bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive map of human elastin cross‐linking during elastogenesis
Authors: Hedtke Tobias , Schräder Christoph U. , Heinz Andrea , Hoehenwarter Wolfgang , Brinckmann Jürgen , Groth Thomas , Schmelzer Christian E. H.
Published: May 2019

Elastin is an essential structural protein in the extracellular matrix of vertebrates. It is the core component of elastic fibers, which enable connective tissues such as those of the skin, lungs or blood vessels to stretch and recoil. This function is provided by elastin's exceptional properties, which mainly derive from a unique covalent cross‐linking between hydrophilic lysine‐rich motifs of units of the monomeric precursor tropoelastin. To date, elastin's cross‐linking is poorly investigated. Here, we purified elastin from human tissue and cleaved it into soluble peptides using proteases with different specificities. We then analyzed elastin's molecular structure by identifying unmodified residues, post‐translational modifications and cross‐linked peptides by high‐resolution mass spectrometry and amino acid analysis. The data revealed the presence of multiple isoforms in parallel and a complex and heterogeneous molecular interconnection. We discovered that the same lysine residues in different monomers were simultaneously involved in various cross‐link types or remained unmodified. Furthermore, both types of cross‐linking domains, Lys‐Pro and Lys‐Ala domains, participate not only in bifunctional inter‐ but also in intra‐domain cross‐links. We elucidated the sequences of several desmosine‐containing peptides and the contribution of distinct domains such as 6, 14 and 25. In contrast to earlier assumptions proposing that desmosine cross‐links are formed solely between two domains, we elucidated the structure of a peptide that proves a desmosine formation with participation of three Lys‐Ala domains. In summary, these results provide new and detailed insights into the cross‐linking process, which takes place within and between human tropoelastin units in a stochastic manner.
Seasonal and diurnal patterns of population vocal activity in avian brood parasites
Authors: Yoo Sohyeon , Kim Hae‐Ni , Lee Jin‐Won , Yoo Jeong‐Chil
Published: May 2019

Patterns of vocal activity may involve information about vocalizations themselves as well as their function. In birds, vocal activity at the individual and population level is generally closely associated with breeding cycles, reaching the peak during territorial and mating competition, and decreasing with the onset of egg incubation and chick feeding. However, little is known about patterns of vocal activity in avian brood parasites that have unusual breeding cycles without parental care. Using passive acoustic monitoring, we determined the seasonal and diurnal patterns of population vocal activity in two avian brood parasites: the Common CuckooCuculus canorusand the Lesser CuckooC. poliocephalus. We found that both species and both sexes showed a similarly highly structured pattern of seasonal vocal activity, reaching a sharp peak in the early breeding season when birds compete for territories and mates, although males sang more frequently than females. Likewise, the diurnal patterns of vocal activity were similar in both species and both sexes of cuckoos, with peak activity occurring around dawn. Nocturnal calls by male cuckoos were also detected in both species, but only in the early breeding season. Collectively, the observed patterns of population vocal activity may suggest that the absence of parental care may not extend the period of vocal activity in these two species of brood parasites.
“Bone marrow aspirate automated counts on hematology analyzers: formulating a scoring system based on hematology parameters, to discriminate reactive versus myelodysplastic syndrome‐related bone marrows”
Authors: Tsagarakis Nikolaos J. , Paterakis Georgios , Papadhimitriou Stefanos I. , Kritikou‐Griva Elpiniki , Goumakou Eleni , Oudatzis Georgios , Theodorakos Ioannis , Vasileiou Paraskevi
Published: May 2019

Introduction

Diagnosis of myelodysplastic syndromes (MDS) is usually challenging. In this context, we have attempted to employ data derived from automated analysis of bone marrow (BM) samples as an ancillary tool for the discrimination between reactive marrow and MDS.

Methods

A total of 101 BM anticoagulated samples referred for flow cytometry (FCM) analysis on the clinical suspicion of MDS had been previously counted in a Mindray BC‐6800 hematology analyzer (testing set). Among them, 22/101 randomly selected BM samples (comparison set) had been also simultaneously counted by an Advia 2120 and a CELL‐DYN Sapphire hematology analyzer. Selected parameters obtained by Mindray BC‐6800 were retrospectively evaluated with ROC and regression analysis in an attempt to formulate a discriminative scoring system (SS) for MDS. This system was further evaluated in the comparison set.

Results

The diagnosis of MDS was established in 37/101 patients assessed (“MDS” group). Three patients were diagnosed with myelodysplastic/myeloproliferative neoplasm (MDS/MPN), while 61 revealed a “reactive” bone marrow (“RBM” group). Statistical analysis revealed significant differences in Hb, RDW‐CV%, NRBC%, and RET% values between the “MDS” and the “RBM” group. Specific cutoff values were then indicated and employed for the formulation of a SS of high sensitivity (86.84%) and specificity (86.89%). The encouraging performance characteristics of the proposed SS were also confirmed in the BM comparison set.

Conclusion

Automated BM counts on hematology analyzers contributed to the formulation of a SS for the screening discrimination between reactive and MDS BM fluids, which seems to be applicable and informative, regardless of the analyzer used.
Er3+ cross‐section spectra of Er3+/Pr3+:Gd3Ga5O12 single‐crystal: Pr3+‐codoping effect
Authors: Xu Qing , Wang Yan , Chen Feng , Wong Wing‐Han , Zhang Zi‐Bo , Zhang De‐Long
Published: May 2019

Fluorescence and absorption spectra at 530 nm (2H11/2→4I15/2), 560 nm (4S3/2→4I15/2), 660 nm (4F9/2→4I15/2), 980 nm (4I11/2→4I15/2), 1530 nm (4I13/2→4I15/2), and 2710 nm (4I11/2→4I13/2) of Er3+ in Gd3Ga5O12 single‐crystal codoped with Pr3+ have been measured. Judd‐Ofelt analysis yields the intensity parameters Ω2 = (0.68 ± 0.03) × 10−20 cm2, Ω4 = (0.60 ± 0.07) × 10−20 cm2, and Ω6 = (0.90 ± 0.17) × 10−20 cm2. A comparison with previously reported values of Er3+‐only doping case shows that Pr3+‐codoping causes slight change of both Ω2 and Ω4, while onefold increase of Ω6. From calculated radiative rates and measured fluorescence spectra, Er3+ emission cross‐section spectra were calibrated at first. Then, the absorption cross‐section spectra were calculated using McCumber relation. In parallel, the absorption cross‐section spectra were also obtained from the measured absorption spectrum, and compared with those obtained from the McCumber relation. The comparison shows that both methods give consistent result of absorption cross‐section spectrum. Further comparison with Er3+‐only doping case shows that Pr3+‐codoping causes considerable change of Er3+ cross‐section value. In spectrally mixing regions of Er3+ and Pr3+, Pr3+ emission affects little the determination of Er3+ emission cross‐section as Pr3+ fluorescence is much weaker than Er3+ fluorescence due to low Pr3+ concentration.
Setting behavior and bioactivity assessment of calcium carbonate cements
Authors: Rodríguez‐Sánchez Jesús , Myszka Barbara , Boccaccini Aldo Roberto , Dysthe Dag Kristian
Published: May 2019

Calcium carbonate cements have emerged in the last few years as an attractive candidate for biomedical applications. They can be easily prepared by mixing water with two metastable calcium carbonate phases––amorphous calcium carbonate (ACC) and vaterite––which (re)crystallize into calcite during setting reaction. The transformation kinetics (and therefore the final surface cement composition) strongly depends on the initial mixture design and is controlled by the dissolution of ACC, whereas calcite nucleation typically controls their recrystallization in fluid batch experiments. Novel compositions are presented in this paper by incorporating organic molecules as a proxy to test their capability to carry on other biomolecules like proteins or antibiotics. The hardened samples are microporous and show excellent bioactivity rates, although their mechanical properties still remain poor. However, this would not be a handicap for in‐vivo applications such as bone filling, especially in low mechanical stress locations.
Evaluating the chemical stability of metal oxides in SO3 and applications of SiO2‐based membranes to O2/SO3 separation
Authors: Yu Xin , Meng Lie , Nagasawa Hiroki , Kanezashi Masakoto , Machida Masato , Tsuru Toshinori
Published: May 2019

The decomposition of sulfur trioxide to produce sulfur dioxide and oxygen using a catalytic membrane reactor is technology that promises to improve the economic viability of the thermochemical water‐splitting Iodine‐Sulfur (IS) process for large‐scale CO2‐free hydrogen production. The chemical stability of membrane materials under SO3, however, is a significant challenge for this strategy. In this study, microporous membranes with a layered structure that consisted of a membrane support prepared from α‐Al2O3, an intermediate layer prepared from silica‐zirconia, and a top layer prepared from bis (triethoxysilyl)ethane‐derived organosilica sols, were examined for stability under SO3 and for use in SO3/O2 separation. An α‐Al2O3 support that features SiO2–ZrO2 intermediate layers with large pore sizes and a high Si/Zr molar ratio showed excellent resistance to SO3, which was confirmed by N2 adsorption, Energy Dispersive X‐ray Spectroscopy (EDS), and Scanning Electron Microscopy (SEM). These membranes also demonstrated a negligible change in gas permeance before and after SO3 exposure. Subsequently, in binary‐component gas separation at 550°C, microporous organosilica‐derived membranes achieved an O2/SO3 selectivity of 10 (much higher than the Knudsen selectivity of 1.6) while maintaining a high O2 permeance of 2.5 × 10−8 mol m–2 s–1 Pa–1.
Metformin shows anti‐inflammatory effects in murine macrophages through Dicer/microribonucleic acid‐34a‐5p and microribonucleic acid‐125b‐5p
Authors: Luo Xi , Hu Rong , Zheng Ying , Liu Shiping , Zhou Zhiguang
Published: May 2019

Aims/Introduction

Metformin, a widely prescribed antidiabetic agent, has been shown to exhibit anti‐inflammatory effects in obese and type 2 diabetes patients, but the mechanism is not well elucidated. Microribonucleic acids (miRNAs) are a group of small non‐coding ribonucleic acids that participate in many biological and pathological processes. The aim of the present study was to investigate whether Dicer, a key miRNA biogenesis enzyme, and miRNAs in macrophages are implicated in the anti‐inflammatory effects of metformin.

Materials and Methods

Enzyme‐linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were carried out to verify the anti‐inflammatory effects of metformin. miRNA microarray was applied to detect the expression profile of miRNA. Western‐blotting, enzyme‐linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were used to examine the role Dicer and miRNAs play in the anti‐inflammatory effects of metformin.

Results

In parallel with the suppression of interleukin‐6 and tumor necrosis factor‐α production in resting and lipopolysaccharide‐stimulated macrophages, metformin could induce an increase in Dicer and most miRNAs. When Dicer was knocked down, the anti‐inflammatory effects of metformin were significantly attenuated. Additionally, the upregulation of miRNA (miR)‐34a‐5p and miR‐125b‐5p by metformin were also blunted in Dicer knockdown macrophages. Furthermore, inhibition of miR‐34a‐5p and miR‐125b‐5p could impair the suppressive action of metformin on pro‐inflammatory factors production, whereas overexpression of the two miRNAs mimicked the anti‐inflammatory effects of metformin.

Conclusions

Metformin might show anti‐inflammatory effects in macrophages through the induction of Dicer and the subsequent upregulation of miR‐34a‐5p and miR‐125b‐5p.
Efficacy and safety of dulaglutide monotherapy compared with glimepiride in Chinese patients with type 2 diabetes: Post‐hoc analyses of a randomized, double‐blind, phase III study
Authors: Shi Li Xin , Liu Xiao Min , Shi Yong Quan , Li Quan Min , Ma Jian Hua , Li Yan Bing , Du Li Ying , Wang Feng , Chen Lu Lu
Published: May 2019

Aims/Introduction

To investigate the efficacy/safety of dulaglutide once‐weekly monotherapy versus glimepiride in Chinese patients with type 2 diabetes.

Materials and Methods

This was a post‐hoc analysis of a Chinese randomized, double‐blind, non‐inferiority, phase III study. Patients (n = 572) with inadequate glycemic control received dulaglutide 1.5 mg (n = 189) or 0.75 mg (n = 194) once‐weekly or glimepiride (1–3 mg/day; n = 189) for 26 weeks. The primary objective of the study was to investigate the non‐inferiority of dulaglutide 1.5 mg versus glimepiride by the change from baseline to week 26 in glycated hemoglobin (non‐inferiority margin 0.4%).

Results

Dulaglutide 1.5 mg and 0.75 mg were non‐inferior (P < 0.001) and superior (P ≤ 0.002) versus glimepiride for the change in glycated hemoglobin from baseline to week 26. The least‐squares mean differences (95% confidence interval) versus glimepiride were dulaglutide 1.5 mg, −0.53% (−0.74, −0.32) and dulaglutide 0.75 mg, −0.32% (−0.53, −0.12). Significantly more patients attained glycated hemoglobin <7.0% at week 26 in the dulaglutide 1.5 mg (71.7%) versus the glimepiride (57.5%; P = 0.005) group. The decrease from baseline to week 26 in fasting blood glucose was significantly more pronounced in both the dulaglutide groups versus the glimepiride group (P < 0.01). The overall incidence and rate of hypoglycemia were lower in both of the dulaglutide groups versus the glimepiride group. At week 26, bodyweight had increased from baseline in the glimepiride group and decreased from baseline in both dulaglutide groups. The most frequent gastrointestinal drug‐related adverse events with dulaglutide were diarrhea, abdominal distension, nausea and vomiting.

Conclusions

These findings support once‐weekly dulaglutide monotherapy as a treatment for Chinese patients with early stage type 2 diabetes.
Disease burden and prescription patterns treating dermatophytosis in North India: salient findings from an online survey of 1041 dermatologists
Authors: Narang T. , Bishnoi A. , Dogra S. , Singh T.D. , Mahajan R. , Kavita K.
Published: May 2019

Linked article:D.M. L Saunte et al.J Eur Acad Dermatol Venereol2019;33: e393–e394.https://doi.org/10.1111/jdv.15685
Chinese facial physiognomy and modern day aesthetic practice
Authors: Samizadeh Souphiyeh
Published: May 2019

Background

Physiognomy is still practiced in China and is a factor influencing the cosmetic procedures offered by aesthetic practitioners, and treatments requested by patients.

Objective

The aim of this study was to assess the prevalence of belief in physiognomy in China and its effect on cosmetic treatments requested and offered by aesthetic practitioners.

Methods and materials

This study consisted of a survey given to the general public (online) and Chinese aesthetic practitioners (face to face).

Results

A total of 1816 responses (1070 general public, 746 aesthetic practitioners) were collected. About 63% of the general population and 86.3% of the aesthetic practitioners stated they believed in facial physiognomy. A majority of the general population surveyed believed that facial appearance can determine various aspects of their life. However, the majority believed changing their facial features would not affect factors believed to be determined by physiognomy. A total of 73.9% of the aesthetic practitioners thought their belief in physiognomy affected the treatments they suggest and most believed belief in physiognomy influences treatments requested.

Conclusion

The belief in facial physiognomy has a direct impact and needs to be taken into consideration during patient consultation.
Modified stall‐side crossmatch for transfusions in horses
Authors: Casenave Pauline , Leclere Mathilde , Beauchamp Guy , Blais Marie‐Claude
Published: May 2019

Background

After‐hours or out‐of‐clinic crossmatches are often limited by the lack of access to specialized material and technical expertise.

Hypothesis/Objectives

The goal was to adapt a stall‐side crossmatch test for pretransfusion evaluation in horses.

Animals

Twelve healthy mares (plasma and blood donors, teaching mares).

Methods

In a prospective study, blood from 12 mares was used to compare the results of 132 crossmatches performed with a rapid gel assay to crossmatches performed with a microgel column assay, and with predicted compatibilities based on blood types and detection of antibodies at a reference laboratory (microplate assay). The rapid gel assay protocol for dogs was adapted to decrease the formation of rouleaux that initially precluded equine erythrocytes migration through the gel.

Results

There was a good agreement between the rapid gel assay and the microgel assay as well as with the predicted compatibilities (κ > .6 for both). Agreement was higher between the microgel assay and the predicted compatibilities (κ = .8). The rapid gel assay failed to detect 6 predicted Aa incompatibilities (agglutinins‐related), 3 of which were also not detected with the microgel assay.

Conclusions and Clinical Importance

Based on these results, the modified rapid gel assay could be useful in settings when access to the microgel assay is not available. Discrepancies between both gel techniques and predicted compatibilities were most often low‐grade agglutination, which warrants further investigation to assess their clinical importance.
Pharmacokinetics and relative bioavailability of tiamulin in broiler chicken as influenced by different routes of administration
Authors: Vinothini Prabhakaran , Ramesh Srinivasan , Sooraj Nair Venugopalan , Preetha Srinivasan Palaninathan , Sriram Padmanabhan
Published: May 2019

The bioavailability and pharmacokinetic disposition of tiamulin in broiler chicken were investigated after administration through the crop, drinking water, and feed at 40 mg/kg body weight. Residues of tiamulin in tissues of broiler chicken were also assessed. Plasma and tissue concentrations of tiamulin were analyzed by reverse‐phase high‐performance liquid chromatography (HPLC) method. Plasma concentration–time data were described by the non‐compartmental model for all three routes, and pharmacokinetic parameters were calculated. There were no significant differences (p > 0.05) in pharmacokinetic parameters and mean plasma concentrations of tiamulin between three routes tested (crop, water, and feed), indicating equal efficacy. Tiamulin residues in edible tissues (muscles, skin, and fat) were lower than the advocated maximum residue limit (MRL of 0.1 µg/g and that of liver was 1 µg/g) on the 3rd day. No traces were found on the 5th day after drug administration. This indicated that the withdrawal period (less than 5 days) is very short, which makes it safer. This study shows that tiamulin can be used with equal efficacy through all routes of administration in broiler chicken (crop, water, and feed).
Surfactin and fengycin contribute to the protection of a Bacillus subtilis strain against grape downy mildew by both direct effect and defence stimulation
Authors: Li Yan , Héloir Marie‐Claire , Zhang Xun , Geissler Mareen , Trouvelot Sophie , Jacquens Lucile , Henkel Marius , Su Xin , Fang Xuewen , Wang Qi , Adrian Marielle
Published: May 2019

Bacillus subtilis GLB191 (hereafter GLB191) is an efficient biological control agent against the biotrophic oomycete Plasmopara viticola, the causal agent of grapevine downy mildew. In this study, we show that GLB191 supernatant is also highly active against downy mildew and that the activity results from both direct effect against the pathogen and stimulation of the plant defences (induction of defence gene expression and callose production). High‐performance thin‐layer chromatography analysis revealed the presence of the cyclic lipopeptides fengycin and surfactin in the supernatant. Mutants affected in the production of fengycin and/or surfactin were thus obtained and allowed us to show that both surfactin and fengycin contribute to the double activity of GLB191 supernatant against downy mildew. Altogether, this study suggests that GLB191 supernatant could be used as a new biocontrol product against grapevine downy mildew.
Electron backscatter diffraction (EBSD) analysis of maniraptoran eggshells with important implications for microstructural and taphonomic interpretations
Authors: Choi Seung , Han Seokyoung , Lee Yuong‐Nam
Published: May 2019

Electron backscatter diffraction (EBSD) is a useful tool for gathering crystallographic information from carbonate biominerals because it maps out the orientation of crystal grains very precisely. EBSD has become popular in invertebrate palaeontology but its application in vertebrate palaeontology remains limited. However, the study of fossil eggshells is a field where EBSD has wide potential applicability and provides a quantitative approach to fossil eggshell research as well as new qualitative data. Here we analyse fossil and extant maniraptoran dinosaur eggshells using EBSD analysis emphasizing four different aspects. The mapping imaging clarifies previously ambiguous characters such as squamatic ultrastructure and allows a more objective evaluation of avian and non‐avian maniraptoran eggshell. In particular, our results imply that the presence of an external zone in the manirpatoran eggshell is not diagnostic of avian eggshell. EBSD analysis can be also used for differentiating true pore canals from cracks in the eggshell radial section, thereby determining the biological genuineness or otherwise of a pore‐like structure. Finally, the misorientation angle distribution of the material shows a clear dichotomy that may reflect reproductive brooding strategy, although further studies on contact incubation of palaeognaths and neognaths are needed to confirm this.
Role of coping with negative emotions in cognitive behavioral therapy for persistent somatoform pain disorder: Is it more important than pain catastrophizing?
Authors: Yoshino Atsuo , Okamoto Yasumasa , Jinnin Ran , Takagaki Koki , Mori Asako , Yamawaki Shigeto
Published: May 2019

Aim

Cognitive behavioral therapy (CBT) is known to be effective for patients with persistent somatoform pain disorder (PSPD). Improvement of negative emotions in interpersonal stressful situations has been reported to reduce PSPD‐related clinical pain. However, these associations in CBT remain unclear. Therefore, we examined the relation between changes in negative emotions and clinical pain symptoms after CBT by using a multiple regression analysis that included pain catastrophizing.

Methods

We analyzed negative emotional intensity scores in stressful situations of 38 patients with PSPD who had completed CBT treatment and all the daily worksheets. Negative emotional intensity scores were recorded in daily worksheets during 12 weekly CBT sessions. Scores for the Pain Catastrophizing Scale (PCS), Visual Analogue Scale (VAS) as clinical pain intensity, Beck Depression Inventory – Second Edition (BDI‐II), and State–Trait Anxiety Inventory (STAI) were also obtained at pre‐ and post‐treatment. A multiple regression analysis was conducted using changes in VAS scores after CBT as the dependent variable, and changes in negative emotional intensity, PCS, BDI‐II, and STAI scores after CBT, age, and sex as independent variables.

Results

Negative emotional intensity scores decreased after CBT. In a multiple regression analysis, the emotional changes resulting from CBT depicted a modest positive relation with changes in VAS scores (β = 0.37; P < 0.05); however, there was no relation between changes in PCS scores after CBT and changes in VAS scores after CBT (β = 0.03).

Conclusion

The results show that negative emotions play an important role in the treatment effects of CBT for PSPD.
Bertrand's Paradox and the Maximum Entropy Principle
Authors: Shackel Nicholas , Rowbottom Darrell P.
Published: May 2019

An important suggestion of objective Bayesians is that the maximum entropy principle can replace a principle which is known to get into paradoxical difficulties: the principle of indifference. No one has previously determined whether the maximum entropy principle is better able to solve Bertrand's chord paradox than the principle of indifference. In this paper I show that it is not. Additionally, the course of the analysis brings to light a new paradox, a revenge paradox of the chords, that is unique to the maximum entropy principle.
Stream channel restoration increases climate resiliency in a thermally vulnerable Appalachian river
Authors: Merriam Eric R. , Petty J. T.
Published: May 2019

We quantified stream temperature response to in‐stream habitat restoration designed to improve thermal suitability and resiliency of a high‐elevation Appalachian stream known to support a temperature‐limited brook trout population. Our specific objectives were to determine if: (1) construction of deep pools created channel unit‐scale thermal refugia and (2) reach scale stream channel reconfiguration reduced peak water temperatures along a longitudinal continuum known to be highly susceptible to summer‐time warming. Contrary to expectations, constructed pools did not significantly decrease channel unit‐scale summer water temperatures relative to paired control sites. This suggests that constructed pools did not successfully intercept a cool groundwater source. However, we did find a significant effect of stream channel restoration on reach‐scale thermal regimes. Both mean and maximum daily stream temperatures experienced significantly reduced warming trends in restored sections relative to control sections. Furthermore, we found that restoration efforts had the greatest effect on stream temperatures downstream of large tributaries. Restoration appears to have significantly altered thermal regimes within upper Shavers Fork, largely in response to changes in channel morphology that facilitated water movement below major cold‐water inputs. Decreased longitudinal warming will likely increase the thermal resiliency of the Shavers Fork main‐stem, sustaining the ability of these key large river habitats to continue supporting critical metapopulation processes (e.g. supplemental foraging and dispersal among tributary populations) in the face of climate change.
An in vitro investigation into the effects of 10 Hz cyclic loading on tenocyte metabolism
Authors: Udeze Chineye P. , Jones Eleanor R. , Riley Graham P. , Morrissey Dylan , Screen Hazel R. C.
Published: May 2019

Tendinopathy is a prevalent, highly debilitating condition, with poorly defined etiology. A wide range of clinical treatments has been proposed, with systematic reviews largely supporting shock wave therapy or eccentric exercise. Characterizing these treatments have demonstrated both generate perturbations within tendon at a frequency of approximately 8‐12 Hz. Consequently, it is hypothesized that loading in this frequency range initiates increased anabolic tenocyte behavior, promoting tendon repair. The primary aim of this study was to investigate the effects of 10 Hz perturbations on tenocyte metabolism, comparing gene expression in response to a 10 Hz and 1 Hz loading profile. Tenocytes from healthy and tendinopathic human tendons were seeded into 3D collagen gels and subjected to 15 minutes cyclic strain at 10 Hz or 1 Hz. Tenocytes from healthy tendon showed increased expression of all analyzed genes in response to loading, with significantly increased expression of inflammatory and degradative genes with 10 Hz, relative to 1 Hz loading. By contrast, whilst the response of tenocytes from tendinopathy tendon also increased with 10 Hz loading, the overall response profile was more varied and less intense, possibly indicative of an altered healing response. Through inhibition of the pathway, IL1 was shown to be involved in the degradative and catabolic response of cells to high‐frequency loading, abrogating the loading response. This study has demonstrated for the first time that loading at a frequency of 10 Hz may enhance the metabolic response of tenocytes by initiating an immediate degradatory and inflammatory cell response through the IL1 pathway, perhaps as an initial stage of tendon healing.
Chronic anterior tibial stress fractures in athletes: No crack but intense remodeling
Authors: Schilcher Jörg , Bernhardsson Magnus , Aspenberg Per
Published: May 2019

Purpose

Delayed healing of anterior tibial stress fractures in athletes is related to high tensional forces acting across a putative fracture gap. These forces lead to crack propagation and create strains that exceed tissue differentiation thresholds for new bone to form in the gap. The “dreaded black line” is a radiographic hallmark sign of stress fractures considered to represent a transverse fracture gap. However, whether a fracture gap truly exists at the microscopic level remains unclear. The aim of this study was to describe the area of the “dreaded black line” microscopically and to identify signs of delayed healing.

Methods

Between 2011 and 2016, we included seven athletes with chronic anterior mid‐shaft tibial stress fractures. The fracture site was excised as a cylindrical biopsy. The biopsy was evaluated with micro‐CT and histology. The formation of new bone in the defect was evaluated radiographically.

Results

The “dreaded black line” seen on pre‐operative radiographs in all patients could not be seen on the microscopic level. Instead, the area of the putative crack showed widened resorption cavities, lined with active osteoblasts, and surrounded by immature bone. This area of intense remodeling seemed to create a false impression of a fracture line on radiographs. Complete cortical continuity was restored at the biopsy site at median 8 months (range 6‐13 months).

Conclusion

Tibial stress fractures in athletes normally show no fracture defect, but a region of increased remodeling. The healing process is already ongoing but seems mechanically insufficient.
Cardiorespiratory fitness as a predictor of short‐term and lifetime estimated cardiovascular disease risk
Authors: Swainson Michelle G. , Ingle Lee , Carroll Sean
Published: May 2019

Development of cardiovascular disease (CVD) remains a public health concern for young to middle‐aged adults, now exacerbated by the increasing prevalence of obesity and sedentary lifestyles. Cardiorespiratory fitness (CRF) improves the reclassification of short‐term (10‐year) CVD risk, but has not been uniformly defined across studies. This study evaluated cross‐sectional differences in short‐term and lifetime CVD risk scores, across both absolute metabolic equivalent (MET) and sex‐ and age‐standardized CRF categories in 805 apparently healthy young to middle‐aged adults (68% male; 47.4 ± 7.2 years). CVD risk factors were evaluated, and estimated cardiorespiratory fitness (CRF) measurements (METS and peak VO2) were derived from a submaximal Bruce treadmill test. CRF measures also included post‐exercise heart rate recovery (HRR) data. Consistent trends showing more favorable risk factor profiles and lower short‐term CVD (QRISK2), and CVD mortality (SCORE) scores, associated with higher levels of CRF were evident in both sexes. Lifetime CVD risk (Q‐Lifetime) was highest in the lowest CRF categories. Peak VO2 and HRR following submaximal exercise testing contributed to the variability in short‐term and lifetime CVD risk. Global CVD risk predictions were examined across different contemporary CRF classifications with inconsistent findings. Recommended absolute MET and sex‐ and age‐standardized CRF categories were significantly associated with both short‐term and lifetime risk of CVD outcomes. However, compared to internationally derived normative CRF standards, cohort‐specific CRF categories resulted in markedly different proportion of individuals classified in the “poor” CRF category at higher CVD risk.
Re‐examination of accelerometer data processing and calibration for the assessment of physical activity intensity
Authors: Arvidsson Daniel , Fridolfsson Jonatan , Börjesson Mats , Andersen Lars Bo , Ekblom Örjan , Dencker Magnus , Brønd Jan Christian
Published: May 2019

This review re‐examines the use of accelerometer and oxygen uptake data for the assessment of activity intensity. Accelerometers capture mechanical work, while oxygen uptake captures the energy cost of this work. Frequency filtering needs to be considered when processing acceleration data. A too restrictive filter attenuates the acceleration signal for walking and, to a higher degree, for running. This measurement error affects shorter (children) more than taller (adults) individuals due to their higher movement frequency. Less restrictive filtering includes more movement‐related signals and provides measures that better capture mechanical work, but may include more noise. An optimal filter cut‐point is determined where most relevant acceleration signals are included. Further, accelerometer placement affects what part of mechanical work being captured. While the waist placement captures total mechanical work and therefore contributes to measures of activity intensity equivalent by age and stature, the thigh and wrist placements capture more internal work and do not provide equivalent measures. Value calibration of accelerometer measures is usually performed using measured oxygen uptake with the metabolic equivalent of task (MET) as reference measure of activity intensity. However, the use of MET is not stringent and is not a measure of activity intensity equivalent by age and stature. A candidate measure is the mass‐specific net oxygen uptake, VO2net (VO2tot − VO2stand). To improve measurement of physical activity intensity using accelerometers, research developments are suggested concerning the processing of accelerometer data, use of energy expenditure as reference for activity intensity, and calibration procedure with absolute versus relative intensity.
Potential and Impediments to Senior Citizens’ Volunteering to Maintain Basic Services in Shrinking Regions
Authors: Mettenberger Tobias , Küpper Patrick
Published: May 2019

Against the background of demographic change and municipal austerity, policy‐makers are evoking the crucial role that younger retirees could play in supplementing the provision of basic services through volunteering. This article ties into this discussion, critically questioning the potential of (younger) senior citizens’ volunteering as a way of maintaining basic services in shrinking regions. Qualitative interviews from two regional case studies in rural Germany provide insights into the motivations, forms and contexts of such volunteering. The empirical results show that the potential for basic service provision is limited. Key players engaged in multiple activities and more‐passive types of contact‐seekers have little interest in taking on further tasks. Traditional basic services do not fit in with the interests of potential volunteers, and time budgets are constrained by alternative activities and commitments. Furthermore, volunteering is hampered by very basic structural conditions of peripheral rural life. Overall, our results reflect the heterogeneity and diversity of (older) rural milieus and lifestyles, and challenge persistent scientific perceptions of rural and, especially, village populations as place‐based closely knit communities.
Early infectious complications after autologous hematopoietic cell transplantation for multiple myeloma
Authors: Rahman Shafia , Rybicki Lisa , Ky Hamilton Betty , Pohlman Brad , Jagadeesh Deepa , Cober Eric , Kalaycio Matt , Dean Robert , Sobecks Ronald , Mossad Sherif B. , Majhail Navneet S.
Published: May 2019

Background

The spectrum of infectious complications in autologous hematopoietic cell transplant recipients (AHCT) with multiple myeloma has not been well described in the recent era of novel agent induction and improved supportive care.

Methods

We conducted a retrospective cohort study of 413 adult myeloma AHCT recipients at our institution from 2007‐2016 to describe the cumulative incidence and risk factors for various infections and FN occurring within the first 100 days after AHCT. Additionally, landmark analysis was done among 404 patients who survived at least 100 days after transplant admission to estimate the association of infections with subsequent non‐relapse mortality (NRM), overall survival (OS), and relapse‐free survival (RFS).

Results

Cumulative incidences (95% CI) of infection events by day 100 were: FN 43% (38‐48), any infection 21% (17‐25), bacterial 17% (14‐21), viral 4% (3‐7) and fungal 1% (0.5‐3), central line‐associated blood stream infection 3% (2‐6), and Clostridium difficile colitis 6% (4‐8). Patients with infection had a longer initial transplant hospitalization (median 17 vs 16 days, P < 0.01), more readmissions (31% vs 8%, P < 0.01), and spent more days in hospital in first 100 days (median 18 vs 16 days, P < 0.01). A 100‐day mortality was low and similar between groups (2% vs 1%, P = 0.28). In landmark analysis of 404 100‐day survivors, OS was worse among patients with early infections (hazard ratio 1.54 [1.03‐2.30], P = 0.03), although there was no difference in NRM and RFS.

Conclusions

Notwithstanding advances in supportive care, early infectious complications remain a relevant source of morbidity and require attention in myeloma AHCT recipients.
Serological and molecular screening of umbilical cord blood for Toxoplasma gondii infection
Authors: Botein Eman F. , Darwish Ahmad , El‐Tantawy Nora L. , EL‐baz Rizk , Eid Mohamed I. , Shaltot Ali M
Published: May 2019

Background

Human umbilical cord blood has proven to be a successful alternate source of hematopoietic stem cells for pediatric patients with major hematologic disorders. Toxoplasma gondii is a global opportunistic protozoan which cause fatal complications in immunocompromised individuals.

Aim

Our goal is to study the prevalence of toxoplasmosis in umbilical cord blood (UCB) and to assess the sensitivity of ELISA and PCR for Toxoplasma infection screening.

Material and Methods

One hundred cord blood samples were collected immediately after delivery. Anti‐Toxoplasma IgG and IgM antibodies were determined using ELISA method; Toxoplasma DNA was detected using nested PCR technique. Total nucleated cells (TNC) and HB were also determined. Demographic data and risk factors data related to the transmission of toxoplasmosis, were collected from mothers.

Results

Among 100 cord blood samples, 36 (36%) were positive for anti‐Toxoplasma IgG antibodies and 6 (6%) were positive for anti‐Toxoplasma IgM antibodies. The nested PCR showed 11 (11%) samples containing Toxoplasma DNA from which, 6 (55%) samples were IgM positive. There was no significant association between the risk of Toxoplasma transmission and cord blood positivity for toxoplasmosis.

Conclusion

Owing to the prevalence of toxoplasmosis, its rapid progression and its fatal outcome in immunocompromised patients, cord blood screening for toxoplasmosis with nested PCR should be incorporated into cord blood bank screening protocols.
A guide to indications, components and interpretation of urodynamic investigations
Authors: Taithongchai Annika , Sultan Abdul H , Thakar Ranee
Published: May 2019

Key content

Indications for urodynamic investigations include urinary tract symptoms such as urge incontinence, stress urinary incontinence (SUI) and neurological urinary incontinence.

Components of urodynamic testing include a physical assessment along with representative uroflowmetry with post‐void residual (PVR), transurethral cystometry and a pressure‐flow study.

It is important for clinicians to understand key physiological measurements and parameters of lower urinary tract function.

There are many factors to consider when interpreting results from urodynamic investigations, and it is vital for documentation to be accurate and methodical.

Learning objectives

To understand the key indications and components of urodynamics and how to define a clear question prior to starting investigations.

To learn accepted physiological parameters for lower urinary tract functions and apply these to a concise method of interpreting urodynamic results.

To acknowledge the limitations of an investigation when attempting to reproduce pathology in an artificial environment.

Ethical issues

Should all women undergoing an incontinence procedure have urodynamic investigations?

Who to believe – the patient or the test?
Multiple sclerosis and pregnancy
Authors: Kanagaraj Priya , Evangelou Nikos , Kapoor Dipanwita
Published: May 2019

Key content

Multiple sclerosis (MS) is a chronic neurological disease that manifests with clinical and subclinical attacks of central nervous system demyelination.

Women are at least twice as likely as men to suffer from MS, with a mean age of onset of 30 years.

Pregnancy has no adverse long‐term effect on disease progression, but it is associated with a higher relapse rate in the immediate postpartum period.

Pregnancy can worsen pre‐existing urinary/bowel dysfunction and motor problems.

MS is not associated with significant obstetric or neonatal complications.

Learning objectives

To understand how to manage pregnant women with MS in the multidisciplinary setting.

To understand the importance of pre‐pregnancy counselling for women with MS who are on disease‐modifying drugs.

To understand the implications of pregnancy on MS symptoms and their management.

To be aware of the benefits of breastfeeding and the safety of disease‐modifying drugs and lactation.

Ethical issues

In the absence of clear guidelines, should women ever be advised to avoid pregnancy?

Should women be offered in vitro fertilisation treatment, which is known to increase disease relapse?
The effect of subchronic oral exposure to zearalenone on hematologic and biochemical analytes, and the blood redox status of adult rabbit bucks
Authors: Tsouloufi Theodora K. , Tsakmakidis Ioannis A. , Tsousis Georgios , Papaioannou Nikolaos , Tzika Eleni , Kritsepi‐Konstantinou Maria
Published: May 2019

Background

Zearalenone (ZEN) is a mycoestrogen with a ubiquitous presence in animal feeds, which also has hematotoxic, hepatotoxic, nephrotoxic, and immunotoxic properties. However, there is a paucity of literature that discusses the effects of ZEN on rabbits.

Objectives

The aim of this study was to evaluate the effect of a prolonged, low‐level (50 μg ZEN/kg body weight) exposure on the clinicopathologic and redox status analytes of rabbit bucks.

Methods

Ten adult bucks were included in the study. Each underwent a 7‐week control period, followed by a 7‐week exposure period. Water or ZEN solutions were daily administered orally (0.5 mL) during the control and exposure periods, respectively. Blood samples were collected weekly for Complete Blood Counts, serum biochemical analyte and reactive oxygen metabolite (ROM) measurements. Data were analyzed using a mixed model, and the level of significance was set at a P of <0.05.

Results

During the ZEN exposure period, significant increases were noted in the red blood cell distribution width (RDW) and mean platelet volumes (MPVs), as well as in the white blood cell, monocyte, and eosinophil counts. Significant increases were observed in aspartate aminotransferase and total bilirubin, whereas urea, creatinine, glucose, total calcium, sodium, and potassium concentrations were significantly decreased. The ROM concentrations did not differ significantly between the control and ZEN exposure periods.

Conclusions

Under the present experimental conditions, ZEN affected some of the clinicopathologic analytes of adult rabbit bucks; these changes were mostly indicative of mild hepatocellular damage and dysfunction, inflammatory and/or allergic responses, and renal tubular damage. A ZEN dose of 50 μg/kg body weight did not seem to affect the blood redox status of bucks, as evaluated by the ROM concentrations.
Thermal Performance and Operating Regimes of a Flat Pulsating Heat Pipe for the Temperature Homogenization of Two Symmetric Plates
Authors: Dell'innocenti Aline , Lips Stéphane , Sartre Valérie , Blet Nicolas , Coulloux Jérôme , Bonjour Jocelyn
Published: May 2019

A copper–water closed flat pulsating heat pipe (PHP), 3.4 m long and of inner diameter 4 mm, was manufactured and tested. This PHP aims both at homogenizing the temperature of a large aluminum plate, of surface area 150 × 420 mm2, and at lowering its mean temperature by transferring the heat to an adjacent heat sink of same dimensions. The PHP thermal resistance is measured at various heat transfer rates, condenser temperatures, and inclination angles. It decreases when the heat transfer rate increases or when the PHP is progressively tilted from the vertical unfavorable orientation to a favorable one. Resistance values as low as 0.04 K/W are measured. Whatever the conditions, a minimum heat input of 200 W is necessary for the correct start-up of the PHP. A map of the operating regimes—no-flow, oscillating, intermittent, and stable behavior—is proposed. Nonreproducibility effects are highlighted in tilted position, leading to different operating regimes at increasing and decreasing heat loads, but also more broadly depending on the history of the working operating conditions of the PHP. However, the concept proposed in this work is very promising for applications involving large heat source and heat sink.
Formal Process to Support Resolution of Functional Trade-Offs in Complex Product Development
Authors: Oizumi Kazuya , Ishida Keita , Tai Muyo , Aoyama Kazuhiro
Published: May 2019

This research study proposes a method to resolve issues with trade-offs between functionalities, which hinder the unconventional improvement of a product. As products have become increasingly complex, it has become difficult to grasp all the aspects of a product. To resolve the problematic trade-off issues of a complex product, it is necessary to model the product in an appropriate form and to gather knowledge from experts in each domain. Although there have been several models to tackle this issue, modeling still poses difficulties due to a lack of clear guidelines. This paper classifies models into three types: function-based, cognition-based, and physics-based models. Next, their roles and description guidelines are clarified. As a function-based model depicts the functionality of a product in a rather simple description, it is employed to specify significant trade-offs. A cognition-based model depicts the designers' recognition of physical phenomena, whereas a physics-based model rigorously depicts the physical phenomena. A cognition-based model is appropriate for ideation, while the physics-based model contributes to the objectivity of a model. This study proposes a strategy of complementary modeling and the use of cognition-and physics-based models. To support the ideation of a solution to the trade-offs, the theory of inventive problem solving (TRIZ) is applied. The proposed method is validated by a case study of continuously variable transmissions (CVT).