bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of galectin‐1 in urinary bladder urothelial carcinoma cell invasion through the JNK pathway
Authors: Shen Kun‐Hung , Li Chien‐Feng , Chien Lan‐Hsiang , Huang Cheng‐Hao , Su Chia‐Cheng , Liao Alex C. , Wu Ting‐Feng
Published: July 2016

Human galectin‐1 is a member of the galectin family, proteins with conserved carbohydrate‐recognition domains that bind galactoside. Galectin‐1 is highly expressed in various tumors and participates in various oncogenic processes. However, detailed descriptions of the function of galectin‐1 in urinary bladder urothelial carcinoma have not been reported. Our previous cohort investigation showed that galectin‐1 is associated with tumor invasiveness and is a possible independent prognostic marker of urinary bladder urothelial carcinoma. The present study aimed to clarify the relevance of galectin‐1 expression level to tumor progression and invasion. In order to decipher a mechanism for the contribution of galectin‐1 to the malignant behavior of urinary bladder urothelial carcinoma, two bladder cancer cell lines (T24 and J82) were established with knockdown of galectin‐1 expression by shRNA. Bladder cancer cells with LGALS1 gene silencing showed reduced cell proliferation, lower invasive capability, and lower clonogenicity. Extensive signaling pathway studies indicated that galectin‐1 participated in bladder cancer cell invasion by mediating the activity of MMP9 through the Ras–Rac1–MEKK4–JNK–AP1 signaling pathway. Our functional analyses of galectin‐1 in urinary bladder urothelial carcinoma provided novel insights into the critical role of galectin‐1 in tumor progression and invasion. These results revealed that silencing the galectin‐1‐mediated MAPK signaling pathway presented a novel strategy for bladder cancer therapy.
Trying to stay ahead of the curve in Chile's economic development: exploring a way out of the middle‐income trap through pragmatic export development
Authors: Dingemans Alfonso
Published: July 2016

Underneath impressive growth levels, the Chilean economy displays signs of being caught in a middle‐income trap. It has been unable to improve its productivity, increase the added value of its exports or upgrade its value chain. Its economy cannot compete either with low‐wage countries or highly productive, innovative countries. Its export strategy based on export promotion seems to have outlived its usefulness. It achieved remarkable quantitative success, but must now attend qualitative attributes. Instead of regarding market‐driven export promotion and state‐led export development as substitutes, this article proposes to view them as alternatives in different stages of development. To choose the appropriate time, more attention should be given to non‐traditional, structural indicators, like export sophistication and political‐institutional capabilities.
Testing patients during seizures: A European consensus procedure developed by a joint taskforce of the ILAE – Commission on European Affairs and the European Epilepsy Monitoring Unit Association
Authors: Beniczky Sándor , Neufeld Miri , Diehl Beate , Dobesberger Judith , Trinka Eugen , Mameniskiene Ruta , Rheims Sylvain , Gil‐Nagel Antonio , Craiu Dana , Pressler Ronit , Krysl David , Lebedinsky Angelina , Tassi Laura , Rubboli Guido , Ryvlin Philippe
Published: July 2016

There is currently no international consensus procedure for performing comprehensive periictal testing of patients in the epilepsy monitoring units (EMUs). Our primary goal was to develop a standardized procedure for managing and testing patients during and after seizures in EMUs. The secondary goal was to assess whether it could be implemented in clinical practice (feasibility). A taskforce was appointed by the International League Against Epilepsy (ILAE)—Commission on European Affairs and the European Epilepsy Monitoring Unit Association, to develop a standardized ictal testing battery (ITB) based on expert opinion and experience with various local testing protocols. ITB contains a comprehensive set of 10 items that evidence the clinically relevant semiologic features, and it is adaptive to the dynamics of the individual seizures. The feasibility of the ITB was prospectively evaluated on 250 seizures from 152 consecutive patients in 10 centers. ITB was successfully implemented in clinical practice in all 10 participating centers and was considered feasible in 93% of the tested seizures. ITB was not feasible for testing seizures of very short duration.
Circulating FVIII‐specific IgG, IgA and IgM memory B cells from haemophilia A patients
Authors: Diaz I. , Bolloré K. , Tuaillon E. , Lapalud P. , Giansily‐Blaizot M. , Vendrell J. P. , Schved J. F. , Lavigne‐Lissalde G.
Published: July 2016

Introduction

Approximately, 25% of haemophilia A (HA) patients treated by factor VIII (FVIII), develop antibodies, known as inhibitors, neutralizing the activity of infused FVIII. This immune response involves B cells (BC), including FVIII‐specific memory B cells (MBC). Production of anti‐FVIII antibodies after stimulation of FVIII‐specific MBC suggests a role of these cells in the immune response to FVIII. Animal models allowed the study of circulating FVIII‐specific cells, however few data are available on HA patients.

Aim and methods

In the present study, we simultaneously detected, via ELISpot assay, different isotypes of MBC in the blood of HA patients, after polyclonal activation. Patients included: three with active inhibitors; three with a history of inhibitors; six without any past or active inhibitor.

Results

FVIII‐specific MBC were detected in peripheral blood of HA patients: (i) patients with active inhibitors (IgG: 4–5.2/106 BC; IgA: 2.9–4/106 BC) (ii) patients with a past of inhibitors (no IgG BC; IgA: 5–7.5/106 BC) (iii) patients without inhibitors (no IgG BC or IgA BC except one patient had two FVIII‐specific IgA BC/106 BC).

Conclusion

FVIII‐specific IgA MBC were detected in HA patients with past and current immune responses against FVIII and FVIII‐specific IgG MBC were found only in those with positive inhibitors. This study shows the possibility to detect and characterize easily and simultaneously the MBC from patient blood and that MBC seem different according to anti‐FVIII immune history. It could be a useful tool to study anti‐FVIII response and Immune Tolerance Induction cellular mechanisms.
FOSL1 immunohistochemistry clarifies the distinction between desmoplastic fibroblastoma and fibroma of tendon sheath
Authors: Kato Ikuma , Yoshida Akihiko , Ikegami Masachika , Okuma Tomotake , Tonooka Akiko , Horiguchi Shinichiro , Funata Nobuaki , Kawai Akira , Goto Takahiro , Hishima Tsunekazu , Aoki Ichiro , Motoi Toru
Published: July 2016

Aims

Although desmoplastic fibroblastoma (DFB) and fibroma of tendon sheath (FTS) are well‐established entities, they may show overlapping clinicopathological features. In addition, cytogenetic data showing a shared 11q12 rearrangement in a small number of cases suggest a close link between these entities. A recent microarray study revealed up‐regulation of FOSL1 mRNA in DFBs with 11q12 rearrangement. The aim of this study was to clarify the relationship between DFB and FTS.

Methods and results

We tested 42 cases diagnosed originally as either DFBs or FTSs for interobserver concordance based on the existing histological criteria and correlated the diagnosis with FOSL1 immunohistochemistry. In addition, FOSL1 gene status was determined by chromogenic in‐situ hybridization (CISH). Using joint histological evaluation, 41 of 42 tumours were classified unanimously by three pathologists into 25 DFBs and 16 FTSs, whereas only one case received discordant opinions. Immunohistochemically, all DFBs showed diffuse, strong FOSL1 nuclear immunoreactivity (25 of 25, 100%), while none of the FTSs showed such overexpression. None of the selected 42 DFB mimics overexpressed FOSL1. FOSL1 was not rearranged in seven DFBs tested by CISH.

Conclusions

We confirm here that DFB and FTS are two distinct entities that can be distinguished using the existing histological criteria. This distinction corresponds perfectly with FOSL1 immunohistochemical expression status, and diffuse strong FOSL1 expression specific to DFBs sharpens the border between the two categories. FOSL1 overexpression in DFB may not be caused directly by FOSL1 gene rearrangement. FOSL1 may also be a diagnostic aid for differentiating DFB from other histological mimics.
Frequent PIK3CA activating mutations in nipple adenomas
Authors: Liau Jau‐Yu , Lee Yi‐Hsuan , Tsai Jia‐Huei , Yuan Chang‐Tsu , Chu Chia‐Yu , Hong Jin‐Bon , Sheen Yi‐Shuan
Published: July 2016

Aims

Nipple adenoma (NA) is a rare benign epithelial tumour occurring in the nipple. Histologically, it exhibits variable and often mixed adenosis‐like and usual ductal hyperplasia‐like growth patterns. Morphologically, it is similar to other benign proliferative breast lesions occurring in the breast parenchyma, which have been shown to harbour activating mutations in PIK3CA, AKT1 or, less frequently, in RAS in more than 50% of cases. In this study, we aimed to analyse the mutation status of PIK3CA, AKT1, RAS and BRAF in NAs and correlated the mutation status with the histological features.

Methods and results

Mutation analysis of PIK3CA, AKT1, RAS and BRAF was performed in 24 NAs by Sanger sequencing. Our results showed that activating PIK3CA mutations were identified in eight of the 15 NAs (53%) with a predominantly adenosis‐like pattern and four of the nine NAs (44%) with a predominantly usual ductal hyperplasia‐like pattern. One tumour with a PIK3CA H1047R mutation also had a KRAS Q61H mutation. Two tumours with an adenosis‐like pattern had BRAF V600E mutations. Overall, half of the NAs (12 of 24, 50%) in our series had PIK3CA mutations and 58% (14 of 24) had PIK3CA, RAS or BRAF mutations.

Conclusions

Our data indicate that, similar to other benign proliferative lesions occurring in the breast parenchyma, activating PIK3CA mutations are very common in NAs, and KRAS mutation may occur concurrently with PIK3CA mutation. In addition, as BRAF mutation has not been identified in benign proliferative lesions in previous studies, BRAF‐mutated NAs appear to have distinct pathogenesis.
Microbial profile and bacterial characterisation of naturally debittered Hurma olives compared to non‐debittered Erkence variety during ripening period
Authors: Sozbilen Gozde Seval , Baysal Ayse Handan
Published: July 2016

Naturally debittered Hurma olive is grown in a specific area in Karaburun peninsula in Turkey. It is characterised by its sweet taste and it differs from other varieties by losing its bitterness caused by phenolic compounds during its maturation period on the tree. Therefore, Hurma olive does not require any further debittering process to be served as table olive. This study was particularly interested in the comparison of the microbial profile of Hurma olive during its 8 weeks of maturation period in two subsequent harvest years and Erkence (not naturally debittered) olive. In addition, main bacterial profile of both Hurma and Erkence olives were isolated and identified. Aerobic mesophilic microorganism (AMM), lactic acid bacteria (LAB), Enterobacteriaceae, Pseudomonadaceae, Staphylococci, Micrococcaceae, yeasts and moulds (Y&Ms) were detected (counted and isolated) in the olive drupes during the maturation period. Isolated bacteria were identified as different spp. of Bacillaceae, Enterobacteriaceae, Micrococcoceae and Pseudomonadaceae.
Total polyphenol extraction from red sorghum grain and effects on the morphological structure of starch granules
Authors: Acquisgrana María del Rosario , Benítez Elisa I. , Gómez Pamies Laura C. , Sosa Gladis L. , Peruchena Nélida M. , Lozano Jorge E.
Published: July 2016

The aim of this study was to propose a treatment to reduce the content of total polyphenols (TPP) and to obtain flour without significant morphological changes in the starch granules. The response surface methodology (RSM) was used to predict the influence of temperature and time on TPP extraction. Research work was conducted using the central composite design methodology. Results showed that the effect of temperature was more significant than that of time. A quadratic fit of data regarding temperature and linear data adjustment as to time was obtained. A scanning electron microscopy analysis of starch showed no morphological change in the granules at the temperature studied. Starch granules presented a size distribution ranging from 6 to 25 μm being 35% of granules <15 μm, and 65% of granules >15 μm in size, respectively.
Initial case report of an extracted tooth root used for lateral alveolar ridge augmentation
Authors: Schwarz Frank , Schmucker Andrea , Becker Jürgen
Published: July 2016

Objectives

Recent animal studies have indicated, that tooth roots reveal a structural and biological potential to serve as alternative autografts for localized ridge augmentation. This proof‐of‐concept initial report aimed at investigating, whether this new surgical concept may be applied to humans.

Material & Methods

In one patient, who was in need for horizontal ridge augmentation, the roots of a retained upper wisdom tooth were separated and rigidly fixed at the defect site. After 24 weeks of submerged healing, the primary endpoint was defined as gain in ridge width (mm) being sufficient to place an adequately dimensioned titanium implant at the respective site. Secondary outcomes included safety assessments.

Results

Soft tissue healing was uneventful during the entire observation period. Clinical re‐entry at 24 weeks revealed, that the transplanted root was homogeneously incorporated at the former defect site and mainly replaced by a newly formed hard tissue. The gain in ridge width amounted to 4.5 mm and allowed for a successful implant placement with good primary stability. The procedure was not associated with any wound infection or adverse events.

Conclusions

This novel approach may be further investigated in implant site development procedures.
Prurigo pigmentosa: a clinical and histopathological study of nine Chinese cases
Authors: Zeng X. , Li L. , Cui B.N.
Published: July 2016

Background

Prurigo pigmentosa (PP) is a chronic and recurrent inflammatory skin disease with the distinctive and prominent feature of reticulate hyperpigmentation. Most known cases have been reported in Japan; here we report nine Chinese cases.

Objective

To determine the clinical manifestation of prurigo pigmentosa and its effects in Chinese individuals compared to patients of other ethnicities.

Methods

We retrospectively analysed nine cases of PP. For all cases, clinical information was collected and reviewed, and skin biopsies were performed. Furthermore, we followed all nine patients to determine the recurrence rate.

Results

All nine patients fulfilled the diagnostic criteria of prurigo pigmentosa. The mean age of the patients at diagnosis was 27.4 years, and the patients were predominantly female. Skin lesions at different stages commonly co‐occurred in the same patient. The most commonly affected part of the body was the back, but the armpit was also often involved. Patients responded well to minocycline treatment for the short duration of 8.62 days, and a lower recurrence rate (28.3%) was recorded after treatment. Biopsy revealed classic neutrophil and/or lymphocyte infiltration, spongiosis and necrotic keratocytes. Abscesses occasionally occurred in the follicular orifice. The abnormal presentation of hair follicles was also discovered. All characteristics were found to co‐exist in different stages.

Conclusion

We conclude that PP is easy to misdiagnose. Histopathological characteristics can co‐exist at different stages, consistent with the clinical finding that different stages of skin lesions presented concurrently, contributing to misdiagnosis. Oral administration of minocycline not only yields an excellent response, but also effectively reduces the recurrence rate.
Cost‐benefit analysis of shrimp farming's flood risk reduction strategies in Thailand
Authors: Seekao C. , Pharino C.
Published: July 2016

Chachoengsao province is a prime shrimp producing area for domestic consumption and exports. The province, however, is often threatened by floods. Improving the effectiveness of current flood damage protection is a major challenge. This research developed a flood risk map by combining the probability of flood events and a vulnerability map based on physical characteristics of the area and socio‐economic conditions of shrimp farmers (victims). Analysis of current risk reduction measures was performed by comparing the net benefits and costs of different strategies. Damage costs to shrimp farming from flooding were also estimated for the base case (a case with no change in actions). The flood risk map shows that two‐thirds of shrimp farms are highly vulnerable to flooding when a 10‐day accumulated rainfall is greater than 250 mm which is likely to occur every 2 years. Increasing dike heights could yield higher net benefits than other flood adaptation measures. Non‐structural flood controls such as early harvesting and shifting the crop calendar are alternative measures for shrimp farmers who lack financial supports. The results show that cost‐benefit analysis based on various scenarios can help in selecting an appropriate mitigation practice especially for shrimp farms located in a high risk area.
Association among interleukin‐6 gene polymorphisms, type 2 diabetes mellitus, and chronic periodontitis: a pilot study
Authors: Kavitha Loganathan , Vijayshree Priyadharshini Jayaseelan , Sivapathasundharam Balasundaram
Published: July 2016

Aim

The purpose of this pilot study was to determine the association between single nucleotide polymorphisms (–174 G>C) in the interleukin‐6 (IL‐6) gene with chronic periodontitis (CP) and type 2 diabetes mellitus (T2DM) in south Indian population.

Methods

Genomic DNA was obtained from the white blood cells of 30 patients with T2DM, 30 patients with CP, 30 patients with T2DM with CP, and 30 controls. DNA was amplified using polymerase chain reaction with specific primers flanking the locus –174 of the IL‐6 gene and further genotyped using the restriction fragment length polymorphism method. The genotype distribution and allele frequencies between the study groups were determined using χ2‐test. The relative risk was estimated with a 95% confidence interval.

Results

The CP group (26.7%) displayed a greater percentage of GC genotype (P = 0.026) when compared to the control group (3.3%). A statistically‐significant difference in the allele frequencies was found between the control and CP group with the C‐allele frequency being greater (0.13) in the CP group than normal controls (0.02).

Conclusion

The GC genotype was found to be the risk genotype and the C allele was found to be the risk allele for the development of CP.
Combined CD44, c‐MET, and EGFR expression in p16‐positive and p16‐negative head and neck squamous cell carcinomas
Authors: Baschnagel Andrew M. , Tonlaar Nathan , Eskandari Mohammad , Kumar Tripti , Williams Lindsay , Hanna Alaa , Pruetz Barbara L. , Wilson George D.
Published: July 2016

Purpose/Objective(s)

To examine the association between CD44 and c‐MET expression in relation to p16 and EGFR in patients with head and neck squamous cell carcinoma (HNSCC).

Materials/Methods

Immunohistochemical staining of CD44, p16, EGFR, and c‐MET was performed on 105 locally advanced HNSCC patients treated with chemoradiation. CD44 expression was correlated with c‐MET, EGFR, and p16, locoregional control (LRC), distant metastases (DM), disease‐free survival (DFS) and overall survival (OS).

Results

High CD44 expression was present in 33% of patients and was associated with non‐oropharynx primaries (P < 0.001), high c‐MET expression (P < 0.001), p16‐negative (P < 0.001) and EGFR‐positive tumors (P < 0.001). Fifty‐seven percent of CD44 high expressing tumors had high c‐MET expression compared to 21% of CD44 low expressing tumors (P < 0.001). High CD44 expression predicted for worse LRC (HR: 2.44; 95% CI: 1.16–5.13; P = 0.018), DFS (HR: 2.61; 95% CI: 1.46–4.67; P = 0.001), and OS (HR: 2.52; 95% CI: 1.30–4.92; P = 0.007) but not DM (P = 0.57) on univariate analysis. Patients with both high CD44 and c‐MET expression had a poor prognosis with a 2‐year DFS of 30% compared to 70% in the rest of the cohort (P = 0.003). On multivariable analysis, after adjusting for site, T‐stage, smoking history, and EGFR status, high c‐MET (P = 0.039) and negative p16 status (P = 0.034) predicted for worse DFS, while high CD44 expression did not (P = 0.43).

Conclusions

High CD44 expression is associated with high c‐MET expression, p16‐negative tumors, and EGFR‐positive tumors. The combination of these markers predicts for poor prognosis in HNSCC patients treated with chemoradiation.
Treating idiopathic hypertrophic pyloric stenosis with sequential therapy: A clinical study
Authors: Fan Jianfeng , Shi Yingzuo , Cheng Ming , Zhu Xiaomin , Wang Dafeng
Published: July 2016

Aim

The aim of this study was to explore the efficacy and safety of treating idiopathic hypertrophic pyloric stenosis with sequential therapy (ST).

Methods

From January 2010 to June 2013, 49 children with idiopathic hypertrophic pyloric stenosis were divided into two groups to accept either atropine ST (ST group, n = 26) or laparoscopic surgery (operation group, n = 23). The remission rate of vomiting, complications, hospital stay and medical expenditure were compared between the two groups. The body weight and the thickness of the pyloric muscle at 6 months after the treatments were also compared.

Results

The remission rate of vomiting was lower in the ST group (88.5%; 23/26) than in the operation group (100%, 23/23). The difference in the incidence rate of complications, body weight and pyloric muscle thickness was not statistically significant between the two groups. However, the hospital stay was significantly longer, while the medical expenditure was significantly lower in the ST group than in the operation group.

Conclusions

Atropine ST is safe, effective and cost‐effective as compared with operation; however, the efficacy of ST is lower than operation.
Melatonin modulates neonatal brain inflammation through endoplasmic reticulum stress, autophagy, and miR‐34a/silent information regulator 1 pathway
Authors: Carloni Silvia , Favrais Géraldine , Saliba Elie , Albertini Maria Cristina , Chalon Sylvie , Longini Mariangela , Gressens Pierre , Buonocore Giuseppe , Balduini Walter
Published: July 2016

Maternal infection/inflammation represents one of the most important factors involved in the etiology of brain injury in newborns. We investigated the modulating effect of prenatal melatonin on the neonatal brain inflammation process resulting from maternal intraperitoneal (i.p.) lipopolysaccharide (LPS) injections. LPS (300 μg/kg) was administered to pregnant rats at gestational days 19 and 20. Melatonin (5 mg/kg) was administered i.p. at the same time as LPS. Melatonin counteracted the LPS sensitization to a second ibotenate‐induced excitotoxic insult performed on postnatal day (PND) 4. As melatonin succeeded in reducing microglial activation in neonatal brain at PND1, pathways previously implicated in brain inflammation regulation, such as endoplasmic reticulum (ER) stress, autophagy and silent information regulator 1 (SIRT1), a melatonin target, were assessed at the same time‐point in our experimental groups. Results showed that maternal LPS administrations resulted in an increase in CHOP and Hsp70 protein expression and eIF2α phosphorylation, indicative of activation of the unfolded protein response consequent to ER stress, and a slighter decrease in the autophagy process, determined by reduced lipidated LC3 and increased p62 expression. LPS‐induced inflammation also reduced brain SIRT1 expression and affected the expression of miR‐34a, miR146a, and miR‐126. All these effects were blocked by melatonin. Cleaved‐caspase‐3 apoptosis pathway did not seem to be implicated in the noxious effect of LPS on the PND1 brain. We conclude that melatonin is effective in reducing maternal LPS‐induced neonatal inflammation and related brain injury. Its role as a prophylactic/therapeutic drug deserves to be investigated by clinical studies.
Effects of in ovo feeding with glycerol for broilers
Authors: Neves D. G. , Retes P. L. , Rocha R. R. , Ferreira L. G. , Naves L. P. , Alvarenga R. R. , Fassani E. J. , Pereira L. J. , Sousa R. V. , Zangeronimo M. G.
Published: July 2016

The objective was to evaluate the effect of in ovo feeding with glycerol on post‐hatch development in broiler chicks. A total of 408 fertile eggs were divided into six experimental groups consisting of five 0.9% saline solutions containing various concentrations of glycerol (12.5, 25.0, 37.5 and 50.0 nmol/ml), and a placebo group (inoculation with saline only) and a control group (without inoculation). Inoculations were performed at 17 days of incubation for the evaluation of hatchability, embryo mortality, body and viscera weights, intestinal epithelium morphometry, blood glucose and liver glycerol kinase activity of chicks at hatching. Inoculation of solutions containing glycerol did not influence body weight at hatching and relative weights of liver, pancreas, intestine and breast. There was a quadratic effect of glycerol levels on the weights of yolk residue and gizzard and on blood glucose, and an increasing linear effect on spleen and heart weights. Higher duodenum and ileum villous height and deeper jejunum and ileum crypts were obtained with 50.0 nmol/ml of glycerol. A linear increasing effect was also observed in liver glycerol kinase activity; however, lower blood glucose was observed with 37.5 and 50 nmol/ml of glycerol. It is therefore concluded that glycerol may be used at doses of 25 nmol/ml as a substrate in in ovo feeding of broiler chickens. However, further studies must be conducted not only to establish an optimal dose but also to evaluate the combination of this substrate with other nutrients used in the in ovo feeding.
Acute hydrogen sulfide–induced neuropathology and neurological sequelae: challenges for translational neuroprotective research
Authors: Rumbeiha Wilson , Whitley Elizabeth , Anantharam Poojya , Kim Dong‐Suk , Kanthasamy Arthi
Published: July 2016

Hydrogen sulfide (H2S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H2S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H2S is known to cause brain damage, leading to neurodegeneration and long‐term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H2S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H2S concentrations. This review focuses on the neuropathology of high acute H2S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H2S‐induced neurodegeneration.
Oropharyngeal and laryngeal sensory innervation in the pathophysiology of swallowing disorders and sensory stimulation treatments
Authors: Alvarez‐Berdugo Daniel , Rofes Laia , Casamitjana J. Francesc , Padrón Andreína , Quer Miquel , Clavé Pere
Published: July 2016

Oropharyngeal dysphagia (OD) affects older and neurological patients, causing malnutrition and dehydration and increasing the risk for aspiration pneumonia. There is evidence that sensory deficits in those populations are closely related to swallowing disorders, and several research groups are developing new therapies based on sensory stimulation of this area. More information on the sensory innervation participating in the swallow response is needed to better understand the pathophysiology of OD and to develop new treatments. This review focuses on the sensory innervation of the human oropharynx and larynx in healthy people compared with patients with swallowing disorders in order to unravel the abnormalities that may lead to the loss of sensitivity in patients with OD. We also hypothesize the pathway through which active sensory‐enhancement treatments may elicit their therapeutic effect on patients with swallowing dysfunctions. As far as we know, this is the first time a review covers the anatomy, histology, ultrastructure, and molecular biology of the sensory innervation of the swallowing function.
Pharmacological and other treatment modalities for esophageal pain
Authors: Hoff Dag Arne Lihaug , Brock Christina , Farmer Adam D. , Dickman Ram , Ruffle James K. , Shaker Anisa , Drewes Asbjørn M.
Published: July 2016

Treatment of esophageal pain remains a major challenge for the clinician. Although many patients have heartburn and may respond to proton pump inhibitors, there in an unmet need for other treatment modalities in patients where there are no obvious pathological findings. Although analgesics are the mainstay in esophageal pain treatment, many patients are nonresponders to these drugs. The current concise review focuses on other systems affecting pain processing, where better understanding may serve as a framework for therapy. These are the parasympathetic nervous system, exercise, and personality profiles. Finally, treatment with analgesics for functional chest pain remains a challenge, and an overview of treatment with antidepressive drugs is provided.
Novel approaches to mitigating parathion toxicity: targeting cytochrome P450–mediated metabolism with menadione
Authors: Jan Yi‐Hua , Richardson Jason R. , Baker Angela A. , Mishin Vladimir , Heck Diane E. , Laskin Debra L. , Laskin Jeffrey D.
Published: July 2016

Accidental or intentional exposures to parathion, an organophosphorus (OP) pesticide, can cause severe poisoning in humans. Parathion toxicity is dependent on its metabolism by the cytochrome P450 (CYP) system to paraoxon (diethyl 4‐nitrophenyl phosphate), a highly poisonous nerve agent and potent inhibitor of acetylcholinesterase. We have been investigating inhibitors of CYP‐mediated bioactivation of OPs as a method of preventing or reversing progressive parathion toxicity. It is well recognized that NADPH–cytochrome P450 reductase, an enzyme required for the transfer of electrons to CYPs, mediates chemical redox cycling. In this process, the enzyme diverts electrons from CYPs to support chemical redox cycling, which results in inhibition of CYP‐mediated biotransformation. Using menadione as the redox‐cycling chemical, we discovered that this enzymatic reaction blocks metabolic activation of parathion in rat and human liver microsomes and in recombinant CYPs important to parathion metabolism, including CYP1A2, CYP2B6, and CYP3A4. Administration of menadione to rats reduces metabolism of parathion, as well as parathion‐induced inhibition of brain cholinesterase activity. This resulted in inhibition of parathion neurotoxicity. Menadione has relatively low toxicity and is approved by the Food and Drug Administration for other indications. Its ability to block parathion metabolism makes it an attractive therapeutic candidate to mitigate parathion‐induced neurotoxicity.
ARGOS8 variants generated by CRISPR‐Cas9 improve maize grain yield under field drought stress conditions
Authors: Shi Jinrui , Gao Huirong , Wang Hongyu , Lafitte H. Renee , Archibald Rayeann L. , Yang Meizhu , Hakimi Salim M. , Mo Hua , Habben Jeffrey E.
Published: July 2016

Maize ARGOS8 is a negative regulator of ethylene responses. A previous study has shown that transgenic plants constitutively overexpressing ARGOS8 have reduced ethylene sensitivity and improved grain yield under drought stress conditions. To explore the targeted use of ARGOS8 native expression variation in drought‐tolerant breeding, a diverse set of over 400 maize inbreds was examined for ARGOS8 mRNA expression, but the expression levels in all lines were less than that created in the original ARGOS8 transgenic events. We then employed a CRISPR‐Cas‐enabled advanced breeding technology to generate novel variants of ARGOS8. The native maize GOS2 promoter, which confers a moderate level of constitutive expression, was inserted into the 5′‐untranslated region of the native ARGOS8 gene or was used to replace the native promoter of ARGOS8. Precise genomic DNA modification at the ARGOS8 locus was verified by PCR and sequencing. The ARGOS8 variants had elevated levels of ARGOS8 transcripts relative to the native allele and these transcripts were detectable in all the tissues tested, which was the expected results using the GOS2 promoter. A field study showed that compared to the WT, the ARGOS8 variants increased grain yield by five bushels per acre under flowering stress conditions and had no yield loss under well‐watered conditions. These results demonstrate the utility of the CRISPR‐Cas9 system in generating novel allelic variation for breeding drought‐tolerant crops.
Iron plaque decreases cadmium accumulation in Oryza sativa L. and serves as a source of iron
Authors: Sebastian A. , Prasad M. N. V.
Published: July 2016

Cadmium (Cd) contamination occurs in paddy soils; hence it is necessary to reduce Cd content of rice. Application and mode of action of ferrous sulphate in minimizing Cd in rice was monitored in the present study.

Pot culture with Indian rice variety Swarna (MTU 7029) was maintained in Cd‐spiked soil containing ferrous sulphates, which is expected to reduce Cd accumulation in rice. Responses in rhizosphere pH, root surface, metal accumulation in plant and molecular physiological processes were monitored.

Iron plaque was induced on root surfaces after FeSO4 application and the amount of Fe in plaque reduced with increases in Cd in the soil. Rhizosphere pH decreased during plaque formation and became more acidic due to secretion of organic acids from the roots under Cd treatment. Moreover, iron chelate reductase activity increased with Cd treatment, but in the absence of Cd, activity of this enzyme increased in plaque‐induced plants. Cd treatment caused expression of OsYSL18, whereas OsYSL15 was expressed only in roots without iron plaque. Fe content of plants increased during plaque formation, which protected plants from Cd‐induced Fe deficiency and metal toxicity. This was corroborated with increased biomass, chlorophyll content and quantum efficiency of photo‐synthesis among plaque‐induced plants.

We conclude that ferrous sulphate‐induced iron plaque prevents Cd accumulation and Fe deficiency in rice. Iron released from plaque via organic acid mediated dissolution during Cd stress.
Discursive Agency: (Re‐)Conceptualizing Actors and Practices in the Analysis of Discursive Policymaking
Authors: Leipold Sina , Winkel Georg
Published: July 2016

Interpretive discourse analysis commonly claims to address the interrelation between actors and discourses. However, the analytical focus of most approaches is on structures (discourses) while much less attention is paid to agency. This paper explicitly addresses discursive agency in two steps. First, we systematically review theoretical and analytical dimensions of agency in existing interpretive discourse analysis approaches. This review reveals a set of shared assumptions; most notably a concept of “trialectic” agency emphasizing the constitution of agency among the individual, the (discursive) structures, and the researcher's interpretation. Second, we propose an analytical heuristic, the Discursive Agency Approach, which is developed on the basis of the review and own empirical data. The proposed approach consists of four elements: (1) policy discourses, (2) political institutions, (3) agents defined via a set of characteristics, and (4) strategic practices. This approach is meant to facilitate a systematic exploration of agency under a discourse perspective, tackling the question of how a policy is constituted through the agency ascribed to its proponents in dynamic discursive processes, and how actors acquire political relevance through discursive means. To enable this goal, we propose distinct research steps and associated methods that link the approach to existing means of analysis.
Clinically remitted childhood asthma is associated with airflow obstruction in middle‐aged adults
Authors: Omori Keitaro , Iwamoto Hiroshi , Yamane Takashi , Nakashima Taku , Haruta Yoshinori , Hattori Noboru , Yokoyama Akihito , Kohno Nobuoki
Published: July 2016

Background and objective

While adult asthma has been shown to be a risk factor for COPD, the effect of remitted childhood asthma on adult lung function has not been clarified. The aim of this study was to examine whether remitted childhood asthma is a risk factor for airflow obstruction in a middle‐aged general population.

Methods

A total of 9896 participants (range: 35–60 years) from five healthcare centres were included in the study. The participants were classified into four categories based on the presence or absence of physician‐diagnosed childhood/adulthood asthma and asthma symptoms as follows: healthy controls (n = 9154), remitted childhood asthma (n = 287), adulthood‐onset asthma (n = 354) and childhood–adulthood asthma (n = 101).

Results

The prevalence of respiratory symptoms was similar in both the participants with remitted childhood asthma and healthy controls. The prevalence of airflow obstruction (forced expiratory volume in 1 s (FEV1
)/forced vital capacity (FVC) < 0.7) was significantly higher in the participants with remitted childhood asthma, those with adult‐onset asthma and those with childhood–adulthood asthma (5.2%, 14.4% and 16.8%, respectively) compared with healthy controls (2.2%). Multivariate logistic regression showed that remitted childhood asthma was independently associated with airflow obstruction. Among the participants with remitted childhood asthma, ever‐smokers had significantly lower FEV1
/FVC than never‐smokers.

Conclusion

Clinically remitted childhood asthma is associated with airflow obstruction in middle‐aged adults. Smoking and remitted childhood asthma may be additive factors for the development of airflow obstruction.
Developing a complex intervention programme for informal caregivers of stroke survivors: The Caregivers’ Guide
Authors: Krieger Theresia , Feron Frans , Dorant Elisabeth
Published: July 2016

Background

Stroke affects the entire family system. Failure to meet the needs of caregivers leads to physical and mental overburdening. Stroke caregivers may benefit from professional support. The literature reviews have shown that there is still no clarity concerning the most appropriate set‐up of a support programme. In Germany, there is no stroke caregiver support programme that operates throughout the course of rehabilitation.

Aim

The aim was to develop a complex intervention programme for stroke caregivers in North‐Rhine Westphalia, Germany.

Methods

A naturalistic enquiry approach, using a mixed‐methods design, was applied. Within one overarching qualitative study, three separate, explorative, inductive, qualitative substudies were conducted: (i) seven explorative interviews with experienced stroke caregivers, (ii) six semi‐structured interviews with professionals working within stroke rehabilitation and (iii) seventeen participant observations with focus on professional–caregiver interactions. Regional stroke units, rehabilitation centres, outpatient services and the home environment of caregivers were included. By means of a four‐step qualitative content analysis, all three data sets were coded, categorised and subsequently condensed into subthemes, clustered into main themes, and finally translated into ‘Conceptual Building Blocks’ of the programme.

Results

The need for a personalised, holistic and multicomponent caregiver support programme emerged from all three substudies. Fourteen themes were condensed from the subthemes. Caregivers should be approached directly after stroke using outreach counselling. Support should be provided by a specially trained focal person across the entire patient's rehabilitation trajectory. The newly developed support programme consists of five flexible ‘Conceptual Building Blocks’: Content, Human Resources, Personalised Approach, Timing and Setting.

Conclusion

Through a qualitative mixed‐methods design, an in‐depth contextual understanding of stroke caregiver needs within the rehabilitative support system was reached. This allowed the development of a context tailored comprehensive caregiver support programme consisting of five ‘Conceptual Building Blocks’.
‘It's a matter of patient safety’: understanding challenges in everyday clinical practice for achieving good care on the surgical ward – a qualitative study
Authors: Jangland Eva , Nyberg Berit , Yngman‐Uhlin Pia
Published: July 2016

Background

Surgical care plays an important role in the acute hospital's delivery of safe, high‐quality patient care. Although demands for effectiveness are high in surgical wards quality of care and patient safety must also be secured. It is therefore necessary to identify the challenges and barriers linked to quality of care and patient safety with a focus on this specific setting.

Aim

To explore situations and processes that support or hinder good safe patient care on the surgical ward.

Method

This qualitative study was based on a strategic sample of 10 department and ward leaders in three hospitals and six surgical wards in Sweden. Repeated reflective interviews were analysed using systematic text condensation.

Findings

Four themes described the leaders’ view of a complex healthcare setting that demands effectiveness and efficiency in moving patients quickly through the healthcare system. Quality of care and patient safety were often hampered factors such as a shift of care level, with critically ill patients cared for without reorganisation of nurses' competencies on the surgical ward.

Conclusions

There is a gap between what is described in written documents and what is or can be performed in clinical practice to achieve good care and safe care on the surgical ward. A shift in levels of care on the surgical ward without reallocation of the necessary competencies at the patient's bedside show consequences for quality of care and patient safety. This means that surgical wards should consider reviewing their organisation and implementing more advanced nursing roles in direct patient care on all shifts. The ethical issues and the moral stress on nurses who lack the resources and competence to deliver good care according to professional values need to be made more explicit as a part of the patient safety agenda in the surgical ward.
Patient participation: causing moral stress in psychiatric nursing?
Authors: Jansen Trine‐Lise , Hanssen Ingrid
Published: July 2016

Aim

The aim of this study was to explore psychiatric nurses’ experiences and perspectives regarding patient participation. Patient participation is an ambiguous, complex and poorly defined concept with practical/clinical, organisational, legal and ethical aspects, some of which in psychiatric units may cause ethical predicaments and moral stress in nurses, for instance when moral caring acts are thwarted by constraints.

Methods

An explorative quantitative pilot study was conducted at a psychiatric subacute unit through three focus group interviews with a total of nine participants. A thematic analytic approach was chosen. Preliminary empirical findings were discussed with participants before the final data analysis. Ethical research guidelines were followed.

Results

Patient participation is a difficult ideal to realise because of vagueness of aim and content. What was regarded as patient participation differed. Some interviewees held that patients may have a say within the framework of restraints while others saw patient participation as superficial. The interviewees describe themselves as patient's spokespersons and contributing to patients participating in their treatment as a great responsibility. They felt squeezed between their ethical values and the ‘system’. They found themselves in a negotiator role trying to collaborate with both the doctors and the patients. Privatisation of a political ideal makes nurses vulnerable to burn out and moral distress.

Conclusion

Nurses have a particular ethical responsibility towards vulnerable patients, and may themselves be vulnerable when caught in situations where their professional and moral values are threatened. Unclear concepts make for unclear division of responsibility. Patient participation is often a neglected value in current psychiatric treatment philosophy. When healthcare workers’ ethical sensibilities are compromised, this may result in moral stress.
Americanizing Latinos, Latinoizing America: The Political Consequences of Latino Incorporation*
Authors: Yang Alan , de la Garza Rodolfo O.
Published: July 2016

Objective

Because of the increased attention Democrats and Republicans are paying to the Latino vote, both parties may find it necessary to change their platforms and rhetoric to appeal to Latino policy preferences. This research examines the impact of Americanization on Latino policy preferences.

Methods

Using data from the 2006 Latino National Survey, we create a continuous scale that measures the extent to which Latinos have Americanized, that is, become incorporated into the U.S. mainstream. We use multivariate analyses to examine the effect of Americanization on a wide range of salient policy preferences.

Results

Our research shows that across a wide array of issues, Latinos vary considerably among themselves in terms of their level of Americanization, even after accounting for a rich set of control variables commonly found to predict policy preferences. Our results also indicate that, regardless of levels of Americanization, Latinos approach unanimity in their support of an expanded socioeconomic safety net supported by the government.

Conclusions

Our results indicate that Latino policy preferences are well to the left of the national mainstream and indeed include policies that are anathema to the Republican Party. The political implications of these preferences are that despite increased outreach, Republicans will find it difficult to woo Latino voters, and it will be challenging for Democrats to maintain or increase their Latino support.
Soluble monomers, dimers and HLA‐G‐expressing extracellular vesicles: the three dimensions of structural complexity to use HLA‐G as a clinical biomarker
Authors: Nardi F. da Silva , König L. , Wagner B. , Giebel B. , Santos Manvailer L. F. , Rebmann V.
Published: July 2016

The HLA‐G molecule belongs to the family of nonclassical human leukocyte antigen (HLA) class I. At variance to classical HLA class I, HLA‐G displays (i) a low number of nucleotide variations within the coding region, (ii) a high structural diversity, (iii) a restricted peptide repertoire, (iv) a limited tissue distribution and (v) strong immune‐suppressive properties. The physiological HLA‐G surface expression is restricted to the maternal–fetal interface and to immune‐privileged adult tissues. Soluble forms of HLA‐G (sHLA‐G) are detectable in various body fluids. Cellular activation and pathological processes are associated with an aberrant or a neo‐expression of HLA‐G/sHLA‐G. Functionally, HLA‐G and its secreted forms are considered to be key players in the induction of short‐ and long‐term tolerance. Thus, its unique expression profile and tolerance‐inducing functions render HLA‐G/sHLA‐G an attractive biomarker to monitor the systemic health/disease status and disease activity/progression for clinical approaches in disease management and treatments. Here, we place emphasis on (i) the current status of the tolerance‐inducing functions by HLA‐G/sHLA‐G, (ii) the current complexity to implement this molecule as a meaningful clinical biomarker regarding the three dimensions of structural diversity (monomers, dimers and HLA‐G‐expressing extracellular vesicles) with its functional implications, and (iii) novel and future approaches to detect and quantify sHLA‐G structures and functions.