bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistance to Tomato leaf curl New Delhi virus in Cucurbita spp.
Authors: Sáez C. , Martínez C. , Ferriol M. , Manzano S. , Velasco L. , Jamilena M. , López C. , Picó B.
Published: March 2016

Tomato leaf curl New Delhi virus (ToLCNDV) is a bipartite begomovirus (family Geminiviridae) first reported in India and its neighbouring countries. ToLCNDV severely affects zucchini crop (Cucurbita pepo) in the main production areas of Southern Spain since 2012. This emerging begomovirus is a serious threat to this and other cucurbit crops. Breeding resistant cultivars is the most promising method for disease control, but requires the identification of sources of resistance in the Cucurbita genus. In this work, we screened for ToLCNDV resistance a large collection of Cucurbita spp. accessions, including landraces and commercial cultivars of the main cultivated species, C. pepo, Cucurbita moschata and Cucurbita maxima and wild species. The screening was performed using mechanical and whitefly inoculation. The level of resistance was assessed by scoring symptom severity and by measuring the virus content with quantitative polymerase chain reaction in selected genotypes. Diversity in the response was observed within and among species. Severe symptoms and high viral amounts were found at 30 days after mechanical and whitefly inoculation in C. pepo, in all accessions belonging to the Zucchini morphotype and to other morphotypes of both subspecies, pepo and ovifera, and even in the wild relative Cucurbita fraterna. C. maxima was also highly susceptible. This species showed characteristic symptoms of leaf decay and intense yellowing, different from those of mosaic, curling and internode shortening found in C. pepo. The only species showing resistance was C. moschata. Four accessions were symptomless or had some plants with only mild symptoms after three independent rounds of mechanical inoculation with different inoculum sources. Two of them also remained symptomless after virus inoculation with viruliferous whiteflies. ToLCNDV was detected in these asymptomatic accessions at 15 and 30 days post inoculation, but viral amounts were much lower than those found in susceptible genotypes, suggesting a high level of resistance. The symptoms in the susceptible accessions of this species were also different, with a characteristic leaf mottling, evolving to a severe mosaic. The newly identified C. moschata resistant accessions are good candidates for breeding programmes to avoid the damage caused by ToLCNDV.
Baseline medical comorbidities in adults randomized in the STRIDE trial for psychostimulant use disorders
Authors: dela Cruz Adriane M. , Carmody Thomas , Greer Tracy L. , Rethorst Chad D. , Warden Diane , Walker Robrina , Trivedi Madhukar H.
Published: March 2016

Background and Objectives

Rates of medical illnesses may be higher among individuals with substance use disorders, complicating their care. This study aimed to expand the understanding of other medical conditions in treatment‐seeking adults with stimulant use disorder (SUD) using data from Stimulant Reduction Intervention using Dose Exercise (STRIDE), a randomized, multisite trial investigating exercise augmentation of treatment as usual.

Methods

Utilizing STRIDE baseline data, we examined demographic and clinical characteristics based on the number of self‐reported diagnosed medical conditions among participants meeting eligibility criteria (passing medical screening exam and maximal exercise test, non‐opioid dependent, no concomitant beta blocker, or opioid replacement therapy).

Results

The majority (59%) of study participants (N = 302, mean age all participants = 39 years) did not report any history of other medical problems. Those with two or more conditions were older (mean age 46 years), reported more pain and worse physical functioning, and more psychiatric disorders (average 1.44). Hypertension was more common among participants with cocaine use disorders only (present in 16%) and liver disease was more common in those with cocaine plus other stimulant use disorders (present in 7%).

Conclusion and Scientific Significance

In this sample, patients with SUD were in surprisingly good health. A subpopulation had an overall higher burden of illness with worsened physical and psychiatric functioning. Provision of coordinated care may optimize treatment outcomes for patients based on medical comorbidity burden as well as type of drug abused, although these conclusions should be considered preliminary as they are based on self‐reported data. (Am J Addict 2016;25:215–220)
An independent replication of the Adolescent‐Community Reinforcement Approach with justice‐involved youth
Authors: Henderson Craig E. , Wevodau Amy L. , Henderson Susan E. , Colbourn Scholar L. , Gharagozloo Laadan , North Lindsey W. , Lotts Vivian A.
Published: March 2016

Background and Objectives

Substance use disorders among youth remain a serious public health problem. Although research has overwhelmingly supported the use of evidenced‐based interventions, one of the primary limitations of the current evidence base is that for the vast majority of treatments, the developers of the treatments are also the ones conducting research on them, raising the possibility of allegiance bias.

Methods

The present study was an independently conducted randomized controlled trial (n = 126) comparing an evidenced‐based treatment for adolescent substance use, Adolescent‐Community Reinforcement Approach (A‐CRA), and assertive continuing care (ACC), to services as usual (SAU) provided by a juvenile probation department. Latent growth curve modeling was used to compare the treatments on change in substance use assessed by the Global Appraisal of Individual Needs (GAIN) at baseline and 3, 6, and 12 months following treatment entry.

Results

All youth evidenced a substantial reduction in substance use frequency and substance‐related problems following treatment; however, youth treated with A‐CRA/ACC evidenced a substantially greater decrease in substance‐related problems.

Conclusions and Scientific Significance

Results are consistent with studies conducted by A‐CRA/ACC model developers supporting the effectiveness of the clinical approach and, because the outcomes resulted from an independent replication, are encouraging for the transportation potential of A‐CRA/ACC. (Am J Addict 2016;25:233–240)
Effects of an Enhanced Recovery After Surgery programme on emergency surgical patients
Authors: Wisely Jessica C. , Barclay Karen L.
Published: March 2016

Background

Enhanced Recovery After Surgery (ERAS) programmes have been used in elective surgery since the 1990s to optimize peri‐operative care, reducing post‐operative complications, length of stay and overall costs. Following the local introduction of an ERAS programme for colorectal elective patients, it was suggested an increase in the use of ERAS‐type principles in emergency patients may have occurred. The aims of this study were to determine whether management changes could be demonstrated and if there was a difference in outcomes.

Method

A retrospective cohort study comparing emergency patients undergoing major abdominal surgery October 2008 to May 2010 (pre‐ERAS) and January 2011 to December 2012 (post‐ERAS) was performed. Details collected included admission and operative details, post‐operative management and outcomes.

Results

A total of 370 patients were studied. Baseline variables were comparable. Post‐ERAS, intra‐operative (P < 0.001) and post‐operative 48 h totals (P < 0.001) of intravenous fluids were significantly reduced. Significantly fewer patients in the post‐ERAS group had a catheter (P < 0.001), drain (P = 0.001) and patient controlled analgesia (P = 0.01) for more than 2 days. Major complications (P = 0.002) and individual minor complications such as urinary tract infections (P = 0.02), urinary retention (P = 0.001) and chest infections (P = 0.001) were all significantly reduced in the post‐ERAS period.

Conclusion

This study demonstrates a significant change in management towards ERAS principles in emergency patients following the introduction of such a programme in elective patients. The lack of increased complications in the second period suggests the use of ERAS principles is not harmful. The wider application of ERAS principles could improve outcomes in emergency surgery and deserves further study.
Update in achalasia: what the surgeon needs to know
Authors: Hamer Peter W. , Holloway Richard H. , Crosthwaite Gary , Devitt Peter G. , Thompson Sarah K.
Published: March 2016

Achalasia is a motility disorder encountered by surgeons during the investigation and treatment of dysphagia. Recent advances in manometry technology, a widely accepted new classification system and a new treatment rapidly gaining international acceptance, have changed the working knowledge required to successfully manage patients with achalasia. We review the Chicago classification subtypes of achalasia with type II achalasia being a predictor of success and type III achalasia a predictor of treatment failure. We review per‐oral endoscopic myotomy as an emerging treatment option and its potential for improving the treatment of type III achalasia.
Should the non‐operative management of appendicitis be the new standard of care?
Authors: Gandy Robert C. , Wang Frank
Published: March 2016

Appendicitis is one of the most commonly encountered emergency presentations to the general surgical services. The operative management of this condition is associated with significant financial costs and represents a significant workload on the emergency surgical services. Negative appendicectomy rates remain high (20–25%) despite advancements in laboratory testing and imaging techniques. Recent data from randomized controlled trials suggests that non‐operative management in patients presenting with uncomplicated or non‐perforated acute appendicitis is a viable alternative, with only 23% of patients requiring an appendicectomy at 1 year and an overall reduction in complications. In view of this, the traditional teaching of mandatory appendicectomy for all patients with acute appendicitis should be challenged. This article briefly reviews the evidence that supports the use of diagnostic tests to reduce the negative appendicectomy rate and examines the potential selection criteria for non‐operative management. The data raises the questions: can a 20–25% negative appendicectomy rate be defended as best practice and can the traditional dogma of early appendicectomy to prevent perforation be supported?
A real‐world study focused on the long‐term efficacy of mycophenolate mofetil as first‐line treatment of autoimmune hepatitis
Authors: Zachou K. , Gatselis N. K. , Arvaniti P. , Gabeta S. , Rigopoulou E. I. , Koukoulis G. K. , Dalekos G. N.
Published: March 2016

Background

Front‐line therapy with mycophenolate mofetil (MMF) in autoimmune hepatitis (AIH) has shown high on‐treatment remission rates.

Aim

To study prospectively in a real‐world fashion the long‐term outcome of a large group of consecutive treatment‐naïve AIH patients.

Methods

Between 2000 and 2014, 158 patients were recruited but only 131 were eligible for treatment (109 MMF/prednisolone; 22 prednisolone ± azathioprine). Long‐term data on outcome after drug withdrawal were evaluated. Patients stopped treatment after having achieved complete response (normal transaminases and IgG) for at least the last 2 years.

Results

At diagnosis, 31.6% of patients had cirrhosis and 72.8% insidious presentation. A total of 102 of 109 (93.6%) responded initially to MMF within 2 (1–18) months. A total of 78 of 109 (71.6%) had complete response on treatment and 61 of 78 (78.2%) maintained remission off prednisolone. MMF‐treated patients had increased probability of complete response compared to those receiving azathioprine (P = 0.03). Independent predictors of complete response were lower ALT at 6 months (P = 0.001) and acute presentation (P = 0.03). So far, treatment withdrawal was feasible in 40/109 patients and 30 (75%) are still in remission after 24 (2–129) months. Remission maintenance was associated with longer MMF treatment (P = 0.005), higher baseline ALT (P < 0.02), lower IgG on 6 months (P = 0.004) and histological improvement.

Conclusions

Mycophenolate mofetil proved to be an efficient first‐line treatment for AIH, achieving so far the highest rates of remission maintenance off treatment (75%) ever published for at least a median of 2 years, although the remission criteria used were strict. However, the risk of potential bias and overestimation of intervention benefits from MMF cannot be completely excluded as this is a real world and not a randomised controlled trial.
Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype
Authors: Kagami T. , Sahara S. , Ichikawa H. , Uotani T. , Yamade M. , Sugimoto M. , Hamaya Y. , Iwaizumi M. , Osawa S. , Sugimoto K. , Miyajima H. , Furuta T.
Published: March 2016

Background

Acid inhibitory effects of proton pump inhibitors (PPIs) are influenced by CYP2C19 genotype. In contrast, the potent acid inhibition of vonoprazan is not influenced by CYP2C19 genotype.

Aim

To compare the acid inhibitory effects of vonoprazan and esomeprazole in relation to CYP2C19 genotype.

Methods

Twenty‐eight healthy Japanese volunteers [7 CYP2C19 poor metabolisers (PMs), 11 intermediate metabolisers (IMs) and 10 rapid metabolisers (RMs)] received four different regimens in a randomised crossover manner: (i) vonoprazan 20 mg twice daily (b.d.), (ii) vonoprazan 20 mg daily, (iii) esomeprazole 20 mg b.d. and (iv) esomeprazole 20 mg daily. The timing of each dosing was 1 h before a meal. Twenty‐four‐hour intragastric pH monitoring was performed on day 7 on each regimen.

Results

In the overall genotype group, pH ≥4 holding time ratios (pH 4 HTRs) with vonoprazan b.d., vonoprazan daily, esomeprazole b.d. and esomeprazole daily were 100%, 95%, 91%, and 68% respectively. pH 5 HTRs were 99%, 91%, 84% and 54% respectively. Vonoprazan b.d. potently suppressed acid for 24 h, and was significantly superior to other regimens irrespective of CYP2C19 genotype. Vonoprazan daily was equivalent to esomeprazole b.d. in IMs and PMs, but superior in RMs. CYP2C19 genotype‐dependent differences were observed in esomeprazole daily but not in vonoprazan b.d. or daily.

Conclusion

Vonoprazan 20 mg b.d. inhibits acid irrespective of CYP2C19 genotype, more potently than esomeprazole 20 mg b.d., pH 4 and 5 holding time ratios reached 100% and 99%, respectively.
Critiquing participatory video: experiences from around the world
Authors: Milne E‐J
Published: March 2016

Over the past decade there has been a growing interest in participatory video, but accounts have often been celebratory and uncritical. At the same time there has been an ever‐increasing multiplicity of interpretations, thus making participatory video seem ‘nebulous’ and ‘perplexing’. This special section seeks to develop some of the critiques developed over the past five years, by bringing together a series of provocative thought pieces. Through this special section we seek to continue to develop a critique of participatory video as both a methodology and method. We also call on researchers, practitioners and participants to commit to engaging in rigorous public debate and intellectual critique in order to strengthen the field.
The effect of colostrum ingestion during the first 24 hours of life on early postnatal development of piglet immune systems
Authors: Ogawa Shohei , Tsukahara Takamitsu , Imaoka Taishi , Nakanishi Nobuo , Ushida Kazunari , Inoue Ryo
Published: March 2016

It has been suggested that colostrum is important not only for direct protection from pathogens but also for proper development of immune systems in piglets. In this study, we focused on the effect of colostrum ingestion during the first 24 h of life on early postnatal development of piglet immune systems. Thirty‐six piglets from five litters were divided into colostrum‐fed (CoF) and colostrum‐deprived (CoD) groups. The former group was allowed to suckle normally while formula milk was fed to the latter group during the first 24 h of life. At the weaning period, the concentrations of fecal immunoglobulin (Ig) A and plasma IgG as well as the number of blood leukocyte subsets were analyzed. Fecal IgA and plasma IgG concentrations in the CoF group were more than twice as high as those in the CoD group (P < 0.01). In addition, the number of blood B cells was significantly higher in the CoF group than that in the CoD group (P < 0.05). This study demonstrates that colostrum ingestion during the first 24 h plays a significant role in early postnatal development of both mucosal and systemic immunity of piglets.
Effect of linseed oil supplementation on performance and milk fatty acid composition in dairy cows
Authors: Suksombat Wisitiporn , Thanh Lam Phuoc , Meeprom Chayapol , Mirattanaphrai Rattakorn
Published: March 2016

Thirty‐six Holstein‐Friesian crossbred lactating dairy cows were used to determine the effects of linseed oil supplementation on performance and milk fatty acid (FA) profile. Three treatments were as follows: basal diet (56:44 Roughage:concentrate [R:C] ratio, dry matter basis) supplemented with 500 g of palm oil as control (PO), 500 g mixture (1:1, w/w) of palm oil and linseed oil (POLSO) and 500 g of linseed oil (LSO). The LSO supplementation had no effects on total dry matter intake (DMI), milk yield and milk composition. Compared to control cows, cows supplemented with LSO increased milk concentrations of cis‐9,trans‐11 conjugated linoleic acid (CLA) and n‐3 FA (P < 0.05), particularly C18:3n‐3, C20:5n‐3 and C22:6n‐3. Feeding LSO reduced concentrations of milk short‐ and medium‐chain saturated fatty acids (P < 0.05) while it increased concentration of milk unsaturated fatty acids (P < 0.05). Milk proportions of n‐3 FA increased, whereas n‐6/n‐3 ratio decreased in the LSO as compared with the control (P < 0.05). In conclusion, supplementing dairy cows' diet based on corn silage with LSO at 500 g/day could improve the nutritional value of milk with potential health‐beneficial FA without detrimental effect on milk composition or cow's performance.
Tirapazamine has no Effect on Hepatotoxicity of Cisplatin and 5‐fluorouracil but Interacts with Doxorubicin Leading to Side Changes in Redox Equilibrium
Authors: Mandziuk Slawomir , Matysiak Wlodzimierz , Korga Agnieszka , Burdan Franciszek , Pasnik Iwona , Hejna Marcin , Korobowicz‐Markiewicz Agnieszka , Grzycka‐Kowalczyk Luiza , Kowalczyk Michal , Poleszak Ewa , Jodlowska‐Jedrych Barbara , Dudka Jaroslaw
Published: March 2016

Tirapazamine is a hypoxia‐activated prodrug which was shown to exhibit up to 300 times greater cytotoxicity under anoxic in comparison with aerobic conditions. Thus, the combined anticancer therapy of tirapazamine with a routinely used anticancer drug seems to be a promising solution. Because tirapazamine undergoes redox cycle transformation in this study, the effect of tirapazamine on redox hepatic equilibrium, lipid status and liver morphology was evaluated in rats exposed to cisplatin, doxorubicin and 5‐fluorouracil. Rats were intraperitoneally injected with tirapazamine and a particular cytostatic. The animals were killed, and blood and liver were collected. Hepatic glucose, total cholesterol, triglycerides, NADH, NADPH glutathione and the activity of glucose‐6‐phosphate dehydrogenase were determined. Liver morphology and the immune expression of HMG‐CoA‐reductase were also assessed. Glucose, total cholesterol, triglycerides, bilirubin concentrations and the activity of aspartate and alanine aminotransferases were determined in the plasma. Tirapazamine displayed insignificant interactions with cisplatin and 5‐fluorouracil referring to hepatic morphology and biochemical parameters. However, tirapazamine interacts with doxorubicin, thus leading to side changes in redox equilibrium and lipid peroxidation, but those effects are not severe enough to exclude that drug combination from further studies. Thus, tirapazamine seems to be a promising agent in successive studies on anticancer activity in similar schedules.
Development of stratum corneum chymotrypsin-like protease activity and natural moisturizing factors from birth to 4 weeks of age compared with adults
Authors: Chittock J. , Cooke A. , Lavender T. , Brown K. , Wigley A. , Victor S. , Cork M.J. , Danby S.G.
Published: March 2016

Background

From birth, the functional properties of the neonatal epidermal barrier mature whereby the stratum corneum (SC) hydrates and the skin surface acidifies. The identification of a thinner infant SC compared with adults suggests underdeveloped mechanisms underlying differentiation and desquamation.

Objectives

To assess the functional properties of the neonatal SC from birth, in conjunction with the quantification of superficial chymotrypsin-like protease activity [kallikrein-7 (KLK-7)] and filaggrin-derived natural moisturizing factors (NMF).

Methods

A total of 115 neonates recruited to the Oil in Baby SkincaRE (OBSeRvE) randomized controlled trial underwent a full evaluation of the SC at birth (< 72 h old) and at 4 weeks of age (n = 39, no oil control group) using minimally invasive instrumentation and methodology. A cohort of 20 unrelated adults was recruited for comparison.

Results

At birth NMF levels correlated with SC hydration (r = 0·50) and skin-surface pH (r = −0·54). From birth to 4 weeks, transepidermal water loss (TEWL), superficial KLK-7 activity and filaggrin-derived NMF significantly elevated. Impaired epidermal barrier function at birth (> 75th percentile TEWL) was accompanied by significantly elevated chymotrypsin-like protease activity and reduced levels of NMF.

Conclusions

The biophysical, biological and functional properties of the developing neonatal SC are transitional from birth to 4 weeks of age and differ significantly from adults. The presence of impaired barrier function with elevated protease activity and reduced NMF at birth suggests why certain infants are predisposed to epidermal barrier breakdown and the development of atopic dermatitis.
Mobile technologies for learning: Exploring critical mobile learning literacies as enabler of graduateness in a South African research‐led University
Authors: Bosman J. P. , Strydom Sonja
Published: March 2016

At Stellenbosch University there is a drive to integrate the development of graduate attributes and the use of emerging technologies in the curriculum. With the aim of discovering the role of emerging mobile technologies in learning a qualitative research project was undertaken with a senior‐student cohort. An inductive thematic analysis was done using Ng's () mLearning literacies framework (cognitive, socio‐emotional and technical), and situating it within the field of graduateness (Barrie ; Bozalek & Watters, ). This paper reports on the research which informs the literature on graduateness with regards to the potential role of critical mobile learning literacies and expands the application of the mLearning literacies framework as part of the digital literacies debate. Resulting themes were: (1) a critical awareness of 21st century learning; (2) an underdeveloped mLearning literacy (with criticality as indicator); and (3) multidimensional expectations regarding the development of mLearning literacy. To support the notion of lifelong learning and graduateness, we call for the development of particularly criticality in mLearning literacy skills at a cognitive, socio‐emotional and technical level with mobile devices in both formal and informal learning. This has implications for curriculum design, pedagogic approaches and a focus on interactions with new forms of knowledge.
A systematic review of the association between depression and health care utilization in children and adults with sickle cell disease
Authors: Jonassaint Charles R. , Jones Victor L. , Leong Sharlene , Frierson Georita M.
Published: March 2016

Patients with sickle cell disease (SCD) experience a disproportionately high use of health care resources. Several studies have examined depression and other negative mood states as risk factors for increased health care utilization; however, there have been no systematic reviews examining and summarizing this evidence in SCD. The aim of this systematic review, therefore, was to determine whether depression or depressive symptoms are associated with health care utilization among children and adults with SCD. We followed a quantitative systematic review protocol based on the Preferred Reporting Items for Systematic Reviews and Meta‐ Analyses guidelines and performed a literature search of records from January 1980 to April 2014 using six databases. Empirical studies were eligible if the sample was primarily composed of patients with SCD and included data on depression, mood disorder diagnosis or depressive symptoms and health care utilization. We included 12 studies involving 54 036 unique participants. The prevalence estimates for depression ranged from 2–57%. Seven studies found a significant, or marginally significant, association between depression and utilization while five did not. Patients reporting depression had an estimated 2·8 times greater relative risk of being a high utilizer, and 2·9 versus 1·8 hospitalizations per year on average compared to patients without depression. Overall, depressive symptoms are common in SCD and may increase risk for poor outcomes including health care utilization. The available studies on depression in SCD, however, are limited by small sample sizes, retrospective designs or short follow‐up. This systematic review found a modest association between depression and health care utilization in SCD.
Patient‐related factors independently impact overall survival in patients with myelodysplastic syndromes: an MDS‐CAN prospective study
Authors: Buckstein Rena , Wells Richard A. , Zhu Nancy , Leitch Heather A. , Nevill Thomas J. , Yee Karen W. L. , Leber Brian , Sabloff Mitchell , St. Hilaire Eve , Kumar Rajat , Geddes Michelle , Shamy April , Storring John , Kew Andrea , Elemary Mohamed , Levitt Max , Lenis Martha , Mamedov Alex , Zhang Liying , Rockwood Ken , Alibhai Shabbir M. H.
Published: March 2016

Little is known about the effects of frailty, disability and physical functioning on the clinical outcomes for myelodysplastic syndromes (MDS). We investigated the predictive value of these factors on overall survival (OS) in 445 consecutive patients with MDS and chronic monomyelocytic leukaemia (CMML) enrolled in a multi‐centre prospective national registry. Frailty, comorbidity, instrumental activities of daily living, disability, quality of life, fatigue and physical performance measures were evaluated at baseline and were added as covariates to conventional MDS‐related factors as predictors of OS in Cox proportional hazards models. The median age was 73 years, and 79% had revised International Prognostic Scoring System (IPSS‐R) risk scores of intermediate or lower. Frailty correlated only modestly with comorbidity. OS was significantly shorter for patients with higher frailty and comorbidity scores, any disability, impaired grip strength and timed chair stand tests. By multivariate analysis, the age‐adjusted IPSS‐R, frailty (Hazard ratio 2·7 (95% confidence interval [CI] 1·7–4·2), P < 0·0001) and Charlson comorbidity score (Hazard ratio 1·8 (95% CI 1·1–2·8), P = 0·01) were independently prognostic of OS. Incorporation of frailty and comorbidity scores improved risk stratification of the IPSS‐R by 30% and 5%, respectively. These data demonstrate for the first time, the importance of considering frailty in prognostic models and a potential target for therapeutic intervention in optimizing clinical outcomes in older MDS patients.

Trial Registration: ClinicalTrials.gov Identifier: NCT02537990.
Increased microcirculation detected by dynamic contrast‐enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma
Authors: Hillengass Jens , Ritsch Judith , Merz Maximilian , Wagner Barbara , Kunz Christina , Hielscher Thomas , Laue Hendrik , Bäuerle Tobias , Zechmann Christian M. , Ho Anthony D. , Schlemmer Heinz‐Peter , Goldschmidt Hartmut , Moehler Thomas M. , Delorme Stefan
Published: March 2016

This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE‐MRI) as a non‐invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE‐MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE‐MRI of the lumbar spine. Regions of interest were drawn manually on T1‐weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut‐off point of 0·89 arbitrary units had a 2‐year progression rate into symptomatic disease of 80%. In conclusion, DCE‐MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS.
Is it all in the reward? Peers influence risk‐taking behaviour in young adulthood
Authors: Reniers Renate L. E. P. , Beavan Amanda , Keogan Louise , Furneaux Andrea , Mayhew Samantha , Wood Stephen J.
Published: March 2016

The presence of peers is suggested to increase risk‐taking behaviour by heightening response to reward. The current study investigated this using a computerized financial risk‐taking task which was performed twice by a group of young adults (n = 201, median age 19.8 years): once alone and once while in the presence of two peers. An overall increase in risk‐taking was observed when with peers compared to when alone (CHANGE). CHANGE was positively associated with self‐reported levels of reward responsiveness and fun seeking while older age and lack of perseverance were associated with reduced CHANGE. The association between risk‐taking when with peers and both resistance to the influence of peers and age was indirect through reward responsiveness. Reward responsiveness was positively associated with impulsiveness. Only in those who showed a peer‐related decrease in risk‐taking (1/3 of participants), risk‐taking in the presence of peers was associated with increased impulsiveness. The current findings suggest an important role for reward responsiveness in risk‐taking behaviour and demonstrate the influence of peers. Increased understanding of these processes has direct implications for prevention and intervention efforts. Placing risk‐taking behaviour within varying (social) contexts with an eye for differences in personality, development, and emotions provides ample scope for future research.
Changing Repertoires and Partisan Ambivalence in the New Brazilian Protests
Authors: ALONSO ANGELA , MISCHE ANN
Published: March 2016

This article analyses the June 2013 wave of political protests in Brazil, highlighting student movement participation. We make three arguments. First, this was not a single student movement, but a cycle of protest, consisting of many different actors, issues, and forms of demonstration. Second, protesters built what we call hybrid performances, drawing on three repertoires of contention: socialist, autonomist and patriotic. Third, the protests presented a strong rejection of political parties, problematising the relationship between social movements, political parties, and institutional politics.
5‐HT3 receptors promote colonic inflammation via activation of substance P/neurokinin‐1 receptors in dextran sulphate sodium‐induced murine colitis
Authors: Utsumi Daichi , Matsumoto Kenjiro , Amagase Kikuko , Horie Syunji , Kato Shinichi
Published: March 2016

Background and Purpose

5‐HT (serotonin) regulates various physiological functions, both directly and via enteric neurons. The present study investigated the role of endogenous 5‐HT and 5‐HT3 receptors in the pathogenic mechanisms involved in colonic inflammation, especially in relation to substance P (SP) and the neurokinin‐1 (NK1) receptor.

Experimental Approach

The effects of 5‐HT3 and NK1 receptor antagonists were examined in dextran sulphate sodium (DSS)‐induced colitis in mice. Inflammatory mediator expression and the distribution of 5‐HT3 and NK1 receptors were also determined.

Key Results

Daily administration of ramosetron and ondansetron (5‐HT3 antagonists) dose‐dependently attenuated the severity of DSS‐induced colitis and up‐regulation of inflammatory mediator expression. Immunohistochemical analysis showed 5‐HT3 receptors are mainly expressed in vesicular ACh transporter‐positive cholinergic nerve fibres in normal colon. DSS increased the number of colonic nerve fibres that were double positive for 5‐HT3 receptors and SP but not of those that were double positive for 5‐HT3 receptors and vesicular ACh transporter. DSS increased colonic SP levels and SP‐positive nerve fibres; these responses were attenuated by ramosetron. DSS‐induced colitis and up‐regulation of inflammatory mediators were attenuated by aprepitant, an NK1 antagonist. Immunohistochemical studies further revealed that DSS treatment markedly increased NK1 receptor expression in CD11b‐positive cells.

Conclusions and Implications

These findings indicate that the 5‐HT/5‐HT3 receptor and SP/NK1 receptor pathways play pathogenic roles in colonic inflammation. 5‐HT acts via 5‐HT3 receptors to up‐regulate inflammatory mediators and promote colonic inflammation. These effects may be further mediated by activation of macrophage NK1 receptors via SP released from 5‐HT3 receptor‐positive nerve fibres.
Caught in the eye of the storm: a qualitative study of views and experiences of planned drug holidays from methylphenidate in child and adolescent ADHD treatment
Authors: Ibrahim Kinda , Vogt Carsten , Donyai Parastou
Published: March 2016

Background

Attention deficit hyperactivity disorder (ADHD) can be treated with stimulant medication such as methylphenidate. Although effective, methylphenidate can cause serious side‐effects, including suppressed appetite, growth retardation and sleep problems. A drug holiday is a deliberate interruption of pharmacotherapy for a defined period of time and for a specific clinical purpose, for example for appeasing side‐effects. While some international guidelines recommend introducing drug holidays in ADHD treatment, this is not practised routinely. Our aim was to examine the views and experiences of planned drug holidays from methylphenidate with adults who have responsibility for treatment decisions in children and adolescents with ADHD.

Method

In‐depth interviews were carried out. Child and Adolescent Mental Health Services practitioners (n = 8), General practitioners (n = 8), teachers (n = 5) and mothers of children with ADHD (n = 4) were interviewed in a UK setting. Interview transcripts were analysed using grounded theory.

Results

Methylphenidate eases the experience of the child amid problems at home and at school and once started is mostly continued long term. Some families do practise short‐term drug holidays at weekends and longer term ones during school holidays. The decision to introduce drug holidays is influenced by the child's academic progress, the parents' ability to cope with the child, as well as medication beliefs. Trialling a drug holiday is thought to allow older children to self‐assess their ability to manage without medication when they show signs of wanting to discontinue treatment prematurely.

Conclusions

Planned drug holidays could address premature treatment cessation by enabling adolescents to assess repercussions under medical supervision.
Conjugation of Uridine with Oleanolic Acid Derivatives as Potential Antitumor Agents
Authors: Cheng Ke‐Guang , Su Chun‐Hua , Huang Jia‐Yan , Liu Jun , Zheng Yuan‐Ting , Chen Zhen‐Feng
Published: March 2016

According to fused two bioactive moieties together by bonds covalently and available as a new single hybrid entity known as pharmacophore hybridization, a total of 10 targeted uridine–oleanolic acid hybrids were synthesized. Most of these hybrids showed excellent proliferation inhibition against tested Hep‐G2, A549, BGC‐823, MCF‐7, and PC‐3 tumor cell lines (IC50 < 8 μm), even with some IC50 values under 0.1 μm. The detection of cytotoxicity selectivity revealed that hybrids 5 and 18 exhibited low cytotoxicity toward normal human liver cell HL‐7702. Further studies revealed that selected hybrid 5 could induce apoptosis in Hep‐G2 cells through the investigation of acridine orange/ethidium bromide, Hoechst 33258 fluorescence stainings, and annexin V/propidium iodide assay. It was also found that hybrid 5 could induce mitochondrial membrane potential disruption, arrest Hep‐G2 cell line at G1 phase, and activate effector caspase‐3/9 to trigger cell apoptosis.
CXCR5 is critically involved in progression of lupus through regulation of B cell and double-negative T cell trafficking
Authors: Wiener A , Schippers A , Wagner N , Tacke F , Ostendorf T , Honke N , Tenbrock K , Ohl K
Published: March 2016

The recruitment of immune cells to sites of tissue inflammation is orchestrated by chemokine/chemokine receptor networks. Among these, the CXCL13/CXCR5 axis is thought to be involved critically in systemic lupus erythematosus (SLE) and lupus nephritis pathogenesis. Beyond B cell abnormalities, another hallmark of SLE disease is the occurrence of aberrant T cell responses. In particular, double-negative (DN) T cells are expanded in the peripheral blood of patients with SLE and in lupus-prone mice. DN T cells induce immunoglobulin production, secrete proinflammatory cytokines and infiltrate inflamed tissue, including kidneys. We aimed to investigate how CXCR5 deficiency changes immune cell trafficking in murine lupus. We therefore crossed CXCR5–/– mice with B6/lpr mice, a well-established murine lupus model. B cell numbers and B cellular immune responses were diminished in CXCR5-deficient B6/lpr mice. In addition, we observed reduced accumulation of DN T cells in spleen and lymph nodes, paralleled by reduced splenomegaly and lymphadenopathy. In-vivo migration assays revealed reduced migration of CXCR5-deficient DN T cells into lymph nodes, and ex-vivo-activated CXCR5-deficient DN T cells failed to infiltrate kidneys of recipients. Moreover, DN T cells and B cells of CXCR5-deficient B6/lpr mice failed to migrate towards CXCL13 in vitro. We propose that CXCR5 is involved critically in B cell trafficking and germinal cell (GC) formation in murine lupus and in guiding pathogenic DN T cells into lymphoid organs and kidneys, and we therefore describe new pathomechanisms for the CXCL13/CXCR5 axis in SLE.
Influence of maintenance care in periodontally susceptible and non‐susceptible subjects following implant therapy
Authors: Tan Wah Ching , Ong Marianne M. A. , Lang Niklaus P.
Published: March 2016

Objectives

To compare the periodontal and peri‐implant conditions of periodontally susceptible and periodontally healthy subjects under maintenance care for a period of at least 3 years.

Material and methods

Sixty periodontally susceptible patients (PSP) and 56 periodontally non‐susceptible subjects (PHS) were treated with dental implants in the National Dental Centre Singapore (NDCS) and were maintained in a regular supportive periodontal care program for a mean of 6 years. Full mouth bleeding on probing (BoP), full mouth probing pocket depths (PPD), implant loss, and absence of crestal bone loss were recorded at the time of prosthesis delivery and following a mean follow‐up of 6 years 2 months.

Results

Although there were significant differences in the BoP and the percentage of subjects with tooth probing pocket depth ≥5 mm between PSP and PHS at the time of implant prosthesis installation (T0), there were no significant differences between the two subject groups in the various parameters assessed at the follow‐up visit (T1) (total number of teeth, percentage of subjects with implant probing pocket depth ≥5 mm, percentage of subjects with implant probing pocket depth ≥ 6 mm, absence of crestal bone loss, implant loss).

Conclusion

Owing to a rigid regular SPT program, implants placed in PSP perform equally well when compared to implants installed in PHS over a mean period of 6‐year follow‐up.
Computer‐assisted template‐guided custom‐designed 3D‐printed implant placement with custom‐designed 3D‐printed surgical tooling: an in‐vitro proof of a novel concept
Authors: Anssari Moin David , Derksen Wiebe , Waars Hugo , Hassan Bassam , Wismeijer Daniel
Published: March 2016

Objectives

The aim of this study was to introduce a new concept for computer‐assisted template‐guided placement of a custom 3D‐designed/3D‐printed implant with congruent custom 3D‐designed/3D‐printed surgical tooling and to test the feasibility and accuracy of this method in‐vitro.

Materials and methods

One partially edentulous human mandibular cadaver was scanned with a cone‐beam computed tomography (CBCT) system and intra‐oral scan system. The 3D data of this cadaver were imported in specialized software and used to analyse the region of a missing tooth. Based on the functional and anatomical parameters, an individual implant with congruent surgical tooling and surgical guided template was designed and 3D‐printed. The guided osteotomy was performed, and the custom implant inserted. To evaluate the planned implant position in comparison with the placed implant position, the mandible with implant was scanned again with the CBCT system and software matching was applied to measure the accuracy of the procedure.

Results

The angular deflection with the planned implant position was 0.40°. When comparing the 3D positions of the shoulder, there is a deviation of 0.72 mm resulting in an apical deviation of 0.72 mm.

Conclusion

With the use of currently available technology, it is very well feasible to create in a virtual simulation a custom implant with congruent custom surgical tooling and to transfer this to a clinical setting. However, further research on multiple levels is needed to explore this novel approach.
Preadolescents Solve Natural Syllogisms Proficiently
Authors: Politzer Guy , Bosc‐Miné Christelle , Sander Emmanuel
Published: March 2016

“Natural syllogisms” are arguments formally identifiable with categorical syllogisms that have an implicit universal affirmative premise retrieved from semantic memory rather than explicitly stated. Previous studies with adult participants (Politzer, 2011) have shown that the rate of success is remarkably high. Because their resolution requires only the use of a simple strategy (known as ecthesis in classic logic) and an operational use of the concept of inclusion (the recognition that an element that belongs to a subset must belong to the set but not vice versa), it was hypothesized that these syllogisms would be within the grasp of non‐adult participants, provided they have acquired the notion of deductive validity. Here, 11‐year‐old children were presented with natural syllogisms embedded in short dialogs. The first experiment showed that their performance was equivalent to adults' highest level of performance in standard experiments on syllogisms. The second experiment, while confirming children's proficiency in solving natural syllogisms, showed that they outperformed children who solved non‐natural matched syllogisms in the same experimental setting. The results are also in agreement with the argumentation theory of reasoning.
LinkLPA: A Link‐Based Label Propagation Algorithm for Overlapping Community Detection in Networks
Authors: Sun Heli , Liu Jiao , Huang Jianbin , Wang Guangtao , Jia Xiaolin , Song Qinbao
Published: March 2016

Community detection is an important methodology for understanding the intrinsic structure and function of complex networks. Because overlapping community is one of the characteristics of real‐world networks and should be considered for community detection, in this article, we propose an algorithm, called link‐based label propagation algorithm (LinkLPA), to detect overlapping communities. Because the link partition is conceptually natural for the problem of overlapping community detection, LinkLPA first transforms node partition problem into link partition problem and employs a new label propagation algorithm with preference on links instead of nodes to detect communities due to the simplicity and efficiency of label propagation algorithm. Then the proposed LinkLPA performs a postprocessing to refine the detected overlapping communities by avoiding over‐overlapping and incorrect partition of weak ties. Experimental results on a large number of real‐world and synthetic networks show that the proposed method achieves high accuracy on detecting overlapping communities in networks.
Role of microRNAs in primary central nervous system lymphomas
Authors: Yu Xin , Li Zheng , Shen Jianxiong , Chan Matthew T.V. , Wu William Ka Kei
Published: March 2016

Primary central nervous system lymphomas (PCNSL) are extranodal non‐Hodgkin lymphomas arising exclusively inside the CNS, and account for about 3% of primary intracranial tumours. This tumour lacks systemic manifestations and prognosis of patients with PCNSL remains poor despite recent advancement of chemoradiotherapy. MicroRNAs are small non‐coding RNAs that post‐transcriptionally downregulate gene expression by binding to target mRNAs, inducing their degradation or translational repression. MicroRNAs play significant roles in almost all malignancy‐related biological processes, including cell proliferation, differentiation, apoptosis and metabolism. Many deregulated miRNAs has been identified in PCNSL but their biological significance remains to be fully elucidated. In this review, we summarize current evidence regarding the pathogenic role of PCNSL‐associated microRNAs and their potential applications for diagnosis and prognostication of this deadly disease.
Detection of an EGFR mutation in cytological specimens of lung adenocarcinoma
Authors: Mohar B. , Smojver Ježek S. , Rajković Molek K. , Štemberger C. , Kurpis M. , Kupanovac Ž. , Samaržija M. , Jonjić N. , Grahovac B.
Published: March 2016

Objective

Epidermal growth factor receptors (EGFR) mutation status is crucial for the prediction of a tumour response to treatment with EGFR tyrosine kinase (EGFR‐TK) inhibitors. The aim of the study was to establish a protocol for the detection of EGFR‐activating somatic mutations on cytological samples collected using a standard bronchoscopy procedure and to determine the frequency of EGFR mutations among pre‐selected Croatian patients with non‐small cell lung cancer (NSCLC) of an adenocarcinoma histological subtype.

Methods

A total of 177 cytological samples were collected from the patients diagnosed with NSCLC. DNA was isolated from the cytological material recovered from the fixed and stained slides. EGFR mutations were analysed using the polymerase chain reaction (PCR)‐ mediated Sanger sequencing method.

Results

Out of 177 collected samples, EGFR mutation analyses were successfully performed on 167 samples (94.4%); 77 (46.1%) of these were from male and 90 (53.9%) from female patients. EGFR mutations/deletions were found in 33 (19.8%) of the tested patients; exon 19 deletions in 17 (10.2%) and point mutations of exon 21 in 16 (9.6%) patients.

Conclusion

The PCR‐mediated Sanger sequencing method was found to be reproducible and reliable. Cytological samples can be used successfully to determine the EGFR mutation status in NSCLC patients providing information for targeted therapy at an early stage of the disease.