bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of porcine epithelial rests of Malassez to stimulation by interleukin‐6
Authors: Sako R. , Kobayashi F. , Aida N. , Furusawa M. , Muramatsu T.
Published: September 2017

Aim

To investigate the proliferation and migration of epithelial cell rests of Malassez (ERM) after stimulation with IL‐6.

Methodology

Porcine‐derived ERM were seeded on Dulbecco's modified Eagle's Medium, and IL‐6 (100 pg mL−1) was incorporated into the culture medium. The WST‐1 assay was performed to evaluate cell proliferation, and absorption was measured at 450 nm. A wound‐healing assay and immunofluorescence assay for integrin α3 were conducted to investigate migration. The Kruskal–Wallis test and the Mann–Whitney U‐test with Bonferroni correction were used to analyse data of WST‐1 and wound‐healing assays.

Results

Cell proliferation following the stimulation by IL‐6 increased over time, with a significant increase being observed at 6 h (P < 0.05), but not in a concentration‐dependent manner. Cell proliferation was significantly greater in IL‐6‐treated ERM than in nontreated ERM (P < 0.05). The results of the wound‐healing assay revealed earlier closure in IL‐6‐treated ERM (P < 0.05). In the immunofluorescence assay, integrin α3 was detected at the edge of cell processes adjacent to the wound area. A neutralized antibody abrogated the effects of the IL‐6 stimulation in cell proliferation and migration.

Conclusion

IL‐6 promoted the proliferation and migration of porcine ERM in vitro.
Influence of indigenous microbiota on experimental toxoplasmosis in conventional and germ‐free mice
Authors: Nascimento Bruna B. , Cartelle Christiane T. , Noviello Maria de L. , Pinheiro Breno V. , de Almeida Vitor Ricardo W. , Souza Danielle da G. , de Vasconcelos Generoso Simone , Cardoso Valbert N. , Martins Flaviano dos S. , Nicoli Jacques R. , Arantes Rosa M. E.
Published: September 2017

Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii, causes a severe innate pro‐inflammatory response. The indigenous intestinal microbiota promotes host animal homoeostasis and may protect the host against pathogens. Germ‐free (GF) animals provide an important tool for the study of interactions between host and microbiota. In this study, we assessed the role of indigenous microorganisms in disease development utilizing a murine toxoplasmosis model, which includes conventional (CV) and GF NIH Swiss mice. CV and GF mice orally inoculated with T. gondii had similar survival curves. However, disease developed differently in the two animal groups. In CV mice, intestinal permeability increased and levels of intestinal pro‐inflammatory cytokines were altered. In GF animals, there were discrete epithelial degenerative changes and mucosal oedema, but the liver and lungs displayed significant lesions. We conclude that, despite similar survival curves, CV animals succumb to an exaggerated inflammatory response, whereas GF mice fail to produce an adequate systemic response.
Hepatocellular carcinoma in a mouse model fed a choline‐deficient, L‐amino acid‐defined, high‐fat diet
Authors: Ikawa‐Yoshida Ayae , Matsuo Saori , Kato Atsuhiko , Ohmori Yusuke , Higashida Atsuko , Kaneko Eiji , Matsumoto Masahiko
Published: September 2017

Hepatocellular carcinoma (HCC) is a common cancer worldwide and represents the outcome of the natural history of chronic liver disease. The growing rates of HCC may be partially attributable to increased numbers of people with non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH). However, details of the liver‐specific molecular mechanisms responsible for the NAFLD–NASH–HCC progression remain unclear, and mouse models that can be used to explore the exact factors that influence the progression of NAFLD/NASH to the more chronic stages of liver disease and subsequent HCC are not yet fully established. We have previously reported a choline‐deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD) as a dietary NASH model with rapidly progressive liver fibrosis in mice. The current study in C57BL/6J mice fed CDAHFD provided evidence for the chronic persistence of advanced hepatic fibrosis in NASH and disease progression towards HCC in a period of 36 weeks. When mice fed CDAHFD were switched back to a standard diet, hepatic steatosis was normalized and NAFLD activity score improved, but HCC incidence increased and the phenotype of fibrosis‐associated HCC development was observed. Moreover, when mice continued to be fed CDAHFD for 60 weeks, HCC further developed without severe body weight loss or carcinogenesis in other organs. The autochthonous tumours showed a variety of histological features and architectural patterns including trabecular, pseudoglandular and solid growth. The CDAHFD mouse model might be a useful tool for studying the development of HCC from NAFLD/NASH, and potentially useful for better understanding pathological changes during hepatocarcinogenesis.
Long‐term kidney transplant survival in patients with continent urinary diversion
Authors: Fournier Romain , Codas‐Duarte Ricardo , Daily Theresa , Martin Xavier , Badet Lionel , Fassi‐Fehri Hakim
Published: September 2017

Objectives

To report the long‐term survival of transplanted kidneys in patients with a continent urinary diversion.

Methods

Between January 1987 and July 2015, 16 patients with a median age of 37 years (range 21–63 years) underwent kidney transplantation on a continent urinary diversion. A total of 14 patients presented irreversible dysfunction of the lower urinary tract, and two patients had required radical cystectomy because of bladder cancer. All continent urinary diversions were carried out before the transplantation. There were nine Kock pouches, five Mainz pouches, one Mainz neobladder and one Hautmann neobladder. A total of 11 patients had a previous non‐continent urinary diversion. Of the transplants, 14 came from brain‐dead donors and two from related living donors.

Results

The median post‐transplantation follow up was 171 months (range 30–298 months). Two patients died, while six patients lost their transplant and resumed hemodialysis. Nine patients (56.2%) were alive with a functional transplant at the end of follow up. The most common allograft complication was acute pyelonephritis, but no graft was lost as a result of urinary diversion complications. The kidney transplant survival rate was 73.3% after 10 years, and 66.6% after 15 years. Among patients who still had a functional transplant at the time of the study, creatinine clearance was >30 mL/min for seven patients and <30 mL/min for two patients.

Conclusions

The present study is the longest series to date of renal transplantation on continent urinary diversions. The long‐term outcome shows that the presence of a continent urinary diversion does not reduce transplant survival.
Integrating high‐throughput screening and sequencing for monoclonal antibody discovery and engineering
Authors: Parola Cristina , Neumeier Daniel , Reddy Sai T.
Published: September 2017

Monoclonal antibody discovery and engineering is a field that has traditionally been dominated by high‐throughput screening platforms (e.g. hybridomas and surface display). In recent years the emergence of high‐throughput sequencing has made it possible to obtain large‐scale information on antibody repertoire diversity. Additionally, it has now become more routine to perform high‐throughput sequencing on antibody repertoires to also directly discover antibodies. In this review, we provide an overview of the progress in this field to date and show how high‐throughput screening and sequencing are converging to deliver powerful new workflows for monoclonal antibody discovery and engineering.
Endogenous lipid antigens for invariant natural killer T cells hold the reins in adipose tissue homeostasis
Authors: van Eijkeren Robert J. , Krabbe Olga , Boes Marianne , Schipper Henk S. , Kalkhoven Eric
Published: September 2017

The global obesity epidemic and its associated co‐morbidities, including type 2 diabetes, cardiovascular disease and certain types of cancers, have drawn attention to the pivotal role of adipocytes in health and disease. Besides their ‘classical’ function in energy storage and release, adipocytes interact with adipose‐tissue‐resident immune cells, among which are lipid‐responsive invariant natural killer T (iNKT) cells. The iNKT cells are activated by lipid antigens presented by antigen‐presenting cells as CD1d/lipid complexes. Upon activation, iNKT cells can rapidly secrete soluble mediators that either promote or oppose inflammation. In lean adipose tissue, iNKT cells elicit a predominantly anti‐inflammatory immune response, whereas obesity is associated with declining iNKT cell numbers. Recent work showed that adipocytes act as non‐professional antigen‐presenting cells for lipid antigens. Here, we discuss endogenous lipid antigen processing and presentation by adipocytes, and speculate on how these lipid antigens, together with ‘environmental factors’ such as tissue/organ environment and co‐stimulatory signals, are able to influence the fate of adipose‐tissue‐resident iNKT cells, and thereby the role of these cells in obesity and its associated pathologies.
Genome‐wide DNA methylation analysis of senescence in repetitively infected memory cytotoxic T lymphocytes
Authors: Shosaku Jumpei
Published: September 2017

The immune system including antigen‐specific CD8 T cells, which are cytotoxic T lymphocytes (CTLs), can acquire the potential for more effective elimination of the pathogen at re‐infection. As memory CTLs could exert protective immunity after the next response, we aimed to elucidate the substantial change of repetitively infected memory CTLs. Currently, DNA methylation status in repetitively infected memory CTLs is unknown, so we performed next‐generation sequencing to evaluate methylation status and transcriptional regulation of naive, primary and secondary memory CD8 T cells on the basis of transcription start sites (TSS). Notably, total CpG sites in the entire regions of all genes were significantly unmethylated in primary memory CTLs (young memory CTLs) and even more unmethylated in secondary memory CTLs (old memory CTLs). However, total proximal regions from TSS, which cover transcriptional promoters, were steadily methylated with repeated infections. In contrast, distal regions from TSS, which are the majority of entire regions and include transcriptional enhancers, were extensively unmethylated by infections. In association between transcriptional and methylation changes, accompanied by genes characteristic of the immune response, natural killer cell signature genes, known to be expressed in senescent CD8 T cells, were transcriptionally up‐regulated and unmethylated in young memory CTLs, and more so in old memory CTLs, whereas ribosomal proteins were transcriptionally down‐regulated and methylated in proximal region from the TSS by infections. Our results suggest that epigenetically augmented enhancers and suppressed promoters, which could consequently lead to global decline of transcription and translation, could represent the senescence of memory CTLs.
Mohs micrographic surgery in the elderly: comparison of tumours, surgery and first‐year follow‐up in patients younger and older than 80 years old in REGESMOHS
Authors: Camarero‐Mulas C. , Delgado Jiménez Y. , Sanmartín‐Jiménez O. , Garcés J.R. , Rodríguez‐Prieto M.A. , Alonso‐Alonso T. , Miñano Medrano R. , López‐Estebaranz J.L. , de Eusebio Murillo E. , Redondo P. , Ciudad‐Blanco C. , Toll‐Abelló A. , Artola Igarza J.L. , Allende Markixana I. , Suarez Fernández R. , Alfaro Rubio A. , Alonso Pacheco M.L. , Vázquez‐Veiga H. , de la Cueva Dobao P. , Ruiz‐Salas V. , Vilarrasa Rull E. , Barchino L. , Morales‐Gordillo V. , Ocerin‐Guerra I. , Navarro Tejedor R. , Hueso L. , Mayor Arenal M. , Seoane‐Pose M.J. , Cano‐Martinez N. , Garcia‐Doval I. , Descalzo M.A. ,   on behalf of REGESMOHS (Registro Español de Cirugía de Mohs)
Published: September 2017

Background

The elderly population is increasing and more patients in this group undergo Mohs micrographic surgery (MMS). The few publications investigating MMS in elderly people conclude that it is a safe procedure; however, these are single‐centre studies without a comparison group.

Objective

To compare the characteristics of patients, tumours, MMS and 1‐year follow‐up in patients younger than 80 years, with patients older than 80 years at the time of surgery.

Methods

Data was analysed from REGESMOHS, a prospective cohort study of patients treated with MMS. The participating centres were 19 Spanish hospitals where at least one MMS is performed per week. Data on characteristics of the patient, tumour and surgery were recorded. Follow‐up data were collected from two visits; the first within 1 month postsurgery and the second within the first year.

Results

From July 2013 to October 2016, 2575 patients that underwent MMS were included in the registry. Of them, 1942 (75.4%) were aged <80 years and 633 (24.6%) were ≥80 years old. In the elderly, the tumour size was significantly higher with a higher proportion of squamous cell carcinoma. Regarding surgery, elderly more commonly had tumours with deeper invasion and required a higher number of Mohs surgery stages, leaving larger defects and requiring more time in the operating room. Despite this, the incidence of postoperative complications was the same in both groups (7%) and there were no significant differences in proportion of relapses in the first‐year follow‐up.

Conclusion

The risk of short‐term complications and relapses were similar in elderly and younger groups. MMS is a safe procedure in the elderly.
Organophosphate and pyrethroid resistances in the tomato leaf miner Tuta absoluta (Lepidoptera: Gelechiidae) from Iran
Authors: Zibaee I. , Mahmood K. , Esmaeily M. , Bandani A. R. , Kristensen M.
Published: September 2017

The tomato leafminer, Tuta absoluta (Meyrich) (Lepidoptera: Gelechiidae), is a serious pest of tomato crops worldwide. The intensive use of chemical pesticides to control it has led to the selection of resistant populations. This study investigated the resistance of T. absoluta populations to pyrethroid and the organophosphate insecticides from ten regions of Iran. The resistance ratios at LC50 for chlorpyrifos and diazinon varied among populations from 4.3 to 12 and from 1.4 to 9.0, respectively. The resistance ratios of the pyrethroids cypermethrin, deltamethrin and permethrin varied from 1.3 to 3.7, 2.7 to 13 and 1.2 to 4.3, respectively. Inclusion of synergists in toxicological bioassays and the variation observed in the activity of esterases, glutathione S‐transferase and cytochrome P450‐dependent monooxygenase suggest the existence of metabolically based resistance. Esterase and P450 biochemical assays were positively correlated with deltamethrin, and cypermethrin tolerance and diazinon tolerance correlated with esterase activity. The genes encoding the organophosphate and pyrethroid target sites acetylcholinesterase (ace1) and sodium channel (kdr) were partly sequenced. The genotyping revealed mutations in high frequencies in all populations leading to an A201S substitution in ace1 and three substitutions in the sodium channel gene L1014F, M918T, T929I. In summary, our results indicate the presence of organophosphate and pyrethroid resistance in Iranian T. absoluta populations with involvement of both detoxification enzymes and target site alterations. Most likely the populations of T. absoluta imported to Iran were resistant upon arrival.
Tick saliva microbiomes isolated from engorged and partially fed adults of Haemaphysalis flava tick females
Authors: He X.‐M. , Cheng T.‐Y.
Published: September 2017

The tick Haemaphysalis flava is one of the most significant blood‐feeding arthropod parasites and is a vector for numerous human and animal pathogens. However, a comprehensive investigation of the microbial communities found in the saliva of this tick species is lacking. This study used 16S rRNA Illumina sequencing to characterize the compositions of microbiomes present in saliva and whole tick samples isolated from engorged and partially fed adult H. flava females. This revealed that the bacterial diversity present in tick saliva increased after a prolonged blood meal, and that the species diversity found in saliva was significantly higher than that of whole ticks. Three bacteria phyla, in particular, made up more than 80% of the microbial community across all samples—Proteobacteria, Firmicutes and Actinobacteria. Furthermore, some of the genera identified in this study had not previously been reported in ticks before, such as Facklamia, Vagococcus, Ruminococcus, Lachnospira, Bradyrhizobium, Peptostreptococcus, Jeotgalicoccus, Roseburia, Brachybacterium, Sporosarcina, u114, Megamonas and Dechloromonas. Finally, we found that many of the isolated bacteria were opportunistic pathogens, indicating a potential risk to humans and livestock exposed to H. flava. These results will contribute to fully understanding the transmission of tick‐borne pathogens.
Lethal and sublethal effects of long‐lasting insecticide‐treated nets on the invasive bug Halyomorpha halys
Authors: Sabbatini Peverieri G. , Binazzi F. , Marianelli L. , Roversi P. F.
Published: September 2017

Halyomorpha halys is a polyphagous insect species with an original eastern Asiatic distribution, which was recently and accidentally introduced in the USA and Europe, where it became a serious agricultural pest. Chemicals have been widely used for its control leading often to failure of IPM programmes. Several approaches aimed at pest monitoring and control are currently under investigation, for example trapping, screening, border management and biological control. In the present work, we investigated the lethal and sublethal effects of the use of a long‐lasting insecticide‐treated net (LLIN with α‐cypermethrin), focusing on the perspective to control H. halys in an integrated approach. All experiments were carried out in the laboratory either in small arenas, at five exposure times (5, 15, 30, 45 and 60 min) or in large cages at 8 hr exposure. In small arenas, the LLIN induced sublethal effects and/or effectively killed the adults. A higher adult mortality was observed after longer exposure times (LT90 was 51.64 min for females and 40.83 min for males). However, several specimens recovered from sublethal effects, with higher recovery rates after shorter exposure times. In the cage experiments, a significantly higher mortality (65% males and 75% of females) was recorded compared with controls. LLINs are physical barriers that can improve crop protection due to their insecticidal activity, and can be reasonably applied in various attract‐and‐kill systems both in glasshouses and in the field.
Influence of prucalopride on esophageal secondary peristalsis in reflux patients with ineffective motility
Authors: Lei Wei‐Yi , Hung Jui‐Sheng , Liu Tso‐Tsai , Yi Chih‐Hsun , Chen Chien‐Lin
Published: September 2017

Background and Aim

Ineffective esophageal motility (IEM) is associated with gastroesophageal reflux disease. Secondary peristalsis contributes to esophageal clearance. Prucalopride promotes secondary peristalsis by stimulating 5‐hydroxytrypatamine 4 receptors in the esophagus. We aimed to determine whether prucalopride would augment secondary peristalsis in gastroesophageal reflux disease patients with IEM.

Methods

After a baseline recording of primary peristalsis, secondary peristalsis was stimulated by slow and rapid mid‐esophageal injections of air in 15 patients with IEM. Two separate sessions with 4‐mg oral prucalopride or placebo were randomly performed.

Results

Prucalopride significantly increased primary peristaltic wave amplitude (68.1 ± 10.0 vs 55.5 ± 8.8 mmHg, P = 0.02). The threshold volume for triggering secondary peristalsis was significantly decreased by prucalopride during slow (9.3 ± 0.8 vs 12.0 ± 0.8 mL; P = 0.04) and rapid air injection (4.9 ± 0.3 vs 7.1 ± 0.1 mL; P = 0.01). Secondary peristalsis was triggered more frequently after application of prucalopride (55% [43–70%]) than placebo (45% [33–50%]) (P = 0.008). Prucalopride did not change pressure wave amplitudes during slow air injection (84.6 ± 8.1 vs 57.4 ± 13.8 mmHg; P = 0.19) or pressure wave amplitudes during rapid air injection (84.2 ± 8.6 vs 69.5 ± 12.9 mmHg; P = 0.09).

Conclusions

Prucalopride enhances primary peristalsis and mechanosensitivity of secondary peristalsis with limited impact on secondary peristaltic activities in IEM patients. Our study suggests that prucalopride appears to be useful in augmenting secondary peristalsis in patients with IEM only via sensory modulation of esophageal secondary peristalsis.
Characterization of hyperbranched core‐multishell nanocarriers as an innovative drug delivery system for the application at the oral mucosa
Authors: Jager J. , Obst K. , Lohan S. B. , Viktorov J. , Staufenbiel S. , Renz H. , Unbehauen M. , Haag R. , Hedtrich S. , Teutloff C. , Meinke M. C. , Danker K. , Dommisch H.
Published: September 2017

Background and Objectives

In the oral cavity, the mucosal tissues may develop a number of different pathological conditions, such as inflammatory diseases (gingivitis, periodontitis) and autoimmune disorders (eg, oral lichen planus) that require therapy. The application of topical drugs is one common therapeutic approach. However, their efficacy is limited. Dilution effects due to saliva hinder the adherence and the penetration of drug formulations. Therefore, the bioavailability of oral topical drugs is insufficient, and patients may suffer from disease over years, if not life‐long.

Material and Methods

In the present study, we characterized core‐multishell (CMS) nanocarriers for their potential use as drug delivery systems at oral mucosal tissues. For this purpose, we prepared porcine masticatory as well as buccal mucosa and performed Franz cell diffusion experiments. Penetration of fluorescently labeled CMS nanocarriers into the mucosal tissue was analyzed using confocal laser scanning microscopy. Upon exposure to CMS nanocarriers, the metabolic and proliferative activity of gingival epithelial cells was determined by MTT and sulforhodamine B assays, respectively.

Results

Here, we could show that the carriers penetrate into both mucosal tissues, while particles penetrate deeper into the masticatory mucosa. Electron paramagnetic resonance spectroscopy revealed that the 3‐carboxy‐2,2,5,5‐tetramethyl‐1‐pyrrolidinyloxy‐labeled glucocorticoid dexamethasone loaded on to the CMS nanocarriers was released from the carriers in both mucosal tissues but with a higher efficiency in the buccal mucosa. The release from the nanocarriers is in both cases superior compared to the release from a conventional cream, which is normally used for the treatment of inflammatory conditions in the oral cavity. The CMS nanocarriers exhibited neither cytotoxic nor proliferative effects in vitro.

Conclusion

These findings suggested that CMS nanocarriers might be an innovative approach for topical drug delivery in the treatment of oral inflammatory diseases.
Decentralizing Pork: Congressional Roll‐Call Voting, Decentralized Administration, and Distributive Politics
Authors: Bertelli Anthony M. , McCann Pamela J. Clouser
Published: September 2017

Congress packages pork‐barrel spending in complicated proposals that belie theories of distributive politics. We theorize that roll‐call voting on such bills depends on grant programs' administrative centralization, party ties with presidents or home‐state governors, and differences in geographic representation between chambers. Analyzing votes between 1973 and 2010 using a within‐legislator strategy reveals that House members are less likely to support decentralized spending when they are copartisans with presidents, while senators support decentralization regardless of such party ties. When House members or senators share affiliation with only governors or with neither chief executive, the likelihood of support rises with decentralization.
Root traits are more than analogues of leaf traits: the case for diaspore mass
Authors: Bergmann Joana , Ryo Masahiro , Prati Daniel , Hempel Stefan , Rillig Matthias C.
Published: September 2017

Root traits are often thought to be analogues of leaf traits along the plant economics spectrum. But evolutionary pressures have most likely shaped above‐ and belowground patterns differentially. Here, we aimed to identify the most important aboveground traits for explaining root traits without an a priori focus on known concepts.

We measured morphological root traits in a glasshouse experiment on 141 common Central European grassland species. Using random forest algorithms, we built predictive models of six root traits from 97 aboveground morphological, ecological and life history traits.

Root tissue density was best predicted by leaf dry matter content, whereas traits related to root fineness were best predicted by diaspore mass: the heavier the diaspore, the coarser the root system. Specific leaf area (SLA) was not an important predictor for any of the root traits.

This study confirms the hypothesis that root traits are more than analogues of leaf traits within a plant economics spectrum. The results reveal a novel ecological pattern and highlight the power of root data to close important knowledge gaps in trait‐based ecology.
Characterization of an antimicrobial and phytotoxic ribonuclease secreted by the fungal wheat pathogen Zymoseptoria tritici
Authors: Kettles Graeme J. , Bayon Carlos , Sparks Caroline A. , Canning Gail , Kanyuka Kostya , Rudd Jason J.
Published: September 2017

The fungus Zymoseptoria tritici is the causal agent of Septoria Tritici Blotch (STB) disease of wheat leaves. Zymoseptoria tritici secretes many functionally uncharacterized effector proteins during infection. Here, we characterized a secreted ribonuclease (Zt6) with an unusual biphasic expression pattern.

Transient expression systems were used to characterize Zt6, and mutants thereof, in both host and non‐host plants. Cell‐free protein expression systems monitored the impact of Zt6 protein on functional ribosomes, and in vitro assays of cells treated with recombinant Zt6 determined toxicity against bacteria, yeasts and filamentous fungi.

We demonstrated that Zt6 is a functional ribonuclease and that phytotoxicity is dependent on both the presence of a 22‐amino‐acid N‐terminal ‘loop’ region and its catalytic activity. Zt6 selectively cleaves both plant and animal rRNA species, and is toxic to wheat, tobacco, bacterial and yeast cells, but not to Z. tritici itself.

Zt6 is the first Z. tritici effector demonstrated to have a likely dual functionality. The expression pattern of Zt6 and potent toxicity towards microorganisms suggest that, although it may contribute to the execution of wheat cell death, it is also likely to have an important secondary function in antimicrobial competition and niche protection.
Sugars and beyond. The role of sugars and the other nutrients and their potential impact on caries
Authors: Giacaman RA
Published: September 2017

The traditional concept of caries as a multifactorial transmittable and infectious disease has been challenged. Novel conceptual ideas have come to add to the complexity of this highly prevalent disease worldwide. Current etiological understanding of the disease has emphasized the pivotal role of sugars in caries. In fact, current definition points toward an ecological disease caused by the commensal microbiota that under ecological imbalances, mainly due to high and or frequent sugars consumption, creates a state of dysbiosis in the dental biofilm. This modern conceptual idea, however, tends to underrate a key issue. As humans are omnivore and consume a mix diet composed by a multitude of substances, the role of the diet in caries must not be restricted only to the presence of fermentable sugars. This review explores the contribution of other food components, ubiquitous to the diet, mostly as potentially protective factors. Anticaries nutrients might determine an environmental change, affecting the ecology of the oral microbiome and partially mitigating the effect of sugars. Understanding the function of the food usually consumed by the people will contribute new knowledge on the mechanisms associated with the onset of caries, on new caries risk variables and on potential novel strategies for the prevention and treatment of the disease.
Characterisation of a sucrose‐independent in vitro biofilm model of supragingival plaque
Authors: Tsutsumi K , Maruyama M , Uchiyama A , Shibasaki K
Published: September 2017

Objectives

Sugar consumption has been decreasing in Japan, suggesting higher rates of sucrose‐independent supragingival plaque formation. For developing an in vitro biofilm model of sucrose‐independent supragingival plaque, this study aimed to investigate the compositions and functions on contributing to cariogenicity in comparison with sucrose‐dependent biofilm.

Materials and Methods

An in vitro multispecies biofilm containing Actinomyces naeslundii, Streptococcus gordonii, S. mutans, Veillonella parvula and Fusobacterium nucleatum was formed on 24‐well plates in the absence or presence of 1% sucrose. Compositions were assessed by plate culture, scanning electron microscopy and confocal laser scanning microscopy after fluorescent in situ hybridisation or labelling of extracellular polymeric substances (EPS). Functions were assessed by acidogenicity, adherence strength and sensitivities to anticaries agents.

Results

Although both biofilms exhibited a Streptococcus predominant bacterial composition, there were differences in bacterial and EPS compositions; in particular, little glucan EPS was observed in sucrose‐independent biofilm. Compared with sucrose‐dependent biofilm, acidogenicity, adherence strength and antimicrobial resistance of sucrose‐independent biofilm were only slightly lower. However, dextranase degradation was substantially lower in sucrose‐independent biofilm.

Conclusion

Our findings suggest that sucrose‐independent biofilm may have cariogenicity as with sucrose‐dependent biofilm. These in vitro models can help further elucidate plaque‐induced caries aetiology and develop new anticaries agents.
A Cost‐Effectiveness Analysis of Intradiscal Electrothermal Therapy Compared with Circumferential Lumbar Fusion
Authors: Stamuli Eugena , Kesornsak Withawin , Grevitt Michael P. , Posnett John , Claxton Karl
Published: September 2017

Study Design

Cost‐effectiveness analysis.

Objective

To evaluate the cost‐effectiveness of intradiscal electrothermal therapy (IDET) relative to circumferential lumbar fusion with femoral ring allograft (FRA) in the United Kingdom.

Summary of Background Data

Circumferential lumbar fusion is an established treatment for discogenic low back pain. However, IDET could be a cost‐effective treatment alternative as it can be carried out as a day case.

Methods

Patient‐level data were available for patients with discogenic low back pain treated with FRA (n = 37) in a randomized trial of FRA vs. titanium cage, and for patients recruited to a separate study evaluating the use of IDET (n = 85). Both studies were carried out at a single institution in the United Kingdom. Patients were followed‐up for 24 months, with data collected on low back disability (Oswestry Disability Index), back and leg pain (visual analog scale), quality of life (Short Form 36), radiographic evaluations, and U.K. National Health Service (NHS) resource use. Cost‐effectiveness was measured by the incremental cost per quality‐adjusted life year (QALY) gained.

Results

Both treatments produced statistically significant improvements in outcome at 24‐month follow‐up. NHS costs were significantly lower with IDET due to a shorter mean procedure time (377.4 minutes vs. 49.9 minutes) and length of stay (7 days vs. 1.2 days). At a threshold of £20,000 per QALY, the probability that IDET is cost effective is high.

Conclusions

Both treatments led to significant improvements in patient outcomes that were sustained for at least 24 months. Costs were lower with IDET, and for appropriate patients IDET is an effective and cost‐effective treatment alternative.
Cold sensing in grapevine—Which signals are upstream of the microtubular “thermometer”
Authors: Wang Lixin , Nick Peter
Published: September 2017

Plants can acquire freezing tolerance in response to cold but non‐freezing temperatures. To efficiently activate this cold acclimation, low temperature has to be sensed and processed swiftly, a process that is linked with a transient elimination of microtubules. Here, we address cold‐induced microtubules elimination in a grapevine cell line stably expressing a green fluorescent protein fusion of Arabidopsis TuB6, which allows to follow their response in vivo and to quantify this response by quantitative image analysis. We use time‐course studies with several specific pharmacological inhibitors and activators to dissect the signalling events acting upstream of microtubules elimination. We find that microtubules disappear within 30 min after the onset of cold stress. We provide evidence for roles of calcium influx, membrane rigidification, and activation of NAD(P)H oxidase as factors in signal susception and amplification. We further conclude that a G‐protein in concert with a phospholipase D convey the signal towards microtubules, whereas calmodulin seems to be not involved. Moreover, activation of jasmonate pathway in response to cold is required for an efficient microtubule response. We summarize our findings in a working model on a complex signalling hub at the membrane‐cytoskeleton interphase that assembles the susception, perception and early transduction of cold signals.
Soil CO2 venting as one of the mechanisms for tolerance of Zn deficiency by rice in flooded soils
Authors: Affholder Marie‐Cecile , Weiss Dominik J. , Wissuwa Matthias , Johnson‐Beebout Sarah E. , Kirk Guy J.D.
Published: September 2017

We sought to explain rice (Oryza sativa) genotype differences in tolerance of zinc (Zn) deficiency in flooded paddy soils and the counter‐intuitive observation, made in earlier field experiments, that Zn uptake per plant increases with increasing planting density. We grew tolerant and intolerant genotypes in a Zn‐deficient flooded soil at high and low planting densities and found (a) plant Zn concentrations and growth increased with planting density and more so in the tolerant genotype, whereas the concentrations of other nutrients decreased, indicating a specific effect on Zn uptake; (b) the effects of planting density and genotype on Zn uptake could only be explained if the plants induced changes in the soil to make Zn more soluble; and (c) the genotype and planting density effects were both associated with decreases in dissolved CO2 in the rhizosphere soil solution and resulting increases in pH. We suggest that the increases in pH caused solubilization of soil Zn by dissolution of alkali‐soluble, Zn‐complexing organic ligands from soil organic matter. We conclude that differences in venting of soil CO2 through root aerenchyma were responsible for the genotype and planting density effects.
The use of case management for community‐dwelling older people: the effects on loneliness, symptoms of depression and life satisfaction in a randomised controlled trial
Authors: Taube Elin , Kristensson Jimmie , Midlöv Patrik , Jakobsson Ulf
Published: September 2017

Aim

To investigate the effects of a case management intervention for community‐dwelling frail older people, with functional dependency and repeated contacts with the healthcare services, focusing on loneliness, depressive symptoms and life satisfaction.

Design

A two‐armed, nonblinded, randomised control trial with repeated follow‐ups, of N = 153 participants at baseline allocated to an intervention (n = 80) and control (n = 73) group.

Method

Inclusion criteria were the following: ≥65 years of age, living in ordinary housing, in need of assistance in two or more self‐reported activities of daily living, having at least two hospital admissions or at least four visits in outpatient care 12 months prior to enrolment. Case managers (nurses and physiotherapists) provided an intervention of general case management, general information, specific information and continuity and safety. The intervention ranged over 12 months with one or more home visit(s) being conducted per month. An intention‐to‐treat analysis was applied for the primary outcomes of loneliness, depressive symptoms and life satisfaction, along with complete case and sensitivity analyses.

Results

During the trial period n = 12 died and n = 33 dropped out. No significant difference was found between the groups at baseline regarding sociodemographic characteristics, subjective health or primary outcomes. The intention‐to‐treat analysis did not result in any significant effects for the primary outcomes at any of the follow‐ups (6 and 12 months). The complete case analysis resulted in a significant difference in favour of the intervention regarding loneliness (RR = 0.49, p = 0.028) and life satisfaction (ES = 0.41, p = 0.028) at 6 months and for depressive symptoms (ES = 0.47, p = 0.035) at 12 months.

Conclusions

The use of case management for frail older people did not result in clear favourable effects for the primary outcomes. However, the study indicates that case management may be beneficial in terms of these outcomes. Due to the complexity of the outcomes, an elaboration of the components and assessments is suggested.
Trayvon Revisited: Race, Fear, and Affect in the Death of Trayvon Martin
Authors: Torres Mauricio T. , Cannito‐Coville Mary , Rodriguez Dalia
Published: September 2017

This theoretical project intervenes in the debates surrounding the death of Trayvon Martin by starting with fear, the center of Martin's encounter with his killer, George Zimmerman. We deploy the work of Sara Ahmed in order to argue that fear, rather than residing positively in an individual, works as an affective economy that opens up past histories of association. Ahmed's work allows us to move beyond the question of whether or not Zimmerman was consciously racist and instead consider how fear is animated by racist histories of association. We argue that the affective charge of these racist histories accomplishes three interrelated things. First, it allows Zimmerman to frame Martin as dangerous as he calls 911 to report Martin's suspicious presence, an act that comes to constitute Zimmerman's fear. Second, it allows for Martin to be seized epistemologically and ontologically by Zimmerman and killed. Last, it makes Martin's death a functional necessity of Zimmerman's defense, making it challenging to leverage any claim for the injustice of Martin's death.
Waiting on Others: Gender in the Medical Waiting Room
Authors: Waltz Margaret
Published: September 2017

In this article, I describe how gendered interactions and power dynamics play out in medical waiting rooms. While people are spending time idle, waiting for the next thing to happen (i.e., to check in, to see the doctor, to pay), social processes continue to occur and reinforce these gendered interactions and dynamics. Using data collected from ethnographic observations of medical waiting rooms in the Midwestern United States, this article illustrates that waiting offers another opportunity to understand the subtle ways that gendered expectations and hierarchies are perpetuated. Patients, their friends, and families do gender in medical waiting rooms through the amount of auditory and physical space they take up and the ways in which they behave and respond to the actors and expectations in this space.
A more stable transition matrix for acoustic target scattering by highly oblate elastic objects
Authors: Lim Raymond
Published: September 2017

In previous work, a variant of Waterman's transition (T) matrix utilizing an ansatz for problematic outgoing basis functions in standard formulations was proposed and demonstrated to improve the stability of free-field acoustic scattering calculations for elongated axisymmetric elastic objects. The ansatz replaced the basis causing instability with one consisting of low-order spherical functions made complete by distributing the functions along the axis within the object. Unfortunately, these bases are not as useful for expanding outgoing source fields along oblate axisymmetric surfaces. However, related work by Doicu, Eremin, and Wriedt, [Acoustic & Electromagnetic Scattering Analysis Using Discrete Sources, Academic Press, London (2000)], suggests using an alternate basis of low-order spherical functions made complete by analytically continuing them into the complex plane of the object's axial coordinate, distributing them along the imaginary axis of this plane. This paper will show that this alternative does extend the range of stability of our T-matrix formulation for highly oblate axisymmetric objects to frequencies attainable with competing spheroidal-basis T-matrix formulations. Nevertheless, the range is not as great as achieved for prolate shapes and an analysis of the residual noise sources suggest more optimal basis sets are possible that further stabilize scattering computations for such shapes.
Comparison of a fiber-gel finite element model of vocal fold vibration to a transversely isotropic stiffness model
Authors: Titze Ingo R. , Alipour Fariborz , Blake Douglas , Palaparthi Anil
Published: September 2017

A fiber-gel vocal fold model is compared to a transversely isotropic stiffness model in terms of normal mode vibration. The fiber-gel finite element model (FG-FEM) consists of a series of gel slices, each with a two-dimensional finite element mesh, in a plane transverse to the tissue fibers. The gel slices are coupled with fibers under tension in the anterior-posterior dimension. No vibrational displacement in the fiber-length direction is allowed, resulting in a plane strain state. This is consistent with the assumption of transverse displacement of a simple string, offering a wide range of natural frequencies (well into the kHz region) with variable tension. For low frequencies, the results compare favorably with the natural frequencies of a transversely isotropic elastic stiffness model (TISM) in which the shear modulus in the longitudinal plane is used to approximate the effect of fiber tension. For high frequencies, however, the natural frequencies do not approach the string mode frequencies unless plane strain is imposed on the TISM model. The simplifying assumption of plane strain, as well as the use of analytical closed-form shape functions, allow for substantial savings in computational time, which is important in clinical and exploratory applications of the FG-FEM model.
Effects of HIV-1 Tat and Methamphetamine on Blood-Brain Barrier Integrity and FunctionIn Vitro
Authors: Patel Sulay , Leibrand Crystal R. , Palasuberniam Preetha , Couraud Pierre-Olivier , Weksler Babette , Jahr Fay M. , McClay Joseph L. , Hauser Kurt F. , McRae MaryPeace
Published: September 2017

Human immunodeficiency (HIV) infection results in neurocognitive deficits in about one half of infected individuals. Despite systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation in fighting central nervous system (CNS)-localized infection. Drug abuse exacerbates HIV-induced cognitive and pathological CNS changes. This study's purpose was to investigate the effects of the HIV-1 protein Tat and methamphetamine on factors affecting drug penetration across anin vitroBBB model. Factors affecting paracellular and transcellular flux in the presence of Tat and methamphetamine were examined. Transendothelial electrical resistance, ZO-1 expression, and lucifer yellow (a paracellular tracer) flux were aspects of paracellular processes that were examined. Additionally, effects on P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP-1) mRNA (via quantitative PCR [qPCR]) and protein (via immunoblotting) expression were measured; Pgp and MRP-1 are drug efflux proteins. Transporter function was examined after exposure of Tat with or without methamphetamine using the P-gp substrate rhodamine 123 and also using the dual P-gp/MRP-1 substrate and protease inhibitor atazanavir. Tat and methamphetamine elicit complex changes affecting transcellular and paracellular transport processes. Neither Tat nor methamphetamine significantly altered P-gp expression. However, Tat plus methamphetamine exposure significantly increased rhodamine 123 accumulation within brain endothelial cells, suggesting that treatment inhibited or impaired P-gp function. Intracellular accumulation of atazanavir was not significantly altered after Tat or methamphetamine exposure. Atazanavir accumulation was, however, significantly increased by simultaneous inhibition of P-gp and MRP. Collectively, our investigations indicate that Tat and methamphetamine alter aspects of BBB integrity without affecting net flux of paracellular compounds. Tat and methamphetamine may also affect several aspects of transcellular transport.
External Evaluation of Two Fluconazole Infant Population Pharmacokinetic Models
Authors: Hwang Michael F. , Beechinor Ryan J. , Wade Kelly C. , Benjamin Daniel K. , Smith P. Brian , Hornik Christoph P. , Capparelli Edmund V. , Duara Shahnaz , Kennedy Kathleen A. , Cohen-Wolkowiez Michael , Gonzalez Daniel
Published: September 2017

Fluconazole is an antifungal agent used for the treatment of invasive candidiasis, a leading cause of morbidity and mortality in premature infants. Population pharmacokinetic (PK) models of fluconazole in infants have been previously published by Wade et al. (Antimicrob Agents Chemother 52:4043–4049, 2008,
https://doi.org/10.1128/AAC.00569-08
) and Momper et al. (Antimicrob Agents Chemother 60:5539–5545, 2016,
https://doi.org/10.1128/AAC.00963-16
). Here we report the results of the first external evaluation of the predictive performance of both models. We used patient-level data from both studies to externally evaluate both PK models. The predictive performance of each model was evaluated using the model prediction error (PE), mean prediction error (MPE), mean absolute prediction error (MAPE), prediction-corrected visual predictive check (pcVPC), and normalized prediction distribution errors (NPDE). The values of the parameters of each model were reestimated using both the external and merged data sets. When evaluated with the external data set, the model proposed by Wade et al. showed lower median PE, MPE, and MAPE (0.429 μg/ml, 41.9%, and 57.6%, respectively) than the model proposed by Momper et al. (2.45 μg/ml, 188%, and 195%, respectively). The values of the majority of reestimated parameters were within 20% of their respective original parameter values for all model evaluations. Our analysis determined that though both models are robust, the model proposed by Wade et al. had greater accuracy and precision than the model proposed by Momper et al., likely because it was derived from a patient population with a wider age range. This study highlights the importance of the external evaluation of infant population PK models.