Eight-day-old male Wistar rats were divided into two groups: sali

Eight-day-old male Wistar rats were divided into two groups: saline-control (C) and morphine-treated (M). Naive animals were housed in home cages made of Plexiglas (65 cm × 25 cm × 15 cm) find more with sawdust covering the floor. Animals

were maintained on a standard 12-h dark/light cycle (lights on between 0700 h and 1900 h) at room temperature (22 ± 2 °C). The animals had free access to food and water. At birth, the litters were standardized to contain up to 8 pups per dam, and the pups remained with their mothers until 21 days of age. Rats at P8 were chosen because it is accepted that animals of this age are at a similar stage of neurological development to that of a human newborn (Fitzgerald and Anand, 1993). It is also accepted

that they are in a physiologically immature state (Pattinson and Fitzgerald, 2004) since this period is characterized by major developmental changes in the brain and plasticity of the Fulvestrant cell line developing pain system (Bishop, 1982, Kim et al., 1996 and Rabinowicz et al., 1996). Animal handling and all experiments were performed in accordance with international guidelines for animal welfare. The protocol of this experimental study was approved by the Ethics Committee of the institution where the work was conducted. Each animal received saline (control group) or morphine (5 μg s.c. in the mid-scapular area; morphine group) starting at P8, then once a day for 7 days. This dose had been chosen based on a previous study by Rozisky et al., 2008 and Rozisky et al., 2010, and Cyclin-dependent kinase 3 it produced analgesia in all animals submitted to the tail-flick test. All treatments were administered at the same time each day (1100 h). One milliliter of morphine sulphate (Dimorf® 10 mg/ml, obtained from Cristália, Porto Alegre, Rio

Grande do Sul, Brazil) was diluted in 9 ml of 0.9% NaCl (saline). The formalin test was performed in 16-, 30-, and 60-day-old rats (Fig. 1). The number of animals used per group was 8 to 15. At the ages where we observed significant differences in the nociceptive behavior in the formalin test, the control and morphine groups were subdivided into four groups, each one designed to evaluate the effect of i.p. administration of an NMDA receptor antagonist or non-steroidal anti-inflammatory drug (NSAID), applied 30 min before the formalin test: (1) non-steroidal anti-inflammatory drug: 10 mg/kg of indomethacin (Indomethacin®, obtained from Sigma-Aldrich, São Paulo, Brazil) (Bastos et al., 2004) diluted in 1.29% sodium bicarbonate solution (control-indomethacin, morphine-indomethacin); (2) vehicle for indomethacin (vehicle I): 10 mg/kg of 1.29% sodium bicarbonate solution (pH = 7.4) (control-vehicle I, morphine-vehicle I); (3) NMDA receptor antagonist: 30 mg/kg of ketamine (Cetamine®, obtained from Hospital de Clínicas de Porto Alegre, Brazil) (Campos et al., 2006) diluted in 0.

Não foi objetivo avaliar o esvaziamento gástrico ou velocidade de

Não foi objetivo avaliar o esvaziamento gástrico ou velocidade de trânsito colônico (fig. 5). Dos 40 animais iniciais, 34 chegaram ao final do experimento. Duas mortes, uma em cada grupo, foram causadas por falsa via na gavagem. Três animais

morreram apresentando insuficiência respiratória Linsitinib prévia, complicação frequente devido à ação da amônia resultante da decomposição dos excrementos, conforme relatado por Ribeiro40. Em apenas um animal não encontramos causa explicável para sua morte. A medição do tubo digestivo pela cintilografia mostrou que o marcador radioativo percorreu menos o trato gastrointestinal no grupo experimental (86,9 ± 12,6 cm) em relação ao grupo controle (93,1 ± 9,1 cm), não ocorrendo diferença significante (p = 0,1). Em nenhum dos

34 tubos digestivos submetidos à avaliação cintilográfica foi notada a presença do traçador no ceco. Outro detalhe que nos chamou atenção foi que em somente 6 animais do grupo experimental houve percurso de mais de 75% da extensão do tubo digestivo, contra 11 animais do grupo controle, no tempo de uma hora após a administração do marcador. Alguns autores, em experimentos com animais, mostraram a ação do tegaserode sobre a motilidade intestinal. Jin et al.27 observaram efeito propulsivo da droga em cólon de porcos‐da‐índia em doses menores que 1 μM, mas em concentrações maiores não relataram tal efeito. Nguyen et al.25 estudaram motilidade colônica de cães, em 2 dias de experimento, administrando Trametinib via endovenosa dosagens de 0,03, 0,1 e 0,3 mg/kg de tegaserode.

Encontraram pouca alteração no trânsito gástrico e do intestino delgado, mas perceberam aceleração no trânsito do intestino grosso após uma hora de administração. Também neste estudo relataram que a menor dose apresentou melhor efeito nas contrações colônicas pós‐prandiais. Nossos resultados apresentam algumas variações comparadas aos estudos anteriores. A administração do marcador radioativo foi realizada sem problemas, conforme discutido adiante, não tendo interferência direta no resultado. O nosso experimento Rebamipide teve duração maior do que os trabalhos citados. Podemos tentar justificar a falta de aceleração do trânsito por uma provável dessensibilização do receptor 5‐HT4, diminuindo a ação do tegaserode no intestino, embora Camilleri5 em revisão de literatura tenha citado um estudo onde mais de 300 pacientes chegaram a utilizar a medicação por mais de 330 dias, sem relato de tolerância à droga. A dose utilizada em nosso trabalho foi 0,03 mg/ml ou 0,09 mg/kg, portanto em concentração ideal para produzir os efeitos no trato gastrointestinal. Em síntese, no presente estudo não evidenciamos aceleração do trânsito intestinal uma hora após a administração do marcador por gavagem, na dose de 0,09 mg/kg.

67 × 1012 m2, cp equal to 4200 J(kg °C)− 1, and calculating the l

67 × 1012 m2, cp equal to 4200 J(kg °C)− 1, and calculating the long-term mean in- and outflows and associated temperatures from the model (Qin, Tin, Qout, Tout = 1.16 × 106 m3 s− 1, 18.1 °C, 1.14 × 106 m3 s− 1 15.32 ° C), we obtain an average Floss of 9 W m− 2; this is in accordance with the value presented in Table 2 and indicates that the net heat loss at the surface was compensated for by the heat transported through the Sicily Channel. Finally, to evaluate the modelling approach, the heat and salt contents of the whole EMB water column changes were simulated using the PROBEEMB model and compared

with observations from the MEDAR ocean database (Figure 16). The comparison indicates a close correlation, with the calculated total heat content deviating approximately 1% from the MEDAR value. For the salt SAHA HDAC cell line content, the modelled value deviates by less than 0.3% from the MEDAR value. The PROBE-EMB can realistically reproduce the water and heat balances of the EMB. The connection between atmospheric conditions over the Mediterranean Basin and the large-scale atmospheric circulation in the Northern Hemisphere is generally strong, for example, as represented by the North Atlantic Oscillation (NAO). There is a

significant link (R = 0.45, n = 52) between winter precipitation over the EMB and the NAO (data not shown Bafilomycin A1 ic50 but available from the National Oceanic and Atmospheric Administration – NOAA – database). Moreover, there is a link (R = 0.3, n = 52) between winter NAO and winter evaporation. Wet (dry) winters are associated with positive (negative) NAO index values. On the other hand, negative (positive) NAO index

values are associated with increased (decreased) evaporation rates in the winter. Changes in the NAO index greatly affect the winter water and heat balances of the EMB, which is in agreement with, for example, the results of Turkes, 1996a and Turkes, selleck chemicals llc 1996b. The study analyses the large-scale features of the EMB using ocean modelling and available meteorological and hydrological datasets. Local features (e.g., the Eastern Mediterranean Transient, EMT) are therefore not included. It is a budget-type method building on horizontal averaging, i.e. strong local forcing might trigger convections that reach the bottom, while the same forcing averaged over the whole basin may have a minor influence. In the future, we will model the EMB as a number of sub-basins and also address local EMB features that may influence the water and heat balances. For example, the Southern Aegean Basin is significantly affected by deep water formation and needs to be considered when modelling deep water formation. The individual terms of the water and heat balances were analysed together with how the climate change signals affect the heat and water cycles. Individual water and heat component values are presented in figures and tables.


“Decorin and biglycan, the two best studied members of the


“Decorin and biglycan, the two best studied members of the small leucine-rich proteoglycan (SLRP)

family, have been implicated in regulating cancer growth and inflammation, respectively. Decorin expression is almost always suppressed by cancer cells but abundantly produced by activated stromal fibroblasts in the tumor microenvironment [1]. Often an inverse relationship exists between cancer growth and decorin expression, suggesting that decorin is an ‘endogenous guardian’ from the matrix. The mechanism of decorin-evoked tumor repression is linked to its ability to potently induce the Bafetinib endogenous synthesis of p21, a key inhibitor of cyclin-dependent kinases. This is carried out by soluble decorin binding in a paracrine fashion to several receptor tyrosine kinases (RTKs) including the EGFR, IGF-IR and Met (see Figure 1) [2]. Thus, decorin

is a natural RTK inhibitor and systemic selleck products delivery of recombinant decorin inhibits the growth of various tumor xenografts [3 and 4]. Currently, it is a matter of debate of how decorin exactly inactivates specific receptors, given the fact that RTKs are ubiquitously expressed. One explanation involves a hierarchical mode of receptor affinity insofar as dissociation constants range from ∼1 nM in the case of Met [5] to ∼90 nM for EGFR. Thus, it could be envisioned that decorin, by acting as a pan-RTK inhibitor, would target many different Rucaparib purchase types of tumors that exhibit differential RTK binding affinities for decorin. In most cases analyzed thus far, decorin evokes a rapid and protracted internalization of both EGFR and Met via caveolar-mediated endocytosis, a process that often leads to silencing of the receptors.

Indeed, decorin blocks several biological processes associated with Met activation, such as cell scatter, evasion and migration [5]. One of the cellular mechanisms affected by this matrix molecule is via downregulation of the non-canonical β-catenin pathway. This leads to suppression of Myc, a downstream target of β-catenin, culminating in Myc proteasomal degradation [6]. Since Myc is a ‘master regulator’ which can affect up to 1500 genes, it is not surprising to predict that novel functional roles for decorin will be discovered in the near future. The other SLRP structurally related to decorin, that is, biglycan, acts as a danger signal and triggers both innate and adaptive immune responses. Under physiological conditions, the ubiquitously expressed biglycan is sequestered in the extracellular matrix and is immunologically inert. Upon tissue stress or injury, resident cells secrete proteolytic enzymes, which degrade the extracellular matrix and thus liberate biglycan and fragments thereof. Soluble biglycan and some of its fragments interact with Toll-like receptor (TLR)-2 and TLR4.

This is a work that will be undertaken in coming years by the Eur

This is a work that will be undertaken in coming years by the European project DEVOTES (DEVelopment Of innovative Tools for understanding marine biodiversity and assessing good Environmental Status; http://www.devotes-project.eu). Therefore, in conclusion: • We advocate that we should buy Tanespimycin have an aim to gather data once but use them many times. These comments are the results of some

discussions within the framework of the project DEVOTES (DEVelopment Of innovative Tools for understanding marine biodiversity and assessing good Environmental Status) funded by the European Union under the 7th Framework Programme, ‘The Ocean for Tomorrow’ Theme (Grant agreement no. 308392), http://www.devotes-project.eu. This Editorial is contribution number 611 from AZTI-Tecnalia (Marine Research Division). “
“Plastic pollution is the dominant type of anthropogenic debris ubiquitous throughout the marine environment (Barnes et al., 2009, Derraik, 2002 and Gregory

buy PLX3397 and Ryan, 1997). Floating plastic fragments have been reported in the Northern Hemisphere subtropical gyres since the early 1970s in the North Atlantic (Carpenter and Smith, 1972, Colton et al., 1974 and Law et al., 2010), and North Pacific (Day et al., 1990, Moore et al., 2001 and Hidalgo-Ruz et al., 2012). Few data exist describing plastic pollution in the Southern Hemisphere subtropical gyres (Morris, 1980 and Thiel et al., 2003), although 81% of the earth’s surface south of the equator is seawater. Plastic pollution, originating from sea- and land-based sources, migrates into subtropical gyres (Maximenko et al., 2012 and Lebreton et al., 2012) where it forms accumulation zones of microplastic particles distinct from surrounding waters relatively free of plastic pollution. These gyres are formed by surface currents that are primarily a combination of Ekman currents driven by local Thalidomide wind and geostrophic currents maintained by the balance between sea level gradients and the Coriolis force. These surface

currents are detectable from the paths taken by satellite-tracked drifting buoys of the Global Drifter Program7 (GDP). Drifters and other objects, floating at the sea surface, are also subject to direct wind force, impact of breaking waves and Stokes drift. Computer models, tuned to simulate trajectories of drifters, predict that plastic pollution and other marine debris will likely form accumulation zones within the five subtropical gyres (Maximenko et al., 2012). To our knowledge, no quantitative data existed for the open-ocean South Pacific Subtropical Gyre (SPSG) prior to this study. Plastic pollution enters the marine environment via rivers, beaches, maritime activities, and illegal dumping at sea (Derraik, 2002 and Ryan et al., 2009).

Therefore, CBA offers not only a classification result, but also

Therefore, CBA offers not only a classification result, but also additional information regarding reliability of classification. This can be another advantage of CBA over LDA, which returns only a classification result. In terms of interpretability, while both CBA and LDA give us information regarding important genes which can discriminate increased liver weights well, LDA does not take the concept of co-expression into account. For example, in our setting, a rule (1368905_at, Inc) occurred 6 times in the CBA-generated

classifier. This rule, however, always occurred with other rules, reflecting the pattern actually observed in the training data set. Therefore, even if the gene, 1368905_at, is highly increased in an unknown sample, it does not necessarily mean increased liver weight. Such co-expressed pattern www.selleckchem.com/products/AZD2281(Olaparib).html was not taken into account by LDA. Besides, while SGI-1776 concentration coefficient values are useful to infer importance of each gene in LDA, the final prediction is determined by the total of all the terms in a polynomial, not by a single or small set of genes. The classification process of CBA is much simpler and easy to understand, because each rule is as simple as a single or small set of genes and the prediction is determined once a rule is satisfied, regardless of the other genes. This characteristic of CBA makes a generated classifier easy to understand, even for a non-expert user, because a CBA-generated classifier can be expressed also in a natural language

(e.g. “If gene A is increased and gene B is decreased, then the classifier predicts liver weight to be increase”), not in a mathematical equation as is case in LDA. Canonical pathway analysis with IPA revealed that the genes included in our CBA-generated classifier for increased liver weight were mostly drug metabolism-related ones. This is reasonable as inductions of hepatic drug metabolizing Dehydratase enzymes are well known to induce hepatocellular hypertrophy [35], of which increases in liver weight is the most sensitive indicator [15]. CBA succeeded in building a biologically relevant classifier without any prior knowledge such as literature.

Intriguingly, the classifier included genes with other functions such as gluconeogenesis and histidine degradation, which are not directly related to increased liver weight or hepatocellular hypertrophy. While it is unclear whether these genes were actually causal or not, CBA can be used to look for genes with an unknown function but high correlation for a specified outcome as well as to build a biologically reasonable classifiers. In addition, it was also considered to be an advantage that CBA automatically selects a small set of genes to build a classifier, while LDA does not. We applied the CBA algorithm to the TG-GATEs database, where both toxicogenomic and other toxicological data of more than 150 compounds in rat and human are stored, to build a predictive classifier of increased or decreased liver weight for an unknown compound.

The latter phenomenon is indicated by the increased release of am

The latter phenomenon is indicated by the increased release of ammonia and urea caused by the drug, in spite of the reduced rates of glucose production. In the absence of any direct effect of juglone on the alanine aminotransferase (ALT), the only possibility for enhancing alanine deamination in the presence of a constant concentration of this amino acid is to raise the concentration of the second substrate of this enzyme, which is α-ketoglutarate. It should be added that no short-term regulation mechanism for ALT is known. The increase OSI-744 solubility dmso in l-glutamate release caused by juglone must be examined in terms of the characteristics of the pertinent transport system. Transport of l-glutamate into the cell is of the concentrative

type. The cellular concentration of l-glutamate is generally much higher than the ATM inhibitor extracellular concentration. In our experiments, for example, a l-glutamate production rate of 0.39 μmol min− 1 g− 1 corresponds to a mean

portal-venous concentration of 0.05 mM, whereas the cellular content reaches 0.5 mM. The high-affinity glutamate transporters mediate transport of l-glutamate by the cotransport of 3 Na+ and 1 H+, and the countertransport of 1 K+ (Kanai and Hediger, 2004 and Mann et al., 2003). It is this coupling that allows uphill transport of glutamate into cells against a concentration gradient. Consequently, it would not be surprising if uncoupling, which changes the membrane permeability to H+, causes an increased leakage of L-glutamate because the inward directed concentration gradient cannot be maintained. Furthermore, the coupling is ultimately energy-dependent, which under energy deficient conditions can also be impaired. This would explain the increased rates of l-glutamate release in the presence of juglone even in the absence of increased cellular concentrations. On the other hand, compartmentation of l-glutamate could equally play some role. Soboll

et al. (1980) have shown that mafosfamide l-glutamate is present at different concentrations in the cytosol and in the mitochondria. In the liver of fasted rats under substrate-free perfusion, for example, the cytosolic and mitochondrial concentration of l-glutamate are 2.65 and 0.65 mM, respectively. It could be that in our experiments, the cytosolic concentration of l-glutamate was raised by juglone whereas the mitochondrial one was decreased in such a way that the total content of the liver cells remained more or less the same. This is a real possibility if one takes into account the fact that uncoupling stimulates l-glutamate deamination in the mitochondria (Quagliariello et al., 1965 and Nilova, 1977; see Fig. 9) a phenomenon that tends to decrease the mitochondrial concentration. The opposite occurs in the cytosol where the l-glutamate concentration can be expected to increase by virtue of the increased α-ketoglutarate concentration which increases the rate of the ALT reaction.

Prior to dilution, the pulp had a pH of 3 18 ± 0 01, total solids

Prior to dilution, the pulp had a pH of 3.18 ± 0.01, total solids content of 17.86 ± 0.1 g/100 g and soluble solids content (Brix) of 13.0 ± 0.5 g/100 g ( Mercali, Sarkis, Jaeschke, Tessaro, & Marczak, 2011). Standards of cyanidin, delphinidin, peonidin, petunidin, malvidin and pelargonidin

were purchased from Sigma Aldrich (St. Louis, USA). HPLC-grade solvents including acetonitrile, methanol, o-phosphoric acid, acetic acid, and hydrochloric acid were obtained from Vetec (Duque de Caxias, Brazil). Experiments were performed in a batch stirred check details reactor with ohmic heating at 60 Hz. The ohmic heating apparatus consists of: a manual transformer (0–240 V); a data acquisition system that recorded temperature, current and voltage data (data logger); and an ohmic heating cell containing platinum electrodes and a water jacket. The cell was built in a Pyrex glass shape with a diameter of 8 cm. The set-up used is selleck products shown in Fig. 1 where VT and A represent

the voltage and current transducers, respectively, and T the temperature sensors. To homogenize the pulp, the ohmic cell was placed above a magnetic stirrer, and to ensure a uniform temperature profile, the temperature was monitored in two different locations inside the ohmic cell, near the electrode and near the cell wall. For these measurements, stainless steel Pt-100 m coated with a nickel–phosphorous alloy were used. For the ohmic heating treatments, the pulp temperature was raised applying the voltage determined by the experimental design until a temperature of 90 °C was reached. The voltage was then lowered to maintain the pulp at this temperature for 2 min. This time/temperature condition was chosen because it is suggested in literature to inactivate anthocyanin-degrading enzymes ADP ribosylation factor (Fennema, 2010). When the thermal treatment was complete, the product was rapidly cooled by passing cold water

(4 °C) through the jacket. The rotatable central composite design was applied to identify the influence of two variables, the applied voltage (V) and the total solids content of the blueberry pulp (g/100 g), on the percentage of anthocyanin degradation (response variable). The coded and uncoded independent variables used in the experimental design are listed in Table 1. Voltage ranges (X1) were selected based on the limitations of the ohmic heating system, and the range of the solids content (X2) was chosen based on the characteristics of the fruit and the stability of the diluted suspension. To determine the influence of the selected parameters on the response variable, experiments were planned according to the central composite design (CCD) using a 22 full factorial and star design with three central points, as shown in Table 2. For the ohmic heating experiments, the error between independent experiments was determined using the central points of the rotatable central composite design.

alcatraz venom Furtado (2005) reported that this venom has low t

alcatraz venom. Furtado (2005) reported that this venom has low toxicity in mice (LD50 i.p.: 5–6 mg/kg compared with 1.5 mg/kg for B. jararaca) and low hemorrhagic activity (minimum hemorrhagic dose, μg/mouse: 0.81–2.28 vs. 0.63 for B. jararaca) but high proteolytic and coagulant activities. To increase our knowledge

of this venom, in the present study we examined the neuromuscular activity and the morphological alterations caused by B. alcatraz venom in chick biventer cervicis preparations. We also assessed the ability of commercial bothropic antivenom to neutralize the neuromuscular Alectinib cell line activity. B. alcatraz venom and commercial bothropic antivenom (BAV; lots 9806053 and 0212143) were provided by the Instituto Butantan (São Paulo, SP, Brazil). Male HY-LINE W36 chicks (4–8 days old) were kindly supplied by Granja Globo Aves Agrícolas Ltda. (Campinas, SP, Brazil) and were housed with free access to food and water. The experiments described here were approved by an institutional Committee

for Ethics in Animal Use (CEUA/UNICAMP, protocol no. 2214-1). Male chicks were killed with isoflurane (Abbott Laboratorios, Buenos Aires, Argentina) inhalation and biventer cervicis muscle-nerve preparations were mounted for indirect stimulation PTC124 mouse (0.1 Hz, 0.2 ms, 6–7 V) in aerated (95% O2, 5% CO2) Krebs solution (composition, in mM: NaCl 118.6, KCl 4.69, CaCl2 1.88, KH2PO4 1.17, MgSO4 1.17, NaHCO3 25.0 and glucose 11.65, pH 7.5) at 37 °C, as described elsewhere (Rodrigues-Simioni et al., 2004).

The preparations were allowed to stabilize for at least 15 min before adding venom (5, 10, 50 or 100 μg/ml). Contractures to exogenous submaximal concentrations of acetylcholine (ACh, 110 μM; Sigma Chemical Co., St. Louis, MO, USA) and KCl (20 mM) were obtained in the absence of nerve stimulation prior to venom addition and at the end of the experiment to test for neurotoxic and myotoxic activities (Harvey et al., 1994). At various intervals during the experiments, aliquots of the organ bath solution were withdrawn for quantification of creatine kinase (CK) release using commercial kits (Bioclin/Quibasa, Brazil); activity was expressed in units/ml (U/ml). In some experiments, learn more the preparations were incubated with d-Tc (10 μg/ml) prior to the addition of venom. At the end of each experiment, the biventer cervicis preparation was fixed in Bouin solution for 24–48 h and processed by standard techniques. Sections 2–3 μm thick were stained with 0.5% (w/v) toluidine blue in 5% (w/v) borax for examination by light microscopy. The extent of muscle damage in control and venom-treated preparations (n = 5 each) was assessed by counting the number of fibers with alterations (edema, darkening, sarcolemmal disruption and myofibril lysis) and expressing this number as a percentage of the total number of fibers counted in three non-overlapping, non-adjacent areas of each muscle ( Oshima-Franco et al., 2001).

1 Kao D, Gomez SZ, Tandon P, et al Managing the post-liver trans

1 Kao D, Gomez SZ, Tandon P, et al. Managing the post-liver transplant anastomotic stricture: multiple plastic versus metal stents-a systematic review. Gastrointest Endosc 2013;77:679-91. Water immersion colonoscopy Colonoscopy is performed with the patient in the left lateral position. The air pump is turned off before colonoscopy. During endoscope insertion, residual air in lumen is suctioned and 37°C water is infused with a peristaltic pump through the biopsy channel to obtain

visualization. Turbid fluid is suctioned and replaced with clean water until colon lumen is clearly visualized again and the endoscope is advanced under water. Water immersion colonoscopy for unsedated patients with prior abdomino-pelvic surgery In the small

study by Luo et al,1 the probability of reaching the cecum was enhanced using the water immersion technique. Other factors noted were a decrease check details in the need for variable scope stiffness, application of abdominal pressure and the use of patient position change. Adenoma detection was not studied, nor were all the patients included in the study being screened for the first time. Cecal intubation time was similar in the two study groups. The role of water immersion colonoscopy technique in patients who receive sedation is unclear. JQ1 ic50 Whether similar benefits could be seen with the use of CO2 insufflation and pediatric colonoscopes is an open question. All but 1 of the 11 patients that could not be studied with air insufflation had complete examinations with sedation. However, in special situations such as the scenario presented above where sedation is not an option, the water immersion technique may facilitate a complete examination.1 Take-home point: Consider water immersion colonoscopy in unsedated patients

enough with prior abdominal or pelvic surgery. 1 Luo H, Zhang L, Liu X et al. Water exchange enhanced cecal intubation in potentially difficult colonoscopy. Unsedated patients with prior abdominal or pelvic surgery: a prospective randomized, controlled trial. Gastrointest Endosc 2013;77:767-73. The GIE: Gastroinintestinal Endoscopy CME Activity can now be completed entirely on-line. To complete do the following: 1 Read the CME articles in this issue carefully and complete the activity: Barkun AN, Moosavi S, Martel M. Topical hemostatis agents: a systematic review with particular emphasis on endoscopic application in GI bleeding. Gastrointest Endosc 2013;77:692-700. Oh HC, Brugge WR. EUS-guided pancreatic cyst ablation: a critical review (with video). Gastrointest Endosc 2013;77:526-33. Kao D, Gomez SZ, Tandon P, et al. Managing the post-liver transplant anastomotic stricture: multiple plastic versus metal stents—a systematic review. Gastrointest Endosc 2013;77:679-91. Luo H, Zhang L, Liu X et al. Water exchange enhanced cecal intubation in potentially difficult colonoscopy.