bluuebunny/crossref_metadata_2025 huggingface dataset:
What functional genomics has taught us about transcriptional regulation in malaria parasites
Authors: Toenhake Christa G , Bártfai Richárd
Published: March 2019

Malaria parasites are characterized by a complex life cycle that is accompanied by dynamic gene expression patterns. The factors and mechanisms that regulate gene expression in these parasites have been searched for even before the advent of next generation sequencing technologies. Functional genomics approaches have substantially boosted this area of research and have yielded significant insights into the interplay between epigenetic, transcriptional and post-transcriptional mechanisms. Recently, considerable progress has been made in identifying sequence-specific transcription factors and DNA-encoded regulatory elements. Here, we review the insights obtained from these efforts including the characterization of core promoters, the involvement of sequence-specific transcription factors in life cycle progression and the mapping of gene regulatory elements. Furthermore, we discuss recent developments in the field of functional genomics and how they might contribute to further characterization of this complex gene regulatory network.
DNA methylation analysis in plants: review of computational tools and future perspectives
Authors: Omony Jimmy , Nussbaumer Thomas , Gutzat Ruben
Published: March 2019

Genome-wide DNA methylation studies have quickly expanded due to advances in next-generation sequencing techniques along with a wealth of computational tools to analyze the data. Most of our knowledge about DNA methylation profiles, epigenetic heritability and the function of DNA methylation in plants derives from the model species Arabidopsis thaliana. There are increasingly many studies on DNA methylation in plants—uncovering methylation profiles and explaining variations in different plant tissues. Additionally, DNA methylation comparisons of different plant tissue types and dynamics during development processes are only slowly emerging but are crucial for understanding developmental and regulatory decisions. Translating this knowledge from plant model species to commercial crops could allow the establishment of new varieties with increased stress resilience and improved yield. In this review, we provide an overview of the most commonly applied bioinformatics tools for the analysis of DNA methylation data (particularly bisulfite sequencing data). The performances of a selection of the tools are analyzed for computational time and agreement in predicted methylated sites for A. thaliana, which has a smaller genome compared to the hexaploid bread wheat. The performance of the tools was benchmarked on five plant genomes. We give examples of applications of DNA methylation data analysis in crops (with a focus on cereals) and an outlook for future developments for DNA methylation status manipulations and data integration.
Conserved Residues Control the T1R3-Specific Allosteric Signaling Pathway of the Mammalian Sweet-Taste Receptor
Authors: Chéron Jean-Baptiste , Soohoo Amanda , Wang Yi , Golebiowski Jérôme , Antonczak Serge , Jiang Peihua , Fiorucci Sébastien
Published: March 2019

Mammalian sensory systems detect sweet taste through the activation of a single heteromeric T1R2/T1R3 receptor belonging to class C G-protein-coupled receptors. Allosteric ligands are known to interact within the transmembrane domain, yet a complete view of receptor activation remains elusive. By combining site-directed mutagenesis with computational modeling, we investigate the structure and dynamics of the allosteric binding pocket of the T1R3 sweet-taste receptor in its apo form, and in the presence of an allosteric ligand, cyclamate. A novel positively charged residue at the extracellular loop 2 is shown to interact with the ligand. Molecular dynamics simulations capture significant differences in the behavior of a network of conserved residues with and without cyclamate, although they do not directly interact with the allosteric ligand. Structural models show that they adopt alternate conformations, associated with a conformational change in the transmembrane region. Site-directed mutagenesis confirms that these residues are unequivocally involved in the receptor function and the allosteric signaling mechanism of the sweet-taste receptor. Similar to a large portion of the transmembrane domain, they are highly conserved among mammals, suggesting an activation mechanism that is evolutionarily conserved. This work provides a structural basis for describing the dynamics of the receptor, and for the rational design of new sweet-taste modulators.
Active Targeted Surveillance to Identify Sites of Emergence of Hantavirus
Authors: Kim Won-Keun , No Jin Sun , Lee Daesang , Jung Jaehun , Park Hayne , Yi Yongjin , Kim Jeong-Ah , Lee Seung-Ho , Kim Yujin , Park Sunhye , Cho Seungchan , Lee Geum-Young , Song Dong Hyun , Gu Se Hun , Park Kkothanahreum , Kim Heung-Chul , Wiley Michael R , Chain Patrick S G , Jeong Seong Tae , Klein Terry A , Palacios Gustavo , Song Jin-Won
Published: March 2019

Background

Endemic outbreaks of hantaviruses pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS) in humans. Using comparative genomic analyses of partial and nearly complete sequences of HTNV from humans and rodents, we were able to localize, with limitations, the putative infection locations for HFRS patients. Partial sequences might not reflect precise phylogenetic positions over the whole-genome sequences; finer granularity of rodent sampling reflects more precisely the circulation of strains.

Methods

Five HFRS specimens were collected. Epidemiological surveys were conducted with the patients during hospitalization. We conducted active surveillance at suspected HFRS outbreak areas. We performed multiplex polymerase chain reaction–based next-generation sequencing to obtain the genomic sequence of HTNV from patients and rodents. The phylogeny of human- and rodent-derived HTNV was generated using the maximum likelihood method. For phylogeographic analyses, the tracing of HTNV genomes from HFRS patients was defined on the bases of epidemiological interviews, phylogenetic patterns of the viruses, and geographic locations of HTNV-positive rodents.

Results

The phylogeographic analyses demonstrated genetic clusters of HTNV strains from clinical specimens, with HTNV circulating in rodents at suspected sites of patient infections.

Conclusions

This study demonstrates a major shift in molecular epidemiological surveillance of HTNV. Active targeted surveillance was performed at sites of suspected infections, allowing the high-resolution phylogeographic analysis to reveal the site of emergence of HTNV. We posit that this novel approach will make it possible to identify infectious sources, perform disease risk assessment, and implement preparedness against vector-borne viruses.
Emotion Recognition by a Hybrid System Based on the Features of Distances and the Shapes of the Wrinkles
Authors: Afdhal Rim , Ejbali Ridha , Zaied Mourad
Published: March 2019

Emotion recognition is a key work of research area in brain computer interactions. With the increasing concerns about affective computing, emotion recognition has attracted more and more attention in the past decades. Focusing on geometric positions of key parts of the face and well detecting them is the best way to increase accuracy of emotion recognition systems and reach high classification rates. In this paper, we propose a hybrid system based on wavelet networks using 1D Fast Wavelet Transform. This system combines two approaches: the biometric distances approach where we propose a new technique to locate feature points and the wrinkles approach where we propose a new method to locate the wrinkles regions in the face. The classification rates given by experimental results show the effectiveness of our proposed approach compared to other methods.
Populism and constitutional tension
Authors: Walker Neil
Published: March 2019

The recent resurgence of populism poses a significant challenge to constitutional law today and to the deeper tradition of modern constitutionalism. Despite resisting formal limitations on their power to represent the “true” popular will, populist regimes nevertheless find instrumental and ideological reasons to endorse their own version of constitutionalism. And despite their nativist commitments, populist leaders across the globe find common constitutional cause and mutual encouragement in their critique of cosmopolitan institutions and values. The distinctiveness of populism’s constitutional orientation rests on its occupation of a space between authoritarian and popular versions of constitutionalism, overlapping both but not reducible to either. There situated, populism involves a reaction against what it condemns as the neglect of the “unitary collective particular” in the liberal version of modern constitutionalism. Many critical of the inflated narratives and methods of populism nevertheless share some its underlying anxieties. For in an age in which an expanding commitment to the democratic pedigree of our constitutional arrangements has unfolded alongside the increasing transnationalization and fragmentation of political authority, the very instability of the balance between various constitutional goods—between plurality and unity, individualism and collectivism, and universal and particular rationalities—that fuels populists’ ire, deepens the defining tension of modern constitutionalism, and poses a challenge to all who continue to endorse it.
Populism as a constitutional project
Authors: Blokker Paul
Published: March 2019

The engagement of conservative, populist governments with constitutional reform and constitution-making is perceived as a significant threat to the rule of law and democracy within the European Union. Constitutionalists often assume a relation of mutual exclusion between populism and constitutionalism. In contrast, I argue that while populism ought to be understood as a rejection of liberal constitutionalism, it equally constitutes a competing political force regarding the definition of constitutional democracy. The article first discusses populist constitutionalism in the context of the two, main modern constitutional traditions: the modernist and the revolutionary ones. Second, I discuss the populist critique of liberal constitutionalism, with a central focus on the recent cases of right-wing populism in power in East-Central Europe. Four dimensions are prominent: (i) popular sovereignty as the key justificatory claim of populism; (ii) majority rule as the main populist mode of government; (iii) instrumentalism as the legal–practical approach of populists; and (iv) legal resentment as the populists’ main attitude toward public law. In conclusion, I argue that while the populist critique of liberal constitutionalism provides significant insights into structural problems of liberal democracy, populist constitutionalism ultimately fails to live up to its own democratic promise.
Piperazine-Derivative MMV665917: An Effective Drug in the Diarrheic Piglet Model of Cryptosporidium hominis
Authors: Lee Sangun , Ginese Melanie , Girouard Don , Beamer Gillian , Huston Christopher D , Osbourn Damon , Griggs David W , Tzipori Saul
Published: March 2019

Background

Cryptosporidiosis, an enteric protozoon, causes substantial morbidity and mortality associated with diarrhea in children <2 years old in low- to middle-income countries. There is no vaccine and treatments are inadequate. A piperazine-based compound, MMV665917, has in vitro and in vivo efficacy against Cryptosporidium parvum. In this study, we evaluated the efficacy of MMV665917 in gnotobiotic piglets experimentally infected with Cryptosporidium hominis, the species responsible for >75% of diarrhea reported in these children.

Methods

Gnotobiotic piglets were orally challenged with C hominis oocysts, and oral treatment with MMV665917 was commenced 3 days after challenge. Oocyst excretion and diarrhea severity were observed daily, and mucosal colonization and lesions were recorded after necropsy.

Results

MMV665917 significantly reduced fecal oocyst excretion, parasite colonization and damage to the intestinal mucosa, and peak diarrheal symptoms, compared with infected untreated controls. A dose of 20 mg/kg twice daily for 7 days was more effective than 10 mg/kg. There were no signs of organ toxicity at either dose, but 20 mg/kg was associated with slightly elevated blood cholesterol and monocytes at euthanasia.

Conclusions

These results demonstrate the effectiveness of this drug against C hominis. Piperazine-derivative MMV665917 may potentially be used to treat human cryptosporidiosis; however, further investigations are required.
Immunogenicity and Safety of an Inactivated Enterovirus 71 Vaccine Administered Simultaneously With Hepatitis B Vaccine and Group A Meningococcal Polysaccharide Vaccine: A Phase 4, Open-Label, Single-Center, Randomized, Noninferiority Trial
Authors: Zhang Zewu , Liang Zhenglun , Zeng Ji , Zhang Jikai , He Peng , Su Jiali , Zeng Yaoming , Fan Renfeng , Zhao Dan , Ma Wenjun , Zeng Gang , Zhang Qiaoli , Zheng Huizhen
Published: March 2019

Background

This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of enterovirus 71 (EV71) vaccine (dose 1) with recombinant hepatitis B vaccine (HepB) on day 1 and EV71 vaccine (dose 2) with group A meningococcal polysaccharide vaccine (MenA) on day 30 is not inferior to separate administration of each vaccine.

Methods

The study was designed as a randomized, open-label, noninferiority trial. A total of 775 healthy infants aged 6 months were randomly assigned in a ratio of 1:1:1 to receive simultaneous administration of EV71 vaccine (dose 1) and HepB on day 1 and EV71 vaccine (dose 2) and MenA on day 30 (the SI group); administration of doses 1 and 2 of EV71 vaccine on days 1 and 30, respectively (the SE1 group); or administration of HepB and MenA on days 1 and 30, respectively (the SE2 group).

Results

According to the per protocol set, antibody responses against EV71, hepatitis B virus (HBV), and group A meningococcal polysaccharide were similar regardless of administration schedule. With the non-inferiority margin setting at 10%, the seroconversion rates of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) were not inferior to those in SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72], respectively). Frequencies of adverse reactions to each vaccination regimen were comparable (60.62% in the SI group vs 52.33% in the SE1 group and 56.98% in the SE2 group; P = .16).

Conclusions

Simultaneous administration of combined EV71 vaccine with HepB and MenA has noninferior immunogenicity and safety, compared with separate administration of these vaccines.

Clinical Trials Registration

NCT03274102.
Intradermal SynCon® Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers
Authors: Tebas Pablo , Kraynyak Kimberly A , Patel Ami , Maslow Joel N , Morrow Matthew P , Sylvester Albert J , Knoblock Dawson , Gillespie Elisabeth , Amante Dinah , Racine Trina , McMullan Trevor , Jeong Moonsup , Roberts Christine C , Park Young K , Boyer Jean , Broderick Kate E , Kobinger Gary P , Bagarazzi Mark , Weiner David B , Sardesai Niranjan Y , White Scott M
Published: March 2019

Background

Nonlive vaccine approaches that are simple to deliver and stable at room temperature or 2–8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA vaccine that generates protection from lethal EBOV challenge in small animals and nonhuman primates, we performed a clinical study to evaluate both intramuscular (IM) and novel intradermal (ID) DNA delivery.

Methods

Two DNA vaccine candidates (INO-4201 and INO-4202) targeting the EBOV glycoprotein (GP) were evaluated for safety, tolerability, and immunogenicity in a phase 1 clinical trial. The candidates were evaluated alone, together, or in combination with plasmid-encoded human cytokine interleukin-12 followed by in vivo electroporation using either the CELLECTRA® IM or ID delivery devices.

Results

The safety profile of all 5 regimens was shown to be benign, with the ID route being better tolerated. Antibodies to EBOV GP were generated by all 5 regimens with the fastest and steepest rise observed in the ID group. Cellular immune responses were generated with every regimen.

Conclusions

ID delivery of INO-4201 was well tolerated and resulted in 100% seroreactivity after 2 doses and elicited interferon-γ T-cell responses in over 70% of subjects, providing a new approach for EBOV prevention in diverse populations.

Clinical Trials Registration. NCT02464670.
It is not collusion unless you get caught: the case of ‘Operation Car Wash’ and unearthing of a Cartel
Authors: Signor Regis , Love Peter E D , Vallim João José C B , Raupp Alexandre B , Olatunji Oluwole
Published: March 2019

In this article, we present findings from the Brazilian Federal Police’s ongoing investigation referred to as ‘Operation Car Wash’, which led to an accusation of collusive bidding being presented to a cartel that comprised 16 construction contractors. While plea bargains from several contractors within the cartel have materialized, additional evidence needs to be provided by the investigations officials to ensure the adequate application of justice. In this article, we provide scientific evidence that can be used by the Brazilian criminal courts to demonstrate the presence of collusive bidding. The contributions of this article are two-fold: (i) a robust and reliable econometric model to prove the presence of collusive bidding is implemented, which meets the basic criteria defined by the judicial system for scientific evidence; and (ii) the negative economic impact of collusive bid rigging is quantified, which was much higher than the percentage admitted by those involved in their leniency agreements.
International Humanitarian Law and Non-State Practice in Armed Conflict: Combatant’s Privilege and Kurdish Fighters in Syria
Authors: Rothkopf Ilana
Published: March 2019

Do fighters associated with non-state armed groups have the combatant’s privilege in armed conflict? Non-state armed groups are commonplace in contemporary armed conflicts. However, international humanitarian law (IHL), particularly the law that pertains to combatant’s privilege and prisoner of war status, was designed with state actors in mind. This article assesses the conditions under which the members of non-state armed groups have combatant’s privilege. Throughout, it uses the case of Kurdish fighters in Syria as an example of the timeliness of this question and its ramifications for conflict actors. This article notes, with support from the Geneva Conventions, Additional Protocols, and other sources of IHL, that IHL does not foresee a combatant’s privilege for armed groups in a non-international armed conflict. It contends, however, that the international community should agree to a generalisable rule for the treatment of fighters as combatants regardless of conflict type, if these fighters demonstrate the capability and willingness to adhere to IHL. Such a rule would reduce the need to assess both conflict type and the status of individual fighters should they be captured, and more importantly, it would incentivise continued compliance with IHL.
Soy Food Consumption, Exercise, and Body Mass Index and Osteoporotic Fracture Risk Among Breast Cancer Survivors: The Shanghai Breast Cancer Survival Study
Authors: Zheng Neil , Hsieh Evelyn , Cai Hui , Shi Liang , Gu Kai , Zheng Ying , Bao Ping-Ping , Shu Xiao-Ou
Published: March 2019

Background

Breast cancer survivors have a high incidence of osteoporosis-related fractures; the associated factors are understudied. We investigated incidence of bone fracture and its associations with soy food consumption, exercise, and body mass index among breast cancer survivors.

Methods

This prospective study included 4139 stage 0–III breast cancer patients and 1987 pre-/perimenopausal and 2152 postmenopausal patients. Fractures were assessed at 18 months and at 3, 5, and 10 years after cancer diagnosis. Osteoporotic fractures were defined as fractures caused by falls from standing height and at sites associated with osteoporosis. Exercise and soy isoflavone intake were assessed at 6 and 18 months postdiagnosis. Weight and height were measured at baseline. Lifetable and Cox regression analyses were employed. All statistical tests were two sided.

Results

The 10-year incidence for osteoporotic fractures was 2.9% and 4.4% for pre-/perimenopausal and postmenopausal patients, respectively. High soy isoflavone intake was associated with reduced risk among pre-/perimenopausal patients (hazard ratio [HR] = 0.22, 95% confidence interval [CI] = 0.09 to 0.53, for soy isoflavone mg/d ≥56.06 vs <31.31; Ptrend < .001) but not among postmenopausal patients (Pinteraction < .01). Overweight (vs normal weight) was a risk factor for pre-/perimenopausal patients (HR = 1.81, 95% CI = 1.04 to 3.14) but not for postmenopausal patients (HR = 0.67, 95% CI = 0.43 to 1.03; Pinteraction = .01). Exercise was inversely associated with osteoporotic fractures in postmenopausal patients (HR = 0.56, 95% CI = 0.33 to 0.97, for metabolic equivalents hours ≥12.6 vs <4.5) following a dose-response pattern (Ptrend = .035), an association not modified by menopausal status.

Conclusions

Our findings, especially the novel association of soy food intake with osteoporotic fractures in breast cancer survivors, if confirmed, can help guide future strategies for fracture risk reduction in this vulnerable population.
CmMYB#7, an R3 MYB transcription factor, acts as a negative regulator of anthocyanin biosynthesis in chrysanthemum
Authors: Xiang Lili , Liu Xiaofen , Li Heng , Yin Xueren , Grierson Donald , Li Fang , Chen Kunsong
Published: March 2019

‘Jimba’, a well-known white flowered chrysanthemum cultivar, occasionally and spontaneously produces red colored petals under natural cultivation, but there is little information about the molecular regulatory mechanism underlying this process. We analysed the expression patterns of 91 MYB transcription factors in ‘Jimba’ and ‘Turning red Jimba’ and identified an R3 MYB, CmMYB#7, whose expression was significantly decreased in ‘Turning red Jimba’ compared with ‘Jimba’, and confirmed it is a passive repressor of anthocyanin biosynthesis. CmMYB#7 competed with CmMYB6, which together with CmbHLH2 is an essential component of the anthocyanin activation complex, for interaction with CmbHLH2 through the bHLH binding site in the R3 MYB domain. This reduced binding of the CmMYB6–CmbHLH2 complex and inhibited its ability to activate CmDFR and CmUFGT promoters. Moreover, using transient expression assays we demonstrated that changes in the expression of CmMYB#7 accounted for alterations in anthocyanin content. Taken together, our findings illustrate that CmMYB#7 is a negative regulator of anthocyanin biosynthesis in chrysanthemum.
Ben Pimlott Memorial Lecture 2018The Women’s Suffrage Movement in the Balfour Family
Authors: Pedersen Susan
Published: March 2019

Given on the centenary of women's suffrage, this lecture explores the tensions and conflicts the claim for the vote raised among elite women already enmeshed in parliamentary and political circles. Drawing on the unbuttoned and sometimes angry correspondence among A.J. Balfour's suffragist sisters-in-law Lady Frances Balfour and Lady Betty Balfour, Frances' collaborator (and suffragist leader) Millicent Fawcett, Lady Betty's militant suffragette sister Lady Constance Lytton, and their old friend (and wife of the anti-suffragist Prime Minister) Margot Asquith, it explores the appeal but also the costs of this democratic claim for such “incorporated” women - and explains why some nevertheless supported it.
Distribution and Stability of Quinone Outside Inhibitor Fungicide Resistance in Populations of Potato PathogenicAlternariaspp. in Wisconsin
Authors: Ding Shunping , Halterman Dennis A. , Meinholz Kiana , Gevens Amanda J.
Published: March 2019

Quinone outside inhibitor (QoI) fungicides have been an important class in managing potato early blight caused by Alternaria solani and brown spot caused by A. alternata. Because of the single-site mode of action character of QoI fungicides, which are relied on for management of diseases in Wisconsin, and the abundant asexual conidia production of the Alternaria species, pathogen isolates with QoI resistance have been detected after just a few years of QoI fungicide usage in commercial production fields. Resistance to QoIs has been attributed to amino acid substitutions F129L and G143A in cytochrome b of A. solani and A. alternata, respectively, as a result of point mutations. The aim of this study was to assess Alternaria populations in Wisconsin for QoI resistance before and after fungicide applications in order to evaluate resistance stability. A TaqMan single nucleotide polymorphism genotyping assay was designed based on the sequences of the cytochrome b gene from Alternaria isolates collected in Wisconsin to profile QoI resistance in Alternaria populations as well as to explore factors that may influence frequency of QoI resistance in the pathogen populations. This assay successfully identified the mutations conferring QoI resistance in isolates collected from four locations each year from 2015 to 2017. During the course of this study, the frequency of A. solani isolates with the F129L mutation was consistently high and showed primarily the TTA mutation type. The frequency of A. alternata isolates with the G143A mutation started relatively low and increased at the end of the production season in each year (P = 0.0109, P = 0.2083, and P = 0.0159). A potato field managed without use of QoI fungicides showed a significantly lower (P < 0.05) frequency of A. alternata isolates carrying G143A than conventionally managed potato fields. The overall frequency of A. alternata isolates carrying G143A in the four locations was similar over the 3 years (P = 0.2971). The QoI resistance characteristics of the isolates were stable even when QoI selection pressure was removed for at least five subculture transfers, and the mutation types of codons 129 and 143 in the cytochrome b gene in A. solani and A. alternata, respectively, remained the same. This indicated that the application of QoIs in the field is not the sole factor responsible for the variation of the frequency of QoI resistance in the pathogen populations.
The First Purification of Functional Proteins from the Unculturable, Genome-Reduced, Bottlenecked α-Proteobacterium ‘Candidatus Liberibacter solanacearum’
Authors: Gilkes Jenna M. , Sheen Campbell R. , Frampton Rebekah A. , Smith Grant R. , Dobson Renwick C. J.
Published: March 2019

‘Candidatus Liberibacter solanacearum’ is an unculturable α-proteobacterium that is the causal agent of zebra chip disease of potato—a major problem in potato-growing areas, because it affects growth and yield. Developing effective treatments for ‘Ca. L. solanacearum’ has been hampered by the difficulty in functionally characterizing the proteins of this organism, largely because they are not easily expressed and purified in standard expression systems. ‘Ca. L. solanacearum’ has a reduced genome and its proteins are predicted to be prone to instability and aggregation. Among intracellular-dwelling bacteria, chaperone proteins are conserved and overexpressed to buffer against problems in protein folding. We mimicked this approach for expressing and purifying ‘Ca. L. solanacearum’ proteins in Escherichia coli by coexpressing them with chaperones. Neither of the representative ‘Ca. L. solanacearum’ enzymes, dihydrodipicolinate synthase (key in lysine biosynthesis) and pyruvate kinase (involved in glycolysis), were overexpressed in standard E. coli expression plasmids or strains. However, soluble dihydrodipicolinate synthase was successfully coexpressed with GroEL/GroES, while soluble pyruvate kinase was successfully coexpressed with either GroEL/GroES, dnaK/dnaJ/grpE, or a trigger factor. Both enzymes, believed to be key proteins for the organism, were purified by a combination of affinity chromatography and size-exclusion chromatography. Additionally, both ‘Ca. L. solanacearum’ enzymes are active and have the canonical tetrameric oligomeric structure in solution, consistent with other bacterial orthologs. This is the first study to successfully isolate and functionally characterize proteins from ‘Ca. L. solanacearum’. Thus, we provide a general strategy for characterizing its proteins, enabling new research and drug discovery programs to study and manage the pathogenicity of the organism.
Improving vaccination rates in older adults
Authors: Wright Wendy L. , Bruns Debra Pettit , Feeney Adele Susan , Strowman Shelley R.
Published: March 2019

Adults age 65 or older are at increased risk for acute and chronic diseases. Patients in this group who are up to date with all CDC-recommended vaccinations can reduce morbidity and mortality. This article discusses a quality improvement project across four NP-owned primary care clinics in which all clinical staff received an educational intervention focused on best vaccination practices and Medicare billing strategies. This project yielded improved vaccination rates in the older adult patient population over a 3-month period.
Effect of Neurally Adjusted Ventilatory Assist on Patient-Ventilator Interaction in Mechanically Ventilated Adults: A Systematic Review and Meta-Analysis
Authors: Pettenuzzo Tommaso , Aoyama Hiroko , Englesakis Marina , Tomlinson George , Fan Eddy
Published: March 2019

Objectives:

Patient-ventilator asynchrony is common among critically ill patients undergoing mechanical ventilation and has been associated with adverse outcomes. Neurally adjusted ventilatory assist is a ventilatory mode that may lead to improved patient-ventilator synchrony. We conducted a systematic review to determine the impact of neurally adjusted ventilatory assist on patient-ventilator asynchrony, other physiologic variables, and clinical outcomes in adult patients undergoing invasive mechanical ventilation in comparison with conventional pneumatically triggered ventilatory modes.

Data Sources:

We searched Medline, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central, CINAHL, Scopus, Web of Science, conference abstracts, and ClinicalTrials.gov until July 2018.

Study Selection:

Two authors independently screened titles and abstracts for randomized and nonrandomized controlled trials (including crossover design) comparing the occurrence of patient-ventilator asynchrony between neurally adjusted ventilatory assist and pressure support ventilation during mechanical ventilation in critically ill adults. The asynchrony index and severe asynchrony (i.e., asynchrony index > 10%) were the primary outcomes.

Data Extraction:

Two authors independently extracted study characteristics and outcomes and assessed risk of bias of included studies.

Data Synthesis:

Of 11,139 unique citations, 26 studies (522 patients) met the inclusion criteria. Sixteen trials were included in the meta-analysis using random effects models through the generic inverse variance method. In several different clinical scenarios, the use of neurally adjusted ventilatory assist was associated with significantly reduced asynchrony index (mean difference, –8.12; 95% CI, –11.61 to –4.63; very low quality of evidence) and severe asynchrony (odds ratio, 0.42; 95% CI, 0.23–0.76; moderate quality of evidence) as compared with pressure support ventilation. Furthermore, other measurements of asynchrony were consistently improved during neurally adjusted ventilatory assist.

Conclusions:

Neurally adjusted ventilatory assist improves patient-ventilator synchrony; however, its effects on clinical outcomes remain uncertain. Randomized controlled trials are needed to determine whether the physiologic efficiency of neurally adjusted ventilatory assist affects patient-important outcomes in critically ill adults.
Colorectal Lymphoma: A Contemporary Case Series
Authors: Skube Steven J. , Arsoniadis Elliot G. , Sulciner Megan L. , Gilles Scott R. , Gaertner Wolfgang B. , Madoff Robert D. , Melton Genevieve B. , Peterson Bruce A. , Kwaan Mary R.
Published: March 2019

BACKGROUND:

Colon and rectal lymphomas are rare and can occur in the context of posttransplant lymphoproliferative disorder. Evidence-based management guidelines are lacking.

OBJECTIVE:

The purpose of this study was to characterize the presentation, diagnosis, and management of colorectal lymphoma and to identify differences within the transplant population.

DESIGN:

This was a retrospective review of patients evaluated for colorectal lymphoma between 2000 and 2017. Patients were identified through clinical note queries.

SETTINGS:

Four hospitals within a single health system were included.

PATIENTS:

Fifty-two patients (64% men; mean age = 64 y; range, 26–91 y) were identified. No patient had <3 months of follow-up. Eight patients (15%) had posttransplant lymphoproliferative disorder.

MAIN OUTCOME MEASURES:

Overall survival, recurrence, and complications in treatment pathway were measured.

RESULTS:

Most common presentations were rectal bleeding (27%), abdominal pain (23%), and diarrhea (23%). The most common location was the cecum (62%). Most frequent histologies were diffuse large B-cell lymphoma (48%) and mantle cell lymphoma (25%). Posttransplant lymphoproliferative disorder occurred in the cecum (n = 4) and rectum (n = 4). Twenty patients (38%) were managed with chemotherapy; 25 patients (48%) underwent primary resection. Mass lesions had a higher risk of urgent surgical resection (35% vs 8%; p = 0.017). Three patients (15%) treated with chemotherapy presented with perforation requiring emergency surgery. Overall survival was 77 months (range, 25–180 mo). Patients with cecal involvement had longer overall survival (96 vs 26 mo; p = 0.038); immunosuppressed patients had shorter survival (16 vs 96 mo; p = 0.006). Survival in patients treated with surgical management versus chemotherapy was similar (67 vs 105 mo; p = 0.62).

LIMITATIONS:

This was a retrospective chart review, with data limited by the contents of the medical chart. This was a small sample size.

CONCLUSIONS:

Colorectal lymphoma is rare, with variable treatment approaches. Patients with noncecal involvement and chronic immunosuppression had worse overall survival. Patients with mass lesions, particularly cecal masses, are at higher risk to require urgent intervention, and primary resection should be considered. See Video Abstract at http://links.lww.com/DCR/A929.
Endocrine Emergencies in Obstetrics
Authors: GOODIER CHRISTOPHER G.
Published: March 2019

Endocrine emergencies in pregnancy can be life threatening and are associated with increased morbidity for both the mother and fetus. Thyroid storm, diabetic ketoacidosis, and hypercalcemic crisis require a high clinical suspicion, rapid treatment, and multidisciplinary care to ensure best outcomes. Critical care consultation and intensive care unit admission are often warranted. Fetal testing may initially be concerning; however often improves with correction of the underlying metabolic derangement(s) and delivery is generally avoided until maternal status improves.
Managing environmental exposure in clinical practice
Authors: Ashiru Oladapo A. , Adeyi Tinuke O. , Iloabachie Ebele C. , Bello Bolanle E. , Okeke Chizara C. , Soyoye Ajibola V.
Published: March 2019

Introduction:

Environmental toxins from various occupational industries like oil and gas, petrochemical, agriculture, and bad eating habits cause serious health hazards. This study describes the clinical success of Modern Mayr therapy type of detoxification in a fertility practice that uses detoxification as a complementary treatment.

Materials and Methods:

A total of 218 infertile patients undergoing in vitro fertilization treatment from January 2014 to December 2017 at the Medical Art Center (MART) Lagos, Nigeria were referred to MART-Life Detox clinic for a supervised Modern Mayr-type of detoxification before further assisted reproductive technology treatment. Patients were placed in 2 groups. Group A consisted of 131 patients with a history of one or more failed IVF cycles at MART before commencing Mayr therapy. Group B consisted of 87 patients with no previous IVF treatment at MART. Mayr therapy using special dietary nutrition and equipment such as hypoxicator and sea oxygenator was performed. Improvement in their fertility outcomes with regards to oocyte yield, pregnancy and live birth rate were assessed in subsequent cycles following detoxification.

Results:

The mean patient age was 41.53 years for group A and 40.6 years for group B. A total of 89% of all patients achieved significant weight reduction and improvement in body mass index. Uniform increase in oocyte yield was observed but this was particularly noticeable in previous poor responders in group A. Records showed positive hCG rates of 41.2% and 30%, clinical pregnancy rates of 27.5% and 21.8%, and live birth rates of 23.7% and 15%, in group A and B, respectively. There are currently 5 ongoing pregnancies in group A and 6 in group B.

Conclusions:

The data suggests that supervised modern Mayr type of detoxification may positively affect fertility indices in infertile couples who undergo assisted reproductive technology. However, there is a need for randomized controlled trials in larger populations to establish pattern of response.
Transpulmonary thermodilution techniques in the haemodynamically unstable patient
Authors: Beurton Alexandra , Teboul Jean-Louis , Monnet Xavier
Published: March 2019

Purpose of review

Transpulmonary thermodilution (TPTD) devices invasively measure not only cardiac output but also several other haemodynamic variables estimating cardiac preload, cardiac preload, systolic function, the lung oedema and systolic function, the lung oedema and the pulmonary permeability. In light of the recent literature, we describe how different indices are measured, emphasize their clinical interest and list potential limits and side-effects of the technique.

Recent findings

Estimation of cardiac output measurement with TPTD is now well established, at least when compared with the pulmonary artery catheter. The advantage of calibrating the pulse contour analysis, as it is allowed by TPTD indices, is clearly established over uncalibrated devices. The greatest advantage of TPTD is to measure extravascular lung water and pulmonary permeability, which may be useful to diagnose acute respiratory distress syndrome and manage fluid therapy in various critical diseases. It also allows a rapid detection of left ventricular systolic failure. The information it provides must be considered complementary to that provided by echocardiography.

TPTD provides several indices that may help in making decisions during the therapeutic management of haemodynamically unstable patients. It should be used for the most critically ill patients, whose management requires a reliable, precise and holistic view of the cardiopulmonary condition.
Asthma in children with sickle cell disease
Authors: Willen Shaina M. , Rodeghier Mark , DeBaun Michael R.
Published: March 2019

Purpose of review

Asthma is common in children with sickle cell disease (SCD) and appears to be associated with increased morbidity. Providers caring for children with SCD have struggled with the question of whether asthma exists as a true comorbidity or whether certain aspects of the chronic inflammatory disease gives children with SCD an asthma-like phenotype.

Recent findings

Clinical signs and symptoms seen in children with asthma in the general population, such as wheezing, airway hyperresponsiveness, atopy, elevated leukotrienes, and abnormal lung function are seen in children with SCD both with and without a diagnosis of asthma.

Current evidence highlights that the presence of lung disease in children with SCD has significant implications irrespective of the underlying cause, including asthma. Further research should focus on well tolerated and effective interventions to prevent disease-related complications for children with pulmonary complications of SCD.
Effectiveness of Discharge Education With the Teach-Back Method on 30-Day Readmission: A Systematic Review
Authors: Oh Eui Geum , Lee Hyun Joo , Yang You Lee , Kim Young Man
Published: March 2019

Objectives

Teach-back methods are reported to improve patient outcomes by encouraging patient understanding and participation and are increasingly being used in various clinical settings. This study attempts to identify the effectiveness of discharge education using the teach-back method on 30-day readmission.

Methods

MEDLINE, CINAHL, Embase, The Cochrane Library, and Web of Science were used to search experimental studies. The search terms were “discharged patient,” “teach-back,” and “30-day readmission” published in English up until July 2017. Two trained reviewers performed a critical appraisal of retrieved studies using the Risk of Bias Assessment tool for Nonrandomized Studies. Data were analyzed using Cochrane Review Manager (Revman) software 5.2.

Results

A total of five studies were analyzed (3 studies on heart failure, 1 study on total joint replacement, and 1 study on a coronary artery bypass graft). The main content of the teach-back education was to confirm and reinforce the patients’ comprehension of health-related information. Among the five studies, three studies were included in the meta-analysis. The odds ratio of 30-day readmission for discharge education with the teach-back method and usual care was 0.55 (95% confidence interval, 0.34–0.91; P = 0.02). The I
2 score was 0%, which means that the analyzed studies are homogeneous.

Conclusions

The results indicate that discharge education with the teach-back method resulted in a 45% reduction in 30-day readmission. However, only a few studies were included in the analysis, and they showed a high risk of selection bias. Therefore, we suggest that well-designed randomized controlled trials be conducted.
A Novel Approach to Crooked Nose in Rhinoplasty: Asymmetric Level Osteotomy Combined With Unilateral Spreader Graft
Authors: Demir Uygar Levent
Published: March 2019

The crooked nose is certainly among the most difficult to treat deformities for rhinoplasty surgeons. This deformity is a complex problem because each structural nasal component can be effected and they may be asymmetric bilaterally. Despite the use of sophisticated techniques and an additional effort, unfortunately the long-term aesthetic results may not be perfect with some minor flaws. Here in this study, the authors introduce a new technique that is used to correct crooked nose deformity. Sixteen consecutive patients who underwent open approach rhinoplasty by the same senior author between January 2015 and January 2018 with the diagnosis of C-shaped, reverse C-shaped, and I-shaped crooked nose deformity were included. The authors performed low-to-low lateral osteotomy with transverse root osteotomy to concave side (wider side) and low-to-high osteotomy to convex side (narrower side) combined with a unilateral spreader graft to concave side. Frontal images were taken preoperatively and 6 months postoperatively to use for further assessments. The authors compared the preoperative deviation angle values at rhinion (RDA) and at nasal tip (tip deviation angle) with postoperative values. In the study group, RDA value showed significant decrease after surgery; the preoperative RDA value was 6.2° (1.66°–16.39°) and it was calculated as 2.44° (0.7°–5.77°) with P < 0.001 postoperatively. The changes at tip deviation angle were also significant (P < 0.001) and tip deviation was successfully decreased from a value of 5.08° (2.8°–10.62°) to 2.13° (0.5°–6.6°) postoperatively. In conclusion, this study offers a new and effective technique to correct crooked nose deformity that can be used safely with satisfying aesthetic results.
Comparison of four Combined Procedures for Correction of Involutional Lower Eyelid Entropion
Authors: Poon Jia Shin , Vahdani Kaveh , Thaller Vladimir Theodor
Published: March 2019

Background:

To evaluate 4 combined techniques for entropion repair which address the horizontal laxity by either lateral tarsal strip (LTS) or Bick's procedure (BP) and the vertical laxity by everting sutures (ESs) or lower lid retractor plication (LLRP).

Methods:

Retrospective, comparative consecutive clinical series. A total of 261 procedures were performed on 227 patients. Patients were divided in the following groups based on the procedure type: Group 1: LTS + ES (n = 115), Group 2: LTS + LLRP (n = 77), Group 3: BP + ES (n = 25), and Group 4: BP + LLRP (n = 44).

Results:

The study cohort included 132 males and 95 females. The mean age was 76.2 ± 8.3 years. The mean follow-up was 13 months (range 3–58). At last follow-up, the cure rate was 92% in the LTS + ES and 90% LTS + LLRP groups, in contrast to 100% in BP + ES and BP + LLRP groups (P = 0.035). Overcorrection was observed in 2 patients from LTS + ES and 5 from LTS + LLRP group. There was no statistically significant difference in terms of symptoms outcomes among 4 groups. Complications were relatively minor with no statistically significant difference between the 2 groups (P = 0.13). The reoperation rate was 7% and 6.5% in groups 1 and 2 (P = 1.0), respectively, to none in groups 3 and 4.

Conclusion:

Bick's procedure in conjunction with either ES or LLRP, provides a quick, simple, and effective means for addressing the main pathogenic factors of involutional entropion. This study found a lower recurrence rate and consecutive ectropion formation in Bick's compared to LTS groups.
Delta Neutrophil Index for the Prediction of the Development of Sepsis-Induced Acute Kidney Injury in the Emergency Department
Authors: Kim Ji Hoon , Park Yoo Seok , Yoon Chang-Yun , Lee Hye Sun , Kim Sinae , Lee Jong Wook , Kong Taeyoung , You Je Sung , Park Jong Woo , Chung Sung Phil
Published: March 2019

Background and Purpose:

The early prediction of acute kidney injury (AKI) in sepsis and provision of timely treatment may improve outcomes. We investigated the efficacy of the delta neutrophil index (DNI)—which reflects the fraction of immature granulocytes—in predicting sepsis-induced AKI and 30-day mortality in cases of severe sepsis or septic shock.

Methods:

This retrospective, observational cohort study was performed with patients prospectively integrated in a critical pathway of early-goal-directed therapy /SEPSIS. We analyzed adult sepsis patients admitted to the emergency department with normal kidney function or stage 1 disease, based on the Acute Kidney Injury Network classification, between January 1, 2014 and September 30, 2017. The outcomes were the development of sepsis-induced severe AKI within 7 days and 30-day mortality.

Results:

A total of 346 patients were enrolled. An increase in the DNI values at Time-0 (odds ratio [OR], 1.060; P < 0.001) and Time-12 (OR, 1.086; P < 0.001) were strong independent predictors of severe AKI development. The increasing predictability of AKI was closely associated with a DNI ≥14.0% at Time-0 (OR, 7.238; P < 0.001) and ≥13.3% at Time-12 (OR, 18.089; P < 0.001). The development of severe AKI was an independent predictor of 30-day mortality (hazard ratio: 25.2, P < 0.001).

Conclusion:

Higher DNI values are independent predictors of severe AKI development and 30-day mortality in sepsis. Physicians can use the DNI to quickly determine the severity of sepsis and initial treatment strategies without additional costs and effort.