bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the role of socioeconomic deprivation in ethnic differences in sexually transmitted infection diagnosis rates in England: evidence from surveillance data
Authors: FUREGATO M. , CHEN Y. , MOHAMMED H. , MERCER C. H. , SAVAGE E. J. , HUGHES G.
Published: August 2016

Differences by ethnic group in STI diagnosis rates have long been recognized in England. We investigated whether these may be explained by ethnic disparities in socioeconomic deprivation (SED). Data on all diagnoses made in sexual health clinics in England in 2013 were obtained from the mandatory STI surveillance system. Poisson regression was used to calculate incidence rate ratios (IRRs) of STIs, by ethnicity, with and without adjustment for index of multiple deprivation (IMD) a measure of area-level deprivation. Unadjusted IRRs (95% confidence intervals) were highest for gonorrhoea [8·18 (7·77–8·61) and 5·76 (5·28–6·29)] and genital herpes [4·24 (3·99–4·51) and 3·58 (3·23–3·98)] for people of black Caribbean and non-Caribbean/non-African black ethnicity and IRRs were highest for syphilis [8·76 (7·97–9·63)] and genital warts [2·23 (2·17–2·29)] for people of non-British/non-Irish white ethnicity compared to white British ethnicity. After adjustment for IMD, IRRs for gonorrhoea [5·76 (5·47–6·07)] and genital herpes [3·73 (3·50–3·97)] declined but remained highest for black Caribbeans and IRRs for syphilis [7·35 (6·68–8·09)] and genital warts [2·10 (2·04–2·16)] declined but remained highest for non-British/non-Irish white compared to white British. In England, ethnic disparities in STI diagnosis rates are partially explained by SED, but behavioural and contextual factors likely contribute. Clinic and community-based interventions should involve social peer networks to ensure they are targeted and culturally sensitive.
Multidrug-resistant surgical site infections in a humanitarian surgery project
Authors: MURPHY R. A. , OKOLI O. , ESSIEN I. , TEICHER C. , ELDER G. , PENA J. , RONAT J.-B. , BERNABÉ K. J.
Published: August 2016

The epidemiology of surgical site infections (SSIs) in surgical programmes in sub-Saharan Africa is inadequately described. We reviewed deep and organ-space SSIs occurring within a trauma project that had a high-quality microbiology partnership and active follow-up. Included patients underwent orthopaedic surgery in Teme Hospital (Port Harcourt, Nigeria) for trauma and subsequently developed a SSI requiring debridement and microbiological sampling. Data were collected from structured chart reviews and programmatic databases for 103 patients with suspected SSI [79% male, median age 30 years, interquartile range (IQR) 24–37]. SSIs were commonly detected post-discharge with 58% presenting >28 days after surgery. The most common pathogens were: Staphylococcus aureus (34%), Pseudomonas aeruginosa (16%) and Enterobacter cloacae (11%). Thirty-three (32%) of infections were caused by a multidrug-resistant (MDR) pathogen, including 15 patients with methicillin-resistant S. aureus. Antibiotics were initiated empirically for 43% of patients and after culture and sensitivity report in 32%. The median number of additional surgeries performed in patients with SSI was 5 (IQR 2–6), one patient died (1%), and amputation was performed or recommended in three patients. Our findings suggest the need for active long-term monitoring of SSIs, particularly those associated with MDR organisms, resulting in increased costs for readmission surgery and treatment with late-generation antibiotics.
Körperliches Gesundheitsscreening in der ambulanten Psychiatrie
Authors: Burr Christian , Hegedüs Anna , Bänziger Sulin , Hubl Daniela
Published: August 2016

Zusammenfassung. Körperliche Gesundheitsprobleme stehen bei psychiatrischen Dienstleistungen meist nicht im Fokus und werden leider häufig übersehen. Daher wurde ein körperliches Gesundheitsscreening im ambulanten Bereich der Universitären Psychiatrischen Dienste Bern, Schweiz eingeführt. Dieser Artikel berichtet über den Prozess der Implementierung, der mit der Durchführung einer Studie initiiert und durch die Integration des Gesundheitsscreenings in den Routineprozess abgeschlossen wurde.
UN-MÖGLICH?
Authors: Clasen Christa , Rantze Silke
Published: August 2016

Zusammenfassung. Körperliche Ursachen bewirken, dass die Lebenserwartung von Menschen mit einer schweren psychischen Erkrankung um 15–20 Lebensjahre reduziert ist. Die Gründe dafür sind komplex. Personenbezogene Faktoren und gesellschaftliche Barrieren, die einen Zugang zu adäquater Behandlung verhindern, wirken einem gesundheitsförderlichen Verhalten entgegen.
Recovery ist (k)ein Würfelspiel
Authors: Holzke Martin , Heinsch Anna
Published: August 2016

Zusammenfassung. Das Spiel beginnt mit der Sichtung vorhandender Manuale zur Schulung der Recovery-Grundlagen (Zuaboni et al., 2012; Slade, 2013). Diese bilden die Basis zur Entwicklung einer Recovery-orientierten Haltung der professionellen Helferinnen und Helfer, sowie die Möglichkeit für Betroffene, sich mit dem Thema Recovery auseinanderzusetzen. Neben diesen Manualen sind die eindrücklichen Erlebnisse von Betroffenen selbst (Prins, 2003; Deegan, 1996), wichtige Quellen, die dazu beitragen ein Verständnis für die Idee von Recovery zu entwickeln.
Transdisziplinäre Zusammenarbeit
Authors: Löhr Michael
Published: August 2016

Zusammenfassung. Michael Löhr im Interview mit der Pflegedirektorin Rita Elpers und dem ärztlichen Direktor Professor Dr. med. Dipl.-Psych. Klaus-Thomas Kronmüller des LWL-Klinikums Gütersloh
Eins-zu-eins-Betreuung in der psychiatrischen Versorgung
Authors: Nienaber André , Groß Regine , Hemkendreis Bruno , Hagemann Tim , Schulz Michael , Löhr Michael
Published: August 2016

Zusammenfassung. Ergebnisse einer Online-Umfrage zur Eins-zu-eins-Betreuung in der psychiatrischen Versorgung in deutschsprachigen Ländern
Das Unmögliche möglich machen
Authors: Röseler Volker
Published: August 2016

Zusammenfassung. Die Betreuung und Behandlung von Menschen, die an einer Zwangsstörung leiden, ist für Fachpersonen in der Psychiatrie häufig eine menschliche und professionelle Herausforderung. Mangelndes Fachwissen über das Erleben der Betroffenen und wirkungsvolle Interventionen erschweren dies oft zusätzlich. Mit diesem Beitrag soll sowohl Verständnis für die Betroffenen geweckt als auch konkrete störungsspezifische Interventionen vorgestellt werden.
Habilitation des Faches Psychiatrische Pflege an deutschsprachigen medizinischen Fakultäten Kontinentaleuropas
Authors: Behrens Johann
Published: August 2016

Zusammenfassung. Habilitation heißt auf Deutsch Beheimatung. Rehabilitation ist entsprechend die Wiederbeheimatung in die gewohnten Teilhabe am Leben nach Krankheit oder rechtlicher bzw. politischer Anklage, Habilitation ist die erstmalige Beheimatung in ein neues Leben.
Glial degeneration with oxidative damage drives neuronal demise in MPSII disease
Authors: Zalfa Cristina , Verpelli Chiara , D'Avanzo Francesca , Tomanin Rosella , Vicidomini Cinzia , Cajola Laura , Manara Renzo , Sala Carlo , Scarpa Maurizio , Vescovi Angelo Luigi , De Filippis Lidia
Published: August 2016

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.
Projected increase in amyotrophic lateral sclerosis from 2015 to 2040
Authors: Arthur Karissa C. , Calvo Andrea , Price T. Ryan , Geiger Joshua T. , Chiò Adriano , Traynor Bryan J.
Published: August 2016

Although amyotrophic lateral sclerosis (ALS) is relatively rare, the socioeconomic significance of the disease is extensive. It is therefore vital to project the epidemiologic trend of ALS. To date, there have been few published studies attempting to estimate the number and distribution of ALS cases in the upcoming years. Here we show that the number of ALS cases across the globe will increase from 222,801 in 2015 to 376,674 in 2040, representing an increase of 69%. This increase is predominantly due to ageing of the population, particularly among developing nations. This projection is likely an underestimate due to improving healthcare and economic conditions. The results should be used to inform healthcare policy to more efficiently allocate healthcare resources.
Increasing flash droughts over China during the recent global warming hiatus
Authors: Wang Linying , Yuan Xing , Xie Zhenghui , Wu Peili , Li Yaohui
Published: August 2016

The recent global warming slowdown or hiatus after the big El Niño event in 1997/98 raises the questions of whether terrestrial hydrological cycle is being decelerated and how do the hydrological extremes respond to the hiatus. However, the rapidly developing drought events that are termed as “flash droughts” accompanied by extreme heat, low soil moisture and high evapotranspiration (ET), occurred frequently around the world, and caused devastating impacts on crop yields and water supply. Here, we investigate the long-term trend and variability of flash droughts over China. Flash droughts are most likely to occur over humid and semi-humid regions, such as southern and northeastern China. Flash drought averaged over China increased by 109% from 1979 to 2010, and the increase was mainly due to a long term warming of temperature (50%), followed by the contributions from decreasing soil moisture and increasing ET. There was a slight drop in temperature after 1997, but the increasing trend of flash droughts was tripled. Further results indicate that the decreasing temperature was compensated by the accelerated drying trends of soil moisture and enhanced ET, leading to an acceleration of flash droughts during the warming hiatus. The anthropogenic warming in the next few decades may exacerbate future flash drought conditions in China.
TRPV4 regulates calcium homeostasis, cytoskeletal remodeling, conventional outflow and intraocular pressure in the mammalian eye
Authors: Ryskamp Daniel A. , Frye Amber M. , Phuong Tam T. T. , Yarishkin Oleg , Jo Andrew O. , Xu Yong , Lakk Monika , Iuso Anthony , Redmon Sarah N. , Ambati Balamurali , Hageman Gregory , Prestwich Glenn D. , Torrejon Karen Y. , Križaj David
Published: August 2016

An intractable challenge in glaucoma treatment has been to identify druggable targets within the conventional aqueous humor outflow pathway, which is thought to be regulated/dysregulated by elusive mechanosensitive protein(s). Here, biochemical and functional analyses localized the putative mechanosensitive cation channel TRPV4 to the plasma membrane of primary and immortalized human TM (hTM) cells, and to human and mouse TM tissue. Selective TRPV4 agonists and substrate stretch evoked TRPV4-dependent cation/Ca2+ influx, thickening of F-actin stress fibers and reinforcement of focal adhesion contacts. TRPV4 inhibition enhanced the outflow facility and lowered perfusate pressure in biomimetic TM scaffolds populated with primary hTM cells. Systemic delivery, intraocular injection or topical application of putative TRPV4 antagonist prodrug analogs lowered IOP in glaucomatous mouse eyes and protected retinal neurons from IOP-induced death. Together, these findings indicate that TRPV4 channels function as a critical component of mechanosensitive, Ca2+-signaling machinery within the TM, and that TRPV4-dependent cytoskeletal remodeling regulates TM stiffness and outflow. Thus, TRPV4 is a potential IOP sensor within the conventional outflow pathway and a novel target for treating ocular hypertension.
Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment
Authors: Kim Yong Sook , Jeong Hye-yun , Kim Ah Ra , Kim Woong-Hee , Cho Haaglim , Um JungIn , Seo Youngha , Kang Wan Seok , Jin Suk-Won , Kim Min Chul , Kim Yong-Chul , Jung Da-Woon , Williams Darren R. , Ahn Youngkeun
Published: August 2016

The cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2′Z,3′E)-6-Bromoindirubin-3′-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI.
Associations between microRNA binding site SNPs in FGFs and FGFRs and the risk of non-syndromic orofacial cleft
Authors: Li Dandan , Zhang Hongchuang , Ma Lan , Han Yue , Xu Min , Wang Zhendong , Jiang Hongbing , Zhang Weibing , Wang Lin , Pan Yongchu
Published: August 2016

We hypothesized that microRNA binding site single nucleotide polymorphisms (SNPs) in fibroblast growth factors (FGFs) and their receptor genes (FGFRs) may affect microRNA and mRNA interactions and are thereby associated with susceptibility of non-syndromic orofacial cleft (NSOC). Ten SNPs among the FGF and FGFR genes were selected and their associations with NSOC susceptibility were investigated in a case-control study of 602 patients with NSOC and 605 healthy controls. FGF2/rs1048201, FGF5/rs3733336 and FGF9/rs546782 showed suggestive association with NSOC susceptibility. In the combination analysis, the observed odds ratios (ORs) decreased with the number of protective alleles (rs1048201-T, rs3733336-G and rs546782-T) but were not statistically significant beyond the first comparison. Hsa-miRNA-496, hsa-miRNA-145 and hsa-miRNA-187 were predicted to be miRNAs with binding sites within/near these SNPs and were expressed in lip tissues. Decreased FGF2, FGF5 and FGF9 expression was observed in three cell lines transfected with the corresponding miRNAs. Moreover, the three SNPs could contribute to differential binding efficacy between hsa-miRNA-496 and FGF2, hsa-miRNA-145 and FGF5, hsa-miRNA-187 and FGF9 in luciferase assay. The results suggest that FGF2/rs1048201, FGF5/rs3733336 and FGF9/rs546782 are associated with the risk of NSOC and that these miRNA-FGF interactions may affect NSOC development.
VHLdb: A database of von Hippel-Lindau protein interactors and mutations
Authors: Tabaro Francesco , Minervini Giovanni , Sundus Faiza , Quaglia Federica , Leonardi Emanuela , Piovesan Damiano , Tosatto Silvio C. E.
Published: August 2016

Mutations in von Hippel-Lindau tumor suppressor protein (pVHL) predispose to develop tumors affecting specific target organs, such as the retina, epididymis, adrenal glands, pancreas and kidneys. Currently, more than 400 pVHL interacting proteins are either described in the literature or predicted in public databases. This data is scattered among several different sources, slowing down the comprehension of pVHL’s biological role. Here we present VHLdb, a novel database collecting available interaction and mutation data on pVHL to provide novel integrated annotations. In VHLdb, pVHL interactors are organized according to two annotation levels, manual and automatic. Mutation data are easily accessible and a novel visualization tool has been implemented. A user-friendly feedback function to improve database content through community-driven curation is also provided. VHLdb presently contains 478 interactors, of which 117 have been manually curated, and 1,074 mutations. This makes it the largest available database for pVHL-related information. VHLdb is available from URL: http://vhldb.bio.unipd.it/.
Fibroproliferative response to urothelial failure obliterates the ureter lumen in a mouse model of prenatal congenital obstructive nephropathy
Authors: Lee Amanda J. , Polgar Noemi , Napoli Josephine A. , Lui Vanessa H. , Tamashiro Kadee-Kalia , Fujimoto Brent A. , Thompson Karen S. , Fogelgren Ben
Published: August 2016

Congenital obstructive nephropathy (CON) is the most prevalent cause of pediatric chronic kidney disease and end-stage renal disease. The ureteropelvic junction (UPJ) region, where the renal pelvis transitions to the ureter, is the most commonly obstructed site in CON. The underlying causes of congenital UPJ obstructions remain poorly understood, especially when they occur in utero, in part due to the lack of genetic animal models. We previously showed that conditional inactivation of Sec10, a central subunit of the exocyst complex, in the epithelial cells of the ureter and renal collecting system resulted in late gestational bilateral UPJ obstructions with neonatal anuria and death. In this study, we show that without Sec10, the urothelial progenitor cells that line the ureter fail to differentiate into superficial cells, which are responsible for producing uroplakin plaques on the luminal surface. These Sec10-knockout urothelial cells undergo cell death by E17.5 and the urothelial barrier becomes leaky to luminal fluid. Also at E17.5, we measured increased expression of TGFβ1 and genes associated with myofibroblast activation, with evidence of stromal remodeling. Our findings support the model that a defective urothelial barrier allows urine to induce a fibrotic wound healing mechanism, which may contribute to human prenatal UPJ obstructions.
Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation
Authors: Bam Marpe , Yang Xiaoming , Zumbrun Elizabeth E. , Zhong Yin , Zhou Juhua , Ginsberg Jay P. , Leyden Quinne , Zhang Jiajia , Nagarkatti Prakash S. , Nagarkatti Mitzi
Published: August 2016

Post-traumatic stress disorder patients experience chronic systemic inflammation. However, the molecular pathways involved and mechanisms regulating the expression of genes involved in inflammatory pathways in PTSD are reported inadequately. Through RNA sequencing and miRNA microarray, we identified 326 genes and 190 miRNAs that were significantly different in their expression levels in the PBMCs of PTSD patients. Expression pairing of the differentially expressed genes and miRNAs indicated an inverse relationship in their expression. Functional analysis of the differentially expressed genes indicated their involvement in the canonical pathways specific to immune system biology. DNA methylation analysis of differentially expressed genes also showed a gradual trend towards differences between control and PTSD patients, again indicating a possible role of this epigenetic mechanism in PTSD inflammation. Overall, combining data from the three techniques provided a holistic view of several pathways in which the differentially expressed genes were impacted through epigenetic mechanisms, in PTSD. Thus, analysis combining data from RNA-Seq, miRNA array and DNA methylation, can provide key evidence about dysregulated pathways and the controlling mechanism in PTSD. Most importantly, the present study provides further evidence that inflammation in PTSD could be epigenetically regulated.
Emotional Modulation of Conflict Processing in the Affective Domain: Evidence from Event-related Potentials and Event-related Spectral Perturbation Analysis
Authors: Ma Jianling , Liu Chang , Chen Xu
Published: August 2016

Previous studies have revealed the impact of emotion on conflict processing. The present study was conducted to investigate whether cognitive control in the affective domain is also affected by emotion. Emotional face-word and body-word Stroop tasks were explored and contrasted and both behavioural and electrophysiological measures were recorded. Behavioural results showed that both tasks replicated previous robust interference effects. At the physiological level, the two tasks showed dissociable neural activity in the early attention and perception stages. It was also found that the face-word task evoked more pronounced N1 and P2 amplitudes than the body-word task. However, the two tasks evoked comparable N450 amplitudes. At later processing stages, positive slow potentials were modulated by target emotion and congruency. In addition, time-frequency analyses also revealed that the face-word task induced enhanced theta activity compared to the body-word task at both early and later stages of processing. The present findings provide support for the dual competition framework and suggest the dynamic modulation of emotion on cognitive control in the affective domain.
Lung Microtissue Array to Screen the Fibrogenic Potential of Carbon Nanotubes
Authors: Chen Zhaowei , Wang Qixin , Asmani Mohammadnabi , Li Yan , Liu Chang , Li Changning , Lippmann Julian M. , Wu Yun , Zhao Ruogang
Published: August 2016

Due to their excellent physical and chemical characteristics, multi-wall carbon nanotubes (MWCNT) have the potential to be used in structural composites, conductive materials, sensors, drug delivery and medical imaging. However, because of their small-size and light-weight, the applications of MWCNT also raise health concerns. In vivo animal studies have shown that MWCNT cause biomechanical and genetic alterations in the lung tissue which lead to lung fibrosis. To screen the fibrogenic risk factor of specific types of MWCNT, we developed a human lung microtissue array device that allows real-time and in-situ readout of the biomechanical properties of the engineered lung microtissue upon MWCNT insult. We showed that the higher the MWCNT concentration, the more severe cytotoxicity was observed. More importantly, short type MWCNT at low concentration of 50 ng/ml stimulated microtissue formation and contraction force generation, and caused substantial increase in the fibrogenic marker miR-21 expression, indicating the high fibrogenic potential of this specific carbon nanotube type and concentration. The presented microtissue array system provides a powerful tool for high-throughput examination of the therapeutic and toxicological effects of target compounds in realistic tissue environment.
Retrieval-Based Model Accounts for Striking Profile of Episodic Memory and Generalization
Authors: Banino Andrea , Koster Raphael , Hassabis Demis , Kumaran Dharshan
Published: August 2016

A fundamental theoretical tension exists between the role of the hippocampus in generalizing across a set of related episodes, and in supporting memory for individual episodes. Whilst the former requires an appreciation of the commonalities across episodes, the latter emphasizes the representation of the specifics of individual experiences. We developed a novel version of the hippocampal-dependent paired associate inference (PAI) paradigm, which afforded us the unique opportunity to investigate the relationship between episodic memory and generalization in parallel. Across four experiments, we provide surprising evidence that the overlap between object pairs in the PAI paradigm results in a marked loss of episodic memory. Critically, however, we demonstrate that superior generalization ability was associated with stronger episodic memory. Through computational simulations we show that this striking profile of behavioral findings is best accounted for by a mechanism by which generalization occurs at the point of retrieval, through the recombination of related episodes on the fly. Taken together, our study offers new insights into the intricate relationship between episodic memory and generalization, and constrains theories of the mechanisms by which the hippocampus supports generalization.
A Retrospective Study of thrombolysis with 0.6 mg/kg Recombinant Tissue Plasminogen Activator (rt-PA) in Mild Stroke
Authors: Yang Jie , Yu Fei , Liu Hong , An Hedi , Xiong Ran , Huang Dongya
Published: August 2016

We sought to assess the safety, effectiveness and cost of 0.6 mg/kg rt-PA treatment for patients with acute mild stroke and to compare that with 0.9 mg/kg. We retrospectively analyzed consecutive acute ischemic stroke patients who had a NIHSS score ≤5 at admission and who were treated with rt-PA within 4.5 hours of symptom onset. The demographic data, clinical outcomes and hospitalization cost were analyzed. A total of 108 patients were included. Forty six patients (42.6%) received a 0.6 mg/kg dosage of rt-PA. The baseline characteristics of the two groups were well matched (p > 0.05). Regarding the safety and effectiveness, the 0.6 mg/kg dosage group had a comparable proportion of symptomatic intracranial hemorrhage (sICH) (0.6 mg/kg, 4.3% vs 0.9 mg/kg, 4.8%; p > 0.05), early neurological deterioration (END) (19.6% vs 17.7%; p > 0.05), in-hospital mortality (4.3% vs 1.6%; p > 0.05), and a similar rate of favorable functional outcome (mRS score 0–1) at 3 months (73.9% vs 71.0%; p > 0.05) to those who received the standard dosage. However, the hospital cost was markedly lower in the 0.6 mg/kg group (0.6 mg/kg, 3,401.7 USD vs 0.9 mg/kg, 4,157.4 USD; p < 0.01). Our study suggest that 0.6 mg/kg rt-PA shared similar effectiveness and safety profile compared with that of 0.9 mg/kg in treating mild stroke, but cost less.
Stratification of responders towards eculizumab using a structural epitope mapping strategy
Authors: Volk Anna-Luisa , Hu Francis Jingxin , Berglund Magnus M. , Nordling Erik , Strömberg Patrik , Uhlen Mathias , Rockberg Johan
Published: August 2016

The complement component 5 (C5)-binding antibody eculizumab is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). As recently reported there is a need for a precise classification of eculizumab responsive patients to allow for a safe and cost-effective treatment. To allow for such stratification, knowledge of the precise binding site of the drug on its target is crucial. Using a structural epitope mapping strategy based on bacterial surface display, flow cytometric sorting and validation via haemolytic activity testing, we identified six residues essential for binding of eculizumab to C5. This epitope co-localizes with the contact area recently identified by crystallography and includes positions in C5 mutated in non-responders. The identified epitope also includes residue W917, which is unique for human C5 and explains the observed lack of cross-reactivity for eculizumab with other primates. We could demonstrate that Ornithodorus moubata complement inhibitor (OmCI), in contrast to eculizumab, maintained anti-haemolytic function for mutations in any of the six epitope residues, thus representing a possible alternative treatment for patients non-responsive to eculizumab. The method for stratification of patients described here allows for precision medicine and should be applicable to several other diseases and therapeutics.
Impact of language on functional connectivity for audiovisual speech integration
Authors: Shinozaki Jun , Hiroe Nobuo , Sato Masa-aki , Nagamine Takashi , Sekiyama Kaoru
Published: August 2016

Visual information about lip and facial movements plays a role in audiovisual (AV) speech perception. Although this has been widely confirmed, previous behavioural studies have shown interlanguage differences, that is, native Japanese speakers do not integrate auditory and visual speech as closely as native English speakers. To elucidate the neural basis of such interlanguage differences, 22 native English speakers and 24 native Japanese speakers were examined in behavioural or functional Magnetic Resonance Imaging (fMRI) experiments while mono-syllabic speech was presented under AV, auditory-only, or visual-only conditions for speech identification. Behavioural results indicated that the English speakers identified visual speech more quickly than the Japanese speakers and that the temporal facilitation effect of congruent visual speech was significant in the English speakers but not in the Japanese speakers. Using fMRI data, we examined the functional connectivity among brain regions important for auditory-visual interplay. The results indicated that the English speakers had significantly stronger connectivity between the visual motion area MT and the Heschl’s gyrus compared with the Japanese speakers, which may subserve lower-level visual influences on speech perception in English speakers in a multisensory environment. These results suggested that linguistic experience strongly affects neural connectivity involved in AV speech integration.
Pretreatment neutrophil-to-lymphocyte ratio and its dynamic changes are associated with the overall survival in advanced cancer patients undergoing palliative care
Authors: Zhao Weiwei , Wu Zhenyu , Li Yintao , Jia Huixun , Chen Menglei , Gu Xiaoli , Liu Minghui , Zhang Zhe , Wang Peng , Cheng Wenwu
Published: August 2016

The objective of this study was to investigate the prognostic value of pretreatment NLR and its dynamic changes responsive to palliative care in advanced cancer patients. The study was retrospectively assessed in 378 consecutive advanced cancer patients receiving palliative care and in an extended follow-up study of 106 of those patients. The cutoff value of pretreatment NLR was determined to be 3.0. In the 378 advanced cancer patients, 89 had pretreatment NLR ≤ 3 and 289 had an NLR > 3. Univariate and multivariate analyses showed that tumor stage, palliative care, albumin level and pretreatment NLR (HR: 1.514, 95% CI: 1.125~2.038, P = 0.006) were independent prognostic indicators of OS. Moreover, in the follow-up cohort of 106 readmitted patients, 43 patients achieved a decreased NLR after palliative care, while the remaining 63 patients showed an increased NLR. Univariate and multivariate analyses showed that an increase in NLR was significantly associated with a poor survival (HR: 2.506, 95% CI: 1.474~4.261, P = 0.001). In conclusion, pretreatment NLR and changes in NLR independently predicted OS in advanced cancer patients undergoing palliative care. Incorporating NLR into clinical practice may better inform the prognosis and therapy decisions of advanced cancer patients in palliative settings.
Proteomic analysis of an engineered isolate of Lactobacillus plantarum with enhanced raffinose metabolic capacity
Authors: Wang Jicheng , Hui Wenyan , Cao Chenxia , Jin Rulin , Ren Caixia , Zhang Heping , Zhang Wenyi
Published: August 2016

Lactic acid bacteria that can produce alpha-galactosidase are a promising solution for improving the nutritional value of soy-derived products. For their commercial use in the manufacturing process, it is essential to understand the catabolic mechanisms that facilitate their growth and performance. In this study, we used comparative proteomic analysis to compare catabolism in an engineered isolate of Lactobacillus plantarum P-8 with enhanced raffinose metabolic capacity, with the parent (or wild-type) isolate from which it was derived. When growing on semi-defined medium with raffinose, a total of one hundred and twenty-five proteins were significantly up-regulated (>1.5 fold, P < 0.05) in the engineered isolate, whilst and one hundred and six proteins were significantly down-regulated (<−1.5 fold, P < 0.05). During the late stages of growth, the engineered isolate was able to utilise alternative carbohydrates such as sorbitol instead of raffinose to sustain cell division. To avoid acid damage the cell layer of the engineered isolate altered through a combination of de novo fatty acid biosynthesis and modification of existing lipid membrane phospholipid acyl chains. Interestingly, aspartate and glutamate metabolism was associated with this acid response. Higher intracellular aspartate and glutamate levels in the engineered isolate compared with the parent isolate were confirmed by further chemical analysis. Our study will underpin the future use of this engineered isolate in the manufacture of soymilk products.
Salt secretion is linked to acid-base regulation of ionocytes in seawater-acclimated medaka: new insights into the salt-secreting mechanism
Authors: Liu Sian-Tai , Horng Jiun-Lin , Chen Po-Yen , Hwang Pung-Pung , Lin Li-Yih
Published: August 2016

Ionocytes in the skin and gills of seawater (SW) teleosts are responsible for both salt and acid secretion. However, the mechanism through which ionocytes secrete acid is still unclear. Here, we hypothesized that apical Na+/H+ exchangers (NHE2/3), carbonic anhydrase (CA2-like) and basolateral HCO3−/Cl− exchanger (AE1) are involved in acid secretion. In addition, the hypothesized involvement of basolateral AE1 suggested that acid secretion may be linked to Cl− secretion by ionocytes. The scanning ion-selective electrode technique (SIET) was used to measure H+ and Cl− secretion by ionocytes in the skin of medaka larvae acclimated to SW. Treatment with inhibitors of NHE, CA and AE suppressed both H+ and Cl− secretion by ionocytes. Short-term exposure to hypercapnic SW stimulated both H+ and Cl− secretion. mRNA of CA2-like and AE1 were localized to ionocytes in the skin. Branchial mRNA levels of NKCC1a, CA2-like and AE1a increased together with the salinity to which fish were acclimated. In addition, both AE1a and AE1b mRNA increased in fish acclimated to acidified (pH 7) SW; NKCC1a mRNA increased in fish acclimated to pH 9 SW. This study reveals the mechanism of H+ secretion by ionocytes and refines our understanding of the well-established mechanism of Cl− secretion by ionocytes of SW fish.
A Comparative Analysis of Sonic Defences in Bombycoidea Caterpillars
Authors: Bura Veronica L. , Kawahara Akito Y. , Yack Jayne E.
Published: August 2016

Caterpillars have long been used as models for studying animal defence. Their impressive armour, including flamboyant warning colours, poisonous spines, irritating sprays and mimicry of plant parts, snakes and bird droppings, has been extensively documented. But research has mainly focused on visual and chemical displays. Here we show that some caterpillars also exhibit sonic displays. During simulated attacks, 45% of 38 genera and 33% of 61 species of silk and hawkmoth caterpillars (Bombycoidea) produced sounds. Sonic caterpillars are found in many distantly-related groups of Bombycoidea and have evolved four distinct sound types- clicks, chirps, whistles and vocalizations. We propose that different sounds convey different messages, with some designed to warn of a chemical defence and others, to startle predators. This research underscores the importance of exploring acoustic communication in juvenile insects and provides a model system to explore how different signals have evolved to frighten, warn or even trick predators.
Bacteria Delay the Jamming of Particles at Microchannel Bottlenecks
Authors: Sendekie Zenamarkos Bantie , Gaveau Arthur , Lammertink Rob G. H. , Bacchin Patrice
Published: August 2016

Clogging of channels by complex systems such as mixtures of colloidal and biological particles is commonly encountered in different applications. In this work, we analyze and compare the clogging mechanisms and dynamics by pure and mixture suspensions of polystyrene latex particles and Escherichia coli by coupling fluorescent microscopic observation and dynamic permeability measurements in microfluidic filters. Pure particles filtration leads to arches and deposit formation in the upstream side of the microfilter while pure bacteria form streamers in the downstream zone. When mixing particle and bacteria, an unexpected phenomenon occurs: the clogging dynamics is significantly delayed. This phenomenon is related to apparent “slippery” interactions between the particles and the bacteria. These interactions limit the arches formation at the channels entrances and favour the formation of dendritic structures on the pillars between the channels. When these dendrites are eroded by the flow, fragments of the deposit are dragged towards the channels entrances. However, these bacteria/particles clusters being lubricated by the slippery interactions are deformed and stretched by the shear thus facilitating their passage through the microchannels.
Non-vitamin K antagonist oral anticoagulation usage according to age among patients with atrial fibrillation: Temporal trends 2011–2015 in Denmark
Authors: Staerk Laila , Fosbøl Emil Loldrup , Gadsbøll Kasper , Sindet-Pedersen Caroline , Pallisgaard Jannik Langtved , Lamberts Morten , Lip Gregory Y. H. , Torp-Pedersen Christian , Gislason Gunnar Hilmar , Olesen Jonas Bjerring
Published: August 2016

Among atrial fibrillation (AF) patients, Danish nationwide registries (2011–2015) were used to examine temporal trends of initiation patterns of oral anticoagulation (OAC) treatment according to age. Overall, 43,299 AF patients initiating vitamin K antagonists (VKA) (42%), dabigatran (29%), rivaroxaban (13%), or apixaban (16%) were included with mean age (SD) 72.1 (11.3), 71.5 (11.0), 74.3 (11.1) and 75.3 (11.1) years, respectively. Patients aged ≥85 years comprised 15%. Trend tests showed increase in patients ≥85 years initiating OAC (p < 0.0001). VKA usage decreased from 92% to 24% (p < 0.0001). This decrease was independent of age. Dabigatran was the most common non-VKA OAC (NOAC) (40% users), but usage decreased from 2014 until study end (6%) (p < 0.0001). Apixaban was the most used OAC at study end (41%), in particular among those ≥85 years (44%). Compared with patients aged <65 years, the odds ratios associated with initiating VKA, dabigatran, rivaroxaban, or apixaban for patients aged ≥85 years were 0.81 (95% CI 0.75–0.86), 0.65 (95% CI 0.60–0.70), 1.52 (95% CI 1.38–1.67) and 2.09 (95% CI 1.89–2.30), respectively. In conclusion, substantial increase in NOAC usage has occurred. Increasing age was associated with upstart of rivaroxaban or apixaban with reference to age <65 within the specific agent.
Leucine Zipper-bearing Kinase promotes axon growth in mammalian central nervous system neurons
Authors: Chen Meifan , Geoffroy Cédric G. , Wong Hetty N. , Tress Oliver , Nguyen Mallorie T. , Holzman Lawrence B. , Jin Yishi , Zheng Binhai
Published: August 2016

Leucine Zipper-bearing Kinase (LZK/MAP3K13) is a member of the mixed lineage kinase family with high sequence identity to Dual Leucine Zipper Kinase (DLK/MAP3K12). While DLK is established as a key regulator of axonal responses to injury, the role of LZK in mammalian neurons is poorly understood. By gain- and loss-of-function analyses in neuronal cultures, we identify LZK as a novel positive regulator of axon growth. LZK signals specifically through MKK4 and JNKs among MAP2Ks and MAPKs respectively in neuronal cells, with JNK activity positively regulating LZK protein levels. Neuronal maturation or activity deprivation activates the LZK-MKK4-JNK pathway. LZK and DLK share commonalities in signaling, regulation, and effects on axon extension. Furthermore, LZK-dependent regulation of DLK protein expression and the lack of additive effects on axon growth upon co-manipulation suggest complex functional interaction and cross-regulation between these two kinases. Together, our data support the possibility for two structurally related MAP3Ks to work in concert to mediate axonal responses to external insult or injury in mammalian CNS neurons.
The Associations of HLA-A*02:01 and DRB1*11:01 with Hepatitis C Virus Spontaneous Clearance Are Independent of IL28B in the Chinese Population
Authors: Huang Jieting , Huang Ke , Xu Ru , Wang Min , Liao Qiao , Xiong Huaping , Li Chengyao , Tang Xi , Shan Zhengang , Zhang Ming , Rong Xia , Nelson Kenrad , Fu Yongshui
Published: August 2016

Spontaneous clearance of hepatitis C virus (HCV) occurs in 10–40% of the infections. Specific human leukocyte antigen (HLA) alleles have been identified in associating with HCV clearance. However, data on the association of HLA with the spontaneous clearance of HCV are scarce in the Chinese population. In the current study we studied the HLA class I and class II genes in 231 Chinese voluntary blood donors who had cleared HCV infection spontaneously compared to 429 subjects with chronic HCV infections. We also studied their IL28B SNP (rs8099917) genotype, since a number of investigators have found a strong association of IL28B with spontaneous or treatment induced HCV clearance. We found that HLA-A*02:01 and DQB1*05:02 distributed differently between the two groups after Bonferroni correction (odds ratio [OR] = 1.839, Pc = 0.024 and OR = 0.547, Pc = 0.016, respectively). Multivariate logistic regression analysis suggested that A*02:01 and DRB1*11:01 (OR = 1.798, P = 0.008 and OR = 1.921, P = 0.005, respectively) were associated with HCV spontaneous clearance, independent of age, gender and IL28B polymorphism. We concluded that in the Chinese population, HLA-A*02:01 and DRB1*11:01 might be associated with the host capacity to clear HCV independent of IL28B, which suggesting that the innate and adaptive immune responses both play an important role in the control of HCV.
Octahedral Tin Dioxide Nanocrystals Anchored on Vertically Aligned Carbon Aerogels as High Capacity Anode Materials for Lithium-Ion Batteries
Authors: Liu Mingkai , Liu Yuqing , Zhang Yuting , Li Yiliao , Zhang Peng , Yan Yan , Liu Tianxi
Published: August 2016

A novel binder-free graphene - carbon nanotubes - SnO2 (GCNT-SnO2) aerogel with vertically aligned pores was prepared via a simple and efficient directional freezing method. SnO2 octahedrons exposed of {221} high energy facets were uniformly distributed and tightly anchored on multidimensional graphene/carbon nanotube (GCNT) composites. Vertically aligned pores can effectively prevent the emersion of “closed” pores which cannot load the active SnO2 nanoparticles, further ensure quick immersion of electrolyte throughout the aerogel and can largely shorten the transport distance between lithium ions and active sites of SnO2. Especially, excellent electrical conductivity of GCNT-SnO2 aerogel was achieved as a result of good interconnected networks of graphene and CNTs. Furthermore, meso- and macroporous structures with large surface area created by the vertically aligned pores can provide great benefit to the favorable transport kinetics for both lithium ion and electrons and afford sufficient space for volume expansion of SnO2. Due to the well-designed architecture of GCNT-SnO2 aerogel, a high specific capacity of 1190 mAh/g with good long-term cycling stability up to 1000 times was achieved. This work provides a promising strategy for preparing free-standing and binder-free active electrode materials with high performance for lithium ion batteries and other energy storage devices.
N-acylhydrazone inhibitors of influenza virus PA endonuclease with versatile metal binding modes
Authors: Carcelli Mauro , Rogolino Dominga , Gatti Anna , De Luca Laura , Sechi Mario , Kumar Gyanendra , White Stephen W. , Stevaert Annelies , Naesens Lieve
Published: August 2016

Influenza virus PA endonuclease has recently emerged as an attractive target for the development of novel antiviral therapeutics. This is an enzyme with divalent metal ion(s) (Mg2+ or Mn2+) in its catalytic site: chelation of these metal cofactors is an attractive strategy to inhibit enzymatic activity. Here we report the activity of a series of N-acylhydrazones in an enzymatic assay with PA-Nter endonuclease, as well as in cell-based influenza vRNP reconstitution and virus yield assays. Several N-acylhydrazones were found to have promising anti-influenza activity in the low micromolar concentration range and good selectivity. Computational docking studies are carried on to investigate the key features that determine inhibition of the endonuclease enzyme by N-acylhydrazones. Moreover, we here describe the crystal structure of PA-Nter in complex with one of the most active inhibitors, revealing its interactions within the protein’s active site.
Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration
Authors: Wang Hui-Chen , Lee Wen-Sen
Published: August 2016

Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells.
Elastic Carbon Aerogels Reconstructed from Electrospun Nanofibers and Graphene as Three-Dimensional Networked Matrix for Efficient Energy Storage/Conversion
Authors: Huang Yunpeng , Lai Feili , Zhang Longsheng , Lu Hengyi , Miao Yue-E , Liu Tianxi
Published: August 2016

Three-dimensional (3D) all-carbon nanofibrous aerogels with good structural stability and elasticity are highly desirable in flexible energy storage/conversion devices. Hence, an efficient surface-induced co-assembly strategy is reported for the novel design and reconstruction of electrospun nanofibers into graphene/carbon nanofiber (CNF) composite aerogels (GCA) with hierarchical structures utilizing graphene flakes as cross-linkers. The as-obtained GCA monoliths possess interconnected macropores and integrated conductive networks, which exhibit high elasticity and great structural robustness. Benefitting from the largely increased surface area and charge-transfer efficiency derived from the multi-form firm interconnections (including pillaring, bridging and jointing) between graphene flakes and CNF ribs, GCA not only reveals prominent capacitive performance as supercapacitor electrode, but also shows excellent hydrogen evolution reaction activity in both acidic and alkaline solutions as a 3D template for decoration of few-layered MoSe2 nanosheets, holding great potentials for energy-related applications.