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Despite the improved survival rates of patients with advanced stage melanoma since the introduction of ICIs, many patients do not have (long‐term) benefit from these treatments. There is evidence that the exposome, an accumulation of host‐extrinsic factors including environmental influences, could impact ICI response. Recently, a survival benefit was observed in patients with BRAF wild‐type melanoma living in Denmark who initiated immunotherapy in summer as compared to winter. As the Netherlands lies in close geographical proximity to Denmark and has comparable seasonal differences, a Dutch validation cohort was established using data from our nationwide melanoma registry. In this study, we did not observe a similar seasonal difference in overall survival and are therefore unable to confirm the Danish findings. Validation of either the Dutch or Danish findings in (combined) patient cohorts from other countries would be necessary to determine whether this host‐extrinsic factor influences the response to ICI‐treatment. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to determine predictive factors for the circumferential resection margin (CRM) within two northern European countries with supposed similarity in providing rectal cancer care. Method: Data for all patients undergoing rectal resection for clinical tumour node metastasis (TNM) stage I–III rectal cancer were extracted from the Swedish ColoRectal Cancer Registry and the Dutch ColoRectal Audit (2011–2015). Separate analyses were performed for cT1–3 and cT4 stage. Predictive factors for the CRM were determined using univariable and multivariable logistic regression analyses. Results: A total of 6444 Swedish and 12 089 Dutch patients were analysed. Over time the number of hospitals treating rectal cancer decreased from 52 to 42 in Sweden, and 82 to 79 in the Netherlands. In the Swedish population, proportions of cT4 stage (17% vs 8%), multivisceral resection (14% vs 7%) and abdominoperineal excision (APR) (37% vs 31%) were higher. The overall proportion of patients with a positive CRM (CRM+) was 7.8% in Sweden and 5.4% in the Netherlands. In both populations with cT1–3 stage disease, common independent risk factors for CRM+ were cT3, APR and multivisceral resection. No common risk factors for CRM+ in cT4 stage disease were found. An independent impact of hospital volume on CRM+ could be demonstrated for the cT1–3 Dutch population. Conclusion: Within two northern European countries with implemented clinical auditing, rectal cancer care might potentially be improved by further optimizing the treatment of distal and locally advanced rectal cancer. [ABSTRACT FROM AUTHOR]

Abstract: Background: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. Methods: Esophageal full‐thickness biopsies from 42 (22 females; age range: 16‐82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the “edgeR” option of R‐Bioconductor. Data were validated by real‐time RT‐PCR, western blotting and immunohistochemistry. Key Results: Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P ≤ 10−3. Nine genes with a P ≤ 10−4 were further validated. CYR61, CTGF, c‐KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c‐KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho‐Akt was significantly reduced in achalasia patients vs controls. Conclusions & Inferences: The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia. [ABSTRACT FROM AUTHOR]

Abstract: Background: Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29‐02 (azelastine hydrochloride (AZE) and fluticasone propionate [FP]) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29‐02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. Methods: A 4‐week double‐blinded placebo‐controlled trial with MP29‐02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction in nasal flow upon cold dry air exposure. The effects of AZE ± FP on barrier integrity and airway inflammation were studied in a murine model of HDM‐induced NHR and on reduced activation of murine sensory neurons and human mast cells. Results: MP29‐02 but not placebo reduced NHR (P < .0001 vs P = .21), levels of substance P (P = .026 vs P = .941), and β‐hexosaminidase (P = .036 vs P = .632) in human nasal secretions. In wild‐type C57BL6 mice, the reduction in β‐hexosaminidase levels (P < .0001) by AZE + FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage (P = .0012) and completely reversed eosinophilic inflammation (P = .0013). In vitro, repeated applications of AZE + FP desensitized sensory neurons expressing the transient receptor potential channels TRPA1 and TRPV1. AZE + FP reduced MC degranulation to the same extent as AZE alone. Conclusion: MP29‐02 treatment reduces inflammatory mediators and NHR in AR. The effects of AZE + FP on MC degranulation, nasal epithelial barrier integrity, and TRP channels provide novel insights into the pathophysiology of allergic rhinitis. [ABSTRACT FROM AUTHOR]

Background Abnormal abdominal pain perception is the most bothersome and difficult to treat symptom of functional gastrointestinal disorders ( FGIDs). Visceral pain stimuli are perceived and transmitted by afferent neurons residing in the dorsal root ganglia that have sensory nerve endings in the gut wall and mesentery. Accumulating evidence indicates that peripheral activation and sensitization of these sensory nerve endings by bioactive mediators released by activated immune cells, in particular mast cells, can lead to aberrant neuroimmune interactions and the development and maintenance of visceral hypersensitivity. Besides direct neuronal activation, low concentrations of proteases, histamine, and serotonin can chronically sensitize nociceptors, such as TRP channels, leading to persistent aberrant pain perception. Purpose This review discusses the potential mechanisms underlying aberrant neuroimmune interactions in peripheral sensitization of sensory nerves. A better understanding of the cells, mediators, and molecular mechanisms triggering persistent aberrant neuroimmune interactions brings new insights into their contribution to the physiology and pathophysiology of visceral pain perception and provides novel opportunities for more efficient therapeutic treatments for these disorders. [ABSTRACT FROM AUTHOR]

Background Infectious gastroenteritis is a major risk factor to develop postinfectious irritable bowel syndrome ( PI- IBS). It remains unknown why only a subgroup of infected individuals develops PI- IBS. We hypothesize that immunogenetic predisposition is an important risk factor. Hence, we studied the effect of Citrobacter rodentium infection on visceral sensitivity in Th1-predominant C57 BL/6 and Th2-predominant Balb/c mice. Methods Eight-week-old mice were gavaged with C. rodentium, followed by 1 h of water avoidance stress ( WAS) at 5 weeks PI. At 10, 14 days, and 5 weeks PI, samples were assessed for histology and inflammatory gene expression by RT- qPCR. Visceral sensitivity was evaluated by visceromotor response recordings ( VMR) to colorectal distension. Key Results Citrobacter rodentium evoked a comparable colonic inflammatory response at 14 days PI characterized by increased crypt length and upregulation of Th1/Th17 cytokine mRNA levels ( puncorrected < 0.05) in both C57 BL/6 and Balb/c mice. At 5 weeks PI, inflammatory gene mRNA levels returned to baseline in both strains. The VMR was maximal at 14 days PI in C57 BL/6 (150 ± 47%; p = 0.02) and Balb/c mice (243 ± 52%; p = 0.03). At 3 weeks PI, the VMR remained increased in Balb/c (176 ± 23%; p = 0.02), but returned to baseline in C57 BL/6 mice. At 5 weeks PI, WAS could not re-introduce visceral hypersensitivity ( VHS). Conclusions & Inferences Citrobacter rodentium infection induces transient VHS in C57 BL/6 and Balb/c mice, which persisted 1 week longer in Balb/c mice. Although other strain-related differences may contribute, a Th2 background may represent a risk factor for prolonged PI- VHS. As PI- VHS is transient, other factors are crucial for persistent VHS development as observed in PI- IBS. [ABSTRACT FROM AUTHOR]

The article discusses the highlights of the TANDEM meeting, a fresh idea that brought primary and clinical scientists together in order to come up with new research discoveries in neurogastroenterology and motility, which was held in Istanbul, Turkey in June 2015. It says that the best project chosen during the meeting will be funded by the European Society for Neurogastroenterology and Motility.

Background To date, genetic-association studies of single nucleotide polymorphisms ( SNP) in selected candidate genes with the symptom phenotype of irritable bowel syndrome ( IBS) have typically involved hundreds to 2000 patients. SNPs in immune-related genes, such as cytokine and cytokine receptor encoding genes, have been reported to associate with IBS risk. Methods We conducted two independent case-control studies on 16 SNPs in IL1R1, IL4, IL6, IL8, IL10, IL23R, TNFA, and TNFSF15, one from the UK (194 patients and 92 healthy volunteers) and one from the USA (137 patients and 96 healthy volunteers). The main aim was to examine the relationship between inherited immunological diversity and IBS risk in a meta-analysis which included 12 additional, earlier studies. The meta-analysis comprised a total of 2894 patients (839 IBS-C, 1073 IBS-D, 502 IBS-M), and 3138 healthy volunteers with self-reported Caucasian ancestry. Key Results The association of SNP rs4263839 ( TNFSF15) was investigated in four studies and confirmed in the meta-analysis: IBS ( OR 1.19, 95% CI 1.08-1.31), and IBS-C ( OR 1.24, 95% CI 1.08-1.42). No additional SNPs residing in immunogenes associated with IBS symptom phenotypes. Conclusions & Inferences Our meta-analysis could not confirm a major role of most investigated SNPs, but a moderate association between rs4263839 TNFSF15 and IBS, in particular IBS-C. The analysis emphasizes the importance of definition and phenotype homogeneity, adequate study size and representativeness of the patient and control collective. [ABSTRACT FROM AUTHOR]

Background Although animal models of the irritable bowel syndrome ( IBS) have provided important insights, there are no models that fully express the features of this complex condition. One alternative approach is the use of human intestinal biopsies obtained during endoscopic procedures to examine peripheral mechanisms in this disorder. These studies have served to confirm the existence of peripheral pathways in humans with IBS and have provided many new mechanistic insights. Two general approaches have been employed; one approach has been to examine the biological activity of mediators within the mucosal tissue of IBS patients and the other has been to examine changes in the structural properties of key signaling pathways contained within the biopsies. Using these approaches, important changes have been discovered involving the enteric nervous system and the extrinsic sensory pathway (dorsal root ganglia neurons), the immune system, and epithelial signaling in IBS patients compared to healthy subjects. Purpose This review will systematically explore these mechanistic pathways, highlight the implications of these novel findings and discuss some of the important limitations of this approach. [ABSTRACT FROM AUTHOR]

Background In irritable bowel syndrome ( IBS), familial clustering and transfer across generations may largely depend on environmental factors but this is difficult to establish in the human setting. Therefore, we aimed to set up a relevant animal model. We investigated whether susceptibility to stress induced visceral hypersensitivity in maternally separated ( MS) Long Evans rats can be transferred across generations without further separation protocols and, if so, whether this depends on maternal care. Methods At adult age, we evaluated pre- vs post water avoidance ( WA) changes in visceromotor response to distension in non-handled second filial generation offspring ( NH-F2) of previously separated MS-F1 dams. Furthermore, the role of maternal care was evaluated by cross-fostering F2 offspring of NH-F1 and MS-F1 dams and subsequent sensitivity measurements at adult age. Involvement of mast cells in post stress hypersensitivity of NH-F2 rats was evaluated by mast cell stabilization. Key Results In adult NH-F2 offspring of MS-F1 dams, post- WA hypersensitivity to colorectal distension was observed in 80% of rats compared with 19% in offspring of NH-F1 dams. Cross-fostered pups adapted to the phenotype of the foster mother: pups of NH-F1 dams nursed by MS-F1 dams showed post- WA hypersensitivity to distension at adult age and vice versa (100% and 20% respectively). In NH-F2 rats, post- WA hypersensitivity was reversed by mast cell stabilizer doxantrazole. Conclusions & Inferences Maternal separated-induced susceptibility to stress-triggered visceral hypersensitivity is transferred across generations and this transfer depends on maternal care. Thus, MS is a suitable model to evaluate environmental triggers relevant to IBS clustering in families. [ABSTRACT FROM AUTHOR]

Aim The study included investigation of factors determining suboptimal adjuvant chemotherapy of patients diagnosed with Stage III colon cancer. Method All 606 patients diagnosed with Stage III colon cancer between 2006 and 2008 in the western part of the Netherlands were included. Patient [gender, age, comorbidity and socio-economic status ( SES)], tumour (location, stage and grade) and treatment (emergency surgery, laparoscopic surgery, reoperation, hospital stay and multidisciplinary meeting) factors were examined in logistic regression analyses predicting a complicated postoperative period and omission, delay and discontinuation of adjuvant chemotherapy. Results Overall, 27% of all patients experienced a complicated postoperative period, which was independently associated with emergency surgery, older age, multiple comorbidity, male gender and poor tumour grade. Of patients who survived this period, 60% received chemotherapy. Chemotherapy was omitted more often in women, the elderly and in patients with Stage IIIB, reoperation, prolonged hospital stay and (borderline) after open surgery. Of patients who received chemotherapy, 86% started within 8 weeks after surgery. Patients with a higher SES, reoperation and prolonged hospital stay had a higher probability of a delayed start. Sixty-seven per cent of patients completed their chemotherapy. For women, elderly patients and patients with prolonged hospital stay a higher probability of discontinuation was noted. Conclusion Age was the most important predictive factor for receiving adjuvant chemotherapy. However, at all ages, complicated postoperative recovery negatively influenced the administration of chemotherapy to Stage III colon cancer patients, as well as a timely start and completion of chemotherapy. [ABSTRACT FROM AUTHOR]

In this article, we report the modification of poly(styrene- alt-maleic anhydride) (PSMA) with monofunctional amine-terminated poly(dimethyl siloxane) (PDMS-NH2) by thermal imidization, followed by the preparation and characterization of a surfactant-free artificial latex thereof and application of this latex onto cotton fabric. The imidization reaction was monitored by NMR and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. 1,2-Cyclohexyldicarboxylic anhydride was chosen as a model compound for the PSMA copolymer; this allowed a more detailed characterization by NMR and ATR-FTIR spectroscopy. After the PSMA/PDMS-NH2 imidization reached completion, a fraction of the anhydrides were ammonolyzed. In this way, a self-emulsifying latex with an average particle diameter of approximately 145 nm and a ζ potential of −56 mV was obtained. It was found that the PDMS-modified PSMA latex in which 30 mol% of the initial amount of anhydride groups were previously imidized by using PDMS-NH2 and a fraction of the anhydrides were ammonolyzed with 0.3 eq. of NH3 (PSMA30) was stable in the pH range 4-10. The water contact angle values of the latex-coated cotton textile fabric indicated a hydrophobized surface, with a static contact angle of 135.7°± 1.2°. The washing studies with a standard soap solution of the cotton samples with or without crosslinker showed that the crosslinked PSMA30 offered a good coating durability to the cotton. This waterborne resin based on surfactant-free latices displayed promising properties for coating applications and seemed to be very suitable for the hydrophobization of polar surfaces. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

Background Early life trauma can predispose to increased visceral pain perception. Human neuroimaging studies emphasize that altered brain processing may contribute to increased visceral sensitivity. The aim of our study was to evaluate brain responses to painful visceral stimuli in maternal-separated rats before and after acute stress exposure in vivo. Methods H215O microPET scanning was performed during colorectal distention in maternal-separated rats before and after water avoidance stress. Brain images were anatomically normalized to Paxinos space and analyzed by voxel-based statistical parametric mapping (SPM2). Colorectal induced visceral pain was assessed by recording of the visceromotor response using abdominal muscle electromyography. Key Results Colorectal distention (1.0-2.0 mL) evoked a volume-dependent increase in visceromotor response in maternal-separated rats. Stress [water avoidance (WA)] induced an increased visceromotor response to colorectal distention in awake and anesthetized rats. In pre-WA rats, colorectal distention evoked significant increases in regional blood flow in the cerebellum and periaquaductal gray (PAG). Colorectal distention post-WA revealed activation clusters covering the PAG as well as somatosensory cortex and hippocampus. At maximal colorectal distention, the frontal cortex was significantly deactivated. Conclusions & Inferences WA stress induced increased pain perception as well as activation of the somatosensory cortex, PAG, and hippocampus in maternal-separated rats. These findings are in line with human studies and provide indirect evidence that the maternal separation model mimics the cerebral response to visceral hypersensitivity in humans. [ABSTRACT FROM AUTHOR]

Background Acute stress-induced hypersensitivity to colorectal distention was shown to depend on corticotropin releasing factor (CRF)-induced mast cell degranulation. At present it remains unclear whether CRF also induces chronic poststress activation of these cells. Accordingly, the objective of this study was to compare pre- and poststress CRF-receptor antagonist treatment protocols for their ability to, respectively, prevent and reverse mast cell dependent visceral hypersensitivity in a rat model of neonatal maternal separation. Methods The visceromotor response to colonic distention was assessed in adult maternally separated and non-handled rats before and at different time points after 1 h of water avoidance (WA). Rats were treated with the mast cell stabilizer doxantrazole and the CRF receptor-antagonist α-helical-CRF (9-41). Western blotting was used to assess mucosal protein levels of the mast cell protease RMCP-2 and the tight junction protein occludin. Key Results In maternally separated, but not in non-handled rats, WA induced chronic hypersensitivity (up to 30 days) to colorectal distention. Visceral hypersensitivity was prevented, but could not be reversed by administration of α-helical-CRF (9-41). In contrast, however, the mast cell stabilizer doxantrazole reversed visceral hypersensitivity. Compared with vehicle-treated rats, pre-WA α-helical-CRF (9-41) treated animals displayed higher mucosal RMCP-2 and occludin levels. Conclusions & Inferences Water avoidance-stress leads to persistent mast cell dependent visceral hypersensitivity in maternally separated rats, which can be prevented, but not reversed by blockade of peripheral CRF-receptors. We conclude that persistent poststress mast cell activation and subsequent visceral hypersensitivity are not targeted by CRF-receptor antagonists. [ABSTRACT FROM AUTHOR]

Genome wide association studies and meta-analyses identified risk factors related to epithelial integrity of the intestinal barrier, innate immune responses and autophagy in inflammatory bowel disorder (IBD) and celiac disease. Irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder (FGID), coexists and shares common, although milder, features with IBD and celiac disease. Although our knowledge on genetic variability in IBS symptom generation is very limited, smaller scale studies attempt to provide insight in the mechanisms underlying IBS. Camilleri et al. identified associations for susceptibility loci in inflammatory and epithelial barrier genes with colonic transit in lower FGID. Their report is the first descriptive study to assess potential genetic factors involved in motor function. Further exploration of genetic variation in IBS will be crucial to unravel its' pathogenesis. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2011; 34: 638-648 Summary Background Functional dyspepsia is one of the most prevalent (15-40%) functional gastrointestinal disorders. Antidepressants such as amitriptyline are often used in these patients, but clinical studies are currently lacking. Aim To evaluate the effect of 8 weeks of treatment with amitriptyline on drinking capacity, symptoms evoked by a standardised drink test (primary endpoint) and clinical symptoms (secondary endpoint). Methods Patients meeting the Rome III criteria for functional dyspepsia (FD) were invited to participate in a double blind, randomised, placebo-controlled trial and were treated with either amitriptyline (12.5-50 mg) or placebo during 8 weeks. All included patients underwent a nutrient drink test before and after treatment. Drinking capacity and evoked symptoms were recorded. In addition, dyspeptic symptoms were weekly assessed using PAGI SYM (patient assessment of upper gastrointestinal symptom severity index) questionnaire. Results Thirty-eight patients (amitriptyline n = 18, placebo n = 20; age 41 ± 2 year, 61% F) completed the study. The drinking capacity of liquid meal was not affected by either amitriptyline or placebo treatment. Postprandial symptoms were not significantly different between amitriptyline and placebo. During the entire treatment, total symptom score (0.47 points, P = 0.02) and nausea (0.86 points, P = 0.004) on PAGI SYM were significantly reduced by amitriptyline compared with placebo. Conclusions Amitriptyline did not affect drinking capacity and postprandial symptoms evoked by the drink test in FD patients. However, total clinical symptom score and nausea were reduced during 8 weeks of treatment. Our data suggest that amitriptyline particularly improves nausea in functional dyspepsia, but larger clinical trials are needed to further confirm our findings. [ABSTRACT FROM AUTHOR]

Background Normal gastrointestinal motility requires intact networks of interstitial cells of Cajal (ICC). Interstitial cells of Cajal numbers are maintained by a balance between cell loss factors and survival/trophic/growth factors. Activation of 5-HT2B receptors expressed on ICC increases ICC proliferation in vitro. It is not known whether 5-HT2B receptors on ICC are activated in vivo. The aims of this study were to investigate if adult ICC proliferate, whether the proliferation of ICC in vivo is affected by knocking out the 5-HT2B receptor, and if alterations in proliferation affect ICC networks. Methods Proliferating ICC were identified by immunoreactivity for Ki67 in both the myenteric and deep muscular plexus regions of the jejunum in mice with a targeted insertion of a neomycin resistance cassette into the second coding exon of the htr2b receptor gene. Key Results Adult ICC do proliferate. The number of proliferating ICC was lower in the myenteric plexus region of Htr2b−/− compared to Htr2b +/+ mice. The volume of Kit-positive ICC was 30% lower in the myenteric plexus region and 40% lower in the deep muscular plexus region in Htr2b−/− mice where the number of ICC was also reduced. Conclusions & Inferences Interstitial cells of Cajal proliferate in adult mice and activation of 5-HT2B receptors results in increased proliferation of ICC in vivo. Furthermore, lack of 5-HT2B receptor signaling reduces the density of ICC networks in mature mice. These data suggest that 5-HT2B receptor signaling is required for maintenance of ICC networks, adding 5-HT to the growing number of factors shown to regulate ICC networks. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome is in part characterized by an increased sensitivity to colonic distension. Stress is an important trigger factor for symptom generation. We hypothesized that stress induces visceral hypersensitivity via mast cell degranulation and transient receptor ion channel 1 (TRPV1) modulation. We used the rat model of neonatal maternal separation (MS) to investigate this hypothesis. The visceromotor response to colonic distention was assessed in adult MS and non-handled (NH) rats before and after acute water avoidance (WA) stress. We evaluated the effect of the mast cell stabilizer doxantrazole, neutralizing antiserum against the mast cell mediator nerve growth factor (NGF) and two different TRPV1 antagonists; capsazepine (non-specific) and SB-705498 (TRPV1-specific). Immunohistochemistry was used to assess post-WA TRPV1 expression in dorsal root ganglia and the presence of immunocytes in proximal and distal colon. Retrograde labelled and microdissected dorsal root ganglia sensory neurons were used to evaluate TRPV1 gene transcription. Results showed that acute stress induces colonic hypersensitivity in MS but not in NH rats. Hypersensitivity was prevented by prestress administration of doxantrazole and anti-NGF. Capsazepine inhibited and SB-705498 reversed poststress hypersensitivity. In MS rats, acute stress induced a slight increase in colonic mast cell numbers without further signs of inflammation. Post-WA TRPV1 transcription and expression was not higher in MS than NH rats. In conclusion, the present data on stress-induced visceral hypersensitivity confirm earlier reports on the essential role of mast cells and NGF. Moreover, the results also suggest that TRPV1 modulation (in the absence of overt inflammation) is involved in this response. Thus, mast cells and TRPV1 are potential targets to treat stress-induced visceral hypersensitivity. [ABSTRACT FROM AUTHOR]

The article discusses a study which explored the wettability and improvement of adhesion of ultraviolet (UV) curable powder coatings on polypropylene substrates. The authors photographed various benzophenone type photoinitiators onto polypropylene. It was observed that the modified samples demonstrated a better wettability and higher surface energies.

The majority of the body's serotonin (5-HT) is produced by the gastrointestinal tract. 5-HT has several functions in the gastrointestinal tract. 5-HT is a paracrine signalling molecule released from enterochromaffin cells, a survival and proliferating factor and a neurotransmitter. The actions of 5-HT are transduced by a large family of 5-HT receptors, several of which are expressed on different gastrointestinal cell types including enteric nerves, smooth muscle and interstitial cells of Cajal (ICC). This review will summarize recent advances in understanding the role of 5-HT in regulating function of ICC, and the expression and function of 5-HT receptors on muscle and enteric nerves in human tissue. Rodent ICC express several 5-HT receptors including 5-HT2B receptors which regulate ICC survival and proliferation. Human smooth muscle and enteric neurons also express several 5-HT receptor subtypes. Expression and function of these receptors is significantly different from small laboratory animals. 5-HT7 receptor activation causes relaxation of muscle, whereas 5-HT2B receptors increase muscle activity. The 5-HT4 receptor appears to mediate both inhibition and activation of smooth muscle involving myogenic as well as neural actions. Despite the abundant expression of 5-HT3 receptors in the human enteric nervous system no functional correlate has been as yet demonstrated. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Cost-Effectiveness of Different Treatment Strategies With Intrapartum Antibiotic Prophylaxis to Prevent Early-Onset Group B Streptococcal Disease," by M. E. van den Akker-van Marle et al., published in a 2005 issue of "BJOG: An International Journal of Obstetrics and Gynaecology."

An abstract of the conference paper "Therapeutical options of Cesarean scar pregnancy: experience of a University Hospital," by M. Bij de Vaate, and colleagues is presented.

Transient receptor ion channel 1 (TRPV1) is a nociceptor involved in visceral hypersensitivity. Aminoglycosides like neomycin are not only potent antibiotics but in vitro data suggest that neomycin also acts as a TRPV1-antagonist and alleviates somatic pain responses. To what extent neomycin reduces visceral hypersensitivity remains unknown. Therefore, we aimed to investigate whether neomycin can inhibit in vivo TRPV1-dependent hypersensitivity responses in two rat models of visceral pain. In the first model rats were pretreated with intraperitoneal (i.p.) capsazepine, the selective TRPV1 antagonist SB-705498, neomycin or vehicle alone and 30 min later instilled with intracolonic TRPV1-activating capsaicin. Likewise, rats were pretreated with 10 days oral neomycin and then subjected to intracolonic capsaicin. The visceromotor response (VMR) to distension was measured before and after capsaicin application. In addition, the VMR to distension was measured in adult maternal separated rats before and after acute stress. Before the 2nd distension protocol these rats were treated with i.p. neomycin, amoxycillin or vehicle alone. Our results showed that capsaicin administration induced an enhanced VMR to distension that was prevented by i.p. capsazepine, SB-705498 and neomycin. Oral neomycin treatment changed bacterial faecal content but could not inhibit capsaicin induced visceral hypersensitivity. In maternal separated rats acute stress induced an enhanced response to distension that was reversed by i.p. neomycin, but not amoxycillin. These data indicate that (i.p.) neomycin can inhibit visceral hypersensitivity to distension in a nonbactericidal manner and suggest that TRPV1-modulation may be involved. [ABSTRACT FROM AUTHOR]

Based on the discomfort/pain threshold during rectal distension, irritable bowel syndrome (IBS) patients may be subtyped as normo- or hypersensitive. We previously showed that mucosal biopsy supernatants from IBS patients activated enteric and visceral afferent neurons. We tested the hypothesis that visceral sensitivity is linked to the degree of neuronal activation. Normo- and hypersensitive IBS patients were distinguished by their discomfort/pain threshold to rectal balloon distension with a barostat. Using potentiometric and Ca(2+) dye imaging, we recorded the response of guinea-pig enteric submucous and mouse dorsal root ganglion (DRG) neurons, respectively, to mucosal biopsy supernatants from normosensitive (n = 12 tested in enteric neurons, n = 9 tested in DRG) and hypersensitive IBS patients (n = 9, tested in both types of neurons). In addition, we analysed the association between neuronal activation and individual discomfort/pain pressure thresholds. The IBS supernatants evoked Ca(2+) transients in DRG neurons and spike discharge in submucous neurons. Submucous and DRG neurons showed significantly stronger responses to supernatants from hypersensitive IBS patients as reflected by higher spike frequency or stronger [Ca(2+)]i transients in a larger proportion of neurons. The neuroindex as a product of spike frequency or [Ca(2+)]i transients and proportion of responding neurons correlated significantly with the individual discomfort/pain thresholds of the IBS patients. Supernatants from hypersensitive IBS patients caused stronger activation of enteric and DRG neurons. The level of activation correlated with the individual discomfort/pain threshold pressure values. These findings support our hypothesis that visceral sensitivity is linked to activation of peripheral neurons by biopsy supernatants., (© 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.)

Objective: To develop a patient decision aid (PtDA) for mode of delivery after caesarean section that integrates personalised prediction of vaginal birth after caesarean (VBAC) with the elicitation of patient preferences and evidence-based information., Design: A PtDA was developed and pilot tested using the International Patients Decision Aid Standards (IPDAS) criteria., Setting: Obstetric health care in the Netherlands., Population: A multidisciplinary steering group, an expert panel, and 25 future users of the PtDA, i.e. women with a previous caesarean section., Methods: The development consisted of a construction phase (definition of scope and purpose, and selection of content, framework, and format) and a pilot testing phase by interview. The process was supervised by a multidisciplinary steering group., Main Outcome Measures: Usability, clarity, and relevance., Results: The construction phase resulted in a booklet including unbiased balanced information on mode of birth after caesarean section, a preference elicitation exercise, and tailored risk information, including a prediction model for successful VBAC. During pilot testing, visualisation of risks and clarity formed the main basis for revisions. Pilot testing showed the availability of tailored structured information to be the main factor involving women in decision-making. The PtDA meets 39 out of 50 IPDAS criteria (78%): 23 out of 23 criteria for content (100%) and 16 out of 20 criteria for the development process (80%). Criteria for effectiveness (n = 7) were not evaluated., Conclusions: An evidence-based PtDA was developed, with the probability of successful VBAC and the availability of structured information as key items. It is likely that the PtDA enhances the quality of decision-making on mode of birth after caesarean section., (© 2013 Royal College of Obstetricians and Gynaecologists.)

Objective: To evaluate the effectiveness of an exercise programme for pregnant women who were overweight or obese and at risk for gestational diabetes mellitus (GDM)., Design: Randomised controlled trial., Setting: Hospitals and midwifery practices in the Netherlands., Population: Pregnant women who were overweight or obese and at risk for GDM between 2007 and 2011., Methods: Normal care was compared with an exercise training programme during pregnancy. The training consisted of aerobic and strength exercises, and was aimed at improving maternal fasting blood glucose, insulin sensitivity, and birthweight. Linear regression analyses were performed to determine the effects., Main Outcome Measures: Maternal outcome measures were fasting blood glucose (mmol/l), fasting insulin (pmol/l) and HbA1c (%), body weight (kg), body mass index (kg/m(2) ), and daily physical activity (minute/week). Offspring outcome measures were birthweight and fetal growth., Results: A total of 121 women were randomly allocated to either a control (n = 59) or an intervention (n = 62) group. Intention-to-treat analysis showed that the exercise programme did not reduce maternal fasting blood glucose levels nor insulin sensitivity. Also, no effect was found on birthweight., Conclusions: The exercise intervention performed over the second and third trimester of pregnancy had no effects on fasting blood glucose, insulin sensitivity, and birthweight, most probably because of low compliance. The high prevalence of women at risk for GDM calls for further research on possible interventions that can prevent GDM, and other types of interventions to engage this target group in physical activity and exercise., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Objective: To predict instrumental vaginal delivery or caesarean section for suspected fetal distress or failure to progress., Design: Secondary analysis of a randomised trial., Setting: Three academic and six non-academic teaching hospitals in the Netherlands., Population: 5667 labouring women with a singleton term pregnancy in cephalic presentation., Methods: We developed multinomial prediction models to assess the risk of operative delivery using both antepartum (model 1) and antepartum plus intrapartum characteristics (model 2). The models were validated by bootstrapping techniques and adjusted for overfitting. Predictive performance was assessed by calibration and discrimination (area under the receiver operating characteristic), and easy-to-use nomograms were developed., Main Outcome Measures: Incidence of instrumental vaginal delivery or caesarean section for fetal distress or failure to progress with respect to a spontaneous vaginal delivery (reference)., Results:   375 (6.6%) and 212 (3.6%) women had an instrumental vaginal delivery or caesarean section due to fetal distress, and 433 (7.6%) and 571 (10.1%) due to failure to progress, respectively. Predictors were age, parity, previous caesarean section, diabetes, gestational age, gender, estimated birthweight (model 1) and induction of labour, oxytocin augmentation, intrapartum fever, prolonged rupture of membranes, meconium stained amniotic fluid, epidural anaesthesia, and use of ST-analysis (model 2). Both models showed excellent calibration and the receiver operating characteristics areas were 0.70-0.78 and 0.73-0.81, respectively., Conclusion:   In Dutch women with a singleton term pregnancy in cephalic presentation, antepartum and intrapartum characteristics can assist in the prediction of the need for an instrumental vaginal delivery or caesarean section for fetal distress or failure to progress., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)