bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeatability of the hyperglycaemic clamp for assessment of β‐cell response and insulin sensitivity in horses
Authors: Lindåse S. , Johansson H. , Månsby M. , Bröjer J.
Published: April 2019

Background

The hyperglycaemic clamp has been used for measurement of insulin sensitivity (IS) but not for measurement of β‐cell response in the horse. However, the repeatability of this test has not been reported for horses.

Objectives

To determine the repeatability and reliability of measures for IS and β‐cell response to glucose using the hyperglycaemic clamp in horses.

Study design

Repeated measures, longitudinal study.

Methods

Six healthy Standardbred mares underwent a 120‐min hyperglycaemic clamp on two occasions with a 10‐day washout period. Indices of repeatability and reliability were calculated from measures of IS and β‐cell response to glucose derived from each hyperglycaemic clamp.

Results

Measures of β‐cell response to glucose, including area under the insulin response curve in the time interval 0–120 min and during steady state (60–120 min), as well as the mean insulin concentration during steady state had coefficient of variations (CV) of 9.5, 10.5 and 9.3 respectively and intraclass correlation coefficients (ICC) of 0.93, 0.93 and 0.95 respectively. The measure of glucose disposal (M) had lower CV (12.4) and ICC (0.71) compared to measure of IS (M/I‐index; CV of 17.4 and ICC of 0.89).

Main limitations

The study was conducted in a small number of horses.

Conclusions

The hyperglycaemic clamp is a diagnostic method for assessing β‐cell response to intravenous glucose with high repeatability and reliability. Insulin sensitivity can be determined with the same test but the repeatability for these measurements is lower compared to the measurements for β‐cell response.
Cooperation between β‐galactosidase and an isoprimeverose‐producing oligoxyloglucan hydrolase is key for xyloglucan degradation in Aspergillus oryzae
Authors: Matsuzawa Tomohiko , Watanabe Masahiro , Kameda Tomoshi , Kameyama Akihiko , Yaoi Katsuro
Published: April 2019

The galactosylation of xyloglucan blocks many of the enzymatic processes targeting this oligosaccharide. We found that the expression of a gene encoding Aspergillus oryzae β‐galactosidase (LacA) is induced in the presence of xyloglucan oligosaccharides. With detailed analyses of the substrate specificity of purified recombinant LacA, we show that LacA cleaves galactopyranosyl residues from xyloglucan oligosaccharides, but not from xyloglucan polysaccharide, and plays a vital role in xyloglucan degradation. LacA acts cooperatively with the isoprimeverose‐producing oligoxyloglucan hydrolase IpeA to hydrolyze xyloglucan oligosaccharides. Galactosylation of the xylopyranosyl side chain at the nonreducing end of oligoxyloglucan saccharides completely abolishes IpeA activity while LacA efficiently removes the galactopyranosyl residue. Conversely, an isoprimeverose unit at the nonreducing end of the main chain of xyloglucan oligosaccharides blocks LacA activity, while IpeA can still remove the isoprimeverose moiety. This is the first study reporting the cooperative action of β‐galactosidase and isoprimeverose‐producing oligoxyloglucan hydrolase on xyloglucan oligosaccharide degradation. Our findings shed light on the true role of LacA and the enzymatic coordination between β‐galactosidase and other hydrolases on xyloglucan degradation.
Structural analyses reveal that MBD3 is a methylated CG binder
Authors: Liu Ke , Lei Ming , Wu Zhibin , Gan Bing , Cheng Harry , Li Yanjun , Min Jinrong
Published: April 2019

The MBD3, a methyl‐CpG‐binding domain (MBD)‐containing protein, is a core subunit of the Mi‐2/NuRD complex. Recent reports show that MBD3 recognizes both methylated CG (mCG)‐ and hydroxymethylated CG (hmCG)‐containing DNA, with a preference for hmCG. However, whether the MBD3‐MBD indeed has methyl‐CG‐binding ability is controversial. In this study, we provided the structural basis to support the ability of MBD3‐MBD to bind mCG‐containing DNA. We found that the MBD3‐MBD bound to mCG‐containing DNA through two conserved arginine fingers, and preferentially bound to mCG over hmCG, similar to other methyl‐CpG‐binding MBD proteins. Compared to its closest homolog MBD2, the tyrosine‐to‐phenylalanine substitution at Phe34 of MBD3 is responsible for a weaker mCG DNA binding ability. Based on the complex structure of MBD3‐MBD with a nonpalindromic AmCGC DNA, we suggest that all the mCG‐binding MBD domains can recognize mCG‐containing DNA without orientation selectivity, consistent with our observations that the sequences outside the mCG dinucleotide do not affect mCG DNA binding significantly. DNA cytosine methylation is evolutionarily conserved in most metazoans, and most invertebrates have only one MBD gene, MBD2/3. We also looked into the mCG DNA binding ability of some invertebrates MBD2/3 and found that the conserved arginine fingers and a conserved structural fold are required for methylated DNA binding by MBD2/3‐MBDs in invertebrates. Hence, our results demonstrate that mCG‐binding arginine fingers embedded into a conserved structural fold are essential structural features for MBD2/3s binding to methylated DNA among metazoans.
The frequency and characteristics of pain and discomfort associated with root filled teeth: a practice‐based study
Authors: Jonsson Sjögren J. , Kvist T. , Eliasson A. ,   EndoReCo, Pigg M.
Published: April 2019

Aim

To (i) investigate the frequency and characteristics of pain and discomfort associated with root filled teeth in adult patients regularly attending the Public Dental Service in Örebro County, Sweden; (ii) assess the association between symptoms and clinical and radiographic findings; and (iii) explore the impact of pain and discomfort from root filled teeth on daily life.

Methodology

Patient records of adult patients (≥20 years) scheduled for routine check‐ups in April 2015 were screened to identify individuals with root filled teeth; all patients with ≥1 root filled tooth were asked to participate. The examination comprised of clinical and radiographic examinations and questionnaires on general health, on pain symptoms from root filled teeth and on the impact of pain on daily activities. In a general estimating equation (GEE), examination findings and patient‐related factors were independently analysed in relation to the outcome ‘presence of pain’.

Results

In total, 550 patients with 1256 root filled teeth participated. Fifty‐three patients (9.6%) experienced pain or discomfort from 62 (4.9%) root filled teeth. Lower age, percussion tenderness and apical tenderness were significantly associated with pain (P > 0.001 to P = 0.044). The average pain intensity was 2.1 on a (0–10) Numeric Rating Scale, and average duration was 28.4 months. The impact on daily life was low.

Conclusions

On average, pain associated with root filled teeth was of mild intensity, >2 years of duration and had low impact on daily life. Although the significantly associated clinical findings may indicate apical periodontitis as the most probable explanation in some teeth, the origin of pain from root filled teeth remains partly unexplained.
Synthesis of Al2O3 coatings on Ti(C, N)‐based cermets by microwave plasma CVD using Al(acac)3
Authors: Tu Rong , Yuan Yang , Guo Litong , Li Jun , Zhang Song , Yang Meijun , Li Qizhong , Zhang Lianmeng , Goto Takashi , Ohmori Hitoshi , Shi Ji , Li Haiwen
Published: April 2019

Aluminum acetylacetonate (Al(acac)3) was used as a precursor to synthesize aluminum oxide (Al2O3) coatings on Ti(C, N)‐based ceramic by microwave plasma CVD (MPCVD). Al2O3 coatings transformed from γ phase to δ phase and α phase and as microwave power (pM) and total pressure (Ptot) increased. The effects of pM and Ptot on the microstructure of the Al2O3 coating and oxidation of the substrate have been investigated. The relationship between phase structure and adhesive strength of the coatings was also studied. Coatings deposited at pM = 1.0‐1.2 kW and Ptot = 400 Pa exhibited good adhesion strength (Class 1).
Study of acrylamide mitigation in model systems and potato crisps: effect of rosmarinic acid
Authors: Yuan Yuan , Qi Mengyuan , Liu Huangyou , Yan Haiyang
Published: April 2019

In the current study, rosmarinic acid (RosA) played a critical role in inhibiting acrylamide (AA) formation in Maillard system and potato chips. Compared to the control group, AA formation was markedly inhibited by RosA of 10−4 and 10−1 mm in asparagine (Asn)‐glucose (Glc) system, and 10−5−1.0 mm in Asn‐fructose (Fru) system. The kinetic study indicated that with heating time ranging from 30 to 60 min, RosA had a significant inhibition effect on AA formation. Mechanism study showed the addition reaction between RosA and AA was the primary pathway to inhibit AA formation. In potato crisps, response surface methodology showed that frying temperature of 140.11 °C, frying time of 6.02 min and RosA concentration of 0.012 μm had the lowest AA formation. In conclusion, RosA inhibited AA formation in both the model systems and potato crisps, and its application in food industry is well expected.
Evolution of functional, thermal and pasting properties of sprouted whole durum wheat flour with sprouting time
Authors: Jribi Sarra , Sahagùn Marta , Debbabi Hajer , Gomez Manuel
Published: April 2019

This research investigated the evolution of functional, pasting and thermal properties of durum wheat (Triticum durum) with sprouting time. Particle size, flour and flour gel hydration properties (Water Holding Capacity (WHC), Swelling Volume (SV), Water Absorption Index (WAI), Water Solubility Index (WSI), Swelling Power (SP)), Oil Absorption Capacity (OAC), Pasting and thermal properties were evaluated on different sprouting time: 12, 24, 36, 48 and 72 h. Results showed that more than 12 h decreased significantly particle size,WHC(−14.8%),SV(−19%),SP(−14%) andWAI(−36.5%) whileWSI(+383%) andOAC(+7.3%) increased. Pasting properties drastically decreased with sprouting time.DSCresults showed a significant increase in onset temperature (T0) (from 55.2 to 58.2 °C), peak temperature (Tp) (from 62.4 to 63.8 °C) while conclusion temperatureTcdecreased (from 76 to 72.6 °C). Despite these changes, sprouted whole wheat flour could be suggested as an improver of some cereal products’ functionality.
Changes in kernel properties, in situ gelatinization, and physicochemical properties of waxy rice with inhibition of starch branching enzyme during cooking
Authors: Pan Ting , Lin Lingshang , Zhang Long , Zhang Changquan , Liu Qiaoquan , Wei Cunxu
Published: April 2019

The kernel properties, gelatinisation and physicochemical properties of rice were investigated in a waxy rice Guang‐ling‐xiang‐nuo (GLXN) and its transgenic line GLXN‐RNAi with inhibition of starch branching enzyme I/IIb. The volume swelling, water content and leached material of cooked kernels increased with increasing cooking time, but they were lower in GLXN‐RNAi than in GLXN. The kernels of GLXN‐RNAi were more difficultly gelatinised and disrupted than those of GLXN during cooking. The starch in the exterior of GLXN‐RNAi endosperm was not completely gelatinised. The CA‐type starch of GLXN‐RNAi was more resistant to cooking than A‐type starch of GLXN. The cooked kernels of GLXN‐RNAi had lower rapidly digestible starch and greater slowly digestible starch than those of GLXN. Brown rice flour had higher peak, hot, final and setback viscosities and lower breakdown viscosity in GLXN than GLXN‐RNAi. These results indicated that GLXN‐RNAi kernels exhibited great potential in applications as health foods.
Revealing the effects of aerosol deposition on the substrate‐film interface using NaCl coating
Authors: Khansur Neamul H. , Eckstein Udo , Li Yizhe , Hall David A. , Kaschta Joachim , Webber Kyle G.
Published: April 2019

Aerosol deposition is a feasible method of fabricating dense ceramic films at room temperature by the impact consolidation of submicron‐sized particles on ceramic, metal, glass, and polymer substrates at a rapid rate. Despite the potential usefulness of the aerosol deposition process, there are issues, such as deposition mechanisms and structure of the film‐substrate interface, that are not well understood. We have used complementary structural and microstructural analysis to capture the state of the substrate surface after the aerosol deposition process. The results reveal that modification of the substrate surface by the ejected submicron‐sized particles is essential for the formation of anchoring layer, thereby, a change in internal residual stress state and surface free energy of the substrate is required to deposit film using AD process. Our analysis also suggests that the adhesion between the metal substrate and ceramic particles is possibly contributed by both physical bonding and mechanical interlocking.
Weakening thermal quenching to enhance luminescence of Er3+ doped β‐NaYF4 nanocrystals via acid‐treatment
Authors: Yang Dandan , Pan Qiwen , Kang Shiliang , Dong Guoping , Qiu Jianrong
Published: April 2019

Rare earth (RE) ions‐doped luminescent nanocrystals (NCs) with numerous unique advantages have attracted tremendous interest for the wide applications from science to engineering, yet suffering from the shortcoming of thermal quenching coming from surface organic ligands. We propose utilizing a facile acid‐base reaction to remove surface organic ligands introduced choosing carboxylic acids as stabilizing agent and weaken thermal quenching. The results showed that the acid‐base reaction displayed an outstanding cleaning effect. After acid‐treatment, most surface organic ligands were removed, and there was no influence on crystal structure and morphology of as‐prepared β‐NaYF4:Er3+ NCs. Meanwhile, with no surface organic ligands capping, β‐NaYF4:Er3+ NCs preferred brighter emission after thermal treatment, including up‐conversion (UC), near‐infrared (NIR), and mid‐infrared (MIR) emission. When calcined the acid‐treated β‐NaYF4:Er3+ NCs in different atmosphere, such as oxygen and reducing atmosphere (15%H2 + 85%N2), an unexpected enhancement of all emission bands in Er3+ was determined under phase transformation temperature, especially in oxygen atmosphere. Furthermore, all the fluorescence lifetimes of Er3+ also exhibited obvious extension. Our results supposed that the β‐NaYF4:Er3+ NCs have promising applications in safety ink, and the acid‐treatment by diluted hydrochloric acid is a general approach to remove deleterious organic ligands on NC surface further to weaken thermal quenching.
A constitutive model for the sintering of suspension plasma‐sprayed thermal barrier coating with vertical cracks
Authors: Lv Bowen , Mücke Robert , Zhou Dapeng , Fan Xueling , Wang Tiejun J. , Guillon Olivier , Vaßen Robert
Published: April 2019

The degradation of mechanical properties due to sintering is one of the major issues during high temperature service of thermal barrier coating system for advanced gas turbines. In this study, a constitutive model was developed by the variational principle, based on the experimentally observed microstructure features of suspension plasma‐sprayed thermal barrier coatings. The constitutive model was further implemented in finite element analysis software, in order to investigate the effect of vertical cracks. The evolution of microstructure during sintering, coating shrinkage and mechanical degradation were predicted. The numerical predictions of Young's modulus were generally in agreement with experimental results. Furthermore, the effect of vertical cracks on the strain tolerance and sintering resistance were discussed. It was confirmed that the introduction of vertical cracks contributed to the improvement of both properties.
Induced p‐type semiconductivity in yttria‐stabilized zirconia
Authors: Vendrell Xavier , West Anthony R.
Published: April 2019

8 mol% yttria‐stabilized zirconia (8YSZ) ceramic is an oxide ion conductor at atmospheric pressure but shows the onset of p‐type semiconduction, in addition to the preexisting oxide ion conduction, on application of a dc bias in the range 4‐66 Vcm−1 and at temperatures in the range 150°C‐750°C. The p‐type behavior is attributed to the location and hopping of holes on oxygen. This contrasts with the commonly observed introduction of n‐type conduction under reducing conditions and high fields. The hole conductivity increases with both dc bias and pO2. Its occurrence may contribute to the early stages of flash phenomena in 8YSZ ceramics.
Impact of anticoagulation therapy on outcomes in patients with cardiac implantable resynchronization devices undergoing transvenous lead extraction: A substudy of the ESC‐EHRA EORP ELECTRa (European Lead Extraction ConTRolled) Registry
Authors: Regoli François , Auricchio Angelo , Di Cori Andrea , Segreti Luca , Blomström‐Lunqvist Carina , Butter Christian , Deharo Jean‐Claude , Kennergren Charles , Kutarski Andrzej , Laroche Cecile , Zalevskiy Valery , Luzzi Giovanni , Cano Oscar , Grabowski Marcin , Rinaldi Christopher , Bongiorni Maria Grazia
Published: April 2019

Introduction

Little data are available on anticoagulation (AC) management in patients with cardiac resynchronization (CRT) devices who undergo transvenous lead extraction (TLE) procedure. We investigated the impact of AC on periprocedural complications in CRT patients undergoing TLE, enrolled in the ESC‐EHRA European Lead Extraction ConTrolled (ELECTRa) registry.

Methods and Results

All CRT patients treated with TLE enrolled in the registry were considered. Perioperative AC management was left to the discretion of the Center. Major and minor intraprocedural and postprocedural complications were compared between patients without AC (Gp1) and patients with AC (Gp2). Regression analyses were performed to identify predictors of complications for Gp2.

Out of 734 CRT pts, 328 (44.7%) were under AC (Gp2). Patients from Gp2 presented lower LVEF (Gp2 32.5 ± 10.9 vs Gp1 34.5 ± 11.9%; P = 0.03), more advanced heart failure disease (NYHA III/IV: Gp2 42.0 vs Gp1 31.5%; P = 0.02), and renal impairment (Gp2 39.0 vs Gp1 24.3%; P < 0.001). Perioperative regimens included AC interruption (Gp2A: n = 169, 51.5%), “bridging” (Gp2B: n = 135, 41.2%), or continued AC (Gp2C: n = 24, 7.3%). TLE complete success rates (98% in both groups) and major complication rates were comparable for both groups; minor bleeding events were more frequent in Gp2 (5.5%) compared to Gp1 (2.5%; P = 0.051). No independent predictors were identified for Gp2, but minor complications were associated with “bridging” approach (Gp2B: 16 events vs Gp2A/C: 9 events; P = 0.020).

Conclusion

CRT patients treated with TLE under AC were more compromised but did not present more major complications compared to patients without AC. More minor complications were associated with “bridging” AC regimen.
First‐line treatment of essential hypertension: A real‐world analysis across four antihypertensive treatment classes
Authors: Stapff Manfred , Hilderbrand Sarah
Published: April 2019

The relative efficacy of antihypertensive treatment has been assessed primarily by randomized clinical trials (RCTs). The increasing availability of electronic medical records (EMR) allows results from RCT to be compared to data from actual clinical practice. EMR from TriNetX were used to compare patients starting and adhering to antihypertensive treatment on diuretics, beta blockers, angiotensin II or ACE inhibitors, or calcium channel blockers for at least 36 months. Cardiovascular (CV) events as defined by ICD‐10 codes were evaluated for an observation period of three years. Outcomes were assessed with and without propensity score matching for confounding factors. A total of 79 288 patients fulfilled the criteria for first‐line therapy and adherence (17.4% diuretics, 25.9% beta blockers, 45.1% inhibitors of the renin‐angiotensin system, and 11.6% calcium channel blockers). Differences in demography and comorbidities were consistent with expectations based on treatment guidelines. RAS blockers showed the best BP control (28.7% episodes of uncontrolled BP) and, together with diuretics, the lowest rate of CV events (diuretics, 5.2%; RAS blockers, 5.4%). Beta blockers were associated with the highest rate of uncontrolled BP (45.9%) and a high CV event rate (9.5%). These trends remained after matching the cohorts for confounding factors. EMR show that actual prescribing behavior for first‐line treatment of essential hypertension reflects treatment guidelines. Patients taking either RAS blockers or diuretics experienced the lowest CV event rates. Beta blockers, even when adjusted for pre‐existing cardiovascular conditions, do not seem to be as protective against CV events as the three other classes.
Hypertension‐induced subclinical vascular and cognitive changes are reversible—An observational cohort study
Authors: Czuriga‐Kovács Katalin Réka , Szekeres Csilla Cecília , Bajkó Zoltán , Csapó Krisztina , Oláh László , Magyar Mária Tünde , Molnár Sándor , Czuriga Dániel , Kardos László , Bojtor Burainé Andrea , Bereczki Dániel , Soltész Pál , Csiba László
Published: April 2019

Beside the well‐known complications of poorly controlled, long‐standing hypertension, milder abnormalities induced by early‐stage hypertension have also been described. In our study, the authors examined the reversibility of changes induced by early‐stage hypertension. The authors performed laboratory testing, ambulatory blood pressure monitoring, carotid intima‐media thickness (IMT) measurement, evaluation of stiffness parameters, assessment of various cardiac and cerebral hemodynamic parameters during head‐up tilt table (HUTT) testing, and neuropsychological examinations in 49 recently diagnosed hypertensive patients. Following baseline assessment, antihypertensive therapy was commenced. After one year of therapy, lower IMT values were found. Pulse wave velocity showed a borderline significant decrease. During HUTT, several hemodynamic parameters improved. The patients performed better on neuropsychological testing and reached significantly lower scores on questionnaires evaluating anxiety. The present study shows that early vascular changes and altered cognitive function observed in newly diagnosed hypertensive patients may improve with promptly initiated antihypertensive management.
Left ventricular cardiac geometry and ambulatory blood pressure in children
Authors: Shilly Steffi , Merchant Kumail , Singer Pamela , Frank Rachel , Gurusinghe Shari , Infante Lulette , Sethna Christine B.
Published: April 2019

Limited information is available regarding the relationship between ambulatory blood pressure monitoring (ABPM) and cardiac geometry in hypertensive children. ABPM and 2D‐echocardiography were retrospectively reviewed in children and adolescents <21 years old with primary hypertension. A total of 119 participants (median age 15.0 [IQR 12, 16] years) with hypertension were included. Left ventricular hypertrophy was diagnosed in 39.5% of participants. Normal geometry was found in 47.1%, concentric remodeling (CR) in 13.4%, concentric hypertrophy (CH) in 15.1%, and eccentric hypertrophy (EH) in 24.4% of children. After adjustment for age, sex, and body mass index z‐score, awake systolic blood pressure (BP) index (BPi) (OR 1.07, 95% CI: 1.001‐1.14, P = 0.045), awake diastolic BPi (OR 1.04, 95% CI: 1.00‐1.09, P = 0.048), awake systolic BP load (OR 1.02, 95% CI: 1.000‐1.04, P = 0.047), and sleep systolic BP load (OR 1.02, 95% CI: 1.001‐1.04, P = 0.03) were directly associated with CH. No ABPM parameters were significant predictors of EH. In conclusion, ABPM parameters were found to be independent predictors of cardiac geometry, specifically CH.
Diversity of dermal fibroblasts as major determinant of variability in cell reprogramming
Authors: Sacco Anna Maria , Belviso Immacolata , Romano Veronica , Carfora Antonia , Schonauer Fabrizio , Nurzynska Daria , Montagnani Stefania , Di Meglio Franca , Castaldo Clotilde
Published: April 2019

Induced pluripotent stem cells (iPSCs) are adult somatic cells genetically reprogrammed to an embryonic stem cell‐like state. Notwithstanding their autologous origin and their potential to differentiate towards cells of all three germ layers, iPSC reprogramming is still affected by low efficiency. As dermal fibroblast is the most used human cell for reprogramming, we hypothesize that the variability in reprogramming is, at least partially, because of the skin fibroblasts used. Human dermal fibroblasts harvested from five different anatomical sites (neck, breast, arm, abdomen and thigh) were cultured and their morphology, proliferation, apoptotic rate, ability to migrate, expression of mesenchymal or epithelial markers, differentiation potential and production of growth factors were evaluated in vitro. Additionally, gene expression analysis was performed by real‐time PCR including genes typically expressed by mesenchymal cells. Finally, fibroblasts isolated from different anatomic sites were reprogrammed to iPSCs by integration‐free method. Intriguingly, while the morphology of fibroblasts derived from different anatomic sites differed only slightly, other features, known to affect cell reprogramming, varied greatly and in accordance with anatomic site of origin. Accordingly, difference also emerged in fibroblasts readiness to respond to reprogramming and ability to form colonies. Therefore, as fibroblasts derived from different anatomic sites preserve positional memory, it is of great importance to accurately evaluate and select dermal fibroblast population prior to induce reprogramming.
Clinical polyneuropathy does not increase with prediabetes or metabolic syndrome in the Japanese general population
Authors: Kurisu Seigo , Sasaki Hideyuki , Kishimoto Shohei , Hirayasu Kazuhiro , Ogawa Kinichi , Matsuno Shohei , Furuta Hiroto , Arita Mikio , Naka Keigo , Nanjo Kishio , Akamizu Takashi
Published: April 2019

Aims/Introduction

The prevalence of clinical polyneuropathies (ClinPNs) or nerve conduction abnormality (NCA) in the groups stratified by glucose tolerance, individual components of metabolic syndrome (metabolic syndrome [MetS] components: hypertension, dyslipidemia, obesity) and MetS defined by the International Diabetes Federation consensus was investigated in the Japanese general population. Factors associated with ClinPN and NCA were also identified.

Materials and Methods

A total of 625 examinees of regional medical checkup programs were recruited to this cross‐sectional study. ClinPNs were diagnosed by the Toronto Consensus. NCA was judged by at least one bilateral abnormality of sural nerve action potential amplitude or conduction velocity measured by a point‐of‐care nerve conduction device (DPNCheck). Clinical factors associated with ClinPNs or NCA were examined by multiple logistic regression analysis. Deteriorating factors of sural nerve action potential amplitude or conduction velocity values were also investigated in participants without diabetes (n = 550).

Results

As for glucose tolerance, ClinPNs or NCA significantly increased only in known diabetes patients compared with other groups. There was no difference between prediabetes and the normal group. The prevalence of ClinPNs and NCA was not significantly related to MetS or MetS’ components, except for frequent NCA in obesity. The factors significantly associated with both NCA and ClinPNs were smoking and known diabetes. In non‐diabetic participants, aging, tall height and hypertension were significant deteriorating factors of nerve conduction functions.

Conclusions

In Japan, ClinPNs and NCA were increased in known diabetes patients, but did not increase in participants with prediabetes, MetS and MetS’ components. Smoking and known diabetes were factors significantly associated with ClinPNs or NCA. Hypertension might be a modifiable deteriorating factor of nerve function.
Formulation evaluation of ketoconazole microemulsion‐loaded hydrogel with nigella oil as a penetration enhancer
Authors: Amra Kesrin , Momin Munira
Published: April 2019

Background

Onychomycosis is an opportunistic fungal infection often infecting people with compromised immune system. Currently available treatment interventions such as physical, surgical, and chemical‐based approaches are successful in treating the condition, however, are painful and nonpatient complaint. Moreover, dermal creams with antifungal agents do not penetrate nail plate as required; hence, there is a necessity of developing a novel formulation with enhanced penetration.

Aims

The aim of the present research work was to develop ketoconazole microemulsion‐loaded hydrogel formulation containing nigella oil as permeation enhancer for the treatment of onychomycosis.

Methods

Screening of oils, surfactants, and cosurfactants were done based on solubility studies followed by the construction of pseudo‐ternary phase diagrams with 2% ketoconazole. The microemulsion was characterized for globule size, zeta potential, viscosity, and thermodynamic stability. Ex‐vivo studies were carried out using Franz diffusion cells using porcine skin membrane. The antifungal activity of microemulsion‐loaded hydrogel was evaluated using cup plate method using Candida albicans and Aspergillus niger.

Results

The optimized microemulsion had a composition of 54.97% Capryol:Nigella (2:1), 36.07% Transcutol:Propylene glycol (2:1), and 7.13% water and was later incorporated into polymeric gel base. The microemulsion‐loaded hydrogel exhibited a 10 hours sustained release profile as compared to the marketed cream and an enhanced activity against marketed ketoconazole cream and compared with marketed ketoconazole formulation.

Conclusion

The thermodynamic stability, sustained drug release with greater permeation, and enhanced activity due to the presence of nigella oil in microemulsion‐loaded hydrogel warrant its application as an excellent vehicle for treating fungal infections.
Effective noninvasive body contouring by using a combination of cryolipolysis, injection lipolysis, and shock waves
Authors: Faulhaber Jörg , Sandhofer Matthias , Weiss Christel , Sattler Gerhard , Sadick Neil S.
Published: April 2019

Background

Cryolipolysis combined with shockwave therapy has been previously shown to have synergistic effects in body contouring results.

Objective

This open‐label, prospective, multicenter, comparative study investigated the safety and efficacy of combined cryolipolysis, shockwave therapy with cryolipolysis, shockwave therapy, and injection polyenylphosphatidylcholine‐based lipolysis.

Methods

Enrolled patients were treated in the abdominal or flank area with cryolipolysis, shockwave therapy and injection lipolysis (n = 10) or cryolipolysis and shockwave therapy (n = 4). All treatments were conducted the same day. Evaluations were conducted 3 months after treatment and included histological analysis, standardized photography, blinded‐investigator efficacy, and safety ratings, as well as patient ratings of satisfaction and tolerance.

Results

Compared to baseline, the 3‐month follow‐up histological analysis revealed a more profound subcutaneous adipose tissue reaction with the triple combination therapy (cryolipolysis, injection lipolysis, radial shock wave) than with the double combination with regard to adipocyte damage and grade of inflammation. Waist circumference was significantly reduced in patients of both groups, but patients in the triple combination group were shown to have a significantly more pronounced reduction in subcutaneous fat. Factors that were shown to influence treatment outcome included baseline BMI and waist circumference. Age and gender had no effect. The abdominal area reacted better to the treatment compared to flanks. No significant side effects or adverse events were reported. The procedure was well‐tolerated, and the majority of patients were satisfied with the treatment results.

Conclusions

Combination of cryolipolysis, radial shockwave, and injection lipolysis is a safe, well‐tolerated treatment for reduction in subcutaneous fat.
Treatment and monitoring of children with chronic hepatitis C in the Pre‐DAA era: A European survey of 38 paediatric specialists
Authors: Indolfi Giuseppe , Bailey Heather , Serranti Daniele , Giaquinto Carlo , Thorne Claire ,   The PENTAHep Study Group
Published: April 2019

The burden of paediatric Hepatitis C virus (HCV) infection across Europe is unknown, as are current policies regarding monitoring and treatment. This collaborative study aimed to collect aggregate data to characterise the population of ≤18‐year‐olds with HCV infection in specialist follow up in a 12‐month period (2016) across the PENTAHep European consortium, and investigate current policies around monitoring and treatment. A cross‐sectional, web‐based survey was distributed in April 2017 to 50 paediatricians in 19 European countries, covering patients' profile, and monitoring and treatment practices. Responses were received from 38/50 clinicians collectively caring for 663 children with chronic HCV infection of whom three‐quarters were aged ≥6 years and 90% vertically infected. HCV genotype 1 was the most common (n 380; 57.3%), followed by genotype 3, 4 and 2. Seventeen children (3%) with chronic HCV infection were diagnosed with cirrhosis, and six were reported to have received liver transplantation for HCV‐related liver disease. The majority (n 425; 64.1%) of the European children with HCV infection remained treatment‐naive in 2016. Age affected clinicians' attitudes towards treatment; 94% reported being willing to use direct‐acting antivirals, if available, in adolescents (aged ≥11 years), 78% in children aged 6‐10 and 42% in those 3‐5 years of age (Pearson correlation coefficient −0.98; P 0.0001). This survey provides the largest characterisation of the population of children in clinical follow‐up for chronic HCV infection in Europe, alongside important contextual information on their management and treatment. Discussion is needed around strategies and criteria for use of direct‐acting antivirals in these children.
Parallel introgression and selection on introduced alleles in a native species
Authors: Bay Rachael A. , Taylor Eric B. , Schluter Dolph
Published: April 2019

As humans cause the redistribution of species ranges, hybridization between previously allopatric species is on the rise. Such hybridization can have complex effects on overall fitness of native species as new allelic combinations are tested. Widespread species introductions provide a unique opportunity to study selection on introgressed alleles in independent, replicated populations. We examined selection on alleles that repeatedly introgressed from introduced rainbow trout (Oncorhynchus mykiss) into native westslope cutthroat trout (Oncorhynchus clarkii lewisi) populations in western Canada. We found that the degree of introgression of individual single nucleotide polymorphisms from the invasive species into the native is correlated between independent watersheds. A number of rainbow trout alleles have repeatedly swept to high frequency in native populations, suggesting parallel adaptive advantages. Using simulations, we estimated large selection coefficients up to 0.05 favoring several rainbow trout alleles in the native background. Although previous studies have found reduced hybrid fitness and genome‐wide resistance to introgression in westslope cutthroat trout, our results suggest that some introduced genomic regions are strongly favored by selection. Our study demonstrates the utility of replicated introductions as case studies for understanding parallel adaptation and the interactions between selection and introgression across the genome. We suggest that understanding this variation, including consideration of beneficial alleles, can inform management strategies for hybridizing species.
Satellite tracking of gulls and genomic characterization of faecal bacteria reveals environmentally mediated acquisition and dispersal of antimicrobial‐resistant Escherichia coli on the Kenai Peninsula, Alaska
Authors: Ahlstrom Christina A. , Bonnedahl Jonas , Woksepp Hanna , Hernandez Jorge , Reed John A. , Tibbitts Lee , Olsen Björn , Douglas David C. , Ramey Andrew M.
Published: April 2019

Gulls (Larus spp.) have frequently been reported to carry Escherichia coli exhibiting antimicrobial resistance (AMR E. coli); however, the pathways governing the acquisition and dispersal of such bacteria are not well described. We equipped 17 landfill‐foraging gulls with satellite transmitters and collected gull faecal samples longitudinally from four locations on the Kenai Peninsula, Alaska to assess: (a) gull attendance and transitions between sites, (b) spatiotemporal prevalence of faecally shed AMR E. coli, and (c) genomic relatedness of AMR E. coli isolates among sites. We also sampled Pacific salmon (Oncorhynchus spp.) harvested as part of personal‐use dipnet fisheries at two sites to assess potential contamination with AMR E. coli. Among our study sites, marked gulls most commonly occupied the lower Kenai River (61% of site locations) followed by the Soldotna landfill (11%), lower Kasilof River (5%) and upper Kenai River (<1%). Gulls primarily moved between the Soldotna landfill and the lower Kenai River (94% of transitions among sites), which were also the two locations with the highest prevalence of AMR E. coli. There was relatively high spatial and temporal variability in AMR E. coli prevalence in gull faeces and there was no evidence of contamination on salmon harvested in personal‐use fisheries. We identified E. coli sequence types and AMR genes of clinical importance, with some isolates possessing genes associated with resistance to as many as eight antibiotic classes. Our findings suggest that gulls acquire AMR E. coli at habitats with anthropogenic inputs and subsequent movements may represent pathways through which AMR is dispersed.
Tinea capitis in adults: A 18‐year retrospective, single‐centre study in Korea
Authors: Park Su‐Kyung , Park Sang‐Woo , Yun Seok‐Kweon , Kim Han‐Uk , Park Jin
Published: April 2019

Background

Tinea capitis (TC) is a dermatophyte infection involving hair and scalp and occurs primarily in prepubertal children. However, data on adults are limited.

Objectives

The aim of this study was to evaluate epidemiological, clinical and mycological characteristics of TC in adults in Korea.

Patients/Methods

We retrospectively evaluated 82 adults (44.3%) among 185 TC patients at a tertiary hospital during June 2000‐2017.

Results

Mean patient age was 66.9 ± 15.8 (20‐90) years with female predominance; mean disease duration until mycological diagnosis, 22.5 (1‐144) weeks; and misdiagnosis rate, 65.9%. Most common presumptive initial diagnoses were seborrhoeic dermatitis (24.4%) and bacterial folliculitis (18.3%). Chronic systemic illness and accompanying alopecia were found in 61 (74.4%) and 46 (56.1%) patients, respectively. Pustular type was found in 26.8% patients, followed by seborrhoeic dermatitis–like 25.6%, grey patch 23.2%, kerion celsi 22.0% and black dot 2.4%. Forty‐eight patients (58.5%) had tinea infection at other skin areas. Microsporum canis (56.5%) and Trichophyton rubrum (21.7%) were the most common causative organisms; 92.7% patients achieved complete resolution, and seven patients (9.2%) had a recurrence.

Conclusions

We report the largest, most recent series of case studies of adult TC. Adult TC is not an uncommon problem, especially in elderly women, and has distinctive epidemiological and clinicomycological characteristics compared to those in prepubertal children. Recognising adult TC profile will help clinicians avoid misdiagnosis and provide appropriate treatment.
Leaves of isoprene‐emitting tobacco plants maintain PSII stability at high temperatures
Authors: Pollastri Susanna , Jorba Ignasi , Hawkins Timothy J. , Llusià Joan , Michelozzi Marco , Navajas Daniel , Peñuelas Josep , Hussey Patrick J. , Knight Marc R. , Loreto Francesco
Published: April 2019

At high temperatures, isoprene‐emitting plants display a higher photosynthetic rate and a lower nonphotochemical quenching (NPQ) compared with nonemitting plants. The mechanism of this phenomenon, which may be very important under current climate warming, is still elusive.

NPQ was dissected into its components, and chlorophyll fluorescence lifetime imaging microscopy (FLIM) was used to analyse the dynamics of excited chlorophyll relaxation in isoprene‐emitting and nonemitting plants. Thylakoid membrane stiffness was also measured using atomic force microscope (AFM) to identify a possible mode of action of isoprene in improving photochemical efficiency and photosynthetic stability.

We show that, when compared with nonemitters, isoprene‐emitting tobacco plants exposed at high temperatures display a reduced increase of the NPQ energy‐dependent component (qE) and stable (1) chlorophyll fluorescence lifetime; (2) amplitude of the fluorescence decay components; and (3) thylakoid membrane stiffness.

Our study shows for the first time that isoprene maintains PSII stability at high temperatures by preventing the modifications of the surrounding environment, namely providing a more steady and homogeneous distribution of the light‐absorbing centres and a stable thylakoid membrane stiffness. Isoprene photoprotects leaves with a mechanism alternative to NPQ, enabling plants to maintain a high photosynthetic rate at rising temperatures.
Observed variation in soil properties can drive large variation in modelled forest functioning and composition during tropical forest secondary succession
Authors: Medvigy David , Wang Gangsheng , Zhu Qing , Riley William J. , Trierweiler Annette M. , Waring Bonnie G. , Xu Xiangtao , Powers Jennifer S.
Published: April 2019

Censuses of tropical forest plots reveal large variation in biomass and plant composition. This paper evaluates whether such variation can emerge solely from realistic variation in a set of commonly measured soil chemical and physical properties.

Controlled simulations were performed using a mechanistic model that includes forest dynamics, microbe‐mediated biogeochemistry, and competition for nitrogen and phosphorus. Observations from 18 forest inventory plots in Guanacaste, Costa Rica were used to determine realistic variation in soil properties.

In simulations of secondary succession, the across‐plot range in plant biomass reached 30% of the mean and was attributable primarily to nutrient limitation and secondarily to soil texture differences that affected water availability. The contributions of different plant functional types to total biomass varied widely across plots and depended on soil nutrient status. In Central America, soil‐induced variation in plant biomass increased with mean annual precipitation because of changes in nutrient limitation.

In Central America, large variation in plant biomass and ecosystem composition arises mechanistically from realistic variation in soil properties. The degree of biomass and compositional variation is climate sensitive. In general, model predictions can be improved through better representation of soil nutrient processes, including their spatial variation.
Dynamics of intracellular mannan and cell wall folding in the drought responses of succulent Aloe species
Authors: Ahl Louise Isager , Mravec Jozef , Jørgensen Bodil , Rudall Paula J. , Rønsted Nina , Grace Olwen M.
Published: April 2019

Plants have evolved a multitude of adaptations to survive extreme conditions. Succulent plants have the capacity to tolerate periodically dry environments, due to their ability to retain water in a specialized tissue, termed hydrenchyma. Cell wall polysaccharides are important components of water storage in hydrenchyma cells. However, the role of the cell wall and its polysaccharide composition in relation to drought resistance of succulent plants are unknown. We investigate the drought response of leaf‐succulent Aloe (Asphodelaceae) species using a combination of histological microscopy, quantification of water content, and comprehensive microarray polymer profiling. We observed a previously unreported mode of polysaccharide and cell wall structural dynamics triggered by water shortage. Microscopical analysis of the hydrenchyma cell walls revealed highly regular folding patterns indicative of predetermined cell wall mechanics in the remobilization of stored water and the possible role of homogalacturonan in this process. The in situ distribution of mannans in distinct intracellular compartments during drought, for storage, and apparent upregulation of pectins, imparting flexibility to the cell wall, facilitate elaborate cell wall folding during drought stress. We conclude that cell wall polysaccharide composition plays an important role in water storage and drought response in Aloe.
Seasonality of i.v. immunoglobulin responsiveness in Kawasaki disease
Authors: Kido Shinji , Ae Ryusuke , Kosami Koki , Matsubara Yuri , Makino Nobuko , Sasahara Teppei , Kuwabara Masanari , Aoyama Yasuko , Yashiro Mayumi , Yanagawa Hiroshi , Nakamura Yosikazu
Published: April 2019

Background

Evidence suggests that seasonal variation in the onset of Kawasaki disease (KD) exists worldwide. Whether a seasonal component to successful i.v. immunoglobulin (IVIG) therapy exists in KD‐positive children, however, is unknown. We addressed this question by focusing on patients with primary onset KD who were non‐responsive to IVIG treatment, in the large nationwide Japanese KD survey datasets from 2009 to 2016.

Methods

In these datasets, the IVIG therapy non‐responders were defined as patients whose fever persisted ≥24 h or recurred ≤24 h after the end of the initial IVIG treatment (dosage, 2,000 mg/kg). Those who successfully responded to this treatment were defined as IVIG responders. The consecutive monthly trend of the proportion of IVIG non‐responders was analyzed throughout the study period to investigate seasonal periodicity on Fourier analysis, and the monthly distributions of non‐responders and responders were compared.

Results

From a total of 113 691 KD‐positive patients, 15.7% were IVIG non‐responders, and 61% were male. The proportion of non‐responders increased across each calendar year with fluctuation, and Fourier analysis indicated seasonal periodicity. The seasonality effect differed between responders and non‐responders, with the proportion of responders tending to increase in autumn through winter, while the non‐responders showed a decreasing trend in autumn. The seasonality effect tended to differ by sex.

Conclusions

The results indicate that the currently unknown etiological agents of KD might differ between IVIG responders and non‐responders. In addition, immune reactivity against such agents possibly differs by sex in the IVIG non‐responders.