Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Epigenetics of Autoimmune Diseases

This chapter provides several examples of epigenetic deregulation in autoimmune diseases, a heterogeneous group of human conditions characterized by a deregulated immune response against the body own organs and tissues. Early studies based on the candidate gene approach have been flanked by genomewide screenings in the last few years, revealing global changes in DNA methylation or histone tail modifications, as well as deregulated methylation and/or expression of hundreds of genes and microRNAs in cells from patients affected by those disorders. This chapter will focus on epigenetic deregulations observed in systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, psoriasis, multiple sclerosis, systemic sclerosis, and autoimmune thyroid diseases, even though epigenetic modifications are increasingly being observed in many other autoimmune diseases. By contrast, only a few environmental factors have been shown or suspected to induce the observed epigenetic changes. Epigenetic drugs and RNA silencing experiments have often reversed autoimmune disease-like phenotypes in rodents or cell cultures, leading researchers to debate on their potential use in the treatment of these human conditions

Biomarkers, genetic association, and genomic studies

Rheumatoid arthritis (RA) is a common autoimmune disorder which shows clinical heterogeneity. IT has multiple treatment options and there is individual variation in response to treatment. These features make RA an ideal condition to develop biomarkers for its pre-clinical detection, diagnosis, subtyping, prognostic stratification and selection of most optimal treatment. While a number of markers have been assessed for their biomarker quality, currently no marker has the statistical properties of a biomarker to be considered as a good classifier. In this chapter, a general review of biomarkers is followed by a detailed discussion of biomarker candidates for various aspects of RA. It is unlikely that a single marker will ever be sufficiently powerful as a biomarker, but combinations of clinical, biochemical, genetic, epigenetic, proteomic and metabolomic markers have the strongest potential to fulfill the requirements of biomarkers. Given the high heritability of RA and the progress in methodology of genome-wide association studies, genetic markers are the most promising group to be developed as biomarkers, in particular when epigenetic markers become more widely used. It is possible that in the near future, biomarkers with documented clinical utility will be available for use in clinical decision making and will most probably use multiple omics platforms

Peptide Synthesis Using Proteases as Catalyst

Proteolytic enzymes (proteases) comprise a group of hydrolases (EC 3.4, NC-IUBMB) which share the common feature of acting on peptide bonds. Proteases are among the best studied enzymes in terms of structure-function relationship (Krowarsch et al., 2005). Proteases, by catalyzing the cleavage of other proteins and even themselves, have an enormous physiological significance, their coding genes representing as much as 2% of the total human genome (Schilling and Overall, 2008).Proteases, together with lipases, represent the most important family of enzymes at industrial level, accounting for well over 50% of the enzyme market (Feijoo-Siota and Villa, 2011). Proteases have been used industrially since the onset of enzyme technology in the first decades of the 20th century; many of the early patents issued for the use of enzymes with commercial purposes were proteases, mostly from plant (papain, bromelain) and animal (trypsin, pepsin) origin. Intended uses were in brewing and in leather and rubber manufacturing (Neidelman, 1991). In the decades that follow many large-scale industrial processes were developed using now mostly microbial proteases. A common feature of them was the degradation of proteins and most relevant areas of applications were the food and beverage (Sumantha et al., 2006), detergent (Maurer 2004), leather (Foroughi et al., 2006) and pharmaceutical sectors (Monteiro de Souza et al., 2015). Acid and neutral proteases are relevant to the food industry for the production of protein hydrolyzates (Nielsen and Olsen, 2002), beer chill-proofing (Monsan et al., 1978), meat tenderization (Ashie et al., 2002) and above all, for cheese production (Kim et al., 2004). Alkaline proteases are of paramount importance for the detergent industry (Sellami-Kamoun et al., 2008) and also in tannery (Varela et al., 1997; Thanikaivelan, 2004) and fish-meal production (Schaffeld et al., 1989; Chalamaiah et al., 2012). These conventional applications are by no means outside of continuous technological development (Monteiro de Souza et al. 2015). This is illustrated by the optimization of detergent enzyme performance under the harsh conditions of laundry at high and low temperatures, which has been a continuous challenge tackled by the construction of subtilisin (alkaline protease) variants by random and site-directed mutagenesis and by directed evolution (Kirk et al., 2002; Jares Contesini et al., 2017). It is also illustrated by the production of chymosin in microbial hosts by recombinant DNA technology and further improvement by protein engineering (Mohanty et al., 1999). Therapeutic application of proteases acting as protein hydrolases goes from conventional digestive-aids and anti-inflammatory agents to more sophisticated uses as trombolytic drugs (i.e. urokinase and tissue plasminogen activator) and more recently for the treatment of haemophilia. A comprehensive review on the therapeutic uses of proteases is suggested for the interested reader (Craik et al., 2011)The potential of hydrolytic enzymes for catalyzing reverse reactions of bond formation has been known for quite some time. However, its technological potential as catalysts for organic synthesis developed in the 1980s (Bornscheuer and Kazlauskas, 1999) paralleling the outburst of biocatalysis in non-conventional (non-aqueous) media (Illanes, 2016).Proteases can not only catalyze the cleavage of peptide bonds but, in a proper reaction medium, they can also catalyze the reaction of peptide bond formation. Proteases are highly stereo- and regiospecific, active under mild reaction conditions, do not require coenzymes and are readily available as commodity enzymes, these properties making them quite attractive catalysts for organic synthesis (Bordusa, 2002; Kumar and Bhalla, 2005). Such reactions will not proceed efficiently in aqueous medium where the hydrolytic potential of the enzyme will prevail, so reaction media at low, and hopefully controlled, water activity is necessary for peptide synthesis. This is a major threat since proteases, different from lipases, are not structurally conditioned to act in such environments. The use of proteases in peptide synthesis is analyzed in depth in section 3.4.Fil: Barberis, Sonia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis; ArgentinaFil: Adaro, Mauricio Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis; ArgentinaFil: Origone, Anabella Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis; ArgentinaFil: Bersi, Grisel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis; ArgentinaFil: Guzman, Fanny. Pontificia Universidad Catolica de Valparaiso. Escuela de Ingeniería Bioquímica; ChileFil: Illanes, Andres. Pontificia Universidad Catolica de Valparaiso. Escuela de Ingeniería Bioquímica; Chil

Kuluttajabarometri maakunnittain 2000, 2. neljännes

Suomen virallinen tilasto (SVT

Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery

This was an investigator-initiated study funded by Nestle Health Sciences through an unrestricted research grant and by a National Institute for Health Research (UK) Professorship held by R.P. The study was sponsored by Queen Mary University of London