Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

IN PRAISE OF ENLIGHTENED PARTICULARITY

Autor u svojoj studiji analizira odnos opće kulture i njenih posebnih segmenata unutar jedinstvene političke zajednice te zaključuje: dok god, dakle, postoje građani, postojat će i sukob između općega i posebnog, i pritom će se uvijek iznova pokazivati da posredovanje između te dvije kategorije nikada nije konačno, nego da uvijek iznova treba određivati što je primjereno, što je ono pravo i obvezujuće. U tome se očituje snaga prosuđivanja kojoj su shematske orijentacije poput univerzalizma i partikularizma potrebne samo da bi se ukazalo na ono što nedostaje, te da bi se to nadopunilo.In this study, the author analyses the relationship between general culture and its particularistic segments within the integral political community and concludes: as long as there are citizens, there will be a conflict between the general and the singular; also, the mediation between these two categories is never final; instead, one should repeatedly define what is appropriate, right and compulsory. This is the strength of the type of reasoning to which the schematic landmarks such as universalism and particularism are necessary only as reminders of what is missing in order to fill in the gaps

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America

Background & Aims: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. / Methods: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. / Results: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03–1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84–3.58) for Native American race vs European American race. / Conclusions: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment

Does administration of non-steroidal anti-inflammatory drug determine morphological changes in adrenal cortex: ultrastructural studies

Rofecoxib (Vioxx© made by Merck Sharp & Dohme, the USA) is a non-steroidal anti-inflammatory drug which belongs to the group of selective inhibitors of cyclooxygenasis-2, i.e., coxibs. Rofecoxib was first registered in the USA, in May 1999. Since then the drug was received by millions of patients. Drugs of this group were expected to exhibit increased therapeutic action. Additionally, there were expectations concerning possibilities of their application, at least as auxiliary drugs, in neoplastic therpy due to intensifying of apoptosis. In connection with the withdrawal of Vioxx© (rofecoxib) from pharmaceutical market, attempts were made to conduct electron-microscopic evaluation of cortical part of the adrenal gland in preparations obtained from animals under influence of the drug. Every morning animals from the experimental group (15 rats) received rofecoxib (suspension in physiological saline)—non-steroidal anti-inflammatory drug (Vioxx©, Merck Sharp and Dohme, the USA), through an intragastric tube in the dose of 1.25 mg during 8 weeks. In the evaluated material, there was found a greater number of secretory vacuoles and large, containing cholesterol and other lipids as well as generated glucocorticoids, lipid drops in cytoplasm containing prominent endoplasmic reticulum. There were also found cells with cytoplasm of smaller density—especially in apical and basal parts of cells. Mitochondria occasionally demonstrated features of delicate swelling. The observed changes, which occurred on cellular level with application of large doses of the drug, result from mobilization of adaptation mechanisms of the organism

Gut Microbiota Is a Key Modulator of Insulin Resistance in TLR 2 Knockout Mice

A genetic and pharmacological approach reveals novel insights into how changes in gut microbiota can subvert genetically predetermined phenotypes from lean to obese

Pharmacological inhibition of ABCC3 slows tumour progression in animal models of pancreatic cancer

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive and lethal disease, lacking effective therapeutic approaches. Available therapies only marginally prolong patient survival and are frequently coupled with severe adverse events. It is therefore pivotal to investigate novel and safe pharmacological approaches. We have recently identified the ABC transporter, ABCC3, whose expression is dependent on mutation of TP53, as a novel target in PDAC. ABCC3-mediated regulation of PDAC cell proliferation and tumour growth in vivo was demonstrated and was shown to be conferred by upregulation of STAT3 signalling and regulation of apoptosis. METHODS: To verify the potential of ABCC3 as a pharmacological target, a small molecule inhibitor of ABCC3, referred to here as MCI-715, was designed. In vitro assays were performed to assess the effects of ABCC3 inhibition on anchorage-dependent and anchorage-independent PDAC cell growth. The impact of ABCC3 inhibition on specific signalling pathways was verified by Western blotting. The potential of targeting ABCC3 with MCI-715 to counteract PDAC progression was additionally tested in several animal models of PDAC, including xenograft mouse models and transgenic mouse model of PDAC. RESULTS: Using both mouse models and human cell lines of PDAC, we show that the pharmacological inhibition of ABCC3 significantly decreased PDAC cell proliferation and clonal expansion in vitro and in vivo, remarkably slowing tumour growth in mice xenografts and patient-derived xenografts and increasing the survival rate in a transgenic mouse model. Furthermore, we show that stromal cells in pancreatic tumours, which actively participate in PDAC progression, are enriched for ABCC3, and that its inhibition may contribute to stroma reprogramming. CONCLUSIONS: Our results indicate that ABCC3 inhibition with MCI-715 demonstrated strong antitumor activity and is well tolerated, which leads us to conclude that ABCC3 inhibition is a novel and promising therapeutic strategy for a considerable cohort of patients with pancreatic cancer

New constraints on tectonism and magmatism from the eastern sector of the Trans-Mexican Volcanic Belt (Chignahuapan Horst, Puebla, México)

The Quaternary Acoculco (<2.7 my) and Los Humeros (<46 ky) calderas, located in the eastern sector of the Trans-Mexican Volcanic Belt (TMVB), are separated by a regional structure known as the Chignahuapan Horst (ChH). The tectonic and magmatic evolution of the ChH comprises four stages: 1) Upper Cretaceous-Paleocene Laramide orogeny, related to the deformation of sedimentary successions; 2) a sedimentary hiatus followed by the initial stage of the TMVB (Middle Miocene); 3) a Miocene NE-SW oriented extension responsible for the NW-SE normal faults that controlled the volcanic processes and the emplacement of calc-alkaline magmas that formed the Aquixtla sequence; 4) a magmatic hiatus prolonged until 1.6 ± 0.15 my; 5) Pliocene-Quaternary normal faults controlled the emplacement of tholeiitic-transitional magmas and the monogenetic volcanism distribution that formed the Apizaco-Chignahuapan sequence. Coevally to the Miocene NE-SW and Pliocene-Quaternary NW-SE tectonic extensional phases, NE-SW and NW-SE transfer faults were developed. NE-SW normal faults and NW-SE strike-slip faults correspond to fault systems optimally oriented with the current stress field, thus, these faults can be considered as potentially active structures controlling magma emplacement and the distribution of volcanic structures at the surface

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial

Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Delta Control: -22.2 +/- 52.6 ml; Delta MOD-EX: -15.5 +/- 62.1 ml, Delta VIG-EX: -6.8 +/- 66.4 ml; P = 0.771) or F-18-fluorodeoxyglucose uptake (SUVpeak Delta Control: -2.6 +/- 3.1 ml; Delta MOD-EX: -1.2 +/- 4.8, Delta VIG-EX: -2.2 +/- 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.Exercise modulates brown adipose tissue (BAT) metabolism in murine models. Here the authors report that there is no evidence that 24 weeks of supervised exercise training modulates BAT volume or function in young sedentary adults in the ACTIBATE randomized controlled trial.Diabetes mellitus: pathophysiological changes and therap

Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics

1. We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip). 2. Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation. 3. Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t(1/2) of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole. 4. Using the fluorescent probe 5 (and 6)-carboxy-2′,7′-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice. 5. These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones