Evaluation and management of emergencies in the patient with cirrhosis.

The approach to and management of critically ill patients is one of the most versatile themes in emergency medicine. Patients with cirrhosis of the liver have characteristics that are inherent to their disease that can condition modification in acute emergency treatment. Pathophysiologic changes that occur in cirrhosis merit the implementation of an analysis as to whether the overall management of a critically ill patient can generally be applied to patients with cirrhosis of the liver or if they should be treated in a special manner. Through a review of the medical literature, the available information was examined, and the evidence found on the special management required by those patients was narratively synthesized, selecting the most representative decompensations within chronic disease that require emergency treatment.

Nuclear Factor Erythroid 2-Related Factor 2 in Vitiligo. / Factor nuclear eritroide similar al factor 2 en el vitíligo.

Vitiligo is a pigmentary disorder, in which oxidative stress has been evidenced as part of the pathogenesis. Pathways responsible for protecting melanocytes from damage caused by reactive oxygen species are known as the nuclear factor erythroid factor 2 (Nrf2) pathway. Nrf2 is a transcription factor that remains inhibited when the organism is in homeostasis, but in the presence of oxidative stress it allows the encoding of phase ii antioxidant enzymes. In vitiligo there are abnormalities in the location and function of Nrf2 as well as polymorphisms that increase the risk of this disease. Currently, multiple molecules that act on Nrf2 have been investigated in order to find useful emerging treatments for vitiligo. A search for articles in Spanish and English was carried out in the PubMed, Ovid, Scopus and Web of Science Clarivate databases, using the keywords "Vitiligo AND nuclear factor erythroid derived 2 like 2 OR NRF2" without time restriction. All in vitro studies, narrative reviews, case series, cohort studies, and randomized and non-randomized clinical trials that specifically addressed the issue of Nrf2 associated with vitiligo were included.

Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain.

BACKGROUND: Prenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology. However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program. RESULTS: Using a pre-clinical in vivo mouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormal de novo DNA methylation profiles in various biological pathways (e.g., neural/brain development). CONCLUSION: These findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD.

The RESPECT trial-Replacement of peripheral intravenous catheters according to clinical reasons or every 96 hours: A randomized, controlled, non-inferiority trial.

BACKGROUND: Peripheral intravenous catheters are widely used for infusion therapy. To prevent phlebitis, routine catheter replacement at 72 or 96 hours remains widely practiced. OBJECTIVE: To investigate the non-inferiority of clinically indicated peripheral intravenous catheter replacement compared with routine replacement every 96 hours to prevent phlebitis. Phlebitis severity, catheter indwelling time, and other catheter failure types were also compared. SETTING: Multi-center trial in wards at two hospitals in Sao Paulo, Brazil. DESIGN: The REplacement of PEripheral intravenous CaTheters according to clinical signs or every 96 hours (RESPECT) trial was a Randomized, non-blinded, controlled, non-inferiority trial. PARTICIPANTS: 1319 patients were enrolled with the following inclusion criteria: aged ≥18 years, expected peripheral intravenous therapy for ≥96 hours; peripheral intravenous catheters inserted in the selected wards, intensive care units, or surgical centers; and informed consent provided. Exclusion criteria were: bloodstream infection and/or sepsis, neutrophil count of ≤1000/mm3, and simultaneous use of more than one peripheral intravenous catheter. Recruitment occurred within 96 hours of peripheral intravenous catheter insertion. Randomization was performed using a computer-generated, concealed list. METHODS: As intervention, clinically indicated replacement group patients underwent peripheral intravenous catheter removal only at the end of therapy or in the presence of phlebitis, infiltration, occlusion, displacement, accidental removal, or bloodstream infection. Routine 96-h replacement group patients (control) had their catheters replaced every 96-h, unless clinical reasons required earlier replacement. The primary outcome was Phlebitis and the analyses were carried out on intention-to-treat and per-protocol bases. RESULTS: Demographic and clinical variables were similar between groups, with the exception to type of admission (p = 0.025) more frequent in clinically indicated patients and surgical on routine replacement group. Of the 1319 patients, 119 (9.0%) developed phlebitis with no between-group difference (p = 0.162); these patients used 2747 peripheral intravenous catheters, being that 134 presented phlebitis. Phlebitis/1000 catheter-days, was 14.9 in the clinically indicated group and 23.8 in the routine replacement group (p = 0.006). The survival analysis showed no significant between-group difference in the occurrence of the first phlebitis episode. CONCLUSIONS: Clinically indicated peripheral intravenous catheter replacement was not inferior to routine (96 hours) replacement regarding phlebitis occurrence, and was associated with significantly less phlebitis per 1000 days. TRIAL REGISTRATION: Registered with www.clinicaltrials.gov (NCT02568670).

Hypertrophy-type Resistance Training Improves Phase Angle in Young Adult Men and Women.

The main purpose of the present study was to investigate the effect of a hypertrophy-type resistance training protocol on phase angle, an indicator of cellular integrity, in young adult men and women. 28 men (22.2±4.3 years, 67.8±9.0 kg and 174.2±6.8 cm) and 31 women (23.2±4.1 years, 58.7±12.1 kg and 162.7±6.4 cm) underwent a progressive RT for 16 weeks (2 phases, 8 weeks each), 3 times per week, consisting of 10 to 12 whole body exercises with 3 sets of 8-12 repetitions maximum. Phase angle, resistance, reactance and total body water (intra and extracellular water compartments) were assessed by bioimpedance spectroscopy (Xitron 4200 Bioimpedance Spectrum Analyzer). Total body water, intracellular water and phase angle increased significantly (P<0.05) in men (7.8, 8.3, and 4.3%, respectively) and women (7.6, 11.7, and 5.8% respectively), with no significant difference between sexes (P>0.05). Bioimpedance resistance decreased (P<0.05) similarly in both sex (men=-4.8%, women=-3.8%). The results suggest that regardless of sex, progressive RT induces an increase in phase angle and a rise in cellular hydration.

Ultrasound-targeted hepatic delivery of factor IX in hemophiliac mice.

Ultrasound-targeted microbubble destruction (UTMD) was used to direct the delivery of plasmid and transposase-based vectors encoding human factor IX (hFIX) to the livers of hemophilia B (FIX-/-) mice. The DNA vectors were incorporated into cationic lipid microbubbles, injected intravenously, and transfected into hepatocytes by acoustic cavitation of the bubbles as they transited the liver. Ultrasound parameters were identified that produced transfection of hepatocytes in vivo without substantial damage or bleeding in the livers of the FIX-deficient mice. These mice were treated with a conventional expression plasmid, or one containing a piggyBac transposon construct, and hFIX levels in the plasma and liver were evaluated at multiple time points after UTMD. We detected hFIX in the plasma by western blotting from mice treated with either plasmid during the 12 days after UTMD, and in the hepatocytes of treated livers by immunofluorescence. Reductions in clotting time and improvements in the percentage of FIX activity were observed for both plasmids, conventional (4.15±1.98%), and transposon based (2.70±.75%), 4 to 5 days after UTMD compared with untreated FIX (-/-) control mice (0.92±0.78%) (P=0.001 and P=0.012, respectively). Reduced clotting times persisted for both plasmids 12 days after treatment (reflecting percentage FIX activity of 3.12±1.56%, P=0.02 and 3.08±0.10%, P=0.001, respectively). Clotting times from an additional set of mice treated with pmGENIE3-hFIX were evaluated for long-term effects and demonstrated a persistent reduction in average clotting time 160 days after a single treatment. These data suggest that UTMD could be a minimally invasive, nonviral approach to enhance hepatic FIX expression in patients with hemophilia.

Dioxins, furans, biphenyls, arsenic, thorium and uranium in natural and anthropogenic sources of phosphorus and calcium used in agriculture.

The aim of this study was to assess the presence of dioxins, furans and biphenyls, and the inorganic contaminants such as arsenic (As), thorium (Th) and uranium (U) in three main products used in Agriculture in Brazil: feed grade dicalcium phosphate, calcined bovine bone meal and calcitic limestone. The first two are anthropogenic sources of phosphorus and calcium, while calcitic limestone is a natural unprocessed mineral. Regarding to dioxin-like substances, all samples analyzed exhibited dioxins (PCDD) and furans (PCDF) and dioxin-like polychlorinated biphenyls (dl-PCBs) concentrations below limit of detection (LOD). In general, achieved is in accordance with regulation in Brazil where is established a maximum limit in limestone used in the citric pulp production (0.50pg WHO-TEQ g(-1)). In addition, reported data revealed very low levels for limestone in comparison with similar materials reported by European legislation. As result for toxic metals, achieved data were obtained using Instrumental Neutron Activation Analysis (INAA). On one hand, limestone sample exhibits the largest arsenic concentration. On another hand, dicalcium phosphate exhibited the largest uranium concentration, which represents a standard in animal nutrition. Therefore, it is phosphorus source in the animal feed industry can be a goal of concern in the feed field.

Bright solitons from the nonpolynomial Schrödinger equation with inhomogeneous defocusing nonlinearities.

Extending the recent work on models with spatially nonuniform nonlinearities, we study bright solitons generated by the nonpolynomial self-defocusing (SDF) nonlinearity in the framework of the one-dimensional (1D) Muñoz-Mateo-Delgado (MM-D) equation (the 1D reduction of the Gross-Pitaevskii equation with the SDF nonlinearity), with the local strength of the nonlinearity growing at |x|→∞ faster than |x|. We produce numerical solutions and analytical ones, obtained by means of the Thomas-Fermi approximation, for nodeless ground states and for excited modes with one, two, three and four nodes, in two versions of the model, with steep (exponential) and mild (algebraic) nonlinear-modulation profiles. In both cases, the ground states and the single-node ones are completely stable, while the stability of the higher-order modes depends on their norm (in the case of the algebraic modulation, they are fully unstable). Unstable states spontaneously evolve into their stable lower-order counterparts.

Changes in skeletal muscle mass assessed by anthropometric equations after resistance training.

The aim of this study was to analyze the validity of anthropometric equations to identify changes in skeletal muscle mass (SMM) after resistance training (RT). Anthropometric and dual energy x-ray absorptiometry (DXA) measurements were obtained at baseline and after RT in 15 trained Caucasian college men. Participants performed RT over 8 weeks, consisting of 8-9 exercises of 4 sets with 12/10/8/6 maximal repetitions and 1-2 min interval between sets. The training loads were gradually increased according to gains in muscular strength. 4 anthropometric equations were used for estimation of SMM: EQ1 (SMM, g=height×[0.0553×corrected thigh girth2 + 0.0987×forearm girth2 + 0.0331×corrected calf girth2] - 2445), EQ2 (SMM, g=height×[0.031×medial thigh girth2 + 0.064×corrected calf girth2 + 0.089×corrected arm girth2] - 3006), EQ3 (SMM, kg=height×[0.00744×corrected arm girth2 + 0.00088×corrected thigh girth2 + 0.00441×corrected calf girth2] + 2.4×gender - 0.048×age + race + 7.8) and EQ4 (SMM, kg=0.244×weight + 7.8×height + 6.6×gender - 0.098×age + race - 3.3). EQ1 and EQ2 overestimated the SMM (41.3% and 19.9%, respectively; P<0.05) while EQ3 and EQ4 were similar (P>0.05) to DXA at baseline. Although all equations and DXA revealed a significant increase in SMM after RT, changes were overestimated by EQ1 and EQ2 (P<0.05), but not by EQ3 and EQ4 (P>0.05). In addition, changes in SMM over time between EQ4 and DXA were significantly correlated (r=0.62; P<0.01). Thus, changes in SMM that occur after RT can be detected by EQ4 in trained young men.

Modulation of localized solutions in a system of two coupled nonlinear Schrödinger equations.

In this work we study localized solutions of a system of two coupled nonlinear Schrödinger equations, with the linear (potential) and nonlinear coefficients engendering spatial and temporal dependencies. Similarity transformations are used to convert the nonautonomous coupled equations into autonomous ones and we use the trial orbit method to help us solving them, presenting solutions in a general way. Numerical experiments are then used to verify the stability of the localized solutions.

One-dimensional reduction of the three-dimenstional Gross-Pitaevskii equation with two- and three-body interactions.

We deal with the three-dimensional Gross-Pitaevskii equation which is used to describe a cloud of dilute bosonic atoms that interact under competing two- and three-body scattering potentials. We study the case where the cloud of atoms is strongly confined in two spatial dimensions, allowing us to build an unidimensional nonlinear equation,controlled by the nonlinearities and the confining potentials that trap the system along the longitudinal coordinate. We focus attention on specific limits dictated by the cubic and quintic coefficients, and we implement numerical simulations to help us to quantify the validity of the procedure.

New data on the ecology and geographic distribution of Saguinus inustus Schwarz, 1951 (Primates, Callitrichidae).

Saguinus inustus (Schwarz, 1951) is one of the neotropical primates least studied. The distribution of the species ranges from the north of the Solimões River, between the Negro and Japurá Rivers in Brazil, and Guayabero-Guaviare Rivers in Colombia. Nevertheless, due to the low number of specimens collected from the lower Japurá and lower Negro Rivers areas, the geographic distribution is so far poorly delineated. In this study, field data was composed of sightings and the collection of specimens during a survey of mammal diversity in the Amana Sustainable Development Reserve (ASDR). For this survey, two 40-day expeditions were carried out in 2004. The first one occurred during the flooded season in June and July, and the second was during the peak of the dry season in October. Direct sightings were made through hiking along transects, navigation along water channels with a 30-hp speedboat, and gliding along flooded trails in the forest. New records of S. inustus were made in 11 different localities in ASDR. The study has confirmed the presence of the species in the Amanã area, carrying out the first records of the species in flooded forest habitats.

Modulation of breathers in the three-dimensional nonlinear Gross-Pitaevskii equation.

In this paper we present analytical breather solutions of the three-dimensional nonlinear generalized Gross-Pitaevskii equation. We use an Ansatz to reduce the three-dimensional equation with space- and time-dependent coefficients into a one-dimensional equation with constant coefficients. The key point is to show that both the space- and time-dependent coefficients of the nonlinear equation can contribute to modulate the breather excitations. We briefly discuss the experimental feasibility of the results in Bose-Einstein condensates.

Solitons with cubic and quintic nonlinearities modulated in space and time.

This work deals with soliton solutions of the nonlinear Schrödinger equation with cubic and quintic nonlinearities. We extend the procedure put forward in a recent paper [J. Belmonte-Beitia, Phys. Rev. Lett. 100, 164102 (2008)], and we solve the equation in the presence of a linear background and cubic and quintic interactions which are modulated in space and time. As a result, we show how a simple parameter can be used to generate brightlike or darklike localized nonlinear waves which oscillate in several distinct ways, driven by the space and time dependence of the parameters that control the trapping potential and the cubic and quintic nonlinearities.

The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel.

Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the closed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.