bluuebunny/crossref_metadata_2025 huggingface dataset:
Burnout in Obstetricians and Gynecologists
Authors: SMITH ROGER P.
Published: March 2019

Professional burnout threatens all high-functioning professionals and affects not only the individual, but, by extension, the patients they serve. The characteristics that make someone competitive for medical school, residency, or successful in academics or practice, make us particularly vulnerable to burnout: compulsive dedication to goals (and patients), motivation to succeed, self-reliance, leadership experience, delayed gratification, and others. Estimates of the prevalence of burnout in medicine vary widely but are consistently >40% and often as high as 75%. Obstetricians and gynecologists are not unique in suffering from burnout but do rank among the top medical specialties for the rate of professional burnout reported. When burnout is present, there is reduced job satisfaction, lower productivity, increased medical errors (and morbidity), degraded interpersonal interactions, and higher physician dropout rates. Career dissatisfaction, early retirement, and even regret surrounding the original choice of career are all common when burnout is present. There is a growing body of individual actions that can be taken to reduce or reverse the impact of burnout, but the first steps are to understand the causes and identify the symptoms.
Influence of Anterior Biometry on Corneal Biomechanical Stiffness of Glaucomatous Eyes Treated With Chronic Medication or Filtration Surgery
Authors: Tejwani Sushma , Francis Mathew , Dinakaran Shoruba , Kamath Vijna , Tilva Bhavinkumar , Das Raunak K. , Shetty Rohit , Sinha Roy Abhijit
Published: March 2019

Précis:

Anterior chamber depth, IOP, and thickness confounded the assessment of corneal biomechanical properties with noncontact applanation in glaucoma eyes. Compared with normal eyes, glaucoma eyes, which underwent long-term treatment or filtration surgery, had similar properties.

Purpose:

The purpose of this study was to evaluate corneal stiffness in primary angle-closure (PACG) and primary open-angle (POAG) glaucoma eyes that were subgrouped on the basis of the type of topical medication and filtration surgery using noncontact applanation.

Methods:

All eyes were retrospectively reviewed for intraocular pressure (IOP) with Corvis-ST (OCULUS Optikgerate Gmbh, Germany). Nonglaucoma (n=140), PACG (n=102 under medication), and POAG (n=154 under medication) eyes were included. Corneal stiffness was calculated using deformation amplitude and a biomechanical model. Multivariate analyses were performed, which evaluated the effect of systemic conditions (diabetes and hypertension), the effect of medication (prostaglandins or beta blockers or combined), and the effect of filtration surgery (PACG: n=23; POAG: n=26). Age, IOP, central corneal thickness (CCT), refractive error, and anterior chamber depth (ACD) were covariates.

Results:

Diabetes and hypertension did not alter corneal stiffness of glaucoma eyes compared with nonglaucoma eyes (P>0.05). Corneal stiffness of POAG and nonglaucoma eyes was similar but significantly different from the stiffness of PACG eyes (P=0.002), irrespective of the type of topical medication. This difference was strongly correlated with ACD (P=0.003) in addition to IOP and CCT. In eyes treated with filtration surgery, ACD (P=0.04) again impacted the trends between nonglaucoma and glaucoma eyes.

Conclusions:

Medication or filtration surgery did not affect the corneal biomechanical parameters differentially from nonglaucoma eyes. However, IOP, CCT, and ACD strongly affected corneal biomechanical parameters in the same glaucoma eyes.
West Indies Glaucoma Laser Study (WIGLS) 3. Anterior Chamber Inflammation Following Selective Laser Trabeculoplasty in Afro-Caribbeans with Open-angle Glaucoma
Authors: Realini Tony , Shillingford-Ricketts Hazel , Burt Darra , Balasubramani Goundappa K.
Published: March 2019

Precis:

In the absence of prophylactic anti-inflammatory therapy, anterior chamber inflammation (characterized by cells and less commonly flare) is minimal and transient after selective laser trabeculoplasty in Afro-Caribbean glaucoma patients.

Purpose:

The purpose of this study was to characterize the prevalence, severity, and duration of anterior chamber inflammation (cells and flare) following selective laser trabeculoplasty (SLT) in Afro-Caribbean eyes with primary open-angle glaucoma (POAG).

Methods:

In total 144 eyes of 72 POAG patients underwent first-time 360-degree SLT treatment following washout of all topical medications in the prospective West Indies Glaucoma Laser Study. No anti-inflammatory therapy was used post-SLT. Anterior chamber cells and flare were characterized pre-SLT after medication washout, and 1 week, 6 weeks, and 3, 6, 9 and 12 months post-SLT using the standardized methodology described by the Society for Uveitis Nomenclature (SUN) in which cells and flare are each graded on a scale of 0-4+ using specific slit-lamp settings.

Results:

Mean cell scores in both right and left eyes rose significantly (P<0.0001) from baseline to week 1 after SLT before returning to baseline values at all subsequent time points. Mean flare scores in right eyes (P=0.0185) but not left eyes (P=0.1816) rose from baseline to week 1 after SLT before returning to baseline values at all subsequent time points. Cells appeared in 40.3% of eyes and flare appeared in 9.7% of eyes after SLT. One subject developed bilateral symptomatic anterior iritis one day postoperatively and reported a previously undisclosed history of recurrent iritis; the iritis resolved with topical steroid therapy.

Conclusions:

SLT in Afro-Caribbean people with POAG is associated with mild, short-lived and self-limited anterior chamber inflammation. Routine anti-inflammatory therapy to suppress posttreatment inflammation after SLT is unnecessary in this population.
Lacrimal Sac Sebaceous Carcinoma
Authors: Vahdani Kaveh , Coupland Sarah E. , Ashdown Morag Evalyn , Garrott Hellen , Ford Rebecca
Published: March 2019

Sebaceous carcinoma is an aggressive malignancy with a high mortality rate that commonly arises in the periorbital area. Rarely, the lacrimal apparatus may be involved by either contiguous or noncontiguous spread. The authors describe 2 unusual cases of sebaceous carcinoma in the lacrimal sac, presenting as a medial canthal mass simulating chronic dacryocystitis. In Case 1, the sebaceous carcinoma occurred primarily in the lacrimal sac, in the absence of concurrent or previous ocular adnexal sebaceous neoplasia. Mapping biopsies found no evidence of intraepithelial disease. Case 2 developed a late noncontiguous disease recurrence involving the lacrimal sac 5 years postprimary resection of an ipsilateral eyelid sebaceous carcinoma. These cases demonstrate atypical mode of spread of sebaceous carcinoma in lacrimal excretory system. It is important to regard the nasolacrimal drainage system as a potential reservoir for neoplastic sebaceous cells and minimize the risk of tumor cell dissemination during surgical management of eyelid or conjunctival sebaceous cell tumors.
The Course of Adverse Events in Venlafaxine XR Treatment in Generalized Anxiety Disorder
Authors: Rickels Karl , Gallop Robert , Cleary Sean
Published: March 2019

Purpose

The time course of adverse events is an important factor for patient management. Clinicians are better able to prepare patients for specific adverse events, which leads to better treatment adherence.

Methods

Adverse events were followed longitudinally for 6 months during the open-label phase of a relapse prevention trial with 264 patients with generalized anxiety disorder. Adverse events were assessed at each treatment visit using a 21-item checklist. Logistic regression modeling, continuation ratio modeling, and hierarchical linear modeling were used to determine whether adverse events led to early attrition and whether adverse events decreased in enrolled patients over time.

Findings

Adverse events were found to have decreased highly significantly during treatment. A highly significant race effect was found in that whites had a significantly higher adverse event rate than did nonwhites. Early attrition rates were predicted by presence of nausea and fatigue, late attrition by dizziness, nervousness, and sexual dysfunction.

Implications

Our findings provide information for clinicians on the course of adverse events over treatment, useful to prepare patients for treatment adherence.
Fatigue, Physical and Functional Mobility, and Obesity in Pediatric Cancer Survivors
Authors: Karimi Masoumeh , Cox Amanda D. , White Sabrina V. , Karlson Cynthia W.
Published: March 2019

Background

Survivors of childhood cancer are prone to an increased risk of chronic issues such as cardiovascular disease, fatigue, weight-related problems, and emotional disturbances.

Objective

This study utilized the biopsychosocial model to examine the hypothesis that greater depression and lower mobility would be significantly associated with greater fatigue and higher body mass index in survivors of childhood cancer.

Methods

Data were analyzed for 144 children treated and followed up for an oncology condition at a southeastern academic medical center. Voluntarily, children completed the Patient-Reported Outcomes Measurement Information System 1.0, and parents completed the Family Symptom Inventory as part of a brief annual psychosocial screening battery. Height and weight were collected by a clinic nurse prior to questionnaire completion.

Results

Hierarchical linear regression showed that shorter time since diagnosis (β = −.154, P < .05), greater child-reported depression (β = .396, P < .01), and lower mobility (β = .427, P < .01) significantly predicted greater fatigue (adjusted R
2 = 0.54). Older age (β = .262, P < .01) and not receiving chemotherapy (β = −.209, P < .05) significantly predicted higher body mass index (adjusted R
2 = 0.051).

Conclusions

Findings showed that fatigue tends to improve over time after treatment but may be predicted by greater depression symptoms and lower mobility in recent survivors of childhood cancer.

Implications for Practice

For survivors of childhood cancer with higher levels of fatigue, treating symptoms of depression and maximizing physical and mobility may be of clinical value. With the impact of psychological and social factors not yet understood in pediatric cancer survivors, weight status in recent survivors of childhood cancer is likely a complex interaction between biological and treatment factors.
Identification of Factors Affecting the Quality of Life Among Patients With Addiction in Lebanon
Authors: Hallit Souheil , Haddad Chadia , Obeid Sahar , Kazour Francois , Nabout Rita , Darwich Mouhamad J. , Tahan Fouad E.
Published: March 2019

Our objective was to assess factors associated with the physical (Short-Form 12–physical component summary [SF-12-PCS]) and mental (Short-Form 12–mental component summary [SF-12-MCS]) quality of life (QOL) in the Lebanese population. A cross-sectional study, conducted between July and September 2017, enrolled 57 patients with substance use disorder from the Psychiatric Hospital of the Cross. The SF-12 scale was used to assess the QOL among participants. A first stepwise linear regression, using the SF-12-PCS score as the dependent variable, showed that females compared with males (β = −4.86) and having a family history of substance use disorder (β = −4.70) were associated with lower physical QOL (lower SF-12-PCS scores). A second stepwise linear regression, using the SF-12-MCS score as the dependent variable, showed that having a generalized anxiety disorder (β = −10.52) and having suicidal ideation (β = −8.05) were associated with lower mental QOL (lower SF-12-MCS scores). Strategic interventions are needed to manage the health-related QOL in those with substance abuse.
Critical Illness and Cardiac Dysfunction in Anthracycline-Exposed Pediatric Oncology Patients*
Authors: Wolfe Katie K. , Reichek Jennifer , Marsillio Lauren E.
Published: March 2019

Objectives:

To determine if the presence of cardiac dysfunction in anthracycline-exposed pediatric oncology patients is associated with an increased frequency of PICU admission or mortality.

Design:

Retrospective parallel cohort study.

Setting:

PICU at an academic freestanding children’s hospital.

Subjects:

Children with oncologic diagnoses who received anthracyclines between January 2006 and December 2014 and were admitted to the hospital within 1 year of completion of therapy.

Interventions:

None.

Measurements and Main Results:

Charts of 734 patients were reviewed and 545 were included in analysis. Anthracycline-exposed pediatric oncology patients with cardiac dysfunction were more likely to be admitted to the PICU than those without cardiac dysfunction (87% vs 37% rate of PICU admission). PICU admission was also associated with identified infection and higher cumulative anthracycline dose. Once admitted to the PICU, those anthracycline-exposed patients with cardiac dysfunction had significantly higher mortality (26% vs 6%) and longer length of stay (7 vs 2 d) than children without cardiac dysfunction. Patients with cardiac dysfunction were more likely to require mechanical ventilation (59% vs 18%), required more vasoactive medications for longer, and were more likely to develop fluid overload. Death within 1 year of ICU admission was associated with higher cumulative anthracycline dose.

Conclusions:

Children with cancer who received anthracyclines, especially at higher doses, and who develop cardiac dysfunction are at higher risk of critical illness, have higher rates of multiple organ dysfunction and higher rates of mortality than anthracycline-exposed patients without cardiac dysfunction.
Animal models of mucositis: critical tools for advancing pathobiological understanding and identifying therapeutic targets
Authors: Wardill Hannah R. , Tissing Wim J.E. , Kissow Hannelouise , Stringer Andrea M.
Published: March 2019

Purpose of review

Mucositis remains a prevalent, yet poorly managed side effect of anticancer therapies. Mucositis affecting both the oral cavity and gastrointestinal tract predispose to infection and require extensive supportive management, contributing to the growing economic burden associated with cancer care. Animal models remain a critical aspect of mucositis research, providing novel insights into its pathogenesis and revealing therapeutic targets. The current review aims to provide a comprehensive overview of the current animal models used in mucositis research.

Recent findings

A wide variety of animal models of mucositis exist highlighting the highly heterogenous landscape of supportive oncology and the unique cytotoxic mechanisms of different anticancer agents. Golden Syrian hamsters remain the gold-standard species for investigation of oral mucositis induced by single dose and fractionated radiation as well as chemoradiation. There is no universally accepted gold-standard model for the study of gastrointestinal mucositis, with rats, mice, pigs and dogs all offering unique perspectives on its pathobiology.

Animal models are a critical aspect of mucositis research, providing unprecedent insight into the pathobiology of mucositis. Introduction of tumour-bearing models, cyclic dosing scheduled, concomitant agents and genetically modified animals have been integral in refining our understanding of mucositis.
ICTV Virus Taxonomy Profile: Nimaviridae
Authors: Wang Han-Ching , Hirono Ikuo , Maningas Mary Beth Bacano , Somboonwiwat Kunlaya , Stentiford Grant ,   ICTV Report Consortium
Published: March 2019

The family Nimaviridae includes the single species White spot syndrome virus, isolates of which infect a wide range of aquatic crustaceans and cause substantial economic losses. Virions are ellipsoid to bacilliform with a terminal thread-like extension. The circular dsDNA genome is 280–307 kbp with several homologous repeat regions. More than 80 structural and functional proteins have been characterized from 531 ORFs. White spot syndrome is a highly lethal, contagious disease associated with white spot syndrome virus infection of shrimps. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Nimaviridae, which is available at www.ictv.global/report/nimaviridae.
Genomics in the jungle: using portable sequencing as a teaching tool in field courses
Authors: Watsa Mrinalini , Erkenswick Gideon A. , Pomerantz Aaron , Prost Stefan
Published: March 2019

Genetic research is a rapidly evolving field of study that is increasingly being utilized as a tool for wildlife conservation. However, researchers and science educators in remote areas can often find it difficult to access the latest genetic technologies, often due to a combination of high costs, bulky equipment, and lack of infrastructure. Recent technological innovations are resulting in portable, low-cost instruments that enable next-generation sequencing in remote environments, offering new opportunities to generate a more widespread network of trained conservation scientists, particularly within regions of high biodiversity. What is currently lacking are formalized educational efforts to teach participants in biodiverse areas with hands-on training in molecular biology and real-time DNA sequencing techniques. To address this challenge, we report the design and summarized feedback/outcomes of a conservation genetics field course, called ‘Genomics in the Jungle’, that took place at a field research station in the Amazon rainforest of southeastern Peru. The program was established by a small US-based NGO, Field Projects International, and facilitated by a local eco-tourism company in Peru, Inkaterra. We utilized portable sequencing technologies from Oxford Nanopore Technologies, and in-kind support from the manufacturers MiniPCR, MiniOne Systems, Promega, and New England Biolabs. Participants included a mix of non-Peruvian students and local/regional students, some of which had no prior exposure to a genetics laboratory. Overall, we maintain that portable sequencing technology is democratizing scientific research and conservation efforts, and is a major step forward for science educators and conservationists.
Microglia actively remodels adult hippocampal neurogenesis through the phagocytosis secretome
Authors: Diaz-Aparicio Irune , Paris Iñaki , Sierra-Torre Virginia , Plaza-Zabala Ainhoa , Rodríguez-Iglesias Noelia , Márquez-Ropero Mar , Beccari Sol , Abiega Oihane , Alberdi Elena , Matute Carlos , Bernales Irantzu , Schulz Angela , Otrokocsi Lilla , Sperlagh Beata , Happonen Kaisa E. , Lemke Greg , Maletic-Savatic Mirjana , Valero Jorge , Sierra Amanda
Published: March 2019

During adult hippocampal neurogenesis, the majority of newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of their intracellular contents. Here, we propose that phagocytosis is not merely a passive process of corpse removal but has an active role in maintaining adult hippocampal neurogenesis. First, we found that neurogenesis was disrupted in mice chronically deficient for two microglial phagocytosis pathways (P2Y12 and MerTK/Axl), but was transiently increased in mice in which MerTK expression was conditionally downregulated. Next, we performed a transcriptomic analysis of microglial phagocytosis in vitro and identified genes involved in metabolism, chromatin remodeling, and neurogenesis-related functions. Finally, we discovered that the secretome of phagocytic microglia limits the production of new neurons both in vivo and in vitro. Our data suggest that reprogrammed phagocytic microglia act as a sensor of local cell death, modulating the balance between cell proliferation and cell survival in the neurogenic niche, thereby supporting the long-term maintenance of adult hippocampal neurogenesis.

GRAPHICAL ABSTRACT
Impact of a caries preventive intervention in remote Indigenous Australian children
Authors: Lalloo Ratilal , SANTOSH KUMAR TADAKAMADLA , Kroon Jeroen , Jamieson Lisa M , Johnson Newell
Published: March 2019

IMPORTANCE: The burden of dental caries in remote Indigenous communities in Australia is unacceptably high. OBJECTIVES: We tested the impact of an annual caries preventive intervention, delivered by a fly-in/fly-out professional team, on Indigenous children residing in a remote Australian community, involving selective fissure sealants, topical povidone iodine and fluoride varnish application. The outcome was caries increment at 12- and 24-month follow-up. DESIGN, SETTING, PARTICIPANTS: Around 600 Indigenous children aged 5 to 17 years were invited to participate at baseline, of which 408 had caregiver consent provided. Of these, 196 consented to both the study and the treatment arm and comprised the experimental group. Two hundred and twelve consented to the epidemiological examination only, and constituted the comparison group. INTERVENTION: The Big Bang intervention, which occurred annually, comprised placement of fissure sealants, and application of povidone-iodine and fluoride varnish, following completion of each childs dental treatment plan. Standard diet and oral hygiene advice was provided. MAIN OUTCOMES AND MEASURES: Caries increment (number of tooth surfaces with new dental caries) in both primary and permanent dentitions at 12- and 24-month follow-up. RESULTS: At 12-month follow-up, children in the experimental group had, on average, 5.05 (5.47) new carious lesions compared to 7.49 (6.94) in the comparison group (p=0.001). The preventive fraction was 33%. At 24-month follow-up, children in the experimental group had, on average, 6.47 (6.07) new carious lesions compared to 8.43 (5.83) in the comparison group (p=0.002). The preventive fraction was 23%. CONCLUSIONS AND RELEVANCE: Indigenous children exposed to the Big Bang caries intervention had significantly less increment in dental disease than those not exposed to the intervention. Benefits were demonstrated at both 12- and 24-month follow-ups, suggesting that the intervention is likely to be sustained if delivered across a childs life. The cost-effectiveness of this approach is being evaluated.
The effect of combined patching and citalopram on visual acuity in adults with amblyopia: a randomized, crossover, placebo-controlled trial
Authors: Lagas Alice K. , Black Joanna M. , Russell Bruce R. , Kydd Robert R. , Thompson Benjamin
Published: March 2019

Non-human animal models have demonstrated that selective serotonin reuptake inhibitors (SSRIs) can enhance plasticity within the mature visual cortex and enable recovery from amblyopia. The aim of this study was to test the hypothesis that the SSRI citalopram combined with part-time patching of the fellow fixing eye would improve amblyopic eye visual acuity in adult humans. Following a cross-over, randomized, double blind, placebo-controlled design (pre-registration: ACTRN12611000669998), participants completed two 2-week blocks of fellow fixing eye patching. One block combined patching with citalopram (20 mg/day) and the other with a placebo tablet. The blocks were separated by a 2-week washout period. The primary outcome was change in amblyopic eye visual acuity. Secondary outcomes included stereoacuity and electrophysiological measures of retinal and cortical function. Seven participants were randomized, fewer than our pre-specified sample size of 20. There were no statistically significant differences in amblyopic eye visual acuity change between the active (mean ± SD change = 0.08±0.16 logMAR) and the placebo (mean change = −0.01±0.03 logMAR) blocks. No treatment effects were observed for any secondary outcomes. However, 3 of 7 participants experienced a 0.1 logMAR or greater improvement in amblyopic eye visual acuity in the active but not the placebo block. These results from a small sample suggest that larger-scale trials of SSRI treatment for adult amblyopia may be warranted. Considerations for future trials include drug dose, treatment duration and recruitment challenges.
Improving spatial normalization of brain diffusion MRI to measure longitudinal changes of tissue microstructure in the cortex and white matter
Authors: Jacobacci Florencia , Jovicich Jorge , Lerner Gonzalo , Amaro Edson , Armony Jorge L. , Doyon Julien , Della-Maggiore Valeria
Published: March 2019

Background

Fractional anisotropy (FA) and mean diffusivity (MD) are frequently used to evaluate longitudinal changes in white matter microstructure. Recently, there has been a growing interest in identifying experience-dependent plasticity in gray matter using MD. Improving registration has thus become a major goal to enhance the detection of subtle longitudinal changes in cortical microstructure.

Purpose

To optimize normalization to improve registration in gray matter and reduce variability associated with multi-session registrations.

Study Type

Prospective longitudinal study

Subjects

Twenty-one healthy subjects (18-31 years old) underwent 9 magnetic resonance imaging (MRI) scanning sessions each.

Field Strength/Sequence

3.0T, diffusion-weighted multiband-accelerated sequence, MP2RAGE sequence.

Assessment

Diffusion-weighted images were registered to standard space using different pipelines that varied in the features used for normalization, namely the non-linear registration algorithm (FSL vs ANTs), the registration target (FA-based vs T1-based templates), and the use of intermediate individual (FA-based or T1-based) targets. We compared the across-session test-retest reproducibility error from these normalization approaches for FA and MD in white and gray matters.

Statistical Tests

Reproducibility errors were compared using a repeated-measures analysis of variance with pipeline as within-subject factor.

Results

The registration of FA data to the FMRIB58 FA atlas using ANTs yielded lower reproducibility errors in white matter (p<0.0001) with respect to FSL. Moreover, using the MNI152 T1 template as the target of registration resulted in lower reproducibility errors for MD (p<0.0001), whereas the FMRIB58 FA template performed better for FA (p<0.0001). Finally, the use of an intermediate individual template improved reproducibility when registration of the FA images to the MNI152-T1 was carried out within modality (FA-FA) (p<0.05), but not via a T1-based individual template.

Data Conclusion

A normalization approach using ANTs to register FA images to the MNI152 T1 template via an individual FA template minimized test-retest reproducibility errors both for gray and white matter.
Tracing foot-and-mouth disease virus phylogeographical patterns and transmission dynamics
Authors: Jara Manuel , Frias-De-Diego Alba , Dellicour Simon , Baele Guy , Machado Gustavo
Published: March 2019

Foot-and-mouth disease virus (FMDV) has proven its potential to propagate across local and international borders on numerous occasions, but yet details about the directionality of the spread along with the role of the different host in transmission remain unexplored. To elucidate FMDV global spread characteristics, we studied the spatiotemporal phylodynamics of serotypes O, A, Asia1, SAT1, SAT2, and SAT3, based on more than 50 years of phylogenetic and epidemiological information. Our results revealed phylogeographic patterns, dispersal rates, and the role of host species in the dispersal and maintenance of virus circulation. Contrary to previous studies, our results showed that three serotypes were monophyletic (O, A, and Asia1), while all SATs serotypes did not evidence a defined common ancestor. Root state posterior probability (RSPP) analysis suggested Belgium as the country of origin for serotype O (RSPP=0.27). India was the ancestral country for serotypes A (RSPP= 0.28), and Asia-1 (RSPP= 0.34), while Uganda appeared as the most likely origin country of all SAT serotypes (RSPP> 0.45). Furthermore, we identified the key centers of dispersal of the virus, being China, India and Uganda the most important ones. Bayes factor analysis revealed cattle as the major source of the virus for most of the serotypes (RSPP> 0.63), where the most important host-species transition route for serotypes O, A, and Asia1 was from cattle Bos taurus to swine Sus scrofa domesticus (BF>500), while, for SAT serotypes was from B. taurus to African buffalo Syncerus caffer. This study provides significant insights into the spatiotemporal dynamics of the global circulation of FMDV serotypes, by characterizing the viral routes of spread at serotype level, especially uncovering the importance of host species for each serotype in the evolution and spread of FMDV which further improve future decisions for more efficient control and eradication.
Single-molecule visualization of the effects of ionic strength and crowding on structure-mediated interactions in supercoiled DNA molecules
Authors: Scott Shane , Shaheen Cynthia , McGuinness Brendon , Metera Kimberly , Kouzine Fedor , Levens David , Benham Craig J. , Leslie Sabrina
Published: March 2019

DNA unwinding is an important cellular process involved in DNA replication, transcription and repair. In cells, molecular crowding caused by the presence of organelles, proteins, and other molecules affects numerous internal cellular structures. Here, we visualize plasmid DNA unwinding and binding dynamics to an oligonucleotide probe as functions of ionic strength, crowding agent concentration, and crowding agent species using single-molecule CLiC microscopy. We demonstrate increased probe-plasmid interaction over time with increasing concentration of 8 kDa polyethylene glycol (PEG), a crowding agent. We show decreased probe-plasmid interactions as ionic strength is increased without crowding. However, when crowding is introduced via 10% 8 kDa PEG, interactions between plasmids and oligos are enhanced. This is beyond what is expected for normal in vitro conditions, and may be a critically important, but as of yet unknown, factor in DNA’s proper biological function in vivo. Our results show that crowding has a strong effect on the initial concentration of unwound plasmids. In the dilute conditions used in these experiments, crowding does not impact probe-plasmid interactions once the site is unwound.
Accurate forecasts of the effectiveness of interventions against Ebola may require models that account for variations in symptoms during infection
Authors: Hart W.S. , Hochfilzer L.F.R. , Cunniffe N.J. , Lee H. , Nishiura H. , Thompson R.N.
Published: March 2019

Epidemiological models are routinely used to predict the effects of interventions aimed at reducing the impacts of Ebola epidemics. Most models of interventions targeting symptomatic hosts, such as isolation or treatment, assume that all symptomatic hosts are equally likely to be detected. In other words, following an incubation period, the level of symptoms displayed by an individual host is assumed to remain constant throughout an infection. In reality, however, symptoms vary between different stages of infection. During an Ebola infection, individuals progress from initial non-specific symptoms through to more severe phases of infection. Here we compare predictions of a model in which a constant symptoms level is assumed to those generated by a more epidemiologically realistic model that accounts for varying symptoms during infection. Both models can reproduce observed epidemic data, as we show by fitting the models to data from the ongoing epidemic in the Democratic Republic of Congo and the 2014-16 epidemic in Liberia. However, for both of these epidemics, when interventions are altered identically in the models with and without levels of symptoms that depend on the time since first infection, predictions from the models differ. Our work highlights the need to consider whether or not varying symptoms should be accounted for in models used by decision makers to assess the likely efficacy of Ebola interventions.
Extended insight into the preponderance of LRRs - a docking & simulation study with members of the TLR1 subfamily
Authors: Dey Debayan , Dhar Dipanjana , Das Sucharita , Maulik Aditi , Basu Soumalee
Published: March 2019

The widespread structural motif of Leucine-rich repeats (LRR) constitute the extracellular part of the Toll-like receptor (TLR) family preceded by an intracellular Toll/interleukin-1 receptor (TIR) domain at the C-terminus. The benefit of using LRRs in these pattern recognition receptors (PRR) that are responsible for early detection of pathogens to elicit inflammatory/innate immune response still remains elusive. Phylogenetic analyses (Maximum Likelihood and Bayesian Inference) of nine TLR (TLR 1-9) genes from 36 mammals reconfirmed the existence of two distinct clades, one (TLR1/2/6) for recognizing bacterial cell wall derivatives and another (TLR7/8/9) for various nucleic acids. TLR3, TLR4 and TLR5 showed independent line of evolution. The distinction of the TLR1 subfamily to form heterodimers within its members and the existence of the paralogs TLR1 and TLR6 therein, was appealing enough to carry out further studies with the extracellular recognition domain. Dimerizing and ligand binding residues from the crystal structures of TLR1 and TLR6 were interchanged to generate chimeric proteins. The dimer forming ability of these variants with their common partner, TLR2, were checked before running MD simulations. The chimeras were compared with wild type dimers to find no significant alterations in the overall structure. Finally, interchanged ligands were docked to the variants to ratify reversal of the binding function. Intriguingly, sequence change in substantial numbers, 16 in TLR1 and 18 in TLR6, preserves the native scaffold offered by LRRs. This exercise thus depicts how the LRR motif has been advantageous to be selected as an evolutionarily conserved motif for essential cellular processes.
A Mechanism for Epithelial-Mesenchymal Heterogeneity in a Population of Cancer Cells
Authors: Tripathi Shubham , Levine Herbert , Kumar Jolly Mohit
Published: March 2019

Epithelial-mesenchymal heterogeneity, wherein cells within the same tumor can exhibit an epithelial, a mesenchymal, or one or more hybrid epithelial-mesenchymal phenotype(s), has been observed across cancer types and implicated in metastatic aggressiveness. Here, we have used computational modeling to show that this heterogeneity can emerge from the noise in the partitioning of RNAs and proteins among the daughter cells during cancer cell division. Our model captures the population-level behavior of murine prostate cancer cells, the hysteresis in the dynamics of epithelial-mesenchymal plasticity, and how hybrid phenotype-promoting factors alter the phenotypic composition of a population. We further used the model to describe the implications of heterogeneity for therapeutics. By linking the dynamics of an intracellular regulatory circuit to the phenotypic composition of a population, the study contributes towards understanding how non-genetic heterogeneity can be generated and propagated from a small, homogeneous population, and towards therapeutic targeting of cancer cell heterogeneity.
Induction of p73, Δ133p53, Δ160p53, pAKT leads to neuroprotection via DNA repair by 5-LOX inhibition
Authors: Shekhar Shashank , Dey Sharmistha
Published: March 2019

Lipooxygenase-5 (5-LOX), protein is involved in the pathologic phenotype of AD which includes amyloid-plague and tau hyperphosphorylation. This study aims to identify the mechanistic role in neuroprotection by peptide YWCS, the 5-LOX inhibitor in neurotoxic SH-SY5Y cell line developed by the treatment of Aβ25-35. The cells were treated with Aβ25-35 and with different doses of YWCS. The effect on cell survival pathways were determined by western blot using polyclonal anti body of p53, anti-Akt and anti-phosphorylated-Akt. Immunoprecipitation and mass spectroscopic studies were done to identify the altered proteins. Over expression of phosphorylated-Akt and 3 bands of p53 isoforms were observed which correspond to p73, Δ133p53 and Δ160p53 in the cells treated only with 80µM of YWCS compare to untreated cells. However, no alteration of total p53 and Akt were observed. The results exposed the novel mechanistic pathway of neuroprotection by 5-LOX inhibition, which is likely to be mediated by DNA DSB repair through p53 isoforms and PI3K/Akt pathway. Our finding has opened a new window in the therapeutic approach for the prevention of AD.
Control of human testis-specific gene expression
Authors: Brown Jay C.
Published: March 2019

Background

As a result of decades of effort by many investigators we now have an advanced level of understanding about several molecular systems involved in the control of gene expression. Examples include CpG islands, promoters, mRNA splicing and epigenetic signals. It is less clear, however, how such systems work together to integrate the functions of a living organism. Here I describe the results of a study to test the idea that a contribution might be made by focusing on genes specifically expressed in a particular tissue, the human testis.

Experimental Design

A database of 239 testis-specific genes was accumulated and each was examined for the presence of features relevant to control of gene expression. These include: (1) the presence of a promoter, (2) the presence of a CpG island (CGI) within the promoter, (3) the presence in the promoter of a transcription factor binding site near the transcription start site, (4) the level of gene expression, and (5) the above features in genes of cell types such as spermatocyte and spermatid that differ in their extent of differentiation.

Results

Of the 107 database genes with an annotated promoter, 56 were found to have one or more transcription factor binding sites near the transcription start site. Three of the binding sites observed, Pax-5, AP-2αA and GRα, stand out in abundance suggesting they may be involved in testis-specific gene expression. Compared to less differentiated testis-specific cells, genes of more differentiated cells were found to be (1) more likely to lack a CGI, (2) more likely to lack introns and (3) higher in expression level. The results suggest genes of more differentiated cells have a reduced need for CGI-based regulatory repression, reduced usage of gene splicing and a smaller set of expressed proteins
Gene Cascade Finder: A tool for identification of gene cascades and its application inCaenorhabditis elegans
Authors: Nomoto Yusuke , Kubota Yukihiro , Kasahara Kota , Tomita Aimi , Oshime Takehiro , Yamashita Hiroki , Fahmi Muhamad , Ito Masahiro
Published: March 2019

Obtaining a comprehensive understanding of the gene regulatory networks, or gene cascades, involved in cell fate determination and cell lineage segregation inCaenorhabditis elegansis a long-standing challenge. Although RNA-sequencing (RNA-Seq) is a promising technique to resolve these questions, the bioinformatics tools to identify associated gene cascades from RNA-Seq data remain inadequate. To overcome these limitations, we developed Gene Cascade Finder (GCF) as a novel tool for building gene cascades by comparison of mutant and wild-type RNA-Seq data along with integrated information of protein-protein interactions, expression timing, and domains. Application of GCF to RNA-Seq data confirmed that SPN-4 and MEX-3 regulate the canonical Wnt pathway during embryonic development. Moreover,lin-35, hsp-3, andgpa-12were found to be involved in MEX-1-dependent neurogenesis, and MEX-3 was found to control the gene cascade promoting neurogenesis throughlin-35andapl-1. Thus, GCF could be a useful tool for building gene cascades from RNA-Seq data.
Assessing the multiple dimensions of poverty. Data mining approaches to the 2004-14 Health and Demographic Surveillance System in Cuatro Santos, Nicaragua
Authors: Källestål Carina , Blandón Elmer Zelaya , Peña Rodolfo , Peréz Wilton , Contreras Mariella , Persson Lars-Åke , Sysoev Oleg , Selling Katarina Ekholm
Published: March 2019

We aimed to describe multiple dimensions of poverty according to the capability approach theory by applying data mining approaches to the Cuatro Santos Health and Demographic Surveillance databases, Nicaragua. Four municipalities in northern Nicaragua constitute the Cuatro Santos area, with 25,893 inhabitants in 5,966 households (2014). A local process analyzing poverty-related problems and prioritizing suggested actions, was initiated 1997 based on a community action plan 2002-2015. Priority interventions were school breakfasts, environmental protection, water and sanitation, preventive healthcare, home gardening, micro credits, technical training, stipends for university education, and the use of Internet. In 2004, a survey of basic health and demographic information was performed in the whole population followed by surveillance updates in 2007, 2009, and 2014 linking households and individuals by unique identifiers. Information included the house (floor, walls) and services (water, sanitation, electricity) as well as demographic data (birth, deaths, migration). Data on participation in interventions, on food security, household assets, and women’s self-rated health were collected in 2014. A K-means algorithm were used to cluster the household data (54 variables). The poverty ranking of household clusters using the unsatisfied basic needs index (UBN) variables changed when including variables describing basic capabilities. The households in the fairly rich cluster, having assets as motorbikes and computers were described as modern. Those in the fairly poor cluster, having different degrees of food insecurity were labeled vulnerable. Poor and poorest clusters of households were traditional e.g. in using horses for transport. Results displayed a society transforming from traditional to a modern, where the forerunners were not the richest but educated, had more working members of household, fewer children and were food secure. Those lagging were the poor, traditional and food insecure. The approach and results may be useful for an improved understanding of poverty and to direct local interventions.
Highly reproducible murine model of oralSalmonellainfection via inoculated food
Authors: Nilsson Olof R. , Kari Laszlo , Steele-Mortimer Olivia
Published: March 2019

Oral infection of mice withSalmonellaTyphimurium is an important model system. In particular C57Bl/6 mice, which are susceptible toSalmonella, are used to study both systemic and gastrointestinal pathogenesis. Pretreatment with streptomycin disrupts the intestinal microbiota and results in colitis resembling human intestinalSalmonellosis. Oral gavage is typically used for delivery of both antibiotic and bacteria. Although convenient, this method requires a moderate level of expertise, can be stressful for experimental animals, and may lead to unwanted tracheal or systemic introduction of bacteria. Here, we demonstrate a simple method for oral infection of mice using small pieces of regular mouse chow inoculated with a known number of bacteria. Mice readily ate chow pieces containing up to 108CFUSalmonella, allowing for a wide range of infectious doses. In mice pretreated with streptomycin, infection with inoculated chow resulted in less variability in numbers of bacteria recovered from tissues compared to oral gavage, and highly consistent infections even at doses as low as 103Salmonella. Mice not treated with streptomycin, as well as resistant Nramp1 reconstituted C57Bl/6J mice, were also readily infected using this method. In summary, we show that foodborne infection of mice by feeding with pieces of chow inoculated withSalmonellaresults in infection comparable to oral gavage but represents a natural route of infection with fewer side effects and less variability among mice.
Circulating Th17.1 cells as candidate for prediction of therapeutic response to abatacept in patients with rheumatoid arthritis: exploratory research
Authors: Maeda Shinji , Osaga Satoshi , Maeda Tomoyo , Takeda Norihisa , Tamechika Shin-ya , Naniwa Taio , Niimi Akio
Published: March 2019

T helper 17.1 cells (Th17.1) are highly pathogenic T cells in inflammatory diseases. This study aimed to identify Th cell biomarkers, including the analysis of Th17.1, that predict therapeutic response to abatacept in patients with rheumatoid arthritis. The circulating Th subsets among CD4+ T lymphocytes in 40 patients with rheumatoid arthritis before abatacept treatment were determined using multicolor flow cytometry. All patients received abatacept treatment for 24 weeks, and the change in disease activity score, including 28-joint count C-reactive protein, and the responsiveness of other indices to abatacept treatment were evaluated according the European League Against Rheumatism criteria [good responders, moderate responders, and non-responders]. The correlation between the abatacept responses and the Th subsets (baseline) was analyzed. Logistic regression analysis with inverse probability weighting method was conducted to calculate odds ratio adjusted for patient characteristics. The proportion of baseline Th17.1 cells was significantly lower in patients categorized as good responders than in those categorized as non-good responders (moderate responders and non-responders; p = 0.0064). The decrease in 28-joint count C-reactive protein after 24 weeks of abatacept therapy also showed a significant negative correlation with the proportion of Th17.1 cells. The adjusted odds ratio for achieving good response in patients with baseline Th17.1 level below the median value was 14.6 (95% confidence interval, 2.9–72.3; p = 0.0021) relative to that in the remaining patients. The proportion of Th17.1 cells at baseline is a good candidate for the prediction of response to abatacept treatment. These novel findings may represent an important step in the pursuit of precision medicine.
Characterisation ofStaphylococcus aureuslipids by nanoelectrospray ionisation tandem mass spectrometry (nESI-MS/MS)
Authors: Young Simon A. , Desbois Andrew P. , Coote Peter J. , Smith Terry K.
Published: March 2019

Staphylococcus aureusis a major opportunistic pathogen that is exposed to antimicrobial innate immune effectors and antibiotics that can disrupt its cell membrane. An understanding ofS. aureuslipid composition and its role in defending the cell against membrane-disrupting agents is of fundamental importance. Common methods for characterising lipid profiles suffer shortcomings such as low sensitivity of detection and inferior resolution of the positional assignments of fatty acid chains in lipids. This present study developed a rapid and sensitive nano-electrospray ionisation tandem mass spectrometry (nESI-MS/MS) method to characterise the lipid composition of three commonly studiedS. aureusisolates: Newman, Mu50 and BB270. Confirming previous studies, nESI-MS/MS revealed that phosphatidylglycerols were most abundant inS. aureusmembranes, while diglucosyldiacylglycerols and lysyl-phosphatidylglycerols were also detected. Positional assignments for individual fatty acid chains within these lipids were also determined. Concomitantly, gas chromatography mass spectrometry of the fatty acids validated the molecular characterization and showed the principal species present in each strain were predominately anteiso- and iso-branched chain fatty acids. Though the fatty acid and lipid profiles were similar between theS. aureusstrains, this method was sufficiently sensitive to distinguish minor differences in lipid composition. In conclusion, this nESI-MS/MS methodology can characterise the role of lipids in antimicrobial resistance, and may even be applied to the rapid diagnosis of drug-resistant strains in the clinic.