bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardioprotective effect of novel sulphonamides‐1,3,5‐triazine conjugates against ischaemic–reperfusion injury via selective inhibition of MMP‐9
Authors: Zheng Xiao‐Zhu , Zhou Jia‐Li , Ye Jing , Guo Pei‐Pei , Lin Chun‐Shui
Published: June 2016

Diseases affecting cardiovascular system are ranked as a top most cause of morbidity and mortality. Herein, a novel class sulphonamides‐1,3,5‐triazine conjugates have been synthesized and tested for inhibitory activity against MMP‐2 and MMP‐9. The results of the study showed that these molecules efficiently inhibit MMP‐9 than MMP‐2, revealing compound 8e as the most potent inhibitor (IC50 = 2.34 ± 0.56 nm). Due to involvement of MMP‐9 in many cardiovascular diseases, particularly in myocardial ischaemia (MI), compound 8e was further subjected for the determination of the protective effect on isoproterenol (ISO)‐induced myocardial injury in rats.
Synthesis and anti‐Candida activity of novel benzothiepino[3,2‐c]pyridine derivatives
Authors: Božinović Nina , Šegan Sandra , Vojnovic Sandra , Pavic Aleksandar , Šolaja Bogdan A. , Nikodinovic‐Runic Jasmina , Opsenica Igor M.
Published: June 2016

A novel series of thiepine derivatives were synthesized and evaluated as potential antimicrobials. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi Candida albicans (ATCC 10231), C. parapsilosis (clinical isolate), Gram‐negative bacterium Pseudomonas aeruginosa (ATCC 44752), and Gram‐positive bacterium Staphylococcus aureus (ATCC 25923). Synthesized compounds showed higher antifungal activity than antibacterial activity, indicating that they could be used as selective antimicrobials. Selected thiepines efficiently inhibited Candida hyphae formation, a trait necessary for their pathogenicity. Thiepine 8‐phenyl[1]benzothiepino[3,2‐c]pyridine (16) efficiently killed Candida albicans at 15.6 μg/mL and showed no embryotoxicity at 75 μg/mL. Derivative 8‐[4‐(4,5‐dihydro‐1H‐imidazol‐2‐yl)phenyl][1]benzothiepino[3,2‐c]pyridine (23) caused significant hemolysis and in vitro DNA interaction. The position of the phenyl ring was essential for the antifungal activity, while the electronic effects of the substituents did not significantly influence activity. Results obtained from in vivo embryotoxicity on zebrafish (Danio rerio) encourage further structure optimizations.
Parent‐related mechanisms underlying the social gradient of childhood overweight and obesity: a systematic review
Authors: Mech P. , Hooley M. , Skouteris H. , Williams J.
Published: June 2016

Background

Low socio‐economic status (SES) is a significant risk factor for childhood overweight and obesity (COWOB) in high‐income countries. Parents to young children buffer and accentuate social and cultural influences, and are central to the development of this disease. An understanding of the parent‐related mechanisms that underlie the SES–COWOB relationship is needed to improve the efficacy of prevention and intervention efforts.

Objective

A systematic review of relevant literature was conducted to investigate the mechanisms by which levels of SES (low, middle and high) are associated to COWOB, by exploring mediation and interaction effects.

Method

Six electronic databases were searched yielding 5155 initial records, once duplicates were removed. Studies were included if they investigated COWOB, SES, parent‐related factors and the multivariate relationship between these factors. Thirty studies were included. Factors found to be mediating the SES–COWOB relationship or interacting with SES to influence COWOB were categorized according to an ecological systems framework, at child, parent, household and social system level factors.

Results

High parent body mass index, ethnicity, child‐care attendance, high TV time (mother and child), breastfeeding (early weaning), food intake behaviours and birthweight potentially mediate the relationship between SES and COWOB. Different risk factors for COWOB in different SES groups were found. For low SES families, parental obesity and maternal depressive symptoms were strong risk factors for COWOB, whereas long maternal working hours and a permissive parenting style were risk factors for higher SES families. None of the studies investigated parental psychological attributes such as attitudes, beliefs, self‐esteem and so on as potential mechanisms/risk factors.

Conclusions

Families from different SES groups have different risk and protective factors for COWOB. Prevention and intervention efforts may have improved efficacy if they are tailored to address specific risk factors within SES.
Controlling and Autonomy‐Supportive Parenting in the United States and China: Beyond Children's Reports
Authors: Cheung Cecilia S. , Pomerantz Eva M. , Wang Meifang , Qu Yang
Published: June 2016

Research comparing the predictive power of parents’ control and autonomy support in the United States and China has relied almost exclusively on children's reports. Such reports may lead to inaccurate conclusions if they do not reflect parents’ practices to the same extent in the two countries. A total of 394 American and Chinese children (Mage = 13.19 years) and their mothers reported on mothers’ controlling and autonomy‐supportive parenting in the academic arena; trained observers coded such parenting in the laboratory. Children's reports were associated modestly with mothers’ reports and weakly, if at all, with observers’ reports in both the United States and China. Parenting predicted children's academic and emotional functioning similarly in the two countries, irrespective of reporter.
Pretty as a Princess: Longitudinal Effects of Engagement With Disney Princesses on Gender Stereotypes, Body Esteem, and Prosocial Behavior in Children
Authors: Coyne Sarah M. , Linder Jennifer Ruh , Rasmussen Eric E. , Nelson David A. , Birkbeck Victoria
Published: June 2016

This study examined level of engagement with Disney Princess media/products as it relates to gender‐stereotypical behavior, body esteem (i.e. body image), and prosocial behavior during early childhood. Participants consisted of 198 children (Mage = 58 months), who were tested at two time points (approximately 1 year apart). Data consisted of parent and teacher reports, and child observations in a toy preference task. Longitudinal results revealed that Disney Princess engagement was associated with more female gender‐stereotypical behavior 1 year later, even after controlling for initial levels of gender‐stereotypical behavior. Parental mediation strengthened associations between princess engagement and adherence to female gender‐stereotypical behavior for both girls and boys, and for body esteem and prosocial behavior for boys only.
H-ferritin and CD68+/H-ferritin+ monocytes/macrophages are increased in the skin of adult-onset Still's disease patients and correlate with the multi-visceral involvement of the disease
Authors: Ruscitti P , Cipriani P , Ciccia F , Di Benedetto P , Liakouli V , Berardicurti O , Carubbi F , Guggino G , Di Bartolomeo S , Triolo G , Giacomelli R
Published: June 2016

Adult-onset Still's disease (AOSD) patients may show an evanescent salmon-pink erythema appearing during febrile attacks and reducing without fever. Some patients may experience this eruption for many weeks. During AOSD, exceptionally high serum levels of ferritin may be observed; it is an iron storage protein composed of 24 subunits, heavy (H) subunits and light (L) subunits. The ferritin enriched in L subunits (L-ferritin) and the ferritin enriched in H subunits (H-ferritin) may be observed in different tissues. In this work, we aimed to investigate the skin expression of both H-and L-ferritin and the number of macrophages expressing these molecules from AOSD patients with persistent cutaneous lesions. We observed an increased expression of H-ferritin in the skin, associated with an infiltrate in the biopsies obtained from persistent cutaneous lesions of AOSD patients. Furthermore, a positive correlation between H-ferritin skin levels as well as the number of CD68+/H-ferritin+ cells and the multi-visceral involvement of the disease was observed. Our data showed an increased expression of H-ferritin in the skin of AOSD patients, associated with a strong infiltrate of CD68+/H-ferritin+ cells. Furthermore, a correlation between the levels of H-ferritin as well as of the number of CD68+/H-ferritin+ cells and the multi-visceral involvement of the disease was observed.
Hydrophilic surface of Ti6Al4V‐ELI alloy improves the early bone apposition of sheep tibia
Authors: Sartoretto Suelen C. , Alves Adriana T. N. N. , Zarranz Laila , Jorge Mônica Z. , Granjeiro José M. , Calasans‐Maia Mônica D.
Published: June 2016

Objective

The aim of this preclinical study was to compare histologically and histomorphometrically both sandblasted/acid‐etched implant surfaces with or without maintained in an isotonic solution of 0.9% sodium chloride in early stages of osseointegration.

Material and methods

Both implant surfaces were composed of a titanium/aluminum/vanadium alloy (Ti6Al4V‐ELI), but they had different surface chemistries: sandblasted/acid‐etched titanium surface (FN) or sandblasted/acid‐etched surface maintained in an isotonic solution of 0.9% sodium chloride (FA). The surface morphology, topography and chemistry were evaluated by scanning electron microscopy (SEM), confocal microscopy (CM) and X‐ray photoelectron spectroscopy (XPS), respectively. Dynamic contact angle (DCA) was employed for wettability evaluation. One implant from each group was placed in the left tibia of twenty healthy, skeletally mature Santa Ines sheep (n = 5). Bone area (BA) and bone‐to‐implant contact (BIC) were performed on thin sections (30 μm) at 7, 14, 21 and 28 days after implant installation.

Results

Despite the roughness and morphology similarities between the groups, at the XPS evaluation, the FA group presented 2.3 times less carbon on the surface (FN: 27.3% and FA: 11.6%), sharply enhanced hydrophilicity and significantly enhanced BA and BIC at 14, 21 and 28 days of healing (P < 0.05) compared with the FN.

Conclusion

The data suggest that the hydrophilic FA accelerates the BA apposition and BIC interface around the implants during early stages of bone formation, providing highest degree of osseointegration.
The lymph node ratio does not provide additional prognostic information compared with the N1/N2 classification in Stage III colon cancer
Authors: Mohan H. M. , Walsh C. , Kennelly R. , Ng C. H. , O'Connell P. R. , Hyland J. M. , Hanly A. , Martin S. , Gibbons D. , Sheahan K. , Winter D. C.
Published: June 2016

Aim

The ratio of positive nodes to total nodes, the lymph node ratio (LNR), is a proposed alternative to the current N1/N2 classification of nodal disease. The true clinical benefit of adopting the LNR, however, has not been definitively demonstrated. This study compared the LNR with the current N1/N2 classification of Stage III colon cancer.

Method

Patients with Stage III colon cancer were identified from a prospectively maintained database (1996–2012). The specificity and sensitivity of the N1/N2 classification in the prediction of overall survival were determined using R. A cut‐off point for the LNR was determined by setting the specificity the same as for the N1/N2 classification. The sensitivity of the two methods was then compared, and bootstrapping 1000‐fold was performed. This was then repeated for disease‐specific survival.

Results

The specificity and sensitivity of the N1/N2 classification in predicting 3‐year overall survival in this cohort (n = 402) was 62.2% and 52.1%, respectively. The cut‐off point for the LNR was determined to be 0.27 for these data. On comparing LNR with the N1/N2 classification showed that for a given specificity, the LNR did not provide a statistically significant improvement in sensitivity (52.8% vs 52.1%, P = 0.31). For disease‐specific death at 3 years, the specificity and sensitivity were 60.8% and 54.6%, respectively. The LNR did not provide a statistically significant improvement (55.4% vs 54.6%, P = 0.44).

Conclusion

Both the N1/N2 system and the LNR predict survival in colon cancer, but both have low specificity and sensitivity. The LNR does not provide additional prognostic value to current staging for overall or disease‐specific survival for a given cut‐off point.
Surgical management of complicated and medically refractory inflammatory bowel disease during pregnancy
Authors: Killeen S. , Gunn J. , Hartley J.
Published: June 2016

Aim

The medical management of inflammatory bowel disease (IBD) in pregnancy and the puerperium is well defined. Data on surgical management of complicated IBD in this setting are lacking. This study aimed to determine the optimal surgical strategy for medically refractory IBD during pregnancy and the puerperium.

Method

Three databases were systematically reviewed to identify all published series or case reports of women undergoing surgery for Crohn's disease (CD) or ulcerative colitis (UC) while pregnant or during the puerperium.

Results

Thirty‐two papers were identified, including 86 patients. Nearly one‐fifth (18%) of cases were de novo presentations and intervention was required at all stages of pregnancy. UC refractory to medical treatment and perforated small bowel CD were the commonest indications for surgery. Operations used included colectomy, colectomy with mucous fistula and Turnbull‐blowhole colostomy for complicated UC and open or laparoscopic small bowel resection with stoma formation for CD. Surgical intervention during the third trimester universally resulted in the onset of labour. Endoscopic and radiological interventions were rarely employed. In studies after 1980 there was no maternal or foetal mortality but there was an almost 50% preterm delivery rate.

Conclusion

Surgical management of complicated IBD during pregnancy and the puerperium needs to be tailored to disease severity, the type of complications and foetal status. It should involve gastroenterologists, colorectal surgeons, obstetricians and neonatal specialists in a multidisciplinary manner within a single unit.
Modified side‐to‐side isoperistaltic strictureplasty over the ileocaecal valve for the surgical treatment of terminal ileal Crohn's disease: the ultimate bowel sparing technique?
Authors: de Buck van Overstraeten A. , Wolthuis A. M. , D'Hoore A.
Published: June 2016

Aim

The study describes the technique of a modified side‐to‐side isoperistaltic strictureplasty over the ileocaecal valve.

Method

The technical details of a modified side‐to‐side isoperistaltic strictureplasty of the terminal ileum for stricturing Crohn's disease is described including Figs. 1 and 2 and a video illustration (Video S1).

Results

Between November 2010 and December 2015, 36 patients underwent a side‐to‐side isoperistaltic strictureplasty of the (neo‐)terminal ileum (men 14/36; median age 35 years [interquartile range (IQR) 26−51 years]). Thirty were operated by either multiport or single port laparoscopy. The median length of hospital stay was 9 (IQR 8−11) days. Anastomotic leakage occurred in two patients both in the first five cases. In both the anastomosis could be rescued by additional suturing. After a median follow‐up of 18.9 (IQR 7.0−36.0) months, 14 patients had developed clinical recurrence and one had a surgical recurrence at 63 months.

Conclusion

A modified side‐to‐side isoperistaltic strictureplasty is a feasible and safe technique, rendering maximal bowel sparing surgery possible.
Indications for and outcome of primary repair compared with faecal diversion in the management of traumatic colon injury
Authors: Fouda E. , Emile S. , Elfeki H. , Youssef M. , Ghanem A. , Fikry A. A. , Elshobaky A. , Omar W. , Khafagy W. , Morshed M.
Published: June 2016

Aim

Injuries of the colon are a serious sequel of abdominal trauma owing to the associated morbidity and mortality. This study aims to assess postoperative outcome and complications of faecal diversion and primary repair of colon injuries when applied according to established guidelines for the management of colon injuries.

Method

This retrospective study was conducted on 110 patients with colon injuries. Guided by estimation of risk factors, patients were managed either by primary repair alone, repair with proximal diversion or diversion alone.

Results

There were 102 (92.7%) male patients and 8 (7.3%) female patients of median age 38 years. Thirty‐seven were managed by primary repair and 73 by faecal diversion. Colon injuries were caused by penetrating abdominal trauma in 65 and blunt trauma in 45 patients. Forty‐three patients were in shock on admission, and were all managed by faecal diversion. Forty patients developed 84 complications after surgery. Primary repair had a significantly lower complication rate than faecal diversion (P = 0.037). Wound infection was the commonest complication. The overall mortality rate was 3.6%.

Conclusion

Primary repair, when employed properly, resulted in a significantly lower complication rate than faecal diversion. Significant predictive factors associated with a higher complication rate were faecal diversion, severe faecal contamination, multiple colon injuries, an interval of more than 12 h after colon injury and shock.
Observational pilot study of reported symptoms of obstructive sleep apnoea in children with epilepsy
Authors: Urquhart Don S , Kehinde Olaniyi O , Mclellan Ailsa E
Published: June 2016

Aim

To estimate symptoms of obstructive sleep apnoea (OSA) and excessive daytime sleepiness (EDS) in children with epilepsy (CWE) compared with those in a typically developing comparison group. CWE are known to have poor sleep, with increased rates of OSA suggested.

Method

The Sleep‐Related Breathing Disorder scale of the Pediatric Sleep Questionnaire (PSQ‐SRBD) was used to estimate OSA symptoms, with scores ≤0.33 known to be highly sensitive and specific for OSA. The Epworth Sleepiness Scale (ESS) was used to assess EDS, with scores of 10 or above considered abnormal.

Results

Thirty‐three CWE (21 males, 12 females) were studied (median age [interquartile range {IQR}] 9y [5–12]), along with 42 comparison children (20 males, 22 females; median age [IQR] 6y [4–8.5]). Fifty‐five per cent of CWE scored 0.33 or higher on the PSQ‐SRBD compared with 7% in the comparison group (p<0.001), and 30% of CWE had an abnormal ESS compared with 5% controls (p=0.003). Within the CWE cohort, PSQ‐SRDB and ESS appeared higher in those taking antiepileptic drugs (AEDs); although PSQ‐SRBD score for CWE not on AEDs was higher than in the comparison group.

Interpretation

This study suggests higher rates of symptoms of OSA and EDS in CWE compared with typically developing children. AEDs may be a confounding factor, but do not alone account for the associations seen. Further studies including polysomnography to verify the presence (rather than suggestion by questionnaire) of OSA are warranted.
Influence of duration of phosphoric acid pre‐etching on bond durability of universal adhesives and surface free‐energy characteristics of enamel
Authors: Tsujimoto Akimasa , Barkmeier Wayne W. , Takamizawa Toshiki , Watanabe Hidehiko , Johnson William W. , Latta Mark A. , Miyazaki Masashi
Published: June 2016

The purpose of this study was to evaluate the influence of duration of phosphoric acid pre‐etching on the bond durability of universal adhesives and the surface free‐energy characteristics of enamel. Three universal adhesives and extracted human molars were used. Two no‐pre‐etching groups were prepared: ground enamel; and enamel after ultrasonic cleaning with distilled water for 30 s to remove the smear layer. Four pre‐etching groups were prepared: enamel pre‐etched with phosphoric acid for 3, 5, 10, and 15 s. Shear bond strength (SBS) values of universal adhesive after no thermal cycling and after 30,000 or 60,000 thermal cycles, and surface free‐energy values of enamel surfaces, calculated from contact angle measurements, were determined. The specimens that had been pre‐etched showed significantly higher SBS and surface free‐energy values than the specimens that had not been pre‐etched, regardless of the aging condition and adhesive type. The SBS and surface free‐energy values did not increase for pre‐etching times of longer than 3 s. There were no significant differences in SBS values and surface free‐energy characteristics between the specimens with and without a smear layer. The results of this study suggest that phosphoric acid pre‐etching of enamel improves the bond durability of universal adhesives and the surface free‐energy characteristics of enamel, but these bonding properties do not increase for phosphoric acid pre‐etching times of longer than 3 s.
An in situ assessment of local adaptation in a calcifying polychaete from a shallow CO2 vent system
Authors: Lucey Noelle M. , Lombardi Chiara , Florio Maurizio , DeMarchi Lucia , Nannini Matteo , Rundle Simon , Gambi Maria Cristina , Calosi Piero
Published: June 2016

Ocean acidification (OA) is likely to exert selective pressure on natural populations. Our ability to predict which marine species will adapt to OA and what underlies this adaptive potential is of high conservation and resource management priority. Using a naturally low‐pH vent site in the Mediterranean Sea (Castello Aragonese, Ischia) mirroring projected future OA conditions, we carried out a reciprocal transplant experiment to investigate the relative importance of phenotypic plasticity and local adaptation in two populations of the sessile, calcifying polychaete Simplaria sp. (Annelida, Serpulidae, Spirorbinae): one residing in low pH and the other from a nearby ambient (i.e. high) pH site. We measured a suite of fitness‐related traits (i.e. survival, reproductive output, maturation, population growth) and tube growth rates in laboratory‐bred F2 generation individuals from both populations reciprocally transplanted back into both ambient and low‐pH in situ habitats. Both populations showed lower expression in all traits, but increased tube growth rates, when exposed to low‐pH compared with high‐pH conditions, regardless of their site of origin suggesting that local adaptation to low‐pH conditions has not occurred. We also found comparable levels of plasticity in the two populations investigated, suggesting no influence of long‐term exposure to low pH on the ability of populations to adjust their phenotype. Despite high variation in trait values among sites and the relatively extreme conditions at the low pH site (pH < 7.36), response trends were consistent across traits. Hence, our data suggest that, for Simplaria and possibly other calcifiers, neither local adaptations nor sufficient phenotypic plasticity levels appear to suffice in order to compensate for the negative impacts of OA on long‐term survival. Our work also emphasizes the utility of field experiments in natural environments subjected to high level of pCO2 for elucidating the potential for adaptation to future scenarios of OA.
Potential seal bypass and caprock storage produced by deformation‐band‐to‐opening‐mode‐fracture transition at the reservoir/caprock interface
Authors: Raduha S. , Butler D. , Mozley P. S. , Person M. , Evans J. , Heath J. E. , Dewers T. A. , Stauffer P. H. , Gable C. W. , Kelkar S.
Published: June 2016

We examined the potential impact on CO2 transport of zones of deformation bands in reservoir rock that transition to opening‐mode fractures within overlying caprock. Sedimentological and petrophysical measurements were collected along an approximately 5 m × 5 m outcrop of the Slick Rock and Earthy Members of the Entrada Sandstone on the eastern flank of the San Rafael Swell, Utah, USA. Measured deformation band permeability (2 mD) within the reservoir facies is about three orders of magnitude lower than the host sandstone. Average permeability of the caprock facies (0.0005 mD) is about seven orders of magnitude lower than the host sandstone. Aperture‐based permeability estimates of the opening‐mode caprock fractures are high (3.3 × 107 mD). High‐resolution CO2–H2O transport models incorporate these permeability data at the millimeter scale. We varied fault properties at the reservoir/caprock interface between open fractures and deformation bands as part of a sensitivity study. Numerical modeling results suggest that zones of deformation bands within the reservoir strongly compartmentalize reservoir pressures largely blocking lateral, cross‐fault flow of supercritical CO2. Significant vertical CO2 transport into the caprock occurred in some scenarios along opening‐mode fractures. The magnitude of this vertical CO2 transport depends on the small‐scale geometry of the contact between the opening‐mode fracture and the zone of deformation bands, as well as the degree to which fractures penetrate caprock. The presence of relatively permeable units within the caprock allows storage of significant volumes of CO2, particularly when the fracture network does not extend all the way through the caprock.
The F, Cl, Br and I Contents of Reference Glasses BHVO‐2G, BIR‐1G, BCR‐2G, GSD‐1G, GSE‐1G, NIST SRM 610 and NIST SRM 612
Authors: Marks Michael A. W. , Kendrick Mark A. , Eby G. Nelson , Zack Thomas , Wenzel Thomas
Published: June 2016

Halogen contents for the widely distributed reference glasses BHVO‐2G, BIR‐1G, BCR‐2G, GSD‐1G, GSE‐1G, NIST SRM 610 and NIST SRM 612 were investigated by pyrohydrolysis combined with ion chromatography, total reflection X‐ray fluorescence analysis, instrumental neutron activation analysis, the noble gas method, electron probe microanalysis and laser ablation‐inductively coupled plasma‐mass spectrometry. Glasses BHVO‐2G, GSD‐1G and GSE‐1G have halogen contents that can be reproduced at the 15% level by all bulk techniques and cover a significant range in halogen mass fractions for F (~ 20–300 μg g−1), Cl (~ 70–1220 μg g−1) and Br (~ 0.2–285 μg g−1) and I (~ 9–3560 ng g−1). The BIR‐1G glass has low F (< 15 μg g−1), Cl (~ 20 μg g−1), Br (15 ng g−1) and I (3 ng g−1). The halogen contents for the silica‐rich NIST SRM 610 and 612 glasses were poorly reproduced by the different techniques. The relatively high Cl, Br and I abundances in glasses GSD‐1G and GSE‐1G mean that these glasses are well suited for calibrating spatially resolved micro‐analytical studies on silicate glasses, melt and fluid inclusions. Combined EPMA and laser ablation‐inductively coupled plasma‐mass spectrometry data for glass GSE‐1G demonstrate homogeneity at the 10% level for Cl and Br.
Factors Influencing Response to Pharmacologic Treatment of Migraine in a Pediatric Headache Clinic
Authors: Markus Tal Eidlitz , Moad Bder , Haimi‐Cohen Yishai , Zeharia Avraham
Published: June 2016

Objective

The responses of different patients to the same drug may vary as a consequence of biologic, psychosocial, and genetic differences. The aim of this study was to identify clinical factors associated with a response to pharmacologic treatment in pediatric patients with migraine.

Methods

The medical files of patients with migraine attending the headache clinic of a tertiary pediatric medical center in 2010‐2015 were reviewed. The children and parents (or only the parents if the child was very young) completed the International Headache Society‐based questionnaire. Patients were treated with at least one of the following medications: propranolol, amitriptyline, topiramate. Response to treatment was rated as no change in migraine pattern (grade 1) or a decrease in migraine attack frequency per month by at least 50% (grade 2) or at least 75% (grade 3). The highest‐grade response to any pharmacologic treatment was defined as the best clinical response.

Results

The study group included 248 patients of mean age 12.71 ± 3.04 years. A grade 3 best clinical response was significantly associated with a positive maternal history of migraine, younger age at treatment onset, lower frequency of headache attacks per month, postpubertal children had a significantly lower rate of grade 3 response than prepubertal children (P < .05). Analysis of the association of overuse of medication and treatment response achieved aPvalue equal to .05.

Conclusions

Several background and clinical factors are identified that may predispose children with migraine to respond better to pharmacologic treatment. Clinicians who see children with migraine in a pediatric headache clinic setting should consider these factors before initiating a treatment program.
The Role of Melatonin in the Treatment of Primary Headache Disorders
Authors: Gelfand Amy A. , Goadsby Peter J.
Published: June 2016

Objective

To provide a summary of knowledge about the use of melatonin in the treatment of primary headache disorders.

Background

Melatonin is secreted by the pineal gland; its production is regulated by the hypothalamus and increases during periods of darkness.

Methods

We undertook a narrative review of the literature on the role of melatonin in the treatment of primary headache disorders.

Results

There are randomized placebo‐controlled trials examining melatonin for preventive treatment of migraine and cluster headache. For cluster headache, melatonin 10 mg was superior to placebo. For migraine, a randomized placebo‐controlled trial of melatonin 3 mg (immediate release) was positive, though an underpowered trial of melatonin 2 mg (sustained release) was negative. Uncontrolled studies, case series, and case reports cover melatonin's role in treating tension‐type headache, hypnic headache, hemicrania continua, SUNCT/SUNA and primary stabbing headache.

Conclusions

Melatonin may be effective in treating several primary headache disorders, particularly cluster headache and migraine. Future research should focus on elucidating the underlying mechanisms of benefit of melatonin in different headache disorders, as well as clarifying optimal dosing and formulation.
Long Lasting Impairment of Taste and Smell as Side Effect of Lithium Carbonate in a Cluster Headache Patient
Authors: de Coo Ilse F. , Haan Joost
Published: June 2016

Background

Preventive treatment with lithium carbonate is a therapeutic option for chronic cluster headache. Lithium can lead to a broad spectrum of severe side effects, many of which are generally unknown.

Case description

One week after starting treatment with lithium, a 55‐year‐old man with chronic cluster headache noticed a strange and unpleasant taste of various foods and a diminished smell. After 4 weeks, he decided to stop the therapy because of these complaints, but 9 months later both taste and smell still had not returned to normal.

Discussion

We present the first description of long‐lasting dysgeusia and hyposmia as a side effect of lithium therapy in cluster headache. Dysgeusia has only rarely been reported as a side effect of lithium in other conditions and hyposmia has not previously been reported. Physicians should be aware of this rare, but severe, side effect when prescribing lithium.
Prediction of hepatic cyst recurrence after minocycline hydrochloride aspiration sclerotherapy using cyst computed tomography values
Authors: Iijima Takashi , Suwabe Tatsuya , Sumida Keiichi , Hayami Noriko , Mise Koki , Hoshino Junichi , Takaichi Kenmei , Ubara Yoshifumi
Published: June 2016

Aim

Polycystic liver disease (PLD) occasionally leads to abdominal pain, distention, and discomfort due to massively enlarged cysts. Patients with a small number of large liver cysts, which correspond to Gigot's classification type 1 PLD, are reported to be good candidates for treatment by aspiration sclerotherapy. However, there is a 21% reported recurrence rate of an enlarged cyst. A rule to predict outcome of aspiration sclerotherapy is explored in this study.

Methods

The medical records of patients with autosomal dominant polycystic kidney disease or isolated polycystic liver disease, who underwent minocycline hydrochloride cyst aspiration sclerotherapy for their symptomatic PLD, were retrospectively analyzed. Changes in the volume of cysts from before to 1 year after treatment were calculated using computed tomography (CT) images. Mean CT values of the largest planes of cysts were also calculated. Specific gravity and other laboratory parameters of aspirated cyst fluid were also retrospectively investigated.

Results

In total, 12 patients were selected and 21 cysts were analyzed that received aspiration sclerotherapy. Mean CT values more than 13.34 HU were predictive for 1‐year non‐sustainability of a cyst volume of less than 30% compared with the volume prior to the therapy. Specific gravity had good positive correlation with mean CT value and other laboratory parameters indicating exudative properties were also high in recurred cysts.

Conclusions

The CT values of cysts may become an aid in appropriate selection of therapy in patients with symptomatic polycystic disease by distinguishing cysts that are resistant to aspiration sclerotherapy.
Polymorphism in the chemokine receptor 7 gene (CCR7) is associated with previous myocardial infarction in patients undergoing elective coronary angiography
Authors: Wołkow P. P. , Drabik L. , Totoń‐Żurańska J. , Kuś K. , Foryś J. , Słowik A. , Pera J. , Godlewski J. , Tomala M. , Żmudka K. , Olszanecki R. , Jawień J. , Korbut R.
Published: June 2016

Coronary artery disease (CAD) remains a major cause of death in developed countries. Both environmental and, less known, genetic factors contribute to progression of CAD to myocardial infarction (MI). Immune system is activated in patients with CAD through dendritic cells (DCs), which present plaque antigens to T lymphocytes. Production of proinflammatory cytokines by activated T cells contributes to plaque rupture in MI. Chemokine receptor 7 (CCR7) on DCs is required for their chemotaxis from plaque to lymph nodes. This makes possible an interaction of DCs with T lymphocytes and initiation of specific immune response. We hypothesized that single nucleotide polymorphisms (SNPs) in CCR7 gene locus are associated with previous MI in patients with CAD. To test this hypothesis, we genotyped six SNPs from the CCR7 gene locus in 300 consecutive patients, admitted for elective coronary angiography. We performed univariate‐, multivariate‐ (including potential confounders) and haplotype‐based tests of association of SNPs with previous MI and results of angiography. Allele A of rs17708087 SNP was associated with previous MI. This association remained significant after adjustment for age, sex, smoking, hypercholesterolaemia and drugs used by patients (odds ratio 2.13, 95% confidence interval: 1.13–3.86). Therefore, we conclude that CCR7 gene locus harbours a polymorphism that modifies risk of MI in patients with CAD. Replication of this association could be sought in a prospective cohort of initially healthy individuals.
CD8 T‐cell responses against the immunodominant Theileria parva peptide Tp249–59 are composed of two distinct populations specific for overlapping 11‐mer and 10‐mer epitopes
Authors: Connelley Timothy K. , Li Xiaoying , MacHugh Niall , Colau Didier , Graham Simon P. , van der Bruggen Pierre , Taracha Evans L. , Gill Andy , Morrison William Ivan
Published: June 2016

Immunity against Theileria parva is associated with CD8 T‐cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp249–59 and Tp1214–224 epitopes dominate CD8 T‐cell responses in BoLA‐A10 and BoLA‐18 MHC I homozygous animals, respectively. In this study, peptide–MHC I tetramers for these epitopes, and a subdominant BoLA‐A10‐restricted epitope (Tp298–106), were generated to facilitate accurate and rapid enumeration of epitope‐specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249–59‐reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250–59 represents a distinct epitope and that tetramers produced with Tp50–59 and Tp49–59 show no cross‐reactivity. The Tp249–59 and Tp250–59 epitopes use different serine residues as the N‐terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptide–MHC I complexes adopt structurally different conformations and Tcell receptor β sequence analysis showed that Tp249–59 and Tp250–59 are recognized by non‐overlapping T‐cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249–59 and Tp250–59 epitopes form distinct ligands for T‐cell receptor recognition. Tetramer analysis of T. parva‐specific CD8 T‐cell lines confirmed the immunodominance of Tp1214–224 in BoLA‐A18 animals and showed in BoLA‐A10 animals that the Tp249–59 epitope response was generally more dominant than the Tp250–59 response and confirmed that the Tp298–106 response was subdominant.
Low‐Temperature Ionic Conductivity of an Acceptor‐Doped Perovskite: I. Impedance of Single‐Crystal SrTiO3
Authors: Maier Russell A. , Randall Clive A.
Published: June 2016

Low‐temperature conductivity mechanisms were identified in acceptor‐doped SrTiO3 single crystals quenched from high temperatures under reducing conditions. Impedance spectroscopy measurements made on samples of the prototypical perovskite structure doped with iron provided a framework for creating a complete conductivity model for a well‐defined point defect system. The dominant conductivity mechanism in the room‐temperature range was identified as being controlled by oxygen vacancy hopping. The activation energy for oxygen vacancy migration, an often debated value in the perovskite community, is determined to lie within the range of 0.59–0.78 eV for the iron‐doped system with the bottom of this range approaching the intrinsic value for oxygen vacancy hopping in an undoped single crystal. At low temperatures, oxygen vacancies form defect complexes with iron impurities, and the observed range of activation energies is explained and modeled in terms of an oxygen vacancy trapping mechanism.
Answering to Future People: Responsibility for Climate Change in a Breaking World
Authors: Mulgan Tim
Published: June 2016

Our everyday notions of responsibility are often driven by our need to justify ourselves to specific others – especially those we harm, wrong, or otherwise affect. One challenge for contemporary ethics is to extend this interpersonal urgency to our relations with those future people who are harmed or affected by our actions. In this article, I explore our responsibility for climate change by imagining a possible ‘broken future’, damaged by the carbon emissions of previous generations (including ourselves), and then asking what its inhabitants might think of our current behaviour, our moral thinking, and our excuses. In particular, I will focus on a simplified scenario where present people can only avoid a broken future by sacrificing Rawlsian favourable conditions. Suppose we refuse to avoid a broken future, on the grounds that we cannot be expected to make such great sacrifices. If the broken future lacks favourable conditions, will its inhabitants accept our excuses? Will they hold us responsible for things we regard as excusable? If so, should we be guided by their judgements or by our own?
The Relationship Between Left Ventricular Wall Thickness, Myocardial Shortening, and Ejection Fraction in Hypertensive Heart Disease: Insights From Cardiac Magnetic Resonance Imaging
Authors: Rodrigues Jonathan C. L. , Rohan Stephen , Dastidar Amardeep Ghosh , Trickey Adam , Szantho Gergely , Ratcliffe Laura E. K. , Burchell Amy E. , Hart Emma C. , Bucciarelli‐Ducci Chiara , Hamilton Mark C. K. , Nightingale Angus K. , Paton Julian F. R. , Manghat Nathan E. , MacIver David H.
Published: June 2016

Hypertensive heart disease is often associated with a preserved left ventricular ejection fraction despite impaired myocardial shortening. The authors investigated this paradox in 55 hypertensive patients (52±13 years, 58% male) and 32 age‐ and sex‐matched normotensive control patients (49±11 years, 56% male) who underwent cardiac magnetic resonance imaging at 1.5T. Long‐axis shortening (R=0.62), midwall fractional shortening (R=0.68), and radial strain (R=0.48) all decreased (P<.001) as end‐diastolic wall thickness increased. However, absolute wall thickening (defined as end‐systolic minus end‐diastolic wall thickness) was maintained, despite the reduced myocardial shortening. Absolute wall thickening correlated with ejection fraction (R=0.70, P<.0001). In multiple linear regression analysis, increasing wall thickness by 1 mm independently increased ejection fraction by 3.43 percentage points (adjusted β‐coefficient: 3.43 [2.60–4.26], P<.0001). Increasing end‐diastolic wall thickness augments ejection fraction through preservation of absolute wall thickening. Left ventricular ejection fraction should not be used in patients with hypertensive heart disease without correction for degree of hypertrophy.
Integrative Approach for the Reliable Detection and Specific Identification of the Microsporidium Loma morhua in Atlantic Cod (Gadus morhua)
Authors: Frenette Aaron P. , Eydal Matthías , Hansen Haakon , Burt Michael D.B. , Duffy Michael S.
Published: June 2016

Microsporidia are fungal parasites that infect diverse invertebrate and vertebrate hosts. Finfish aquaculture supports epizootics due to high host density and the high biotic potential of these parasites. Reliable methods for parasite detection and identification are a necessary precursor to empirical assessment of strategies to mitigate the effects of these pathogens during aquaculture. We developed an integrative approach to detect and identify Loma morhua infecting Atlantic cod. We show that the spleen is more reliable than the commonly presumed gills as best organ for parasite detection in spite of substantial morphological plasticity in xenoma complexes. We developed rDNA primers with 100% sensitivity in detecting L. morhua and with utility in distinguishing some congeneric Loma species. ITS sequencing is necessary to distinguish L. morhua from other congeneric microsporidia due to intraspecific nucleotide variation. 64% of L. morhua ITS variants from Atlantic cod have a 9‐nucleotide motif that distinguishes it from Loma spp. infecting non‐Gadus hosts. The remaining 36% of ITS variants from Atlantic cod are distinguished from currently represented Loma spp., particularly those infecting Gadus hosts, based on a 14‐nucleotide motif. This research approach is amenable to developing templates in support of reliable detection and identification of other microsporidian parasites in fishes.
Surplus Ore Potential as a Scarcity Indicator for Resource Extraction
Authors: Vieira Marisa D. M. , Ponsioen Thomas C. , Goedkoop Mark J. , Huijbregts Mark A. J.
Published: June 2016

The importance of increase in the scarcity of resources can be assessed using different approaches. Here, we propose a method that is based on the amount of extra ore mined to assess the importance of the extraction of resources. The surplus ore potential (SOP) indicator quantifies the extra amount of ore mined per additional unit of resource extracted by applying log‐logistic cumulative grade‐tonnage relationships and reserve estimates. We derived SOPs for 18 resources (17 metals including uranium and phosphorus) with 5 orders of magnitude difference (between 4.1 × 10−1 kilograms [kg] of extra ore per kg of manganese extracted and 5.5 × 104 kg of extra ore per kg of gold extracted). The sensitivity of the SOP values to the choice of reserve estimates (reserves vs. ultimate recoverable resource) are within a factor of 3 of each other. Combining the SOP values with the 2012 global extraction rates of these 18 resources resulted in a 236 to 372 kgore/capita surplus ore extracted. Iron, phosphorus, copper, gold, and aluminium were the largest contributors. The large variation in SOP values we observed between resources emphasizes the potential relevance of including resource‐specific SOP values to assess the contribution to resource scarcity by specific products and technologies.
Beneficial roles of melanoma cell adhesion molecule in spinal cord transection recovery in adult zebrafish
Authors: Liu Chun‐Jie , Xie Lin , Cui Chun , Chu Min , Zhao Hou‐De , Yao Li , Li Yu‐Hong , Schachner Melitta , Shen Yan‐Qin
Published: June 2016

Melanoma cell adhesion molecule (MCAM) is a multifunctional protein involved in miscellaneous processes, including development and tumor angiogenesis. Here, spinal cord transection in adult zebrafish was used to investigate the effects of MCAM on spinal cord injury (SCI) and subsequent recovery. Expression of MCAM mRNA increased and co‐localized with motoneurons in the spinal cord after SCI. With MCAM morpholino treatment, inhibition of MCAM retarded both axon regrowth and locomotor recovery in the spinal cord injured zebrafish. Furthermore, MCAM mRNA expression was also observed in fli1a:EGFP transgenic zebrafish, which specifically show labeled blood vessels. Inhibition of MCAM down‐regulated the expression of angiogenesis‐related factors, such as VEGFR‐2, p‐p38 and p‐AKT, and the inflammatory factors TNF‐α, IL‐1β and IL‐8. Taken together, these data suggest that MCAM may have a beneficial role in the recovery from SCI, via the promotion of neurogenesis and angiogenesis.

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In the context of adult zebrafish spinal cord injury, we proved that Melanoma cell adhesion molecule (MCAM) is beneficial to the recovery, possibly via mechanisms of angiogenensis and inflammation. MCAM promotes angiogenesis by adjusting VEGFR‐2, p‐p38 and p‐AKT. MCAM affects inflammatory factors such as TNF‐α, IL‐1β and IL‐8. Our results extend the beneficial role of MCAM in the regeneration of central nervous system.
Psychometric Properties of the Italian Adaptation of a Quality of Life Instrument as Applied to Adults With Intellectual and Developmental Disabilities
Authors: Bertelli Marco O. , Bianco Annamaria , Piva Merli Micaela , Scuticchio Daniela , Lassi Stefano , Lorenzoni Lorenzo , Carbone Viviani Dominga , Brown Ivan
Published: June 2016

In the field of intellectual disability (ID) generic quality of life (G‐QoL) has been reported to be much more useful than health‐related QoL. Despite this, Italian‐language tools with validated assessment of G‐QoL in people with ID are lacking. The authors undertook a study to test the psychometric properties of the BASIQ, an Italian adaptation of the Quality of Life Instrument Package developed at the Centre for Health Promotion, University of Toronto, Canada, in the early 1990s. This instrument package integrates qualitative and quantitative measures and subjective and objective approaches in assessing nine domains of QoL using a direct interview (DI), a proxy questionnaire (PQ), and an external assessor questionnaire (EAQ). Using BASIQ, the study assessed the QoL of a sample of 281 adults with ID (47 DI by 11 raters, 260 PQ by 23 proxies, and 69 EAQ by 5 physicians) drawn randomly from a three services populations in central Italy. The adults, 69% men and 31% women, ranged in age from 16 to 86 (X = 41.57); most (67.6%) functioned in the mild and moderate ranges of ID. QoL assessments were carried out in Italian, and were completed by specially trained disability professionals. The instrument had good internal consistency (Cronbach's alpha 0.990) and satisfactory inter‐rater reliability (Cohen's K > 0.7). For each of the DI and the PQ, all nine domains correlated positively (p < .05), and this was also the case for most domains of the EAQ. Post hoc analyses found no differences in QoL on any of the three scales for gender or co‐occurrence of mental or physical problems, but revealed some differences for level of disability. Overall, the authors present evidence for considering the BASIQ to be a valid instrument to assess QoL and put it forward as a useful tool to use in practice and policy development.