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• Gut function and transit change following the initiation of ETI, measured using MRI. • Small bowel transit and small bowel response to food improves after starting ETI. • After 18 months of ETI use, colonic volume reduces. • First imaging study to find changes in gut physiology following ETI initiation. Gastrointestinal (GI) symptoms in cystic fibrosis (CF) are common and disruptive. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the GI tract is not fully understood. The aim was to use magnetic resonance imaging (MRI) to determine if elexacaftor/tezacaftor/ivacaftor (ETI) changed GI function and transit. This was an 18 month prospective, longitudinal, observational study. We enrolled 24 people with CF aged 12 years or older to undergo MRI scans before starting ETI and 3, 6, and 18 months after starting ETI. The primary outcome measure was change in oro-caecal transit time (OCTT) at 6 and 18 months. Secondary outcome measures included change in small bowel water content (SBWC), change in the reduction in small bowel water content following a meal (DeltaSBWC) and change in total colonic volume (TCV). A total of 21 participants completed MRI scans at 6 months and 11 completed at 18 months. After 18 months of ETI, median OCTT significantly reduced, from >360 min [IQR 240->360] to 240 min [IQR 180–300] (p = 0.02, Wilcoxon signed-rank). Both SBWC and DeltaSBWC increased after starting ETI. TCV reduced significantly after 18 months (p = 0.005, Friedman). Our findings suggest an improvement in small bowel transit, small bowel response to food and a reduction in colonic volume after starting ETI. These effects may relate to CFTR activation in the small bowel. To our knowledge this is the first study to show a physiological change in GI transit and function in response to CFTR modulator use through imaging studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Upper gastrointestinal bleeding (UGIB) is a condition commonly seen in the emergency department (ED). Therefore, it is important for emergency clinicians to be aware of the current evidence regarding the diagnosis and management of this disease. This paper evaluates key evidence-based updates concerning UGIB for the emergency clinician. UGIB most frequently presents with hematemesis. There are numerous causes, with the most common peptic ulcer disease, though variceal bleeding in particular can be severe. Nasogastric tube lavage for diagnosis is not recommended based on the current evidence. A hemoglobin transfusion threshold of 7 g/dL is recommended (8 g/dL in those with myocardial ischemia), but patients with severe bleeding and hemodynamic instability require emergent transfusion regardless of their level. Medications that may be used in UGIB include proton pump inhibitors, prokinetic agents, and vasoactive medications. Antibiotics are recommended for those with cirrhosis and suspected variceal bleeding. Endoscopy is the diagnostic and therapeutic modality of choice and should be performed within 24 h of presentation in non-variceal bleeding after resuscitation, though patients with variceal bleeding may require endoscopy within 12 h. Transcatheter arterial embolization or surgical intervention may be necessary. Intubation should be avoided if possible. If intubation is necessary, several considerations are required, including resuscitation prior to induction, utilizing preoxygenation and appropriate suction, and administering a prokinetic agent. There are a variety of tools available for risk stratification, including the Glasgow Blatchford Score. An understanding of literature updates can improve the ED care of patients with UGIB. [ABSTRACT FROM AUTHOR]

Lower gastrointestinal bleeding (LGIB) is a condition commonly seen in the emergency department. Therefore, it is important for emergency medicine clinicians to be aware of the current evidence regarding the diagnosis and management of this disease. This paper evaluates key evidence-based updates concerning LGIB for the emergency clinician. LGIB is most commonly due to diverticulosis or anorectal disease, though there are a variety of etiologies. The majority of cases resolve spontaneously, but patients can have severe bleeding resulting in hemodynamic instability. Initial evaluation should focus on patient hemodynamics, the severity of bleeding, and differentiating upper gastrointestinal bleeding from LGIB. Factors associated with LGIB include prior history of LGIB, age over 50 years, and presence of blood clots per rectum. Computed tomography angiography is the imaging modality of choice in those with severe bleeding to diagnose the source of bleeding and guide management when embolization is indicated. Among stable patients without severe bleeding, colonoscopy is the recommended modality for diagnosis and management. A transfusion threshold of 7 g/dL hemoglobin is recommended based on recent data and guidelines (8 g/dL in those with myocardial ischemia), though patients with severe bleeding and hemodynamic instability should undergo emergent transfusion. Anticoagulation reversal may be necessary. If bleeding does not resolve, embolization or endoscopic therapies are necessary. There are several risk scores that can predict the risk of adverse outcomes; however, these scores should not replace clinical judgment in determining patient disposition. An understanding of literature updates can improve the care of patients with LGIB. [ABSTRACT FROM AUTHOR]

[Display omitted] • HMT enhanced thermal stability and RS content of the complex prepared using extrusion. • Eight hours of HMT (HMT-8) significantly increased RS content by 34.2 %. • HMT-8 had lowest pGI values of 54.5 and 64.2, as predicted by two different methods. • Recombinant rice composed of HMT-8 helped in maintaining blood glucose homeostasis. The utilization of resistant starch in food industry is restricted due to its susceptibility to thermal degradation. This work aimed to address this issue by preparing a starch-linoleic acid complex (RS5) via extrusion method combined with heat moisture treatment, obtaining VII-type crystal (melting temperature ∼110 °C). The complex obtained through an 8-hour heat moisture treatment exhibited a high RS content of 46.7 %. The glycemic index (pGI) values predicted by two different methods for this complex were 54.5 and 64.2. The complex was further processed into recombinant rice, which exhibited similar textural properties to commercial rice products after cooking. Notably, the recombinant rice maintained an anti-enzyme structure (VII-type complex) as evidenced by its significant resistant starch content of 38.1 %, the lowest pGI values of 59.6 and 72.5. These findings could serve as a useful reference to aid in developing low glycemic index foods based on starch. [ABSTRACT FROM AUTHOR]

Effective reduction of urban flood risk can be accomplished through structural mitigation measures such as underground drainage tunnels and implementing drainage practices, such as green infrastructure (GI) techniques. In this study, we employed an urban runoff model to quantitatively evaluate the impact of these flood mitigation measures and GI technology in reducing urban flood vulnerability (UFV). Specifically, we assessed the flood control capabilities of underground drainage tunnels and detention reservoirs, among others, exploring various combinations to formulate a comprehensive flood prevention plan (CFPP) for the studied basin. Additionally, our study analyzes the effectiveness of GI technologies, such as impervious area reduction (IAR) and ground retention (GR) and introduces a method for assessing their impact on flood-prone areas. To enhance flood mitigation strategies, we propose a hybrid approach that combines CFPP with GI techniques. The effectiveness of this hybrid strategy was assessed through comparisons with a basic scenario and multiple GI technology scenarios. As a result of applying the hybrid strategy proposed in this study, the reduction rates of peak flow (PF), flood volume (FV), and flooded area (FA) in this basin were up to 37.3 %, 71.5 %, and 93.6 %, respectively. These findings offer valuable insights for designing strategies to enhance urban flood resilience in the face of a changing climate. [ABSTRACT FROM AUTHOR]

To identify the association between the dietary carbohydrate indexes, such as dietary glycemic index (DGI) and load (DGL), dietary insulin index (DII) and load (DIL), with the possibility of cataract. This case–control study consisted of 101 new cases of cataract and 202 controls. DGI and DGL were computed through DGI values previously published. DII was also calculated based on dietary insulin index data published previously. There was a significant positive association between the highest quartiles of DGI (OR = 6.56; 95% CI = 2.67–16.06; P < 0.001), DGL (OR = 6.17; 95% CI = 1.93–19.37; P = 0.002) and DIL (OR = 4.17; 95% CI = 1.41–12.27; P = 0.004) with risk of cataract, compared to those on the lowest quartile, but not for DII (OR = 0.85; 95% CI = 0.39–1.86; P = 0.82). Furthermore, after stratifying groups by BMI, a significant direct association between highest quartile of DGI (OR = 6.76; 95% CI = 2.49–18.38; P < 0.001) and DGL (OR = 3.45; 95% CI = 0.96–12.37; P = 0.05) with risk of cataract was evident in individuals with elevated BMI (BMI≥25). We found a significant, direct, relationship between DGI, DGL and DIL with risk of cataract. However, the association between DII and the risk of cataract was not significant, even after adjusting for related confounders. [ABSTRACT FROM AUTHOR]

Depression is a major health issue in the United States and is highly comorbid with gastrointestinal conditions. We collected data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of the US population, to study the relationship between depression and bowel habits. Using data from the NHANES (2009–2010), we identified 495 depressed and 4709 non-depressed adults who filled out the Bowel Health Questionnaire. Depression was defined according to a validated questionnaire. We used multivariable analysis, controlling for clinical and demographic variables, to evaluate the relationship between mood and bowel habits. In our weighed sample, 24.6% of depressed individuals and 12.6% of non-depressed individuals reported disordered bowel habits. Chronic diarrhea was significantly more prevalent in depressed individuals (15.53%; 95% CI, 11.34%–20.90%) than non-depressed individuals (6.05%; 95% CI, 5.24%–6.98%; P =.0001). Chronic constipation was also more common in depressed individuals (9.10%; 95% CI, 7.02%–11.69%) than non-depressed individuals (6.55%; 95% CI, 5.55%–7.70% CI; P =.003). Mean depression scores in patients with chronic diarrhea (4.9 ± 5.8) and with chronic constipation (4.4 ± 4.93) were significantly higher than mean depression scores for individuals with normal bowel habits (3.2 ± 4.6) (P <.001). Moderate and severe depression were significantly associated with chronic diarrhea but not chronic constipation. Only mild depression was significantly associated with chronic constipation. In an analysis of the NHANES database, we found a higher proportion of depressed individuals to have chronic diarrhea and constipation than non-depressed individuals; chronic diarrhea was more strongly associated with depression. Our findings provide support for the relationship between mood and specific bowel habits, accounting for multiple co-variables in a large sample of the general US population. [ABSTRACT FROM AUTHOR]

Introduction: The current surgical landscape reflects a continual trend towards sub-specialization, evidenced by an increasing number of US surgeons who pursue fellowship training after residency. Despite this growing trend, however, the effect of advanced gastrointestinal (GI)/minimally invasive surgery (MIS) fellowship programs on patient outcomes following foregut/esophageal operations remains unclear. This study looks at two representative foregut surgeries (laparoscopic fundoplication and esophagomyotomy) performed in New York State (NYS), comparing hospitals which do and do not possess a GI/MIS fellowship program, to examine the effect of such a program on perioperative outcomes. We also aimed to identify any patient or hospital factors which might influence perioperative outcomes.Methods: The SPARCS database was examined for all patients who underwent a foregut procedure (specifically, either an esophagomyotomy or a laparoscopic fundoplication) between 2012 and 2014. We compared the following outcomes between institutions with and without a GI/MIS fellowship program: 30-day readmission, hospital length of stay (LOS), and development of any major complication.Results: There were 3175 foregut procedures recorded from 2012 to 2014. Just below one third (n = 1041; 32.8%) were performed in hospitals possessing a GI/MIS fellowship program. Among our entire included study population, 154 patients (4.85%) had a single 30-day readmission, with no observed difference in readmission between hospitals with and without a GI/MIS fellowship program, even after controlling for potential confounding factors (p = 0.6406 and p = 0.2511, respectively). Additionally, when controlling for potential confounders, the presence/absence of a GI/MIS fellowship program was found to have no association with risk of having a major complication (p = 0.1163) or LOS (p = 0.7562). Our study revealed that postoperative outcomes were significantly influenced by patient race and payment method. Asians and Medicare patients had the highest risk of suffering a severe complication (10.00 and 7.44%; p = 0.0311 and p = 0.0036, respectively)-with race retaining significance even after adjusting for potential confounders (p = 0.0276). Asians and uninsured patients demonstrated the highest readmission rates (15.00 and 12.50%; p = 0.0129 and p = 0.0012, respectively)-with both race and payment method retaining significance after adjustment (p = 0.0362 and p = 0.0257, respectively). Lastly, payment method was significantly associated with postoperative LOS (p < 0.0001), with Medicaid patients experiencing the longest LOS (mean 3.99 days) and those with commercial insurance experiencing the shortest (mean 1.66 days), a relationship which retained significance even after adjusting for potential confounders (p < 0.0001).Conclusion: The presence of a GI/MIS fellowship program does not impact short-term patient outcomes following laparoscopic fundoplication or esophagomyotomy (two representative foregut procedures). Presence of such a fellowship should not play a role in choosing a surgeon. Additionally, in these foregut procedures, patient race (particularly Asian race) and payment method were found to be independently associated with postoperative outcomes, including postoperative LOS. [ABSTRACT FROM AUTHOR]

Purpose To investigate whether inter-institutional cohort analysis uncovers more reliable dose–response relationships exemplified for late rectal bleeding (LRB) following prostate radiotherapy. Material and methods Data from five institutions were used. Rectal dose–volume histograms (DVHs) for 989 patients treated with 3DCRT or IMRT to 70–86.4 Gy@1.8–2.0 Gy/fraction were obtained, and corrected for fractionation effects ( α/β  = 3 Gy). Cohorts with best-fit Lyman–Kutcher–Burman volume-effect parameter a were pooled after calibration adjustments of the available LRB definitions. In the pooled cohort, dose–response modeling (incorporating rectal dose and geometry, and patient characteristics) was conducted on a training cohort (70%) followed by final testing on the remaining 30%. Multivariate logistic regression was performed to build models with bootstrap stability. Results Two cohorts with low bleeding rates (2%) were judged to be inconsistent with the remaining data, and were excluded. In the remaining pooled cohorts ( n  = 690; LRB rate = 12%), an optimal model was generated for 3DCRT using the minimum rectal dose and the absolute rectal volume receiving less than 55 Gy (AUC = 0.67; p  = 0.0002; Hosmer–Lemeshow p -value, p HL  = 0.59). The model performed nearly as well in the hold-out testing data (AUC = 0.71; p  < 0.0001; p HL  = 0.63), indicating a logistically shaped dose–response. Conclusion We have demonstrated the importance of integrating datasets from multiple institutions, thereby reducing the impact of intra-institutional dose–volume parameters explicitly correlated with prescription dose levels. This uncovered an unexpected emphasis on sparing of the low to intermediate rectal dose range in the etiology of late rectal bleeding following prostate radiotherapy. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) can damage the gastrointestinal tract, causing widespread morbidity and mortality. Although mechanisms of damage involve the activities of prostaglandin-endoperoxide synthase 1 (PTGS1 or cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review the mechanisms of gastrointestinal damage induction by NSAIDs via COX-mediated and COX-independent processes. NSAIDs interact with phospholipids and uncouple mitochondrial oxidative phosphorylation, which initiates biochemical changes that impair function of the gastrointestinal barrier. The resulting increase in intestinal permeability leads to low-grade inflammation. NSAID inhibition of COX enzymes, along with luminal aggressors, results in erosions and ulcers, with potential complications of bleeding, protein loss, stricture formation, and perforation. We propose a model for NSAID-induced damage to the gastrointestinal tract that includes these complex, interacting, and inter-dependent factors. This model highlights the obstacles for the development of safer NSAIDs. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal (GI) surgeries represent a significant proportion of the surgical site infection (SSI) burden in pediatric patients, resulting in significant morbidity. Previous studies have shown that perioperative bundles reduce SSIs, but few have focused on pediatric GI operations. We hypothesized that a GI bundle would decrease SSI rates, length of stay (LOS), and hospital charges. Methods After establishing baseline SSI rates, a GI bundle was created and implemented in November 2014. We prospectively collected data including demographics, procedure type, LOS, inpatient charges, bundle compliance, and SSI development. We analyzed SSI rates, LOS, and charges using process control charts. Results The baseline SSI rate for all GI operations was 3.4%, which increased to 7.1%, then decreased to 4.7%. Midgut/hindgut and stoma closure SSI rates decreased from 11.3% to 8.0% (p < 0.05) and 21.4% to 7.9%, respectively ( p < 0.05). Although overall LOS and charges were unchanged, average LOS for midgut/hindgut surgeries and stoma closures decreased from 20.3 to 13.6 days ( p = 0.015) and 12.6 to 7.9 days ( p = 0.04), respectively. Stoma closure charges decreased from $94,262 to $50,088 ( p = 0.01). Conclusions Our perioperative GI bundle decreased SSI rates, primarily among midgut/hindgut operations. Bundle usage decreased LOS and charges most effectively in stoma closures. Type of study Prognosis Study. Level of evidence Level 2. [ABSTRACT FROM AUTHOR]

Objective: Epidemiological data on genitourinary infections (GUIs) comparing patients with and without type 2 diabetes (T2DM) is scant. We aimed to estimate the incidence of urinary tract infections (UTIs), genital infections (GIs), or any GUI in total and stratified by history of GUI and sex.Research Design and Methods: We identified 39,295 patients in the Kaiser Permanente Northwest health plan with T2DM and an equal number of age and sex matched patients without diabetes. The cohort was followed for up to 9years (2006-2014). We calculated incidence rates and corresponding 95% confidence intervals (CI) of any GUI, UTIs and GIs adjusting for age, sex, race, BMI, presence of chronic kidney disease, annual number of outpatient visits, and diuretic use.Results: Adjusted incidence of any GUI was 97.2/1000person-years (p-y) (95% CI 95.5-98.8) among the T2DM cohort vs. 79.7/1000 p-y (78.3-81.2) among those without diabetes. T2DM was associated with an adjusted 25% increased risk of UTI (rate ratio 1.25, 95% CI 1.22-1.29), a 26% increased risk of GI (1.26, 1.22-1.31) and a 22% increased risk of any GUI (1.22, 1.19-1.25). Incidence rates were lower among those with no GUI history, but the relative risks were similar. Women in both groups had higher incidence rates of GUIs than men.Conclusions: T2DM was associated with increased risks of any GUI, UTIs and GIs. Incidence rates of UTIs were higher than rates of GIs, but the relative risk of GIs was essentially identical. A similar pattern was observed when stratifying by sex.Significance Of the Study: RESEARCH QUESTIONS. [ABSTRACT FROM AUTHOR]

Background This study was to assess effects of carvedilol on ventricular remodeling and expression of β 3 -adrenergic receptor (β 3 -AR) and Gi protein in a rat model of diabetes subjected to myocardial infarction (MI). Methods Rat model of type II diabetes was established by injection of streptozotion. MI was then induced by ligating the left anterior descending coronary artery. Rats were then randomly divided into two groups treated with either placebo (PL) or carvedilol (CA - 10 mg·kg − 1 ·d − 1 ). Additional controls consisted of sham-operated rats with diabetes (DS) and rats fed a normal diet subjected to myocardial infarction (NM). Echocardiographic and hemodynamic studies were performed to assess the structural and functional changes. β 3 -AR and Gi mRNA in the myocardium distal from the infarction region were measured, and β 3 -AR and Gi protein were measured with western blot. Results There were no significant differences in MI size among the three MI groups. In the PL group, LVEDd, LVWI, E/A and CVF were significantly increased, while LVEF and PW% significantly decreased as compared with the DS and NM groups. Compared with the DS group, the expression of β 3 -AR and Gi mRNA and protein in the PL group was significantly increased, however, in the CA group, β 3 -AR and Gi mRNA and protein were decreased. Conclusions The expression of β 3 -AR and Gi mRNA and protein was increased in diabetic rats subjected to MI as compared with rats subject to either condition alone. Carvedilol treatment prevented many of these deleterious effects. [ABSTRACT FROM AUTHOR]

Chemokine receptors are members of the G-protein-coupled receptor (GPCR) family coupled to members of the Gi class, whose primary function is to inhibit the cellular adenylate cyclase. We used a cAMP-related and PKA-based luminescent biosensor (GloSensor™ F-22) to monitor the real-time downstream response of chemokine receptors, especially CX3CR1 and CXCR4, after activation with their cognate ligands CX3CL1 and CXCL12. We found that the amplitudes and kinetic profiles of the chemokine responses were conserved in various cell types and were independent of the nature and concentration of the molecules used for cAMP prestimulation, including either the adenylate cyclase activator forskolin or ligands mediating Gs-mediated responses like prostaglandin E2 or beta-adrenergic agonist. We conclude that the cAMP chemokine response is robustly conserved in various inflammatory conditions. Moreover, the cAMP-related luminescent biosensor appears as a valuable tool to analyze the details of Gi-mediated cAMP-inhibitory cellular responses, even in native conditions and could help to decipher their precise role in cell function. [ABSTRACT FROM AUTHOR]

In the present work, we comparatively studied the corrosion attack of Zn-based coatings on interstitial free steel. For this, the electrochemical behavior of industrially coated hot-dip galvanized (GI), galvanneal (GA) and galvalume (Zn55Al) interstitial free (IF) steels was analyzed by cyclic voltammetry in quiescent and stirred 0.1 mol/L NaCl solution and by scanning vibrating electrode technique (SVET). All three coatings protect the steel substrate by their localized corrosion leading to final coating perforation. However, Zn55Al corrodes more homogenously due to a well-distributed interdendritic η phase and the barrier effect of interfacial Al–Fe intermetallics. Due to its surface cracks, GA presents the opposite behavior, suffering a substrate attack with only 70% of the charge density expected for GI. [ABSTRACT FROM AUTHOR]

Background & aims Glycaemic index testing is conducted in the morning, however postprandial glycaemia has a diurnal rhythm. The study aimed to evaluate the effect of glycaemic index on glucose tolerance at different times during the day. Methods A randomised controlled crossover study was conducted in ten healthy participants after a standardised premeal and eight hour fast. Low (37) and high glycaemic index (73) meals, matched for energy, available carbohydrate, protein and fat, were consumed at 08:00 h and 20:00 h. Blood samples were taken for 2 h postprandially. Results Postprandial glucose area under curve showed effect with time of day after both meals (Low p < 0.001, High p = 0.003), and a trend (p = 0.06) to higher glycaemic responses in the evening for low glycaemic index meal. No differences were observed in insulin responses. Despite the calculated difference in meal glycaemic index little difference was observed in morning responses, but differences were seen in the evening when insulin insensitivity is increasing, the glycaemic response increase was proportionally greater for low glycaemic index meals. Conclusions Low glycaemic index foods are of less value in glycaemic control in the evening than the morning. Consuming food late in the day has a detrimental metabolic impact irrespective of glycaemic index. [ABSTRACT FROM AUTHOR]

Abstract: Substance P (SP) is well known for its immunoregulatory influence on NK cells. The biological actions of SP are mediated primarily through the high-affinity neurokinin-1 receptor (NK-1R), a G protein-coupled receptor (GPCR). Receptor binding triggers a cAMP signaling pathway and intracellular levels of cAMP are regulated via Gαs and Gαi. In this study NF449, a Gαs-selective G protein antagonist, was used to study the role of Gαs in the activation of NK92-MI cells by SP. Results show that 10−12 M SP enhances the expression of Gαs and Gαi3 in NK92-MI cells promoting a cytotoxic phenotype characterized by expression of perforin and granzyme B. Development of a cytotoxic phenotype in NK92-MI cells stimulated with SP is blunted by inhibition of Gαs by NF449. In summary, SP signaling through NK-1R promotes a cytotoxic phenotype in NK92-MI cells characterized by upregulation of both Gαs and Gαi3. NF449 inhibits Gαs, blunts SP-induced expression of perforin and granzyme B, and represents a potential therapeutic avenue for reducing NK-cell mediated cytotoxicity. [Copyright &y& Elsevier]

Background & Aims: Bowel perforation is a rare but serious complication of colonoscopy. Its prevalence is increasing with the rapidly growing volume of procedures performed. Although colonoscopies have been performed for decades, the risk factors for perforation are not completely understood. We investigated risk factors for perforation during colonoscopy by assessing variables that included sedation type and endoscopist specialty and level of training. Methods: We performed a retrospective multivariate analysis of risk factors for early perforation (occurring at any point during the colonoscopy but recognized during or immediately after the procedure) in adult patients by using the Clinical Outcomes Research Initiative National Endoscopic Database. Risk factors were determined from published articles. Additional variables assessed included endoscopist specialty and years of experience, trainee involvement, and sedation with propofol. Results: We identified 192 perforation events during 1,144,900 colonoscopies from 85 centers entered into the database from January 2000–March 2011. On multivariate analysis, increasing age, American Society of Anesthesia class, female sex, hospital setting, any therapy, and polyps >10 mm were significantly associated with increased risk of early perforation. Colonoscopies performed by surgeons and endoscopists of unknown specialty had higher rates of perforation than those performed by gastroenterologists (odds ratio, 2.00; 95% confidence interval, 1.30–3.08). Propofol sedation did not significantly affect risk for perforation. Conclusions: In addition to previously established risk factors, non-gastroenterologist specialty was found to affect risk for perforations detected during or immediately after colonoscopy. This finding could result from differences in volume and style of endoscopy training. Further investigation into these observed associations is warranted. [Copyright &y& Elsevier]

Abstract: The use of Geographic Information or GI, has grown rapidly in recent years. Previous research has identified the importance of usability and user centred design in enabling the proliferation and exploitation of GI. However, the design and development of usable GI is not simply a matter of applying the tried and tested usability methods that have been developed for software and web design. Dealing with data and specifically GI brings with it a number of issues that change the way usability and user centred design can be applied. This paper describes the outcomes of a workshop held in March 2010 exploring the core issues relating to GI usability. The workshop brought together an international group of twenty experts in both human factors and GI, from a wide range of academic and industrial backgrounds. These experts considered three key issues, the stakeholders in GI, key challenges applying usability to GI and the usability methods that can be successfully applied to GI. The result of this workshop was to identify some areas for future research, such as the production of meaningful metadata and the implications of blurring of the line between data producers and data consumers. [Copyright &y& Elsevier]

Abstract: It is well known that multipath channel and carrier frequency offset (CFO) destroy the orthogonality between subcarriers in the downlink of MC-CDMA and degrade the system performance. In this paper, a new low complexity algorithm is proposed to iteratively estimate the CFO and the channel equalizer using only the guard interval (GI) redundancy, or excess codes (EC) or both GI and EC without additional pilots. Simulations illustrate and compare the performance efficiency of these schemes in different scenarios. [Copyright &y& Elsevier]

Abstract: Antigen/IgE-mediated mast cell activation via FcɛRI can be markedly enhanced by the activation of other receptors expressed on mast cells and these receptors may thus contribute to the allergic response in vivo. One such receptor family is the G protein-coupled receptors (GPCRs). Although the signaling cascade linking FcɛRI aggregation to mast cell activation has been extensively investigated, the mechanisms by which GPCRs amplify this response are relatively unknown. To investigate this, we utilized prostaglandin (PG)E2 based on initial studies demonstrating its greater ability to augment antigen-mediated degranulation in mouse mast cells than other GPCR agonists examined. This enhancement, and the ability of PGE2 to amplify antigen-induced calcium mobilization, was independent of phosphoinositide 3-kinase but was linked to a pertussis toxin-sensitive synergistic translocation to the membrane of phospholipase (PL)Cγ and PLCβ and to an enhancement of PLCγ phosphorylation. This “trans-synergistic” activation of PLCβ and γ, in turn, enhanced production of inositol 1,4,5-trisphosphate, store-operated calcium entry, and activation of protein kinase C (PKC) (α and β). These responses were critical for the promotion of degranulation. This is the first report of synergistic activation between PLCγ and PLCβ that permits reinforcement of signals for degranulation in mast cells. [Copyright &y& Elsevier]

Abstract: This research investigates the role of spatial aggregation and the modifiable area unit problem (MAUP) on the correlation between drinking water quality and gastrointestinal (GI) illness. Using water quality estimates from hydraulic modeling of a water distribution system and a linear dose–response model, we simulate illness point patterns with a theoretically determined correlation to average pathogen concentrations. We then assess the sensitivity of the Pearson’s correlation statistic (r) to different aggregation units. Because public health data are often geocoded illness events, we assess the importance of their network-clustered structure by comparing two spatial scenarios. The first scenario uses a random spatial distribution for illness point patterns. Randomly located points are then compared to network-clustered illness event patterns where the set of possible illness locations is limited to network nodes. We then analyze multiple illness simulations with various sets of commonly used areal units, such as census units, regular grids, and Voronoi tessellations. A systematic bias on r due to the MAUP is estimated by showing an average reduction in r of 0.65. Consideration of the spatial network constraint of illness data during aggregation reduces this MAUP bias estimate 41% from 0.65 to 0.38. [Copyright &y& Elsevier]

Abstract: Formyl peptide receptor (FPR) and C5a receptor (C5aR) are chemoattractant G protein-coupled receptors (GPCRs) involved in the innate immune response against bacterial infections and tissue injury. Like other GPCRs, they recruit β-arrestin1/2 to the plasma membrane and activate the extracellular signal-regulated kinases 1 and 2 (ERK1/2). Previous studies with several GPCRs have suggested that β-arrestins play an important role as signal transducers by scaffolding signaling molecules such as ERK1/2. This function of the β-arrestins was not discovered until several years after their role in desensitization and endocytosis had been reported. In this study, we investigated the role of the β-arrestins in the activation of ERK1/2 and receptor endocytosis. We took advantage of previously described mutants of FPR that have defects in Gi coupling or β-arrestin recruitment. The results obtained with the mutant FPRs, as well as experiments using an inhibitor of Gi and cells overexpressing β-arrestin2, showed that activation of ERK1/2 takes place through Gi and is not affected by β-arrestins. However, overexpression of β-arrestin2 does enhance FPR sequestration from the cell surface, suggesting a role in desensitization, as shown for many other GPCRs. Experiments with CHO C5aR cells showed similar sensitivity to the Gi inhibitor as CHO FPR cells, suggesting that the predominant activation of ERK1/2 through G protein may be a common characteristic among chemoattractant receptors. [Copyright &y& Elsevier]

Abstract: This paper describes a field experimental investigation of the effects of frost formation on the performance of a low-temperature large-scale evaporator coil used in industrial refrigeration systems. A series of experiments were conducted to determine the in situ coil cooling capacity of the evaporator over time as frost builds on its surfaces. Field-measured quantities include inlet and outlet air temperatures, inlet and outlet air relative humidity, and air volume flow rate. These measurements provide a baseline set of experimental data that can be used to validate numerical models of industrial evaporators operating under frosting conditions. [Copyright &y& Elsevier]

Abstract: The present study evaluated the effect of 5-hydroxytryptamine (5-HT) on intestinal Na+/H+ exchanger (NHE) activity and the cellular signaling pathways involved in T84 cells. T84 cells express endogenous NHE1 and NHE2 proteins, detected by immunoblotting, but not NHE3. The rank order for inhibition of NHE activity in acid-loaded T84 cells was 5-(N-ethyl-N-isopropyl)-amiloride (EIPA; IC50 =519 [465, 579] nM)>cariporide (IC50 =630 [484, 819] nM)>amiloride (IC50 =19 [16, 24] μM); the NHE3 inhibitor S3226 was found to be devoid of effect. This different inhibitory sensitivity indicates that both NHE1 and NHE2 isoforms may play an active role in Na+-dependent intracellular pH (pHi) recovery in T84 cells. Short-term exposure (0.5 h) of T84 cells to 5-HT increased NHE activity in a concentration-dependent manner. The stimulation induced by 5-HT (30 μM) was partially inhibited by both WAY 100135 (300 nM) and ketanserin (300 nM), antagonists of 5-HT1A and 5-HT2 receptors, respectively. NHE activity was significantly increased by 8-OH-DPAT and α-methyl-5-HT, agonists of, respectively, 5-HT1A and 5-HT2 receptors. An incubation of T84 cells with anti-Gs and anti-Gβ antibodies complexed with lipofectin did not prevent the 5-HT-induced stimulation of NHE activity. Overnight treatment with anti-Giα1,2 and anti-Gq/11 antibodies complexed with lipofectin blocked the stimulatory effect induced by 8-OH-DPAT and α-methyl-5-HT, respectively. It is concluded that in T84 cells 5-HT enhances intestinal NHE activity through stimulation of Giα1,2-coupled 5-HT1A and Gq/11-coupled 5-HT2 receptors. [Copyright &y& Elsevier]

Abstract: β-adrenoceptor mediated vasorelaxation and cAMP production decline during maturation and aging in rat aorta. β-adrenoceptor-stimulated vasorelaxation is mainly triggered by Gsα-mediated activation of adenylyl cyclase. β2-adrenoceptors can also activate Gi protein which inhibits adenylyl cyclase activity. In this study, we examined the role of Gi proteins in the decreased β-adrenoceptor mediated responses during maturation. Pertussis toxin treatment of aortic rings to inhibit Giα activation completely restored age related decline in isoproterenol-stimulated maximal vasorelaxation in 3-month old rats. This treatment increased the potency, but not the maximal response of isoproteronol to produce vasorelaxation in 6 month old rats. The maximal isoproteronol stimulated cAMP responses were also partially restored in pertussis toxin-treated rings from 3 or 6-month old rats. We also examined β-adrenoceptor stimulated binding of 35[S]GTPγS to Gsα and Giα1/2 in aortic membranes from 1, 3 and 6-month old rats. In 1-month old rats, isoproterenol-stimulated 35[S]GTPγS binding to Gsα was significantly higher than that of 3 or 6-month old rats. Isoproterenol-stimulated 35[S]GTPγS binding to Giα1/2 was found to be significantly increased in 3 or 6-month old rats compared to 1-month old rats. The results of this study showed that β-adrenoceptor-mediated activation of Gs and Gi proteins was declined and increased, respectively, and inhibition of the Gi mediated activity by pertussis toxin treatment partially restored impaired vasorelaxation and cAMP response to β-adrenoceptor stimulation during maturation in rat aorta. The decrease in β-adrenoceptor mediated activation of Gs gradually increased during maturation. All together these results indicated that β-adrenoceptor mainly activates Gs protein in aorta from 1-month old rats, while it activates Gi and with a certain degree of decline it also activates Gs in aorta from 3 and 6-months old rats and not only the increase in β-adrenoceptor coupling to Gi but also the decrease in its coupling to Gs play a role in the impaired β-adrenoceptor responses in rat aorta during maturation. [Copyright &y& Elsevier]

Abstract: Several authors report changes in the volume and degree of cortical folding in several presumptive regions of schizophrenia patients. However, no research, to our knowledge, has looked for schizophrenia related differences in cortical volume and degree of cortical folding in post-mortem posterior cingulate cortex (PCCx). Method: Brain tissues from 9 people who suffered from schizophrenia (DSM-IV) and 9 controls were cut into 3 mm coronal slices. Three alternative PCCx blocks were available for research. The 3 PCCx blocks were cut into 50 μm sections. The volume and gyrification index (GI) were measured in 15 tissue sections per brain (5 sections per block). Results: People who suffered with schizophrenia showed significant reductions in GI in rostral PCCx, trend reductions were seen in medial and caudal PCCx. In addition, the average volume of the rostral tissue sections was significantly lower in the schizophrenia cohort, suggesting that schizophrenia is associated with reduced volume in the rostral PCCx. However, a true volumetric assessment of the whole PCCx, rather than a limited number of sections from three alternative blocks, is needed to confirm such a hypothesis. [Copyright &y& Elsevier]

Accurate estimates of vegetation biophysical variables are valuable as input to models describing the exchange of carbon dioxide and energy between the land surface and the atmosphere and important for a wide range of applications related to vegetation monitoring, weather prediction, and climate change. The present study explores the benefits of combining vegetation index and physically based approaches for the spatial and temporal mapping of green leaf area index (LAI), total chlorophyll content (TC ab ), and total vegetation water content (VWC). A numerical optimization method was employed for the inversion of a canopy reflectance model using Terra and Aqua MODIS multi-spectral, multi-temporal, and multi-angle reflectance observations to aid the determination of vegetation-specific physiological and structural canopy parameters. Land cover and site-specific inversion modeling was applied to a restricted number of pixels to build multiple species-and environmentally dependent formulations relating the three biophysical properties of interest to a number of selected simpler spectral vegetation indices (VI). While inversions generally are computationally slow, the coupling with the simple and computationally efficient VI approach makes the combined retrieval scheme for LAI, TC ab , and VWC suitable for large-scale mapping operations. In order to facilitate application of the canopy reflectance model to heterogeneous forested areas, a simple correction scheme was elaborated, which was found to improve forest LAI predictions significantly and also provided more realistic values of leaf chlorophyll contents. The inversion scheme was designed to enable biophysical parameter retrievals for land cover classes characterized by contrasting canopy architectures, leaf inclination angles, and leaf biochemical constituents without utilizing calibration measurements. Preliminary LAI validation results for the Island of Zealand, Denmark (57°N, 12°E) provided confidence in the approach with root mean square (RMS) deviations between estimates and in-situ measurements of 0. 62, 0. 46, and 0. 63 for barley, wheat, and deciduous forest sites, respectively. Despite the independence on site-specific in-situ measurements, the RMS deviations of the automated approach are in the same range as those established in other studies employing field-based empirical calibration. Being completely automated and image-based and independent on extensive and impractical surface measurements, the retrieval scheme has potential for operational use and can quite easily be implemented for other regions. More validation studies are needed to evaluate the usefulness and limitations of the approach for other environments and species compositions. [Copyright &y& Elsevier]

Abstract: Adenosine is known to modulate the function of neostriatal neurons. Adenosine acting on A2A receptors increases the phosphorylation of dopamine- and cAMP-regulated phosphoprotein of M r 32 kDa (DARPP-32) at Thr34 (the cAMP-dependent protein kinase [PKA] site) in striatopallidal neurons, and opposes dopamine D2 receptor signaling. In contrast, the role of adenosine A1 receptors in the regulation of dopamine/DARPP-32 signaling is not clearly understood. Here, we investigated the effect of adenosine A1 receptors on D1, D2 and A2A receptor signaling using mouse neostriatal slices. An A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (100 nM), caused a transient increase, followed by a transient decrease, in DARPP-32 Thr34 phosphorylation. Our data support the following model for the actions of the A1 receptor agonist. The A1 receptor-induced early increase in Thr34 phosphorylation was mediated by presynaptic inhibition of dopamine release, and the subsequent removal of tonic inhibition by D2 receptors of A2A receptor/Golf/cAMP/PKA signaling. The A1 receptor-induced late decrease in Thr34 phosphorylation was mediated by a postsynaptic Gi mechanism, resulting in inhibition of D1 and A2A receptor-coupled Golf/cAMP/PKA signaling in direct and indirect pathway neurons, respectively. In conclusion, A1 receptors play a major modulatory role in dopamine and adenosine receptor signaling. [Copyright &y& Elsevier]

Abstract: As birds do not have a urinary bladder, the kidneys and lower gastrointestinal tract must function in concert to maintain fluid and electrolyte homeostasis. In birds, urine is conveyed to the cloaca, and moved by reverse peristalsis into the colon and digestive ceca. Digestive ceca have been well studied for non-passerine birds and have been shown to absorb substrates and water. The ceca of passerine birds have been suggested to be non-functional because of their small size. The present study was undertaken to examine the morphology and cytochemistry of the small ceca of the English sparrow (Passer domesticus). Three-dimensional reconstruction of the ceca from serially sectioned tissue showed these organs to have a central channel with a large number of side channels. Electron micrographs indicated that all of the channels are lined by epithelial cells with a very dense microvillus brush border as well as a region densely packed with mitochondria just below the brush border. Specific staining for Na+, K+-ATPase indicated the enzyme to be localized to the brush border. Quantification of Na+, K+-ATPase activity showed it to be comparable to the coprodeum of domestic fowl. The data suggest that the small ceca of passerine birds may function in fluid and electrolyte homeostasis. [Copyright &y& Elsevier]

Abstract: In this work, a role for the genes encoding glycoproteins I (gI) and E (gE) and the US9 protein of bovine herpesvirus type 5 (BHV-5) in neuropathogenicity and reactivation of latent infections was examined. Calves infected intranasally with a gI/gE/US9 deleted recombinant shed up to 102.85 TCID50/ml infectious virus in nasal secretions. Calves infected with the wild type BHV-5 parental virus shed up to 105 TCID50/ml virus. No signs of disease were observed in calves infected with the recombinant virus, whereas those infected with wild type virus displayed respiratory and neurological signs. The recombinant was only able to reach the basal portions of the central nervous system. In contrast, wild type virus was found widespread within the brain. Reactivation with dexamethasone 60 days post-infection resulted in reactivation of wild type virus, whereas the recombinant virus could not be reactivated. These studies demonstrate that genes gI, gE and US9 of BHV-5 are important for its neuropathogenicity and its ability to reactive from latency. [Copyright &y& Elsevier]

Coeliac disease, epilepsy and cerebral calcifications (CEC) syndrome is a rare clinical condition. One hundred and seventy-one patients have been reported in the literature. Patients are mostly from Italy, Spain, and Argentina, suggesting a geographically restricted condition. Epilepsy is more frequently characterized by occipital seizures. It may be benign or drug-resistant, sometime evolving into severe epileptic encephalopathy. Gluten free diet (GFD) efficacy seems to be inversely related to the duration of epilepsy and the young age of the patient. Patients with cerebral calcifications (CC) and coeliac disease (CD) without epilepsy are considered as having an incomplete form of CEC syndrome. Some patients with epilepsy and CC without CD are supposed to have a CEC syndrome with silent or latent CD.Whether CEC syndrome is a genetic condition, or whether epilepsy and/or CC are a consequence of an untreated CD is unknown yet. Since histopathological findings seem to be the expression of vascular calcifyied malformation, CEC syndrome may be considered a genetically determined entity, such as a type of Sturge-Weber-like phacomatosis. Moreover, CEC, as well as CD, is associated with HLA-DQ2 and HLA-DQ8 phenotype and genotype. The progressive growth and late occurrence of CC before beginning a GFD, the demonstration of anti-gliadin antibodies in the cerebro-spinal fluid and the association with HLA class II genes, suggest that an immune reaction originating from the jejunal mucosa, triggered by gliadin in gluten intolerance predisposed subjects (HLA phenotype) may be responsible for seizures and CC. Moreover, a long-lasting untreated CD folic acid deficiency may cause calcifications.Probably, CEC is considered a genetic, non-inherited, ethnically and geographically restricted syndrome associated with environmental factors. [Copyright &y& Elsevier]

In previous studies, we have shown that agonists influence the ability of D2 dopamine receptors to couple to G proteins and here we extend this work. The human D2Short dopamine receptor and a natural polymorphism of this D2Short(Ser311Cys), have been studied by co-expressing the receptors in insect cells with Gβ1γ2 and either Gαo, Gαi1, Gαi2 or Gαi3 G protein subunits. These preparations have been used to study the G protein coupling profiles of the two receptors and the influence of agonists. Receptor/G protein coupling was analysed in dopamine/[3H]spiperone competition binding experiments and through stimulation of [35S]GTPγS binding. Although the Ser311Cys polymorphism itself had no appreciable effect on the G protein coupling specificity of the D2 receptor, agonist stimulation of [35S]GTPγS binding, revealed that both dopamine and (+)-3PPP showed a clear preference for Gαo compared to the Gαi subtypes, but quinpirole did not. These results indicate that agonists are able to stabilise different receptor conformations with different abilities to couple to G proteins. [Copyright &y& Elsevier]

Membrane-associated processes may be particularly susceptible to perturbation by the high hydrostatic pressures and low temperatures of the deep ocean. Transmembrane signaling by guanyl nucleotide binding protein (G protein) coupled receptors (GPCRs) is affected at a number of steps: (1) agonist activation of the GPCR; (2) the interaction of the receptor with the heterotrimeric G protein; (3) the G protein GTPase cycle; and (4) the activation and function of the effector element, adenylyl cyclase. The effects of low temperature and high hydrostatic pressures on the A1 adenosine receptor–inhibitory G protein (Gi)–adenylyl cyclase signaling complex were examined in teleost fishes from three families, Scorpaenidae, Macrouridae and Moridae. In a comparison of teleost fishes, rat and chicken, species with body temperatures from 1 to 40 °C, at atmospheric pressure, A1 adenosine receptor agonist binding is conserved at the body temperature of the species. In the marine teleost fishes examined, increased pressure decreases agonist efficacy. There are differences among species in the effects of increased hydrostatic pressure on G protein interactions with receptors, GTP binding to G protein α subunits and the intrinsic GTPase activity of α subunits. Adenylyl cyclase activity and modulation are affected by increased pressure in all the species examined, except Antimora rostrata which was unaffected by pressure changes. At pressures approximating those which the species experience in situ adenylyl cyclase activity retains its sensitivity to modulators. To understand the physiological consequences of impaired cell signaling several prototypical human diseases are discussed. [Copyright &y& Elsevier]

There is growing awareness of the price disparities for equivalent services in healthcare. We aimed to characterize regional variations in fees charged by gastroenterologists in Manhattan, NY. All private practice gastroenterologists in Manhattan were contacted and asked what they charge fee-paying patients for initial consultations for nonspecific gastrointestinal symptoms. Cost information was obtained from 89 offices, and practices were classified on the basis of location in Manhattan. We observed significant regional variation; gastroenterologists on the Upper East Side (1.20-fold the overall mean) charged more than twice as those on the Upper West Side (0.58-fold the mean) and 50% more than gastroenterologists in South Manhattan (0.76-fold the mean). The coefficient of variation was 46%; the most expensive gastroenterologist charged 14-fold more than the least expensive. We provide evidence for significant regional variation in prices for medical services. Future studies are needed to characterize regional price variations in other aspects of healthcare. [ABSTRACT FROM AUTHOR]

With the expansion of urbanization caused by the growth of population and industrial activities, the urban/city and suburban areas are facing a variety of environmental threats. Although more research and urban policy has advocated and practiced the development of green infrastructure (GI) to support urban sustainable environment, the evaluation framework for the development of GI for promoting environmental sustainability is still insufficient. Moreover, the Analytic Hierarchy Process (AHP) commonly applied in published literature, makes an unrealistic assumption of independent relationships among dimensions/criteria in decision making for satisfying the real-world problem. Therefore, the purpose of this study is to construct the evaluation framework, including four dimensions and related ten criteria, using a new hybrid-modified multiple attribute decision-making (MADM) model for developing and improving the GI for promoting environmental sustainability. This MADM model is combined with three different methodologies of MADM, including the Decision-Making Trial and Evaluation Laboratory (DEMATEL) for constructing the influential network relation map (INRM) to explore the complex influential inter-relationships and DEMATEL based on Analytic Network Process (DANP) for determining the influential weights with the VIse Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR) for evaluating and presenting improvement strategies for six different GIs. The empirical study indicates that DEMATEL and DANP Results suggest that decision-makers should pay more attention to the improvement of Design (D 4) and Materials (D 2) in terms of dimensions when utilizing the GI to promote environmental sustainability. Because these dimensions are enhanced, Species (D 1) and Energy (D 3) will be improved in synchronization. From the perspective of criteria, five are key core criteria and need to be focused on first: increasing the green coverage rate (B 9), utilizing sustainable materials (B 4), using ecological engineering (B 8), shaping species biodiversity (B 1), and reducing energy consumption (B 5). Modified VIKOR reveals that "grass swales" are a comparatively better choice among six GIs for promoting environmental sustainability toward achieving the aspiration level. Therefore, this MADM model is beneficial to provide a more convincing assessment framework and improvement strategies for the development of GI for promoting environmental sustainability. As a result, these modified MADM models can be shown more conveniently and reasonably than traditional methods such as traditional AHP or ANP method. • Providing an evaluation framework for green infrastructure (GI) for promoting environmentally sustainability. • A new hybrid modified multiple attribute decision-making (MADM) model is presented. • Considering the influential relationship among dimension/criteria improves the un-realistic shortcoming. • The result of DEMATEL and DANP indicate that Design (D 2) and Materials (D 2) and relevant criteria should be focused. • Modified VIKOD suggests that "Grass swales" have better performance among six GI. [ABSTRACT FROM AUTHOR]

Guidelines recommend testing patients with peptic ulcer disease for Helicobacter pylori infection. We sought to identify factors associated with adherence to testing for H pylori in patients hospitalized for bleeding ulcers and to evaluate whether performing these tests affect risk for rebleeding. We performed a retrospective study of 830 inpatients who underwent endoscopy from 2011 through 2016 for gastrointestinal bleeding from gastric or duodenal ulcers. We searched electronic medical records for evidence of tests to detect H pylori by biopsy, serologic, or stool antigen analyses. We used multivariable models to identify clinical, demographic, and endoscopic factors associated with testing for H pylori. Kaplan-Meier analysis was performed to determine whether H pylori testing altered risk for the composite outcome of rebleeding or death within 1 year of admission. Among the patients hospitalized for bleeding peptic ulcer disease during the 6-year period, 19% were not tested for H pylori within 60 days of index endoscopy. Hospitalization in the intensive care unit (ICU) was the factor most frequently associated with nonadherence to H pylori testing guidelines (only 66% of patients in the ICU were tested vs 90% of patients not in the ICU; P <.01), even after we adjusted for ulcer severity, coagulation status, extent of blood loss, and additional factors (adjusted odds ratio, 0.42; 95% CI, 0.27–0.66). Testing for H pylori was associated with a 51% decreased risk of rebleeding or death during the year after admission (adjusted hazard ratio 0.49; 95% CI, 0.36–0.67). In an analysis of hospitalized patients who underwent endoscopy for gastrointestinal bleeding from gastric or duodenal ulcers, we found admission to the ICU to be associated with failure to test for H pylori infection. Failure to test for H pylori was independently associated with increased risk of rebleeding or death within 1 year of hospital admission. We need strategies to increase testing for H pylori among inpatients with bleeding ulcers. [ABSTRACT FROM AUTHOR]

Abstract: The antagonism of 5-HT3 receptor by mirtazapine results in an antiemetic effect, suggesting that mirtazapine could be considered a successful antiemetic agent in patients suffering from severe nausea and vomiting. There have been several reports of successful mirtazapine treatment for nausea or vomiting from secondary causes but cases of primary severe nausea and vomiting are still lacking, in particular, there are no reported cases in Asians. The authors report two cases with severe nausea and vomiting that were dramatically treated with mirtazapine in the Korean population. [Copyright &y& Elsevier]

Background & Aims Chronic granulomatous disease (CGD) is an inherited disorder of the reduced nicotinamide adenine dinucleotide phosphate oxidase complex within phagocytic cells that predisposes people to bacterial and fungal infections. Approximately 40% of patients with CGD have gastrointestinal involvement. We aimed to characterize the endoscopic features of gastrointestinal CGD and define the role of endoscopy in patients. Methods We created a database of all patients with CGD seen at the National Institutes of Health from 1990 through 2010. We identified patients who had an endoscopy, and collected information from those with CGD-associated inflammatory bowel disease. We analyzed clinical data (demographic information and symptoms), endoscopic data (indication, preparation quality, degree of inflammation, mucosal findings, and complications), and pathologic data. Results A total of 211 endoscopies (96 esophagogastroduodenoscopies, 82 colonoscopies, and 33 flexible sigmoidoscopies) were performed at the National Institutes of Health on 78 patients with CGD. Esophageal, gastric, and duodenal inflammation were detected in 21%, 74%, and 37% of patients, respectively. Esophageal dysmotility and structural abnormalities were noted in 26%. Of the patients who had colonic CGD–inflammatory bowel disease, 74% had skip lesions and 93% had anorectal disease. Enteric fistulae were found in 18% of patients; 73% of these were perianal. Colonic strictures were observed in 24% of patients; 80% were in the anorectal area. Conclusions Based on an analysis of clinical and endoscopic data from 78 patients, CGD–inflammatory bowel disease is a distinct entity, primarily involving the anus and rectum, with skip lesions in the remaining bowel. Bowel strictures and fistulae are present in a significant number of patients. Upper gastrointestinal tract inflammatory disease is common, although typically not as severe as colonic disease. Upper and lower endoscopies are important in characterizing the gastrointestinal features of CGD. [ABSTRACT FROM AUTHOR]

Background & Aims: Matrix metalloproteinase (MMP)-9, a member of the gelatinase family of MMPs, mediates leukocyte migration during inflammation. Inflammation contributes to development of postoperative ileus (POI), which is caused by physical disturbances to the bowel during abdominal surgery. We evaluated the role of MMP-9 in POI and investigated whether disruption of MMP-9 or administration of an inhibitor of MMP-9 activity reduced cellular inflammation and bowel dysmotility in rat and mouse models of POI. Methods: Mice and rats underwent laparotomy and bowel manipulation; bowel tissues were collected 3 to 24 hours later and analyzed by real-time reverse-transcriptase polymerase chain reaction, immunoblot, in situ zymography, and functional analyses. Results: Bowel manipulation resulted in a time-dependent increase in MMP-9 expression within the intestinal muscularis; increases in MMP-9 messenger RNA were inducible nitric oxide synthase dependent. Immunoblot analyses confirmed the presence of the proenzyme and the catalytically active form of MMP-9. Administration of MMP-2/MMP-9 II, a dual active-site inhibitor, reduced the number of myeloperoxidase-positive immune cells that infiltrated the muscularis and prevented the surgically induced reduction in bowel smooth muscle contractility. Zymography analysis, performed in muscularis whole mounts in situ, indicated that MMP-9 and not MMP-2 mediated the gelatinase activity observed in infiltrating cells. MMP-9 knockout mice were protected from the inflammation and dysmotility associated with POI. Conclusions: MMP-9 mediates cellular inflammatory responses within the intestinal muscularis in mouse and rat models of POI. Inhibition of MMP-9 activity reduced recruitment of immune cells to the intestinal muscularis, preventing loss of smooth muscle contractility. Induction of MMP-9 expression requires inducible nitric oxide synthase. [Copyright &y& Elsevier]

Background & Aims: Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that acts on dendritic cells, mast cells, T cells, and B cells. TSLP is involved in the pathogenesis of allergic inflammation in the lung and skin, but data indicate a regulatory role in the gastrointestinal tract. We tested the functional role of TSLP in mouse models of gastrointestinal allergy and tolerance. Methods: TSLP Receptor (TSLPR) +/+ and TSLPR−/− mice were sensitized and challenged with ovalbumin; models of allergic diarrhea or systemic anaphylaxis were studied. To induce oral tolerance, mice were fed with low-dose ovalbumin before they were immunized with it. Tolerance was measured from inhibition of ear swelling in a delayed-type hypersensitivity reaction. Results: TSLPR−/− mice were protected from the onset of allergic diarrhea; they did not develop mastocytosis in the jejunum and had reduced ovalbumin-immunoglobulin E in their serum, compared with TSLPR+/+ mice. TSLPR−/− mice also lost T helper cell (Th) 2-mediated inflammation in the jejunum. In contrast, sensitization and oral tolerance were not impaired in TSLPR−/− mice. Transfer of wild-type, Th2-primed cells to TSLPR−/− mice completely restored the development of allergic diarrhea. Antigen presentation assays showed that TSLPR on T cells, but not dendritic cells, was required to mediate the Th2 response. Conclusions: TSLP is required for allergic inflammation but not primary sensitization or tolerance to food proteins in the gastrointestinal tract; it amplifies Th2 responses directly from CD4+ T cells. [ABSTRACT FROM AUTHOR]