bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnicity‐Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta‐Analysis
Authors: Founti Panayiota , Haidich Anna‐Bettina , Chatzikyriakidou Anthoula , Salonikiou Angeliki , Anastasopoulos Eleftherios , Pappas Theofanis , Lambropoulos Alexandros , Viswanathan Ananth C. , Topouzis Fotis
Published: September 2015

Pseudoexfoliation (PEX) is an age‐related disorder of the extracellular matrix; it is strongly associated with glaucoma, the leading cause of irreversible blindness worldwide. We conducted an ethnic‐based meta‐analysis of the association of LOXL1 polymorphisms with PEX/pseudoexfoliative glaucoma (PEXG). Association studies were retrieved systematically from PubMed, EMBASE, and Web of Knowledge. Allelic and genotype frequencies of rs3825942, rs1048661, and rs2165241 were compared between PEX/PEXG and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model. Overall, 39 independent cohorts were included. Rs3825942 (G) was an at risk allele for PEX/PEXG in Caucasians, Japanese, Koreans, Chinese, South Asians, and Middle Easterners, but protective in Black South Africans (OR = 0.10, 95%CI:0.06–0.16). Rs1048661 (G) was an at risk allele for PEX/PEXG in Caucasians, South Asians, Middle Easterners and Black South Africans, but was protective in Japanese (OR = 0.03, 95%CI:0.02–0.06) and Koreans (OR = 0.10, 95%CI:0.05–0.22). These associations we‐re confirmed for the genotypic recessive models. Rs2165241 (C) was a protective allele for PEX/PEXG in Caucasians, but was an at risk allele in Japanese (OR = 7.49, 95%CI:3.22–17.41) and Koreans (OR = 6.63, 95%CI:2.60–16.90). This was confirmed for the genotypic dominant model. Other genetic and/or environmental factors may modify the effect of LOXL1 polymorphisms in certain ethnic groups.
Decreased expression of ectonucleotidase E‐NPP1 in leukocytes from subjects with severe asthma exacerbation
Authors: Montaño L. M. , Vargas M. H. , Díaz‐Hernández V. , De Ita M. , Kazakova R. , Barajas‐López C.
Published: September 2015

Several studies suggest that ATP and related nucleotides play a role in the pathophysiology of asthma. However, the functionality of ectonucleotidases in this disease has been scantly investigated. We studied total ectonucleotidase activity in leukocytes from patients suffering from asthma exacerbation and explored the expression of E‐NTPDase 1, 2, 3, and 8, and E‐NPP1, 2, and 3, in their polymorphonuclear cells by immunofluorescence and qPCR. Leukocytes from patients with mild or moderate asthma exacerbation had similar ectonucleotidase activity than leukocytes from healthy subjects, while in patients with severe asthma exacerbation, this activity was lower. Of the ectonucleotidases studied, only E‐NPP1 displayed diminished immunofluorescence and a significant decrease in its mRNA expression, both in patients with severe asthma exacerbation. This reduced E‐NPP1 expression could be responsible for increased amounts of ATP or other nucleotides, capable of worsening asthma exacerbation, and warranting further investigation.
Relationships between behavioral symptoms of non‐medicated Chinese children with attention deficit hyperactivity disorder and parenting stress: Comparison of different subtypes and comorbidities
Authors: Li Yan , Jiang Wen‐Qing , Du Ya‐Song , Coghill David
Published: September 2015

Introduction

To identify the characteristics of behavior problems among children with attention deficit hyperactivity disorder (ADHD) and their relation with parenting stress.

Methods

The Conners Parent Symptom Questionnaire (PSQ) and Parenting Stress Index (PSI) were used to assess the symptoms and parenting stress of 132 non‐medicated children with ADHD as compared with 88 healthy controls.

Results

Every PSQ factor of ADHD children was higher than in the control group; children with the combined subtype of ADHD had the highest scores in conduct and learning problems, impulsivity/hyperactivity, and overall hyperactivity index; the PSI total stress, child domain, and parent domain scores were all higher in the ADHD group than in the control group; children with the combined subtype of ADHD had the highest score in the competence subscale of the parent domain, whereas the PSI total stress score of parents of children with ADHD and comorbid oppositional defiant disorder (ODD) was higher than that of parents of children with only ADHD. The PSI total stress score was positively correlated with all PSQ factor scores. The PSQ factors of conduct problems and learning problems were found to be significant predictors in a regression analysis.

Discussion

The children with ADHD exhibited abnormal parenting stress compared with healthy controls, which was much more pronounced when the children had comorbid ODD. Furthermore, parenting stress was related with the severity of ADHD symptoms, suggesting that children with the combined subtype of ADHD require particular attention in the future.
HMGCR rs17671591 SNP Determines Lower Plasma LDL‐C after Atorvastatin Therapy in Chilean Individuals
Authors: Cuevas Alejandro , Fernández César , Ferrada Luis , Zambrano Tomás , Rosales Alexy , Saavedra Nicolás , Salazar Luis A.
Published: September 2015

Lipid‐lowering response to statin therapy shows large interindividual variability. At a genome‐wide significance level, single nucleotide polymorphisms (SNPs) in PCSK9 and HMGCR have been implicated in this differential response. However, the influence of these variants is uncertain in the Chilean population. Hence, we aimed to evaluate the contribution of PCSK9 rs7552841 and HMGCR rs17671591 SNPs as genetic determinants of atorvastatin response in Chilean hypercholesterolaemic individuals. One hundred and one hypercholesterolaemic patients received atorvastatin 10 mg/day for 4 weeks. Plasma lipid profile (TC, HDL‐C, LDL‐C and TG) was determined before and after statin treatment, and SNPs were identified by allelic discrimination using TaqMan® SNP Genotyping Assays. Adjusted univariate and multivariate analyses' models were used for statistical analyses, and a p‐value <0.05 was considered significant. From baseline (week 0) to the study end‐point (week 4), significant reductions were observed in plasma TC, LDL‐C and TG (p < 0.001), while HDL‐C levels were increased (p < 0.001). Multivariate analysis showed no association between lipid levels and atorvastatin therapy for the PCSK9 variant. However, the HMGCR rs17671591 T allele contributed to basal HDL‐C concentration variability along with a higher increase in this lipid fraction after statin medication. In addition, this allele determined greater plasma LDL‐C reductions after therapy with atorvastatin. Our data suggest that the HMGCR rs17671591 polymorphism can constitute a genetic marker of lower plasma LDL‐C and enhanced HDL‐C concentration after atorvastatin therapy in the Chilean population.
Can closeness, conflict, and dependency be used to characterize students’ perceptions of the affective relationship with their teacher? Testing a new child measure in middle childhood
Authors: Koomen Helma M. Y. , Jellesma Francine C.
Published: September 2015

Background

The constructs of closeness, conflict, and dependency, which are derived from attachment theory, are widely used to qualify teachers’ perceptions of relationships with individual children.

Aims

Our main aim was to reveal whether similar and reliable dimensions could be identified in middle childhood with a newly developed student measure Student Perception of Affective Relationship with Teacher Scale (SPARTS). Additional validity support was sought by examining gender differences and associations with (1) teacher relationship perceptions and (2) problem and prosocial behaviours in children.

Sample(s)

Factor structure was determined in a sample of 586 children (46.5% boys) from 26 regular elementary Dutch classrooms (grade 4–6). Associations with teacher relationship reports (n = 82) and child behaviours (n = 64) were analysed in random subsamples.

Methods

Students’ relationship perceptions were assessed with the SPARTS; teachers’ relationship perceptions with the Student–Teacher Relationship Scale (STRS; closeness, conflict, and dependency); and problem and prosocial behaviours in children with the teacher‐reported Strengths and Difficulties Questionnaire.

Results

Exploratory factor analysis and confirmatory factor analysis supported a 3‐factor model of conflict, closeness, and a third factor, unexpectedly reflecting negative expectations of the student instead of dependency. Satisfactory internal consistency was found for all three scales. Additional validity evidence included the following: Substantial student–teacher agreement for conflict and closeness; meaningful associations with problem and prosocial behaviours in children; and expected gender differences showing that, compared to boys, girls share more favourable relationships (more closeness and less conflict) with teachers.

Conclusions

The 3‐dimensional SPARTS comes close to the attachment‐derived teacher STRS, as far as conflict and closeness are concerned. The third dimension, negative expectations, represents a new and relevant attachment‐related dimension reflecting a lack of confidence of students in the relationship with their teacher.
Adenosine A1 receptor activation attenuates cardiac hypertrophy and fibrosis in response to α1‐adrenoceptor stimulation in vivo
Authors: Puhl S‐L , Kazakov A , Müller A , Fries P , Wagner D R , Böhm M , Maack C , Devaux Y
Published: September 2015

Background and Purpose

Adenosine has been proposed to exert anti‐hypertrophic effects. However, the precise regulation and the role of the different adenosine receptor subtypes in the heart and their effects on hypertrophic signalling are largely unknown. We aimed to characterize expression and function of adenosine A1 receptors following hypertrophic stimulation in vitro and in vivo.

Experimental Approach

Pro‐hypertrophic stimuli and adenosine A1 receptor stimulation of neonatal rat cardiomyocytes and male C57/Bl6 mice, sc. drug administration, real‐time PCR, 3[H]‐leucine‐incorporation assay, immunostaining, tissue staining, Western blots, gravimetric analyses and echocardiography were applied in this study.

Key Results

In neonatal rat cardiomyocyte cultures, phenylephrine, but not angiotensin II or insulin‐like growth factor 1 (IGF1), up‐regulated adenosine A1 receptors concentration‐dependently. The hypertrophic phenotype (cardiomyocyte size, sarcomeric organization, total protein synthesis, c‐fos expression) mediated by phenylephrine (10 μM), but not that by angiotensinII (1 μM) or IGF1 (20 ng·mL−1), was counteracted by the selective A1 receptor agonist, N6‐cyclopentyladenosine. In C57/BL6 mice, continuous N6‐cyclopentyladenosine infusion (2 mg·kg−1·day−1; 21 days) blunted phenylephrine (120 mg·kg−1·day−1; 21 days) induced hypertrophy (heart weight, cardiomyocyte size and fetal genes), fibrosis, MMP 2 up‐regulation and generation of oxidative stress – all hallmarks of maladaptive remodelling. Concurrently, phenylephrine administration increased expression of adenosine A1 receptors.

Conclusions and Implications

We have presented evidence for a negative feedback mechanism attenuating pathological myocardial hypertrophy following α1‐adrenoceptor stimulation. Our results suggest adenosine A1 receptors as potential targets for therapeutic strategies to prevent transition from compensated myocardial hypertrophy to decompensated heart failure due to chronic cardiac pressure overload.
The cost‐effectiveness of smoking cessation services provided by general dental practice, general medical practice, pharmacy andNHSStop Smoking Services in theNorth ofEngland
Authors: Csikar Julia I. , Douglas Gail V. , Pavitt Sue , Hulme Claire
Published: September 2015

Objectives

To compare the cost‐effectiveness of smoking cessation services in general dental practice (dental), general medical practice (GMP), pharmacy andNHSStop Smoking Services (NHS SSS) from the perspective of the provider and the perspective of theNHS.

Methods

Retrospective monitoring data fromNHSBradford were accessed for any client attending a smoking cessation advisor within one of four commissioned smoking cessation services delivered by and within dental,GMP, pharmacy andNHS SSS(July 2011–December 2011). The treatment outcome of interest was ‘quits’ (effectiveness), and costs were assessed using incremental cost‐effectiveness ratios (ICER) which compared each service setting against usual care (NHS SSS). All data were analysed usingSPSS19.

Results

For verified quits, only pharmacy services showed a lower mean cost per client and a higher proportion ofCOverified quits than the other services. For both verified and self‐reported quits dental services showed a slightly higher proportion of quits thanNHS SSS; however, the mean cost per client was higher (£278.38 for an increase in quits of 1%). TheGMPservices were dominated by theNHS SSS, in as much as they were both less effective (a smaller proportion of quits and more expensive). This finding also holds true when we comparedGMPservices and pharmacy services.

Conclusions

From the perspective of the service provider and theNHS, the service considered to be ‘cost‐effective’ when compared with ‘usual care’ (NHS SSS) was pharmacy services. This research has identified variations in service costs and effectiveness of services through the analysis of a pragmatic data set. Given the exploratory nature of this research, further research should explore the impact of service/location selection on uptake and cessation rates.
Prevalence of cleft lip and/or palate in children from Lodz between years 1981–2010
Authors: Antoszewski Bogusław , Fijałkowska Marta
Published: September 2015

Congenital malformations constitute a serious problem of both medical and social nature. Cleft lip and/or palate represent the most common congenital anomaly of the face that is why it is essential to know the real frequency of the described phenomenon. The aim of this paper is to determine the frequency of cleft lip and/or palate and the types of malformations that occurred in Lodz city between the years 1981–2010. Our clinic has been carrying on the studies concerning the incidence of cleft lip and/or palate since 1981. The Polish Registry of Congenital Malformations has been operating in Poland since 1 April 1997. The team has managed to obtain data, from the Registry, concerning the total number of all live born infants and the number of children with cleft lip and/or palate, who were born in Lodz, between 1998 and 2010. In years 1981–2010, 319 children, in 210 952 live born infants, were born with cleft lip and/or palate in Lodz. The isolated cleft palate was observed more frequently in girls and the unilateral cleft of lip and palate in boys. In all three decades palate clefts are more common whereas bilateral lip, alveolus and palate clefts are more infrequent. A small tendency to decrease in actual cleft lip and/or palate frequency among children, in the period of 30 years, is observed in Lodz. Over the years it has still been observed that the isolated cleft palate is the most common type of defect.
Comparison of radiographic and histological assessment of peri‐implant bone around oral implants
Authors: Stokholm Rie , Spin‐Neto Rubens , Nyengaard Jens R. , Isidor Flemming
Published: September 2015

Objectives

The aim of this study was to compare the radiographic bone mineral density and the histological assessment of relative volume density of bone and bone‐to‐implant contact (BIC) of single implants placed in the posterior mandible of monkeys.

Materials and methods

Five mature, male cynomolgus monkeys (Macaca fascicularis) with a total of 20 implants inserted 3–6 months previously were available for investigation. Digital intra‐oral radiographs were obtained with two different sensors and one phosphor plate system. The marginal bone level was measured on both sides of the implant on digital radiographs. Furthermore, bone density was evaluated using histogram analysis of the grey shades in a distance of 1 mm from the implant surface. The radiographic assessments were compared to histomorphometric analyses.

Results

The marginal bone level, the distance from the margin of the implant to the most coronal bone in direct contact with the implant evaluated histologically, was on average 1.4 mm, whereas this distance was significantly shorter (0.3 mm) on the digital radiographs. Still, a statistical significant correlation between the two bone level measurements was observed. The average radiographic bone density evaluated with the three different systems varied considerably. The histologic bone density was statistically significantly lower than the radiographic bone density measured with all the three techniques for acquiring digital radiographic images. Furthermore, the histologic bone density was statistically significantly correlated with the radiographic bone density only when measured with one of the sensors. On the other hand, the histologic BIC was statistically significantly correlated with the radiographic bone density obtained with all three techniques for acquiring digital radiographic images.

Conclusions

The distance from the margin of the implant to the most coronal bone in direct contact with the implant showed lower values on digital intra‐oral radiographs than histologically. Furthermore, the bone density assessed on intra‐oral radiographs reflected to some extend the amount of bone at or near the implant surfaces evaluated histologically.
The anatomy of the perineal body in relation to abdominoperineal excision for low rectal cancer
Authors: Kraima A. C. , West N. P. , Treanor D. , Magee D. , Roberts N. , van de Velde C. J. H. , DeRuiter M. C. , Quirke P. , Rutten H. J. T.
Published: September 2015

Aim

Dissection of the perineal body (PB) during abdominoperineal excision (APE) for low rectal cancer is often difficult due to the lack of a natural plane of dissection. Understanding the PB and its relation to the anorectum is essential to permit safe dissection during the perineal phase of the operation and avoid damage to the anorectum and urogenital organs. This study describes the anatomy and histology of the PB relevant to APE.

Method

Six human adult cadaver pelvic exenteration specimens (three male, three female) from the Leeds GIFT Research Tissue Programme were studied. Paraffin‐embedded mega‐blocks were produced and serially sectioned at 50‐ and 250‐μm intervals. Sections were stained by immunohistochemistry to show collagen, elastin and smooth muscle.

Results

The PB was cylindrically shaped in the male specimens and wedge‐shaped in the female ones. Although centrally located between the anal and urogenital triangles, it was nearly completely formed by muscle fibres derived from the rectal muscularis propria. Thick bundles of smooth muscle, mostly arising from the longitudinal muscle, inserted into the PB and levator ani muscle (LAM). The recto‐urethralis muscle originated from the PB and separated the anterolateral PB from the urogenital organs.

Conclusion

Smooth muscle fibres derived from the rectal muscularis propria extend into the PB and LAM and appear to fix the anorectum. Dissection of the PB during APE is safe only when the smooth muscle fibres that extend into the PB are divided.
Assessing the clinical outcome of nab‐paclitaxel in Chinese patients with advanced non‐small‐cell lung cancer
Authors: Zeng Junli , Yin Jie , Yuan Dongmei , Yang Wen , Liang Wenjun , Wu Guannan , Song Yong
Published: September 2015

Purpose

Nab‐paclitaxel [nab‐P, 130‐nm albumin‐bound paclitaxel particles] is a new solvent‐free paclitaxel that allows for high intratumoral concentration and has been approved for use in various solid tumours. The aim of our study was to evaluate the efficacy and safety of nab‐paclitaxel in the treatment of advanced non‐small‐cell lung cancer [NSCLC].

Patients and Methods

We assessed 101 Chinese patients who were diagnosed with Stage IIIB or IV NSCLC from August 2009 to November 2014.The patients were injected with nab‐paclitaxel [260 mg/m2, day1] with or without platinum. Patients who completed more than two treatment cycles were assessed for response and survival. All patients were assessed for adverse events.

Results

The efficacy was evaluated in 79 patients; the overall response rate was 32.9%, and the disease control rate was 89.9%. Subgroup analysis found patients with squamous cell carcinoma, and combination therapies showed better outcomes. The median progression‐free survival was 5.3 months [95%CI: 4.6–5.9], and the median overall survival was 8.9 months [95%CI: 6.1–11.6]. The main grades 3/4 adverse events were peripheral neuropathy [5.9%], leukopenia [5.0%], and anaemia [3.0%]. Additionally, severe abnormal hepatic function [2.0%], alopecia [2.0%], thrombocytopenia [1.0%] and fatigue [1.0%] could also be identified in some patients.

Conclusion

The nab‐paclitaxel chemotherapy could achieve significant tumour responses and encourage survival in advanced NSCLC patients with tolerable toxicities. Further clinical studies are needed to explore the optimal therapy regimen and target users.
Squamous cell carcinomas in chronic venous leg ulcers. Data of the German Marjolin Registry and review
Authors: Reich‐Schupke Stefanie , Doerler Martin , Wollina Uwe , Dissemond Joachim , Horn Thomas , Strölin Anke , Erfurt‐Berge Cornelia , Stücker Markus
Published: September 2015

Background

Secondary squamous cell carcinoma (SCC) is a rare complication of chronic venous leg ulcers. So far, little is known about its pathophysiology and clinical behavior. Initiated by the working group “Wound Healing” (AGW) of the German Society of Dermatology (DDG), it is the objective of the current Marjolin registry to collect cases of SCC arising in venous ulcers, in order to evaluate diagnostic characteristics.

Patients and Methods

All members of the AGW received questionnaires inquiring about basic patient data, ulcer characteristics, and therapy conducted.

Results

From 2010 to 2013, 30 patients (20 women, 10 men) from six tertiary wound care centers were registered. Mean age was 76.17 years. The average duration of venous leg ulcers prior to SCC diagnosis was 15.93 years. Suspicious wound characteristics primarily included: pain (n = 3), therapy resistance (n = 27), and fetor (n = 12) as well as clinical appearance (n = 10) with atypical morphology, nodular wound bed, and hypergranulation.

Conclusions

Atypical morphology or changes in appearance as well as therapy resistance despite optimal care (6–12 weeks) should prompt physicians to take spindle‐shaped, if necessary multiple and serial, biopsies. Primary risk factors for malignant transformation include patient age and ulcer duration.
Energy balance and metabolic changes with sodium‐glucose co‐transporter 2 inhibition
Authors: Rajeev S. P. , Cuthbertson D. J. , Wilding J. P. H.
Published: September 2015

Sodium‐glucose co‐transporter 2 (SGLT2) inhibitors are the latest addition to the class of oral glucose‐lowering drugs. They have been rapidly adopted into clinical practice because of therapeutic advantages, including weight loss and reduction in blood pressure, in addition to glycaemic benefits and a low intrinsic risk of hypoglycaemia. Although there are extensive data on the clinical effects of SGLT2 inhibition, the metabolic effects of inhibiting renal glucose reabsorption have not been fully described. Recent studies have identified compensatory metabolic effects, such as an increase in endogenous glucose production, and have also shown an increase in glucagon secretion during SGLT2 inhibition. In addition, there is a discrepancy between the expected and observed weight loss found in clinical studies on SGLT2 inhibitors, probably as a result of changes in energy balance with this treatment approach. SGLT2 inhibition is likely to have intriguing effects on whole body metabolism which have not been fully elucidated, and which, if explained, might help optimize the use of this new class of medicines.
Use of traction screw to aid in fracture reduction in bilateral parasymphysis fracture of mandible
Authors: Jaisani Mehul R , Pradhan Leeza , Dongol Ashok , Acharaya Pradeep , Sagtani Alok
Published: September 2015

Treatment of bilateral parasymphysis fracture often requires special attention due to airway considerations and difficulty in achieving precise anatomic reduction. The central fracture fragment is often displaced posteriorly and inferiorly due to muscle pull, and this adds to difficulty in reduction and stabilization of the central fracture fragment during plate fixation. With this article, we advocate a technique using stainless steel screw and self‐holding screwdriver to manipulate the central fragment and achieve an anatomic reduction. We have used this technique in 12 patients with bilateral parasymphysis fracture without any complications and have found it very effective.
Survival of cabbage stem flea beetle larvae, Psylliodes chrysocephala, exposed to low temperatures
Authors: Mathiasen H. , Bligaard J. , Esbjerg P.
Published: September 2015

The cabbage stem flea beetle, Psylliodes chrysocephala (L.) (Coleoptera: Chrysomelidae), is a major pest of winter oilseed rape. The larvae live throughout winter in leaf petioles and stems. Winter temperatures might play an important role in survival during winter and hence population dynamics, yet to what degree is unknown. This study investigates the effect of exposure time, cold acclimation, and larval stage on survival at −5 and −10 °C. Exposure time at −5 °C was 1, 2, 4, 8, 12, 16, and 20 days and 6, 12, 24, 36, 48, 72, 96, 120, and 144 h at −10 °C. Mortality increased with increasing exposure time and was significantly lower for cold‐acclimated larvae. Estimated time until an expected mortality of 50% (LT50) and 90% (LT90) of larvae exposed to −5 °C was 7.4 and 9.6 days (non‐acclimated) and 11.0 and 15.1 days (acclimated), respectively. Estimated LT50 for non‐acclimated and acclimated larvae exposed to −10 °C was 32.6 and 70.5 h, respectively, and estimated LT90 66.8 and 132.2 h. Significant differences in mortality between larval stages were observed only at −5 °C. When exposed to −5 °C for 8 days, mortality of first and second instars was 81.2 and 51.3%, respectively. When exposed to −10 °C for 2 days, mortality of first and second instars was 70.5 and 76.1%. Data on winter temperatures in Denmark from 1990 to 2013 showed that larvae were rarely exposed to a number of continuous days at −5 or −10 °C causing a potential larval mortality of 50–90%.
Association between CMYA5 gene polymorphisms and risk of schizophrenia in Uygur population and a meta‐analysis
Authors: Han Shuxian , An Zhiguo , Luo Xiao , Zhang Lili , Zhong Xianjiang , Du Wen , Yi Qizhong , Shi Yongyong
Published: September 2015

Aim

Previous evidence has found that some single nucleotide polymorphisms (SNPs) in cardiomyopathy‐associated 5 gene (CMYA5) were associated with schizophrenia in the Caucasian and Chinese Han populations. In this study, we aimed to investigate the relationship between CMYA5 gene polymorphisms and schizophrenia in Chinese Uygur population and perform a meta‐analysis to synthetically analyse the association of CMYA5 gene polymorphisms with schizophrenia in Asian populations.

Method

We retrospectively analysed 985 schizophrenia cases and 1123 healthy controls in Chinese Uygur population. Four SNPs (rs259127, rs3828611, rs4704591 and rs6883197) of CMYA5 were genotyped using TaqMan SNP genotyping assay. Meta‐analysis was conducted across Asian studies by Review Manager 5.2.

Results

Results showed no significant difference in either allelic or genotypic frequency in four SNPs of the CMYA5 gene between cases and controls (P > 0.05). However, the age of onset and the PANSS positive‐factor subscale score were significantly lower in schizophrenia patients with the A/A genotype of rs6883197 than those with A/G and G/G genotypes (P < 0.05). In addition, the meta‐analysis showed the significant association of rs3828611 with risk of schizophrenia (P = 0.03, OR = 0.92, 95% CI: 0.91–0.99).

Conclusions

Our results support the association between CMYA5 rs6883197 and schizophrenia in Chinese Uygur population. Meta‐analysis demonstrated that rs3828611 was significantly associated with schizophrenia in Asian population. Genetic heterogeneity among populations may be the main reason of results conflict between studies. In conclusion, association between CMYA5 gene polymorphisms and schizophrenia was confirmed in Asian population.
Conservative treatment of acquired oesophageal strictures by endoscopic‐guided balloon dilation in two horses
Authors: Stucchi L. , Zucca E. , Stancari G. , Conturba B. , Roncon S. , Ferro E. , Gualtieri M. , Ferrucci F.
Published: September 2015

Oesophageal stricture is an uncommon condition in horses that results in an obstructive syndrome with regurgitation of food and possible aspiration pneumonia. Currently, in both human and small animal practice, one of the preferred treatment options for oesophageal strictures consists of pneumatic or hydrostatic balloon dilation. The aim of this article is to report 2 cases of severe oesophageal stricture in the horse, successfully treated with endoscopic‐guided hydrostatic balloon dilation.
Generic medicines: issues and relevance for global health
Authors: Rana Proteesh , Roy Vandana
Published: September 2015

Generic medicine is a pharmaceutical product which is bioequivalent to the innovator product in terms of dosage form, strength, route of administration, quality, safety, performance characteristics, and intended use. Generic medicines are a cornerstone for providing affordable medicines to patients. The major generic markets in the world include United States of America followed by European Union, Canada, Japan, and Australia. The major suppliers of generic medicines China and India are showing tremendous growth in the generic medicine sector. There are many legal and regulatory issues along with quality concerns associated with the use of the generic products. Lately, bilateral international agreements called free trade agreements, delaying tactics by originator companies like strategic patenting and litigations on generic manufacturers, have been a major setback for the generic medicine industry. These issues need to be addressed to optimize the use of generic medicines. The sustainability of generic medicine sector is crucial for improving access to essential medicines for the worldwide.
Are ciprofloxacin dosage regimens adequate for antimicrobial efficacy and prevention of resistance? Pseudomonas aeruginosa bloodstream infection in elderly patients as a simulation case study
Authors: Cazaubon Yoann , Bourguignon Laurent , Goutelle Sylvain , Martin Olivier , Maire Pascal , Ducher Michel
Published: September 2015

The aim of this work was to define the optimal dosage (OD) of ciprofloxacin in order to prevent the emergence of bacterial resistance of Pseudomonas aeruginosa in a geriatric population with a bloodstream infection. A thousand pharmacokinetic profiles were simulated with a ciprofloxacin pharmacokinetic model from the literature. Three dosing regimens were tested for five days: once daily (QD), twice daily (BID), and thrice daily (TID). First of all, effective dosages (ED) of ciprofloxacin were defined as those achieving a target AUC24/MIC ≥ 125. Then, these ED were simulated in order to calculate the percentage of time spent within the mutant selection window (TMSW) and to select optimal dosage (OD) defined as those achieving TMSW ≤ 20%. Based on the AUC24/MIC, for low MICs (0.125 μg/mL), all dosing regimens recommended by French guidelines were effective. For intermediate MICs (0.25 and 0.5 μg/mL), simulated doses higher than those recommended were needed to achieve the efficacy target. About prevention of resistance for low MICs, dosages recommended were only effective in patients with creatinine clearance (CLCR) ≥ 60 mL/min. For intermediate MICs, dosages higher than recommended were needed to achieve the optimality target. This study shows that current ciprofloxacin dosing guidelines have not been optimized to prevent the emergence of bacterial resistance, especially in geriatric patients with mild to severe renal impairment. To achieve both efficacy and prevention of resistance, ciprofloxacin dosages greater than those recommended would be needed. Tolerance of such higher doses needs to be evaluated in clinical studies.
Hypointense hepatocellular carcinomas on apparent diffusion coefficient mapping: Pathological features and metastatic recurrence after hepatectomy
Authors: Mori Yoshiyuki , Tamai Hideyuki , Shingaki Naoki , Hayami Shinya , Ueno Masaki , Maeda Yoshimasa , Moribata Kosaku , Deguchi Hisanobu , Niwa Toru , Inoue Izumi , Maekita Takao , Iguchi Mikitaka , Kato Jun , Terada Masaki , Yamaue Hiroki , Ichinose Masao
Published: September 2015

Aim

The present study aimed to evaluate pathological features of hepatocellular carcinomas (HCC) appearing hypointense on the apparent diffusion coefficient (ADC) map, and to elucidate the association between the signal intensity on the ADC map and metastatic recurrences after hepatectomy.

Methods

In total, 52 consecutive patients with initial hypervascular HCC (solitary lesion ≤5 cm in diameter) without vascular invasion on imaging were examined by diffusion‐weighted magnetic resonance imaging before hepatectomy. The signal intensities of HCC on the ADC map were visually compared with the surrounding liver and categorized as hypointense or non‐hypointense. Intrahepatic metastatic recurrence was defined as more than three intrahepatic recurrences.

Results

The 52 HCC were evaluated as 26 hypointense and 26 non‐hypointense tumors. No significant differences between the hypointense and non‐hypointense groups were seen for age, sex, etiology, tumor size and tumor marker levels. However, in resected specimens, significant differences between the two groups were noted for histological grade and microscopic portal invasion. The percentages of poorly differentiated HCC and microscopic portal invasion in the hypointense group were significantly higher than those in the non‐hypointense group. The cumulative 3‐year metastatic recurrence rates of the hypointense and non‐hypointense groups on the ADC map were 56% and 13% (P = 0.001), respectively. Multivariate analyses indicated that hypointensity on the ADC map was the only independent factor related to metastatic recurrence.

Conclusion

Hypointense HCC on ADC mapping are characterized by poor histological differentiation and more frequent microscopic portal invasion, and are significantly associated with metastatic recurrences after hepatectomy.
Validation of digital pathology imaging for primary histopathological diagnosis
Authors: Snead David R J , Tsang Yee‐Wah , Meskiri Aisha , Kimani Peter K , Crossman Richard , Rajpoot Nasir M , Blessing Elaine , Chen Klaus , Gopalakrishnan Kishore , Matthews Paul , Momtahan Navid , Read‐Jones Sarah , Sah Shatrughan , Simmons Emma , Sinha Bidisa , Suortamo Sari , Yeo Yen , El Daly Hesham , Cree Ian A
Published: September 2015

Aims

Digital pathology (DP) offers advantages over glass slide microscopy (GS), but data demonstrating a statistically valid equivalent (i.e. non‐inferior) performance of DP against GS are required to permit its use in diagnosis. The aim of this study is to provide evidence of non‐inferiority.

Methods and results

Seventeen pathologists re‐reported 3017 cases by DP. Of these, 1009 were re‐reported by the same pathologist, and 2008 by a different pathologist. Re‐examination of 10 138 scanned slides (2.22 terabytes) produced 72 variances between GS and DP reports, including 21 clinically significant variances. Ground truth lay with GS in 12 cases and with DP in nine cases. These results are within the 95% confidence interval for existing intraobserver and interobserver variability, proving that DP is non‐inferior to GS. In three cases, the digital platform was deemed to be responsible for the variance, including a gastric biopsy, where Helicobacter pylori only became visible on slides scanned at the ×60 setting, and a bronchial biopsy and penile biopsy, where dysplasia was reported on DP but was not present on GS.

Conclusions

This is one of the largest studies proving that DP is equivalent to GS for the diagnosis of histopathology specimens. Error rates are similar in both platforms, although some problems e.g. detection of bacteria, are predictable.
Alternatives to restrictive feeding practices to promote self‐regulation in childhood: a developmental perspective
Authors: Rollins B. Y. , Savage J. S. , Fisher J. O. , Birch L. L.
Published: September 2015

Intake of energy‐dense snack foods is high among US children. Although the use of restrictive feeding practices has been shown to be counterproductive, there is very limited evidence for effective alternatives to restriction that help children moderate their intake of these foods and that facilitate the development of self‐regulation in childhood. The developmental literature on parenting and child outcomes may provide insights into alternatives to restrictive feeding practices. This review paper uses a model of parental control from the child development and parenting literatures to (i) operationally define restrictive feeding practices; (ii) summarize current evidence for antecedents and effects of parental restriction use on children's eating behaviours and weight status, and (iii) highlight alternative feeding practices that may facilitate the development of children's self‐regulation and moderate children's intake of palatable snack foods. We also discuss recent empirical evidence highlighting the role of child temperament and food motivation related behaviours as factors that prompt parents to use restrictive feeding practices and, yet, may increase children's dysregulated intake of forbidden foods.
The Investigation of the Phenomenological YIG Phase Formation Within 1000°C to 1250°C: A Kinetic Approach
Authors: Wan Ali Wan Fahmin Faiz , Othman Mohamadariff , Ain Mohd Fadzil , Abdullah Norazharuddin Shah , Ahmad Zainal Arifin
Published: September 2015

Presence of unwanted phase(s) such as yttrium iron perovskite (YIP) in yttrium iron garnet (YIG) ceramics has limited the utilization of YIG in the wireless communication domain. These unwanted phase(s) have been deemed responsible for the high dielectric losses, thus contributing to poor performance. This paper focuses on understanding the phenomenological phase transformation during the conventional solid state synthesis of YIG. This is done in order to monitor conditions which favor formation of unwanted phase(s), which shall later be reduced. The phase changes during YIG formation as a function of reaction times and temperatures were determined through XRD analysis. The amounts of YIG formed at various reaction times were fitted into various kinetic models in order to mathematically link what occurs experimentally to the available theoretical descriptions of reactions. It is found that the Ginstling‐Brounstein‐Habert (GBH) model exhibited good mathematical correlation to the formation of YIG. Meanwhile the activation energy (Ea) indicated 490 kJ/mol is required for the formation of YIG. At the end, a reaction model and mechanism between Fe2O3 and Y2O3 were established and illustrated to underline the effect of diffusion controlled environment on the formation of phases in YIG ceramics.
Multidisciplinary Treatment of the Metabolic Syndrome Lowers Blood Pressure Variability Independent of Blood Pressure Control
Authors: Marcus Yonit , Segev Elad , Shefer Gabi , Sack Jessica , Tal Brurya , Yaron Marianna , Carmeli Eli , Shefer Lili , Margaliot Miri , Limor Rona , Gilad Suzan , Sofer Yael , Stern Naftali
Published: September 2015

Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1‐year multidisciplinary intervention on BPV in patients with the metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty‐four nondiabetic patients underwent clinical and biochemical profiling, 24‐hour ambulatory BP monitoring (ABPM), body composition, carotid intima‐media thickness, and carotid‐femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high‐variability group had higher values of low‐density lipoprotein and leg fat. The 1‐year intervention resulted in weight reduction but not BP‐lowering. BPV declined in the high‐variability group in association with lowering of PWV, C‐reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high‐density lipoprotein cholesterol. A multidisciplinary intervention independent of BP‐lowering normalized BPV, lowered PWV, and enhanced metabolic control.
Inhibition of TRPC6 by protein kinase C isoforms in cultured human podocytes
Authors: Ambrus Lídia , Oláh Attila , Oláh Tamás , Balla György , Saleem Moin A. , Orosz Petronella , Zsuga Judit , Bíró Klára , Csernoch László , Bíró Tamás , Szabó Tamás
Published: September 2015

Transient receptor potential canonical‐6 (TRPC6) ion channels, expressed at high levels in podocytes of the filtration barrier, are recently implicated in the pathogenesis of various forms of proteinuric kidney diseases. Indeed, inherited or acquired up‐regulation of TRPC6 activities are suggested to play a role in podocytopathies. Yet, we possess limited information about the regulation of TRPC6 in human podocytes. Therefore, in this study, we aimed at defining how the protein kinase C (PKC) system, one of the key intracellular signalling pathways, regulates TRPC6 function and expression. On human differentiated podocytes, we identified the molecular expressions of both TRPC6 and several PKC isoforms. We also showed that TRPC6 channels are functional since the TRPC6 activator 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG) induced Ca2+‐influx to the cells. By assessing the regulatory roles of the PKCs, we found that inhibitors of the endogenous activities of classical and novel PKC isoforms markedly augmented TRPC6 activities. In contrast, activation of the PKC system by phorbol 12‐myristate 13‐acetate (PMA) exerted inhibitory actions on TRPC6 and suppressed its expression. Importantly, PMA treatment markedly down‐regulated the expression levels of PKCα, PKCβ, and PKCη reflecting their activation. Taken together, these results indicate that the PKC system exhibits a ‘tonic’ inhibition on TRPC6 activity in human podocytes suggesting that pathological conditions altering the expression and/or activation patterns of podocyte‐expressed PKCs may influence TRPC6 activity and hence podocyte functions. Therefore, it is proposed that targeted manipulation of certain PKC isoforms might be beneficial in certain proteinuric kidney diseases with altered TRPC6 functions.
In vivo confocal microscopic substrate of grey colour in melanosis
Authors: Cinotti E. , Couzan C. , Perrot J.L. , Habougit C. , Labeille B. , Cambazard F. , Moscarella E. , Kyrgidis A. , Argenziano G. , Pellacani G. , Longo C.
Published: September 2015

Background

Melanosis is the most common cause of mucosal pigmentation and can be clinically difficult to differentiate from early melanoma (MM). Dermoscopy can help in the distinction between melanosis and MM, but in some instances, melanoses may exhibit overlapping features with MM such as the presence of grey colour.

Objective

We sought to evaluate whether reflectance confocal microscopy (RCM) can help to better understand the dermoscopic features of melanoses in order to assist clinicians in their diagnosis.

Methods

All melanoses diagnosed between June 2011 and December 2014 in the Departments of Dermatology of the University of Saint‐Etienne (France) and of Modena and Reggio Emilia (Italy), for which dermoscopic and RCM images were available, were included. Twenty‐two lesions were biopsied to confirm the clinical diagnosis, whereas the others did not present any change at a follow‐up of at least 6 months. The correlation between dermoscopic and RCM features were evaluated by the Spearman's rho correlation coefficient.

Results

55 melanoses were studied: 31 of the oral mucosa and 24 of the genital mucosa. 49% (n = 27) of melanoses exhibited a grey colour under dermoscopy. The grey colour correlated with the presence of melanophages under RCM (ρ = 0.424, P = 0.002).

Conclusion

Our findings highlight that the presence of the grey colour on dermoscopy, considered as an alerting feature, is common in melanoses and it is related to the presence of melanin‐laden inflammatory cells in the papillary dermis on RCM. When it is present as a ‘pure’ feature not associated to other colours than brown or to atypical dermoscopical structures, it could be related to the diagnosis of melanosis.
The Water Metabolism of Socio‐Ecological Systems: Reflections and a Conceptual Framework
Authors: Madrid‐López Cristina , Giampietro Mario
Published: September 2015

Water accounting is an unresolved issue in metabolism studies. Through epistemological analysis, we show that the problem resides in the conceptualization of social metabolism. Social metabolism has its origins in the analysis of societal energetics, which has led to an exclusive focus on society and a representation based on linear throughputs at a single scale. Whereas fossil energy resources constitute a mere stock flow for society, water constitutes a set of both funds and flows essential for the maintenance of the internal organization and stability of society and ecosystems. This means that societies and ecosystems need water for different reasons. Consequently, the analysis of water requires the simultaneous adoption of multiple narratives and scales. The development of hydrology toward a socio‐eco‐hydrology (SE‐hydrology) deals with this multidimensionality, but lacks a conceptualization of the coupled human‐water system useful to integrate the assessment of water processes at different rates and scales. We propose a conceptual framework, based on the multiscale integrated analysis of societal and ecosystem metabolism approach, that combines the perspectives of SE‐hydrology and social metabolism. This framework describes society and the embedding ecosystem as two distinct levels of the same hierarchical system (i.e., the socioecological system), expressing two distinct, but tightly interconnected, metabolic patterns (societal and ecosystem) at different spatiotemporal scales. Using food grain production in Punjab as an example, we show that this framework can accommodate the multiple interpretations of social metabolism found in different scientific fields.