Showing papers by "Marche Polytechnic University published in 2014"
TL;DR: It is shown that adipocyte-specific deletion of the coregulatory protein PRDM16 caused minimal effects on classical brown fat but markedly inhibited beige adipocyte function in subcutaneous fat following cold exposure or β3-agonist treatment, indicating that PRDM 16 and beige fat cells are required for the "browning" of white fat and the healthful effects of sub cutaneous adipose tissue.
716 citations
TL;DR: Caution should be taken in monitoring studies where mRNA levels of antioxidants could represent a snapshot of cell activity at a given time, not an effective endpoint of environmental pollutants, and conflicting results between molecular and biochemical responses are quite frequent.
640 citations
TL;DR: Consolidation therapy with high-dose melphalan plus stem-cell transplantation, as compared with MPR, significantly prolonged progression-free and overall survival among patients with multiple myeloma who were 65 years of age or younger.
Abstract: Background This open-label, randomized, phase 3 study compared melphalan at a dose of 200 mg per square meter of body-surface area plus autologous stem-cell transplantation with melphalan–prednisone–lenalidomide (MPR) and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diagnosed multiple myeloma. Methods We randomly assigned 273 patients 65 years of age or younger to high-dose melphalan plus stem-cell transplantation or MPR consolidation therapy after induction, and 251 patients to lenalidomide maintenance therapy or no maintenance therapy. The primary end point was progression-free survival. Results The median follow-up period was 51.2 months. Both progression-free and overall survival were significantly longer with high-dose melphalan plus stem-cell transplantation than with MPR (median progression-free survival, 43.0 months vs. 22.4 months; hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.32 to 0.61; P<0.001; and 4-year overall su...
623 citations
TL;DR: Although SCAF is associated with an increased risk of stroke and embolism, very few patients had SCAF in the month before their event, and only 1 of these 4 patients was experiencing SCAF at the time of the stroke.
Abstract: Background—Among patients with implantable pacemakers and defibrillators, subclinical atrial fibrillation (SCAF) is associated with an increased risk of stroke; however, there is limited understanding of their temporal relationship. Methods and Results—The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) enrolled 2580 pacemaker and defibrillator patients aged ≥65 years with a history of hypertension but without a history of atrial fibrillation. Pacemakers and implantable cardioverter-defibrillators precisely logged the time and duration of all episodes of SCAF and recorded electrograms that were adjudicated by experts. We examined the temporal relationship between SCAF >6 minutes in duration and stroke or systemic embolism. Of 51 patients who experienced stroke or systemic embolism during follow-up, 26 (51%) had SCAF. In 18 patients (35%), SCAF was detected before stroke or systemic embolism. However, only 4 pat...
531 citations
TL;DR: This article used an instrumental variable approach to study whether public debt has a causal effect on economic growth in a sample of OECD countries and found that there is no evidence that public debt is associated with economic growth.
451 citations
TL;DR: Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of wheat was associated with a delayed onset of disease.
Abstract: BACKGROUND The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child’s diet and a child’s early dietary pattern is unclear. METHODS We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P = 0.002) and overt celiac disease (12% vs. 5%, P = 0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P = 0.59) or overt disease (16% and 16%, P = 0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P = 0.001), as was the risk of overt celiac disease (26% vs. 16%, P = 0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.)
392 citations
TL;DR: It is shown that panitumumab is non-inferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients, and small but meaningful differences in the rate of grade 3-4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment.
Abstract: Summary Background The anti-EGFR monoclonal antibodies panitumumab and cetuximab are effective in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. We assessed the efficacy and toxicity of panitumumab versus cetuximab in these patients. Methods For this randomised, open-label, phase 3 head-to-head study, we enrolled patients (from centres in North America, South America, Europe, Asia, Africa, and Australia) aged 18 years or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and wild-type KRAS exon 2 status. Using a computer-generated randomisation sequence, we assigned patients (1:1; stratified by geographical region and ECOG performance status, with a permuted block method) to receive panitumumab (6 mg/kg once every 2 weeks) or cetuximab (initial dose 400 mg/m 2 ; 250 mg/m 2 once a week thereafter). The primary endpoint was overall survival assessed for non-inferiority (retention of ≥50% of the cetuximab treatment effect; historical hazard ratio [HR] for cetuximab plus best supportive care vs best supportive care alone of 0·55). The primary analysis included patients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment. Recruitment for this trial is closed. The trial is registered with ClinicalTrials.gov, number NCT01001377. Findings Between Feb 2, 2010, and July 19, 2012, we enrolled and randomly allocated 1010 patients, 999 of whom began study treatment: 499 received panitumumab and 500 received cetuximab. For the primary analysis of overall survival, panitumumab was non-inferior to cetuximab ( Z score −3·19; p=0·0007). Median overall survival was 10·4 months (95% CI 9·4–11·6) with panitumumab and 10·0 months (9·3–11·0) with cetuximab (HR 0·97; 95% CI 0·84–1·11). Panitumumab retained 105·7% (81·9–129·5) of the effect of cetuximab on overall survival seen in this study. The incidence of adverse events of any grade and grade 3–4 was similar across treatment groups. Grade 3–4 skin toxicity occurred in 62 (13%) patients given panitumumab and 48 (10%) patients given cetuximab. The occurrence of grade 3–4 infusion reactions was lower with panitumumab than with cetuximab (one [ vs nine [2%] patients), and the occurrence of grade 3–4 hypomagnesaemia was higher in the panitumumab group (35 [7%] vs 13 [3%]). We recorded one treatment-related fatal adverse event: a lung infection in a patient given cetuximab. Interpretation Our findings show that panitumumab is non-inferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients. Both agents had toxicity profiles that were to be expected. In view of the consistency in efficacy and toxicity seen, small but meaningful differences in the rate of grade 3–4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment. Funding Amgen Inc.
338 citations
TL;DR: A systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up.
326 citations
TL;DR: Although positive margins in prostate cancer are considered an adverse oncologic outcome, their long-term impact on survival is highly variable and largely influenced by other risk modifiers.
315 citations
TL;DR: Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events.
Abstract: Objectives This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF). Background CoQ10 is an essential cofactor for energy production and is also a powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints. Methods Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro–B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis. Results A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028). Conclusions Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234 )
297 citations
TL;DR: Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk.
Abstract: Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (−8.78%, −13.72% and −20.80%, respectively; P P P P P
Cedars-Sinai Medical Center1, Johns Hopkins University2, Indiana University – Purdue University Indianapolis3, Washington University in St. Louis4, New York University5, Memorial Sloan Kettering Cancer Center6, Karolinska Institutet7, Marche Polytechnic University8, McMaster University9, University of Córdoba (Spain)10, University of Otago11, Queen Mary University of London12
TL;DR: This Special Article summarizes the overall recommendations made by the four working groups and is anticipated that this ISUP effort will be valuable to the entire practicing community in the appropriate use of IHC in diagnostic urologic pathology.
Abstract: Primary renal neoplasms comprise multiple distinct entities, some of which are well understood and others that are not. It is not uncommon for some of these entities to have overlapping morphologic features. Their clinical behavior is varied, ranging from highly malignant to benign, and metastatic renal cell carcinoma oftentimes enters into the differential diagnosis of tumors of unknown primary. In this age of personalized medicine, identifying biomarkers that can better predict clinical outcome and response to therapy is a pressing need. In 2013 the International Society of Urological Pathology held a meeting in which best practices recommendations on the use of immunohistochemical markers in urologic malignancies were discussed. In this review we make recommendations regarding immunohistochemical markers that are best suited to aid in establishing a diagnosis of renal primary, panels of antibodies that are most useful in classifying renal tumors, and the current status of prognostic and predictive biomarkers. Although no prognostic or predictive marker and set of markers have yet to be validated, ongoing research suggests that this fact is likely to change in the near future.
TL;DR: This work redefined deep-sea ecology and the role of Earth's largest biome in global biosphere functioning, and recognized greater habitat complexity, new ecological interactions and the importance of 'dark energy', and chemosynthetic production in fuelling biodiversity.
Abstract: Deep-sea ecosystems represent Earth's major ecological research frontier. Focusing on seafloor ecosystems, we demonstrate how new technologies underpin discoveries that challenge major ecological hypotheses and paradigms, illuminating new deep-sea geosphere–biosphere interactions. We now recognize greater habitat complexity, new ecological interactions and the importance of ‘dark energy’, and chemosynthetic production in fuelling biodiversity. We also acknowledge functional hotspots that contradict a food-poor, metabolically inactive, and minor component of global carbon cycles. Symbioses appear widespread, revealing novel adaptations. Populations show complex spatial structure and evolutionary histories. These new findings redefine deep-sea ecology and the role of Earth's largest biome in global biosphere functioning. Indeed, deep-sea exploration can open new perspectives in ecological research to help mitigate exploitation impacts.
TL;DR: Hyperoxia may be associated with increased mortality in patients with stroke, traumatic brain injury and those resuscitated from cardiac arrest, but results are limited by significant heterogeneity between studies.
Abstract: The safety of arterial hyperoxia is under increasing scrutiny. We performed a systematic review of the literature to determine whether any association exists between arterial hyperoxia and mortality in critically ill patient subsets. Medline, Thomson Reuters Web of Science and Scopus databases were searched from inception to June 2014. Observational or interventional studies evaluating the relationship between hyperoxia (defined as a supranormal arterial O2 tension) and mortality in adult intensive care unit (ICU) patients were included. Studies primarily involving patients with exacerbations of chronic pulmonary disease, acute lung injury and perioperative administration were excluded. Adjusted odds ratio (OR) of patients exposed versus those not exposed to hyperoxia were extracted, if available. Alternatively, unadjusted outcome data were recorded. Data on patients, study characteristics and the criteria used for defining hyperoxia exposure were also extracted. Random-effects models were used for quantitative synthesis of the data, with a primary outcome of hospital mortality. In total 17 studies (16 observational, 1 prospective before-after) were identified in different patient categories: mechanically ventilated ICU (number of studies (k) = 4, number of participants (n) = 189,143), post-cardiac arrest (k = 6, n = 19,144), stroke (k = 2, n = 5,537), and traumatic brain injury (k = 5, n = 7,488). Different criteria were used to define hyperoxia in terms of PaO2 value (first, highest, worst, mean), time of assessment and predetermined cutoffs. Data from studies on ICU patients were not pooled because of extreme heterogeneity (inconsistency (I2) 96.73%). Hyperoxia was associated with increased mortality in post-cardiac arrest patients (OR = 1.42 (1.04 to 1.92) I2 67.73%) stroke (OR = 1.23 (1.06 to 1.43) I2 0%) and traumatic brain injury (OR = 1.41 (1.03 to 1.94) I2 64.54%). However, these results are limited by significant heterogeneity between studies. Hyperoxia may be associated with increased mortality in patients with stroke, traumatic brain injury and those resuscitated from cardiac arrest. However, these results are limited by the high heterogeneity of the included studies.
TL;DR: Current information about the potential mechanisms involved in the effects elicited by strawberry polyphenols on human health are reviewed, devoting special attention to the latest findings.
Abstract: The usefulness of a diet rich in vegetables and fruits on human health has been widely recognized: a high intake of antioxidant and bioactive compounds may in fact play a crucial role in the preven...
TL;DR: A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study, and a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.
Abstract: In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.
French Institute of Health and Medical Research1, Paris Descartes University2, University of Turin3, Ludwig Maximilian University of Munich4, Pierre-and-Marie-Curie University5, Technische Universität München6, University of Padua7, Charité8, University of Würzburg9, University of Pisa10, Marche Polytechnic University11
TL;DR: Investigation of the prevalence of somatic mutations in aldosterone-producing adenomas in unselected patients with APA found that young women with APAs are more likely to be KCNJ5 mutation carriers; identification of specific characteristics or surrogate biomarkers of mutation status may lead to targeted treatment options.
Abstract: Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been described in aldosterone-producing adenomas (APAs). Our aim was to investigate the prevalence of somatic mutations in these genes in unselected patients with APA (n=474), collected through the European Network for the Study of Adrenal Tumors. Correlations with clinical and biochemical parameters were first analyzed in a subset of 199 patients from a single center and then replicated in 2 additional centers. Somatic heterozygous KCNJ5 mutations were present in 38% (180/474) of APAs, whereas ATP1A1 mutations were found in 5.3% (25/474) and ATP2B3 mutations in 1.7% (8/474) of APAs. Previously reported somatic CACNA1D mutations as well as 10 novel CACNA1D mutations were identified in 44 of 474 (9.3%) APAs. There was no difference in the cellular composition of APAs or in CYP11B2, CYP11B1, KCNJ5, CACNA1D, or ATP1A1 gene expression in APAs across genotypes. Patients with KCNJ5 mutations were more frequently female, diagnosed younger, and with higher minimal plasma potassium concentrations compared with CACNA1D mutation carriers or noncarriers. CACNA1D mutations were associated with smaller adenomas. These associations were largely dependent on the population structure of the different centers. In conclusion, recurrent somatic mutations were identified in 54% of APAs. Young women with APAs are more likely to be KCNJ5 mutation carriers; identification of specific characteristics or surrogate biomarkers of mutation status may lead to targeted treatment options.
TL;DR: Dietary habits, by increasing the percentage of intestinal Gram‐negative endotoxin producers, may accelerate liver fibrogenesis, introducing dysbiosis as a cofactor contributing to chronic liver injury in NAFLD.
TL;DR: Minimum energy (as photon) costs are predicted for core reactions of photosynthesis, for photorespiratory metabolism in algae lacking CO2 concentrating mechanisms (CCMs) and for various types of CCMs; in algae, withCCMs; allowance was made for leakage of CO2 from the internal pool.
Abstract: Minimum energy (as photon) costs are pre- dicted for core reactions of photosynthesis, for photore- spiratory metabolism in algae lacking CO2 concentrating mechanisms (CCMs) and for various types of CCMs; in algae, with CCMs; allowance was made for leakage of CO2 from the internal pool. These predicted values are just compatible with the minimum measured photon costs of photosynthesis in microalgae and macroalgae lacking or expressing CCMs. More energy-expensive photorespira- tion, for example for organisms using Rubiscos with lower CO2-O2 selectivity coefficients, would be less readily accommodated within the lowest measured photon costs of photosynthesis by algae lacking CCMs. The same applies to the cases of CCMs with higher energy costs of active transport of protons or inorganic carbon species, or greater allowance for significant leakage from the accu- mulated intracellular pool of CO2. High energetic efficiency can involve a higher concentration of catalyst to achieve a given rate of reaction, adding to the resource costs of growth. There are no obvious mechanistic inter- pretations of the occurrence of CCMs algae adapted to low light and low temperatures using the rationales adopted for the occurrence of C4 photosynthesis in terrestrial flowering plants. There is an exception for cyanobacteria with low- selectivity Form IA or IB Rubiscos, and those dinoflagel- lates with low-selectivity Form II Rubiscos, for which very few natural environments have high enough CO2:O2 ratios to allow photosynthesis in the absence of CCMs.
TL;DR: In this review, several tools including varietal and clonal choice, possible diversification of wines produced, suitable training system and rootstocks, traditional and innovative management techniques able to regulate a too much accelerated and/or unbalanced grape ripening process, will be presented and discussed.
TL;DR: A greater understanding of adipocyte transdifferentiation mechanisms would have the potential to shed light on their biology as well as inspire novel therapeutic strategies against metabolic syndrome (browning) and breast cancer (pinking).
Abstract: In mammals, adipocytes are lipid-laden cells making up the parenchyma of the multi-depot adipose organ. White adipocytes store lipids for release as free fatty acids during fasting periods; brown adipocytes burn glucose and lipids to maintain thermal homeostasis. A third type of adipocyte, the pink adipocyte, has recently been characterised in mouse subcutaneous fat depots during pregnancy and lactation. Pink adipocytes are mammary gland alveolar epithelial cells whose role is to produce and secrete milk. Emerging evidence suggests that they derive from the transdifferentiation of subcutaneous white adipocytes. The functional response of the adipose organ to a range of metabolic and environmental challenges highlights its extraordinary plasticity. Cold exposure induces an increase in the 'brown' component of the organ to meet the increased thermal demand; in states of positive energy balance, the 'white' component expands to store excess nutrients; finally, the 'pink' component develops in subcutaneous depots during pregnancy to ensure litter feeding. At the cell level, plasticity is provided not only by stem cell proliferation and differentiation but also, distinctively, by direct transdifferentiation of fully differentiated adipocytes by the stimuli that induce genetic expression reprogramming and through it a change in phenotype and, consequently function. A greater understanding of adipocyte transdifferentiation mechanisms would have the potential to shed light on their biology as well as inspire novel therapeutic strategies against metabolic syndrome (browning) and breast cancer (pinking).
TL;DR: In this article, a bottom-up statistical methodology based on a Geographical Information System (GIS) to estimate the energy consumption of residential stocks across an entire city is introduced.
TL;DR: In this article, the influence of land use change on landslide susceptibility was evaluated for a small study area located in the southern part of the Briga catchment, along the Ionian coast of Sicily (Italy).
Abstract: The spatial distribution of landslides is influenced by different climatic conditions and environmental settings including topography, morphology, hydrology, lithology, and land use. In this work, we have attempted to evaluate the influence of land use change on landslide susceptibility (LS) for a small study area located in the southern part of the Briga catchment, along the Ionian coast of Sicily (Italy). On October 1, 2009, the area was hit by an intense rainfall event that triggered abundant slope failures and resulted in widespread erosion. After the storm, an inventory map showing the distribution of pre-event and event landslides was prepared for the area. Moreover, two different land use maps were developed: the first was obtained through a semi-automatic classification of digitized aerial photographs acquired in 1954, the second through the combination of supervised classifications of two recent QuickBird images. Exploiting the two land use maps and different land use scenarios, LS zonations were prepared through multivariate statistical analyses. Differences in the susceptibility models were analyzed and quantified to evaluate the effects of land use change on the susceptibility zonation. Susceptibility maps show an increase in the areal percentage and number of slope units classified as unstable related to the increase in bare soils to the detriment of forested areas.
San Antonio River Authority1, University of Turin2, University of Eastern Piedmont3, University of Catania4, Sapienza University of Rome5, University of Rome Tor Vergata6, University of Padua7, University of Milan8, Casa Sollievo della Sofferenza9, University of Bari10, Marche Polytechnic University11, University of Bologna12
TL;DR: Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation and were significantly more frequent in the VMPT-VT patients.
Abstract: Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The...
TL;DR: An automatic, privacy-preserving, fall detection method for indoor environments, based on the usage of the Microsoft Kinect® depth sensor in an “on-ceiling” configuration, and on the analysis of depth frames, which shows the effectiveness of the proposed solution, even in complex scenarios.
Abstract: We propose an automatic, privacy-preserving, fall detection method for indoor environments, based on the usage of the Microsoft Kinect® depth sensor, in an “on-ceiling” configuration, and on the analysis of depth frames. All the elements captured in the depth scene are recognized by means of an Ad-Hoc segmentation algorithm, which analyzes the raw depth data directly provided by the sensor. The system extracts the elements, and implements a solution to classify all the blobs in the scene. Anthropometric relationships and features are exploited to recognize one or more human subjects among the blobs. Once a person is detected, he is followed by a tracking algorithm between different frames. The use of a reference depth frame, containing the set-up of the scene, allows one to extract a human subject, even when he/she is interacting with other objects, such as chairs or desks. In addition, the problem of blob fusion is taken into account and efficiently solved through an inter-frame processing algorithm. A fall is detected if the depth blob associated to a person is near to the floor. Experimental tests show the effectiveness of the proposed solution, even in complex scenarios.
TL;DR: The critical role of NOX in hepatic fibrogenesis provides a rationale to assess pharmacological NOX inhibitors that treat liver fibrosis in patients with chronic liver disease.
Abstract: Significance: Hepatic fibrosis is the common pathophysiologic process resulting from chronic liver injury, characterized by the accumulation of an excessive extracellular matrix. Multiple lines of evidence indicate that oxidative stress plays a pivotal role in the pathogenesis of liver fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a multicomponent enzyme complex that generates reactive oxygen species (ROS) in response to a wide range of stimuli. In addition to phagocytic NOX2, there are six nonphagocytic NOX proteins. Recent Advances: In the liver, NOX is functionally expressed both in the phagocytic form and in the nonphagocytic form. NOX-derived ROS contributes to various kinds of liver disease caused by alcohol, hepatitis C virus, and toxic bile acids. Recent evidence indicates that both phagocytic NOX2 and nonphagocytic NOX isoforms, including NOX1 and NOX4, mediate distinct profibrogenic actions in hepatic stellate cells, the main fibrogenic cell type in the liver. The critical role of NOX in hepatic fibrogenesis provides a rationale to assess pharmacological NOX inhibitors that treat hepatic fibrosis in patients with chronic liver disease. Critical Issues: Although there is compelling evidence indicating a crucial role for NOX-mediated ROS generation in hepatic fibrogenesis, little is known about the expression, subcellular localization, regulation, and redox signaling of NOX isoforms in specific cell types in the liver. Moreover, the exact mechanism of NOX-mediated fibrogenic signaling is still largely unknown. Future Directions: A better understanding through further research about NOX-mediated fibrogenic signaling may enable the development of novel anti-fibrotic therapy using NOX inhibition strategy. Antioxid. Redox Signal. 20, 2854–2872.
TL;DR: In this article, the authors used Remotely Operated Vehicle (ROV) surveys to assess the extent of fishing impacts on rocky substrata on four offshore banks between 70 and 280m depth in the Mediterranean Sea.
TL;DR: This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds from plant foods affect mitochondria functionality in healthy and pathological in vitro and in vivo models, paying particular attention to the pathways involved in mitochondrial biogenesis and apoptosis.
TL;DR: Several aging-related mitomiRs may play a direct role in controlling mitochondrial function by regulating mitochondrial protein expression, which could mediate the loss of mitochondrial integrity and function in aging cells, inducing or contributing to the inflammatory response and to age-related diseases.
TL;DR: The new epidemiology of CD is now characterized by an increase of new cases in the historical CD areas (northern Europe and the United States and more interestingly in a spread of the disease in new regions (Asian countries).
Abstract: The prevalence of celiac disease (CD) varies greatly, but several reports have shown that CD is increasing in frequency in different geographic areas The increase in prevalence can be partially attributed to the improvement in diagnostic techniques and disease awareness; however the equally well documented rise in incidence in the last 30-40 years cannot be so easily explained The new epidemiology of CD is now characterized by an increase of new cases in the historical CD areas (northern Europe and the United States) and more interestingly in a spread of the disease in new regions (Asian countries) A significant change in diet habits, particularly in gluten consumption as well as in infant feeding patterns are probably the main factors that can account for these new trends in CD epidemiology