malignancies, including breast cancer. Here, we show that high miR-155-5p levels are associated with unfavorable prognostic factors in two independent breast cancer cohorts (CSS cohort, n = 283; and TCGA-BRCA dataset, n = 1,095). Consistently, miR-155-5p results as differentially expressed in the breast cancer subgroups identified by the surrogate molecular classification in the CSS cohort and the PAM50 classifier in TCGA-BRCA dataset, with the TNBC and HER2-amplified tumors carrying the highest levels. Since the analysis of TCGA-BC dataset also demonstrated a significant association between miR-155-5p levels and the presence of mutations in homologous recombination (HR) genes, we hypothesized that miR-155-5p might affect cell response to the PARP-1 inhibitor Olaparib. As expected, miR-155-5p ectopic overexpression followed by Olaparib administration resulted in a greater reduction of cell viability as compared to Olaparib administration alone, suggesting that miR-155-5p might induce a synthetic lethal effect in cancer cells when coupled with PARP-1-inhibition. Overall, our data point to a role of miR-155-5p in homologous recombination deficiency and suggest miR-155-5p might be useful in predicting response to PARP1 inhibitors in the clinical setting

Chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome

<p>Abstract</p> <p>Background</p> <p>Differential diagnosis between acute cardiogenic pulmonary edema (APE) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) may often be difficult. We evaluated the ability of chest sonography in the identification of characteristic pleuropulmonary signs useful in the diagnosis of ALI/ARDS and APE.</p> <p>Methods</p> <p>Chest sonography was performed on admission to the intensive care unit in 58 consecutive patients affected by ALI/ARDS or by acute pulmonary edema (APE).</p> <p>Results</p> <p>Ultrasound examination was focalised on finding in the two groups the presence of: 1) alveolar-interstitial syndrome (AIS) 2) pleural lines abnormalities 3) absence or reduction of "gliding" sign 4) "spared areas" 5) consolidations 6) pleural effusion 7) "lung pulse".</p> <p>AIS was found in 100% of patients with ALI/ARDS and in 100% of patients with APE (p = ns). Pleural line abnormalities were observed in 100% of patients with ALI/ARDS and in 25% of patients with APE (p < 0.0001). Absence or reduction of the 'gliding sign' was observed in 100% of patients with ALI/ARDS and in 0% of patients with APE. 'Spared areas' were observed in 100% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001). Consolidations were present in 83.3% of patients with ALI/ARDS in 0% of patients with APE (p < 0.0001). A pleural effusion was present in 66.6% of patients with ALI/ARDS and in 95% of patients with APE (p < 0.004). 'Lung pulse' was observed in 50% of patients with ALI/ARDS and in 0% of patients with APE (p < 0.0001).</p> <p>All signs, except the presence of AIS, presented a statistically significant difference in presentation between the two syndromes resulting specific for the ultrasonographic characterization of ALI/ARDS.</p> <p>Conclusion</p> <p>Pleuroparenchimal patterns in ALI/ARDS do find a characterization through ultrasonographic lung scan. In the critically ill the ultrasound demonstration of a dyshomogeneous AIS with spared areas, pleural line modifications and lung consolidations is strongly predictive, in an early phase, of non-cardiogenic pulmonary edema.</p

Narrowband CCD Photometry of Giant HII Regions

We have obtained accurate CCD narrow band H_beta and H_alpha photometry of Giant HII Regions in M 33, NGC 6822 and M 101. Comparison with previous determinations of emission line fluxes show large discrepancies; their probable origins are discussed. Combining our new photometric data with global velocity dispersion (sigma) derived from emission line widths we have reviewed the L(H_beta)-sigma relation. A reanalysis of the properties of the GEHRs included in our sample shows that age spread and the superposition of components in multiple regions introduce a considerable spread in the regression. Combining the information available in the literature regarding ages of the associated clusters, evolutionary footprints on the interstellar medium, and kinematical properties of the knots that build up the multiple GEHRs, we have found that a subsample - which we refer to as young and single GEHRs - do follow a tight relation in the L-sigma plane.Comment: Accepted for publication in MNRAS, large figures available on a separate tarfil