Obesity and metabolic syndrome: clinical and therapeutic review

The recent ATP III classification defines metabolic syndrome as including ≥3 of the following characteristics: abdominal adiposity, atherogenic dyslipidemia, high blood pressure, and insulin resistance. In these patients the visceral fat may produce inflammatory cytochines that may account for an enhanced cardiovascular risk. The treatment of obese patients is complex and often ineffective: patients may initially reduce weight but subsequently regain or even increase it, according to the socalled “yo-yo syndrome”. Given the difficulties of treatment of patients with incresed BMI, visceral adiposity, or metabolic syndrome, a multidisciplinary approach to these patients may yield more frequent positive results. The different strategies that may be applied, in varying mix targeted to the individual patient, include diet, drugs, educational and psychological support and, in few selected cases, surgery

The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs): a review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

Introduction: Different DNA and RNA viruses exploit common strategies to support their persistence and replication in infected individuals. In particular, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause major health problems worldwide. These pathogens exert an immunosuppressive role by inducing the persistent activation of cyclooxygenase-2 (COX-2) and an increased synthesis of prostaglandin E2 (PGE2). The suppression of this proinflammatory network by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as a therapeutic approach to decrease viral replication. Materials and methods: In this review, the role of inflammation in the support of viral replication and NSAIDs and ketoprofen pharmacology are briefly discussed. In addition, studies that have investigated the use of NSAIDs for the treatment of HBV and HCV chronic hepatitis, which were identified by a systematic literature search of PubMed and MEDLINE, are reported. Results: To date, pegylated-interferon (PEG-IFN) and/or nucleot(s)ide analogues and PEG-IFN and ribavirin remain the standard therapy for HBV and HCV chronic hepatitis, respectively. Discussion: The use of NSAIDs in patients with chronic viral hepatitis has only a ''historical'' interest. Nevertheless, the possible usefulness of ketoprofen with PEG-IFN and ribavirin for HCVinfected patients, non-responders to standard therapy or with genotype 1, should be evaluated in future clinical studies

Severe exacerbations of chronic obstructive pulmonary disease: management with noninvasive ventilation on a general medicine ward

Introduction: Recent evidence suggests that, with a well-trained staff, severe exacerbations of chronic obstructive pulmonary disease (COPD) with moderate respiratory acidosis (pH > 7.3) can be successfully treated with noninvasive mechanical ventilation (NIMV) on a general respiratory care ward. We conducted an open prospective study to evaluate the efficacy of this approach on a general medicine ward. Material and methods: This study population consisted in 27 patients admitted to a general medicine ward (median nurse:patient ratio 1:12) December 1, 2004 May 31, 2006 for acute COPD exacerbation with hypercapnic respiratory failure and acidosis (arterial pH 45 mmHg). All received assist-mode NIMV (average 12 h / day) via oronasal masks (inspiratory pressure 10-25 cm H2O, expiratory pressure 4-6 cm H2O) to maintain O2 saturation at 90-95%. Treatment was supervised by an experienced pulmonologist, who had also provided specific training in NIMV for medical and nursing staffs (90-day course followed by periodic refresher sessions). Arterial blood pressure, O2 saturation, and respiratory rate were continuously monitored during NIMV. Based on baseline arterial pH, the COPD was classified as moderate (7.25-7.34) or severe (< 7.25). Results: In patients with moderate and severe COPD, significant improvements were seen in arterial pH after 2 (p < 0.05) and 24 h (p< 0.05) of NIMV and in the PaC02 after 24 hours (p < 0.05). Four (15%) of the 27 patients died during the study hospitalization (in-hospital mortality 15%), in 2 cases due to NIMV failure. For the other 23, mean long-term survival was 14.5 months (95% CI 10.2 to 18.8), and no significant differences were found between the moderate and severe groups. Over half (61%) the patients were alive 1 year after admission. Conclusions: NIMV can be a cost-effective option for management of moderate or severe COPD on a general medicine ward. Its proper use requires: close monitoring of ventilated subjects, optimum staff:patient ratio, well-trained staff dedicated to NIMV, and supervision by a pulmonologist with experience in NIMV. The treatment was effective at improving arterial blood gases in both groups of COPD patients. The severity of the COPD did not significantly affect length of hospital stay, in-hospital mortality, or long-term survival

INVESTIGATING PLATFORMS. A CRITICAL LEXICON

The aim of this article is to propose an interpretative grid and a critical lexicon through which it is possible to frame in theoretical and methodological terms the disruptions and tendencies of platform urbanism and the main platform labour challenges. The article is organized along seven keywords as a set of tools for expanding and enriching the current debate on these transformations. We will start framing main features of platforms in terms of space and time organization, and then consider their role in social infrastructure as well as their impact on labour organization, not only in terms of value production but also in terms of production of inequalities and resistances. Finally, we will highlight how political categories as sovereignty must be reconsidered due to platforms expansion.El objetivo de este artículo es proponer una retícula interpretativa y un léxico crítico a través de los cuales sea posible enmarcar en términos teóricos y metodológicos las disrupciones y tendencias del urbanismo de plataforma y los principales retos laborales de la plataforma. El artículo se organiza en torno a siete palabras clave como un conjunto de herramientas para ampliar y enriquecer el debate actual sobre estas transformaciones. Empezaremos enmarcando las principales características de las plataformas en términos de organización del espacio y el tiempo, y luego consideraremos su papel en la infraestructura social, así como su impacto en la organización del trabajo, no sólo en términos de producción de valor, sino también en términos de producción de desigualdades y resistencias. Por último, destacaremos cómo categorías políticas como la soberanía deben ser reconsideradas debido a la expansión de las plataformas

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies