bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigations on Croconic Acid in Superacidic Media
Authors: Schickinger Manuel , Jessen Christoph , Morgenstern Yvonne , Muggli Katharina , Zischka Florian , Kornath Andreas
Published: September 2018

Croconic acid reacts in superacidic solutions HF/MF5 (M = As, Sb) to yield its corresponding salts [H3O5C5][MF6] and [(H3O5C5)H(H3O5C5)][MF6]3·2HF (M = As, Sb). The degree of protonation is strongly dependent on the stoichiometric ratio of the Lewis acid regarding croconic acid. Monoprotonated salts were characterized by vibrational spectroscopy and in the case of [H3O5C5][AsF6] (1) by a single‐crystal X‐ray structure analysis. [H3O5C5][AsF6] crystallizes in the monoclinic space group P21/c with four formula units per unit cell. The sesquiprotonated species of croconic acid [(H3O5C5)H(H3O5C5)][SbF6]3·2HF (4) was also characterized by single‐crystal X‐ray structure analysis. It crystallizes in the triclinic space group P1 with one formula unit per unit cell. The vibrational spectra of the monoprotonated salts were compared to quantum chemical calculations of the [H3O5C5]+·3HF cation and experimental data reported for croconic acid.
Carbohydrate‐Scaffolded Thymine Multimers: Scope and Limitations of the Allylation–Hydroboration Sequence
Authors: Ciuk Anna K. , Gloe Tobias‐Elias , Lindhorst Thisbe K.
Published: September 2018

Carbohydrates serve as versatile molecular scaffolds and platforms in organic chemistry, for example in combinatorial chemistry or for the multivalent presentation of ligands. Carbohydrate scaffolds are frequently employed in the synthesis of multivalent glycoconjugates and utilized for the study of fundamental parameters of carbohydrate recognition. However, facile procedures are required to achieve a useful variety of sugar platforms. Here, we report on the synthesis of a series of divalent und tetravalent hydroxypropylated mannosides, using an allylation‐hydroboration sequence. The hydroxypropyl‐linkers were further functionalized with thymine in a Mitsunobu reaction to achieve multivalent glycothymine scaffolds for intramolecular [2+2] photocyclization. This will be of importance to further investigate the influence of the 3D orientation in carbohydrate recognition. We discuss the scope of the allylation‐hydroboration sequence comparing 2,3‐, 2,6‐, and 4,6‐difunctionalization and 2,3,4,6‐tetrafunctionalization of protected 2‐aminoethyl α‐d‐mannopyranosides.
People with low back pain show reduced movement complexity during their most active daily tasks
Authors: Gizzi Leonardo , Röhrle Oliver , Petzke Frank , Falla Deborah
Published: September 2018

Background

Actigraphy is a quantitative method for the investigation of human physical activity and is normally based on accelerometric and/or kinematic data.

Methods

A multichannel actigraphy system, able to record both acceleration and spine angles, was employed in this study to measure the quality of movement in 17 individuals with chronic low back pain (LBP) and 18 healthy individuals during unrestricted daily activities. An indication of movement complexity was computed by means of non‐negative matrix factorization throughout the 24 hr period and in the 60 min of highest activity.

Results

Movement complexity differed only when the 60 min of highest activity was taken into account, with the LBP group showing reduced complexity (e.g., for dimensionality = 8, over 90% of the comparisons showed a significant reduction in the LBP group).

Conclusions

The results are compatible with the hypothesis that pain induces a reduction in the available kinematic trajectories and degrees of freedom during natural movements, which becomes more evident when more demanding tasks are performed. A reduced movement complexity suggests a persistent alteration of the descending neural pathways and/or a disrupted somatosensory information processing, which could be possibly contrasted by administering highly variable motor tasks.

Significance

People with chronic pain move differently. Movement quality is difficult to evaluate during daily activities, yet it may prove more informative than quantitative measurements. We proposed a new approach for computing movement complexity and found out that patients’ movements get more stereotyped when higher spinal acceleration is required.
Graphite/Nanocrystalline Zeolite Platform for Selective Electrochemical Determination of Hepatitis C Inhibitor Ledipasvir
Authors: Atty Shimaa A. , Mohamed Mona A. , Abd El Halim Lobna M. , Fouad Fatma A. , Boukherroub Rabah
Published: September 2018

A simple and efficient procedure is described for the electrochemical determination of ledipasvir (LDP) in presence of co‐formulated drug sofosbuvir (SOF). Herein, a highly sensitive, low‐cost electrochemical protocol was utilized to fabricate a zeolite modified carbon paste electrode (ZY/CPE) through mixing of zeolite nanostructures with graphite powder. The fabricated sensor displayed high sensitivity, allowing optimal charge transfer/electrode kinetics. Different experimental and chemical factors, including electrode composition, effect of pH, scan rate and amount of ZY were evaluated carefully to obtain the highest electrochemical response. Under optimized conditions and using square wave voltammetry (SWV), the current response of the ZY/CPE electrochemical sensing platform exhibited a detection limit of 7.5×10−9 M and a large linear range from 5.0×10−8 to 1.0×10−4 M. The practical applicability of the suggested electrochemical platform was verified in the assessment of LDP in pharmaceutical formulations with excellent recoveries in the range of 99.50–98.87 %. Moreover, a biological relevance of the developed sensor was established by the analysis of LDP in human urine and plasma samples with satisfactory recoveries of 99.00 and 99.68 %, respectively. Due to the simplicity and ease of preparation of the proposed sensor, it can be used in quality control laboratories and for clinical analysis.
On‐line electroextraction in capillary electrophoresis: Application on the determination of glutamic acid in soy sauces
Authors: Campos Camila D. M. , Reyes Felix G. R. , Manz Andreas , da Silva José A. F.
Published: September 2018

We present an on‐line, single step coupling between liquid‐liquid extraction and capillary electrophoresis with capacitively coupled contactless conductivity detection, which allows an efficient analysis of complex food matrices with high sodium content. The sodium depletion was demonstrated using an aqueous two‐phase system. The aqueous two‐phase system enables the electrically driven extraction of the target compounds. The sample was prepared in Dextran‐rich phase (8% w/v 500 kDa Dextran, DEX). The background electrolyte (acetic acid 5.0 mol/L) contained 6% w/v of 6 kDa PEG. As proof of applicability, we employed the developed method for glutamic acid quantification on soy sauces. The peak area of glutamic acid presents no significant difference (α = 0.05), while the peak area of the sodium presented a reduction of 11.7 ± 0.2 and 19 ± 3% for premium and low‐cost soy sauce samples analyzed. The glutamic acid concentration for premium soy sauce sample was 2.7 ± 0.8 and 4.8 ± 0.4 g/L, and for low‐cost soy sauce sample, the concentration was 9.9 ± 0.9 g/L, which agreed with those obtained by other analytical techniques.
A companion to the preclinical common data elements and case report forms for rodent EEG studies. A report of the TASK3 EEG Working Group of the ILAE/AES Joint Translational Task Force
Authors: Ono Tomonori , Wagenaar Joost , Giorgi Filippo S. , Fabera Petr , Hanaya Ryosuke , Jefferys John , Moyer Jason T. , Harte‐Hargrove Lauren C. , Galanopoulou Aristea S.
Published: September 2018

Electroencephalography (EEG) is commonly used in epilepsy and neuroscience research to study brain activity. The principles of EEG recording such as signal acquisition, digitization, and conditioning share similarities between animal and clinical EEG systems. In contrast, preclinical EEG studies demonstrate more variability and diversity than clinical studies in the types and locations of EEG electrodes, methods of data analysis, and scoring of EEG patterns and associated behaviors. The TASK3 EEG working group of the International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force has developed a set of preclinical common data elements (CDEs) and case report forms (CRFs) for recording, analysis, and scoring of animal EEG studies. This companion document accompanies the first set of proposed preclinical EEG CRFs and is intended to clarify the CDEs included in these worksheets. We provide 7 CRF and accompanying CDE modules for use by the research community, covering video acquisition, electrode information, experimental scheduling, and scoring of EEG activity. For ease of use, all data elements and input ranges are defined in supporting Excel charts (Appendix S1).
Long noncoding RNA HOTAIR is upregulated in an aggressive subgroup of gastrointestinal stromal tumors (GIST) and mediates the establishment of gene‐specific DNA methylation patterns
Authors: Bure Irina , Geer Sandra , Knopf Jasmin , Roas Maike , Henze Sabine , Ströbel Philipp , Agaimy Abbas , Wiemann Stefan , Hoheisel Jörg D. , Hartmann Arndt , Haller Florian , Moskalev Evgeny A.
Published: September 2018

Aberrant alterations of DNA methylation are common events in oncogenesis. The origin of cancer‐associated epigenetic defects is of interest for mechanistic understanding of malignant transformation and—in the long run—therapeutic modulation of DNA methylation in a locus‐specific manner. Given the ability of certain long noncoding RNAs to operate as an interface between DNA and the epigenetic modification machinery which can interact with DNA methyltransferases, we hypothesized—considering HOTAIR as an example—that this transcript may contribute to gene specificity of DNA methylation. Using gastrointestinal stromal tumors (GISTs, n = 67) as a model, we confirmed upregulation of HOTAIR in tumors with high risk of recurrence and showed high abundance of the transcript in GIST cell lines. HOTAIR knockdown in GIST‐T1 cells triggered transcriptional response of genes involved in the organization and disassembly of the extracellular matrix and, notably, induced global locus‐specific alterations of DNA methylation patterns. Hypomethylation was induced at a total of 507 CpG sites, whereas 382 CpG dinucleotides underwent gain of methylation upon HOTAIR depletion. Importantly, orchestrated gain or loss of methylation at multiple individual CpG sites was shown for cancer‐related DPP4, RASSF1, ALDH1A3, and other targets. Collectively, our data indicate that HOTAIR enables target specificity of DNA methylation in GIST and is capable of dual (hypo‐ and hypermethylation) regulation by a yet to be defined mechanism. The results further suggest the feasibility of manipulating DNA methylation in a targeted manner and are of interest in the context of epigenetic cancer therapy.
Timely diagnosis of dementia? Family carers' experiences in 5 European countries
Authors: Woods Bob , Arosio Francesca , Diaz Ana , Gove Dianne , Holmerová Iva , Kinnaird Lindsay , Mátlová Martina , Okkonen Eila , Possenti Mario , Roberts Jennifer , Salmi Anna , van den Buuse Susanne , Werkman Wendy , Georges Jean
Published: September 2018

Objectives

Timely diagnosis of dementia is recommended in national strategies. To what extent is it occurring across Europe, what factors are associated with it, and what is the impact on carers emotions of quality of diagnostic disclosure?

Methods/design

Survey of family carers recruited through 5 Alzheimer's associations (Czech Republic, Finland, Italy, the Netherlands, and Scotland). One thousand four hundred and nine carers participated, 84% completing online. Fifty‐two percent were adult children, and 37% were spouses, with median age 57. Most (83%) were female.

Results

Nearly half (47%) of carers reported that an earlier diagnosis would have been preferable. Delaying factors included reluctance of the person with dementia, lack of awareness of dementia, the response of professionals, and delays within health systems. Recent diagnoses were no more likely to be considered timely, although professional responses appeared to be improving. Delayed diagnoses were more often reported by adult child carers and where the diagnosis was made in the later stages of dementia, or another condition had been previously diagnosed. In all countries except Italy, the diagnosis was shared with the person with dementia in the majority of cases. Timely diagnoses and higher quality diagnostic disclosure are associated with better adjustment and less negative emotional impact on carers in the short and medium term.

Conclusions

Although the study sample were well educated and likely to be in touch with an Alzheimer organisation, many continued to experience the diagnosis of dementia as coming too late, and further work on public awareness, as well as on professional responses, is needed.
Memory Image Completion: Establishing a task to behaviorally assess pattern completion in humans
Authors: Vieweg Paula , Riemer Martin , Berron David , Wolbers Thomas
Published: September 2018

For memory retrieval, pattern completion is a crucial process that restores memories from partial or degraded cues. Neurocognitive aging models suggest that the aged memory system is biased toward pattern completion, resulting in a behavioral preference for retrieval over encoding of memories. Here, we built on our previously developed behavioral recognition memory paradigm—the Memory Image Completion (MIC) task—a task to specifically target pattern completion. First, we used the original design with concurrent eye‐tracking in order to rule out perceptual confounds that could interact with recognition performance. Second, we developed parallel versions of the task to accommodate test settings in clinical environments or longitudinal studies. The results show that older adults have a deficit in pattern completion ability with a concurrent bias toward pattern completion. Importantly, eye‐tracking data during encoding could not account for age‐related performance differences. At retrieval, spatial viewing patterns for both age groups were more driven by stimulus identity than by response choice, but compared to young adults, older adults' fixation patterns overlapped more between stimuli that they (wrongly) thought had the same identity. This supports the observation that older adults choose responses perceived as similar to a learned stimulus, indicating a bias toward pattern completion. Additionally, two shorter versions of the task yielded comparable results, and no general learning effects were observed for repeated testing. Together, we present evidence that the MIC is a reliable behavioral task that targets pattern completion, that is easily and repeatedly applicable, and that is made freely available online.
Higher diet‐dependent acid load is associated with risk of breast cancer: Findings from the sister study
Authors: Park Yong‐Moon Mark , Steck Susan E. , Fung Teresa T. , Merchant Anwar T. , Elizabeth Hodgson M. , Keller Jean A. , Sandler Dale P.
Published: September 2018

Dietary factors that contribute to chronic low‐grade metabolic acidosis have been linked to breast cancer risk, but to date no epidemiologic study has examined diet‐dependent acid load and breast cancer. We used data from 43,570 Sister Study participants who completed a validated food frequency questionnaire at enrollment (2003–2009) and satisfied eligibility criteria. The Potential Renal Acid Load (PRAL) score was used to estimate diet‐dependent acid load. Higher scores reflect greater consumption of protein and phosphorus, and lower consumption of potassium, calcium and magnesium. The association between PRAL and breast cancer was evaluated using multivariable Cox proportional hazards regression. We identified 1,614 invasive breast cancers diagnosed at least 1 year after enrollment (mean follow‐up, 7.6 years). The highest PRAL quartile, reflecting greater acid‐forming potential, was associated with increased risk of breast cancer (HRhighest vs. lowest quartile: 1.21 [95% CI, 1.04–1.41], ptrend = 0.04). The association was more pronounced for estrogen receptor (ER)‐negative (HRhighest vs. lowest quartile: 1.67 [95% CI, 1.07–2.61], ptrend = 0.03) and triple‐negative breast cancer (HRhighest vs. lowest quartile: 2.20 [95% CI, 1.23–3.95], ptrend = 0.02). Negative PRAL scores, representing consumption of alkaline diets, were associated with decreased risk of ER‐negative and triple‐negative breast cancer, compared to a PRAL score of 0 representing neutral pH. Higher diet‐dependent acid load may be a risk factor for breast cancer while alkaline diets may be protective. Since PRAL scores are positively correlated with meat consumption and negatively correlated with fruit and vegetable intake, results also suggest that diets high in fruits and vegetables and low in meat may be protective against hormone receptor negative breast cancer.
Explaining trust in large biometric infrastructures: A critical realist case study of India's Aadhaar project
Authors: Masiero Silvia
Published: September 2018

The need for formulation of solid explanatory theories is heightened in information and communication technologies for development (ICT4D) by the high incidence of failure, which involves substantial costs for the countries affected. A core argument of this paper is that a critical realist ontology offers intellectual tools that can ground the formulation of causal theory in ICT4D. The paper illustrates such potential through the case study of India's Unique Identity Project (Aadhaar), which Indian states are increasingly using within their anti‐poverty programmes. Following a critical realist retroductive methodology, the paper seeks to explain the incorporation of Aadhaar into India's main food security system, the Public Distribution System; an incorporation somewhat paradoxical given the mistrust often associated with biometric infrastructures in social protection. Critical realism allows construction of a theory of trust‐building in Aadhaar, based on mechanisms of institutionalisation (state governments framing Aadhaar as a core institutional means to receive benefits) and image formation (authorities systemically associating Aadhaar with an image of effective pro‐poor reform). Based on primary and secondary data collected over the course of six years, this paper contributes a theoretical explanation of an important phenomenon in Indian development, and illustrates how a critical realist philosophy is instrumental in building the type of causal theory that is needed in ICT4D.
Four steps to identify mechanisms of ICT4D: A critical realism‐based methodology
Authors: Thapa Devinder , Omland Hans Olav
Published: September 2018

Questions such as ‘What is ICT?’ and ‘What is development?’ are relatively well‐answered and well‐documented in literature but work connecting the two has been limited. Existing ICT4D studies tend to be descriptive or prescriptive in nature, and hence the explanation of how and why ICT works in the contexts of developing countries needs further investigation. ICT cannot by itself lead to development: it has to be deployed by actors in a given social, political, cultural, and technical context, under conditions at the time of deployment. The interplay of the above‐mentioned elements in any given development situation relies on underlying mechanisms that may explain how and why ICT leads to development. Therefore, it is important to investigate questions like “What mechanisms link ICT and development?” and “How do we identify these mechanisms?”. To research and answer these questions, we propose a critical realism‐based four‐step methodological approach. The core idea of the critical realism‐based approach suggested in this study is to identify the underlying mechanism (s), particularly in ICT4D contexts, to explain how and why ICT leads to development. We illustrate the proposed methodology by applying it in a case study from Nepal.
TIEG1 is upregulated in Lrp5/6‐mediated valve osteogenesis
Authors: Rajamannan Nalini M
Published: September 2018

We have previously demonstrated that Lrp5/6/β‐catenin plays an important role in valve calcification with a specific osteogenic phenotype defined by increased bone mineral content and overall valve thickening. Recent studies indicate that TIEG1 may be involved in mediating the Wnt signaling pathway in bone, which is known to play critical roles in osteoblast differentiation and bone mineralization. Therefore, we sought to test the role of TIEG1 in mediating Wnt signaling, in an established model of hypercholesterolemic valve disease. Our previous model treated null mice with cholesterol diets: Lrp5
−/−/ApoE
−/− mice versus wild‐type control (n = 180). Group I (n = 60) normal diet, Group II (n = 60) 0.25% chol diet (w/w), and Group III (n = 60) 0.25% (w/w) chol diet + atorv was tested for gene expression for TIEG1, Lrp6, and Runx2. Real‐time polymerase chain reaction confirmed that there is upregulation of the gene expression for TIEG1 and Runx2 in the hypercholesterolemic double knockout and single knockout valves as compared with controls with a mild increase in Lrp6. To confirm the mechanism, coexpression of β‐catenin, TIEG1, and LEF1 in valve cells in vitro, led to the coactivation of the TOPFLASH reporter, which was further confirmed by the observation that TIEG1 and β‐catenin colocalize with one another in the nucleus of valvular interstitial cells (VICs) following stimulation with transforming growth factor‐β treatment, an established activator of TIEG1. Taken together, these data implicate an important role for TIEG1 in mediating valve osteogenesis.
The pathogenesis of thyroid autoimmune diseases: New T lymphocytes – Cytokines circuits beyond the Th1−Th2 paradigm
Authors: Li Qian , Wang Bin , Mu Kaida , Zhang Jin‐An
Published: September 2018

Autoimmune thyroid disease (AITD) is one of the most common organ‐specific autoimmune disorders. It mainly manifests as Hashimoto's thyroiditis (HT) and Graves’ disease (GD). HT is characteristic of hypothyroidism resulting from the destruction of the thyroid while GD is characteristic of hyperthyroidism due to excessive production of thyroid hormone induced by thyrotropin receptor‐specific stimulatory autoantibodies. T lymphocytes and their secretory cytokines play indispensable roles in modulating immune responses, but their roles are often complex and full of interactions among distinct components of the immune system. Dysfunction of these T cells or aberrant expressions of these cytokines can cause the breakdown of immune tolerance and result in aberrant immune responses during the development of AITDs. This review summarizes recently identified T subsets and related cytokines and their roles in the pathogenesis of AITDs with the hope to provide a better understanding of the precise roles of notably identified T subsets in AITDs and facilitate the discovery of functional molecules or novel immune therapeutic targets for AITDs.
Angiotensin (1–7) inhibits arecoline‐induced migration and collagen synthesis in human oral myofibroblasts via inhibiting NLRP3 inflammasome activation
Authors: You Yuehua , Huang Yun , Wang Dan , Li Yang , Wang Guozhen , Jin Siyi , Zhu Xintao , Wu Bin , Du Xinya , Li Xu
Published: September 2018

Arecoline induces oral submucous fibrosis (OSF) via promoting the reactive oxygen species (ROS). Angiotensin (1–7) (Ang‐(1–7)) protects against fibrosis by counteracting angiotensin II (Ang‐II) via the Mas receptor. However, the effects of Ang‐(1–7) on OSF remain unknown. NOD‐like receptors (NLRs) family pyrin domain containing 3 (NLRP3) inflammasome is identified as the novel mechanism of fibrosis. Whereas the effects of arecoline on NLRP3 inflammasome remain unclear. We aimed to explore the effect of Ang‐(1–7) on NLRP3 inflammasome in human oral myofibroblasts. In vivo, activation of NLRP3 inflammasomes with an increase of Ang‐II type 1 receptor (AT1R) protein level and ROS production in human oral fibrosis tissues. Ang‐(1–7) improved arecoline‐induced rats OSF, reduced protein levels of NADPH oxidase 4 (NOX4) and the NLRP3 inflammasome. In vitro, arecoline increased ROS along with upregulation of the angiotensin‐converting enzyme (ACE)/Ang‐II/AT1R axis and NLRP3 inflammasome/interleukin‐1β axis in human oral myofibroblasts, which were reduced by NOX4 inhibitor VAS2870, ROS scavenger N‐acetylcysteine, and NOX4 small interfering RNA (siRNA). Furthermore, arecoline induced collagen synthesis or migration via the Smad or RhoA‐ROCK pathway respectively, which could be inhibited by NLRP3 siRNA or caspase‐1 blocker VX‐765. Ang‐(1–7) shifted the balance of RAS toward the ACE2/Ang‐(1–7)/Mas axis, inhibited arecoline‐induced ROS and NLRP3 inflammasome activation, leading to attenuation of migration or collagen synthesis. In summary, Ang‐(1–7) attenuates arecoline‐induced migration and collagen synthesis via inhibiting NLRP3 inflammasome in human oral myofibroblasts.
2‐Methoxyestradiol attenuates chronic‐intermittent‐hypoxia‐induced pulmonary hypertension through regulating microRNA‐223
Authors: Hao Shengyu , Jiang Liyan , Fu Cuiping , Wu Xu , Liu Zilong , Song Jieqiong , Lu Huan , Wu Xiaodan , Li Shanqun
Published: September 2018

Pulmonary hypertension (PH) is prevalent in patients with obstructive sleep apnea (OSA) syndrome, and coexistence of PH and OSA indicates a worse prognosis and higher mortality. Chronic intermittent hypoxia (CIH) is the key pathogenesis of OSA. Also, microRNA‐223 (miR‐223) plays a role in the regulation of CIH‐induced PH process. However, the detailed mechanism of CIH inducing PH is still unclear. This study aimed to investigate the pathological process of CIH associated PH and explore the potential therapeutic methods. In this study, adult Sprague–Dawley rats were exposed to CIH or normoxic (N) conditions with 2‐methoxyestradiol (2‐Me) or vehicle treatment for 6 weeks. The results showed that 2‐Me treatment reduced the progression of pulmonary angiogenesis in CIH rats, and alleviated proliferation, cellular migration, and reactive oxygen species formation was induced by CIH in pulmonary artery smooth muscle cells (PASMCs). CIH decreased the expression of miR‐223, whereas 2‐Me reversed the downregulation of miR‐223 both in vivo and in vitro. Furthermore, the antiangiogenic effect of 2‐Me observed in PASMCs was abrogated by miR‐223 inhibitor, while enhanced by miR‐223 mimic. These findings suggested that miR‐223 played an important role in the process of CIH inducing PH, and 2‐Me might reverse CIH‐induced PH via upregulating miR‐223.
Tannic acid protects against experimental acute lung injury through downregulation of TLR4 and MAPK
Authors: Sivanantham Ayyanar , Pattarayan Dhamotharan , Bethunaickan Ramalingam , Kar Amrita , Mahapatra Santanu Kar , Thimmulappa Rajesh K. , Palanichamy Rajaguru , Rajasekaran Subbiah
Published: September 2018

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) remain a major cause of morbidity and mortality in critically ill patients, and no specific therapies are still available to control the mortality rate. Thus, we explored the preventive and therapeutic effects of tannic acid (TA), a natural polyphenol in the context of ALI. We used in vivo and in vitro models, respectively, using lipopolysaccharide (LPS) to induce ALI in mice and exposing J774 and BEAS‐2B cells to LPS. In both preventive and therapeutic approaches, TA attenuated LPS‐induced histopathological alterations, lipid peroxidation, lung permeability, infiltration of inflammatory cells, and the expression of proinflammatory mediators. In addition, in‐vitro study showed that TA treatment could reduce the expression of proinflammatory mediators. Further studies revealed that TA‐dampened inflammatory responses by downregulating the LPS‐induced toll‐like receptor 4 (TLR4) expression and inhibiting extracellular‐signal‐regulated kinase (ERK)1/2 and p38 mitogen‐activated protein kinase (MAPK) activation. Furthermore, cells treated with the inhibitors of ERK1/2 (PD98059) and p38 (SB203580) mitigated the expression of cytokines induced by LPS, thus suggesting that ERK1/2 and p38 activity are required for the inflammatory response. In conclusion, TA could attenuate LPS‐induced inflammation and may be a potential therapeutic agent for ALI‐associated inflammation in clinical settings.
Optimizing Antibiotic Drug Therapy in Pediatrics: Current State and Future Needs
Authors: Le Jennifer , Bradley John S.
Published: September 2018

The selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age‐related physiologic maturation and the pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population‐based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta‐lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated.
Drug Formulations: Standards and Novel Strategies for Drug Administration in Pediatrics
Authors: Thabet Yasmin , Klingmann Viviane , Breitkreutz Jörg
Published: September 2018

Child‐appropriate drug formulations are a prerequisite of successful drug therapy in children. Efficacy and safety must be given for the active pharmaceutical ingredient, but safety also for the used excipients, components of primary packaging materials, and devices. We are presently experiencing exciting times for pediatric drug development, stimulated by previous governmental incentives in both the European Union and the United States. The most important advances in pediatric drug formulation development are reviewed and evaluated in this article. Scientific publications and recent industry strategies indicate a clear shift from liquid dosage forms to novel solid dosage forms. Solid formulations are usually composed from excipients generally regarded as safe, whereas many liquid formulations contain excipients such as preservatives, antioxidants, or taste‐masking agents that raise concerns. Further, some recent clinical studies on swallowability, acceptability, and preference indicate superiority for small‐sized tablets, so‐called mini‐tablets, over conventional liquids. In general, multiparticulate solid dosage forms could partly replace the liquids and provide more stable and cheaper alternatives to existing drug products or new developments. Dispersible solid drug dosage forms like orodispersible tablets, mini‐tablets and films are even better opportunities for efficient and safe use in pediatrics. Novel measuring and administration devices may facilitate the handling and drug administration of these modern drug dosage forms. Combination products (drug‐device combinations) can easily be linked with new e‐health technologies in near future to further improve pediatric drug therapy.
Vaccine Update: Recent Progress With Novel Vaccines, and New Approaches to Safety Monitoring and Vaccine Shortage
Authors: Ndaya‐Oloo Paul , Pitisuttithum Punnee , Tornieporth Nadia G. , Desgrandchamps Daniel , Munoz Flor M . , Kochhar Sonali , Buttery Jim , Bauwens Jorgen , Bonhoeffer Jan
Published: September 2018

Vaccines are increasingly based on new constructs, new technologies, and new compounds. Novel immunization programs are rapidly implemented globally. In this article, we highlight selected hot topics of this highly dynamic and broad field of scientific and public health development. The first section focuses on novel vaccines including malaria, dengue, serogroup B meningococcal, and respiratory syncytial virus vaccines and antibodies. The second section is addressing emerging strategies and programmatic challenges including maternal immunization, integrated mother‐child safety monitoring, and finally coping strategies with vaccine shortages.
Identifying the “Blip on the Radar Screen”: Leveraging Big Data in Defining Drug Safety and Efficacy in Pediatric Practice
Authors: Christensen Michael L. , Davis Robert L.
Published: September 2018

The immense amount of electronic health data (pharmacy and administrative claims, electronic health records, and clinical registries) that is being generated every day in the care of patients has the potential to be leveraged for improving clinical decisions at the point of care, uncovering or validating drug efficacy and drug safety. The potential use of big data for improving safe and effective use of medications is especially important in children because of their low drug exposure relative to adults. Electronic health data is collected primarily for clinical or billing purposes and not for research purposes. The major steps involved in data acquisition, extraction, aggregation, analysis, modeling, and interpretation are discussed. It is important to understand the limitation of big data and utilize appropriate study design and statistical methods. Possible applications are presented along with specific examples of how big data has been used in drug research to find that blip on the radar screen that may give an efficacy or safety signal that can lead to further investigation.
A dichotomy for the kernel by H‐walks problem in digraphs
Authors: Galeana‐Sánchez Hortensia , Hernández‐Cruz César
Published: September 2018

Let be a digraph which may contain loops, and let be a loopless digraph with a coloring of its arcs . An ‐walk of is a walk of such that is an arc of , for every . For , we say that reaches by ‐walks if there exists an ‐walk from to in . A subset is a kernel by ‐walks of if every vertex in reaches by ‐walks some vertex in , and no vertex in can reach another vertex in by ‐walks.

A panchromatic pattern is a digraph such that every ‐arc‐colored digraph has a kernel by ‐walks. In this study, we prove that every digraph is either a panchromatic pattern, or the problem of determining whether an arc‐colored digraph has a kernel by ‐walks is ‐complete.
Air temperature and lapse rate variation in the ice‐free and glaciated areas of northern James Ross Island, Antarctic Peninsula, during 2013–2016
Authors: Ambrozova Klara , Laska Kamil , Hrbacek Filip , Kavan Jan , Ondruch Jakub
Published: September 2018

Studies assessing air temperature variations and their dependence on altitude from the eastern side of the Antarctic Peninsula are sparse. In this paper, we analyse air temperature and near‐surface lapse rates from the Ulu Peninsula (James Ross Island, Antarctic Peninsula). The temperature data were acquired from nine sites both in ice‐free areas and glaciers of the Ulu Peninsula in 2013–2016. The most important factors influencing air temperature differences were sea‐ice conditions, topography and ground surface properties. During the study period, air temperature decreased with height with the mean lapse rate of 0.40 °C 100 m−1 for the ice‐free sites (10–375 m a.s.l.) and 0.43 °C 100 m−1 for the glaciated sites (268–539 m a.s.l.). However, the values were lower in winter (ice‐free: 0.02 °C 100 m−1 and glacier: 0.31 °C 100 m−1) than in summer (ice‐free: 0.62 °C 100 m−1 and glacier: 0.51 °C 100 m−1) for both categories. The air layer between 10 and 56 m a.s.l. in the ice‐free area revealed an almost year‐round air temperature inversion resulting in a mean lapse rate of −0.79 °C 100 m−1 and an air temperature inversion frequency reaching up to 43%. The temperature inversion frequency was 10% lower for the lowest air layer for the glacier category, which was between 268 and 356 m a.s.l. The land surface air temperature was the highest when the wind was from the northwest and lowest when it was from the south–southwest. The near‐surface lapse rate–wind direction relationship was the most pronounced for the air layer between 10 and 56 m a.s.l. with the lowest mean lapse rate for west–southwest wind (−2.83 °C 100 m−1) and the highest for east–northeast wind (0.41 °C 100 m−1).
Paediatric use of medications and adherence apps: a qualitative analysis of the perspectives of children and parents
Authors: Abraham Olufunmilola , Wytiaz Rebecca M. , Feathers Alison M.
Published: September 2018

Background

The number of children diagnosed with chronic medical conditions is increasing, with a high percentage struggling with medication adherence. Non‐adherence in children may lead to negative health outcomes. Parents are typically responsible for managing their child's medications. Medication adherence mobile apps are an innovative approach to address non‐adherence and actively engage children.

Aim

This study explored children's and parents’ perceptions of using medication adherence apps to facilitate self‐management.

Methods

Children (aged 7–17 years) taking one or more medications for a chronic condition and their parents were recruited from an outpatient pharmacy and adolescent clinic. Semistructured interviews were conducted with 8 children and 10 parents. An app interaction (guided and independent), followed by a brief questionnaire with the child was also administered. Interviews and interactions were audio recorded, transcribed and reviewed for accuracy. The technology acceptance model guided data collection and analysis. Prevalent codes were identified and thematic analysis was conducted.

Results

Most children were 12–17 years of age and most parents were 30–49 years of age. Parents and children received adherence apps as an innovative approach to the child's medication management. Nine themes emerged: ability to earn rewards for adherence; having security functionality to protect user information; customisable graphics and appealing colour schemes; medication‐specific information; ease of accessibility to mobile devices; sharing child‐friendly medication information; children's limited knowledge and involvement in medication management; and communication challenges with healthcare providers.

Conclusions

Adherence apps incorporating user‐centred needs of children and educating them about chronic diseases and medication use may positively affect self‐care.
Microbial acidification, alcoholization, and aroma production during spontaneous lambic beer production
Authors: De Roos Jonas , De Vuyst Luc
Published: September 2018

Acidic beers, such as Belgian lambic beers and American and other coolship ales, are becoming increasingly popular worldwide thanks to their refreshing acidity and fruity notes. The traditional fermentation used to produce them does not apply pure yeast cultures but relies on spontaneous, environmental inoculation. The fermentation and maturation process is carried out in wooden barrels and can take up to three years. It is characterized by different microbial species belonging to the enterobacteria, acetic acid bacteria, lactic acid bacteria, and yeasts. This review provides an introduction to the technology and four fermentation strategies of beer production, followed by the microbiology of acidic beer production, focusing on the main microorganisms present during the long process used for the production of Belgian lambic beers. © 2018 Society of Chemical Industry
Does Bowel Preparation Improve the Performance of Rectal Water Contrast Transvaginal Ultrasonography in Diagnosing Rectosigmoid Endometriosis?
Authors: Ferrero Simone , Barra Fabio , Stabilini Cesare , Vellone Valerio Gaetano , Leone Roberti Maggiore Umberto , Scala Carolina
Published: September 2018

Objectives

The primary objective of the study was to compare the performance of the rectal water transvaginal ultrasonography (RWC‐TVS) with and without bowel preparation (BP) in diagnosing rectosigmoid endometriosis. The secondary objectives were to compare the performance of the 2 exams in estimating infiltration of the mucosa, length of the largest rectosigmoid nodules, distance of the nodules from the anal verge, and presence of multifocal disease.

Methods

This prospective study included patients with pain symptoms and intestinal complaints suggestive of endometriosis. Patients underwent RWC‐TVS with and without BP within an interval of 1 week to 2 months. Two independent and blinded gynecologists performed the exams. The results of the 2 exams were compared with surgical and histologic findings.

Results

A total of 155 patients were included in the study; 92 patients had rectosigmoid endometriosis. There was no significant difference in the performance of RWC‐TVS with or without BP in diagnosing rectosigmoid endometriosis (P = .727). There was no significant difference in the performance of RWC‐TVS with or without BP in diagnosing infiltration of the mucosa (P = .424) and multifocal disease (P = .688), in estimating the main diameter of the largest nodule (P = .644) and the distance between the more distal rectosigmoid nodule and the anal verge (P = .090). The patients similarly tolerated the 2 exams (P = .799).

Conclusions

Bowel preparation does not improve the performance of RWC‐TVS in diagnosing rectosigmoid endometriosis and in assessing the characteristics of these nodules.
Pre‐emptive action as a measure for conserving nomadic species
Authors: Stojanovic Dejan , Cook Henry C. L. , Sato Chloe , Alves Fernanda , Harris Grant , McKernan Andrew , Rayner Laura , Webb Matthew H. , Sutherland William J. , Heinsohn Robert
Published: September 2018

Nomadic species are globally threatened by anthropogenic habitat change, but management options to address their decline are limited. Their unpredictable settlement patterns pose major challenges for conservation because identifying where to implement action is difficult. We address this challenge by pre‐empting settlement patterns in a nomadic species using data from a long‐term study of the critically endangered, cavity‐nesting swift parrot (Lathamus discolor) and by taking action at the sites identified. We detected flower bud growth (the primary settlement cue) and deployed artificial nests at 3 predicted breeding sites before the birds arrived. At the broad breeding‐range scale, swift parrots settled wherever bud abundance was highest, including the study area. Within the study area, artificial nest occupancy was greatest at the site with abundant historical natural nesting sites. At the local scale, we found significant effects of study site and distance to forest edges on nest box occupancy by swift parrots. Despite significant differences in thermal properties between artificial and natural nests, we found no differences in clutch size, brood size, or body condition of swift parrots in each. Monitoring settlement patterns and future food availability of nomadic wildlife can empower conservation managers to make predictions about breeding and target ecologically relevant times and locations when deploying conservation resources. Our study is an example of how conservation challenges posed by nomadic species can be overcome, and demonstrates that with effective monitoring, practical action can be targeted to address acute conservation needs and augment habitat availability. © 2018 The Wildlife Society.
The Role of Maxillofacial Prosthetics for the Surgically Treated Patient at National Cancer Institute–Designated Comprehensive Cancer Centers
Authors: Rosen Evan B. , Palin Charles L. , Huryn Joseph M. , Wong Richard J.
Published: September 2018

Objectives/Hypothesis

The current role of maxillofacial prosthetic care for head and neck cancer patients is not well understood. Additionally, perceived barriers for service provision are unknown. The purpose of this study was to evaluate the current role of maxillofacial prosthetic care at National Cancer Institute (NCI)–designated comprehensive cancer centers and to identify perceived barriers to care.

Study Design

Multicenter, cross‐sectional survey of head and neck division leaders at NCI‐designated comprehensive cancer centers.

Methods

Each head and neck division leader from the 47 NCI‐designated comprehensive cancer centers was invited to participate. The main outcomes of this study were: 1) to evaluate the current role of maxillofacial prosthetics for the surgically treated head and neck cancer patient within NCI‐designated comprehensive cancer centers and 2) to identify perceived barriers to care. Measured outcomes were obtained from an anonymous online survey and reported.

Results

Twenty‐eight of the 47 head and neck service chiefs responded (60% response rate). Respondents expressed preference for prosthetic rehabilitation for hard palate/upper gum, auricular, and nasal defects. Local flap or free tissue transfer was preferred for lower gum and soft palate defects. Cost‐related factors were among the most reported perceived barriers to maxillofacial prosthetic care.

Conclusions

Maxillofacial prosthetics have an important role in the rehabilitation of the head and neck cancer patient. Perceived barriers for services exist, particularly as it relates to cost. Providers should be aware that these issues are likely to be more severe in regional or community centers.

Level of Evidence

NA Laryngoscope, 129:409–414, 2019
Transfusion in Head and Neck Cancer Patients Undergoing Pedicled Flap Reconstruction
Authors: Abt Nicholas B. , Puram Sidharth V. , Sinha Sumi , Sethi Rosh K. V. , Goyal Neerav , Emerick Kevin S. , Lin Derrick T. , Deschler Daniel G.
Published: September 2018

Objective

Blood product utilization is monitored to prevent unnecessary transfusions. Head‐and‐neck pedicled flap reconstruction transfusion‐related outcomes were assessed.

Methods

One hundred and thirty‐six pedicled flap patients were reviewed: 64 supraclavicular artery island flaps (SCAIF), 57 pectoralis major (PM) flaps, and 15 submental (SM) flaps. Outcome parameters included flap‐related complications, medical complications, length of stay (LOS), and flap survival. Multivariable logistic regression analyses were performed. Multivariable logistic regression analyses were performed to adjust for relevant pre‐ and perioperative factors.

Results

Of all head‐and‐neck pedicled flap patients included in our analyses (n = 136), 40 (29.4%) received blood transfusions. The average pretransfusion hematocrit (Hct) was 24.3% ± 0.5%, with 2.65 ± 0.33 units transfused and a posttransfusion Hct increase of 5.0% ± 0.6%. Transfusion rates differed with PM (47.4%), SCAIF (17.2%), and SM (13.3%) flaps (P < 0.005). Patients undergoing PM reconstruction trended toward higher transfusion requirements (PM 2.89 ± 0.47 units, SC 2.18 ± 0.28 units, and SM 2.00 ± 0.0 units), with transfusion occurring later in the postoperative course (4.9 ± 1.3 days vs. 2.4 ± 0.1 days for all other flaps; P = 0.08). Infection, dehiscence, fistula, or medical complications were not different. Transfusion thresholds of Hct < 21 versus Hct < 27 exhibited no difference in LOS, flap‐survival, or medical/flap‐related complications.

Conclusion

Transfusion is not associated with surgical or medical morbidity following head and neck pedicled flap reconstruction. There were no differences in outcomes between transfusion triggers of Hct < 21 versus Hct < 27, suggesting that a more conservative transfusion trigger may not precipitate adverse patient complications. Our data recapitulate findings in free flap patients and warrant further investigation of transfusion practices in head and neck flap reconstruction.

Level of Evidence

4. Laryngoscope, 128:E409–E415, 2018