bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of DNMT3b gene variants with sporadic Parkinson's disease in a Chinese Han population
Authors: Chen Xiang , Xiao Yousheng , Wei Lei , Wu Yijuan , Lu Jianjun , Guo Wenyuan , Huang Shuxuan , Zhou Miaomiao , Mo Mingshu , Li Zhe , Cen Luan , Li Shaomin , Yang Chaohao , Wu Zhuohua , Hu Sophie , Pei Zhong , Yang XinLing , Qu Shaogang , Xu Pingyi
Published: October 2017

Background

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Epigenetic modifications, specifically DNA methylation, have been implicated in the development of this disease. Genetic variants of DNA methyltransferase 3b (DNMT3b), one of the most important DNA methyltransferases, were shown to be associated with PD in a Brazilian population. However, it is unclear whether genetic variants of DNMT3b increase the risk of PD in the Chinese Han people. The present study aimed to investigate the association of the DNMT3b variants rs2424913, rs998382 and rs2424932 with PD in a Chinese Han population.

Methods

We studied 487 Chinese Han patients with sporadic PD and 485 healthy age‐, sex‐ and ethnicity‐matched controls. DNA was extracted from peripheral blood leukocytes and the individual genotypes were determined using the SNaPshot method.

Results

We found that the rs2424932 and rs998382 variants were significantly associated with an increased risk of PD compared to the controls [rs2424932: odds ratio (OR) = 1.632, 95% confidence interval (CI) = 1.108–2.406, p = 0.013; rs998382: OR = 1.612, 95% CI = 1.103–2.382, p = 0.014]. Subgroup analysis suggested that female patients carrying the rs2424932 or rs998382 variants were more likely to develop PD than female controls (rs2424932: OR = 3.863, 95% CI = 2.004–7.445, p < 0.001; rs998382: OR = 3.679, 95% CI = 1.943–6.964, p < 0.001). Haplotype analysis indicated that the three variants comprised one block and that the Trs2424913‐Crs998382‐A rs2424932 haplotype was correlated with an increased risk of PD (p = 0.0046), especially for Chinese Han females (p < 0.0001).

Conclusions

The results of the present study strongly suggest that DNMT3b variants are associated with PD in the Chinese Han people, especially females.
Does Social Spending Improve Welfare in Low‐income and Middle‐income Countries?
Authors: Haile Fiseha , Niño‐Zarazúa Miguel
Published: October 2017

Over the past two decades, there has been unprecedented attention to the promotion of human development via government spending in the social sectors as a conditio sine qua non for economic growth and improved aggregate welfare. Yet the existing evidence on the subject remains limited and contested. This paper contributes to the literature by examining the causal effect of government spending on the social sectors (health, education and social protection) on three measures of aggregate welfare: the Human Development Index, the Inequality‐adjusted Human Development Index and child mortality rates, using longitudinal data from 55 low‐income and middle‐income countries from 1990 to 2009. We find strong evidence to support the proposition that government social spending has played a significant role in improving aggregate welfare in the developing world. Our results are fairly robust to, inter alia, the method of estimation, the set of control variables and the use of alternative samples and instruments. © 2017 UNU‐WIDER. Journal of International Development published by John Wiley & Sons, Ltd.
Baseline NS5A resistance associated substitutions may impair DAA response in real‐world hepatitis C patients
Authors: Carrasco Itzíar , Arias Ana , Benítez‐Gutiérrez Laura , Lledó Gemma , Requena Silvia , Cuesta Miriam , Cuervas‐Mons Valentín , de Mendoza Carmen
Published: October 2017

Oral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance‐associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real‐life setting. All hepatitis C patients treated with DAA including NS5A inhibitors at our institution were retrospectively examined. The virus NS5A gene was analyzed using population sequencing at baseline and after 24 weeks of completing therapy in all patients that failed. All changes recorded at positions 28, 29, 30, 31, 32, 58, 62, 92, and 93 were considered. A total of 166 patients were analyzed. HCV genotypes were as follows: G1a (31.9%), G1b (48.2%), G3 (10.2%), and G4 (9.6%). Overall, 69 (41.6%) patients were coinfected with HIV and 46.7% had advanced liver fibrosis (Metavir F3‐F4). Sixty (36.1%) patients had at least one RAS at baseline, including M28A/G/T (5), Q30X (12), L31I/F/M/V (6), T58P/S (25), Q/E62D (1), A92 K (7), and Y93C/H (15). Overall, 4.8% had two or more RAS, being more frequent in G4 (12.5%) followed by G1b (6.3%) and G1a (1.9%). Of 10 (6%) patients that failed DAA therapy, five had baseline NS5A RAS. No association was found for specific baseline RAS, although changes at position 30 were more frequent in failures than cures (22.2% vs 6.4%, P = 0.074). Moreover, the presence of two or more RAS at baseline was more frequent in failures (HR: 7.2; P = 0.029). Upon failure, six patients showed emerging RAS, including Q30C/H/R (3), L31M (1), and Y93C/H (2). Baseline NS5A RAS are frequently seen in DAA‐naïve HCV patients. Two or more baseline NS5A RAS were found in nearly 5% and were significantly associated to DAA failure. Therefore, baseline NS5A testing should be considered when HCV treatment is planned with NS5A inhibitors.
Updating the research on the chemopreventive and therapeutic role of the peptide lunasin
Authors: Hsieh Chia‐Chien , Martínez‐Villaluenga Cristina , de Lumen Ben O , Hernández‐Ledesma Blanca
Published: October 2017

Chronic diseases have become the medical challenge of the 21st century because of their high incidence and mortality rates. Modulation of diet and lifestyle habits is considered as the best strategy for the prevention of these disorders. Health promoting benefits beyond their nutritional effects have been described for multiple dietary compounds. Among these compounds, the peptide lunasin is considered as one of the most promising. Naturally present in soybean, lunasin has been extensively studied in the last two decades because of its potential against chronic diseases such as cancer, cardiovascular and immunological disorders. The purpose of this article is to summarise the evidence on the presence of lunasin in soybean and derived foods, and its bioavailability once it is orally ingested. The protective and therapeutic effects of this peptide against cancer, oxidative stress, inflammation, and high cholesterol levels as well as the molecular mechanisms of action involved in these effects are also described in this review. © 2017 Society of Chemical Industry
Effects of late‐stage nitrogen fertilizer application on the starch structure and cooking quality of rice
Authors: Cao XianMei , Sun HuiYan , Wang ChunGe , Ren XiaoJia , Liu HongFei , Zhang ZuJian
Published: October 2017

BACKGROUND

With the rapid development of modern agriculture, high‐quality rice production and consumption has become the current urgent demand for the development of rice production. In this paper, the effects of late‐stage nitrogen fertilizer application on rice quality were studied under the same genetic background. Wx near‐isogenic lines were used as test materials to study the starch composition, amylopectin structure and cooking quality of rice.

RESULTS

Results showed that rice amylose content and gel consistency significantly differed when different Wx genes were tranformed into waxy rice. The law of apparent amylose content in rice is Wxa > Wxin > Wxb > wx at the same nitrogen level, while the trend of gel consistency was opposite to that of apparent amylose content, presenting obvious characteristics of Indica and Japonica varieties. As the amount of fertilizer application increased, apparent amylose content increased, gel consistency decreased, breakdown and peak viscosities dropped and setback viscosity and peak time increased. Moreover, the cooking quality of rice significantly decreased with the use of nitrogen fertilizer, especially under low‐level nitrogen fertilizer application. Amylopectin structure varied significantly in different genotypes of the Wx gene, and the degree of branching was as follows: wx > Wxb > Wxin > Wxa. This result indicated that the closer to Indica rice, the fewer short chains of amylopectin. Starch crystallinity and swelling potential were negatively correlated with amylose content but significantly positively correlated with amylopectin branching degree, decreasing with the increase of late‐stage nitrogen fertilization.

CONCLUSION

Late‐stage nitrogen fertilization reduced the cooking quality of rice by increasing amylose content and reducing amylopectin branching degree, which decreased starch crystallinity and aggravated pasting properties. Obviously, controlling late nitrogen application is essential to optimize rice quality. © 2017 Society of Chemical Industry
Protective effects of dietary polyphenols from black soybean seed coats on islet and renal function in streptozotocin‐induced diabetic rats
Authors: Qiu Ju , Zhu Hong , Liu Peng , Wang Jing , Lu Lingang
Published: October 2017

BACKGROUND

The aim of this study was to investigate the antidiabetic effects of the crude polyphenol extract (BSCP) from black soybean seed coats (BSC) and the whole flour of BSC and illustrate the mechanism in terms of islet and renal protection.

RESULTS

BSCP and BSC effectively controlled the increased blood glucose level and impaired glucose tolerance in streptozotocin (STZ)‐induced diabetic rats after 8 weeks of treatment. They increased the concentrations of serum insulin, C‐peptide and Glp‐1 (P < 0.05) by improving the STZ‐induced damage of islet β‐cells and increasing their insulin expression (P < 0.05). Lipid profiles and antioxidant activities were also improved. Moreover, BSCP and BSC tended to decrease serum creatinine (0.05 < P < 0.1), and blood urea nitrogen was decreased by BSC significantly (P < 0.05). They also led to significantly lower glomerular volume (P < 0.05).

CONCLUSION

Long‐term intervention with BSC at a low dose of polyphenols plays a role in controlling blood glucose and lipids levels by promoting insulin secretion and restoring islet β‐cell function, the same as BSCP. These benefits are accompanied by their potential protection of diabetic renal dysfunction. BSCP is mainly responsible for the antidiabetic effect of BSC. © 2017 Society of Chemical Industry
Functional Limitations Among Responders to the World Trade Center Attacks 14 Years After the Disaster: Implications of Chronic Posttraumatic Stress Disorder
Authors: Clouston Sean A. P. , Guralnik Jack M. , Kotov Roman , Bromet Evelyn J. , Luft Benjamin J.
Published: October 2017

Posttraumatic stress disorder (PTSD) is associated with self‐reported difficulties navigating the social and physical world and may also be associated with risk of functional limitations. The Short Physical Performance Battery (SPPB), an objective functional assessment, was administered during monitoring exams between January and December 2015 to a consecutive sample of 1,268 rescue workers, volunteers, and other responders who had aided in response, recovery, and cleanup efforts at the World Trade Center (WTC) in New York after the September 11, 2011 attacks. Data were linked with diagnostic and longitudinal data from the WTC monitoring study. Multivariable analyses were used to examine predictors of functional limitations. Prevalence estimates weighted to the general responder population revealed a relatively high prevalence of functional limitations, SPPB ≤ 9; 16.0%, 95% CI [13.7, 18.4]. Current PTSD was associated with a twofold increased risk of functional limitations after controlling for predisposing factors, trauma severity, behavioral factors, and WTC‐related medical conditions, adjusted risk ratio (aRR) = 2.11, 95% CI [1.48, 3.01]. Exposure to ergonomic risk factors at the WTC also increased the risk of functional impairments, aRR = 1.34 95% CI [1.05, 1.70]. Longitudinal results suggest that individuals with current functional limitations experienced high baseline PTSD severity, B = 2.94, SE = 1.33, and increasing PTSD symptom severity, B = 0.29, SE = 0.10, since September 11, 2001. This study identified a cross‐sectional relationship between functional limitations and PTSD and a worsening of PTSD symptoms in persons who eventually demonstrated functional limitations. Results highlight the potential role of chronic PTSD in functional limitations.
Ultrasonic Perfluorohexane‐Loaded Monocyte Imaging: Toward a Minimally Invasive Technique for Selective Detection of Liver Inflammation in Fatty Liver Disease
Authors: Reesink Koen D. , Hendrikx Tim , van Gorp Patrick J. , Hoeks Arnold P. , Shiri‐Sverdlov Ronit
Published: October 2017

Objectives

To investigate the utility of ultrasonic (US) perfluorohexane (PFH)‐loaded monocyte imaging for detection of liver inflammation in fatty liver disease.

Methods

C57Bl6 mice were injected intraperitoneally with tumor necrosis factor α and assessed by US PFH‐loaded monocyte imaging 3 hours later. Echogenic monocytes were injected intravenously, leading to a transient increase in liver tissue intensity on a US perfusion scan. The contrast wash‐out time constant was hypothesized to reflect the degree of inflammation. Next, we evaluated US PFH‐loaded monocyte imaging in Ldlr−/− mice fed a 1‐week high‐fat/high‐cholesterol diet as model for early developing nonalcoholic steatohepatitis. Adjunct analyses included tissue markers of liver inflammation.

Results

Tumor necrosis factor α–injected mice showed a reduced wash‐out time constant (mean ± SEM, 0.013 ± 0.003; n = 8) compared to controls (0.054 ± 0.009; n = 7; P = .0006), indicative of increased inflammatory adhesion molecule expression on the endothelium. The Ldlr−/− mice fed the high‐fat/high‐cholesterol diet showed liver inflammation, as reflected by increased (3‐ to 4‐fold) infiltration of inflammatory cells and increased (3‐ to 4‐fold) gene expression of tumor necrosis factor α, integrin αM, intracellular adhesion molecule, and vascular cell adhesion molecule. However, in these mice, no difference was detected in the wash‐out time constant as assessed by US PFH‐loaded monocyte imaging (high‐fat/high‐cholesterol, 0.050 ± 0.017; n = 5; chow, 0.048 ± 0.006; n = 6; P = .91).

Conclusions

Our results indicate that US PFH‐loaded monocyte imaging is able to detect vascularly expressed inflammatory adhesion molecules in the mouse liver on direct endothelial stimulation. However, in our mouse model of early developing nonalcoholic steatohepatitis, we did not detect inflammation by this method, which may suggest that the time‐dependent relationship between parenchymal and endothelial inflammation remains a fundamental issue to be addressed.
Round window plugging in the treatment of superior semicircular canal dehiscence
Authors: Succar Eric F. , Manickam Periakaruppan V. , Wing Sara , Walter Jeffrey , Greene Joseph S. , Azeredo William J.
Published: October 2017

Objectives/Hypothesis

Objectives were to describe the use of round window plugging for superior semicircular canal dehiscence syndrome and review further recommendations regarding the procedure based on our experience and to compare results with recent literature on round window plugging.

Study Design

Retrospective case series.

Methods

Fourteen patients underwent round window plugging for superior semicircular canal dehiscence at our institution from 2012 to 2015. All patients underwent the same surgical procedure. Available pre‐ and postoperative data were reviewed.

Results

Fourteen patient charts were reviewed. Symptoms of autophony improved in nine of 14 (64%) patients. Symptoms of pressure‐induced vertigo improved in seven of 12 (58%) patients. Hennebert's sign that was positive preoperatively only improved in one of six (17%) patients. A positive preoperative vestibular evoked myogenic potential improved in only one of six (17%) patients. Six of 13 (46%) patients had increased air conduction thresholds postoperatively.

Conclusions

Round window plugging has been described as a less‐invasive treatment for patients with superior semicircular canal dehiscence. Although the procedure did benefit some of our patients, successful outcomes were not predictable. Improvement in at least one objective finding was seen in only 21% of the patients studied. Hennebert's sign and vestibular evoked myogenic potentials that were positive preoperatively only improved in 17% of patients. At our institution, round window plugging is no longer considered a reasonable treatment option for most patients with superior semicircular canal dehiscence. We recommend that further study on this topic follow a standardized pre‐ and postoperative assessment.

Level of Evidence

4. Laryngoscope, 128:1445–1452, 2018
Adaptation and validation of the Spanish version of the Tonsil and Adenoid Health Status Instrument
Authors: Samara Laura , Esteller Eduard , Dura Maria J. , Guirao Miquel , Cardesin Alda , Stewart Michael , Larrosa Francisco
Published: October 2017

Objectives/Hypothesis

The Tonsil and Adenoid Health Status Instrument (TAHSI) is a disease‐specific questionnaire, intended for completion by parents, for assessing quality of life related to tonsil and adenoid disease or its treatment in children with throat disorders. The aim of this study was to validate the Spanish adaptation of the TAHSI, thus allowing comparison across studies and international multicenter projects.

Study Design

Multicenter prospective instrument validation study.

Methods

Guidelines for the cross‐cultural adaptation process from the original English‐language scale into a Spanish‐language version were followed. The psychometric properties (reproducibility, reliability, validity, responsiveness) of the Spanish version of the TAHSI (s‐TAHSI) were assessed in 51 consecutive children undergoing adeno/tonsillectomy (both before and 6 months after surgery) and a separate cohort of 50 unaffected children of comparable age range.

Results

Test‐retest reliability (γ = 0.8) and internal consistency reliability (α = 0.95) were adequate. The s‐TAHSI demonstrated satisfactory content validity (r > 0.40). The instrument showed excellent between‐groups discrimination (P < .0001) and high responsiveness to change (effect size = 2.09).

Conclusions

Psychometric testing of the s‐TAHSI yielded satisfactory results, thus allowing assessment of the subjective severity of throat disorders in children.

Level of Evidence

2c. Laryngoscope, 128:1469–1475, 2018
The radioanatomy of endonasal flap coverage of skull base defects: A tool for preoperative planning
Authors: MacArthur Francisco J. D. , McGarry Gerald W.
Published: October 2017

Objectives/Hypothesis

To develop a tool for the calculation of surgical skull base defects and endonasal flap dimensions on preoperative computed tomography (CT) to aid surgical planning.

Study Design

Case series.

Methods

A literature search was conducted to identify all endonasal flaps. There were five basic models identified. These are the nasoseptal flap, anterior lateral nasal wall flap, bipedicled anterior septal flap, posterior pedicled inferior turbinate flap, and middle turbinate flap. Publications on the radioanatomy of endonasal flaps and surgical skull base defects were also identified. Using these descriptions as a reference, 38 radioanatomic variables were measured on CT scans obtained from 60 preoperative endonasal skull base surgery patients. These were then used to model endonasal flap coverage of six defects: transfrontal, transcribriform, transplanar, transsellar, transsphenoidal, and transclival.

Results

The nasoseptal provides adequate coverage for most defects. The posteriorly pedicled inferior turbinate flap is a good alternative, and provides better coverage of posterior skull base defects. The anterior lateral nasal wall flap is the best choice for transfrontal defects. The middle turbinate flap and bipedicled anterior septal flaps provide secondary options when larger flaps are not available.

Conclusions

We have developed a simple tool for the calculation of endonasal flap coverage of surgical skull base defects on preoperative CT scans.

Level of Evidence

4. Laryngoscope, 128:1287–1293, 2018
Second tympanostomy tube placement in children with recurrent acute otitis media
Authors: Huyett Phillip , Sturm Joshua J. , Shaffer Amber D. , Kitsko Dennis J. , Chi David H.
Published: October 2017

Objectives/Hypothesis

To determine the rate and predictors of electing for a second bilateral myringotomy and tympanostomy tube placement (BMT) in children with recurrent acute otitis media (RAOM).

Study Design

Retrospective chart review.

Methods

Charts of 600 children who underwent BMT for RAOM between 2012 and 2014 were reviewed.

Results

The overall rate of a second BMT was 15.2% (91/600) and occurred a median of 1.58 years after the initial BMT. The most common indication was continued RAOM with extruded tubes. There was a higher rate of second BMT in patients of younger age (1.06 vs. 1.32 years old, P < .001) and those with a positive family history of RAOM/BMT in a first‐degree relative (odds ratio [OR]: 1.67, 95% confidence interval [CI]: 1.02‐2.73, P = .041). Identification of middle ear fluid intraoperatively (OR: 1.99, 95% CI: 1.22‐3.26, P = .005) but not preoperatively (OR: 1.88, 95% CI: 0.98‐3.57, P = .051) was associated with higher rates of second BMT. Children with bilateral intraoperative fluid (OR: 2.25, 95% CI: 1.42‐3.58, P < .001) or fluid both preoperatively and intraoperatively (OR: 2.25, 95% CI: 1.40‐3.61, P = .001) had greater higher risk of requiring second BMT. In this series, the finding of blocked tubes or tube otorrhea at the first postoperative visit were not predictive of an increased risk of second BMT.

Conclusions

Children who underwent BMT for RAOM were more likely to undergo second BMT if they were of younger age, had a family history of RAOM/BMT, or were found to have middle ear fluid intraoperatively. The overall second BMT rate for children with RAOM is lower than in studies examining all BMT indications.

Level of Evidence

4. Laryngoscope, 128:1476–1479, 2018
The futility of intraoperative frozen section in the evaluation of follicular thyroid lesions
Authors: Bollig Craig A. , Lesko David , Gilley David , Dooley Laura M.
Published: October 2017

Objective

Investigate the utility of intraoperative frozen section (iFS) in patients with follicular thyroid lesions following publication of the 2015 American Thyroid Association (ATA) guidelines.

Study Design

Retrospective chart review.

Methods

Patient demographics, preoperative cytology, frozen pathology, and final pathology were reviewed on patients undergoing thyroid surgery at a tertiary care hospital in which iFS was utilized over a 5‐year period. The test performance of iFS and the frequency of indicated completion/total thyroidectomies pre‐ and postpublication of the 2015 ATA guidelines were calculated.

Results

One hundred and one patients met inclusion criteria: 54 patients with follicular lesions of undetermined significance (FLUS) and 47 patients with a cytologic diagnosis of suspicious for follicular neoplasm/follicular neoplasm. The malignancy rate was 36%, but only 14% of malignancies were identified on iFS. A definitive benign or malignant diagnosis was given on iFS in only 21% of cases, and operative management was altered in two cases as a result of iFS. There was a statistically significant reduction in the frequency of indicated total/completion thyroidectomies based on high‐risk features as a result of the 2015 ATA guidelines compared to prior recommendations (20.8% vs. 5.0%, P = < 0.001). None of these patients had findings on iFS that would have altered management intraoperatively.

Conclusion

Intraoperative frozen section offers minimal diagnostic utility in the evaluation of follicular thyroid lesions. Updates in the 2015 ATA guidelines further diminish its potential to impact management intraoperatively. Significant improvements in its ability to identify malignancies would be needed to justify its use.

Level of Evidence

4. Laryngoscope, 128:1501–1505, 2018
Impact of medialization laryngoplasty on dynamic nanomechanical vocal fold structure properties
Authors: Dion Gregory R. , Benedict Peter A. , Coelho Paulo G. , Amin Milan R. , Branski Ryan C.
Published: October 2017

Objectives/Hypothesis

Although the primary goal of medialization laryngoplasty is to improve glottic closure, implant placement is also likely to alter the biomechanical properties of the vocal fold (VF). We sought to employ novel, nanoscale technology to quantify these properties following medialization based on the hypothesis that different medialization materials will likely yield differential biomechanical effects.

Study Design

Ex vivo.

Methods

Nine pig larynges were divided into three groups: control, Silastic (Dow Corning, Midland, Michigan, U.S.A.) block medialization, or Gore‐Tex (W.L. Gore & Associates, Newark, Delaware) medialization. Laryngoplasty was performed on excised, intact larynges. The larynges were then bisected in the sagittal plane and each subjected to dynamic nanomechanical analysis (nano‐DMA) at nine locations using a 250‐μm flat‐tip punch and frequency sweep‐load profile across the free edge of the VF and inferiorly along the conus elasticus.

Results

Silastic block and Gore‐Tex implant introduced increased storage and loss moduli. Overall, storage moduli mean (maximum) increased from 38 kilopascals (kPa) (119) to 72 kPa (422) and 129 kPa (978) in control, Gore‐Tex, and Silastic implants, respectively. Similarly, loss moduli increased from 13 kPa (43) to 22 kPa (201) and 31 kPa (165), respectively. Moduli values varied widely by location in the Silastic block and Gore‐Tex groups. At the free VF edge, mean (maximum) storage moduli were lowest in the Gore‐Tex group, 20 kPa (44); compared to control, 34.5 kPa (86); and Silastic, 157.9 kPa (978), with similar loss and complex moduli trends.

Conclusion

Medialization laryngoplasty altered VF structure biomechanical properties; Silastic and Gore‐Tex implants differentially impact these properties.

Level of Evidence

NA. Laryngoscope, 128:1163–1169, 2018
Low and variable ecosystem calcification in a coral reef lagoon under natural acidification
Authors: Shamberger Kathryn E. F. , Lentz Steven J. , Cohen Anne L.
Published: October 2017

Laboratory‐based CO2 experiments and studies of naturally low pH coral reef ecosystems reveal negative impacts of ocean acidification on the calcifying communities that build coral reefs. Conversely, in Palau's low pH lagoons, coral cover is high, coral communities are diverse, and calcification rates of two reef‐building corals exhibit no apparent sensitivity to the strong natural gradient in pH and aragonite saturation state (Ωar). We developed two methods to quantify rates of Net Ecosystem Calcification (NEC), the ecosystem‐level balance between calcification and dissolution, in Risong Lagoon, where average daily pH is ∼ 7.9 and Ωar ∼ 2.7. While coral cover in the lagoon is within the range of other Pacific reefs (∼ 26%), NEC rates were among the lowest measured, averaging 25.9 ± 13.7 mmol m−2 d−1 over two 4 d study periods. NEC rates were highly variable, ranging from a low of 13.7 mmol m−2 d−1 in March 2012 to a high of 40.3 mmol m−2 d−1 in November 2013, despite no significant changes in temperature, salinity, inorganic nutrients, Ωar, or pH. Our results indicate that the coral reef community of Risong Lagoon produces just enough calcium carbonate to maintain net positive calcification but comes dangerously close to net zero or negative NEC (net dissolution). Identifying the factors responsible for low NEC rates as well as the drivers of NEC variability in naturally low pH reef systems are key to predicting their futures under 21st century climate change.
Network Polydispersity and Deformation‐Induced Damage in Filled Elastomers
Authors: Tehrani Mohammad , Moshaei Mohammad Hossein , Sarvestani Alireza S.
Published: October 2017

An a priori assumption in micromechanical analysis of polymeric networks is that the constitutive polymer strands are of equal length. Monodisperse distribution of strands, however, is merely a simplifying assumption. This paper relaxes this assumption and considers a vulcanized network with a broad distribution of strand length. In the light of this model, this study predicts the damage initiation and stress–stretch dependency in filled polymer networks with random internal structures. The degradation of network mechanical behavior is assumed to be controlled by the adhesive failure of the strands adsorbed to the filler surface. This study shows that the short adsorbed strands are the culprits for damage initiation and their finite extensibility is a key determinant of the mechanical strength.
Failure of Sequential Pallidal and Motor Thalamus DBS for Rapid‐Onset Dystonia‐Parkinsonism (DYT12)
Authors: Fearon Conor , McKinley John , McCarthy Allan , Rebelo Pedro , Goggin Carole , Magennis Brian , Aziz Tipu , Green Alexander L. , Lynch Timothy
Published: October 2017

View Supplementary Video 1
Comprehensive analysis of mutations in the MEFV gene reveal that the location and not the substitution type determines symptom severity in FMF
Authors: Moradian Mike M. , Babikyan Davit , Banoian Dion , Hayrapetyan Hasmik , Manvelyan Hakob , Avanesian Nareh , Sarkisian Tamara
Published: October 2017

Background

Familial Mediterranean Fever (FMF) is an autoinflammatory disorder caused by mutations in the MEFV gene. These mutations appear in different populations with different frequencies and their caused symptom severities vary from mild to moderate to severe depending on the mutation type.

Methods

In this study, we analyzed the mutations that have been reported in the MEFV gene from symptomatic FMF patients and compared their frequencies in different populations from the 1000 Genome and the Exome databases, using statistical clustering. We also analyzed the nucleotide and amino acid substitution patterns across the MEFV gene.

Results

We found 16 (8%) nonsynonymous mutations outside exon 10 that did not cluster with known disease‐causing mutations (DCMs), due to their high frequencies in other populations. We also studied the substitution patterns for nucleotides and amino acids to determine the conserved and variable regions in the MEFV gene. In general more nonsynonymous substitutions were reported in exons 2, 3, and 10 from the FMF database (symptomatic FMF patients) compared to the 1000 Genome and the Exome databases. The same was true for amino acid (AA) substitutions where there were 1.5 times more radical (RAD) to conservative (CON) changes. However, when it came to AA substitutions exon 10 was quite conserved with a RAD/CON ratio of 0.9. In fact, we report that the most severe FMF symptoms are caused by conservative mutations in two highly conserved exon 10 regions.

Conclusion

We found presumptive FMF‐causing mutations that did not cluster with DCMs based on their allele frequencies. We also observed that the type of mutation is less likely to determine the severity of the FMF symptoms; rather it was the location of the mutations that was the determining factor.
Developing a protocol for normothermic ex‐situ limb perfusion
Authors: Duraes Eliana F. R. , Madajka Maria , Frautschi Russell , Soliman Basem , Cakmakoglu Cagri , Barnett Addison , Tadisina Kashyap , Liu Qiang , Grady Patrick , Quintini Cristiano , Okamoto Toshihiro , Papay Francis , Rampazzo Antonio , Bassiri Gharb Bahar
Published: October 2017

Background

Ischemia time represents a significant limitation for successful extremity transplantation because of the rapid deterioration of ischemic muscle. Normothermic ex‐situ preservation is an emergent method to prolong the organ viability following procurement, by replicating the physiologic conditions. The aim of this study was to develop an ex‐situ normothermic limb perfusion system to preserve the viability and function of porcine limbs for 12 hours following procurement.

Methods

A total of 18 swine limbs were perfused. Thirteen limbs were used to develop the perfusion protocol. Five limbs were perfused according to the optimized protocol. These limbs were perfused at 39°C for twelve hours using an oxygenated colloid solution containing red blood cells. Glucose and electrolytes were kept within physiologic range by partial perfusate exchange. Limb specific perfusion quality was assessed by muscle contractility upon electrical nerve stimulation, compartment pressure, creatine kinase (CK) and myoglobin concentrations, tissue oxygen saturation (near infrared spectroscopy), indocyanine green angiography, and infrared radiation by thermographic imaging.

Results

The last five limbs reached the 12 hours' perfusion target maintaining normal compartment pressure (16.4  ± 8.20 mmHg), minimal weight increase (0.54 ± 7.35%), and mean muscle temperature of 33.6 ± 1.67°C. Myoglobin and CK concentrations were 875 ± 291.4 ng/mL, and 53344 ± 14850.34 U/L, respectively, at the end of perfusion. Muscle contraction was present in all limbs until cessation of perfusion. Differences in uniformity and quality of distal perfusion were identified with thermography and angiography imaging at 12 hours of perfusion.

Conclusions

Ex‐situ normothermic limb perfusion preserves swine limb physiology and function for at least 12 hours.
Functional results of free tissue transfer for complex heel‐calcaneal defects
Authors: Chou Chang‐Yi , Chiao Hao‐Yu , Wang Chi‐Yu , Sun Yu‐Shan , Lin Chin‐Ta , Dai Niann‐Tzyy , Chen Shyi‐Gen , Chang Shun‐Cheng
Published: October 2017

Background

Loss of soft tissue in heel‐calcaneal region is frequently caused by trauma, infection, or tumors. Limited availability of similar tissue becomes challenging, therefore, the use of free tissue transfer offers a solution. Our aim is to describe long term functional outcome of different free tissue transfers for these defects.

Patients and methods

We retrospectively reviewed 24 consecutive cases of the heel‐calcaneal defect between January 2009 and December 2014. The free fasciocutaneous perforator (FCP) flaps were performed in 14 cases and free muscle flaps with skin graft in 10 cases. The postoperative complications, range of motion and ability of ambulation or exercise were administered to evaluate functional results.

Results

The average follow‐up period was 26.5 months. The survival of free flap was 100%. Early complication included venous thrombosis, infection and edge dehiscence was noted in 8 cases. Late complication with insensate ulcers developed in 3 cases (1 cases in FCP flap, 2 cases in muscle flap). All ulcers healed spontaneously without surgical intervention. The postoperative average range of motion of ankle regained 52.79 degree in FCP flap group and 56.4 degree in muscle flap group. The ability of ambulation or exercise returned in 13 cases in FCP group (13/14) and 9 cases in muscle flap group (9/10). No differences of complication rate (P = .403), ROM (P = .363) or functional evaluation (P = .803) could be found between these two groups.

Conclusions

Both FCP flap and muscle flaps provided the similar and excellent functional results in resurfacing of heel‐calcaneal defects after long term follow up.
Limb‐sparing sarcoma reconstruction with functional composite thigh flaps
Authors: Stranix John T. , Lee Z‐Hye , Lam Gretl , Mirrer Joshua , Rapp Timothy , Saadeh Pierre B.
Published: October 2017

Introduction

Innervated muscle transfer can improve functional outcomes after extensive limb‐sparing sarcoma resections. We report our experience using composite thigh flaps for functional reconstruction of large oncologic extremity defects.

Patients and methods

Between 2011 and 2014, four limb‐sparing oncologic resections (3 lower extremities, 1 upper extremity) underwent immediate functional reconstruction with composite thigh free flaps in three males and one female. The age of the patients ranged from 36 to 73 years. There were 3 soft‐tissue sarcomas and one giant cell tumor, all required resection of entire muscle compartments. Flap components included fasciocutaneous tissue with sensory nerve, plicated iliotibial band (ITB), and variable amounts of motorized vastus lateralis (VL).

Results

All flaps survived without complications. All patients showed VL motor innervation by six months. Follow‐up ranged from 20 to 36 months. Motor strength ranged from 2 to 5 out of 5, active range of motion was 25–92% of normal, and Musculoskeletal Tumor Society (MSTS) Scores were between 22 and 29 out of 30.

Conclusions

Limb‐sparing techniques for upper and lower extremity sarcomas continue to evolve. Our experience has validated the composite thigh free flap as an excellent option for one‐stage functional reconstruction of large limb defects.
Is adjustment disorder unidimensional or multidimensional? Implications for ICD‐11
Authors: Lorenz Louisa , Hyland Philip , Perkonigg Axel , Maercker Andreas
Published: October 2017

In preparation for ICD‐11, the adjustment disorder (AjD) diagnosis has undergone considerable revisions; however, the latent structure of AjD remains uncertain. It is unclear whether AjD is best represented as a unidimensional or multidimensional construct. This study performed a comprehensive assessment of the latent structure of AjD symptomatology and assessed its concurrent and discriminant validity. Individuals who experienced involuntary job loss (N = 333) completed a self‐report measure of AjD symptoms. Seven alternative models of AjD were tested using confirmatory factor analysis. General psychological distress, impairment in social functioning, occupational self‐efficacy, and sense of coherence were used as criterion variables for construct validity. In the confirmatory factor analysis, a bifactor solution with one dominant general AjD factor and 5 correlated group factors (preoccupation, failure‐to‐adapt, avoidance, affective reaction, and impulsivity) provided optimal fit. As expected, the AjD factor showed strong positive associations with general psychological distress and impairments in social functioning and moderately negative associations with occupational self‐efficacy and sense of coherence. With regard to unidimensionality or multidimensionality of AjD symptoms, the current results indicate the plausibility of a unidimensional conceptualization. Future research should focus on essential key characteristics and a reduction of symptoms for the AjD definition.
Measuring the hierarchical general factor model of psychopathology in young adults
Authors: Lahey Benjamin B. , Zald David H. , Perkins Scott F. , Villalta‐Gil Victoria , Werts Katherine B. , Van Hulle Carol A. , Rathouz Paul J. , Applegate Brooks , Class Quetzal A. , Poore Holly E. , Watts Ashley L. , Waldman Irwin D.
Published: October 2017

There is evidence that models of psychopathology specifying a general factor and specific second‐order factors fit better than competing structural models. Nonetheless, additional tests are needed to examine the generality and boundaries of the general factor model. In a selected second wave of a cohort study, first‐order dimensions of psychopathology symptoms in 499 23‐ to 31‐year‐old twins were analyzed. Using confirmatory factor analysis, a bifactor model specifying a general factor and specific internalizing and externalizing factors fit better than competing models. Factor loadings in this model were sex invariant despite greater variances in the specific internalizing factor among females and greater variances in the general and specific externalizing factors among males. The bifactor structure was robust to the exclusion of any single first‐order dimension of psychopathology. Furthermore, the results were essentially unchanged when all overlapping symptoms that define multiple disorders were excluded from symptom dimensions. Furthermore, the best‐fitting bifactor model also emerged in exploratory structural equation modeling with freely estimated cross‐loadings. The general factor of psychopathology was robust across variations in measurement and analysis.
A Monte Carlo Method to Quantify the Effect of Reactor Residence Time Distribution on Polyolefins Made with Heterogeneous Catalysts: Part I—Catalyst/Polymer Particle Size Distribution Effects
Authors: Soares João B. P. , Romero Jazmín
Published: October 2017

Polyolefins are commercially produced in continuous reactors that have a broad residence time distribution (RTD). Most of these polymers are made with heterogeneous catalysts that also have a particle size distribution (PSD). These are totally segregated systems, in which the catalyst/polymer particle can be seen as a microreactor operated in semibatch mode, where the reagents (olefins, hydrogen, etc.) are fed continuously to the catalyst/polymer particle, but no polymer particle can leave. The reactor RTD has a large influence on the PSD of the polymer particles leaving the reactor, as well as in polymer microstructure and properties, polymerization yield, and composition of reactor blends. This article proposes a Monte Carlo model that can describe how particle RTD in a single or a series of reactors can affect the PSD of polymer particles made under a variety of operation conditions. It is believed that this is the most flexible model ever proposed to model this phenomenon, and can be easily modified to track all properties of interest during polyolefin production in continuous reactors with heterogeneous catalysts.
MicroRNA‐495‐3p functions as a tumor suppressor by regulating multiple epigenetic modifiers in gastric carcinogenesis
Authors: Eun Jung Woo , Kim Hyung Seok , Shen Qingyu , Yang Hee Doo , Kim Sang Yean , Yoon Jung Hwan , Park Won Sang , Lee Jung Young , Nam Suk Woo
Published: October 2017

MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Here, we demonstrate that microRNA‐495‐3p (miR‐495‐3p) functions as a potent tumor suppressor by governing ten oncogenic epigenetic modifiers (EMs) in gastric carcinogenesis. From the large cohort transcriptome datasets of gastric cancer (GC) patients available from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we were able to recapitulate 15 EMs as significantly overexpressed in GC among the 51 EMs that were previously reported to be involved in cancer progression. Computational target prediction yielded miR‐495‐3p, which targets as many as ten of the 15 candidate oncogenic EMs. Ectopic expression of miRNA mimics in GC cells caused miR‐495‐3p to suppress ten EMs, and inhibited tumor cell growth and proliferation via caspase‐dependent and caspase‐independent cell death processing. In addition, in vitro metastasis assays showed that miR‐495‐3p plays a role in the metastatic behavior of GC cells by regulating SLUG, vimentin, and N‐cadherin. Furthermore, treatment of GC cells with 5‐aza‐2'‐deoxcytidine restored miR‐495‐3p expression; sequence analysis revealed hypermethylation of the miR‐495‐3p promoter region in GC cells. A negative regulatory loop is proposed, whereby DNMT1, among ten oncogenic EMs, regulates miR‐495‐3p expression via hypermethylation of the miR‐495‐3p promoter. Our findings suggest that the functional loss or suppression of miR‐495‐3p triggers overexpression of multiple oncogenic EMs, and thereby contributes to malignant transformation and growth of gastric epithelial cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Processing and properties of short wood fiber/acrylate resin composites
Authors: Akpan Emmanuel I. , Wetzel Bernd , Friedrich Klaus
Published: October 2017

Short wood fibers (SWF) and a water based and formaldehyde free cross linking acrylate resin have been used to produce bulk biocomposites, as a possible material for automotive and friction applications. SWFs of 200–400 µm in length were mixed with the resin in various proportions (40–60 wt%) using a kneading device. The mixture was dried in an oven and later cured in a hot press. Two curing cycles were used for this study: (a) curing at a temperature of 150°C and a pressure of 70 bar and (b) curing at 170°C and a pressure of 80 bar. Various morphological features, flexural and thermal properties, density, and specific wear rate under sliding against smooth steel were examined. Results show that increase in fiber weight fraction led to increase in tensile strength when the material was processed with 170°C and a pressure of 80 bar. Composites with 60 wt% SWF processed with 170°C and a pressure of 80 bar exhibited the highest flexural strength (64 MPa) and flexural modulus (7.2 GPa). Composites processed at lower temperature and pressure (150°C and 70 bar) are found to possess inferior mechanical properties compared with those processed at higher temperature and pressure (170°C and 80 bar). This composite also possessed a nearly stable storage modulus up to 50°C. All composites showed specific wear rate between 10−5and 10−6mm3/(Nm) and a very high friction coefficient of μ = 1.25 against smooth steel surfaces. SEM images revealed that there is a very good interfacial adhesion between the fibers and the matrix. POLYM. COMPOS., 40:91–98, 2019. © 2017 Society of Plastics Engineers
Evolution of the strain energy release rate during ductile or brittle failure in woven‐ply reinforced thermoplastic laminates under high temperature conditions
Authors: Vieille B.
Published: October 2017

Depending on laminates’ stacking sequence, the contribution of matrix behavior to the strain energy release rate is evaluated during failure in brittle and ductile composite laminates subjected to high temperature conditions (T > Tg) when matrix toughness is enhanced. The purpose of this work is therefore to investigate the strain energy released along with crack growth in 5‐harness satin weave carbon fabric reinforced polyphenylene sulfide (PPS) structures with a Single Edge Notch. The crack growth appears to be self‐similar in quasi‐isotropic (QI) laminates, and nonself‐similar in angle‐ply (AP) laminates. Based on fracture mechanics concepts, semianalytical representations of the translaminar failure are combined with an Acoustic Emission (AE) technique to correlate the cumulative AE energy to the strain energy release rate. The experimental results reveal that the fracture toughness increases with increasing precrack length in QI laminates, whereas the effect of increase in precrack length exhibits reduced fracture toughness in AP laminates. The energy released during a non‐self‐similar crack growth is all the more significant than the stress concentration factor is reduced. A small defect (e.g., precrack) means a larger portion of the mechanical energy brought to the specimen to be dissipated during failure by means of large plastic deformations. With respect to QI laminates, the contribution of PPS matrix toughness to the fracture energy released is more significant in highly ductile AP laminates, resulting in higher fracture toughness. POLYM. COMPOS., 40:121–131, 2019. © 2017 Society of Plastics Engineers
Proteogenomics Gets onto the Regulation of mRNA Decoding and Translation into Protein
Authors: Hondermarck Hubert
Published: October 2017

Proteogenomics, the integrative analysis of the proteome and the genome, increasingly provides protein‐level insights about the regulation of gene expression and protein translation. Armengaud et al. (Proteomics 2017, 17, 1700211) nicely illustrate this trend with the first in‐depth proteomic analysis of the eukaryotic and unicellular intestinal parasite Blastocystis sp. Not only this work constitutes an important milestone toward the proteogenomics profile of this human pathogen, but also it demonstrates at the protein level the occurrence of a specific mechanism of mRNA decoding. GU‐rich motifs located downstream of mRNA polyadenylation sites create termination codons that ultimately result in the synthesis of proteins with lower molecular weight than predicted from gene sequence. Thus, the scope of proteogenomics now extends to the regulation of mRNA translation into proteins, providing a proof of concept for future studies in multicellular eukaryotes such as humans and plants.