bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Plasma Exchange in Neuromyelitis Optica Spectrum Disorders and Related Disorders in Resource‐Limited Settings: Outcomes in a Multiethnic Single‐Center Population
Authors: Ong Zhi Miin , Schee Jie Ping , Viswanathan Shanthi
Published: October 2019

We evaluated therapeutic plasma exchange (TPE) efficiency in treatment of a single relapse in steroid‐refractory patients with neuromyelitis optica spectrum disorders (NMOSD) in a multi‐ethnic resource‐limited setting. This was a historical cohort study on the clinical outcomes post‐TPE in a multiethnic cohort of 53 steroid‐refractory NMOSD patients at a single Malaysian tertiary center. Primary outcomes, assessed both pre‐ and post‐TPE, were Medical Research Council scale of muscle power, Modified Rankin Scale, Expanded Disability Status Scale (EDSS), and visual acuity. Secondary outcomes were ambulatory status and target neurological deficit (TND)‐based TPE response. Significant improvements in Medical Research Council, Modified Rankin Scale, EDSS, and visual acuity (P < 0.001) were observed at 1‐month post‐TPE with further improvement of EDSS at 6 months (EDSSΔ6) post‐TPE (P < 0.001). At 6 months post‐TPE, 87% of patients has successful TND‐based TPE response and 69.8% were ambulating without support. Patients with anti‐aquaporin 4 seronegativity (P = 0.004), myelitis and brainstem features at first relapse (P = 0.004), longer cord lesions (P = 0.030), higher pre‐TPE EDSS of ≥8 (P = 0.018) and delayed TPE initiation of >14 days (P = 0.047) were significantly associated with improved EDSSΔ6. TND‐based TPE response was significant in absence of cord atrophy (P = 0.030). TPE is an effective treatment for steroid‐refractory acute relapses of NMOSD in a multiethnic Malaysian population despite its resource‐limited setting. The predictive factors of EDSSΔ6 improvement were anti‐aquaporin 4 seronegativity, longer cord lesions, and higher pre‐TPE EDSS. Absence of cord atrophy was predictive of better TND‐based TPE response. Unexpectedly, our study showed that delayed TPE initiation of more than 14 days and up to 60 days may also be beneficial.
Genetic polymorphisms of ATG16L1 and IRGM genes in Malaysian patients with Crohn's disease
Authors: Kee Boon Pin , Ng Jin Guan , Ng Ching Ching , Hilmi Ida , Goh Khean Lee , Chua Kek Heng
Published: October 2019

Objective

To investigate the association between genetic polymorphisms in ATG16L1 and IRGM genes and the development of Crohn's disease (CD) in Malaysian patients.

Methods

Altogether 335 participants were recruited, including 85 patients with CD and 250 unrelated healthy controls, and their informed consent was obtained. Genomic DNA was extracted via a conventional phenol‐chloroform extraction method. Six single nucleotide polymorphisms (SNPs) in ATG16L1 and IRGM genes were genotyped using TaqMan SNP genotyping assays. Associations between SNP and CD were determined using Fisher's exact test, odds ratio, and 95% confidence interval. Statistical power and the Hardy‐Weinberg equilibrium were also calculated.

Results

Two SNPs (rs2241880 and rs6754677) in the ATG16L1 gene were significantly associated with the onset of CD in the Malaysian population. The A allele and homozygous A/A genotype of the rs2241880 A/G polymorphism were protective against CD in the overall Malaysian and Malay population. The G allele and homozygous G/G genotype of the rs6754677 G/A polymorphism were protective in the Indian population, whereas the homozygous A/A genotype showed a risk of developing CD. The homozygous G/G genotype of IRGM rs11747270 was significantly present in the controls. However, this significance was not observed in a race‐stratified analysis. All three ATG16L1 SNPs were associated with inflamed terminal ileum. IRGM rs4958847 and rs11747270 increased the risk of developing arthritis in patients with CD.

Conclusion

We found a significant association between SNP, which are located in autophagy‐related genes, and CD in a Malaysian population.
Pregnancy outcome in women with gestational diabetes – A longitudinal study of changes in demography and treatment modalities
Authors: Moll Ulrika , Landin‐Olsson Mona , Nilsson Charlotta , Ursing Dag , Strevens Helena
Published: October 2019

Introduction

Gestational diabetes is on the rise and demographics are changing in many countries due to increased migration. Simultaneously, the treatment of gestational diabetes in our clinic has shifted towards metformin with substantially less insulin treatment. The aim was to study the impact of these changes on metabolic control and pregnancy outcome by comparing women diagnosed with gestational diabetes during 2012‐2013 and 2016‐2017.

Material and methods

Our universal Oral Glucose Tolerance Test screening program for gestational diabetes diagnosed 199 women with singleton pregnancies during 2012‐2013 and 203 during 2016‐2017. Treatment and achieved metabolic control in the two different time periods were compared. Pregnancy outcome data related to gestational diabetes were retrieved from case notes and compared between the different time periods.

Results

When comparing results from 2016‐2017 with 2012‐2013 there was no difference in maternal weight or weight gain. There was a higher frequency of heredity (52.6 vs 35.4%; P = 0.001) and non‐Scandinavian ethnicity (46.5 vs 33.8%; P = 0.011).The frequency of smoking during pregnancy was significantly lower (2.6 vs 7.7%; P = 0.023) There was an improved metabolic control as measured by median glucose in 2016‐2017 compared with 2012‐2013 (5.8 vs 6.2 mmol/L; P < 0.001). Insulin was less frequently used in 2016‐2017 than in 2012‐2013 (32.5 vs 44.7%; P = 0.012). There was a significant increase in the use of metformin (14.8 vs 0%; P < 0.001). There were no differences regarding the frequency of large‐for‐gestational‐age infants (8.2% vs 7.3%; P = 0.762) or macrosomia (16.3 vs 15.1%; P = 0.745), median birthweight (3510 vs 3521; P = 0.879), frequency of cesarean section (28.1 vs 27.8%; P = 0.951) or Apgar scores at 10 minutes (10 [3‐10] vs 10 [7‐10]; P = 0.290).

Conclusions

In an increasing but changing population of gestational diabetes women in our region, with more hereditary and non‐Scandinavian origins, but with fewer smokers, metabolic control has improved with maintained favorable pregnancy outcomes, with more frequent use of metformin and substantially less use of insulin treatment.
Timing of delivery in women with diabetes: A population‐based study
Authors: Metcalfe Amy , Hutcheon Jennifer A. , Sabr Yasser , Lyons Janet , Burrows Jason , Donovan Lois E. , Joseph K. S.
Published: October 2019

Introduction

Women with diabetes, and their infants, have an increased risk of adverse events due to excess fetal growth. Earlier delivery, when fetuses are smaller, may reduce these risks. This study aimed to evaluate the week‐specific risks of maternal and neonatal morbidity/mortality to assist with obstetrical decision making.

Material and methods

In this population‐based cohort study, women with type 1 diabetes (n = 5889), type 2 diabetes (n = 9422) and gestational diabetes (n = 138 917) and a comparison group without diabetes (n = 2 553 243) who delivered a singleton infant at ≥36 completed weeks of gestation between 2004 and 2014 were identified from the Canadian Institute of Health Information Discharge Abstract Database. Multivariate logistic regression was used to determine the week‐specific rates of severe maternal and neonatal morbidity/mortality among women delivered iatrogenically vs those undergoing expectant management.

Results

For all women, the absolute risk of severe maternal morbidity/mortality was low, typically impacting less than 1% of women, and there was no significant difference in gestational age‐specific severe maternal morbidity/mortality between iatrogenic delivery and expectant management among women with any form of diabetes. Among women with gestational diabetes, iatrogenic delivery was associated with an increased risk of neonatal morbidity/mortality compared with expectant management at 36 and 37 weeks’ gestation (76.7 and 27.8 excess cases per 1000 deliveries, respectively) and a lower risk of neonatal morbidity/mortality at 38, 39 and 40 weeks’ gestation (7.9, 27.3 and 15.9 fewer cases per 1000 deliveries, respectively). Increased risks of severe neonatal morbidity following iatrogenic delivery compared with expectant management were also observed for women with type 1 diabetes at 36 (98.3 excess cases per 1000 deliveries) and 37 weeks’ gestation (44.5 excess cases per 1000 deliveries) and for women with type 2 diabetes at 36 weeks’ gestation (77.9 excess cases per 1000 deliveries) weeks.

Conclusions

The clinical decision regarding timing of delivery is complex and contingent on maternal‐fetal wellbeing, including adequate glycemic control. This study suggests that delivery at 38, 39 or 40 weeks’ gestation may optimize neonatal outcomes among women with diabetes.
The national comprehensive cancer network distress thermometer as a screening tool for the evaluation of quality of life in uveal melanoma patients
Authors: Klingenstein Annemarie , Samel Christina , Garip‐Kuebler Aylin , Miller Christina , Liegl Raffael G. , Priglinger Siegfried G. , Foerster Paul I.
Published: October 2019

Purpose

To assess quality of life (QoL) status via the National Comprehensive Cancer Network (NCCN) distress thermometer as a psychooncological screening tool in uveal melanoma patients.

Methods

One hundred and six consecutive patients suffering from uveal melanoma completed the distress thermometer between 04/2018 and 12/2018. Practical, emotional, family concerned, spiritual, physical and overall distress levels, distribution of distress and subgroup analyses defining groups of potential high distress levels in need of intervention were assessed. Descriptive statistics, cross‐tabulations, chi‐square and Fisher's exact test as well as correlation coefficients (Spearman's rho) and receiver operating characteristic (ROC) were used for analysis.

Results

Patients with higher T‐category had significantly more emotional problems and spiritual concerns (p = 0.046 and p = 0.023, respectively). Female patients accounted for higher rates of physical issues (p = 0.034). Lower best corrected visual acuity (BCVA) was correlated with higher distress levels (p = 0.037). Patients resulting in loss of BCVA of ≥3 lines reported higher distress levels (p = 0.029). A distress threshold of 5 on the basis of ROC analysis showed a corresponding sensitivity of 100% and specificity of 76%.

Conclusion

The NCCN distress thermometer could be integrated well into our clinical routine and proved to be a rapid, yet sensible screening tool for emotional and physical distress in patients with uveal melanoma. Special attention should be paid to patients with higher T‐category and patients resulting in lower levels of BCVA. As in patients with different tumour entities, the established distress threshold of ≥5 proposing intervention proved to be adequate for uveal melanoma patients.
Alterations in retinal arteriolar microvascular structure associate with higher treatment burden in patients with diabetic macular oedema: results from a 12‐month prospective clinical trial
Authors: Blindbæk Søren L , Peto Tunde , Grauslund Jakob
Published: October 2019

Purpose

This study was based on data from a 12‐month prospective clinical trial and aimed to examine changes in retinal microvascular structure in eyes treated with intravitreal aflibercept in combination with focal/grid laser photocoagulation for diabetic macular oedema (DME).

Methods

We included 32 treatment naïve eyes of 22 patients with centre involving DME. The treatment algorithm comprised a loading phase of three monthly injections of aflibercept and focal/grid laser photocoagulation [baseline (BL)‐month 3 (M3)] followed by a pro re nata (PRN) aflibercept phase until month 12 (M12). Eyes were divided into groups with and without need for PRN treatment after loading. Parameters of retinal microvascular structure were measured in 45° optic disc centred fundus images at BL, M3 and M12 using a semi‐automated software (VAMPIRE®, Vessel Assessment and Measurement Platform for Images of the Retina, Universities of Dundee and Edinburgh, UK).

Results

A significant decrease in retinal arteriolar calibre was demonstrated at both M3 (−11.2 μm, p = 0.005) and M12 (−11.5 μm, p = 0.04) as compared to BL in eyes that needed PRN treatment during follow‐up. In contrast, arteriolar calibre remained unchanged in eyes without need for PRN treatment (M3: −1.6 μm, p = 0.79 and M12: −7.0 μm, p = 0.22). For retinal venules, vessel calibre decreased both in eyes with and without need for PRN therapy at M3 (−9.5 μm, p = 0.01 and −11.6 μm, p = 0.01) as well as at M12 (−15.6 μm, p = 0.001 and −11.0 μm, p = 0.04).

Conclusion

Early changes in retinal arteriolar calibre are associated with an increased treatment burden during the first year of DME treatment.
The association study of lipid metabolism gene polymorphisms withAMDidentifies a protective role forAPOE‐E2 allele in the wet form in a Northern Spanish population
Authors: Fernández‐Vega Beatriz , García Montserrat , Olivares Lorena , Álvarez Lydia , González‐Fernández Adrián , Artime Enol , Fernández‐Vega Cueto Andrés , Cobo Teresa , Coca‐Prados Miguel , Vega José A. , González‐Iglesias Héctor
Published: October 2019

Purpose

To elucidate the potential role of eleven single nucleotide polymorphisms (SNPs) in the most relevant lipid metabolism genes in Northern Spanish patients with age‐related macular degeneration (AMD).

Methods

A case‐control study of 228 unrelated native Northern Spanish patients diagnosed withAMD(73 dry and 155 wet) and 95 healthy controls was performed.DNAwas isolated from peripheral blood and genotyped for theSNPsAPOErs429358 and rs7412;CTEPrs3764261;LIPCrs10468017 and rs493258;LPLrs12678919;ABCA1rs1883025;ABCA4rs76157638, rs3112831 and rs1800555; andSCARB1rs5888, using TaqMan probes. An additional association study ofε2,ε3 andε4 major isoforms ofAPOEgene withAMDhas been carried out.

Results

The allele and genotype frequencies for each of the eleven sequence variants in the lipid metabolism genes did not show significant differences when comparingAMDcases and controls. Statistical analysis revealed thatAPOE‐ε2 carrier genotypes were less frequently observed in patients with wetAMDcompared to controls (5.8% versus 13.7%, respectively: p = 3.28 × 10−2;OR = 0.42, 95%CI: 0.19–0.95). The frequency of the allele T of rs10468017 (LIPCgene) was lower in dryAMDcases compared to controls (15.8 versus 27.9%, respectively: p = 8.4 × 10−3OR = 0.57, 95%CI: 0.33–0.98).

Conclusions

Our results suggest a protective role forAPOE‐ε2 allele to wetAMDin the Northern Spanish population.
Safety of soft contact lenses in children: retrospective review of six randomized controlled trials of myopia control
Authors: Cheng Xu , Brennan Noel A. , Toubouti Youssef , Greenaway Nathan L.
Published: October 2019

Purpose

To examine the rate and types of ocular adverse events among children wearing soft contact lenses.

Methods

This study is a retrospective review of ocular adverse event data from six randomized controlled trials among a total of 581 myopic children (aged 7–15 years at baseline) administered daily disposable hydrogel contact lenses (etafilcon A).

Results

During 816 patient years of contact lens wear, no significant or serious ocular adverse events were reported. A total of 86 non‐significant ocular adverse events occurred in 53 children. The crude rate of ocular adverse events was 10.6 per 100 patient years with the estimated pooled incidence being 8.9 per 100 patient years (95% CI: 4.5–17.4). Two asymptomatic corneal infiltrative events were reported (both non‐significant), which is an incidence of 0.3 (95% CI: 0.1–0.9) per 100 patient years. The most common ocular adverse events (n) were slit‐lamp findings of Grade 2 or less requiring treatment (26), unspecified conjunctivitis (14), and allergic conjunctivitis (13). No cases of microbial keratitis were observed. Of the 86 adverse events, 37 were classified as highly likely or possibly lens‐related, giving a crude incidence of 4.5 per 100 patient years for contact lens‐related events. The crude incidence of ocular adverse events among spectacle wearers was 1.8 per 100 patient years.

Conclusion

These data suggest that daily disposable soft contact lenses can be safely worn by children. Additional studies will be needed to precisely quantify the adverse event rate of soft contact lenses in normal clinical practice.
Histological findings of levator muscle in unilateral congenital ptosis in different age groups
Authors: Quaranta‐Leoni Francesco M. , Secondi Roberto , Quaranta‐Leoni Flavia , Nardoni Stefano
Published: October 2019

Purpose

To evaluate the different degree of muscle atrophy in specimens of levator muscle of patients operated on for unilateral congenital ptosis, as related to the age of the patient.

Methods

Histological analysis of the specimen of the levator muscle of 29 patients who underwent a unilateral levator muscle resection under the care of one surgeon was performed. The study population was divided into two different groups according to the timing of surgery: group 1 included 15 children operated on at 2 to 4 years, and group 2 included 14 children operated on at 4.1 to 11 years.

Results

Levator muscle of 12 patients of group 1 showed mild degree of muscle atrophy, with striated muscle fibres separated by thin fibrous septa incorporating groups of cells with peripheral nuclei and non‐hyalinized cytoplasm (Masson's trichrome stain). In eight cases of group 2, levator muscle showed instead severe atrophy, with discontinuous striated muscle fibres separated by thick fibrous septa including cells with centralization of nuclei, hyalinization of cytoplasm (Masson's trichrome stain) and fatty infiltration.

Conclusion

Myofibres found in specimens of levator muscle following levator resection for congenital ptosis show characteristics of a degenerative process. This study seems to demonstrate that atrophy in the levator muscle appears to be related to the age of the patient at surgery, as atrophy tends to be more evident in older children with congenital ptosis.
Spontaneous closure of small full‐thickness macular holes: Presumed role of Müller cells
Authors: Bringmann Andreas , Duncker Tobias , Jochmann Claudia , Barth Thomas , Duncker Gernot I. W. , Wiedemann Peter
Published: October 2019

Purpose

To document with spectral domain optical coherence tomography the formation and spontaneous closure of small full‐thickness macular holes and to propose the active role of Müller cells in macular hole closure.

Methods

A retrospective case series of five patients with spontaneous closure of macular holes is reviewed. In one patient, foveal images were recorded over a period of 18 months.

Results

In a 66‐year‐old man, vitreofoveal traction caused a detachment of the inner Müller cell layer of the foveola from the outer nuclear layer (ONL) which was associated with a large pseudocyst and a horizontal gap in the central ONL. The traction caused an elongation and subsequent disruption of the stalk of the Müller cell cone in the foveola. A small full‐thickness macular hole developed when a portion of the inner Müller cell layer of the foveola was pulled out. After phacoemulsification and shortly before the subsequent spontaneous closure of the hole, there were rapid increases in the number and size of the cystic cavities in the foveal walls resulting in a narrowing of the hole. The hole closed by bridging the gap in the inner part of the central ONL; a new inner Müller cell layer of the foveola was formed, and the gap of the external limiting membrane (ELM) was closed. The cystic cavities in the foveal walls rapidly disappeared within 2 weeks after the closure of the hole. One to 2.5 months after hole closure, the thickness of the central ONL increased which decreased the distance between the central ELM and retinal pigment epithelium. In three of the four other patients, the hole also closed by bridging the gap in the inner part of the ONL.

Conclusion

It is suggested that the spontaneous closure of small macular holes and the subsequent reconstruction of the normal foveal structure are mediated by active mechanisms of Müller cells which resemble those involved in ontogenetic foveal development.
Quality improvement programme to improve compliance with initial respiratory support guideline at preterm birth
Authors: Hoyle Emily S. , Patino Francesca , Yoxall Charles W.
Published: October 2019

Aim

CPAP (continuous airway pressure) use as respiratory support from birth increases the proportion of babies who survive without bronchopulmonary dysplasia. Although we introduced a guideline for CPAP use in 2015, our intubation rate remained high (61.7%). We aimed to reduce the intubation rate into the interquartile range for the Vermont Oxford Neonatal (VON) network.

Methods

A multi‐disciplinary team was established. Data relating to resuscitation in all babies born before 32 weeks gestation or with a birth weight below 1500 g during 2017/2018 were collected prospectively. Episodes when CPAP was not used were identified, and series of Plan, Do, See, Act (PDSA) cycles performed. Performance data were displayed graphically to staff along with lessons learnt.

Results

The rate of intubation at birth for VLBW babies fell from 61.7% into the VON interquartile range at 49.6% during the project (P = .02). Intubation rate in babies born between 26 and 30 weeks gestation fell from 66% to 41% (the VON network mean).

Conclusion

The NICU is a complex system. Altering clinical practice is challenging, even with good clinical evidence to support change. Quality improvement using frequent PDSA cycles enabled us to alter our practice. Preterm intubation rates are now within the desired range.
ADHD and emotional engagement with school in the primary years: Investigating the role of student–teacher relationships
Authors: Rushton Sophie , Giallo Rebecca , Efron Daryl
Published: October 2019

Background

Attention deficit hyperactivity disorder (ADHD) is consistently associated with poor school‐level outcomes. Although school engagement is recognized as a protective factor associated with increased academic achievement, school retention/completion, and student well‐being in the general population, little research has focused on school engagement in children with ADHD.

Aims

To explore a model of the relationships between ADHD symptoms at age 7, student–teacher closeness and conflict at age 10, and emotional engagement with school at age 10 and 12.

Sample

Participants were 498 grade one children (mean age = 7.3), recruited from 43 socio‐economically diverse government primary schools in Melbourne. Follow‐up occurred at 36 months (mean age = 10.5) and 54 months (mean age = 12.0).

Methods

Data were drawn from a controlled community‐based longitudinal study examining the long‐term effects of ADHD on children's behaviour, learning, and day‐to‐day living. Data were collected via direct assessment and child, parent, and teacher surveys.

Results

Path analysis revealed a significant, negative relationship between ADHD symptoms and emotional engagement with school, which was partially mediated by student–teacher conflict. This remained significant after controlling for differences in ADHD status (ADHD, high‐risk, or control group), ADHD medication use, and socio‐economic status.

Conclusions

These findings highlight the negative impact of ADHD symptoms on children's emotional engagement with school. Given the role of student–teacher conflict in mediating this relationship, interventions aiming to reduce conflict in the student–teacher relationship may promote school engagement for students with ADHD, with potential to improve longer‐term outcomes.
The interplay of reading‐related emotions and updating in reading comprehension performance
Authors: Zaccoletti Sonia , Altoè Gianmarco , Mason Lucia
Published: October 2019

Background

Reading comprehension can be considered the main learning activity. All learning experiences are infused with emotions; however, to date, few studies have focused on the role of emotional aspects in reading comprehension performance. The impact of emotions on academic achievement is thought to be mediated or moderated by cognitive aspects. Among them, working memory updating is an executive function that plays a crucial role in reading comprehension.

Aims

This study aimed to investigate the relationships between reading‐related emotions and reading comprehension performance. We also consider the role that updating may play in these relationships.

Sample

Two hundred and eight 8th graders were involved in four sessions.

Method

Students completed measures of achievement emotions specifically related to reading comprehension activity, updating, and reading comprehension performance. Gender and general cognitive ability were also considered as control variables. Mixed‐effects models were used for statistical analyses. According to the Akaike information criterion (AIC; Akaike, 1974), we selected the most plausible model among a set of candidate models fitted to the same data.

Results

Results showed that activating‐negative emotions (i.e., anxiety, anger, and shame), deactivating‐negative emotions (i.e., boredom and hopelessness), and updating are related with reading comprehension performance. Moreover, the interaction between activating‐negative emotions and updating also emerged. When activating‐negative emotions interact with low and moderate updating, students’ reading comprehension performance gets worse.

Conclusions

The study indicates the moderating role of a main cognitive ability in the link between reading‐related emotions and reading comprehension performance. Strategies can be taught to improve students’ ability to self‐regulate negative emotions and to update information in working memory.
Novel highly potent OXE receptor antagonists with prolonged plasma lifetimes that are converted to active metabolites in vivo in monkeys
Authors: Ye Qiuji , Chourey Shishir , Reddy Chintam Nagendra , Wang Rui , Cossette Chantal , Gravel Sylvie , Slobodchikova Irina , Vuckovic Dajana , Rokach Joshua , Powell William S.
Published: October 2019

Background and Purpose

The 5‐lipoxygenase product 5‐oxo‐6E,8Z,11Z,14Z‐eicosatetraenoic acid (5‐oxo‐ETE), acting through the OXE receptor, is a potent eosinophil chemoattractant that may be an important proinflammatory mediator in eosinophilic diseases such as asthma. We previously identified a series of indole‐based OXE receptor antagonists that rapidly appear in the blood following oral administration but have limited lifetimes. The objective of this study was to increase the potency and plasma half‐lives of these compounds and thereby identify the optimal candidate for future preclinical studies in monkeys, as rodents do not have an OXE receptor orthologue.

Experimental Approach

We synthesized a series of substituted phenylalkyl indoles and compared their antagonist potencies, pharmacokinetics, and metabolism to those of our earlier compounds. The potencies of some of their metabolites were also investigated.

Key Results

Among the compounds tested, the S‐enantiomer of the m‐chlorophenyl compound (S‐Y048) was the most potent, with an pIC50 of about 10.8 for inhibition of 5‐oxo‐ETE‐induced calcium mobilization in human neutrophils. When administered orally to cynomolgus monkeys, S‐Y048 rapidly appeared in the blood and had a half‐life in plasma of over 7 hr, considerably longer than any of the other OXE analogues tested. A major hydroxylated metabolite, with a potency close to that of its precursor, was identified in plasma.

Conclusion and Implications

Because of its highly potent antagonist activity and its long lifetime in vivo, S‐Y048 may be a useful anti‐inflammatory agent for the treatment of eosinophilic diseases such as asthma, allergic rhinitis, and atopic dermatitis.
CuII(atsm) inhibits ferroptosis: Implications for treatment of neurodegenerative disease
Authors: Southon Adam , Szostak Kathryn , Acevedo Karla M. , Dent Krista A. , Volitakis Irene , Belaidi Abdel A. , Barnham Kevin J. , Crouch Peter J. , Ayton Scott , Donnelly Paul S. , Bush Ashley I.
Published: October 2019

Background and Purpose

Diacetyl‐bis(4‐methyl‐3‐thiosemicarbazonato)copperII(CuII(atsm)) ameliorates neurodegeneration and delays disease progression in mouse models of amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), yet the mechanism of action remains uncertain. Promising results were recently reported for separate Phase 1 studies in ALS patients and PD patients. Affected tissue in these disorders shares features of elevated Fe, low glutathione and increased lipid peroxidation consistent with ferroptosis, a novel form of regulated cell death. We therefore evaluated the ability of CuII(atsm) to inhibit ferroptosis.

Experimental Approach

Ferroptosis was induced in neuronal cell models by inhibition of glutathione peroxidase‐4 activity with RSL3 or by blocking cystine uptake with erastin. Cell viability and lipid peroxidation were assessed and the efficacy of CuII(atsm) was compared to the known antiferroptotic compound liproxstatin‐1.

Key Results

CuII(atsm) protected against lipid peroxidation and ferroptotic lethality in primary and immortalised neuronal cell models (EC50: ≈130 nM, within an order of magnitude of liproxstatin‐1). NiII(atsm) also prevented ferroptosis with similar potency, whereas ionic CuIIdid not. In cell‐free systems, CuII(atsm) and NiII(atsm) inhibited FeII‐induced lipid peroxidation, consistent with these compounds quenching lipid radicals.

Conclusions and Implications

The antiferroptotic activity of CuII(atsm) could therefore be the disease‐modifying mechanism being tested in ALS and PD trials. With potencyin vitroapproaching that of liproxstatin‐1, CuII(atsm) possesses favourable properties such as oral bioavailability and entry into the brain that make it an attractive investigational product for clinical trials of ferroptosis‐related diseases.
Bruit aérien et équité environnementale dans les quatre plus grandes métropoles canadiennes
Authors: Audrin Thomas , Apparicio Philippe , Séguin Anne‐Marie , Gelb Jérémy
Published: October 2019

Messages clés

Respectivement 419 000 et 57 000 personnes résident à l'intérieur des courbes NEF 25 et NEF 30 dans les quatre RMR étudiées, soit des zones de bruit aérien assez élevé.

Il y a des situations contrastées en termes d'iniquité selon les métropoles.

L'iniquité quant au niveau de bruit aérien mesuré dans le milieu résidentiel est peu prononcée pour les groupes de population étudiés.
Night Awakening and Its Association With Executive Functioning Across the First Two Years of Life
Authors: Mäkelä Tiina E. , Peltola Mikko J. , Saarenpää‐Heikkilä Outi , Himanen Sari‐Leena , Paunio Tiina , Paavonen E. Juulia , Kylliäinen Anneli
Published: October 2019

Longitudinal associations between signaled night awakening and executive functioning (EF) at 8 and 24 months in children with (≥ 3 awakenings, n = 77) and without parent‐rated fragmented sleep (≤ 1 awakening, n = 69) were studied. EF was assessed with the Switch task at 8 and 24 months. At 24 months, behavioral tasks and parental ratings of EF (Behavior Rating Inventory of Executive Function–Preschool version) were also used. In the Switch task, children with fragmented sleep were less able to learn stimulus sequences and inhibit previously learned responses than children without fragmented sleep. The groups differed only marginally in parental ratings of EF, and no differences were found in behavioral EF tasks. These results suggest that eye movement‐based measures may reveal associations between sleep and EF already in infancy and toddlerhood.
Decisional conflict among adolescents and parents making decisions about genomic sequencing results
Authors: Raghuram Pillai Preethi , Prows Cynthia A. , Martin Lisa J. , Myers Melanie F.
Published: October 2019

Genomic testing of adolescents is increasing yet engaging them in decision‐making is not routine. We assessed decisional conflict in adolescents and a parent making independent decisions about actual genomic testing results and factors that influenced their choices. We enrolled 163 dyads consisting of an adolescent (13‐17 years) not selected based on a specific clinical indication and one parent. After independently choosing categories of conditions to learn for the adolescent, participants completed the validated Decisional Conflict Scale and a survey assessing factors influencing their respective choices. Adolescents had higher decisional conflict scores than parents (15.6 [IQR:4.7‐25.6] vs 9.4 [IQR:1.6‐21.9]; P = .0007). Adolescents with clinically significant decisional conflict were less likely to choose to learn all results than adolescents with lower decisional conflict (19.6% vs 80.4%; P < .0001) and less likely to report their choices were influenced by actionability of results (33.3% vs 18.9%; P = .044) and feeling confident they can deal with the results (71.2% vs 91.9%; P = .0005). Our findings suggest higher decisional conflict in adolescents may influence the type and amount of genomic results they wish to learn. Additional research assessing decisional conflict and factors influencing testing choices among adolescents in clinical settings are required.
Clinical denture base deformation with different attachments used to stabilize implant overdentures: A crossover study
Authors: ELsyad Moustafa Abdou , Fathe Mahanna Fatma , Samir Khirallah Ahmed , Ali Habib Ahmed
Published: October 2019

Objectives

The aim of this crossover study was to compare clinical denture base deformation with different attachments used for mandibular implant overdentures.

Materials and methods

Twenty‐four patients with edentulous mandibular ridges received two implants in the former canine regions. Three months thereafter, each patient was randomly given the following implant overdentures in a crossover design: (a) bar implant overdentures (BOD), (b) resilient telescopic implant overdentures (TOD), and (c) stud implant overdentures (SOD). Six linear strain gauges were attached to the lingual surface of the implant overdentures opposite to the abutments (Ch1and Ch2 at clenching [left] side and Ch5and Ch6 at non‐clenching [right] side) and at midline (Ch3 and Ch4). Three months after wearing each implant overdenture, strain registrations were performed during clenching without food and during clenching on soft (cake) and hard (carrot) foods. Kruskal–Wallis test was used to compare denture strains between group, channels, and clenching conditions.

Results

Bar implant overdentures showed significantly higher (p < .001) total microstrains (403.7 ± 306.8 μɛ) than TOD (146.9 ± 131.8 μɛ) and SOD (99.8 ± 75.6 μɛ). No difference in microstrain was noted between TOD and SOD (p = .06, n.s.). Channels opposite to the abutments at clenching side (ch2) recorded the highest total strain during clenching hard (390.4 ± 381.6 μɛ) and soft (223.5 ± 220.2 μɛ) foods. Clenching hard food was associated with significant higher total microstrain than clenching soft food (p = .002).

Conclusion

Telescopic and stud attachments are recommended to be used for two‐implant mandibular over dentures as they were associated with reduced denture base deformation compared with bar attachments.
Systematic review and meta‐analysis of the anatomical variants of the left colic artery
Authors: Cirocchi R. , Randolph J. , Cheruiyot I. , Davies J. R. , Wheeler J. , Lancia M. , Gioia S. , Carlini L. , di Saverio S. , Henry B. M.
Published: October 2019

Aim

To provide a comprehensive evidence‐based assessment of the anatomical variations of the left colic artery (LCA).

Method

A thorough systematic search of the literature up until 1 April 2019 was conducted on the electronic databases PubMed, SCOPUS and Web of Science (WOS) to identify studies eligible for inclusion. Data were extracted and pooled into a meta‐analysis using the Metafor package in R. The primary outcomes of interest were the absence of the LCA and the anatomical variants of its origin. The secondary outcomes were the distance (mean ± SD) between the origin of the inferior mesenteric artery (OIMA) and the origin of the left colic artery (OLCA).

Results

A total of 19 studies (n = 2040 patients) were included. The pooled prevalence estimate (PPE) of LCA absence was 1.2% (95% CI 0.0–3.6%). Across participants with either a Type I or Type II LCA, the PPE of a Type I LCA was 49.0% (95% CI 40.2–57.8%). The PPE of a Type II LCA was therefore 51.0%. The pooled mean distance from the OIMA to the OLCA was 40.41 mm (95 CI% 38.69–42.12 mm). The pooled mean length of a Type I LCA was 39.12 mm (95% CI 36.70–41.53 mm) while the pooled mean length of a Type IIa and Type IIb LCA was 41.43 mm (95% CI 36.90–43.27 mm) and 39.64 mm (95% CI 37.68–41.59 mm), respectively.

Conclusion

Although the absence of the LCA is a rare occurrence (PPE 1.2%), it may be associated with an important risk of anastomotic leakage as a result of insufficient vascularization of the proximal colonic conduit. It is also necessary to distinguish variants I and II of Latarjet, the frequency of which is identical, with division of the LCA being technically more straightforward in variant I of Latarjet. Surgeons should be aware that technical difficulties are likely to be more common with variant II of Latarjet, as LCA ligation may be more difficult due to its close proximity to the inferior mesenteric vein (IMV).
Prognostication of inflammatory cells in liver transplantation: Is the waitlist neutrophil‐to‐lymphocyte ratio really predictive of tumor biology?
Authors: McVey John C. , Sasaki Kazunari , Firl Daniel J. , Fujiki Masato , Diago‐Uso Teresa , Quintini Cristiano , Eghtesad Bijan , Miller Charles C. , Hashimoto Koji , Aucejo Federico N.
Published: October 2019

Objective

The objective of this retrospective study was to characterize the neutrophil to lymphocyte ratio (NLR) on the waitlist and determine its prognostic utility in liver transplantation (LT) for hepatocellular carcinoma (HCC) with special focus on longitudinal data. Biomarkers such as pre‐operative NLR have been suggested to predict poor oncological outcomes for patients with HCC seeking LT. NLR's utility is thought to be related to tumor biology. However, recent studies have demonstrated that a high NLR conveys worse outcomes in non‐HCC cirrhotics. This study investigated the relationship between NLR, liver function, tumor factors and patient prognosis.

Methods

Patients with HCC undergoing LT were identified between 2002 and 2014 (n = 422). Variables of interest were collected longitudinally from time of listing until LT. The prognostic utility of NLR was assessed using Kaplan‐Meier and Cox Proportional Hazard regression. Associations between NLR and MELD‐Na, AFP, and tumor morphology were also assessed.

Results

NLR demonstrated a positive correlation with MELD‐Na at LT (R2 = 0.125, P < 0.001) and had parallel trends over time. The lowest NLR quartile had a median MELD‐Na of 9 while the highest had a median MELD‐Na of 19. There were minimal differences in AFP, tumor morphology, and rates of vascular invasion between quartiles. NLR was a statistically significant predictor of OS (HR = 1.64, P = 0.017) and recurrence (HR = 1.59, P = 0.016) even after controlling for important tumor factors. However, NLR lost its statistical significance when MELD‐Na was added to the Cox regression model (OS: HR = 1.46, P = 0.098) (recurrence: HR = 1.40, P = 0.115).

Conclusions

NLR is a highly volatile marker on the waitlist that demonstrates a significant correlation and collinearity with MELD‐Na temporally and at the time of LT. These characteristics of NLR bring into question its utility as a predictive marker in HCC patients.
Diminished school‐based support for the management of type 1 diabetes in adolescents compared to younger children
Authors: McCollum D. C. , O'Grady M. J.
Published: October 2019

Aims

To evaluate diabetes management at school in a large cohort of adolescents with type 1 diabetes and to compare the level of support provided to adolescents with that provided to younger children.

Methods

Questionnaires were distributed to adolescents with type 1 diabetes attending nine regional and tertiary paediatric diabetes services in the Republic of Ireland. The data collected included patient demographics, treatment regimen and support provided for self‐care management. Results were compared with a similar cohort of primary school children with type 1 diabetes, studied using similar methodology.

Results

The study cohort comprised 405 adolescents with a median age of 15 years, of whom 215 (54%) were on multiple daily injections and 128 (32%) were on pump therapy. Eighty‐five percent of pump users administered their bolus insulin in classrooms, whereas 76% of those on a multiple daily injection regimen injected outside the classroom. Girls were less likely to administer bolus insulin in an office (10% vs 19%) and more likely to administer it in the bathroom (50% vs 34%; P=0.01). Twenty‐five adolescents (12%) on multiple daily injection regimens did not administer bolus insulin at school. Compared to primary school children with type 1 diabetes, adolescents were less likely to use pump therapy, have an emergency treatment plan and have a designated staff member responsible for care needs.

Conclusions

Support provided to adolescents with type 1 diabetes is diminished compared with that provided to younger schoolchildren.
Benign pericardial schwannoma with massive pericardial effusion in a Chinese man: A case report
Authors: Li Cuiling , Zhang Jingwei , Fan Rui , Chen Lili , Liu Donghong , Lin Hong
Published: October 2019

Primary cardiac neoplasms are rare, and the pericardial schwannoma has an even lower occurrence. We report a case of pericardial schwannoma in China, which is the eighth reported case adding to the existing literature on pericardial schwannoma, and this is the first case reported complicated with massive pericardial effusion. Pericardial schwannomas are usually benign, but they can sometimes have a malignant tendency and cause life‐threatening complications. Thus, it should be managed aggressively and completely resected.
Instantaneous interjoint rescaling and adaptation to balance perturbation under muscular fatigue
Authors: Rinaldin Carla Daniele Pacheco , Ávila de Oliveira Júlia , Coelho Daniel Boari , Scheeren Eduardo Mendonça , Teixeira Luis Augusto
Published: October 2019

Adaptation of automatic postural responses (APR) to balance perturbations might be thought to be impaired by muscle fatigue, given the associated proprioceptive and effector deficits. In this investigation, we aimed to evaluate the effect of muscular fatigue on APR adaptation over repetitive balance perturbations through support base backward translations. APR adaptation was evaluated in three epochs: (a) pre‐fatigue; (b) post‐fatigue, immediately following fatigue of the plantiflexor muscles through isometric contractions and (c) post‐recovery, 30 min after the end of fatiguing activity. Results showed the following: (a) Decreasing amplitudes of joints' maximum excursion over repetitive perturbations in the three fatigue‐related epochs. (b) Modulation of joints' excursion was observed in the first trial in the post‐fatigue epoch. (c) In the post‐fatigue epoch, we found interjoint rescaling, with greater amplitude of hip rotation associated with reduced amplitude of ankles' rotation. (d) Amplitudes of ankles' rotation were similar between the post‐fatigue and post‐recovery epochs. These findings lead to the conclusions that adaptation of automatic postural responses over repetitive trials was effective under focal muscular fatigue; modulation of the postural response took place in the first perturbation under fatigue, and generalization of response characteristics from post‐fatigue to post‐recovery suggests that feedforward processes in APRs generation are affected by the recent history of postural responses to stance perturbations.
Anxiety‐like behavior in female mice changes by feeding, possible effect of guanylate cyclase C
Authors: Dugandzic Aleksandra , Ratko Martina , Habek Nikola
Published: October 2019

Anxiety disorders are the most frequent mental disorders and are more prevalent in the female population. Up to date, an involvement of guanylate cyclase A and B in anxiety‐like behavior has been suggested. In this study, we showed an expression of guanylate cyclase C (GC‐C) in the amygdala which is regulated by feeding. Therefore, we further investigated sex differences of GC‐C effects on anxiety levels with special attention to female estrous cycle and feeding. The effects of estrous cycle and feeding were investigated by several behavior tests: elevated plus maze, home cage escape and novelty‐induced hypophagy. Possible changes in GC‐C expression in amygdala and hypothalamus during estrous cycle were established by qPCR. When GC‐C is activated (after a meal), the sex difference in all behavior tests used was abolished. As the expression of mRNA for GC‐C in the amygdala increases 2 hr after a meal only in female animals, the anxiety levels change after a meal again only in female animals. When the anxiety levels are investigated, it is very important to pay attention not only to estrous cycle in female animals but also when animals were fed compared to the time point of the experiments. Concluding from our results, the sex differences in the incidence of anxiety disorders in humans could be GC‐C dependent.
Impact of near‐surface hydraulic gradient on the interrill erosion process
Authors: Wang Chenfeng , Wang Bin , Wang Yunqi , Wang Yujie , Zhang Wenlong , Yan Yuke
Published: October 2019

The impact of near‐surface hydraulic gradients on interrill erosion is still obscure. The objective of this study is to distinguish the dominant interrill erosion process in areas impacted by near‐surface hydraulic gradients. A series of rainfall simulations were conducted on a clay loam soil subjected to near‐surface hydraulic gradients that shifted from drainage/saturation conditions to seepage conditions under three rainfall intensities (30, 60 and 90 mm hr−1) and two slope gradients (5° and 10°). The results showed significant differences in soil loss between all the treatments. The sediment concentrations for seepage conditions were 0.57 to 7.02 times greater than those for drainage conditions. The correlation analysis indicated that the near‐surface hydraulic gradient was a governing factor affecting interrill erosion. The critical flow rate was larger than 90 mm hr−1, suggesting that thin sheet flow does not have sufficient power to detach soil particles without raindrop impact. Furthermore, the detachment rates by raindrop impact were 1.12 to 4.60 times greater for seepage conditions than for drainage conditions. As the near‐surface hydraulic gradient shifted from drainage conditions to seepage conditions, it transitioned from transport‐limited to detachment‐limited, and the contribution of interrill erosion to overall erosion increased from 20.19 to 75.30%. The critical point of dominant interrill erosion process transition existed between saturation (SA) and artesian seepage in 20 cm of hydrostatic pressure head (SP20). The results emphasize the importance of the near‐surface hydraulic gradients’ impact on the interrill erosion process. Further investigations need to be verified in different soil types, steeper slopes and natural storms.

Highlights

The impact of near‐surface hydraulic gradients on interrill erosion is only partially understood.

Dominant interrill erosion processes are identified under near‐surface hydraulic gradients.

The critical point of dominant interrill erosion process transition exists between SA and SP20.

The dominant erosion process varied as a function of near‐surface hydraulic gradients.