bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin delivery of hydrophilic molecules from liposomes and polysaccharide‐coated liposomes
Authors: Belhaj N. , Arab‐Tehrany E. , Loing E. , Bézivin C.
Published: March 2017

Objectives

Liposomes are commonly used in cosmetic formulations to increase the bioavailability of active ingredients. We have previously shown that polysaccharide coating of liposomes improves their resistance to surfactants and electrolytes. In the current study, we have assessed the impact of coating on the skin penetration enhancer properties of liposomes.

Methods

The physicochemical properties of coated liposomes (Ionosomes™) were evaluated before and after encapsulation of two different hydrophilic molecules (caffeine and a hexapeptide), and compared to those observed with non‐coated liposomes. Moreover, in vitro permeation experiments were performed using Franz™‐modified diffusion cells, with normal human skin as membranes.

Results

Results showed that both coated and non‐coated liposomes significantly improved the bioavailability of hydrophilic active molecules in skin, compared to reference solutions. Although liposome coating slightly reduced entrapment efficiency, the delivery of active molecules was not adversely affected by the process. In conclusion, polysaccharide coating of liposomes allows for better protection of their integrity without compromising the skin bioavailability of the active molecules that they convoy.
IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population
Authors: Queiroz G. A. , Costa R. S. , Alcantara‐Neves N. M. , Nunes de Oliveira Costa G. , Barreto M. L. , Carneiro V. L. , Figueiredo C. A.
Published: March 2017

Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin‐4 (IL‐4), interleukin‐5 (IL‐5) and interleukin‐13 (IL‐13). Interleukin‐33 (IL‐33) appears to be a potent inducer of Th2 immune response. This occurs when IL‐33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL‐5 and IL‐13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53–0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL‐5 production (OR 1.36, 95% CI: 1.09–1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07–1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08–2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.
Effectiveness of a polyhexanide irrigation solution on methicillin‐resistant Staphylococcus aureus biofilms in a porcine wound model
Authors: Davis Stephen C , Harding Andrew , Gil Joel , Parajon Fernando , Valdes Jose , Solis Michael , Higa Alex
Published: March 2017

Irrigation and removal of necrotic debris can be beneficial for proper healing. It is becoming increasingly evident that wounds colonized with biofilm forming bacteria, such as Staphylococcus aureus (SA), can be more difficult to eradicate. Here we report our findings of the effects of an irrigation solution containing propyl‐betaine and polyhexanide (PHMB) on methicillin‐resistant Staphylococcus aureus (MRSA) biofilms in a porcine wound model. Thirty‐nine deep partial thickness wounds were created with six wounds assigned to one of six treatment groups: (i) PHMB, (ii) Ringer's solution, (iii) hypochlorous acid/sodium hypochlorite, (iv) sterile water, (v) octenidine dihydrochloride, and (vi) octenilin. Wounds were inoculated with MRSA and covered with a polyurethane dressing for 24 hours to allow biofilm formation. The dressings were then removed and the wounds were irrigated twice daily for 3 days with the appropriate solution. MRSA from four wounds were recovered from each treatment group at 3 days and 6 days hours after initial treatment. Irrigation of wounds with the PHMB solution resulted in 97·85% and 99·64% reductions of MRSA at the respective 3 days and 6 days assessment times when compared to the untreated group. Both of these reductions were statistically significant compared to all other treatment groups (P values <0·05).
Low‐temperature preparation of titanium diboride fine powder via magnesiothermic reduction in molten salt
Authors: Bao Ke , Wen Yan , Khangkhamano Matthana , Zhang Shaowei
Published: March 2017

Phase pure titanium diboride (TiB2) powder of 100‐200 nm was synthesized from TiO2 and B2O3 using a molten‐salt‐assisted magnesiothermic reduction technique. The effects of salt type, Mg amount, reaction temperature, and TiO2 raw materials on the synthesis process were examined and the relevant reaction mechanisms discussed. Among the three chloride salts (NaCl, KCl, and MgCl2), MgCl2 showed the best accelerating‐effect. To synthesize phase pure TiB2, 20 mol% excessive Mg had to be used to compensate for the evaporation loss of Mg. Particle shape and size of raw material TiO2 showed little effect on the formation of TiB2 and its shape and size, suggesting that relatively cheaper and coarser TiO2 raw materials could be used for low‐temperature synthesis of TiB2 fine particles. The “dissolution‐precipitation” mechanism governed the overall molten salt synthesis process.
High fidelity: extra‐pair fertilisations in eight Charadrius plover species are not associated with parental relatedness or social mating system
Authors: Maher Kathryn H. , Eberhart‐Phillips Luke J. , Kosztolányi András , Remedios Natalie dos , Carmona‐Isunza María Cristina , Cruz‐López Medardo , Zefania Sama , St Clair James J. H. , Alrashidi Monif , Weston Michael A. , Serrano‐Meneses Martín A. , Krüger Oliver , Hoffman Joseph I. , Székely Tamás , Burke Terry , Küpper Clemens
Published: March 2017

Extra‐pair paternity is a common reproductive strategy in many bird species. However, it remains unclear why extra‐pair paternity occurs and why it varies among species and populations. Plovers (Charadrius spp.) exhibit considerable variation in reproductive behaviour and ecology, making them excellent models to investigate the evolution of social and genetic mating systems. We investigated inter‐ and intra‐specific patterns of extra‐pair parentage and evaluated three major hypotheses explaining extra‐pair paternity using a comparative approach based on the microsatellite genotypes of 2049 individuals from 510 plover families sampled from twelve populations that constituted eight species. Extra‐pair paternity rates were very low (0 to 4.1% of chicks per population). No evidence was found in support of the sexual conflict or genetic compatibility hypotheses, and there was no seasonal pattern of extra‐pair paternity (EPP). The low prevalence of EPP is consistent with a number of alternative hypotheses, including the parental investment hypothesis, which suggests that high contribution to care by males restricts female plovers from engaging in extra‐pair copulations. Further studies are needed to critically test the importance of this hypothesis for mate choice in plovers.
Campylobacter jejuni infection associated with relatively poor condition and low survival in a wild bird
Authors: Taff Conor C. , Townsend Andrea K.
Published: March 2017

Campylobacter jejuni is the most common foodborne pathogen in industrialized countries. Most human infections come from contaminated poultry, but wild birds are also known to harbor C. jejuni. Wild birds are often described as asymptomatic carriers, but this assumption is based on domestic poultry research. We studied the effects of C. jejuni infection on body condition and survival of adult and nestling American crows Corvus brachyrhynchos in Davis, California. Previous work demonstrated that more than half of the crows in this population are infected with C. jejuni and that at least some of the isolates carried by crows are similar to those found in domestic animals and humans. In this study, we compared the body condition of infected and uninfected individuals at the time of capture among adults (n = 44; 52% infected) and nestlings (n = 97; 77% infected). We subsequently monitored these banded individuals for up to 3 yr and used mark–recapture survival analysis to estimate relationships between infection status and later survival. We found that adult crows infected with C. jejuni were in poor condition relative to uninfected adults: average body mass of infected birds was 12% lower, whereas average body size did not differ between the two groups. Likewise, apparent survival probability was lower for infected adults. In contrast, nestling body condition, fledging success, and survival did not differ by infection status. This is the first study to document adverse effects of C. jejuni infection in a free‐living, wild bird. If these effects are widespread, C. jejuni exposure may be a cause of conservation concern for some species, especially when human activities increase exposure to infections or introduce novel strains to wild bird populations. Our results add to the growing body of work demonstrating hidden long‐term costs of seemingly mild infections in wild populations.
Mitochondrial PKC‐ε deficiency promotes I/R‐mediated myocardial injury via GSK3β‐dependent mitochondrial permeability transition pore opening
Authors: Wang Shijun , Zhang Feng , Zhao Gang , Cheng Yong , Wu Ting , Wu Bing , Zhang You‐en
Published: March 2017

Mitochondrial fission is critically involved in cardiomyocyte apoptosis, which has been considered as one of the leading causes of ischaemia/reperfusion (I/R)‐induced myocardial injury. In our previous works, we demonstrate that aldehyde dehydrogenase‐2 (ALDH2) deficiency aggravates cardiomyocyte apoptosis and cardiac dysfunction. The aim of this study was to elucidate whether ALDH2 deficiency promotes mitochondrial injury and cardiomyocyte death in response to I/R stress and the underlying mechanism. I/R injury was induced by aortic cross‐clamping for 45 min. followed by unclamping for 24 hrs in ALDH2 knockout (ALDH2−/−) and wild‐type (WT) mice. Then myocardial infarct size, cell apoptosis and cardiac function were examined. The protein kinase C (PKC) isoform expressions and their mitochondrial translocation, the activity of dynamin‐related protein 1 (Drp1), caspase9 and caspase3 were determined by Western blot. The effects of N‐acetylcysteine (NAC) or PKC‐δ shRNA treatment on glycogen synthase kinase‐3β (GSK‐3β) activity and mitochondrial permeability transition pore (mPTP) opening were also detected. The results showed that ALDH2−/− mice exhibited increased myocardial infarct size and cardiomyocyte apoptosis, enhanced levels of cleaved caspase9, caspase3 and phosphorylated Drp1. Mitochondrial PKC‐ε translocation was lower in ALDH2−/− mice than in WT mice, and PKC‐δ was the opposite. Further data showed that mitochondrial PKC isoform ratio was regulated by cellular reactive oxygen species (ROS) level, which could be reversed by NAC pre‐treatment under I/R injury. In addition, PKC‐ε inhibition caused activation of caspase9, caspase3 and Drp1Ser616 in response to I/R stress. Importantly, expression of phosphorylated GSK‐3β (inactive form) was lower in ALDH2−/− mice than in WT mice, and both were increased by NAC pre‐treatment. I/R‐induced mitochondrial translocation of GSK‐3β was inhibited by PKC‐δ shRNA or NAC pre‐treatment. In addition, mitochondrial membrane potential (∆Ψm) was reduced in ALDH2−/− mice after I/R, which was partly reversed by the GSK‐3β inhibitor (SB216763) or PKC‐δ shRNA. Collectively, our data provide the evidence that abnormal PKC‐ε/PKC‐δ ratio promotes the activation of Drp1 signalling, caspase cascades and GSK‐3β‐dependent mPTP opening, which results in mitochondrial injury‐triggered cardiomyocyte apoptosis and myocardial dysfuction in ALDH2−/− mice following I/R stress.
Histone deacetylase inhibitors promote eNOS expression in vascular smooth muscle cells and suppress hypoxia‐induced cell growth
Authors: Tan Xiaoling , Feng Lan , Huang Xiaoyong , Yang Yidong , Yang Chengzhong , Gao Yuqi
Published: March 2017

Hypoxia stimulates excessive growth of vascular smooth muscle cells (VSMCs) contributing to vascular remodelling. Recent studies have shown that histone deacetylase inhibitors (HDIs) suppress VSMC proliferation and activate eNOS expression. However, the effects of HDI on hypoxia‐induced VSMC growth and the role of activated eNOS in VSMCs are unclear. Using an EdU incorporation assay and flow cytometry analysis, we found that the HDIs, butyrate (Bur) and suberoylanilide hydroxamic acid (SAHA) significantly suppressed the proliferation of hypoxic VSMC lines and induced apoptosis. Remarkable induction of cleaved caspase 3, p21 expression and reduction of PCNA expression were also observed. Increased eNOS expression and enhanced NO secretion by hypoxic VSMC lines were detected using Bur or SAHA treatment. Knockdown of eNOS by siRNA transfection or exposure of hypoxic VSMCs to NO scavengers weakened the effects of Bur and SAHA on the growth of hypoxic VSMCs. In animal experiments, administration of Bur to Wistar rats exposed to hypobaric hypoxia for 28 days ameliorated the thickness and collagen deposition in pulmonary artery walls. Although the mean pulmonary arterial pressure (mPAP) was not obviously decreased with Bur in hypoxic rats, right ventricle hypertrophy index (RVHI) was decreased and the oxygen partial pressure of arterial blood was elevated. Furthermore, cell viability was decreased and eNOS and cleaved caspase 3 were induced in HDI‐treated rat pulmonary arterial SMCs. These findings imply that HDIs prevent hypoxia‐induced VSMC growth, in correlation with activated eNOS expression and activity in hypoxic VSMCs.
Nutrition, dental caries and periodontal disease: a narrative review
Authors: Hujoel Philippe P. , Lingström Peter
Published: March 2017

Aim

To provide a narrative review of the role of macro‐ and micronutrients in relation to dental caries, gingival bleeding and destructive periodontal disease.

Materials & Methods

This review is based on systematic reviews (when available) and comparative human studies.

Results

Dental caries cannot develop without the presence of dietary fermentable carbohydrates, in particular sugar. The susceptibility to develop caries in the presence of carbohydrates may be influenced by genetics and micronutrients such as vitamin D. Gingival bleeding and destructive periodontal disease are sensitive markers to both abnormalities in macronutrient content (excessive carbohydrates or poly‐unsaturated fat intake, deficient protein intake) and micronutrient intake (e.g. vitamin C and B12).

Conclusion

Dental caries and periodontal diseases are a sensitive alarm bell for an unhealthy diet, which predicts the future onset of the diseases of civilizations.
Age‐related changes in immune function (immune senescence) in caries and periodontal diseases: a systematic review
Authors: Preshaw Philip M. , Henne Karsten , Taylor John J. , Valentine Ruth A. , Conrads Georg
Published: March 2017

Aim

To systematically review the evidence regarding immune senescence in the pathogenesis of periodontitis and dental caries.

Methods

A systematic search of electronic databases utilizing medical subject headings (MeSH terms) supplemented by screening of review articles and other relevant texts was undertaken.

Results

Seventy‐three articles were included (43 for periodontitis, 30 for caries). Study results were found to be generally heterogeneous. Regarding periodontitis, human studies suggest evidence for altered neutrophil function and increased production of pro‐inflammatory mediators (e.g. interleukin‐1β, interleukin‐6 and prostaglandin E2) in older compared to younger subjects, and animal experiments suggest increased expression of genes that contribute to a pro‐inflammatory state in older compared to younger animals. Regarding dental caries, research relating to changes in immune functioning and the impact of ageing is in its infancy. A small number of studies have reported components of innate and adaptive immunity that affect the composition of saliva and dental biofilms with possible impacts on caries progression.

Conclusion

There is evidence that immune functioning related to periodontitis and (less investigated) dental caries alters with increasing age. In both conditions, age‐associated mechanistic changes in immune functioning are complex and incompletely understood and it is not clear how these relate to disease susceptibility.
Global epidemiology of dental caries and severe periodontitis – a comprehensive review
Authors: Frencken Jo E. , Sharma Praveen , Stenhouse Laura , Green David , Laverty Dominic , Dietrich Thomas
Published: March 2017

Background

Dental caries and periodontitis are the most common oral diseases and major causes of tooth loss.

Aim

To perform a review of global prevalence and incidence of dental caries and periodontitis.

Methodology

Inclusion and exclusion criteria were developed. MEDLINE database and EMBASE database were used to search for eligible publications using keywords and MeSH terms. Additionally, WHO databank was used for obtaining dental caries information and PUBMED for a search on trends of dental caries prevalence and severity.

Results

Over the last four decades, the prevalence and severity of dentine carious lesions among 5‐ and 12‐year‐olds have declined; the decay‐component is very high, with the lowest prevalence among 12‐year‐olds in high‐income countries, which also had the lowest prevalence among 35‐ to 44‐year‐olds; and the number of retained teeth has increased around the globe. The prevalence of periodontitis is high, with approximately 10% of the global population affected by severe periodontitis. Study heterogeneity and methodological issues hamper comparisons across studies and over time.

Conclusion

While the prevalence of dental caries has decreased, the disease is prevalent in all age groups. The prevalence of periodontitis is high. There is insufficient evidence to conclude that the prevalence of periodontitis has changed over time.
Dental biofilm: ecological interactions in health and disease
Authors: Marsh P. D. , Zaura Egija
Published: March 2017

Background

The oral microbiome is diverse and exists as multispecies microbial communities on oral surfaces in structurally and functionally organized biofilms.

Aim

To describe the network of microbial interactions (both synergistic and antagonistic) occurring within these biofilms and assess their role in oral health and dental disease.

Methods

PubMed database was searched for studies on microbial ecological interactions in dental biofilms. The search results did not lend themselves to systematic review and have been summarized in a narrative review instead.

Results

Five hundred and forty‐seven original research articles and 212 reviews were identified. The majority (86%) of research articles addressed bacterial–bacterial interactions, while inter‐kingdom microbial interactions were the least studied. The interactions included physical and nutritional synergistic associations, antagonism, cell‐to‐cell communication and gene transfer.

Conclusions

Oral microbial communities display emergent properties that cannot be inferred from studies of single species. Individual organisms grow in environments they would not tolerate in pure culture. The networks of multiple synergistic and antagonistic interactions generate microbial inter‐dependencies and give biofilms a resilience to minor environmental perturbations, and this contributes to oral health. If key environmental pressures exceed thresholds associated with health, then the competitiveness among oral microorganisms is altered and dysbiosis can occur, increasing the risk of dental disease.
Bundling and joint marketing by rival firms
Authors: Jeitschko Thomas D. , Jung Yeonjei , Kim Jaesoo
Published: March 2017

We study joint marketing by firms who price discriminate between consumers who patronize only one firm (single purchasers) and those who purchase from both (bundle purchasers). Firms either set the price of the bundle and then compete along side the bundle; or they determine a rebate that is applied to joint purchasers and then set prices. Even though the pricing structure in the joint marketing scheme is determined noncooperatively, the commitment to the joint marketing agreement allows firms to leverage their stand‐alone prices—leading to higher profits and lower consumer surplus in either case, compared to both uniform pricing and independent price discrimination without a joint marketing agreement. Nevertheless the two schemes differ dramatically, in that rebates increase joint purchasing, whereas bundle pricing diminishes bundle purchases.
Motivate and select: Relational contracts with persistent types
Authors: Nikolowa Radoslawa
Published: March 2017

We develop a model of relational contracts with moral hazard and asymmetric persistent information about an employee's type. We find that the form of the optimal contract depends on the job characteristics and the distribution of employees' talent. Bonus contracts are more likely to be adopted in complex jobs and when high talent is not too common or too rare. Firms with “normal” jobs are more likely to adopt termination contracts. In labor market equilibrium, different contracts may be adopted byex anteidentical firms. Hence, we offer an explanation for the coexistence of different employment systems within the same industry.
What can morphology tell us about ecology of four invasive goby species?
Authors: Jakubčinová K. , Simonović P. , Števove B. , Čanak Atlagić J. , Kováč V.
Published: March 2017

This study presents a detailed comparative analysis of external morphology of four of the most invasive goby species in Europe (round goby Neogobius melanostomus, bighead goby Ponticola kessleri, monkey goby Neogobius fluviatilis and racer goby Ponticola gymnotrachelus) and interprets some ecological requirements of these species based on their morphological attributes. The results are evaluated within an ontogenetic context, and the morphological differences between the species are discussed in terms of the question: can special external shape adaptations help to assess the invasive potential of each species? The morphometric analyses demonstrate important differences between the four invasive gobies. Neogobius melanostomus appears to have the least specialized external morphology that may favour its invasive success: little specialization to habitat or diet means reduced restraints on overall ecological requirements. The other three species were found to possess some morphological specializations (P. kessleri to large prey, N. fluviatilis to sandy habitats and P. gymnotrachelus to macrophytes), but none of these gobies have managed to colonize such large areas or to reach such overall abundances as N. melanostomus.
A zinc finger protein, interacted with cyclophilin, affects root development via IAA pathway in rice
Authors: Cui Peng , Liu Hongbo , Ruan Songlin , Ali Basharat , Gill Rafaqat Ali , Ma Huasheng , Zheng Zhifu , Zhou Weijun
Published: March 2017

The plant hormone auxin plays a crucial role in lateral root development. To better understand the molecular mechanisms underlying lateral root formation, an auxin‐responsive gene OsCYP2 (Os02g0121300) was characterized from rice. Compared to the wild type, OsCYP2‐RNAi (RNA interference) lines exhibited distinctive defects in lateral root development. Yeast two‐hybrid and glutathione S‐transferase pull‐down results confirmed that OsCYP2 interacted with a C2HC‐type zinc finger protein (OsZFP, Os01g0252900) which is located in the rice nucleus. T2 OsZFP‐RNAi lines had significantly fewer lateral roots than did wild‐type plants, which suggests a role for OsCYP2 and OsZFP in regulating lateral root development. Quantitative real‐time polymerase chain reaction showed that the expression of certain Aux/IAA (auxin/indole‐3‐acetic acid) genes was altered in OsCYP2‐ and OsZFP‐RNAi lines in response to IAA. These findings imply that OsCYP2 and OsZFP participate in IAA signal pathways controlling lateral root development. More importantly, OsIAA11 showed functional redundancy not only in OsCYP2‐RNAi lines but also in OsZFP‐RNAi lines, which provides important clues for the elucidation of mechanisms controlling lateral root development in response to auxin.
Effects of p75NTR deficiency on cholinergic innervation of the amygdala and anxiety‐like behavior
Authors: Busch Ruben , Baldus Marian , Vogt Miriam A. , Berger Stefan M. , Bartsch Dusan , Gass Peter , von Bohlen und Halbach Oliver
Published: March 2017

The p75 neurotrophin receptor (p75NTR) is a low‐affinity receptor that is capable of binding neurotrophins. Two different p75NTR knockout mouse lines are available either with a deletion in Exon III (p75NTRExIII−/−) or in Exon IV (p75NTRExIV−/−). In p75NTRExIII knockout mice, only the full‐length p75NTR is deleted, whereas in p75NTRExIV knockout mice, the full‐length as well as the truncated isoform of the receptor is deleted. Deletion of p75NTR has been shown to affect, among others, the septohippocampal cholinergic innervation pattern and neuronal plasticity within the hippocampus. We hypothesize that deletion of p75NTR also alters the morphology and physiology of a further key structure of the limbic system, the amygdala. Our results indicate that deletion of p75NTR also increases cholinergic innervation in the basolateral amygdala in adult as well as aged p75NTRExIII−/− and p75NTRExIV−/− mice. The p75NTRExIV−/− mice did not display altered long‐term potentiation (LTP) in the basolateral amygdala as compared to age‐matched control littermates. However, p75NTRExIII−/− mice display stronger LTP in the basolateral amygdala compared to age‐matched controls. Bath‐application of K252a (a trk antagonist) did not inhibit the induction of LTP in the basolateral amygdala, but reduced the level of LTP in p75NTRExIII−/− mice to levels seen in respective controls. Moreover, p75NTRExIII−/− mice display altered behavior in the dark/light box. Thus, deletion of p75NTR in mice leads to physiological and morphological changes in the amygdala and altered behavior that is linked to the limbic system.

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A detailed musculoskeletal study of a fetus with anencephaly and spina bifida (craniorachischisis), and comparison with other cases of human congenital malformations
Authors: Alghamdi Malak A. , Ziermann Janine M. , Gregg Lydia , Diogo Rui
Published: March 2017

Few descriptions of the musculoskeletal system of humans with anencephaly or spina bifida exist in the literature. Even less is published about individuals in which both phenomena occur together, i.e. about craniorachischisis. Here we provide a detailed report on the musculoskeletal structures of a fetus with craniorachischisis, as well as comparisons with the few descriptions for anencephaly and with musculoskeletal anomalies found in other congenital malformations. We focused in particular on the comparison with trisomies 13, 18, and 21 because neural tube defects have been associated with such chromosomal defects. Our results showed that many of the defects found in the fetus with craniorachischisis are similar not only to anomalies previously described in the available works on musculoskeletal phenotypes seen in fetuses with anencephaly and spina bifida, but also to a wide range of other different conditions/syndromes including trisomies 13, 18 and 21, and cyclopia. The fact that similar anomalies are seen commonly not only in a wide range of different syndromes, but also as variants of the normal human population and as the ‘normal’ phenotype of other animals, supports Pere Alberch's unfortunately named idea of a ‘logic of monsters’. That is, it supports the idea that development is so constrained that both in ‘normal’ and abnormal development one sees certain outcomes being produced again and again because ontogenetic constraints only allow a few possible outcomes, thus also leading to cases where the anatomical defects of some organisms are similar to the ‘normal’ phenotype of other organisms. In fact, this applies not only to specific anomalies but also to general patterns, such as the fact that in pathological conditions affecting different regions of the body, one consistently sees more defects on the upper limbs than on the lower limbs. Such general patterns are, again, seen in the fetus examined for this study, which had 29 muscle anomalies on the right upper limb and 22 muscle anomalies on the left upper limb, vs. seven muscle anomalies on the right lower limb and two on the left lower limb. It is therefore hoped that this work, which is part of our effort to describe and compile information on human musculoskeletal defects found in a wide range of conditions, will contribute not only to a better understanding of craniorachischisis in particular and of human congenital malformations in general, but also to broader discussions on the fields of comparative anatomy, and developmental and evolutionary biology.
MIS‐SPECIFICATION TESTING IN RETROSPECT
Authors: Spanos Aris
Published: March 2017

The primary objective of this paper is threefold. First, to undertake a retrospective view of Mis‐Specification (M‐S) testing, going back to the early 20th century, with a view to (i) place it in the broader context of modeling and inference and (ii) bring out some of its special features. Second, to call into question several widely used arguments undermining the importance of M‐S testing in favor of relying on weak probabilistic assumptions in conjunction with generic robustness claims and asymptotic inference. Third, to bring out the crucial role of M‐S testing in securing trustworthy inference results. This is achieved by extending/modifying Fisher's statistical framework with a view to draw a clear line between the modeling and the inference facets of statistical induction. The proposed framework untangles the statistical from the substantive (structural) model and focuses on how to secure the adequacy of the statistical model before probing for substantive adequacy. A case is made for using joint M‐S tests based on custom‐built auxiliary regressions with a view to enhance the effectiveness and reliability of probing for potential statistical misspecifications.
Spatial Coregistration of Functional Near‐Infrared Spectroscopy to Brain MRI
Authors: Chen Michelle , Blumen Helena M. , Izzetoglu Meltem , Holtzer Roee
Published: March 2017

BACKGROUND AND PURPOSE

Traditional neuroimaging techniques restrict movement and make it difficult to study the processes that require oral, upper limb, or lower limb motor execution. Functional near‐infrared spectroscopy (fNIRS) is an optical neuroimaging modality that measures brain oxygenation and permits movement during data acquisition. A key limitation of fNIRS, however, is the lack of a standard method to coregister quantitative fNIRS measurements to structural images such as magnetic resonance imaging (MRI). Additionally, fNIRS‐MRI coregistration studies have not been reported in older adults.

METHODS

fNIRS and structural MRI were acquired from 30 nondemented older adults. Sixteen fNIRS channels that assess hemodynamic changes in the prefrontal cortex (PFC; an area crucial in various age‐related processes) were coregistered to structural MRI. Vitamin E capsules were used to mark the locations of fNIRS detectors and light sources on the scalp. We used the balloon‐inflation algorithm to project fNIRS channel locations on the scalp to underlying cortical surface.

RESULTS

We provide coordinates for the 16 fNIRS channels in the PFC on the cortical surface in both MNI and Talairach spaces, with minimal variability that is within the spatial resolution of our fNIRS system.

CONCLUSIONS

Our study provides useful spatial information for stand‐alone fNIRS data in future studies, particularly investigations in age‐related processes.
Decreased expression of SOX7 induces cell proliferation and invasion and correlates with poor prognosis in oral squamous cell carcinoma
Authors: Oh Kyu‐Young , Hong Kyoung‐Ok , Huh Young‐Sung , Lee Jae‐Il , Hong Seong‐Doo
Published: March 2017

Background

SOX7, a member of the SOX family of transcription factors, acts as a tumor suppressor in multiple cancers. Downregulation of SOX7 has been reported in advanced tumors and correlates with poor prognosis. The aims of this study were to investigate the effects of SOX7 on cell proliferation, invasion, and colony formation in oral squamous cell carcinoma (OSCC) cells and to evaluate the effectiveness of SOX7 protein as a prognostic indicator for OSCC patients.

Methods

oral squamous cell carcinoma (OSCC) cell lines were treated with SOX7 small interfering RNA or SOX7 peptide, and their effects on cell proliferation, invasiveness, and colony formation were investigated by proliferation, in vitro invasion, and clonogenic assays. SOX7 protein expression in OSCC and normal oral mucosal tissues was examined by immunohistochemistry. Associations between SOX7 protein expression and clinicopathological parameters of OSCC patients were statistically analyzed.

Results

SOX7 silencing‐induced cell proliferation and invasion in SCC‐4 cells. SOX7 peptide treatment inhibited cell proliferation, colony formation, and invasion in SCC‐9 and SCC‐25 cells. Expression of SOX7 protein was decreased in OSCC tissues compared with normal oral mucosal tissues (P<.001). Negative SOX7 expression in patients with OSCC was significantly associated with positive lymph node metastasis (P=.041), advanced TNM stage (P=.024), and poor prognosis (P=.017).

Conclusions

These results suggest that SOX7 inhibits cell proliferation, colony formation, and invasion in OSCC as a tumor suppressor and that negative SOX7 expression could be a poor prognostic indicator for patients with OSCC.
Paediatric horse‐related trauma
Authors: Theodore Jane E , Theodore Sigrid G , Stockton Kellie A , Kimble Roy M
Published: March 2017

Aim

This retrospective cohort study reported on the epidemiology of horse‐related injuries for patients presenting to the only tertiary paediatric trauma hospital in Queensland. The secondary outcome was to examine the use of helmets and adult supervision. Traumatic brain injury (TBI) was examined in relation to helmet use. Morbidity and mortality were also recorded.

Methods

Included were all patients presenting with any horse‐related trauma to the Royal Children's Hospital in Brisbane from January 2008 to August 2014. Data were retrospectively collected on patient demographics, hospital length of stay (LOS), mechanism of injury (MOI), safety precautions taken, diagnoses and surgical procedures performed.

Results

Included in the analysis were 187 incidents involving 171 patients. Most patients were aged 12–14 years (36.9%) and female (84.5%). The most common MOI were falls while riding horses (97.1%). Mild TBI (24.6%) and upper limb fractures (20.9%) were common injuries sustained. Patients who wore helmets had significantly reduced hospital LOS and severity of TBI when compared with those who did not wear helmets (P < 0.001 and P = 0.028, respectively). Morbidity was reported in 7.5% of patients. There were three deaths in Queensland.

Conclusion

Helmet use is recommended for non‐riders when handling horses, in addition to being a compulsory requirement whilst horse riding. Prompts in documentation may assist doctors to record the use of safety attire and adult supervision. This will allow future studies to further investigate these factors in relation to clinical outcomes.
Personalised dosing of medicines for children
Authors: Al-Metwali Basma , Mulla Hussain
Published: March 2017

Objectives

Doses for most drugs are determined from population-level information, resulting in a standard ?one-size-fits-all’ dose range for all individuals. This review explores how doses can be personalised through the use of the individuals’ pharmacokinetic (PK)-pharmacodynamic (PD) profile, its particular application in children, and therapy areas where such approaches have made inroads.

Key findings

The Bayesian forecasting approach, based on population PK/PD models that account for variability in exposure and response, is a potent method for personalising drug therapy. Its potential utility is even greater in young children where additional sources of variability are observed such as maturation of eliminating enzymes and organs. The benefits of personalised dosing are most easily demonstrated for drugs with narrow therapeutic ranges such as antibiotics and cytotoxics and limited studies have shown improved outcomes. However, for a variety of reasons the approach has struggled to make more widespread impact at the bedside: complex dosing algorithms, high level of technical skills required, lack of randomised controlled clinical trials and the need for regulatory approval.

Personalised dosing will be a necessary corollary of the new precision medicine initiative. However, it faces a number of challenges that need to be overcome before such an approach to dosing in children becomes the norm.
Branched‐chain amino acid ratios in low‐protein diets regulate the free amino acid profile and the expression of hepatic fatty acid metabolism‐related genes in growing pigs
Authors: Duan Y. H. , Li F. N. , Wen C. Y. , Wang W. L. , Guo Q. P. , Li Y. H. , Yin Y. L.
Published: March 2017

Liver metabolism is affected by nutrients. The aim of this study was to explore the effects of low‐protein diets (17% crude protein, CP) supplemented with branched‐chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile) and valine (Val), on hepatic amino acid profile and lipid metabolism in growing pigs. The ratio of Leu : Ile : Val in all groups was 1 : 0.51 : 0.63 (20% crude protein, CP), 1 : 1 : 1 (17% CP), 1 : 0.75 : 0.75 (17% CP), 1 : 0.51 : 0.63 (17% CP) and 1 : 0.25 : 0.25 (17% CP) respectively. Results revealed that compared to the positive control group (1 : 0.51 : 0.63, 20% CP), the low‐protein diets significantly augmented the concentrations of most essential amino acids and non‐essential amino acids (p < .05), with the greatest values observed in the 1 : 0.25 : 0.25 group. Moreover, relative to the control, the low‐protein diets with the Leu : Ile : Val ratio ranging from 1 : 0.75 : 0.75 to 1 : 0.25 : 0.25 markedly downregulated the mRNA abundance of acetyl‐CoA carboxylase (ACC), lipoprotein lipase (LPL) and fatty acid‐binding protein 4 (FABP‐4) (p < .05), and upregulated the mRNA expression of hormone‐sensitive lipase (HSL), peroxisome proliferator‐activated receptor‐g coactivator‐1α (PGC‐1α), uncoupling protein 3 (UCP3) and liver carnitine palmitoyltransferase 1 (L‐CPT‐1) (p < .05). Therefore, our data suggest that protein‐restricted diets supplemented with optimal BCAA ratio, that is, 1 : 0.75 : 0.75–1 : 0.25 : 0.25, induce a shift from fatty acid synthesis to fatty acid oxidation in the liver of growing pigs. These effects may be associated with increased mitochondrial biogenesis.
Clinical presentation, diagnostic findings and outcome in dogs diagnosed withpresumptive spinal‐only meningoen‐cephalomyelitis of unknown origin
Authors: Cornelis I. , Volk H. A. , Van Ham L. , De Decker S.
Published: March 2017

Objectives

To summarise clinical presentation, diagnostic findings and long‐term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone.

Methods

Medical records were reviewed for dogs diagnosed with presumptive spinal‐only meningoencephalomyelitis of unknown origin between 2006 and 2015.

Results

21 dogs were included; the majority presented with an acute (43%) or chronic (52%) onset of neurological signs. Ambulatory paresis was the most common neurological presentation (67%). Neurological examination most commonly revealed a T3‐L3 myelopathy, and spinal hyperaesthesia was a common finding (71%). A spinal cord lesion was visible in 90% of cases on magnetic resonance imaging. Eighteen lesions (86%) showed parenchymal contrast enhancement and 17 lesions (81%) showed contrast enhancement of overlying meninges. All dogs were treated with immunosuppressive doses of glucocorticosteroids, sometimes combined with cytosine arabinoside. At time of data capture, 10/21 dogs (48%) had died or been euthanased because of the condition. Overall median survival time was 669 days.

Clinical Significance

Meningoencephalomyelitis of unknown origin should be considered in the differential diagnosis of dogs presenting with a progressive myelopathy. Magnetic resonance imaging features can possibly help to distinguish presumptive meningoencephalomyelitis of unknown origin from other more common spinal diseases. Overall, long‐term survival is guarded, approximately 50% of dogs will die or be euthanased despite appropriate therapy.
Neurological manifestations in dogs naturally infected by Leishmania infantum: descriptions of 10 cases and a review of the literature
Authors: Giannuzzi A. P. , Ricciardi M. , De Simone A. , Gernone F.
Published: March 2017

In order to evaluate possible nervous system involvement in canine leishmaniasis, retrospective evaluation of all medical records of leishmaniotic dogs exhibiting neurological signs referred to our hospital over a 5‐year period was performed. The records of 10 dogs were reviewed. Depending on the neuroanatomical localisation, the dogs underwent advanced diagnostic imaging, cerebrospinal fluid analysis, electrodiagnostic testing and histopathologic evaluations. The final neurological diagnosis was: meningoencephalitis (n=2), brain haemorrhagic stroke (n=1), haemorrhagic choroiditis (n=1), meningomyelitis (n=2), ischaemic myelopathy (n=1), polymyositis (n=2) and peripheral neuropathy (n=1). This study confirms that both central and peripheral nervous systems can be affected by leishmaniasis and provides an overview on the possible etiopathogenetic mechanisms. In addition, clinical and diagnostic findings, therapy and follow‐up of affected dogs are described.
Augmentation of hepatitis C virus‐specific immunity and sustained virologic response
Authors: Shrivastava S. , Wilson E. , Poonia B. , Tang L. , Osinusi A. , Kohli A. , Kottilil S.
Published: March 2017

Treatment for chronic hepatitis C virus (HCV) infection has rapidly evolved into interferon‐free directly acting antiviral regimens (DAA) that result in high sustained virologic response. DAAs primarily work by suppressing HCV replication and rely less on the immune system than interferon‐based therapies. However, it is unclear whether the immune system recovers with suppression of HCV replication and contributes to HCV clearance with DAA therapy. We previously demonstrated HCV clearance is associated with increased HCV‐specific immunity in CHCV‐GT‐1‐infected patients during treatment with sofosbuvir (SOF)+ribavirin (RBV). Here, we aimed to analyse changes in HCV‐specific immunological responses associated with viral clearance with combination DAA therapy of SOF+ledipasvir (LDV) for 12 weeks in CHCV‐GT1 (N=14) patients who relapsed without augmentation of HCV‐specific immunity during treatment with SOF+RBV. Phenotypic and functional changes within the T‐cell compartment of PBMCs pre‐ and post‐treatment were analysed. Retreatment of relapsers with LDV/SOF resulted in all patients attaining SVR12. Suppression of HCV was associated with a decline in T‐cell exhaustion markers (CD57; Tim3; PD1) along with augmented of HCV‐specific T‐cell IFN‐gamma responses post‐treatment. Addition of LDV to SOF was associated with augmentation of HCV‐specific immunity and SVR in patients who previously failed SOF+RBV therapy without increased immunity. These findings demonstrate a novel effect of DAA in inducing host immune responses to aid HCV clearance and achieve SVR.
Comparative transcriptomic analysis of key genes involved in flavonoid biosynthetic pathway and identification of a flavonol synthase from Artemisia annua L.
Authors: Liu S. , Liu L. , Tang Y. , Xiong S. , Long J. , Liu Z. , Tian N.
Published: March 2017

The regulatory mechanism of flavonoids, which synergise anti‐malarial and anti‐cancer compounds in Artemisia annua, is still unclear.

In this study, an anthocyanidin‐accumulating mutant callus was induced from A. annua and comparative transcriptomic analysis of wild‐type and mutant calli performed, based on the next‐generation Illumina/Solexa sequencing platform and de novo assembly.

A total of 82,393 unigenes were obtained and 34,764 unigenes were annotated in the public database. Among these, 87 unigenes were assigned to 14 structural genes involved in the flavonoid biosynthetic pathway and 37 unigenes were assigned to 17 structural genes related to metabolism of flavonoids. More than 30 unigenes were assigned to regulatory genes, including R2R3‐MYB, bHLH and WD40, which might regulate flavonoid biosynthesis. A further 29 unigenes encoding flavonoid biosynthetic enzymes or transcription factors were up‐regulated in the mutant, while 19 unigenes were down‐regulated, compared with the wild type. Expression levels of nine genes involved in the flavonoid pathway were compared using semi‐quantitative RT‐PCR, and results were consistent with comparative transcriptomic analysis. Finally, a putative flavonol synthase gene (AaFLS1) was identified from enzyme assay in vitro and in vivo through heterogeneous expression, and confirmed comparative transcriptomic analysis of wild‐type and mutant callus.

The present work has provided important target genes for the regulation of flavonoid biosynthesis in A. annua.
Implementation of green innovations – The impact of stakeholders and their network relations
Authors: Fliaster Alexander , Kolloch Michael
Published: March 2017

Green innovation is becoming increasingly important for companies and whole societies, and the research in this field has essentially increased in recent years. As green innovation is expected to ensure both environmental sustainability and economical profitability, it might seriously affect the partly colliding interests of various groups of stakeholders. However, from previous studies less is known about the impact that various groups of stakeholders and particularly the relationships among these stakeholders exert on the implementation of green innovations. To address this gap we first substantiate the relevance of the stakeholder theory for innovation studies in general and green innovations in particular. Furthermore, we argue that from the innovator's perspective green innovations are likely to be affected by the interactions with as well as between many primary and secondary stakeholders. To explore this issue in‐depth we conducted a case study of the implementation of an offshore wind farm in Germany. Our research revealed that network ties among stakeholders can be both conducive and detrimental to the green innovation. The insights gained in our study contribute to the stakeholder analysis for the implementation of green innovations.