bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex as a biological variable in irritable bowel syndrome
Authors: Camilleri Michael
Published: January 2020

Background

The pathophysiology and mechanisms of irritable bowel syndrome (IBS) involve both central and peripheral mechanisms that result in altered perception, as well as changes in bowel functions. These dysfunctions are associated with motor, sensory, immune, barrier, and intraluminal perturbations, including the microbiota, and their products and endogenous molecules with bioactive properties. There is evidence that these mechanisms are altered in both females and males. However, there is also increasing evidence that sex is a biological variable that impacts a number of aspects of the mechanisms, epidemiology, and manifestations of IBS.

Purpose

The objective of this article is to review the evidence of the differences among genders of the following factors in IBS: the brain‐gut axis and sex hormones, epidemiology, diagnostic criteria and prognosis, pain perception, colonic transit, abdominal distension, overlap with urogynecological conditions, psychologic issues, anorexia, fibromyalgia, serotonin, and responsiveness to treatment of IBS. It is important to consider the variations attributable to sex in order to enhance the management of patients with IBS and the research of mechanisms involved in IBS.
The complete functional characterisation of the terpene synthase family in tomato
Authors: Zhou Fei , Pichersky Eran
Published: January 2020

Analysis of the updated reference tomato genome found 34 full‐length TPS genes and 18 TPS pseudogenes.

Biochemical analysis has now identified the catalytic activities of all enzymes encoded by the 34 TPS genes: one isoprene synthase, 10 exclusively or predominantly monoterpene synthases, 17 sesquiterpene synthases and six diterpene synthases. Among the monoterpene and sesquiterpene and diterpene synthases, some use trans‐prenyl diphosphates, some use cis‐prenyl diphosphates and some use both. The isoprene synthase is cytosolic; six monoterpene synthases are plastidic, and four are cytosolic; the sesquiterpene synthases are almost all cytosolic, with the exception of one found in the mitochondria; and three diterpene synthases are found in the plastids, one in the cytosol and two in the mitochondria.

New trans‐prenyltransferases (TPTs) were characterised; together with previously characterised TPTs and cis‐prenyltransferases (CPTs), tomato plants can make all cis and trans C10, C15 and C20 prenyl diphosphates. Every type of plant tissue examined expresses some TPS genes and some TPTs and CPTs.

Phylogenetic comparison of the TPS genes from tomato and Arabidopsis shows expansions in each clade of the TPS gene family in each lineage (and inferred losses), accompanied by changes in subcellular localisations and substrate specificities.
Multidisciplinary education improves school personnel’s self‐efficacy in managing food allergy and anaphylaxis
Authors: Polloni Laura , Baldi Ileana , Lazzarotto Francesca , Bonaguro Roberta , Toniolo Alice , Gregori Dario , Muraro Antonella
Published: January 2020

Background

Despite a relatively high risk for allergic reactions, including anaphylaxis, schools are not sufficiently trained and confident in handling children suffering from food allergy. This study aimed to measure the improvement of school personnel's self‐efficacy in managing food allergy and anaphylaxis at school after a specific multidisciplinary training course.

Methods

A total of 592 teachers and school caretakers completed the School Personnel Self‐Efficacy‐Food Allergy and Anaphylaxis Questionnaire (S.PER.SE‐FAAQ) before and after the course. The median difference, along with I quartile and III quartile, in scores between baseline and post‐intervention assessment was calculated. A conditional regression tree was fitted for each outcome measured after the educational intervention.

Results

At baseline, school personnel reported low self‐efficacy in anaphylaxis management (AM), especially in recognizing anaphylaxis symptoms and administering proper drugs. After the specific multidisciplinary training course, all scores improved. AM scores particularly showed a significant increase. School personnel's post‐training self‐efficacy was found to be related to initial levels. Some indicative threshold values emerged. Remarkably, participants with a low self‐efficacy at baseline seemed to particularly benefit from the training.

Conclusions

Results highlighted the effectiveness of specific multidisciplinary training courses in improving teachers’ and school caretakers’ self‐efficacy in managing food allergy and anaphylaxis. The S.PER.SE‐FAAQ is confirmed to be an easy and helpful tool to assess the level of food allergy and anaphylaxis management in the school staff and training effectiveness.
[11C]raclopride positron emission tomography study of dopamine‐D2/3 receptor binding in patients with severe major depressive episodes before and after electroconvulsive therapy and compared to control subjects
Authors: Tiger Mikael , Svensson Jonas , Liberg Benny , Saijo Tomoyuki , Schain Martin , Halldin Christer , Farde Lars , Lundberg Johan
Published: January 2020

Aim

The aim of the study was to test: (i) if D2/D3 binding in three functional subsections of striatum is different in patients with severe major depressive episodes than in controls; and (ii) if this difference is normalized after electroconvulsive therapy (ECT).

Methods

Nine inpatients were examined with positron emission tomography (PET) and the radioligand [11C]raclopride before and after an average of 8.4 ECT sessions. Treatment response was assessed using the Montgomery–Åsberg Depression Rating Scale. Nine age‐ and sex‐matched controls were examined twice with PET and [11C]raclopride.

Results

[11C]raclopride binding was significantly lower in all three subsections of striatum in patients compared to controls (Cohen's dz, 1.14–1.68; P = 0.003–0.027). Montgomery–Åsberg Depression Ratings decreased significantly after ECT (P < 0.001; Cohen's dz, 2.9). ECT had no statistically significant effect on [11C]raclopride binding, although post‐ECT binding estimates were more similar to those obtained in controls in all subsections of striatum.

Conclusion

Using PET and [11C]raclopride, we found support for the notion that severe major depressive episodes are associated with significantly lower dopamine D2/D3 binding in all three subsections of striatum compared to controls. We noted no significant effect on D2/D3 binding in the patient group after response to ECT.
Contemporary outcomes of the pediatric kidney transplant program in Johannesburg, South Africa, between 2004 and 2017: Better or not—And which way forward?
Authors: Mshumpela Cleopatra N. , Loveland Jerome , Botha Rene , Britz Russel , Levy Cecil , Maher Heather , Withers Aletha , Fabian June , Botha Jean
Published: January 2020

Background

Outcomes for the pediatric kidney transplant program in Johannesburg (1984‐2003) were found to be suboptimal. In this study, we compared (a) early (era 1:1984‐2003) to contemporary (era 2:2004‐2017) outcomes and (b) compared contemporary outcomes between the public and private sector hospitals in our program.

Methods

We conducted a retrospective record review of all pediatric (<18 years) KA transplants performed in our kidney transplant program at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and Wits Donald Gordon Medical Centre (WDGMC) from 2004 to 2017. We collected the following data per site: number of recipients, transplants performed, mean follow‐up time, and grafts lost; per recipient: age at time of transplant, sex, self‐reported population group; transplant history; donor type; etiology of ESKD; recipient and graft survival. Outcomes for era 1 were based on data published on our kidney transplant program, based at CMJAH.

Results

At CMJAH (public sector), there was no improvement in recipient and graft survival over time. In the contemporary analysis, 1‐, 5‐, and 10‐year recipient survival, as % (95% CI) was 93 (84‐97); 76 (64‐84); 59 (44‐70) for CMJAH, and 98 (90‐99); 95 (86‐99); 82 (54‐94) for WDGMC (private sector). Similarly, 1‐, 5‐ and 10‐year graft survival was 75 (63‐84); 55 (42‐66); 36 (24‐49) for CMJAH, and 96 (87‐99); 84 (73‐91); 64 (48‐76) at WDGMC.

Conclusion

Contemporary outcomes for the pediatric kidney transplant program at WDGMC are comparable to outcomes achieved in middle‐ and high‐income settings. However, outcomes at CMJAH are suboptimal, reflecting numerous health system, infrastructural and human resource challenges.
Responses of grassland snakes to tallgrass prairie restoration
Authors: King Richard B. , Vanek John P.
Published: January 2020

Understanding faunal responses to habitat restoration is important in assessing restoration success. We investigated occupancy and abundance of snakes at Nachusa Grasslands, a large‐scale grassland restoration in the midwestern United States. Using artificial cover objects, we sampled within a chronosequence of 12 units converted from row‐crop agriculture 2–25 years before the start of our study. Recaptures of marked snakes revealed that movement distances differed among species in accordance with differences in body size, being least in Dekay's Brownsnakes, intermediate in the Plains Gartersnakes and Common Gartersnakes, and greatest in Eastern Foxsnakes. Consistent with this result, occupancy increased with restoration age in Dekay's Brownsnakes but was unrelated to restoration age in the three larger, more mobile species. Similarly, abundance increased with restoration age in Dekay's Brownsnake but was unrelated to restoration age in other species. The Smooth Greensnake, another small‐bodied snake with limited mobility, and an Illinois species of greatest conservation need, was not detected at Nachusa Grasslands. Given detection probabilities observed during a parallel study at a nearby large grassland‐dominated preserve, we infer that the Smooth Greensnake is truly absent from Nachusa Grasslands. Taken together, our results demonstrate that establishment of faunal components following restoration may be time‐dependent with more sedentary species colonizing only slowly (e.g. Dekay's Brownsnakes) or not at all (e.g. Smooth Greensnakes). These results emphasize the need to clearly identify faunal restoration goals and the means to achieve them.
Chewing ability and oral health‐related quality of life in frail elders after new complete dentures insertion: A paired controlled clinical trial
Authors: Figueredo Olívia Maria Costa , Câmara‐Souza Mariana Barbosa , Carletti Talita Malini , Rodrigues Garcia Renata Cunha Matheus
Published: January 2020

Aims

To compare the effect of new complete dentures (CDs) on self‐perceived masticatory ability (MA) and oral health‐related quality of life (OHRQoL) in frail and nonfrail elders.

Methods and results

Twenty completely edentulous elders were assigned to two groups: frail and nonfrail (n = 10/each). MA was evaluated using a visual analogue scale. OHRQoL was assessed with the Oral Health Impact Profile (OHIP‐Edent). Variables were evaluated with volunteers wearing their old and unsatisfactory CDs. Then, a new set of CDs was manufactured and all outcomes were reassessed 2 months after the insertion. Data were analyzed by repeated measures’ analyses of variance and Tukey tests. MA for lettuce and peanuts was improved (P < .05) for the frail group after new CD insertion. Psychological discomfort and handicap OHIP‐Edent domain improved (P < .05) for both groups after prosthetic treatment. Before treatment, controls reported greater psychological discomfort than the frail group. Meanwhile, the handicap domain score of frail patients improved to a level similar to that of the nonfrail group after treatment. Regardless of frailty, elders showed better MA scores for most food types after treatment and decreased OHIP‐Edent domain values.

Conclusion

Self‐reported MA and OHRQoL of frail elderly people were greatly improved after new CD use.
Public policy and programs – Missing links in growing home dialysis in the United States
Authors: Abra Graham , Schiller Brigitte
Published: January 2020

Patients with end‐stage kidney disease (ESKD) require dialysis or a kidney transplant for survival and over 760 000 patients now benefit from these therapies in the United States. Dialysis in the United States in the late 1960s and early 1970s was often done in the home. After the advent of Medicare coverage for ESKD in 1972 and the subsequent easier access to center based hemodialysis, the use of home modalities dramatically declined. This stands in contrast to home dialysis uptake in other industrialized healthcare systems where both peritoneal dialysis and home hemodialysis are more frequently used. Characteristics unique to the US healthcare system as well as the cultures of providers (physicians and dialysis providers) and recipients of ESKD care are hypothesized as the main reasons for observed differences in home dialysis use. To address these issues, the Centers for Medicare and Medicaid Services have recently proposed new payment programs under an Executive Order from the President of the United States, with the explicit goal of increasing the number of patients using home dialysis. This perspective outlines policy opportunities and programs with a proven track record of home dialysis growth in other countries or hypothesized promise based on identified barriers and needs.
Inference under pivotal sampling: Properties, variance estimation, and application to tesselation for spatial sampling
Authors: Chauvet Guillaume , Le Gleut Ronan
Published: January 2020

Unequal probability sampling is commonly used for sample selection. In the context of spatial sampling, the variables of interest often present a positive spatial correlation, so that it is intuitively relevant to select spatially balanced samples. In this article, we study the properties of pivotal sampling and propose an application to tesselation for spatial sampling. We also propose a simple conservative variance estimator. We show that the proposed sampling design is spatially well balanced, with good statistical properties and is computationally very efficient.
Hypothesis testing for quantitative trait locus effects in both location and scale in genetic backcross studies
Authors: Liu Guanfu , Li Pengfei , Liu Yukun , Pu Xiaolong
Published: January 2020

Testing the existence of a quantitative trait locus (QTL) effect is an important task in QTL mapping studies. Most studies concentrate on the case where the phenotype distributions of different QTL groups follow normal distributions with the same unknown variance. In this paper we make a more general assumption that the phenotype distributions come from a location‐scale distribution family. We derive the limiting distribution of the likelihood ratio test (LRT) for the existence of the QTL effect in both location and scale in genetic backcross studies. We further identify an explicit representation for this limiting distribution. As a complement, we study the limiting distribution of the LRT and its explicit representation for the existence of the QTL effect in the location only. The asymptotic properties of the LRTs under a local alternative are also investigated. Simulation studies are used to evaluate the asymptotic results, and a real‐data example is included for
illustration.
Model approaches to advance crassulacean acid metabolism system integration
Authors: Chomthong Methawi , Griffiths Howard
Published: January 2020

This review summarises recent progress in understanding crassulacean acid metabolism (CAM) systems and the integration of internal and external stimuli to maximise water‐use efficiency. Complex CAM traits have been reduced to their minimum and captured as computational models, which can now be refined using recently available data from transgenic manipulations and large‐scale omics studies. We identify three key areas in which an appropriate choice of modelling tool could help capture relevant comparative molecular data to address the evolutionary drivers and plasticity of CAM. One focus is to identify the environmental and internal signals that drive inverse stomatal opening at night. Secondly, it is important to identify the regulatory processes required to orchestrate the diel pattern of carbon fluxes within mesophyll layers. Finally, the limitations imposed by contrasting succulent systems and associated hydraulic conductance components should be compared in the context of water‐use and evolutionary strategies. While network analysis of transcriptomic data can provide insights via co‐expression modules and hubs, alternative forms of computational modelling should be used iteratively to define the physiological significance of key components and informing targeted functional gene manipulation studies. We conclude that the resultant improvements of bottom‐up, mechanistic modelling systems can enhance progress towards capturing the physiological controls for phylogenetically diverse CAM systems in the face of the recent surge of information in this omics era.
Keloid scarring or disease: Unresolved quasi‐neoplastic tendencies in the human skin
Authors: Ud‐Din Sara , Bayat Ardeshir
Published: January 2020

Keloids are benign fibroproliferative dermal scars of unknown etiopathogenesis resulting in an exophytic protuberant growth with persistent and progressive peri‐lesional expansile behavior. Keloids are likened to benign neoplastic lesions due to their aggressive clinical behavior, genotypic‐phenotypic tissue characteristics, and resistance to treatment. Keloids are traditionally viewed as scars on the healing spectrum; however, keloids are a distinct pathology provoked by cutaneous injury rather than a continuum. In order to elucidate the etiopathogenesis of keloids, the distinction between scar and disease must be made. Therefore, we hypothesize that the link between keloids and their quasi‐neoplastic tendencies distinguish it as a disease rather than a scar alone. The biomarker expression profile in these diseases highlight the striking parallels between keloids and both benign and malignant mesenchymal tumors. Signaling pathways common to these diseases have been found to guide the matrix composition of keloids. This hypothesis underscores the need to identify keloids not as a scar but as a disease in order to develop targeted therapy, which can lead to enhanced diagnosis and theranosis.
Computational and Experimental Study of Hot Streak Transport Within the First Stage of a Gas Turbine
Authors: Gaetani Paolo , Persico Giacomo , Pinelli Lorenzo , Marconcini Michele , Pacciani Roberto
Published: January 2020

The paper discusses the migration, the interaction with the blades, and the attenuation of hot streaks generated by combustor burners, during their propagation within the first turbine stage of aero-engines. Experiments and computational fluid dynamics (CFD) simulations were carried out in the framework of the European Project RECORD and on its follow-up. Measurements considering burner-representative temperature perturbations injected upstream of an un-cooled high-pressure gas turbine stage were performed in the high-speed closed-loop test-rig of the Politecnico di Milano (Italy). The hot streaks were injected in a streamwise direction at the stage inlet in four different circumferential positions with respect to the stator blade. They feature a 20% over-temperature with respect to the main flow. Detailed temperature measurements as well as unsteady aerodynamic measurements upstream and downstream of the blade rows were performed. Time-accurate CFD simulations of the flow upstream and within the turbine stage were performed with the TRAF code, developed by the Università degli Studi di Firenze (Italy). Measurements show a relevant attenuation of hot streaks throughout their transport within the stator and the rotor blade rows, highly depending on the injection azimuthal position. The perturbations were observed to lose their spatial coherence, especially in the transport within the rotor, and to undergo severe spanwise migration. Simulations exhibit a good agreement with the experiments on the measurement planes and allow tracking the complex flow phenomena occurring within the blade rows. Finally, the aerodynamic and thermal implications of the inlet temperature perturbations are properly highlighted and discussed.
Improving Healthcare Access: A Preliminary Design of a Low-Cost Arm Rehabilitation Device
Authors: Piovesan Davide , Kumar Shanmugam Santhosh , Arumugam Yuvarajan , Restifo Adam , Jackson Corey , Devine Nicholas , Legters Kristine
Published: January 2020

A low-cost continuous passive motion (CPM) machine, the Gannon Exoskeleton for Arm Rehabilitation (GEAR), was designed. The focus of the machine is on the rehabilitation of primary functional movements of the arm. The device developed integrates two mechanisms consisting of a four-bar linkage and a sliding rod prismatic joint mechanism that can be mounted to a normal chair. When seated, the patient is connected to the device via a padded cuff strapped on the elbow. A set of springs have been used to maintain the system stability and help the lifting of the arm. A preliminary analysis via analytical methods is used to determine the initial value of the springs to be used in the mechanism given the desired gravity compensatory force. Subsequently, a multibody simulation was performed with the software simwise 4D by Design Simulation Technologies (DST). The simulation was used to optimize the stiffness of the springs in the mechanism to provide assistance to raising of the patient's arm. Furthermore, the software can provide a finite element analysis of the stress induced by the springs on the mechanism and the external load of the arm. Finally, a physical prototype of the mechanism was fabricated using polyvinyl chloride (PVC) pipes and commercial metal springs, and the reaching space was measured using motion capture. We believed that the GEAR has the potential to provide effective passive movement to individuals with no access to postoperative or poststroke rehabilitation therapy.
Improved Treatment of Postpartum Hemorrhage: Design, Development, and Bench-Top Validation of a Reusable Intrauterine Tamponade Device for Low-Resource Settings
Authors: Hu Katherine , Lapinski Maya M. , Mischler Gavin , Allen Robert H. , Manbachi Amir , Seay Rachel Chan
Published: January 2020

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide, and effective interventions for addressing PPH are urgently needed. Uterine balloon tamponade (UBT) is a technique to control PPH. Commercially available UBT devices are expensive and frequently require imaging technology to ensure placement. Condom-catheter uterine tamponade (C-UBT) is a technique appropriate for low-resource settings. Testing of the C-UBT is needed to better understand and optimize this technique for use in a variety of clinical settings including low-resource contexts. We describe here the design, development, and bench-top validation of a reusable C-UBT device optimized for low-resource settings. The device was tested in three differently sized uterine models using a variety of condom balloon configurations. Intrauterine wall pressure application was measured to evaluate the device capacity to apply pressure of at least 90 mmHg, estimating the mean arterial pressure within the uterine vasculature. Bench-top experimental validation of pressure exerted in uterine models demonstrated the device's capability of reaching hemostatic pressure in uterine volumes ranging from 170 to 1740 mL. Device adaptability and versatility were shown through its ability to reach the target pressure of 90 mmHg in different uterine sizes by varying balloon parameters, including condom thickness and condom configuration. The results of this study show the potential of a low-cost, reusable C-UBT device optimized to treat PPH in a variety of clinical settings, including low-resource contexts.
A Novel Intermediate Attachment to Reduce Contamination in Reusable Core Needle Biopsy Devices
Authors: Berges Alexandra J. , Callanan Megan , Zawicki Valerie , Shi Richard , Athey Thomas , Ayyappan Vinay , Metzger Schuyler , Farrell Alanna , Manbachi Amir , Harvey Susan , Durr Nicholas J.
Published: January 2020

One barrier to breast cancer diagnosis in low-resource settings is that devices for core needle biopsy (CNB) are either disposable and expensive, or reusable and susceptible to internal contamination. Through interviews with field workers and verification experiments, we identified that a common, commercially available, reusable CNB device allows contaminants to enter the driver chamber during firing, necessitating laborious cleaning of the entire device after every use. We introduce a novel CNB device attachment that eliminates this contamination mode and interfaces with existing commercial reusable drivers and low-cost disposable needles. This attachment repositions the driver–needle connection to the exterior of the driver, preventing retrograde flow of blood. Using an unmodified commercial CNB, we replicate chamber contamination by firing into a body fluid-mimicking glycerol solution. Prototypes were tested for their performance in eliminating this contamination. We tested the effectiveness of a cleaning procedure to reduce trace contamination by using a fluorescent dye and measuring the intensity of fluorescence after cleaning. The device's ability to reliably and consistently biopsy tissue with the novel attachment was evaluated using breast tissue models. In these tests, a reusable CNB with our attachment exhibited no measurable internal contamination, and maintained full biopsy functionality as measured by tissue sample weight and length. Minimizing internal device contamination would simplify the cleaning process for reusable biopsy devices. This would improve the accessibility of breast cancer biopsies in low- and middle-income countries (LMICs).
Thermal etching of AlF3 and thermal atomic layer etching of Al2O3
Authors: Fischer Andreas , Routzahn Aaron , Lee Younghee , Lill Thorsten , George Steven M.
Published: January 2020

Thermal etching of AlF3 with dimethyl-aluminum chloride (DMAC) and thermal isotropic atomic layer etching (ALE) of Al2O3 with alternating anhydrous hydrogen fluoride (HF) and DMAC steps were studied. DMAC vapor etches AlF3 spontaneously at substrate temperatures above 180 °C. The thermal etching reaction of AlF3 with DMAC exhibited no self-limitation and showed a linear dependence on DMAC pressure. The authors determined an activation energy of 1.2 eV for this reaction. When Al2O3 is fluorinated, DMAC removes the fluorinated layer partially. The etch amount per cycle (EPC) in thermal isotropic ALE of Al2O3 with HF/DMAC is primarily determined by the fluorination step placing significant importance on its design. Fluorination with HF gas was found to be more effective and repeatable than with NF3. Plasma fluorination is faster and provides higher EPC, but the selectivity to Si3N4 or SiO2 mask materials is compromised. For pressures between 10 and 110 mTorr and a substrate temperature of 250 °C, thermal ALE of Al2O3 with HF/DMAC was found to have a very high selectivity to SiO2 and amorphous silicon. HfO2, however, etched with similar EPC as Al2O3.
Sediment interval velocities from a monostatic multibeam sonar
Authors: Holland Charles W. , Pinson Samuel
Published: January 2020

Interval velocities for marine sediments are generally obtained from source-receiver separations at various offsets. A method is described for estimating interval velocities using a monostatic configuration. Testing is performed using simulated data from rough layered seabeds and interval velocity is estimated within less than 1% of the true value. Monostatic multibeam data from the Gulf of Lion are also presented which exhibit many characteristics similar to the simulated data. The method applied to the measured data yield an interval velocity of 1569 m/s in an 18 m sediment layer. This accords with nearby independent data from cores and wide-angle reflection analysis.
Silver Ions Caused Faster Diffusive Dynamics of Histone-Like Nucleoid-Structuring Proteins in Live Bacteria
Authors: Sadoon Asmaa A. , Khadka Prabhat , Freeland Jack , Gundampati Ravi Kumar , Manso Ryan H. , Ruiz Mason , Krishnamurthi Venkata R. , Thallapuranam Suresh Kumar , Chen Jingyi , Wang Yong
Published: January 2020

As so-called “superbug” bacteria resistant to commonly prescribed antibiotics have become a global threat to public health in recent years, noble metals, such as silver, in various forms have been attracting broad attention due to their antimicrobial activities. However, most of the studies in the existing literature have relied on the traditional bioassays for studying the antimicrobial mechanism of silver; in addition, temporal resolution is largely missing for understanding the effects of silver on the molecular dynamics inside bacteria. Here, we report our study of the antimicrobial effect of silver ions at the nanoscale on the diffusive dynamics of histone-like nucleoid-structuring (H-NS) proteins in live bacteria using single-particle-tracking photoactivated localization microscopy. This work highlights the importance of dynamic study of single proteins in live cells for understanding the functions of antimicrobial agents in bacteria.
Stepping Up to the Plate(let) against Candida albicans
Authors: Schultz Christina M. , Goel Arukshita , Dunn Allison , Knauss Hanna , Huss Chadwick , Launder Dylan , Wuescher Leah M. , Conti Heather R. , Worth Randall G.
Published: January 2020

Candida albicans
is a pervasive commensal fungus that is the most common pathogen responsible for invasive fungal infection (IFI). With incidence of IFI on the rise due to increasing susceptible populations, it is imperative that we investigate how
Candida albicans
interacts with blood components. When stimulating either human or mouse whole blood with thrombin, we saw a significant decrease in
C. albicans
survival. We then repeated
Candida
killing assays with thrombin-stimulated or unstimulated washed platelets and saw a similar decrease in CFU.
Nascent Transcriptomics Reveal Cellular Prolytic Factors Upregulated Upstream of the Latent-to-Lytic Switch Protein of Epstein-Barr Virus
Authors: Frey Tiffany R. , Brathwaite Jozan , Li Xiaofan , Burgula Sandeepta , Akinyemi Ibukun A. , Agarwal Saurabh , Burton Eric M. , Ljungman Mats , McIntosh Michael T. , Bhaduri-McIntosh Sumita
Published: January 2020

Transition from latency to the lytic phase is necessary for herpesvirus-mediated pathology as well as viral spread and persistence in the population at large. Yet, viral genomes in only some cells in a population of latently infected cells respond to lytic triggers, resulting in subpopulations of responsive/lytic and refractory cells. Our investigations into this partially permissive phenotype of the herpesvirus Epstein-Barr virus (EBV) indicate that upon exposure to lytic triggers, certain cellular genes are transcriptionally upregulated, while viral latency genes are downregulated ahead of expression of the viral latent-to-lytic switch protein. These cellular genes contribute to lytic susceptibility to various degrees. Apart from indicating that there may be a cellular “prolytic” state, our findings indicate that (i) early transcriptional upregulation of cellular genes counters the well-known viral-nuclease-mediated host shutoff and (ii) subsequent transcriptional downregulation of a subset of early upregulated cellular genes is a previously undescribed mode of host shutoff.
Roles of the Different Isoforms of the Pseudorabies Virus Protein Kinase pUS3 in Nuclear Egress
Authors: Sehl Julia , Pörtner Sandy , Klupp Barbara G. , Granzow Harald , Franzke Kati , Teifke Jens P. , Mettenleiter Thomas C.
Published: January 2020

A plethora of substrates and functions have been assigned to the alphaherpesviral pUS3 kinase, including a role in nuclear egress. In PrV, two different pUS3 isoforms are expressed, which differ in size, abundance, and intracellular localization. Their respective role in replication is unknown, however. Here, we show that efficient nuclear egress of PrV requires the smaller isoform and intact kinase activity, whereas absence of the larger isoform has no significant effect on viral replication. Thus, there is a clear distinction in function between the two US3 gene products of PrV.
Influences of Ingredients and Bakers on the Bacteria and Fungi in Sourdough Starters and Bread
Authors: Reese Aspen T. , Madden Anne A. , Joossens Marie , Lacaze Guylaine , Dunn Robert R.
Published: January 2020

Sourdough starters are complex communities of yeast and bacteria which confer characteristic flavor and texture to sourdough bread. The microbes present in starters can be sourced from ingredients or the baking environment and are typically consistent over time. Herein, we show that even when the recipe and ingredients for starter and bread are identical, different bakers around the globe produce highly diverse starters which then alter bread acidity and flavor. Much of the starter microbial community comes from bread flour, but the diversity is also associated with differences in the microbial community on the hands of bakers. These results indicate that bakers may be a source for yeast and bacteria in their breads and/or that bakers’ jobs are reflected in their skin microbiome.
Children and young people with inflammatory bowel disease attend less school than their healthy peers
Authors: Barnes Claire , Ashton James John , Borca Florina , Cullen Mick , Walker Dawn-Marie , Beattie Robert Mark
Published: January 2020

Objective

Chronic diseases, such as inflammatory bowel disease (IBD), can impact negatively on education and social development. Examining the impact of IBD on school/college attendance for children and young people (CYP) is vital to provide targeted support to patients, families and schools.

Methods

We performed a cross-sectional survey to determine the school/college attendance rates, the reasons for absence related to IBD and facilitators or barriers to school/college attendance. In a subset of patients followed up locally, we performed a detailed review of hospital attendance data to assess healthcare burden.

Results

Two hundred and thirty-one questionnaires were given to CYP with IBD aged 5–17 years. Response rate was 74% (final sample 169). The median school/college attendance rate was 92.5%, significantly lower than all children in England (95.2%). 39.6% of children with IBD were persistently absent, defined nationally as missing 10% or more of school. Only five children (3%) had a 100% attendance record. Increasing age and use of monoclonal therapy were predictors of poor school attendance. Concerns about feeling unwell at school/college, access to toilets, keeping up with work and teachers’ understanding of IBD are the main issues for CYP with IBD. There was a significant negative correlation between number of days in hospital and school attendance.

Conclusion

IBD has a significant impact on school/college attendance, with hospital attendance, disease burden and school difficulties being major factors. Employing strategies to minimise healthcare burden and developing a partnership between health and education to support children with IBD will serve to facilitate school/college attendance.
Patterns of long-term ADHD medication use in Australian children
Authors: Efron Daryl , Mulraney Melissa , Sciberras Emma , Hiscock Harriet , Hearps Stephen , Coghill David
Published: January 2020

Objective

Adherence to attention-deficit/hyperactivity disorder (ADHD) medication treatment is often suboptimal. This can compromise patient outcomes. We aimed to describe the patterns of ADHD medication use in Australian children, and characteristics associated with patterns of use.

Design

Dispensing data were analysed for all redeemed prescriptions of methylphenidate, dexamphetamine and atomoxetine between May 2002 and March 2015 from waves 1 to 6 of the Longitudinal Study of Australian Children (n=4634, age 4–5 years at wave 1). Medication coverage was defined as the proportion of time between the first and the last redeemed prescriptions in which the child was taking medication. Associations between predictor variables (child sex, ADHD symptom severity, age at first prescription, family socioeconomic status (SES), single parent status, parent education and parent mental health) and medication coverage were examined using regression analyses.

Results

166 (3.6%) children had ever redeemed a prescription for an ADHD medication. Boys had higher odds of having taken ADHD medication than girls (OR=3.9; 95% CI 2.7 to 5.7). The mean medication coverage was 59.8%. Medication coverage was lower in children from families of lower SES (β=4.0; 95% CI 0.2 to 7.8, p=0.04). Medication coverage was relatively high in the first year of prescription, then decreased progressively, only increasing again after 5 or 6 years of treatment.

Conclusions

Children with ADHD from socially disadvantaged families were less likely to receive medication consistently. Prescribers need to continue to support families over many years to ensure medication is used consistently for children with ADHD.
Temporal trends in incidence of Rolandic epilepsy, prevalence of comorbidities and prescribing trends: birth cohort study
Authors: Stephen Jacqueline , Weir Christopher J , Chin Richard FM
Published: January 2020

Objective

To examine temporal trends in incidence of Rolandic epilepsy (RE), prevalence of comorbidities and antiepileptic drug (AED) prescribing patterns.

Design

Retrospective cohort study.

Setting

The UK.

Patients

Children aged 0–16 years born 1994–2012 were followed from birth until September 2017, transfer to another general practitioner practice or death or practice withdrawal from The Health Improvement Network (THIN), whichever occurred first.

Main outcome measures

Incidence of RE, prevalence of comorbidity and AED prescribing patterns. Read codes for comorbidities and AEDs were adapted from other UK population-based epilepsy studies.

Results

There were 379 children with first RE event recorded between 2000 and 2014 from active THIN practices with available mid-year population counts. Crude annual incidence across all years was 5.31/100 000 (95% CI 4.81 to 5.88). There was no significant time trend in adjusted incidence rate ratios (aIRR) (0.99/year, 95% CI 0.96 to 1.02). Males had higher aIRR (1.48, 95% CI 1.20 to 1.82) as did children aged 6–8 and 9–11 years compared with 4–5 years (aIRR 2.43, 95% CI 1.73 to 3.40; aIRR 2.77, 95% CI 1.97 to 3.90, respectively). There was recorded comorbidity in 12% with 6% with a recorded diagnosis of pervasive developmental disorder. Half of children with RE had a record of being prescribed AEDs.

Conclusions

UK incidence of RE has remained stable with crude incidence of 5/100 000/year. Carers and clinicians need to be aware that comorbidities may exist, particularly pervasive developmental disorders. Carbamazepine is consistently the most commonly prescribed AED for RE in the UK.
Mixed methods protocol for a realist evaluation of electronic personal health records design features and use to support medication adherence (ePHRma)
Authors: Andrikopoulou Elisavet , Scott Philip J , Herrera Helena
Published: January 2020

Background

National Health Service policy suggests that increasing usage of electronic personal health records (PHR) by patients will result in cost savings and improved public health. Medication adherence means that patients take their prescribed medication as agreed with their doctors. Some of the claimed benefits of PHRs are decreasing healthcare costs and improving medication adherence and patient outcomes.

Methods

This is a mixed methods convergent study, primarily qualitative. The qualitative and quantitative data collection and analysis will occur in parallel, and then be synthesised. We are interviewing and surveying adults with long-term conditions to identify what are the most important and useful features of their current PHR. The data collection comprises patient demographics, the Medication Adherence Questionnaire, the personality scale Big Five Inventory-2 Extra-Short Form and the WHO Quality of Life-BREF scale. Qualitative data will be analysed using the Framework method.

Ethics

We have received a favourable ethical opinion from the Health Research Authority/Research Ethics Committee.
Design and pilot testing of a church-based intervention to address interpersonal and intrapersonal barriers to uptake of family planning in rural Tanzania: a qualitative implementation study
Authors: Aristide Christine , Mwakisole Agrey , Mwakisole Nelusigwe , Emmanuel Mary , Laizer Evarist , Kihunrwa Albert , Downs David , Wamoyi Joyce , Downs Jennifer
Published: January 2020

Background

Use of family planning (FP) saves the lives of mothers and children, and contributes to better economic outcomes for households and empowerment for women. In Tanzania, the overall unmet need for FP is high. This study aimed: (1) to use focus group data to construct a theoretical framework to understand the multidimensional factors impacting the decision to use FP in rural Tanzania; (2) to design and pilot-test an educational seminar, informed by this framework, to promote uptake of FP; and (3) to assess acceptability and further refine the educational seminar based on focus group data collected 3 months after the education was provided.

Methods

We performed a thematic analysis of 10 focus group discussions about social and religious aspects of FP from predominantly Protestant church attenders prior to any intervention, and afterwards from six groups of church leaders who had attended the educational seminar.

Results

Key interpersonal influences included lack of support from husband/partner, family members, neighbours and church communities. Major intrapersonal factors impeding FP use were lack of medical knowledge and information, misconceptions, and perceived incompatibility of FP and Christian faith. Post-seminar, leaders reported renewed intrapersonal perspectives on FP and reported teaching these perspectives to community members.

Conclusions

Addressing intrapersonal barriers to FP use for leaders led them to subsequently address both intrapersonal and interpersonal barriers in their church communities. This occurred primarily by increasing knowledge and support for FP in men, family members, neighbours and church communities.
Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations
Authors: Szeto Cheuk-Chun , Sugano Kentaro , Wang Ji-Guang , Fujimoto Kazuma , Whittle Samuel , Modi Gopesh K , Chen Chen-Huen , Park Jeong-Bae , Tam Lai-Shan , Vareesangthip Kriengsak , Tsoi Kelvin K F , Chan Francis K L
Published: January 2020

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed medications, but they are associated with a number of serious adverse effects, including hypertension, cardiovascular disease, kidney injury and GI complications.

Objective

To develop a set of multidisciplinary recommendations for the safe prescription of NSAIDs.

Methods

Randomised control trials and observational studies published before January 2018 were reviewed, with 329 papers included for the synthesis of evidence-based recommendations.

Results

Whenever possible, a NSAID should be avoided in patients with treatment-resistant hypertension, high risk of cardiovascular disease and severe chronic kidney disease (CKD). Before treatment with a NSAID is started, blood pressure should be measured, unrecognised CKD should be screened in high risk cases, and unexplained iron-deficiency anaemia should be investigated. For patients with high cardiovascular risk, and if NSAID treatment cannot be avoided, naproxen or celecoxib are preferred. For patients with a moderate risk of peptic ulcer disease, monotherapy with a non-selective NSAID plus a proton pump inhibitor (PPI), or a selective cyclo-oxygenase-2 (COX-2) inhibitor should be used; for those with a high risk of peptic ulcer disease, a selective COX-2 inhibitor plus PPI are needed. For patients with pre-existing hypertension receiving renin-angiotensin system blockers, empirical addition (or increase in the dose) of an antihypertensive agent of a different class should be considered. Blood pressure and renal function should be monitored in most cases.

Conclusion

NSAIDs are a valuable armamentarium in clinical medicine, but appropriate recognition of high-risk cases, selection of a specific agent, choice of ulcer prophylaxis and monitoring after therapy are necessary to minimise the risk of adverse events.
Haptoglobin genotype and outcome after aneurysmal subarachnoid haemorrhage
Authors: Morton Matthew J , Hostettler Isabel C , Kazmi Nabila , Alg Varinder S , Bonner Stephen , Brown Martin M , Durnford Andrew , Gaastra Benjamin , Garland Patrick , Grieve Joan , Kitchen Neil , Walsh Daniel , Zolnourian Ardalan , Houlden Henry , Gaunt Tom R , Bulters Diederik O , Werring David J , Galea Ian
Published: January 2020

Objective

After aneurysmal subarachnoid haemorrhage (aSAH), extracellular haemoglobin (Hb) in the subarachnoid space is bound by haptoglobin, neutralising Hb toxicity and helping its clearance. Two exons in theHPgene (encoding haptoglobin) exhibit copy number variation (CNV), giving rise to HP1 and HP2 alleles, which influence haptoglobin expression level and possibly haptoglobin function. We hypothesised that theHPCNV associates with long-term outcome beyond the first year after aSAH.

Methods

TheHPCNV was typed using quantitative PCR in 1299 aSAH survivors in the Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, a retrospective multicentre cohort study with a median follow-up of 18 months. To investigate mediation of theHPCNV effect by haptoglobin expression level, as opposed to functional differences, we used rs2000999, a single nucleotide polymorphism associated with haptoglobin expression independent of theHPCNV. Outcome was assessed using modified Rankin and Glasgow Outcome Scores. SAH volume was dichotomised on the Fisher grade. Haemoglobin-haptoglobin complexes were measured in cerebrospinal fluid (CSF) of 44 patients with aSAH and related to theHPCNV.

Results

The HP2 allele associated with a favourable long-term outcome after high-volume but not low-volume aSAH (multivariable logistic regression). However rs2000999 did not predict outcome. The HP2 allele associated with lower CSF haemoglobin-haptoglobin complex levels. The CSF Hb concentration after high-volume and low-volume aSAH was, respectively, higher and lower than the Hb-binding capacity of CSF haptoglobin.

Conclusion

The HP2 allele carries a favourable long-term prognosis after high-volume aSAH. Haptoglobin and the Hb clearance pathway are therapeutic targets after aSAH.