bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanded Endoscopic Endonasal Transtuberculum Approach for Tuberculum Sellae Meningioma: Operative Video With 360-Degree Fly-Through and Surgical Rehearsal in Virtual Reality: 2-Dimensional Operative Video
Authors: Jean Walter C , Singh Ameet
Published: July 2020

This video demonstrates the technique of the “Expanded Endoscopic Endonasal Transtuberculum Approach” and the utility of preoperative planning and surgical rehearsal in virtual reality (VR).

 VR can be utilized to improve endoscopic skull base surgery in various ways. The patient is a 57-yr-old woman with sudden right abducens palsy. Transcranial surgery has been the gold-standard treatment of the tuberculum sellae meningioma that was found, but for suitable tumors, the endoscopic endonasal approach is equally effective for tumor resection with better visual outcomes.
1-4

 The three-dimensional, 360°, multicolored VR rendering (Surgical Theater SRP7.4.0, Cleveland, Ohio) of her tuberculum sellae meningioma clearly demonstrated that there was no encasement of the anterior cerebral arteries, the tumor did not extend lateral to the carotid arteries, and the surgical corridor was wide enough for endoscopic endonasal resection. The surgical exposure was then rehearsed with the sphenoidectomy and drilling of the sella floor and tuberculum performed in VR space. The step-by-step process of the endoscopic endonasal transtuberculum resection is demonstrated in the operative video.

 Surgical planning in VR can be helpful to the early-career endoscopic surgeon. The three-dimensional renderings are quick to set up (15 min), and the examination of the anatomy is useful for choosing the surgical approach. Despite the lack of haptic feedback and tissue response such as vascularity and firmness in the current software, rehearsing the drilling for exposure can improve the efficiency in surgery.

 Patient consent was obtained prior to the creation of the video and is available on request.
Slow Ascent of Unusually Hot Intermediate Magmas Triggering Strombolian to Sub-Plinian Eruptions
Authors: Lormand C , Zellmer G F , Kilgour G N , Németh K , Palmer A S , Sakamoto N , Yurimoto H , Kuritani T , Iizuka Y , Moebis A
Published: July 2020

To assess whether magma ascent rates control the style of volcanic eruption, we have studied the petrography, geochemistry and size distribution of microlites of plagioclase and pyroxene from historical eruptions from Tongariro, Ruapehu and Ngauruhoe volcanoes located in the southern Taupo Volcanic Zone, New Zealand. The studied deposits represent glassy andesitic and dacitic tephra shards from the Mangamate, Mangatawai, Tufa Trig and Ngauruhoe tephra formations, ranging in age from 11 000 years bp to ad 1996. Covering a range in eruption styles and sizes from Strombolian to Plinian, these samples provide an excellent opportunity to explore fundamental volcanic processes such as pre-eruptive magma ascent processes. Our quantitative petrographic analysis shows that larger microlites (>30 µm) display complex growth zoning, and only the smallest crystals (<30 µm) have formed during magma ascent in the conduit. Using a combination of orthopyroxene geothermometry, plagioclase hygrometry, and MELTS modelling, we show that these microlites nucleated at maximum pressures of 550 MPa (c. 16·5 km) from hot andesitic magmas (1010–1130 °C) with low H2O content (0–1·5 wt%). Size distributions of a total of >60 000 microlites, involving 22 tephras and 99 glass shards, yield concave-up curves, and the slopes of the pyroxene microlite size distributions, in combination with well-constrained orthopyroxene crystal growth rates from one studied tephra, indicate microlite population growth times of ∼3 ± 1 days, irrespective of eruption style. These data imply that microlites form in response to cooling of melts ascending at velocities of <5 cm s–1 prior to H2O exsolution, which occurs only at <33 MPa. Maximum magma ascent rates in the upper conduit, calculated using the exsolution of water during final decompression, range between 3 and 12 m s–1; that is, at least an order of magnitude lower than the hypersonic vent velocities typical of Vulcanian or sub-Plinian eruptions (up to 400 m s–1). This implies that magma ascent from depths of an average of 4 km occurs in dykes, and that vent velocities at the surface are controlled by a reduction of conduit cross-section towards the surface (e.g. dyke changing to cylindrical conduit).
Long-term treatment with tocilizumab in giant cell arteritis: efficacy and safety in a monocentric cohort of patients
Authors: Regola Francesca , Cerudelli Elisabetta , Bosio Giovanni , Andreoli Laura , Tincani Angela , Franceschini Franco , Toniati Paola
Published: July 2020

Objective

The efficacy of tocilizumab (TCZ) in GCA is supported by two randomized controlled studies, in which TCZ allowed remission to be achieved after 52 weeks of treatment. However, after discontinuation of treatment, half of the patients relapsed. The aim of this study was to analyse the efficacy and safety of long-term treatment with TCZ and the role of fluorodeoxyglucose (FDG)-PET/CT scanning in the follow-up of these patients.

Methods

We collected the clinical data of a monocentric cohort of GCA patients retrospectively.

Results

Thirty-two patients were treated with TCZ [25 males and 7 females; age = 74 (59–81) years]. Most of them achieved and maintained clinical remission (1 month: 69%; 3 months: 91%; 6 months: 96%; 12 months: 100%), with serological and FDG-PET/CT scan improvement and a reduction of concomitant glucocorticoid therapy. Nineteen patients were treated for >52 weeks, and in 13 of them a dose tapering was performed, whereas in 2 cases TCZ was suspended for disease remission. Only two patients relapsed: one during TCZ tapering and one after TCZ discontinuation. Ten cases of mild infections and a case of urinary sepsis were reported; in patients treated for >1 year there was no increase in the incidence of side effects compared with patients treated for <12 months.

Conclusion

In our cohort of patients, we confirmed the efficacy of TCZ in the induction and maintenance of remission of GCA, demonstrating an important steroid-sparing effect and a good safety profile. Long-term treatment seems to prevent relapse of the disease, suggesting that TCZ treatment can be continued for >52 weeks with efficacy and safety.
Advancing Reproductive Justice to Close the Health Gap: A Call to Action for Social Work
Authors: Gomez Anu Manchikanti , Downey Margaret Mary , Carpenter Emma , Leedham Usra , Begun Stephanie , Craddock Jaih , Ely Gretchen
Published: July 2020

Reproductive justice is an intersectional social movement, theory, and praxis well aligned with social work’s mission and values. Yet, advancing reproductive justice—the right to have children, to not have children, to parent with safety and dignity, and to sexual and bodily autonomy—has not been a signature area of scholarship and practice for the field. This article argues that it is critical for social work to advance reproductive justice to truly achieve the grand challenge of closing the health gap. The article starts by discussing the history and tenets of reproductive justice and how it overlaps with social work ethics. The authors then highlight some of the ways by which social workers have been disruptors of and complicit in the oppression of individuals, families, and communities with regard to their reproductive rights and outcomes. The article concludes with a call to action and recommendations for social work to foreground reproductive justice in research, practice, and education efforts by centering marginalized voices while reimagining the field’s pursuit of health equity.
Origin and evolution of turiasaur dinosaurs set by means of a new ‘rosetta’ specimen from Spain
Authors: Royo-Torres Rafael , Cobos Alberto , Mocho Pedro , Alcalá Luis
Published: July 2020

Turiasauria is a non-neosauropod eusauropod clade of dinosaurs known since 2006, when the description of Turiasaurus was published. This group, including Losillasaurus, was originally thought to have been restricted to the Late Jurassic of Spain. However, over the last decade, our knowledge of this group has improved with the discovery of new taxa such as Zby from the Portuguese Late Jurassic, Tendaguria from the Tanzanian Late Jurassic and Mierasaurus and Moabosaurus from the Early Cretaceous of the USA. Here, we describe a new specimen of Losillasaurus from Spain, which allows us to better understand the character variation in the cranial and postcranial skeleton. The review of some sauropod fauna of Madagascar, and inclusion of some specimens of Turiasauria, suggest that this clade might have arisen in the Middle Jurassic. According to our phylogenetic results, a specimen found in the early 19th century in Madagascar is shown to be the oldest and only member of Turiasauria represented in the Middle Jurassic thus far. This is named Narindasaurus thevenini gen. & sp. nov.. Turiasauria is thus known from the Middle Jurassic in Pangaea, diversified in the Late Jurassic in Gondwana and Laurasia, and dispersed during the Early Cretaceous to North America.
Tomato Genotype Modulates Selection and Responses to Root Microbiota
Authors: French Elizabeth , Tran Tri , Iyer-Pascuzzi Anjali S.
Published: July 2020

Using microbial inoculants to enhance plant health is promising for crop improvement. However, for success, knowledge of how different cultivars within a crop species select and respond to the root microbiome is critical. The aims of this study were to (i) determine the contribution of tomato genotype to the tomato root bacterial microbiome and (ii) investigate whether closely related tomato genotypes differ in their selection of and response to root endophytes. We used 16S ribosomal RNA amplicon sequencing to examine the root bacterial communities of six Solanum lycopersicum (domesticated tomato) and two S. pimpinellifolium (wild tomato) accessions. We found that, across accessions, both the root endosphere and rhizosphere were affected by genotype. Genotype accounted for 10% of the variation in root microbiota. Two bacterial families, Bacillaceae and Rhizobiaceae, were significantly enriched in the root endosphere in at least six of the eight tomato genotypes. To investigate whether closely related tomato genotypes differed in selection of these endosphere-enriched taxa, we profiled the root endosphere of 20 recombinant inbred lines (RILs) derived from two of the genotypes. The abundance of Bacillaceae and Rhizobiaceae isolates varied quantitatively in the root endosphere of the RILs. Inoculation of 16 RILs with a Bacillaceae isolate identified from the root endosphere of field-grown tomato showed that RIL responses, in terms of shoot and root growth, varied from less than 5% growth enhancement to more than 40%. Our data show that tomato genotypes have distinct but overlapping root bacterial microbiomes and respond differently to specific bacterial endophytes.
The gut microbiota-related metabolite phenylacetylglutamine associates with increased risk of incident coronary artery disease
Authors: Ottosson Filip , Brunkwall Louise , Smith Einar , Orho-Melander Marju , Nilsson Peter M. , Fernandez Céline , Melander Olle
Published: July 2020

Objective:

The gut microbiota is increasingly being implicated in cardiovascular health. Metabolites produced by bacteria have been suggested to be mediators in the bacterial action on cardiovascular health. We aimed to identify gut microbiota-related plasma metabolites and test whether these metabolites associate with future risk of coronary artery disease (CAD).

Methods:

Nontargeted metabolomics was performed using liquid chromatography-mass spectrometry in order to measure 1446 metabolite features in the Malmö Offspring Study (MOS) (N = 776). The gut microbiota was characterized using 16S rRNA sequencing. Gut bacteria-related metabolites were measured in two independent prospective cohorts, the Malmö Diet and Cancer – Cardiovascular Cohort (MDC-CC) (N = 3361) and the Malmö Preventive Project (MPP) (N = 880), in order to investigate the associations between gut bacteria-related metabolites and risk of CAD.

Results:

In MOS, 33 metabolite features were significantly (P < 4.8e-7) correlated with at least one operational taxonomic unit. Phenylacetylglutamine (PAG) was associated with an increased risk of future CAD, using inverse variance weighted meta-analysis of age and sex-adjusted logistic regression models in MDC-CC and MPP. PAG remained significantly associated with CAD (OR = 1.17, 95% CI = 1.06–1.29, P = 1.9e-3) after adjustments for cardiovascular risk factors.

Conclusion:

The levels of 33 plasma metabolites were correlated with the gut microbiota. Out of these, PAG was associated with an increased risk of future CAD independently of other cardiovascular risk factors. Our results highlight a link between the gut microbiota and CAD risk and should encourage further studies testing if modification of PAG levels inhibits development of CAD.
A Case Study of Cutaneous Mastocytoma in a 9-Month-Old Infant
Authors: Jellerichs Bradley , Kim Mary Elizabeth
Published: July 2020

This is a case study of a 9-month-old infant presenting with a blistering lesion on the left foot previously misdiagnosed as a benign birthmark. Pathology revealed cutaneous mastocytoma, which required no further intervention.
The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Pancreatic Neuroendocrine Tumors
Authors: Halfdanarson Thorvardur R. , Strosberg Jonathan R. , Tang Laura , Bellizzi Andrew M. , Bergsland Emily K. , O'Dorisio Thomas M. , Halperin Daniel M. , Fishbein Lauren , Eads Jennifer , Hope Thomas A. , Singh Simron , Salem Riad , Metz David C. , Naraev Boris G. , Reidy-Lagunes Diane L. , Howe James R. , Pommier Rodney F. , Menda Yusuf , Chan Jennifer A.
Published: July 2020

This article is the result of the North American Neuroendocrine Tumor Society consensus conference on the medical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The guidelines panel consisted of medical oncologists, pathologists, gastroenterologists, endocrinologists, and radiologists. The panel reviewed a series of questions regarding the medical management of patients with pancreatic neuroendocrine tumors as well as questions regarding surveillance after resection. The available literature was reviewed for each of the question and panel members voted on controversial topics, and the recommendations were included in a document circulated to all panel members for a final approval.
Improving Accuracy of Handoff by Implementing an Electronic Health Record–generated Tool: An Improvement Project in an Academic Neonatal Intensive Care Unit
Authors: Koo Jenny K. , Moyer Laurel , Castello Michael A. , Arain Yassar
Published: July 2020

Background:

Written patient handoffs are susceptible to errors or incompleteness. The accuracy is dependent on the person inputting the information. Thus, handoff printouts generated by electronic health records (EHR) with automation reduces the risk of transcription errors and improves consistency in format. This single-center quality improvement project aims to increase the accuracy of handoff printouts with an EHR-generated handoff tool.

Methods:

This project used a plan-do-study-act methodology. Participants included registered nurses, neonatal nurse practitioners, neonatal hospitalists, pediatric residents, neonatal fellows, and neonatologists. The goals were to (1) increase accuracy of information to 80%, (2) reduce verbal handoff time by 20%, (3) reduce the frequency of incorrectly listed medications below 20%, and (4) improve user satisfaction by 1 point (on a 5-point Likert scale) over 6 months. Baseline assessment included a survey and a review of handoff reports 4 months before transitioning to the new handoff tool. We created a new handoff tool using EHR autogenerated phrases (Epic SmartPhrases) and autopopulated fields for pertinent Neonatal Intensive Care Unit patient data.

Results:

After the unit-wide implementation of the new tool, the accuracy of 16 patient data points increased from 51% to 97%, while the frequency of patients with incorrectly listed medications decreased from 51% to 0%. Handoff time remained unchanged, while a 5-question user satisfaction survey showed an increase on the Likert scale.

Conclusions:

We demonstrated that handoff printouts generated by EHR have fewer inaccuracies than manually scripted versions and do not add to the time required to give verbal handoff.
Variation in estimated viral suppression associated with the definition of viral suppression used
Authors: Lesko Catherine R. , Chander Geetanjali , Moore Richard D. , Lau Bryan
Published: July 2020

Objective:

The proportion of people living with HIV with suppressed viral load is a key indicator of the HIV care continuum. We explored how this proportion varied depending on how it was calculated.

Design:

Observational cohort study.

Methods:

We calculated the proportion of the Johns Hopkins HIV Clinical Cohort who were virally suppressed each year, 2010–2018, based on different denominators; thresholds for suppression (≤20, ≤50, ≤200, or ≤400 copies/ml); and strategies for summarizing multiple viral load measurements (we classified persons as suppressed if they had any lab, ≥50% of labs, last lab, or all labs below the threshold). We also calculated 5-year risk of all-cause mortality associated with each classification of viral suppression.

Results:

Three thousand eleven persons contributed 60 858 viral load values to this analysis. Proportion classified as virally suppressed ranged from 51.8 to 92.5%, depending on the definition used and persons included in the calculation. Requiring more labs below the threshold; using a lower threshold; and assuming persons lost to follow-up were not suppressed (stricter definitions) resulted in a lower proportion estimated to be suppressed. Suppression by stricter definitions were associated with better 5-year survival.

Discussion:

The proportion suppressed varied greatly as a function of the subset of persons in whom it was calculated, the threshold used for suppression, and the way multiple viral loads per person per year were summarized. Measures of durable viral suppression, and low-level viremia (20–400 copies/ml), should be considered in describing the health of people with HIV, in addition to the standard estimates of suppression.
A Balancing Act
Authors: Manyang Christina , Stene Julie , Pagel Erin M. , Niesen Cynthia
Published: July 2020

High workload and unpredictable shift end times can contribute to employee turnover, dissatisfaction, and low staff engagement. The aim of this project was to improve nurse and patient satisfaction within a hospital-based outpatient gastrointestinal endoscopy unit while moving from an existing three-shift procedure staffing model to a two-shift model with defined expectations and predictable shift end times. The shift modification led to an 82% decrease in nurse turnover rates after the first 6 months. There was a 12% decrease in the number of nurses calling in ill to work. Nurse satisfaction, compared to 2 years prior, demonstrated 21% improvement related to “having a sense of achievement”; 39% improvement with “being involved in work unit decisions”; 62% decrease in burnout; and 7% improvement in overall satisfaction. The number of nurses attending and presenting at national, regional, and local conferences increased. Furthermore, overall unit patient satisfaction improved by 1.94% (p = .063) between first-quarter 2014 preimplementation data (n = 183) and first-quarter 2015 postimplementation survey data (n = 140). The created shared governance environment supported nurses' involvement in decision-making and creating a new shift model that led to greater staff and patient satisfaction.
Achieving Hepatitis C Elimination By Using Person-Centered, Nurse-Led Models of Care
Authors: Richmond Jacqueline A. , Gallagher Lesley , McDonald Lucy , O'Sullivan Margaret , Fitzsimmons Christine , Pedrana Alisa
Published: July 2020

Nurse-led models of care are an important strategy in the management of patients with chronic disease because of the person-centered approach that allows the needs of the individual to be prioritized and addressed in accessible settings. Hepatitis C is caused by a blood-borne virus that can cause liver disease and liver cancer; it predominantly affects marginalized populations, including people who inject drugs. Since 2013, all oral, direct-acting antiviral regimens have been available to cure hepatitis C. Nurses are well placed to be involved in the delivery of hepatitis C testing and treatment because of their extensive reach within marginalized communities and holistic approach to patient care. Four case studies of nurse-led models of care operating in Australia, Canada, the United Kingdom, and the United States are presented to illustrate the important role nurses have in delivering accessible, person-centered hepatitis C testing and treatment. Each case study demonstrates the success of overcoming barriers to hepatitis C testing and treatment such as geographic isolation, incarceration, social marginalization, and inflexible healthcare systems. Achieving the global target to eliminate hepatitis C by 2030 will require the nursing profession to embrace its role as the first point of contact to the healthcare system for many members of marginalized communities potentially at risk of hepatitis C. Nurses are well placed to reduce barriers and facilitate access to healthcare by scaling up activities focused on hepatitis C testing and treatment.
Modelling the maximal active consumption rate and its plasticity in humans—perspectives from hot dog eating competitions
Authors: Smoliga James M.
Published: July 2020

Gut capacity and plasticity have been examined across multiple species, but are not typically explored in the context of extreme human performance. Here, I estimate the theoretical maximal active consumption rate (ACR) in humans, using 39 years of historical data from the annual Nathan's Famous Hot Dog Eating Contest. Through nonlinear modelling and generalized extreme value analysis, I show that humans are theoretically capable of achieving an ACR of approximately 832 g min
−1
fresh matter over 10 min duration. Modelling individual performances across 5 years reveals that maximal ACR significantly increases over time in ‘elite’ competitive eaters, likely owing to training effects. Extreme digestive plasticity suggests that eating competition records are quite biologically impressive, especially in the context of carnivorous species and other human athletic competitions.
Ocean winter warming induced starvation of predator and prey
Authors: Melzner Frank , Buchholz Björn , Wolf Fabian , Panknin Ulrike , Wall Marlene
Published: July 2020

Ocean warming impacts the fitness of marine ectothermic species, leading to poleward range shifts, re-shuffling of communities, and changes in ecosystem services. While the detrimental effects of summer heat waves have been widely studied, little is known about the impacts of winter warming on marine species in temperate regions. Many species benefit from low winter temperature-induced reductions in metabolism, as these permit conservation of energy reserves that are needed to support reproduction in spring. Here, we used a unique outdoor mesocosm system to expose a coastal predator–prey system, the sea star
Asterias
and the blue mussel
Mytilus
, to different winter warming scenarios under near-natural conditions. We found that the body condition of mussels decreased in a linear fashion with increasing temperature. Sea star growth also decreased with increasing temperature, which was a function of unaltered predation rates and decreased mussel body condition.
Asterias
relative digestive gland mass strongly declined over the studied temperature interval (
ca
twofold). This could have severe implications for reproductive capacity in the following spring, as digestive glands provide reserve compounds to maturing gonads. Thus, both predator and prey suffered from a mismatch of energy acquisition versus consumption in warmer winter scenarios, with pronounced consequences for food web energy transfer in future oceans.
Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers
Authors: Kulmuni Jonna , Butlin Roger K. , Lucek Kay , Savolainen Vincent , Westram Anja Marie
Published: July 2020

Speciation, that is, the evolution of reproductive barriers eventually leading to complete isolation, is a crucial process generating biodiversity. Recent work has contributed much to our understanding of how reproductive barriers begin to evolve, and how they are maintained in the face of gene flow. However, little is known about the transition from partial to strong reproductive isolation (RI) and the completion of speciation. We argue that the evolution of strong RI is likely to involve different processes, or new interactions among processes, compared with the evolution of the first reproductive barriers. Transition to strong RI may be brought about by changing external conditions, for example, following secondary contact. However, the increasing levels of RI themselves create opportunities for new barriers to evolve and, and interaction or coupling among barriers. These changing processes may depend on genomic architecture and leave detectable signals in the genome. We outline outstanding questions and suggest more theoretical and empirical work, considering both patterns and processes associated with strong RI, is needed to understand how speciation is completed.

This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers'.
Sympatric speciation in mountain roses (Metrosideros) on an oceanic island
Authors: Osborne Owen G. , Kafle Tane , Brewer Tom , Dobreva Mariya P. , Hutton Ian , Savolainen Vincent
Published: July 2020

Shifts in flowering time have the potential to act as strong prezygotic reproductive barriers in plants. We investigate the role of flowering time divergence in two species of mountain rose (Metrosideros) endemic to Lord Howe Island, Australia, a minute and isolated island in the Tasman Sea.Metrosideros nervulosaandM. sclerocarpaare sister species and have divergent ecological niches on the island but grow sympatrically for much of their range, and likely speciatedin situon the island. We used flowering time and population genomic analyses of population structure and selection, to investigate their evolution, with a particular focus on the role of flowering time in their speciation. Population structure analyses showed the species are highly differentiated and appear to be in the very late stages of speciation. We found flowering times of the species to be significantly displaced, withM. sclerocarpaflowering 53 days later thanM. nervulosa. Furthermore, the analyses of selection showed that flowering time genes are under selection between the species. Thus, prezygotic reproductive isolation is mediated by flowering time shifts in the species, and likely evolved under selection, to drive the completion of speciation within a small geographical area.

This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers’.
Prevalence of Agr phase variants in Staphylococcus aureus
Authors: Gor Vishal , Hoshi Mitsuaki , Takemura Aya , Higashide Masato , Romero Veronica , Ohniwa Ryosuke , Morikawa Kazuya
Published: July 2020

Staphylococcus aureus is an important human pathogen whose success is largely attributed to its vast arsenal of virulence factors that facilitate its invasion into, and survival within, the human host. The expression of these virulence factors is controlled by the quorum sensing Accessory Gene Regulator (Agr) system. However, a large proportion of clinical S. aureus isolates are consistently found to have a mutationally inactivated Agr system. These mutants have a survival advantage in the host but are considered irreversible mutants. Here we show, for the first time, that a fraction of Agr-negative mutants can revert their Agr activity. By serially passaging Agr negative strains and screening for phenotypic reversion of haemolysis and subsequent sequencing, we identified two mutational events responsible for reversion: a genetic duplication plus inversion event and a poly(A) tract alteration. Additionally, we demonstrate that one clinical Agr-negative MRSA isolate could reproducibly generate Agr-revertant colonies with a poly(A) tract genetic mechanism. We also show that these revertants activate their Agr system upon phagocytosis. To assess the significance of our findings we screened a series of primary clinical isolates, which had undergone minimal handling post-isolation, and successfully identified a fraction which were Agr phase variants. Taken together, we propose a model where some Agr-negative S. aureus strains are phase variants who can revert their Agr activity and may act as a cryptic insurance strategy against host-mediated stress.
Aeromonas caviae motility and glycosylation
Authors: Allihaybi Laila
Published: July 2020

Aeromonas are Gram-negative facultative anaerobic rods, which inhabit various aquatic environments and are pathogens of both warm and cold-blooded animals. In humans they cause gastro-enteritis and wound infections. They are motile in liquid environments by a single polar type of flagellum. The flagellum plays an important role for the bacterial colonisation and the adhesion to the host cells. The Aeromonaspolar flagella filament is a polymer composed of two flagellins, FlaA and FlaB. The flagellins are O-linked glycosylated through the addition of the unusual bacterial sugar pseudaminic acid to serine and threonine residues within the flagellins D2/D3 domain. The addition of this sugar is essential for flagella filament assembly and bacterial motility. The flagellin’s are modified by between 6 – 8 sugar residues that occupy the potential 14 sites of attachment. Motility accessory factors (Maf proteins) are candidate enzymes for transferring glycan molecules to the flagellin (glycosyltransferases transferring sugar to flagellin) due to their genetic location and motility phenotypes associated with disruption mutants.

This study utilised site-directed mutagenesis to change the potential sites of flagellin glycosylation to assess the effect of these mutations on motility by swimming assays and flagella filament formation by electron microscopy. The analysis of different numbers of site-directed mutants suggest that some sites are more important than others and that the removal of 4 sites results in greatly reduced motility.
Epidemiological studies of malaria parasite on HIV patients attending General Hospital Awo-Omamma, Oru East, Imo State,Nigeria
Authors: Njoku-Obi Treasure
Published: July 2020

HIV and malaria are the two most prevalent and deadly diseases in the world. Malaria and HIV accounted for about 255 million cases in 2017, with malaria having 86% of this distribution and HIV having 14% of the distribution. Given the overlap of their geographic distribution and resultant rates of coinfection, interactions between the two diseases pose major public health problems. This study was aimed at investigating the epidemiology of malaria –HIV co-infection in respect to sex, age and its association with CD4+ count and viral load. 230 HIV sero-positive participants and 100 HIV sero-negative participants(control) were employed for this study. 52 (22.6%) of the HIV infected participants tested positive for malaria while only 9(9.0%) of the non-HIV participants tested positive to malaria. The prevalence of malarial infection in HIV positive individuals was higher in females (23.9%) than in males (18.5%). While in age group of 30-39 showed the highest prevalence (35.3%) of co-infection. A high prevalence of 47.7% was recorded with CD4+ below 200 cells/μl than 7.6% in participants with CD4+ greater than 200 cells/μl. A highprevalence (49.2%) was also detected in patients with viral load of above 10,000 copies/μl compared to that of those with viral load less than 10,000 copies/μl(12.6%). This study showed a high prevalence of malaria in HIV patients in Awo-Omamma,Oru East, Imo state. This should be considered a great concern to public health. Thus, more effort should be put in research to curb this health issue.
Defining the RND-binding residues of AcrA
Authors: Alav Ilyas , Torres Ricardo , Bavro Vassiliy , Blair Jessica
Published: July 2020

The resistance-nodulation-division (RND) family of efflux pumps confer clinically relevant antibiotic resistance in Gram-negative bacteria, such as Salmonella enterica. RND pumps, including AcrB, are organized as tri-partite systems, consisting of an inner membrane RND pump, a periplasmic adaptor protein (PAP) and an outer membrane channel. Previously, inactivation of the PAPs AcrA and AcrE in S. enterica has been shown to significantly increase susceptibility to antimicrobials and reduce virulence. Therefore, PAPs are seen as attractive targets for the development of efflux pump inhibitors. However, the role of PAPs in the assembly of tri-partite pumps and the residues involved in PAP-RND pump binding is poorly understood. In this study, point mutations in the predicted RND binding residues of AcrA were generated by site-directed mutagenesis. The point mutants were characterised phenotypically through ethidium bromide efflux assays and antimicrobial susceptibility testing. Furthermore, Western blotting was used to verify that the phenotypic effect of the point mutations was not due to destabilisation of the AcrA protein. Point mutations in certain residues, such as G58, F292, R294 and G363 were found to significantly impair efflux activity and increase susceptibility to various antibiotics and dyes, suggesting an important role for these AcrA residues in RND pump binding. Western blotting confirmed that these point mutants were stable and exhibited similar expression levels to the wild-type. These residues could be important targets for the design and development of PAP inhibitors to restore the activity of existing antibiotics and reduce virulence of Salmonella.
Food safety knowledge and hygiene practices among the staff of school feeding scheme in the basic schools of Sewoto, South Africa
Authors: Kwashie Madilo Felix , Z. Mgqibandaba Pretty
Published: July 2020

The study was to evaluate the food safety knowledge and hygiene practices of the staff of the school feeding scheme in Soweto. A total of 42 food handlers in 13 basic schools under the School Feeding Scheme, Soweto, South Africa were recruited for the study using purposive and convenience sampling methods for the respondents and institutions respectively. A piloted self-administered questionnaire was used. All the respondents were female (100%) with majority being between the ages of 31 and 40 (40%) and had secondary education (63%). About 38 (90.5%) of the respondents indicated that food safety is important, hence, identified “promotion of good health 41 (97.6%), avoidance of bacterial infection 39 (92.9%) and prevention of food poisoning 39 (92.9)” as the major importance. Frequent hand washing 40 (95.2%); cleaning and sanitizing knives/cutting boards 40 (95.3%); checking best before date 39 (92.8); keeping kitchen surfaces clean (80.9%) and checking freshness/appearance of the food upon delivery (88.1%) were indicated as very important food safety and hygiene practices. However, they failed to agree that frozen foods, particularly meat are to be thawed using room temperature (4.8%) and also in the lower shelf in the refrigerators (26.2%) as the best practices. Spearman’s correlation coefficient revealed that no correlation exists between food safety knowledge and hygiene practices. However, there was strong positive correlations among educational level, knowledge and practices (P>0.05). Eventhough they have good knowledge and understanding of food safety issues, they still need training and workshops particularly in HACCP to cover-up the lapses.
The fall and rise of group B Streptococcus in dairy cattle: suspected reintroduction from a human reservoir
Authors: Crestani Chiara , Forde Taya , Lycett Samantha , Holmes Mark , Persson-Waller Karin , Zadoks Ruth
Published: July 2020

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a pathogen of humans and cattle, in which it is responsible for carriage or invasive disease and subclinical mastitis, respectively. From the 1950s to 1970s, thanks to successful mastitis control programs, the prevalence of GBS fell in the Swedish cattle population, but it re-emerged in the late 1990s. GBS was thought to consist of host-specific subpopulations but recent studies have shown that human and cattle subpopulations overlap, with different accessory genome elements providing survival advantages in each host species. We hypothesized that cattle-adapted GBS was eradicated and replaced by new GBS strains of human origin.

Our aim was to explore the differences in GBS cattle population over six decades (pre-post non-detection), with a focus on the possible role of MGE in the evolution of these strains.

Historical (n = 44, 1953 to 1978) and contemporary (n = 76, 1997 to 2012) GBS isolates from bovine milk samples were sequenced and analysed for WGS-MLST. Phylogenetic network analysis revealed the presence of six major clades: two of these were detected only up to 1970, two were only detected after 2004, and two were detected in both periods. Historical isolates were all tetracycline sensitive, whereas 51% of recent isolates harboured tet(M), which is considered a marker of human adaptation. Our data support the elimination of a bovine specific clade (CC61/67) and the emergence of new clades (CC1, CC103/314) that are likely of human of origin.
Identification of dengue virus immunodeficiency (IMD) pathway antagonists in Aedes Aegypti cells
Authors: Russell Tiffany , Wallace Louisa , Maringer Kevin
Published: July 2020

The flavivirus dengue virus (DENV) is the most significant arthropod borne virus (arbovirus) of humans, causing serious morbidity and mortality, with nearly half of the world’s population at risk of infection. Due to a lack of antivirals and limited vaccine options, vector control remains a vital defence against dengue disease. The mosquito Aedes aegypti is the major vector for DENV, and understanding mosquito immune responses and how DENV may evade them is critical. We have shown that DENV-2 can inhibit the exogenous induction of immune deficiency (IMD) signalling by classical immune stimuli. Therefore, we aimed to identify DENV antagonists of the IMD pathway, and define the molecular virus and host determinants of IMD antagonism in a well characterised Ae. aegypti derived cell line, Aag2. Each DENV protein was expressed individually in Aag2 cells and tested for their ability to block IMD signalling induced by exogenous stimuli. This screen identified NS4A as a potential antagonist of the IMD pathway. Further, we have found that the N-terminus of NS4A is responsible for this inhibition. The antagonism of IMD signalling is specific to flaviviruses transmitted by a mosquito vector, illustrating the importance of both the IMD pathway for mosquito immunity and the antagonism of this pathway by DENV. By enhancing our understanding of how DENV evades the mosquito immune response at a molecular level, we will gain insight into virus-host interactions constraining arbovirus transmission and emergence, which may be exploited for developing transmission-incompetent vectors to reduce the burden of dengue disease.
Identifying and characterizing a novel Sindbis virus capsid and IRAK1 interaction
Authors: Landers V , Sokoloski Kevin
Published: July 2020

Alphaviruses are arthropod-borne positive-sense RNA viruses that have the capacity to cause large scale outbreaks of severe disease. As of now, there are no effective therapeutic strategies with which alphaviral disease may be treated. Thus, there is a need for research that defines the mechanism(s) by which the alphaviruses establish infection and cause pathogenesis. Our previous work identified non-assembly interactions between the SINV Capsid protein and the viral genomic RNA that were important for viral RNA stabilization early during infection. These efforts led us to evaluate the Protein:Protein interactions of the SINV Capsid protein using the BioID2 discovery approach to define the mechanism of action underlying the SINV Capsid-mediated genome stability.

To our surprise, these efforts indicated that the SINV CP protein interacts with the host IRAK1 protein in tissue culture models of infection. To validate the interface we utilized a Bimolecular Fluorescence Complementation approach to confirm the SINV Capsid-IRAK1 interaction. After confirming the novel Capsid Protein:Protein interaction we hypothesized that the SINV Capsid protein may interfere with IRAK1-dependent signaling during infection. To this end, we assessed the dose-responsiveness of several IRAK1-dependent signaling pathways, including TLRs 4 and 7 in the presence of the SINV Capsid protein. We found that the TLR-agonist response, was significantly decreased in the presence of the SINV Capsid protein. Collectively, these data are highly suggestive that the SINV Capsid protein interferes with TLR signaling during viral infection contributing to the evasion of the host innate immune response.
Analysis of β-lactam, azithromycin and fosfomycin resistance in non-typhoidal Salmonella: Characterisation of an S. Infantis plasmid
Authors: Lee Winnie , Bloomfield Samuel , Mather Alison , Edwards Andrew , Chattaway Marie , Nair Satheesh
Published: July 2020

Non-typhoidal Salmonella (NTS)infections are associated with high morbidity and mortality. β-lactams are used as first-line treatment but resistance to these has increased considerably in recent years. Azithromycin and fosfomycin are used as alternatives; however, the incidence of resistance in these drugs is also increasing. Epidemiological surveillance on 35,372 NTS received by Public Health England was conducted for analysis of demographics, including global travel. Genomic typing and antimicrobial resistance data for Salmonellaisolates were used to determine the prevalence of β-lactam, azithromycin and fosfomycin resistance in NTSover a four year period. No isolates were resistant to β-lactams, azithromycin or fosfomycin alone but all isolates were resistant to multiple antimicrobial classes. IncHI2, IncY and IncN plasmids were predominantly found in the most multi-drug resistant isolates. Multi-drug resistance (MDR) was particularly a concern in the S. Infantis population. Therefore, long read sequencing was used to characterise an MDR S. Infantis isolate. Three drug regions were identified in a IncFIB, a mega plasmid identified in this isolate. The resistance determinants fosA, arsA, arsD and blaCTXM65,were discovered on the same drug region. Analysis of IncFIB in this S.Infantis isolate revealed 99% similarity to a IncFIB plasmid in S. Infantis isolated from chickens in the USA. Thishas not been reported before, warranting efforts for enhanced surveillance programmes to identify sources of emerging resistance, which will aid in establishing control measures for prevention of spread of resistance.
The role of flagella in Pseudomonas-Pedobacter social motility across a surface
Authors: McCully Lucy , Seaton Sarah , McGraw Alana , Silby Mark
Published: July 2020

Bacteria often reside in multi-species communities where many behaviors result from interspecies relationships. In a two-species community, we show that co-culture of Pseudomonas fluorescens and Pedobacter sp. permits motility across a hard agar surface where neither species moves alone. Pseudomonas species engage in surface motility, including swimming and swarming, but these require moist environments. We are exploring the role of the Pseudomonas flagella in social motility. We deleted genes related to flagellar structure and function to study the importance of flagellar elements on the social phenotype. Using microscopy and swimming assays, we evaluate the effects of gene deletions on the presence and function of flagella in the resulting mutants, and evaluate the effect on social motility by observing the phenotype on both hard (2% w/v) and soft agar (1% w/v). Removal of the flagellar filament abolishes social motility, indicating a requirement for flagella in social motility. Removal of the flagellar motor also abolishes social motility, demonstrating that flagella must be functional. However, removal of membrane-spanning structural components, or part of the type III secretion system, results in mutants that lack flagella, but participate in a similar motile behavior with Pedobacter. Here we describe a role for flagella in motility of a two-species consortium across a hard agar surface, an environment considered non-permissive for flagellar motility. The requirement for both bacterial species indicates we are observing motility as a social phenotype, with a contribution from Pedobacter that enables the Pseudomonas flagella to function under conditions relevant in the natural soil environment.
How environment shapes horizontal gene transfer
Authors: Bhatia Rama , Kirit Hande , Bollback Jonathan
Published: July 2020

The evolutionary fate of a horizontal gene transfer (HGT) event is determined by its fitness on the recipient cell, i.e., whether it is beneficial, neutral or deleterious. The distribution of fitness effects (DFE), thus is a fundamental predictor of the outcome of an HGT event.

The environment plays a considerable role in determining the fitness cost of a horizontally transferred gene. We have studied the fitness effects of genes transferred from Salmonella enterica serovar Typhimurium to Escherichia coli in six environments, that potentially represent the conditions experienced by the two species. The data suggests high variability of genes in different environments. Genes, whose fitness varies substantially between environments, may be able to persist in populations while being deleterious in one environment, they may be neutral or even beneficial in another environment, suggesting that environmental fluctuations may increase the likelihood of HGT.

In addition to the in vitro environments, we are also looking at, how changes in the intrinsic environment of a cell, after an HGT event, could affect fitness. An increase in protein dosage due to functional similarity of the horizontally transferred gene to the endogenous gene can cause an imbalance in the cell, thereby leading to a negative fitness effect. By comparing the growth rates of each ortholog gene with the wild type strain, we can elucidate when gene dosage acts as a barrier to HGT.