bluuebunny/crossref_metadata_2025_split huggingface dataset:
The UL21 Tegument Protein of Herpes Simplex Virus 1 Is Differentially Required for the Syncytial Phenotype
Authors: Sarfo Akua , Starkey Jason , Mellinger Erica , Zhang Dan , Chadha Pooja , Carmichael Jillian , Wills John W. 
Published: August 2017

ABSTRACT

The initial goal of this study was to reexamine the requirement of UL21 for herpes simplex virus 1 (HSV-1) replication. Previous studies suggested that UL21 is dispensable for replication in cell cultures, but a recent report on HSV-2 challenges those findings. As was done for the HSV-2 study, a UL21-null virus was made and propagated on complementing cells to discourage selection of compensating mutations. This HSV-1 mutant was able to replicate in noncomplementing cells, even at a low multiplicity of infection (MOI), though a reduction in titer was observed. Also, increased proportions of empty capsids were observed in the cytoplasm, suggesting a role for UL21 in preventing their exit from the nucleus. Surprisingly, passage of the null mutant resulted in rapid outgrowth of syncytial (Syn) variants. This was unexpected because UL21 has been shown to be required for the Syn phenotype. However, earlier experiments made use of only the A855V syncytial mutant of glycoprotein B (gB), and the Syn phenotype can also be produced by substitutions in glycoprotein K (gK), UL20, and UL24. Sequencing of the syncytial variants revealed mutations in the gK locus, but UL21 was shown to be dispensable for UL20
Syn
and UL24
Syn
. To test whether UL21 is needed only for the A855V mutant, additional gB
Syn
derivatives were examined in the context of the null virus, and all produced lytic rather than syncytial sites of infection. Thus, UL21 is required only for the gB
Syn
phenotype. This is the first example of a differential requirement for a viral protein across the four
syn
loci.

IMPORTANCE
UL21 is conserved among alphaherpesviruses, but its role is poorly understood. This study shows that HSV-1 can replicate without UL21, although the virus titers are greatly reduced. The null virus had greater proportions of empty (DNA-less) capsids in the cytoplasm of infected cells, suggesting that UL21 may play a role in retaining them in the nucleus. This is consistent with reports showing UL21 to be capsid associated and localized to the nuclei of infected cells. UL21 also appears to be needed for viral membrane activities. It was found to be required for virus-mediated cell fusion, but only for mutants that harbor syncytial mutations in gB (not variants of gK, UL20, or UL24). The machinery needed for syncytial formation is similar to that needed for direct spread of the virus through cell junctions, and these studies show that UL21 is required for cell-to-cell spread even in the absence of syncytial mutations.
The Divided Bacterial Genome: Structure, Function, and Evolution
Authors: diCenzo George C. , Finan Turlough M. 
Published: August 2017

SUMMARY

Approximately 10% of bacterial genomes are split between two or more large DNA fragments, a genome architecture referred to as a multipartite genome. This multipartite organization is found in many important organisms, including plant symbionts, such as the nitrogen-fixing rhizobia, and plant, animal, and human pathogens, including the genera
Brucella
,
Vibrio
, and
Burkholderia
. The availability of many complete bacterial genome sequences means that we can now examine on a broad scale the characteristics of the different types of DNA molecules in a genome. Recent work has begun to shed light on the unique properties of each class of replicon, the unique functional role of chromosomal and nonchromosomal DNA molecules, and how the exploitation of novel niches may have driven the evolution of the multipartite genome. The aims of this review are to (i) outline the literature regarding bacterial genomes that are divided into multiple fragments, (ii) provide a meta-analysis of completed bacterial genomes from 1,708 species as a way of reviewing the abundant information present in these genome sequences, and (iii) provide an encompassing model to explain the evolution and function of the multipartite genome structure. This review covers, among other topics, salient genome terminology; mechanisms of multipartite genome formation; the phylogenetic distribution of multipartite genomes; how each part of a genome differs with respect to genomic signatures, genetic variability, and gene functional annotation; how each DNA molecule may interact; as well as the costs and benefits of this genome structure.
Persisting fatigue and myalgia as the presenting features in a case of hypokalaemic periodic paralysis
Authors: Neame Matthew Thomas , Wright David , Chandrasekaran Surendran 
Published: August 2017

We report a case of a 9-year-old boy who developed hypokalaemic periodic paralysis (HypoPP) following a prodrome of persistent fatigue and muscle aches associated with mildly elevated creatine kinase (CK) levels.HypoPP is usually associated with a sudden onset of weakness and hypokalaemia at presentation. A review of published cases failed to identify any other reports of individuals with a similar onset of symptoms and elevated CK levels prior to the development of frank HypoPP.In the case described above, the association of these symptoms with elevated levels of CK may have been related to the underlying mutation in the skeletal muscle calcium channels that was subsequently identified.In cases of persisting fatigue and myalgia associated with elevated CK levels it may be helpful to consider HypoPP in the differential diagnosis.
The incidence of acute angle closure in Scotland: a prospective surveillance study
Authors: Chua Paul Y , Day Alexander C , Lai Ken L , Hall Nikki , Tan Lai L , Khan Kamran , Lim Lik Thai , Foot Barny , Foster Paul J , Azuara-Blanco Augusto 
Published: August 2017

PurposeTo estimate the incidence, and describe the clinical features and short-term clinical outcomes of acute angle closure (AAC).MethodsPatients with newly diagnosed AAC were identified prospectively over a 12-month period (November 2011 to October 2012) by active surveillance through the Scottish Ophthalmic Surveillance Unit reporting system. Data were collected at case identification and at 6 months follow-up.ResultsThere were 114 cases (108 patients) reported, giving an annual incidence of 2.2 cases (95% CI 1.8 to 2.6) or 2 patients (95% CI 1.7 to 2.4) per 1 00 000 in the whole population in Scotland. Precipitating factors were identified in 40% of cases. Almost one in five cases was associated with topical dilating drops. Best-corrected visual acuity (BCVA) at presentation ranged from 6/6 to perception of light. The mean presenting intraocular pressure (IOP) was 52 mm Hg (SD 11). Almost 30% cases had a delayed presentation of 3 or more days. At 6 months follow-up, 75% had BCVA of 6/12 or better and 30% were found to have glaucoma at follow-up. Delayed presentation (≥3 days) was associated with higher rate of glaucoma at follow-up (22.6% vs 60.8%, p<0.001), worse VA (0.34 vs 0.74 LogMAR, p<0.0001) and need for more topical medication (0.52 vs 1.2, p=0.003) to control IOP.ConclusionThe incidence of AAC in Scotland is relatively low compared with the Far East countries, but in line with previous European data. Almost one in five cases were associated with pupil dilation for retinal examination.
Pulmonary vasodilator therapy is associated with greater survival in Eisenmenger syndrome
Authors: Arnott Clare , Strange Geoff , Bullock Andrew , Kirby Adrienne C , O’Donnell Clare , Radford Dorothy J , Grigg Leeanne E , Celermajer David S 
Published: August 2017

ObjectiveEisenmenger syndrome (ES) is a severe form of pulmonary hypertension in adults with congenital heart disease (CHD) and has a poor prognosis. We aimed to understand factors associated with survival in ES and particularly to assess the potential benefits of advanced pulmonary vasodilator therapy (AT).MethodsFrom January 2004, when AT became generally available for patients with ES, we followed 253 ES adults from 12 adult congenital heart disease centres across Australia and New Zealand. Demographic, medical and outcome data were collected and analysed prospectively and retrospectively.ResultsThe patients with ES were predominantly female (60%), aged 31 (SD 12) years. At diagnosis of ES, 64% were WHO functional class ≥3. The most common underlying lesion was ventricular septal defect (33%) with 21% having ‘complex’ anatomy. Over a median follow-up time of 9.1 years, the majority (72%) had been prescribed at least one AT (49% single agent), mostly bosentan (66%, 168 patients). The mean time on AT was 6 (SD 3.6) years. Those on AT were more functionally impaired at presentation (69% WHO ≥3 vs 51%, p=0.007) and more likely to have been prescribed anticoagulation (47% vs 27%, p=0.003). The risk of death/transplant was 4.8 %/year in AT exposed versus 8.4% in those never exposed. On multivariable analysis, exposure to AT was independently associated with greater survival (survival HR 2.27, 95% CI 1.49 to 3.45; p<0.001). WHO ≥3 at presentation was associated with a worse prognosis (mortality HR 1.82, 95% CI 1.19 to 2.78; p=0.006).ConclusionTreatment with AT was independently associated with greater survival in patients with ES, even though they were comparatively sicker prior to treatment.
Children forgotten in hot cars: a mental models approach for improving public health messaging
Authors: Williams Castle A , Grundstein Andrew J 
Published: August 2017

IntroductionOn average, in the USA, 37 young children die every year due to vehicular heatstroke. Additionally, over half of these incidents occur when a parent/caregiver forgets a child in a vehicle. While various governmental and child safety advocacy groups have worked to raise awareness about these tragedies, rigorous studies have yet to be conducted that examine the current understanding and effectiveness of this public health messaging.MethodsThis study will employ a mental models approach in order to identify differences that exist between experts’ and parents’/caregivers’ knowledge and beliefs surrounding the topic of children forgotten in hot cars. We interviewed a diverse set of 25 parents/caregivers and seven experts in order to construct and explore these mental models.ResultsA comparative analysis was conducted, and three key differences were observed between these mental models. Unlike the experts, the parents/caregivers in the study emphasised perceived lifestyle factors (eg, low-income parent) as important elements in increasing an individual’s likelihood of forgetting a child in a car. Importantly, the parents/caregivers primarily obtained information from news reports, while experts believed public health campaigns would reach more parents/caregivers. Lastly, while experts stressed that this tragedy could happen to anyone, most parents/caregivers failed to acknowledge that they could forget their own child in a car.ConclusionsTo confront this denial, future public health messaging must strive to engage and reach all parents/caregivers. This can be accomplished using a multifaceted messaging strategy that includes personalising core messaging, providing additional resources to media outlets and building rapport between key partners.
A refined method to study gene dosage changes in vitro using CRISPR/Cas9
Authors: Raposo Teresa P , Ebili Henry O , Ilyas Mohammad 
Published: August 2017

AimsGene dosage can have a major impact on cell biology, although, hitherto, it has been difficult to study using in vitro models. We sought to refine and accelerate the development of ‘gene dosage’ models through using CRISPR/Cas9 (a gene editing technology) for sequential knockout of gene alleles.MethodsOur method involved (1) using Cas9 nuclease mRNA rather than expression plasmids, (2) using a fluorescently labelled FAM-6 tracr complexed with guide RNA and (3) using high-resolution melting (HRM) analysis to screen for mutations. HCT116 cells, wild-type forTP53, were transfected with different molarities of FAM-6 tracr-labelled and guide RNA targeting different exons of TP53 and selected by fluorescence-activated cell sorting. Single-cell colonies were then isolated, expanded and tested for mutation in the targeted region by PCR/HRM.ResultsOut of 32 clones tested, 12 have shown aberrant melting by HRM, giving a targeting efficiency of 37.5%. One clone was sequenced and a heterozygous mutation found — in this case comprising a single base deletion in exon 3. mRNA sequencing confirmed the mutation was expressed, and western blotting for p53 showed the presence of both wild-type and truncated protein bands. Changes in expression of MDM-2 isoforms suggested a functional effect of the induced TP53 mutation.ConclusionsWe have developed an in vitro model to study TP53 gene dosage effects. The protocol is efficient and applicable to any gene. Importantly, we have used Cas9 mRNA and labelled tracr/guide RNA to isolate likely mutated cells and HRM for rapid mutation detection.
Socioeconomic position and markers of adiposity among female teachers in Mexico
Authors: Hirko Kelly A , Lajous Martin , Ortiz-Panozo Eduardo , Lopez-Ridaura Ruy , Christine Paul J , Lȇ-Scherban Felice , Rice Megan S , Barrientos-Gutierrez Tonatiuh 
Published: August 2017

BackgroundOccupation is often used as an indicator of socioeconomic position (SEP) in epidemiological studies, although it is unclear whether variation in SEP within a single occupational group is associated with health outcomes, including adiposity measures.MethodsWe created a multidimensional SEP index using principal component analysis based on self-reported data from 36 704 female teachers in Mexico from 2008 to 2011. Multivariable Poisson regression models with robust variance were used to evaluate cross-sectional associations of SEP and markers of adiposity, including obesity (body mass index (BMI) ≥30 kg/m2), elevated waist-to-hip ratio (WHR >85) and high waist circumference (WC >88 cm).ResultsThe most relevant indicators of SEP in this study were internet access and private health insurance. We observed significant inverse trends in obesity, WHR and WC in relation to SEP (all ptrend<0.001). Compared with women with low SEP, women in the middle (prevalence ratio (PR) 0.97, 95% CI 0.93 to 1.02) and high (PR 0.85, 95% CI 0.81 to 0.90) SEP tertiles were less likely to be obese in multivariable models. Results were similar in models of WHR and WC adjusting for BMI. For example, women with high versus low SEP were 14% less likely to have an elevated WHR (PR 0.86, 95% CI 0.83 to 0.89) and 7% less likely to have a high WC (PR 0.93, 95% CI 0.89 to 0.97).ConclusionsOur findings suggest that SEP remains relevant for adiposity within a single occupational setting and indicate that a stronger conceptualisation of SEP in epidemiological studies may be warranted.
An integrated microfluidic analysis microsystems with bacterial capture enrichment and in-situ impedance detection
Authors: Liu Hai-Tao , Wen Zhi-Yu , Xu Yi , Shang Zheng-Guo , Peng Jin-Lan , Tian Peng 
Published: August 2017

In this paper, an integrated microfluidic analysis microsystems with bacterial capture enrichment and in-situ impedance detection was purposed based on microfluidic chips dielectrophoresis technique and electrochemical impedance detection principle. The microsystems include microfluidic chip, main control module, and drive and control module, and signal detection and processing modulet and result display unit. The main control module produce the work sequence of impedance detection system parts and achieve data communication functions, the drive and control circuit generate AC signal which amplitude and frequency adjustable, and it was applied on the foodborne pathogens impedance analysis microsystems to realize the capture enrichment and impedance detection. The signal detection and processing circuit translate the current signal into impendence of bacteria, and transfer to computer, the last detection result is displayed on the computer. The experiment sample was prepared by adding Escherichia coli standard sample into chicken sample solution, and the samples were tested on the dielectrophoresis chip capture enrichment and in-situ impedance detection microsystems with micro-array electrode microfluidic chips. The experiments show that the Escherichia coli detection limit of microsystems is [Formula: see text] CFU/mL and the detection time is within 6 min in the optimization of voltage detection 10 V and detection frequency 500 KHz operating conditions. The integrated microfluidic analysis microsystems laid the solid foundation for rapid real-time in-situ detection of bacteria.
Hyperalgesia and sensitization of dorsal horn neurons following activation of NK-1 receptors in the rostral ventromedial medulla
Authors: Khasabov Sergey G. , Malecha Patrick , Noack Joseph , Tabakov Janneta , Giesler Glenn J. , Simone Donald A. 
Published: August 2017

Neurons in the rostral ventromedial medulla (RVM) project to the spinal cord and are involved in descending modulation of pain. Several studies have shown that activation of neurokinin-1 (NK-1) receptors in the RVM produces hyperalgesia, although the underlying mechanisms are not clear. In parallel studies, we compared behavioral measures of hyperalgesia to electrophysiological responses of nociceptive dorsal horn neurons produced by activation of NK-1 receptors in the RVM. Injection of the selective NK-1 receptor agonist Sar9,Met(O2)11-substance P (SSP) into the RVM produced dose-dependent mechanical and heat hyperalgesia that was blocked by coadministration of the selective NK-1 receptor antagonist L-733,060. In electrophysiological studies, responses evoked by mechanical and heat stimuli were obtained from identified high-threshold (HT) and wide dynamic range (WDR) neurons. Injection of SSP into the RVM enhanced responses of WDR neurons, including identified neurons that project to the parabrachial area, to mechanical and heat stimuli. Since intraplantar injection of capsaicin produces robust hyperalgesia and sensitization of nociceptive spinal neurons, we examined whether this sensitization was dependent on NK-1 receptors in the RVM. Pretreatment with L-733,060 into the RVM blocked the sensitization of dorsal horn neurons produced by capsaicin. c-Fos labeling was used to determine the spatial distribution of dorsal horn neurons that were sensitized by NK-1 receptor activation in the RVM. Consistent with our electrophysiological results, administration of SSP into the RVM increased pinch-evoked c-Fos expression in the dorsal horn. It is suggested that targeting this descending pathway may be effective in reducing persistent pain.NEW & NOTEWORTHY It is known that activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM), a main output area for descending modulation of pain, produces hyperalgesia. Here we show that activation of NK-1 receptors produces hyperalgesia by sensitizing nociceptive dorsal horn neurons. Targeting this pathway at its origin or in the spinal cord may be an effective approach for pain management.
Colistin dampens fibrinolysis and endothelial activation during endotoxaemia
Authors: Schoergenhofer Christian , Matzneller Peter , Mußbacher Marion , Schmid Johannes A. , Jilma-Stohlawetz Petra , Zeitlinger Markus , Jilma Bernd 
Published: August 2017

SummaryColistin electrostatically interacts with lipopolysaccharides (LPS). Preclinical studies demonstrated beneficial effects of colistin on LPS-induced coagulation and fibrinolysis. The objective of this trial was to investigate the effects of colistin during experimental endotoxaemia. In this randomised, double-blind, placebo-controlled, crossover trial 16 healthy volunteers received a 2 ng/kg LPS bolus after infusion of 2.5 million IU colistin or placebo. Plasma levels of F1+2 prothrombin fragments, thrombin-antithrombin complexes (TAT), von Willebrand factor antigen levels (vWF), E-selectin, plasmin-antiplasmin complexes (PAP), tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor-1 (PAI-1) were measured. Infusion of colistin significantly reduced peak concentrations of PAP complexes by 70 %, t-PA antigen levels by 63 % and t-PA activity by 48 %, while PAI-1 levels decreased numerically by 63 %. Two hours after the LPS bolus F1+2 levels and TAT complexes were slightly reduced in the colistin period, but peak concentrations were similar in both periods. Colistin blunted the LPS induced four-fold increase in soluble E-Selectin levels by ∼50 % and the two-fold increase in vWF antigen levels by ∼70 %. The LPS-scavenging actions of colistin significantly reduce endothelial activation and fibrinolytic response in the human endotoxaemia model, while the activation of the coagulation system remains largely unaffected.Note: This work was conducted at the Medical University of Vienna.EudraCT-Nr.: 2014–00285720Supplementary Material to this article is available online at http://www.thrombosis-online.com
OS ESTUDOS DE CASO DOS INIBIDORES DE APETITE E DA FOSFOETANOLAMINA SINTÉTICA: A FRAGILIZAÇÃO DO PAPEL DA ANVISA
Authors: Faleiros Ana Carolina Perdigão 
Published: August 2017

Este artigo trata sobre a fragilização do importante papel da Agência Nacional de Vigilância Sanitária que é de proteção da saúde da população – exercido, principalmente, pela mitigação dos riscos decorrentes do consumo de produtos sujeitos a seu controle, tais como os medicamentos. Essa desvalorização da agência está sendo causada pelas crescentes ameaças as suas competências, em grande parte por decisões do Congresso Nacional movidas por pressões de alguns grupos ou mesmo por comoções sociais iludidas por panaceias. São analisados dois casos emblemáticos: o dos inibidores de apetite e o da fosfoetanolamina sintética (a "pílula do câncer").
A UTILIZAÇÃO DOS PROTOCOLOS CLÍNICOS E DIRETRIZES TERAPÊUTICAS E A RACIONALIZAÇÃO DA JUDICIALIZAÇÃO DO DIREITO À SAÚDE
Authors: Duarte Clarice Seixas , Braga Paulo Vitor Bérgamo 
Published: August 2017

O artigo analisa a adoção dos Protocolos Clínicos e Diretrizes Terapêuticas (PCDTs) como parâmetro objetivo a ser utilizado pelos tribunais nas ações judiciais cujo objeto são prestações de natureza positiva voltadas à efetivação do direito à saúde. Tal referencial pode auxiliar o juiz na tarefa de decidir as demandas judiciais de fornecimento de medicamentos, garantindo a prevalência da racionalidade prevista pelo formulador das políticas públicas correlatas e, consequentemente, a utilização de argumentos técnico-políticos na distribuição de bens e recursos de saúde. Contudo, não se trata de um parâmetro absoluto, podendo o conteúdo do PCDT ser questionado, até mesmo judicialmente. Com isso, a ação judicial passa a ser utilizada como um instrumento de democratização e de controle social de escolhas públicas, o que pode vir a impactar a própria política de saúde.