bluuebunny/crossref_metadata_2025 huggingface dataset:
Population‐based study shows that Hirschsprung disease does not have a negative impact on education and income
Authors: Granström Anna Löf , Svenningsson Anna , Nordenskjöld Agneta , Wester Tomas
Published: September 2016

Aim

Hirschsprung disease is a multifactorial disease, which is mainly treated during childhood. There is a risk of impaired bowel function for a long time after surgery, and its impact on adult life has not been well studied. This study assessed whether having Hirschsprung disease affected social parameters such as educational level and income.

Methods

This nationwide, population‐based cohort study included all patients with Hirschsprung disease, registered in the Swedish National Patient Register from 1964 and 2013, who were each matched by age and sex to ten individuals randomly selected from the Swedish Population Register. The study outcomes were the highest educational level and individual disposable income in 2013 registered by Statistics Sweden.

Results

The study comprised 389 patients and 3847 controls, both 76% male, with a median age of 25 years. There were no statistically significant differences in highest educational level between the groups (p = 0.327). The median individual disposable income was 142 200 (0–817 200) Swedish Krona in the patient group and 159 000 (0–3 418 900) in the control group (p = 0.615).

Conclusion

The highest educational level and the individual disposable income did not differ between patients with Hirschsprung disease and controls, indicating that the disease had a low impact on these parameters.
Proliferative Properties of 17β‐aminoestrogens in MCF‐7 Human Breast Cancer Cells
Authors: Lemini Cristina , Estela Avila María , Medina Martha , Sánchez Carlos , Figueroa Alejandra , García‐Mondragón Maria Juana , Vargas‐Vázquez Arsenio , Jiménez‐Orozco Alejandro
Published: September 2016

The 17β‐aminoestrogens (AEs) prolame, butolame and pentolame are weakly oestrogenic in rodents and display anticoagulant properties in contrast to oestradiol (E2) which presents pro‐coagulant effects, potentially thrombogenic. They possess anti‐anxiety and antidepressive properties, being good candidates for menopausal hormone therapy (MHT). Their capability to induce proliferation of MCF‐7 human breast cancer cells, in which proliferative rate depends on oestrogens, has not been explored; thus, the aim of this work was to characterize it. AEs’ proliferation properties were evaluated compared with E2 in MCF‐7 carcinoma cell line cultures using established methods. Receptor mediation on cell proliferation was studied by co‐incubating them with the oestrogen receptor antagonists tamoxifen, ICI 182,780 and the selective antagonists MPP (ERα) and PHTPP (ERβ). E2 and AEs increased MCF‐7 cell proliferation; their proliferative effect was between 1.5‐2 and E2 = 3.6 compared with controls (0); their relative proliferative effect was 18–38% (E2 = 100%) with a relative proliferative potency of 4.5–8.9 (E2 = 100). The ERα antagonist MPP inhibited the MCF‐7 cell proliferation induced by E2 and AEs; on the contrary, the ERβ antagonist PHTPP exacerbated the proliferative response, showing that the AEs’ proliferative activity was mainly ERα‐mediated and apparently controlled by ERβ. Preliminary cytometric DNA flow analysis showed that AEs’ cell cycle S phase inducer property was lower than E2 following the proliferative order: E2 > butolame > prolame > pentolame, indicating pentolame with the weakest proliferative properties and being the safest of this series as a candidate for MHT.
Use of a Target‐Mediated Drug Disposition Model to Predict the Human Pharmacokinetics and Target Occupancy of GC1118, an Anti‐epidermal Growth Factor Receptor Antibody
Authors: Park Wan‐Su , Han Seunghoon , Lee Jongtae , Hong Taegon , Won Jonghwa , Lim Yangmi , Lee Kyuhyun , Byun Han Yeul , Yim Dong‐Seok
Published: September 2016

GC1118 is an anti‐epidermal growth factor receptor (EGFR) monoclonal antibody that is currently under clinical development. In this study, the pharmacokinetics (PK) of GC1118 were modelled in monkeys to predict human PK and receptor occupancy (RO) profiles. The serum concentrations of GC1118 and its comparator (cetuximab) were assessed in monkeys with a non‐compartmental analysis and a target‐mediated drug disposition (TMDD) model after intravenous infusion (3–25 mg/kg) of these drugs. The scaling exponent of the EGFR synthesis rate was determined using a sensitivity analysis. The human cetuximab exposures were simulated by applying different exponents (0.7–1.0) for the EGFR synthesis rate in the allometric monkey PK model. Simulated Cmax and area under the curve values therein were compared with those previously reported in the literature to find the best exponent for the EGFR synthesis rate in human beings. The TMDD model appropriately described the monkey PK profile, which showed a decrease in clearance (CL; 1.2–0.4 ml/hr/kg) as the dose increased. The exponents for CL (0.75) and volume of distribution (Vd; 1.0) were used for the allometric scaling to predict human PK. The allometric coefficient for the EGFR synthesis rate chosen by the sensitivity analysis was 0.85, and the RO profiles that could not be measured experimentally were estimated based on the predicted concentrations of the total target and the drug–target complex. Our monkey TMDD model successfully predicts human PK and RO profiles of GC1118 and can be used to determine the appropriate dose for a first‐in‐human study investigating this drug.
Students and Doctors are Unaware of the Cost of Drugs they Frequently Prescribe
Authors: Schutte Tim , Tichelaar Jelle , Nanayakkara Prabath , Richir Milan , van Agtmael Michiel
Published: September 2016

Given the increasing healthcare costs of an ageing population, there is growing interest in rational prescribing, which takes costs of medication into account. We aimed to gain insight into the attitude to and knowledge of medication costs of medical students and doctors in daily practice. This was a cross‐sectional electronic survey among medical students (bachelor/master) and doctors (consultants/registrars). Attitude to costs was evaluated using a cost‐consciousness scale. In open questions, the participants estimated the cost of commonly prescribed (generic/non‐generic) drugs (including separate pharmacy dispensing costs). They were asked where they could find information about drug costs. Overall, a reasonable cost‐consciousness was found. Students were less conscious of the cost than were doctors (15.56 SD 3.25 versus 17.81 SD 2.25; scale 0–24; p = 0.001). In contrast to this consciousness, actual estimated drug costs were within a 25% margin for only 5.4% of generic and 13.7% of proprietary drugs (Wilcoxon signed‐rank, p < 0.001). The price of generic drugs was frequently overestimated (77.5%) and that of proprietary drugs was underestimated (51.4%). The dispensing costs were estimated correctly for 30% of the drugs. Most doctors (84%) and a minority of students (40%) were able to identify at least one source of information about drug costs. While doctors and students considered it important to be aware of the cost of drugs, this attitude is not reflected in their ability to estimate the cost of frequently prescribed drugs. Cost awareness is important in therapeutic reasoning and cost‐effective prescribing. Both should be better addressed in (undergraduate) pharmacotherapy education.
Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors, AZM475271 and PP2
Authors: Wang Yiming , Gratzke Christian , Tamalunas Alexander , Rutz Beata , Ciotkowska Anna , Strittmatter Frank , Herlemann Annika , Janich Sophie , Waidelich Raphaela , Liu Chunxiao , Stief Christian G , Hennenberg Martin
Published: September 2016

Background and Purpose

In benign prostatic hyperplasia, increased prostate smooth muscle tone and prostate volume may contribute alone or together to urethral obstruction and voiding symptoms. Consequently, it is assumed there is a connection between smooth muscle tone and growth in the prostate, but any molecular basis for this is poorly understood. Here, we examined effects of Src family kinase (SFK) inhibitors on prostate contraction and growth of stromal cells.

Experimental Approach

SFK inhibitors, AZM475271 and PP2, were applied to human prostate tissues to assess effects on smooth muscle contraction, and to cultured stromal (WPMY‐1) and c‐Src‐deficient cells to examine effects on proliferation, actin organization and viability.

Key Results

SFKs were detected by real time PCR, western blot and immunofluorescence in human prostate tissues, some being located to smooth muscle cells. AZM475271 (10 μM) and PP2 (10 μM) inhibited SFK in prostate tissues and WPMY‐1 cells. Both inhibitors reduced α1‐adrenoceptor‐mediated and neurogenic contraction of prostate strips. This may result from cytoskeletal deorganization, which was observed in response to AZM475271 and PP2 in WPMY‐1 cells by staining of actin filaments with phalloidin. This was paralleled by reduced proliferation of wildtype but not of c‐Src‐deficient cells; cytotoxicity was mainly observed at higher concentrations (>50 μM).

Conclusions and Implications

In human prostate, smooth muscle tone and growth are both controlled by an SFK‐dependent process, which may explain their common role in bladder outlet obstruction. Targeting prostate smooth muscle tone and prostate growth simultaneously by a single compound may, in principal, be possible.
Continuous administration of the mTORC1 inhibitor everolimus induces tolerance and decreases autophagy in mice
Authors: Kurdi Ammar , De Doncker Mireille , Leloup Arthur , Neels Hugo , Timmermans Jean‐Pierre , Lemmens Katrien , Apers Sandra , De Meyer Guido R Y , Martinet Wim
Published: September 2016

Background and Purpose

Everolimus is an allosteric inhibitor of the mechanistic target of rapamycin complex 1 (mTORC1) widely known for its potent autophagy stimulating properties. Because everolimus shows poor solubility and stability in aqueous solutions, long‐term in vivo administration in preclinical models is challenging. The aim of the present study was to evaluate the effects of short‐term and long‐term everolimus administration on mTORC1 inhibition and autophagy induction in mice.

Experimental Approach

We developed a vehicle in which everolimus was solubilized and stable at 37°C for at least 1 month. Using osmotic minipumps, GFP microtubule‐associated protein light chain 3 transgenic mice were treated continuously either with vehicle or everolimus (1.5 mg·kg−1 per day) for 3 or 28 days. Alternatively, a regimen consisting of intermittent everolimus administration (every other day) for 56 days by oral gavage was used. Autophagy markers and mTORC1 activation status were investigated in the liver.

Key Results

As expected, everolimus inhibited mTORC1 and stimulated autophagy in the liver after 3 days of treatment. However, continuous administration for 28 days resulted in hyperactivation of the Akt1‐mTORC1 pathway accompanied by a remarkable decrease in autophagy markers. Everolimus given intermittently for 56 days partially rescued mTORC1 sensitivity to the drug but without inducing autophagy. The failure to induce autophagy following long‐term everolimus administration was due to uncoupling of the mTORC1 substrate unc‐51 like autophagy activating kinase 1.

Conclusions and Implications

Our data encourage the use of intermittent everolimus regimens to prevent tolerance and to extend its activity.
Construction of explicit models to correlate the structure and the inhibitory activity of aldose reductase: Flavonoids and sulfonyl‐pyridazinones as inhibitors
Authors: Cui Fengchao , Liu Lunyang , Tang Haifeng , Yang Kecheng , Li Yunqi
Published: September 2016

The correlation between binding energies and bioactivities is the core of structure‐based computer‐aided drug design. However, many models to address this correlation are still strongly system‐dependent at current stage. We constructed two explicit models to correlate the binding energies with the inhibitory activities of flavonoids and sulfonyl‐pyridazinones as inhibitors of aldose reductase. The introduction of multiple complex states comprised of protein, coenzyme, substrate, and inhibitor can remarkably improve the correlation coefficients, compared with that using single complex state. Recombination of energy terms from complex structures and molecular descriptors of inhibitors can further improve the correlation. The explicit models provide correlation coefficients of 0.90 and 0.92 for flavonoids and sulfonyl‐pyridazinones, respectively. These models also steadily present the contribution from each energy term and the favorite of protein–inhibitor complex states. Meanwhile, we also observed that some inhibitors can accommodate alternative sites out of the conserved binding pocket at the presence/absence of coenzyme and substrate. It is responsible for the remarkable change in the binding energies and thus significantly influences the correlation between the structures and the inhibitory activities. Overall, this work presents a rational way to construct reliable explicit models through the combination of multiple physically accessible complex states, even though each of them only bears marginal information related to their activities.
Preparation, characterization, and in vitro evaluation of bleomycin‐containing nanoliposomes
Authors: Chiani Mohsen , Shokrgozar Mohammad Ali , Azadmanesh Kayhan , Norouzian Dariush , Mehrabi Mohammad Reza , Najmafshar Aazam , Akbarzadeh Azim
Published: September 2016

Bleomycin is an anticancer drug used against various types of cancers. The aim of this study was to prepare a new PEGylated and non‐PEGylated nanoliposomal formulation of bleomycin (PEG‐nLip‐BLM and nLip‐BLM) and evaluate their anticancer activity in different tumor cell lines. The liposomes were prepared by thin‐film hydration method, and then, bleomycin (BLM) was loaded to the prepared vesicles. The size, zeta potential, entrapment efficiency, loading rate, release profile, and cytotoxicity of liposomal formulations in TC‐1, LLC1, and HFLF‐PI5 cell lines were investigated. Mean particle size and zeta potential of the PEG‐nLip‐BLM and nLip‐BLM were found to be 99.4 ± 4.6 nm and −34.83 ± 4.7 mV; and 112.2 ± 7.2 nm and −27.5 ± 3.2 mV, respectively, which were stable for at least 2 months. Encapsulation and loading efficiency of BLM for PEG‐nLip‐BLM and nLip‐BLM were obtained about 83.1 ± 4.2% and 14.3 ± 2.5%; and 78.3 ± 8.6% and 11.1 ± 3.3%, respectively. Drug release study showed a slow release pattern without considerable burst effect. The liposomal formulations indicated lower toxicity compared to free drug in case of TC‐1 and HFLF‐PI5 cells, but their cytotoxicity against LLC1 cells was significantly higher than free drug. The results of this study indicated that PEG‐nLip‐BLM can be a suitable candidate for drug delivery to solid tumors.
Language Brokering and Depressive Symptoms in Mexican‐American Adolescents: Parent–Child Alienation and Resilience as Moderators
Authors: Kim Su Yeong , Hou Yang , Gonzalez Yolanda
Published: September 2016

This study aimed to untangle the mixed effects of language brokering by examining a contextual factor (i.e., parent–child alienation) and a personal attribute (i.e., resilience) that may relate to adolescents’ feelings during translating (i.e., sense of burden and efficacy) and that may moderate the association between such feelings and adolescent depressive symptoms. Participants included 557 adolescent language brokers (Mage = 12.96) in Mexican‐American families. Results showed that adolescents with a strong sense of alienation from parents or low resilience (a) experienced more burden or less efficacy in translating and (b) were more susceptible to the detrimental effects of feeling a sense of burden and the beneficial effects of experiencing a sense of efficacy, as measured by depressive symptoms.
The influence of titanium surface characteristics on macrophage phenotype polarization during osseous healing in type I diabetic rats: a pilot study
Authors: Lee Ryan S. B. , Hamlet Stephen M. , Ivanovski Saso
Published: September 2016

Objectives

This study assessed the effect of titanium surface modification on macrophage phenotype polarization and osseous healing under diabetic conditions.

Materials and methods

Critical‐sized calvarial defects were created in healthy and streptozotocin‐induced type I diabetic Sprague‐Dawley rats. Titanium (Ti) discs with either large‐grit sandblasted and acid‐etched micro‐rough (SLA) or hydrophilic‐modified SLA (modSLA) surfaces were used to cover the healing defect for a period of up to 28 days. Samples of the exudate within the calvarial defect and beneath the titanium discs were collected 1, 4 and 7 days post‐surgery for inflammatory cytokine analysis using an ELISA. The macrophage phenotype(s) on the Ti disc surfaces were determined by CD11c+ (M1) and CD163+ (M2) immunofluorescent staining. Samples of the healing defects at days 14 and 28 were also prepared for histomorphometric analysis.

Results

Cytokine levels in the diabetic animals were higher than those of the healthy group throughout the observation period. The modSLA surface significantly reduced MIP‐2 levels at day 1 in both diabetic and healthy animals, and MCP‐1 levels at day 4 in the diabetic animals. Immuno‐fluorescent staining showed that an M2‐like macrophage phenotype was more frequently found on the modSLA surface at day 1 in healthy and day 4 in both healthy and diabetic animals. Histomorphometric analysis showed more new bone formation on the modSLA surface at days 14 and 28 in both groups, although statistically significant differences were only found in the healthy group.

Conclusion

Diabetic conditions greatly increased the expression of proinflammatory cytokines during osseous healing. The modSLA surface was shown to promote an M2‐like macrophage phenotypic response in titanium adherent macrophages despite the significantly elevated inflammatory environment induced by uncontrolled type I diabetes. Modulation of the macrophage phenotype by the modSLA surface in the early healing period was associated with osseous healing under both healthy and uncontrolled diabetic conditions.
Effect of two designs of implant‐supported overdentures on peri‐implant and posterior mandibular bone resorptions: a 5‐year prospective radiographic study
Authors: Elsyad Moustafa A. , Alokda Mohammed Mahmoud , Gebreel Ashraf Anwer , Hammouda Nelly Ibrahim , Habib Ahmed Ali
Published: September 2016

Objectives

The aim of this study was to evaluate and compare the effect of two designs of implant‐supported overdentures on peri‐implant and posterior mandibular bone resorptions after 5 years of follow‐up.

Materials and methods

Twenty edentulous patients were randomly assigned into two equal groups: Group I (GI), patients received overdentures supported and retained by cantilevered bars on two canine implants and Group II (GII), patients received overdentures retained by straight bars on two canine implants and supported by two‐first molar implants. Peri‐implant vertical (VBL) and horizontal (HBLO) bone losses were assessed on periapical radiographs at the time of overdenture insertion (T0), 6 months (T6 m), 1 year (T1), 3 years (T3), and 5 years (T5) after insertion. Posterior mandibular bone resorption was evaluated using proportional measurements (posterior area index, PAI) made on panoramic radiographs at T0 and T5.

Results

Group I recorded significant higher VBL than GII. VBL increased significantly with advance of time in both groups. Posterior implant recorded significant higher VBL than anterior implants in GII. HBLO did not differ significantly between groups or between observation times. Group I recorded significant higher PAI than GII at T5. Group, age, and initial height of the mandibular ridge were significantly correlated with PAI.

Conclusion

Within the limitations of this study, regarding the small sample size, it could be concluded that overdentures retained by straight bars on two canine implants and supported by two‐first molar implants present a clinical advantage in terms of peri‐implant and posterior mandibular bone preservation compared to overdentures supported and retained by cantilevered bars on two canine implants after 5 years.
Overexpression of Paxillin Correlates with Tumor Progression and Predicts Poor Survival in Glioblastoma
Authors: Sun Li‐Hua , Yang Fu‐Qiang , Zhang Chuan‐Bao , Wu Yi‐Ping , Liang Jing‐Shan , Jin Shuai , Wang Zheng , Wang Hong‐Jun , Bao Zhao‐Shi , Yang Zheng‐Xiang , Jiang Tao
Published: September 2016

Aims

To explore the prognostic and clinicopathological features of glioma with Paxillin (PXN) expression based on a large number of samples.

Methods

RNA sequencing data of 325 glioma samples from Chinese Glioma Genome Atlas (CGGA) database were obtained as discovery set. Three additional datasets were further obtained as validation sets. The protein expression pattern of PXN in glioma was measured by IHC. Kaplan–Meier survival and multivariate Cox analysis were used to estimate the survival distributions. Moreover, the functional annotation of PXN was also analyzed.

Results

In the discovery set, PXN overexpression was significantly associated with high‐grade glioma as well as the higher mortality in survival analysis (log‐rank test, P < 0.01). The results of the other validation datasets showed similar findings. PXN also served as an independent prognostic biomarker in glioblastoma patients. Functional assays showed that PXN contributed to glioma cell proliferation and invasion.

Conclusion

PXN plays as an oncogene in glioma progression and suggests a new potential biotarget for therapy.
Predictors of success for double balloon‐assisted endoscopic retrograde cholangiopancreatography in patients with Roux‐en‐Y anastomosis
Authors: Liu Ken , Joshi Vikram , Saxena Payal , Kaffes Arthur J.
Published: September 2016

Background and Aim

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with roux‐en‐Y anastomosis (REYA) is challenging. Use of double balloon enteroscope‐assisted ERCP (DBE‐ERCP) has been successful. We aim to determine predictors of successful biliary cannulation with DBE‐ERCP in patients with REYA.

Methods

We retrospectively studied patients with REYA who had DBE‐ERCP between 2009 and 2015.

Results

86 DBE‐ERCP were done on 52 patients. Patients had REYA for liver transplant (n = 26), gastrojejunostomy (n = 9), previous bile duct injury (n = 9), biliary atresia (n = 2) and other (n = 6). The biliary‐enteric anastomosis was reached in 76% and cholangiogram was successful in 70%. Highest success rates were in patients with previous bile duct injury (94%) or gastrojejunostomy (89%). Post‐transplant patients had intermediate success (64%). Patients with redo surgery (46%) and childhood surgery (38%), especially Kasai procedure (20%), had low success. Patients with previous bile duct injury were more likely to succeed (94% vs 63%, P = 0.010). Those more likely to fail were patients with childhood surgery (38% vs 73%, P = 0.037), biliary atresia (20% vs 73%, P = 0.013) and second operation post‐transplant (25% vs 70%, P = 0.046).

Conclusion

Indication for REYA impacts on successful biliary cannulation in patients undergoing DBE‐ERCP. The procedure is most successful in non‐liver transplant adult surgery and post‐transplant patients without a second operation. It is least successful in patients with surgically corrected biliary atresia and post‐transplant patients with second operation. Alternative methods of biliary access should be considered in these patients.
Double guidewire endoscopic technique, a major evolution in endoscopic retrograde cholangiopancreatography: Results of a retrospective study with historical controls comparing two therapeutic sequential strategies
Authors: Laquiere Arthur , Desilets Etienne , Belle Arthur , Castellani Paul , Grandval Philippe , Laugier René , Penaranda Guillaume , Lecomte Laurence , Boustiere Christian
Published: September 2016

Background and Aim

Endoscopic access to the common bile duct (CBD) remains difficult in 10% of cases, requiring alternative techniques .CBD access was difficult after either five unsuccessful attempts, five unintentional insertions into the pancreatic duct or >10‐min‐long unsuccessful attempts. This retrospective study with historical controls aimed to evaluate the benefit of the double guidewire (DGW) technique after failure of standard CBD cannulation.

Methods

From January 2012 to December 2014, all patients requiring therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with difficult access to CBD were included in a Studied group. This group was compared to a historical ERCP control group from January 2009 to December 2011. In the Studied group, a sequential strategy including DGW technique was done when the guidewire was unintentionally passed into the pancreatic duct. In the control group, only pre‐cut technique was used.

Results

Among the 538 patients with naive papilla eligible for ERCP, 73 had difficult CBD access. Successful CBD access rate was higher in the Studied group: 91% (50/55) versus 67% (12/18) P = 0.0215. Complication rates were similar in both groups: 28% versus 20%, P = 0.5207. LOS was shorter in the Studied group (9.2 ± 8.5 vs 14.4 ± 7.4 days, P = 0.0028). Post‐ERCP cholangitis were lower in the Studied group: 2% (1/55) versus 22% (4/18), P = 0.0118.

Conclusion

After standard cannulation failure, DGW technique increased successful CBD access rate and decreased LOS without increasing complications.
Feather melanin and microstructure variation in dark‐eyed juncoJunco hyemalisacross an elevational gradient in the Selkirk Mountains
Authors: de Zwaan Devin R. , Greenwood Jennifer L. , Martin Kathy
Published: September 2016

Variation in feather melanism and microstructure can arise through sexual selection and ecological functional drivers. Melanin‐based plumage traits are associated with sexual dichromatism and the intensity of sexual selection in many avian species, but also have several ecological benefits such as protection against ultra‐violet (UV) radiation, camouflage, and feather strength. Additionally, feather microstructure influences thermoregulation. Plumage variation across species is well documented; however, the relative role of sexual selection and ecological drivers in intra‐specific and within‐population variation is less established. We investigated UV reflectance, melanism, and feather microstructure in a population of Oregon dark‐eyed juncosJunco hyemalis oreganusbetween high (1900–2200 m a.s.l.) and low (450–800 m a.s.l.) elevations in the Selkirk Mountains to evaluate potential sexual selection and ecological drivers of variation. We found no difference in UV reflectance or lightness (melanism) of head feathers between elevations, but individuals at high elevation had lighter (less melanism) and less brown (less pheomelanin) body contour feathers than at low elevations. High elevation individuals also had longer contour feathers with more pronounced plumulaceous regions. Sexual dichromatism did not vary between elevations, leading us to reject sexual selection in favour of ecological functional drivers of plumage variation in this system. To our knowledge, this is the first study to identify within‐population differences in feather melanism and microstructure between different elevations.
Dynamic computed tomography is useful for prediction of pathological grade in pancreatic neuroendocrine neoplasm
Authors: Horiguchi Shigeru , Kato Hironari , Shiraha Hidenori , Tsutsumi Koichiro , Yamamoto Naoki , Matsumoto Kazuyuki , Tomoda Takeshi , Uchida Daisuke , Akimoto Yutaka , Mizukawa Syou , Tanaka Takehiro , Ichimura Koichi , Takaki Akinobu , Yagi Takahito , Okada Hiroyuki
Published: September 2016

Background and Aim

Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)‐guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS–FNA and dynamic CT in the diagnosis and pathological grading of PNEN.

Methods

In this retrospective study, 39 PNEN patients finally diagnosed via EUS–FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD.

Results

By using EUS–FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r = 0.83, P < 0.0001) and pathological grade (P = 0.0074).

Conclusions

Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult.
Overall and cause‐specific mortality in Korean patients with inflammatory bowel disease: A hospital‐based cohort study
Authors: Lee Ho‐Su , Choe Jaewon , Kim Seon‐Ok , Lee Sun‐Ho , Lee Hyo Jeong , Seo Hyungil , Kim Gwang‐Un , Seo Myeongsook , Song Eun Mi , Hwang Sung Wook , Park Sang Hyoung , Yang Dong‐Hoon , Kim Kyung‐Jo , Ye Byong Duk , Byeon Jeong‐Sik , Myung Seung‐Jae , Yoon Yong Sik , Yu Chang Sik , Kim Jin‐Ho , Yang Suk‐Kyun
Published: September 2016

Background and Aim

Limited data are available regarding mortality from inflammatory bowel disease in non‐Caucasian populations. Herein, we evaluated overall and cause‐specific mortality in a hospital‐based cohort of Korean inflammatory bowel disease patients.

Methods

We determined mortality in 2414 Crohn's disease patients and 2798 ulcerative colitis patients diagnosed between 1977 and 2013. Standardized mortality ratios were calculated in several demographic and phenotypic subgroups.

Results

During the mean 9‐year follow up, 114 patients died: 35 with Crohn's disease and 79 with ulcerative colitis. The overall standardized mortality ratios were 1.40 (95% confidence interval: 0.97–1.94) in Crohn's disease and 0.73 (0.58–0.91) in ulcerative colitis. In Crohn's disease, female sex, age < 30 years at diagnosis, disease duration > 10 years, ileocolonic disease at diagnosis, perianal fistula, intestinal resection, and ever‐use of corticosteroids were associated with higher mortality. In ulcerative colitis, male sex, age ≥ 30 years at diagnosis, disease duration ≤ 5 years, proctitis at diagnosis, and no history of colectomy were associated with lower mortality, while primary sclerosing cholangitis was associated with higher mortality. In both Crohn's disease and ulcerative colitis, high mortality rates due to nonmalignant gastrointestinal causes (standardized mortality ratios: 4.59 and 2.32, respectively) and gastrointestinal malignancies (standardized mortality ratios: 16.59 and 3.45, respectively) were observed. Cardiovascular mortality was lower in ulcerative colitis (standardized mortality ratio: 0.47).

Conclusions

The overall mortality tended to be higher in Crohn's disease patients than in the general population; it was slightly lower in ulcerative colitis patients than in the general population.
Disease severity and erythropoiesis in chronic hepatitis C
Authors: Huang Chung‐Feng , Huang Ching‐I , Yeh Ming‐Lun , Hou Chen , Hou Nai‐Jen , Hsieh Ming‐Yen , Huang Jee‐Fu , Chen Shinn‐Cherng , Lin Zu‐Yau , Dai Chia‐Yen , Chuang Wan‐Long , Yu Ming‐Lung
Published: September 2016

Background/Aims

The erythropoiesis in hepatitis C virus infection is unclear. We aimed to evaluate the erythropoietic components in chronic hepatitis C (CHC) patients.

Methods

The red blood cell (RBC) components, serum erythropoietin (EPO) levels, and their relationship to clinical characteristics were evaluated between 124 age‐matched and sex‐matched healthy controls and 248 histology‐proven CHC patients.

Results

Chronic hepatitis C patients had significantly higher serum levels of EPO (1.44 ± 0.36 log mIU/mL versus 1.03 ± 0.31 log mIU/mL, P < 0.0001) and lower hemoglobin (Hb) concentrations (14.6 ± 1.4 g/dL versus 15.3 ± 1.2 g/dL, P < 0.001) as compared with healthy controls. Among the CHC patients, the serum EPO level was negatively associated with the Hb concentration (β = −0.227; 95% confidence intervals [CI]: −0.09–0.027; P < 0.001) and RBC counts (β = −0.204; 95% CI: −0.245–0.061; P = 0.001) and was positively correlated with necroinflammatory activity (β = 0.201; 95% CI: 0.009–0.046; P = 0.003) and fibrosis (β = 0.143; 95% CI: 0.003–0.076; P = 0.04) of liver histopathology. For non‐cirrhotic CHC patients, the severity of liver necroinflammatory activity was positively correlated with the reticulocyte and serum EPO levels (P = 0.001 and 0.008, respectively), and negatively related to the RBC counts (P = 0.03). Using stepwise multivariate linear regression analysis, the grade of necroinflammatory activity was positive (β = 0.214; 95% CI: 0.046–0.209, P = 0.002), whereas the Hb concentration was inversely (β = −0.205; 95% CI: −0.09–0.018, P = 0.004) associated with the serum EPO levels in CHC patients.

Conclusions

The disease activity in CHC patients had a negative impact on erythropoiesis with compensatory higher but blunted EPO responses.
Cross‐linking for the analysis of α‐synuclein in the enteric nervous system
Authors: Corbillé Anne‐Gaëlle , Neunlist Michel , Derkinderen Pascal
Published: September 2016

Since the observation that aggregated α‐synuclein, the pathological hallmark of Parkinson's disease (PD), is found in the gut in almost all patients, it has been suggested that the enteric nervous system (ENS) could be a starting point for α‐synuclein pathology. α‐synuclein has long been thought to occur as a monomer in living cells, but recent studies reported that it instead exists as a tetramer in non‐neuronal cells and in neurons. Given the possible key role of the ENS in PD pathophysiology, we undertook the current research to characterize the native state of α‐synuclein in rat primary culture of ENS and in adult human healthy ENS. Using amine‐reactive cross‐linking, we showed that, by contrast to cell lines and brain neurons, α‐synuclein exists primarily as a monomer in intact enteric neurons, suggesting that the native state of α‐synuclein is different between the ENS and the brain. Our results provide new insights into the widely discussed concepts of α‐synuclein aggregation and misfolding in PD and raise issue about the possible transmission of α‐synuclein from the ENS to the brain.

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Mice lacking Faim2 show increased cell death in the MPTP mouse model of Parkinson disease
Authors: Komnig Daniel , Schulz Jörg B. , Reich Arno , Falkenburger Björn H.
Published: September 2016

The death receptor Fas/CD95 mediates apoptotic cell death in response to external stimuli. In neurons, Fas‐induced apoptosis is prevented by Fas‐apoptotic inhibitory molecule 2 (Faim2). Mice lacking Faim2 showed increased neurodegeneration in animal models of stroke and bacterial meningitis. We therefore tested the relevance of Faim2 in a classical animal model of Parkinson disease and determined the toxicity of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) in Faim2‐deficient mice. Without MPTP treatment, there was no difference in the dopaminergic system between Faim2‐deficient mice and control mice. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. Fourteen days after the last MPTP injection, the number of dopaminergic neurons in the lateral substantia nigra, assayed by stereological counting, was reduced by 39% in control mice and 53% in Faim2‐deficient mice. The density of dopaminergic fibers in the dorsal striatum was reduced by 36% in control mice and 69% in Faim2‐deficient mice, in the ventral striatum 44% in control mice and 76% in Faim2‐deficient mice. Fiber density recovered at 90 days after MPTP with similar density in both groups. Striatal catecholamine levels were reduced by 81–84% in both groups and recovered at 90 days. Faim2 expression was documented in mouse midbrain using quantitative reverse transcription‐PCR (qRT‐PCR) and found decreased after MPTP administration. Taken together, our findings demonstrate increased degeneration of dopaminergic neurons with Faim2 deficiency, indicating that Fas‐induced apoptosis contributes to cell death in the MPTP mouse model. Along with the decreased expression of Faim2 after MPTP, this finding indicates that boosting Faim2 function might represent a therapeutic strategy for Parkinson disease.

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Association between preschool eczema and medication for attention‐deficit/hyperactivity disorder in school age
Authors: Johansson Emma Kristin , Ballardini Natalia , Kull Inger , Bergström Anna , Wahlgren Carl‐Fredrik
Published: September 2016

Background

Several studies show an association between eczema and attention‐deficit/hyperactivity disorder (ADHD) in childhood, but the mechanisms and time sequence remain unclear. Information on the association between eczema and other disorders involving the central nervous system (CNS) is limited. The aim was to explore whether preschool eczema was associated with ADHD or other CNS‐associated disorders requiring pharmacotherapy at school age and to analyze whether eczema at other ages of childhood was associated with medication for ADHD.

Methods

From a Swedish birth cohort, 3606 children were included in the analyses. At 1, 2, 4, 8, 12, and 16 years of age, their parents answered questionnaires regarding eczema the last year. Information on prescribed medications during school age (10–18 years of age) was derived by record linkage to the Swedish Prescribed Drug Register.

Results

A total of 1178 (32.7%) of the children had preschool eczema (eczema at 1, 2, and/or 4 years), and 162 (4.5%) of the children had dispensed ADHD medication at school age. Preschool eczema was not associated with ADHD medication at school age (crude odds ratio 1.16; 95% Confidence Intervals: 0.83–1.61). There was no significant association between preschool eczema and use of antidepressants, migraine drugs, or anti‐epileptics at school age. Infantile eczema, school‐age eczema, and eczema ever up to 16 years of age were not associated with ADHD medication at school age.

Conclusions

In this large birth cohort, there were no significant associations between preschool eczema and medications for ADHD, depression/anxiety/phobia, migraine, or epilepsy at school age.
Non‐IgE‐mediated gastrointestinal food allergies in children
Authors: Caubet Jean‐Christoph , Szajewska Hania , Shamir Raanan , Nowak‐Węgrzyn Anna
Published: September 2016

Non‐IgE‐mediated gastrointestinal food allergic disorders (non‐IgE‐GI‐FA) including food protein‐induced enterocolitis syndrome (FPIES), food protein‐induced enteropathy (FPE), and food protein‐induced allergic proctocolitis (FPIAP) are relatively uncommon in infants and young children, but are likely under‐diagnosed. Non‐IgE‐GI‐FA have a favorable prognosis, with majority resolving by age 3–5 years. Diagnosis relies on the recognition of symptoms pattern in FPIAP and FPIES and biopsy in FPE. Further studies are needed for a better understanding of the pathomechanism, which will lead eventually to the development of diagnostic tests and treatments. Limited evidence supports the role of food allergens in subsets of constipation, gastroesophageal reflux disease, irritable bowel syndrome, and colic. The immunologic pathomechanism is not fully understood and empiric prolonged avoidance of food allergens should be limited to minimize nutrient deficiency and feeding disorders/food aversions in infants.
Streptococcus pyogenes as the cause of vulvovaginitis and balanitis in children
Authors: Randjelovic Gordana , Otasevic Suzana , Mladenovic‐Antic Snezana , Mladenovic Vesna , Radovanovic‐Velickovic Radmila , Randjelovic Marina , Bogdanovic Dragan
Published: September 2016

Background

Streptococcus pyogenes (group A Streptococcus) is the etiological agent of perineal infection in children, consisting of perianal infection, vulvovaginitis and balanitis. If it is not properly diagnosed and treated, it can persist for many months and can cause severe complications. Furthermore, treatment with penicillin can be followed by failures and recurrences.

Methods

We report here the prevalence of S. pyogenes isolates in genital tract specimens from girls (n = 1692) with symptoms of vulvovaginitis and from boys (n = 52) with balanitis in the municipality of Nis, Southeast‐Serbia (the Western Balkans) in a 10 year period, and the seasonal distribution, patient age and sensitivity to bacitracin and antimicrobial drugs used in the treatment of streptococcal infection.

Results

Streptococcal vulvovaginitis was diagnosed in 2.30% of examinees. Of those cases, 64.10% were detected from April to September, and it was most common (71.79%) in girls aged 3–7 years. Streptococcal balanitis was diagnosed in two instances: in a 4‐year‐old boy and in a 7‐year‐old boy. S. pyogenes strains resistant to bacitracin were identified in five girls. Two isolates with M phenotype and five isolates with cMLSB phenotype were identified.

Conclusions

Streptococcal vulvovaginitis was diagnosed less often in the present study, but it was still far more common than streptococcal balanitis in childhood. Bacitracin resistance of S. pyogenes strains should be taken into account in routine microbiological identification, and the detection of S. pyogenes isolates resistant to erythromycin requires surveillance in the present geographical territory.
Incidence of BK polyomavirus infection after kidney transplantation is independent of type of immunosuppressive therapy
Authors: Radtke Josephine , Dietze Nina , Fischer Lutz , Achilles Eike‐Gert , Li Jun , Scheidat Silke , Thaiss Friedrich , Nashan Bjoern , Koch Martina
Published: September 2016

Background

BK polyomavirus (BKV) infection and BKV nephropathy (BKVN) are risk factors for allograft function and survival.

Methods

We retrospectively analyzed BK viremia and BKVN in 348 patients who received a kidney transplantation donated after brain death (n=232) or living donation (n=116) between 2008 and 2013. A total of 266 patients were treated with standard immunosuppression consisting of basiliximab induction, calcineurin inhibitor (CNI), and mycophenolic acid (MPA, n=219) or everolimus (n=47); 82 patients received more intense immunosuppression with lymphocyte depletion, CNI and MPA (n=38) or everolimus (n=44).

Results

BK viremia occurred in 33 (9.5%) patients in the first year and in 7 (2.0%) recipients in the second year after transplantation. BKVN occurred in 4 (1.1%) patients in the first year. Donor and recipient age, diabetes, previous transplantation, and type of transplantation (donated after brain death vs living donation) were not risk factors (P>.05). BK incidence did not differ depending on induction or maintenance immunosuppression.

Conclusion

Incidence of BK viremia is independent of recipient characteristics, type of transplantation as well as induction and maintenance immunosuppression.
Control of colloidal placement by modulated molecular orientation in nematic cells
Authors: Peng Chenhui , Turiv Taras , Guo Yubing , Shiyanovskii Sergij V. , Wei Qi-Huo , Lavrentovich Oleg D.
Published: September 2016

Control of colloidal placement is achieved in nematic cells with photopatterned, spatially modulated molecular orientation.
Direct carbon-carbon coupling of furanics with acetic acid over Brønsted zeolites
Authors: Gumidyala Abhishek , Wang Bin , Crossley Steven
Published: September 2016

Zeolite-catalyzed acylation is used for selective formation of C–C bonds and could have applications in bioenergy.
Listeria monocytogenes Strains Underrepresented during Selective Enrichment with an ISO Method Might Dominate during Passage through Simulated Gastric Fluid and
In Vitro
Infection of Caco-2 Cells
Authors: Zilelidou Evangelia , Karmiri Christina-Vasiliki , Zoumpopoulou Georgia , Mavrogonatou Eleni , Kletsas Dimitris , Tsakalidou Effie , Papadimitriou Konstantinos , Drosinos Eleftherios , Skandamis Panagiotis
Published: September 2016

Various
Listeria monocytogenes
strains may contaminate a single food product, potentially resulting in simultaneous exposure of consumers to multiple strains. However, due to bias in strain recovery,
L. monocytogenes
strains isolated from foods by selective enrichment (SE) might not always represent those that can better survive the immune system of a patient. We investigated the effect of cocultivation in tryptic soy broth with 0.6% yeast extract (TSB-Y) at 10°C for 8 days on (i) the detection of
L. monocytogenes
strains during SE with the ISO 11290-1:1996/Amd 1:2004 protocol and (ii) the
in vitro
virulence of strains toward the Caco-2 human colon epithelial cancer cell line following exposure to simulated gastric fluid (SGF; pH 2.0)-HCl (37°C). We determined whether the strains which were favored by SE would be effective competitors under the conditions of challenges related to gastrointestinal passage of the pathogen. Interstrain competition of
L. monocytogenes
in TSB-Y determined the relative population of each strain at the beginning of SE. This in turn impacted the outcome of SE (i.e., favoring survival of competitors with better fitness) and the levels exposed subsequently to SGF. However, strong growth competitors could be outcompeted after SGF exposure and infection of Caco-2 cells by strains outgrown in TSB-Y and underdetected (or even missed) during enrichment. Our data demonstrate a preferential selection of certain
L. monocytogenes
strains during enrichments, often not reflecting a selective advantage of strains during infection. These findings highlight a noteworthy scenario associated with the difficulty of matching the source of infection (food) with the
L. monocytogenes
isolate appearing to be the causative agent during listeriosis outbreak investigations.

IMPORTANCE
This report is relevant to understanding the processes involved in selection and prevalence of certain
L. monocytogenes
strains in different environments (i.e., foods or sites of humans exposed to the pathogen). It highlights the occurrence of multiple strains in the same food as an important aspect contributing to mismatches between clinical isolates and infection sources during listeriosis outbreak investigations.