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The idea that women do not support the far right endures despite the contemporary resurgence and global electoral successes of the far right in its many guises. The aim of this article is to critically interrogate four dominant assumptions surrounding women's alleged lack of support for the far right and unpack whether they 'tell' researchers anything new about this support or merely consolidate existing blind spots in the scholarly literature on the topic. The article makes the case that for researchers to understand women's far‐right support, they must take a more holistic approach to the topic of gender and political behaviour, and pay closer attention not only to the socio‐cultural, historical, and political factors which underpin far‐right support in this context, but the different ways in which some women 'do' politics in order to make their voices heard. [ABSTRACT FROM AUTHOR]

Summary: Aim: To examine the relationship between periodontal disease and tooth loss and risk of inflammatory bowel disease (IBD). Methods: We conducted a prospective cohort study of 86,602 women from the Nurses' Health Study (1992–2016) and 50,349 men from the Health Professionals Follow‐up Study (1986–2016) with available data on periodontal disease and tooth loss. Cases of IBD were initially reported by participants and then confirmed by medical record review. We used Cox proportional hazards modelling to estimate multivariable‐adjusted hazard ratios (aHRs) and 95% CIs. Results: Through the end of follow‐up, we documented 175 cases of Crohn's disease (CD) and 209 cases of ulcerative colitis (UC). After adjustment for potential risk factors, there was no association between periodontal disease and risk of CD (pooled aHR: 0.99, 95% CI: 0.65–1.52, p = 0.970) or UC (aHR: 0.99, 95% CI: 0.68–1.45, p = 0.971). Similarly, we did not observe an association between tooth loss and risk of CD (aHR: 0.72, 95% CI: 0.43–1.21, p = 0.218) or UC (aHR: 0.89, 95% CI: 0.58–1.36, p = 0.581) in the pooled analysis. The associations were not modified by sex, age, body mass index (BMI), smoking status or NSAID use (all pinteraction > 0.87). Conclusion: In two large prospective cohort studies, we did not observe an association between periodontal disease and tooth loss and risk of CD or UC. [ABSTRACT FROM AUTHOR]

OER-enabled pedagogy, one form of open pedagogy, is gaining popularity as a method for increasing student engagement and motivation. Realising the potential of this approach, however, depends on faculty implementation and reducing resistance to change. This study explores the experience of instructors during their first and second courses when facilitating OER-enabled pedagogy. Specifically, the research sought to determine how their view of the approach and teaching practices changed between classes, and if this prescribed experience increased their likelihood of using OER-enabled pedagogy in other classes. Interviews with faculty suggest that when teaching OER-enabled pedagogy for the first time, there is a lack of understanding of the value of this approach impacting their perceived mentorship of students. By the second iteration, however, instructors recognise an evolution in their view of teaching generally as well as OER-enabled pedagogy more specifically. This growth increases the quality of interaction with students and fosters broader use of open practices. [ABSTRACT FROM AUTHOR]

A photo quiz is presented about the case of a 12-month old male with a history of right eyelid lesion and was diagnosed with cutaneous leishmaniasis.

Mesenchymal stem cells (MSCs) have been proven to promote tissue repair. However, concerns related to their clinical application and regulatory hurdles remain. Recent data has demonstrated the proregenerative secretome of MSCs can result in similar effects in the absence of the cells themselves. Within the secretome, exosomes have emerged as a promising regenerative component. Exosomes, which are nanosized lipid vesicles secreted by cells, encapsulate micro‐RNA (miRNA), RNA, and proteins that drive MSCs regenerative potential with cell specific content. As such, there is an opportunity to optimize the regenerative potential of MSCs, and thus their secreted exosome fraction, to improve clinical efficacy. Exercise is one factor that has been shown to improve muscle progenitor cell function and regenerative potential. However, the effect of exercise on MSC exosome content and function is still unclear. To address this, we used an in vitro culture system to evaluate the effects of mechanical strain, an exercise mimetic, on C2C12 (muscle progenitor cell) exosome production and proregenerative function. Our results indicate that the total exosome production is increased by mechanical strain and can be regulated with different tensile loading regimens. Furthermore, we found that exosomes from mechanically stimulated cells increase proliferation and myogenic differentiation of naïve C2C12 cells. Lastly, we show that exosomal miRNA cargo is differentially expressed following strain. Gene ontology mapping suggests positive regulation of bone morphogenetic protein signaling, regulation of actin‐filament‐based processes, and muscle cell apoptosis may be at least partially responsible for the proregenerative effects of exosomes from mechanically stimulated C2C12 muscle progenitor cells. [ABSTRACT FROM AUTHOR]

Background Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. Methods Participants ages 4–21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. Results The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. Conclusions Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. Clinical Trials No NCT03982069 [ABSTRACT FROM AUTHOR]

• Age and baseline HAI titers were associated with immune response to egg-free influenza vaccine. • HAI response differed by antigen level contained in prior season's influenza vaccine. • The ideal sequence of vaccine formulations across influenza seasons remains unknown. Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults. Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018–2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen. Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1). Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed. [ABSTRACT FROM AUTHOR]

Covering: up to early 2022 Maleidrides are a family of polyketide-based dimeric natural products isolated from fungi. Many maleidrides possess significant bioactivities, making them attractive pharmaceutical or agrochemical lead compounds. Their unusual biosynthetic pathways have fascinated scientists for decades, with recent advances in our bioinformatic and enzymatic understanding providing further insights into their construction. However, many intriguing questions remain, including exactly how the enzymatic dimerisation, which creates the diverse core structure of the maleidrides, is controlled. This review will explore the literature from the initial isolation of maleidride compounds in the 1930s, through the first full structural elucidation in the 1960s, to the most recent in vivo, in vitro, and in silico analyses. [ABSTRACT FROM AUTHOR]

Age‐related changes in bone microstructure can inform our understanding the biology of both extant and fossil birds, but to date, histological work in birds, and particularly work using high‐resolution 3D imaging, has largely been restricted to limited growth stages. We used minimally destructive synchrotron radiation‐based X‐ray computed tomography to visualise and measure key morphological and histological traits in 3D across development in the domestic duck and ring‐necked pheasant. We use these measurements to build on the database of key reference material for interpreting bone histology. We found that growth patterns differed between the two species, with the ducks showing rapid growth in their lower limbs and early lower limb maturation, while pheasants grew more slowly, reflecting their later age at maturity. In the pheasant, both walking and flight occur early and their upper and lower limbs grew at similar rates. In the duck, flight and wing development are delayed until the bird is almost at full body mass. Through juvenile development, the second moment of area for the duck wing was low but increased rapidly towards the age of flight, at which point it became significantly greater than that of the lower limb, or the pheasant. On a microstructural level, both cortical porosity and canal diameter were related to cortical bone deposition rate. In terms of orientation, vascular canals in the bone cortex were more laminar in the humerus and femur compared with the tibiotarsus, and laminarity increased through juvenile development in the humerus, but not the tibiotarsus, possibly reflecting torsional vs compressive loading. These age‐related changes in cortical bone vascular microstructure of the domestic duck and pheasant will help understanding the biology of both extant and fossil birds, including age estimation, growth rate and growth patterns, and limb function. [ABSTRACT FROM AUTHOR]

A robust left digit effect arises in number line estimation such that adults' estimates for numerals with different hundreds place digits but nearly identical magnitudes are systematically different from one another (e.g., 299 is placed too far to the left of 302). In two experiments, we investigate whether brief feedback interventions designed to increase task effort can reduce or eliminate the left digit effect in a self-paced 0–1,000 number line estimation task. Participants were assigned to complete three blocks of 120 trials each where the middle block contained feedback or no feedback. Feedback was in the form of summary accuracy scores (Experiment 1; N = 153) or competitive (summary) accuracy scores (Experiment 2; N = 145). In both experiments, planned analyses revealed large left digit effects in all blocks regardless of feedback condition. Feedback did not lead to a reduction in the left digit effect in either experiment, but improvements in overall accuracy were observed. We conclude that there are no changes in the left digit effect resulting from either summary accuracy feedback or competitive accuracy feedback. Also reported are exploratory analyses of trial characteristics (e.g., whether 299 is presented before or after 302) and the left digit effect. [ABSTRACT FROM AUTHOR]

Gastrointestinal nematode (GIN) parasite infections can be detrimental to not only cattle health and immunity, but also result in economic loss and poor performance. Cattle grazing in the southeast are challenged even further by the favorable environmental conditions for parasite development, especially those animals who have yet to develop an immunity to combat parasitism. To diminish potential economic and performance-based losses, many beef producers treat animals for GIN parasites with anthelmintics on a regular basis without proper diagnosis. Anthelmintic resistance(AR) develops when deworming products are overused and misused. To minimize the development of AR, selective deworming and sustainable management practices should be implemented. However, the severity of parasite burden over the production cycle needs to be better understood in beef cattle herds before recommendations can be made. Thus, the objective was to investigate the rates of GIN parasite infections through fecal egg counts (FEC) and the impact on body weight (BW) and body condition score (BCS). Angus-based cattle (6 mo-13 yr, n = 1,154) on a were utilized from five different research and educational herds across North Carolina. Cattle were categorized based on their age at the start of the project as either calves (n = 446), yearling heifers (n = 205), 2 year old (n = 260), 3-5 year old (n = 501), or 6+ year old (n = 206). Starting in September, FEC, BW, and BCS were collected and analyzed every 90 d at critical production timepoints (calving, breeding, weaning, and 90d post-weaning) to monitor the severity of GIN parasite challenge. Cattle on study were not treated with anthelmintics regardless of parasite load, with the exception of calves at four of the locations at the time of weaning. All data were analyzed using Proc MIXED in SAS with repeated measures. Statistical significance was declared at P ≤ 0.05 and a trend at 0.10 > P > 0.05. Age of cattle had an impact on FEC overall (P < 0.05), however, there was no difference between FEC of mature cattle over 3 yr (4.29 ± 4.9 eggs/gm). Calves had the greatest FEC (120.59 ± 4.2 eggs/gm) while cattle 6+ yr had the least (3.68 ± 4.5 eggs/gm). Cattle age at each location affected BCS and BW (P < 0.05). Between age groups across locations, time had an impact on FEC, BW, and BCS (P < 0.05). There was also a tendency (P = 0.6) for location to impact FEC. Calf sex did not affect (P > 0.05) FEC. Further FEC analysis of cattle under 2 yrof age is required to better understand when a natural immune response to GIN parasite infections develops. [ABSTRACT FROM AUTHOR]

Patients with choroidal detachments were more likely to have a history of glaucoma surgery than corneal or retinal surgeries ( I P i =0.0495), but the rates were similar between trabeculectomies and glaucoma drainage implants ( I P i =0.399). In eyes with appositional choroidal detachments after glaucoma tube surgery, the surgeon may consider ligating the tube with a nonabsorbable suture to try to prevent recurrence. Anterior chamber sulfur hexafluoride (SF6) injection for the management of postsurgery hypotony in glaucoma patients. With the advent of minimally invasive glaucoma surgery, it would be interesting to compare the rates of choroidal and RDs in eyes with traditional tube shunts, trabeculectomies, or minimally invasive glaucoma surgery. [Extracted from the article]

In recent years, extracellular vesicles (EVs) have emerged as prominent mediators of the homeostasis, repair, and regeneration of musculoskeletal tissues including bone, skeletal muscle, and cartilage. Accordingly, the therapeutic potential of EVs for regenerative medicine applications has not gone unnoticed. The use of EVs for the treatment of musculoskeletal injury and disease in veterinary species is a nascent but rapidly expanding area of research. Recent studies in this area have demonstrated the safety and feasibility of EV products in dogs and horses. While early clinical responses to EV-based therapeutics in companion animals have been favorable, more rigorously designed, sufficiently powered, and placebo-controlled clinical trials are required to fully elucidate the clinical benefits and best-use scenarios for EV therapeutics in veterinary medicine. Additionally, clinical translation of EV-based therapeutics will require Good Manufacturing Practice-compliant methods to scale up and purify EV products. Despite these challenges, EVs hold great promise in the regenerative medicine landscape, particularly in the treatment of musculoskeletal injury and disease in companion animals. [ABSTRACT FROM AUTHOR]

Aim: In intestinal failure, delineation of both structure and function are key to controlling symptoms and planning further intervention. We have developed a template for developing an 'anatomy at a glance' patient‐specific map to aid decision making and counselling. Method: A core dataset was developed and used to create an editable template to demonstrate the gastrointestinal tract, its relationship to the genitourinary tract, and specific anterior abdominal wall features. This was then used to create an anatomical template, specific to each patient, and stored in the electronic patient record and imaging archive. Results: We have developed a technique for integration of multi‐modal information into one diagram, easily referenced by the multidisciplinary team. Radiology, endoscopy and previous operation notes can be used to fill out a core dataset, which is then transposed into a standardized template. A worked example is shown. Conclusion: The mapping template has been successfully integrated into practice and aided decision making at all stages of the patient's therapeutic journey. It has been found helpful in planning routes of nutrition, preoperative optimization, surgical planning, interpreting postoperative imaging and managing patient expectations. [ABSTRACT FROM AUTHOR]

Number line estimation (NLE) tasks are widely used to investigate numerical cognition, learning, and development, and as an instructional tool. Interpretation of these tasks generally involves an implicit expectation that responses are driven by the overall magnitudes of target numerals, in the sense that the particular digits conveying those magnitudes are unimportant. However, recent evidence shows that numbers with similar magnitudes but different leftmost digits are estimated very differently. For example, "798" is placed systematically much too far to the left of "801" in a 0–1000 NLE task by children aged 7–11 and adults. Here we ask whether this left digit effect generalizes to two-digit numerals in a 0–100 NLE task and whether it emerges in younger children. Children aged 5–8 (Study 1, N = 73), adults (Study 2, N = 44), and children aged 9–11 (Study 3, N = 27) completed a standard 0–100 NLE task on a touchscreen tablet. We observed left digit effects for two-digit numerals in children aged 8–11 and adults, with large effect sizes, demonstrating that these effects generalize to smaller numerical ranges. Left digit effects were not apparent in 5- to 7-year-olds, suggesting that these effects do not emerge at younger ages for smaller, more familiar numerical ranges. We discuss developmental emergence of left digit effects in number line estimation and implications within and beyond the field of cognitive development. [ABSTRACT FROM AUTHOR]

Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019–2020 LAIV4 and ccIIV4. Participants aged 4–21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21–35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4–3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178–237); cell = 136 (95% CI:113–165); LAIV4 day 28: egg = 96 (95% CI: 83–112); cell = 63 (95% CI: 58–74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups. [ABSTRACT FROM AUTHOR]

During human pregnancy, cytotrophoblasts (CTBs) from the placenta differentiate into specialized subpopulations that play crucial roles in proper fetal growth and development. A subset of these CTBs differentiate along an invasive pathway, penetrating the decidua and anchoring the placenta to the uterus. A crucial hurdle in pregnancy is the ability of these cells to migrate, invade and remodel spiral arteries, ensuring adequate blood flow to nourish the developing fetus. Although advances continue in describing the molecular features regulating the differentiation of these cells, assessment of their global proteomic changes at mid-gestation remain undefined. Here, using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), which is a data-independent acquisition strategy, we characterized the protein repertoire of second trimester human CTBs during their differentiation towards an invasive phenotype. This mass spectrometry-based approach allowed identification of 3026 proteins across four culture time points corresponding to sequential stages of differentiation, confirming the expression dynamics of established molecules and offering new information into other pathways involved. The availability of a SWATH CTB global spectral library serves as a beneficial resource for hypothesis generation and as a foundation for further understanding CTB differentiation dynamics. [ABSTRACT FROM AUTHOR]

Citizen science projects are an increasingly popular way to engage the public in the process of science. However, few studies have evaluated learning outcomes beyond knowledge gains in formal learning settings with youth. This study evaluated the effects of a classroom-based citizen science project in which middle and high school students collected data about hummingbirds and their habitat use as part of a long-term study on declining hummingbird populations. We explored changes in science identity, nature connectedness, and knowledge of curricular material using quantitative pre- and post-test questionnaires (n = 367). While curricular knowledge scores increased modestly, the project had no meaningful impacts on science identity or nature connectedness. Nevertheless, students reported that the citizen science aspect motivated them and made them feel that they were contributing to science. Results suggest that, while citizen science has potential as an effective mode for educating students about the processes and content of science, one should not assume that it necessarily conveys additional benefits. Supplemental data for this article is available online at https://doi.org/10.1080/13504622.2021.1927990. [ABSTRACT FROM AUTHOR]

Understanding the neutral, biological, and environmental processes driving species distributions is valuable in informing conservation efforts because it will help us predict how species will respond to changes in environmental conditions. Environmental processes affect species differently according to their biological traits, which determine how they interact with their environment. Therefore, functional, trait-based modeling approaches are considered important for predicting distributions and species responses to change but even for data-rich primate communities our understanding of the relationships between traits and environmental conditions is limited. Here we use a large-scale, high-resolution data set of African diurnal primate distributions, biological traits, and environmental conditions to investigate the role of biological traits and environmental trait filtering in primate distributions. We collected data from published sources for 354 sites and 14 genera with 57 species across sub-Saharan Africa. We then combined a three-table ordination method, RLQ, with the fourth-corner approach to test relationships between environmental variables and biological traits and used a mapping approach to visually assess patterning in primate genus and species' distributions. We found no significant relationships between any groups of environmental variables and biological traits, despite a clear role of environmental filtering in driving genus and species' distributions. The most important environmental driver of species distributions was temperature seasonality, followed by rainfall. We conclude that the relative flexibility of many primate genera means that not any one particular set of traits drives their species–environment associations, despite the clear role of such associations in their distribution patterns. [ABSTRACT FROM AUTHOR]

Upper and lower eyelid blepharoplasty are common procedures performed to provide a more youthful and rejuvenated appearance. However, this seemingly straightforward procedure may result in lid malpositions, frustrating the patient and surgeon alike, which ultimately require further treatment. We review preoperative assessment pearls to avoid these lid malpositions, as well as options for treating any postoperative complications related to lid position. Many of the techniques discussed in this article, in addition to many other oculoplastic procedures, are available to view in Dr. Richard C. Allen's operative video library at: http://webeye.ophth.uiowa.edu/eyeforum/video/plastics/ . [ABSTRACT FROM AUTHOR]

Describing and quantifying vascular canal orientation and volume of osteocyte lacunae in bone is important in studies of bone growth, mechanics, health and disease. It is also an important element in analysing fossil bone in palaeohistology, key to understanding the growth, life and death of extinct animals. Often, bone microstructure is studied using two‐dimensional (2D) sections, and three‐dimensional (3D) shape and orientation of structures are estimated by modelling the structures using idealised geometries based on information from their cross sections. However, these methods rely on structures meeting strict geometric assumptions. Recently, 3D methods have been proposed which could provide a more accurate and robust approach to bone histology, but these have not been tested in direct comparison with their 2D counterparts in terms of accuracy and sensitivity to deviations from model assumptions. We compared 2D and 3D methodologies for estimating key microstructural traits using a combination of experimental and idealised test data sets. We generated populations of cylinders (canals) and ellipsoids (osteocyte lacunae), varying the cross‐sectional aspect ratios of cylinders and orientation of ellipsoids to test sensitivity to deviations from cylindricality and longitudinal orientation, respectively. Using published methods, based on 2D sections and 3D data sets, we estimated cylinder orientation and ellipsoid volume. We applied the same methods to six CT data sets of duck cortical bone, using the full volumes for 3D measurements and single CT slices to represent 2D sections. Using in silico test data sets that did deviate from ideal cylinders and ellipsoids resulted in inaccurate estimates of cylinder or canal orientation, and reduced accuracy in estimates of ellipsoid and lacunar volume. These results highlight the importance of using appropriate 3D imaging and quantitative methods for quantifying volume and orientation of 3D structures and offer approaches to significantly enhance our understanding of bone physiology based on accurate measures for bone microstructures. [ABSTRACT FROM AUTHOR]

Phosphorus is an essential nutrient for crops. Precise spatiotemporal application of P fertilizer can improve plant P acquisition and reduce run‐off losses of P. Optimizing application would benefit from understanding the dynamics of P release from a fertilizer pellet into bulk soil, which requires space‐ and time‐resolved measurements of P concentration in soil solutions. In this study, we combined microdialysis and X‐ray computed tomography to investigate P transport in soil. Microdialysis probes enabled repeated solute sampling from one location with minimal physical disturbance, and their small dimensions permitted spatially resolved monitoring. We observed a rapid initial release of P from the source, producing high dissolved P concentrations within the first 24 h, followed by a decrease in dissolved P over time compatible with adsorption onto soil particles. Soils with greater bulk density (i.e., reduced soil porosity) impeded the P pulse movement, which resulted in a less homogeneous distribution of total P in the soil column at the end of the experiment. The model fit to the data showed that the observed phenomena can be explained by diffusion and adsorption. The results showed that compared with conventional measurement techniques (e.g., suction cups), microdialysis measurements present a less invasive alternative. The time‐resolved measurements ultimately highlighted rapid P dynamics that require more attention for improving P use efficiency. [ABSTRACT FROM AUTHOR]

Introduction: Recent work reveals a new source of error in number line estimation (NLE), the left digit effect (Lai, Zax, et al., 2018), whereby numerals with different leftmost digits but similar magnitudes (e.g., 399, 401) are placed farther apart on a number line (e.g., 0 to 1,000) than is warranted. The goals of the present study were to: (1) replicate the left digit effect, and (2) assess whether it is related to mathematical achievement. Method: Participants were all individuals (adult college students) who completed the NLE task in the laboratory between 2014 and 2019 for whom SAT scores were available (n = 227). Results: We replicated the left digit effect but found its size was not correlated with SAT math score, although it was negatively correlated with SAT verbal score for one NLE task version. Conclusions: These findings provide further evidence that individual digits strongly influence estimation performance and suggest that this effect may have different cognitive contributors, and predict different complex skills, than overall NLE accuracy. [ABSTRACT FROM AUTHOR]

Fescue toxicosis decreases beef cattle performance in a multitude of ways, including decreased health and immunity. Cattle challenged by fescue toxicosis are often grazing in an environment favorable for development of gastrointestinal nematodes (GIN). Interactions of fescue toxicosis and parasite challenge may result in further performance and economic losses. Many beef producers treat animals regularly for GIN parasites with little insight on necessity or effectiveness of anthelmintic products. Overuse of anthelmintics can result in development of anthelmintic resistance in GIN populations. To minimize the development of anthelmintic resistance, implementation of selective deworming practices should be considered. However, level of parasite burden and effects of fescue toxicosis on parasite burden need to be better understood in beef cattle herds before recommendations can be offered. Therefore, the objective was to investigate the impact of fescue toxicosis on GIN parasite infection rates through fecal egg counts (FEC), body weight (BW), hematocrit (HCT), and body condition score (BCS). Starting in April, for 14 consecutive weeks post-weaning, pregnant Angus-based cows (2 to 4 years old, n = 65) were rotationally grazed on either novel endophyte (EN) fescue or endophyteinfected (EI) fescue pastures. Hematocrit, BCS, and BW were assessed weekly, while FEC were measured bi-weekly to monitor the physiological changes as a result of consuming endophyte-infected tall fescue. All data were analyzed using Proc MIXED in SAS with repeated measures. Statistical significance was declared at P = 0.05 and a trend at 0.10 > P > 0.05. Overall, FEC were low (4.2 ± 0.9 eggs/gm) in these mature cattle and grazing EI or EN fescue did not have any overall effect (P > 0.05) on the FEC. However, FEC decreased (P < 0.05) over the course of the study from week 1 to week 13. Body weight, HCT, and BCS were not affected (P > 0.05) by the type of fescue grazed. There was a tendency (P < 0.10) for 2-3 and 4-6 year old cattle to have lower BW when grazing EI compared with EN fescue while cattle >7 were not affected. Cattle gained BW (P < 0.05) over the 14-week study (471.4 and 527.7 ± 0.6 kg, 0 and4 week respectively). For cattle grazing EI fescue, HCT linearly decreased (P < 0.05) from week 1 to week 14 whereas cattle grazing EN fescue had a linear increase (P < 0.05) in HCT from week 1 to week 14. More research is warranted to investigate beef cattle FEC and the potential impact of fescue type on FEC in younger beef cattle. [ABSTRACT FROM AUTHOR]

Partition dependence, the tendency to distribute choices differently based on the way options are grouped, has important implications for decision making. This phenomenon, observed in adults across a variety of contexts such as allocating resources or making selections from a menu of items, can bias decision makers toward some choices and away from others. Only one study to date (Reichelson, Zax, Patalano, & Barth, Quarterly Journal of Experimental Psychology, 72, 1029–1036, 2019) has investigated the developmental trajectory of this phenomenon. In the current study we investigate children's and adults' susceptibility to partitioning effects in a child-friendly resource allocation task. In Experiment 1 (N = 80), adults distributed 12 food tokens to animals at the zoo. Based on previous findings that older children show weaker partition dependence in this task, we predicted that adults might exhibit reduced partition dependent behavior: they showed none. In Experiment 2 (N = 272), we used a less transparent task with only five food tokens, predicting that both adults and children (ages 3–10 years) would show partition dependence. Children, but not adults, made partition dependent resource allocations, with younger children exhibiting greater effects than older children. These experiments provide further evidence that children's decisions, like adults' (in other tasks), are influenced by the arbitrary partitioning of the available options. This work supports previous findings that younger children may be more susceptible to these effects, and maps developmental change in partition dependent behavior from early childhood to adulthood on this child-friendly partition dependence task. [ABSTRACT FROM AUTHOR]

FSHD is characterized by the misexpression of DUX4 in skeletal muscle. Although DUX4 upregulation is thought to be the pathogenic cause of FSHD, DUX4 is lowly expressed in patient samples, and analysis of the consequences of DUX4 expression has largely relied on artificial overexpression. To better understand the native expression profile of DUX4 and its targets, we performed bulk RNA-seq on a 6-day differentiation time-course in primary FSHD2 patient myoblasts. We identify a set of 54 genes upregulated in FSHD2 cells, termed FSHD-induced genes. Using single-cell and single-nucleus RNA-seq on myoblasts and differentiated myotubes, respectively, we captured, for the first time, DUX4 expressed at the single-nucleus level in a native state. We identified two populations of FSHD myotube nuclei based on low or high enrichment of DUX4 and FSHD-induced genes ("FSHD-Lo" and "FSHD Hi", respectively). FSHD-Hi myotube nuclei coexpress multiple DUX4 target genes including DUXA, LEUTX and ZSCAN4, and also upregulate cell cycle-related genes with significant enrichment of E2F target genes and p53 signaling activation. We found more FSHD-Hi nuclei than DUX4-positive nuclei, and confirmed with in situ RNA/protein detection that DUX4 transcribed in only one or two nuclei is sufficient for DUX4 protein to activate target genes across multiple nuclei within the same myotube. DUXA (the DUX4 paralog) is more widely expressed than DUX4, and depletion of DUXA suppressed the expression of LEUTX and ZSCAN4 in late, but not early, differentiation. The results suggest that the DUXA can take over the role of DUX4 to maintain target gene expression. These results provide a possible explanation as to why it is easier to detect DUX4 target genes than DUX4 itself in patient cells and raise the possibility of a self-sustaining network of gene dysregulation triggered by the limited DUX4 expression. Author summary: Although misexpression of DUX4 has been known as the major cause in FSHD, it is lowly expressed in patient samples and analysis of the consequences of DUX4 expression has largely relied on artificial overexpression. Here, we took advantage of recent methodological advances to observe native DUX4 expression at the single-nucleus level in FSHD2 patient-derived myotubes. Using single-nucleus RNA-seq (snRNA-seq), we were able to detect endogenous DUX4-expressing nuclei and the extent of spreading of DUX4-target gene expression across many nuclei. Our highly sensitive snRNA-seq method further allowed us to identify two populations of FSHD myotube nuclei with distinct transcriptional profiles. One is highly enriched with DUX4 and target genes (FSHD-Hi) while the other has sparser DUX4 and FSHD-induced genes expressed (FSHD-Lo), reflecting two potentially different pathological states of patient myotubes. We observed a set of transcription factors specifically upregulated in FSHD-Hi myotube nuclei associated with the cell cycle, and significant upregulation of DUX4 paralog DUXA that contributes to further upregulation of DUX4 target genes. We propose that transcription factors downstream of DUX4 may amplify DUX4 signal and thus act to perpetuate FSHD. [ABSTRACT FROM AUTHOR]

When allocating resources, people often diversify across categories even when those categories are arbitrary, such that allocations differ when identical sets of options are partitioned differently ("partition dependence"). The first goal of the present work (Experiment 1) was to replicate an experiment by Fox and colleagues in which graduate students exhibited partition dependence when asked how university financial aid should be allocated across arbitrarily partitioned income brackets. Our sample consisted of community members at a liberal arts college where financial aid practices have been recent topics of debate. Because stronger intrinsic preferences can reduce partition dependence, these participants might display little partition dependence with financial aid allocations. Alternatively, a demonstration of strong partition dependence in this population would emphasize the robustness of the effect. The second goal was to extend a "high transparency" modification to the present task context (Experiment 2) in which participants were shown both possible income partitions and randomly assigned themselves to one, to determine whether partition dependence in this paradigm would be reduced by revealing the study design (and the arbitrariness of income categories). Participants demonstrated clear partition dependence in both experiments. Results demonstrate the robustness of partition dependence in this context. [ABSTRACT FROM AUTHOR]

Similar estimation biases appear in a wide range of quantitative judgments, across many tasks and domains. Often, these biases (those that occur, for example, when adults or children indicate remembered locations of objects in bounded spaces) are believed to provide evidence of Bayesian or rational cognitive processing, and are explained in terms of relatively complex Bayesian models (e.g., the Category Adjustment Model). Here, we suggest that some of these phenomena may be accounted for instead within a simpler alternative theoretical framework that has previously been found to explain bias in common numerical estimation tasks across development. We report data from university undergraduate students and 7- through 10-year-olds completing a speeded linear position reproduction task. Bias in both adults' and children's responses was effectively explained in terms of a relatively simple psychophysical model of proportion estimation. These data clearly show that the proportion estimation framework is a viable alternative to theories that explain biases as the result of a Bayesian cognitive adjustment process. We also discuss our view that these data are not easily reconciled with the requirements of the more complex Category Adjustment Model that assumes estimates should exhibit a central tendency bias. [ABSTRACT FROM AUTHOR]

Aims: The aim was to determine if persistent c-peptide in long duration childhood onset (<17 years) type 1 diabetes (T1D) related to microvascular complications.Methods: Pittsburgh Epidemiology of Diabetes Complications (EDC) participants (n = 185) had serum c-peptide levels measured by Mercodia ultra-sensitive ELISA at the 25-year follow-up exam. Microvascular complications between those with and without detectable c-peptide were compared.Results: Eighteen (9.7%) participants had detectable median c-peptide levels of 3.8 (2.6, 12.2) pmol/L and did not differ from those without detectable levels. No differences in microalbuminuria, confirmed distal symmetric polyneuropathy, renal failure, or between those with one or more complications were found between the two groups. Proliferative retinopathy (PR) was marginally lower in those with detectable c-peptide (33.3% vs 55.1%, p = 0.08). However, those with c-peptide were somewhat less likely to have fasted for a full 8-h (66.7% vs. 84.9%, p = 0.09). Excluding those not fully fasted, PR no longer approached significance but macroalbuminuria became marginally lower in those with detectable levels (23.4% vs 0%, p = 0.07).Conclusions: Low levels of c-peptide in T1D patients of long duration were detected but were not strongly related to microvascular complications. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants and recognized developmental toxicants that are detectable in placental tissues. Higher levels of in utero PBDE exposure have been associated with an increased risk of adverse birth outcomes. During pregnancy, cytotrophoblasts (CTBs) from the placenta play critical roles in the formation of the maternal-fetal interface via uterine invasion and vascular remodeling. The differentiation of these cells towards an invasive phenotype is crucial for proper placental development. We previously have shown that BDE-47 can impact CTB viability and hinder the ability of these cells to migrate and invade. To expand on potential toxicological mechanisms, we utilized quantitative proteomic approaches to identify changes in the global proteome of mid-gestation primary human CTBs after exposure to BDE-47. Using sequential window acquisition of all theoretical fragment-ion spectra (SWATH), we identified 3024 proteins in our CTB model of differentiation/invasion. Over 200 proteins were impacted as a function of BDE-47 exposure (1 μM and 5 μM) across the treatment period (15, 24, and 39 h). The differentially expressed molecules displayed time- and concentration-dependent changes in expression and were enriched in pathways associated with aggregatory and adhesive processes. Network analysis identified CYFIP1, a molecule previously unexplored in a placental context, to be dysregulated at BDE-47 concentrations previously seen to impact CTB migration/invasion. Our SWATH-MS dataset thus demonstrates BDE-47 impacts the global proteome of differentiating CTBs and serves as a valuable resource for further understanding of the relationship between environmental chemical exposures and placental development and function. Raw chromatograms are deposited on the MassIVE proteomic database (https://massive.ucsd.edu) under accession number MSV000087870. Normalized relative abundances are also available as Table S1. [ABSTRACT FROM AUTHOR]

Research on climate change media coverage is growing. Few studies, however, have investigated how the media portrays climate change impacts on human health. This review, therefore, presents a quantitative spatiotemporal analysis of Canadian newspaper coverage of climate change impacts on health between 2005 and 2015. Using the ProQuest® and Eureka® databases, a multiphase systematic review strategy was employed to identify relevant English and French articles from two national and six regional high-circulation newspapers. Quantitative and qualitative data were extracted from 145 articles and analyzed to characterize the range, extent, and nature of climate-health newspaper coverage in Canada and to compare these characteristics by region and over time. Coverage varied by region, with the highest proportion of climate-health coverage in Northern Territories (Yukon, Northwest Territories, Nunavut). Over time, there was a decreasing publication frequency trend. Almost all articles described negative climate change impacts on health, with a predominant focus on infectious and chronic noninfectious diseases; however, less than half of the articles discussed climate change solutions. These trends suggest that current media coverage might not drive widespread public support for policies and actions needed to protect against projected climate-health risks. Consequently, as climate change continues to challenge human health, increasing media emphasis on climate change impacts on human health, as well as a shift toward enabling and empowering climate change communication, in which viable mitigation and adaptation options are emphasized, could help to spur action to reduce climate change health risks. [ABSTRACT FROM AUTHOR]

Antibodies that mediate killing of HIV-infected cells through antibody-dependent cellular cytotoxicity (ADCC) have been implicated in protection from HIV infection and disease progression. Despite these observations, these types of HIV antibodies are understudied compared to neutralizing antibodies. Here we describe four monoclonal antibodies (mAbs) obtained from one individual that target the HIV transmembrane protein, gp41, and mediate ADCC activity. These four mAbs arose from independent B cell lineages suggesting that in this individual, multiple B cell responses were induced by the gp41 antigen. Competition and phage peptide display mapping experiments suggested that two of the mAbs target epitopes in the cysteine loop that are highly conserved and a common target of HIV gp41-specific antibodies. The amino acid sequences that bind these mAbs are overlapping but distinct. The two other mAbs were competed by mAbs that target the C-terminal heptad repeat (CHR) and the fusion peptide proximal region (FPPR) and appear to both target a similar unique conformational epitope. These gp41-specific mAbs mediated killing of infected cells that express high levels of Env due to either pre-treatment with interferon or deletion of vpu to increase levels of BST-2/Tetherin. They also mediate killing of target cells coated with various forms of the gp41 protein, including full-length gp41, gp41 ectodomain or a mimetic of the gp41 stump. Unlike many ADCC mAbs that target HIV gp120, these gp41-mAbs are not dependent on Env structural changes associated with membrane-bound CD4 interaction. Overall, the characterization of these four new mAbs that target gp41 and mediate ADCC provides evidence for diverse gp41 B cell lineages with overlapping but distinct epitopes within an individual. Such antibodies that can target various forms of envelope protein could represent a common response to a relatively conserved HIV epitope for a vaccine. [ABSTRACT FROM AUTHOR]

• A continuous, autonomous mathematical model for the cell cycle is developed. • Cycle tasks such as licensing, replication, kinetochore attachment are included. • Cycle progression is contingent on completion of tasks with adequate fidelity. • Potential mechanisms postulated to prevent DNA rereplication are assessed. A mathematical model for the mammalian cell cycle is developed as a system of 13 coupled nonlinear ordinary differential equations. The variables and interactions included in the model are based on detailed consideration of available experimental data. A novel feature of the model is inclusion of cycle tasks such as origin licensing and initiation, nuclear envelope breakdown and kinetochore attachment, and their interactions with controllers (molecular complexes involved in cycle control). Other key features are that the model is autonomous, except for a dependence on external growth factors; the variables are continuous in time, without instantaneous resets at phase boundaries; mechanisms to prevent rereplication are included; and cycle progression is independent of cell size. Eight variables represent cell cycle controllers: the Cyclin D1-Cdk4/6 complex, APCCdh1, SCFβTrCP, Cdc25A, MPF, NuMA, the securin-separase complex, and separase. Five variables represent task completion, with four for the status of origins and one for kinetochore attachment. The model predicts distinct behaviors corresponding to the main phases of the cell cycle, showing that the principal features of the mammalian cell cycle, including restriction point behavior, can be accounted for in a quantitative mechanistic way based on known interactions among cycle controllers and their coupling to tasks. The model is robust to parameter changes, in that cycling is maintained over at least a five-fold range of each parameter when varied individually. The model is suitable for exploring how extracellular factors affect cell cycle progression, including responses to metabolic conditions and to anti-cancer therapies. [ABSTRACT FROM AUTHOR]

Fescue toxicosis negatively impacts cattle productivity. Previous data from our laboratory has demonstrated that cattle within a herd respond differently when grazing tall fescue, thus variation within a breed may provide genetic tolerance to the negative effects on performance. Fescue toxicosis results in major impacts on the cardiovascular system, thus it was hypothesized that exposure to ergot alkaloids negatively impacts pulmonary arterial pressure (PAP). The objective of this study was to examine changes in PAP and other production parameters in cattle consuming endophyte-infected tall fescue. Pregnant Angus cows (2 to 4 years; n = 65) were randomly divided to graze either endophyteinfected (EI) or novel endophyte (EN) pastures for4 consecutive weeks starting in April. Weekly measurements were collected to monitor physiological responses to consuming endophyte-infected tall fescue. In addition, PAP was measured every 4 weeks. Data were analyzed using a MIXED procedure of SAS, and statistical significance was determined at P < 0.05 and a tendency at 0.05 < P < 0.10, and evaluated the effects of treatment, age, week, and its interactions on BW, ADG, BCS, HCS, HSS and PAP. Exposure to EI did not affect BW, ADG, or BCS (P >0.05). Whereas, hair coat scores (1-5 scale) were significantly less for cattle consuming EN pastures (2.15 ± 0.05) compared with consuming EI pastures (2.31 ± 0.05; P < 0.05). Additionally, shedding scores (1-5 scale) were reduced in cattle consuming EN pastures (2.3±0.05) compared with consuming EI pastures (2.5±0.05; P< 0.05). There was a significant difference in PAP measurements in cattle exposed to EN pastures (37.16 ± 0.59 mm Hg) compared with EI pastures (31.31 ± 0.56 mm Hg; P < 0.0001). Additionally, PAP scores tended to deviate over the 14-week study between treatment groups (P = 0.0677). As expected, exposure to EI tall fescue resulted in greater HCS and HSS. However, the decrease in PAP in cattle consuming EI fescue was unexpected. Thus, further investigations are needed to examine the interaction between ergot alkaloid exposure on cardiovascular parameters such as PAP to potentially predict genetic differences in beef cattle to identify animals that would have a lower risk of developing fescue toxicosis. [ABSTRACT FROM AUTHOR]

Objective Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, is a significant cause of morbidity and mortality, affecting one in 1000 adults per year. Neuromuscular electrical stimulation is the transcutaneous application of electrical impulses to elicit muscle contraction, preventing venous stasis. This review aims to investigate the evidence underlying the use of neuromuscular electrical stimulation in thromboprophylaxis. Methods The Medline and Embase databases were systematically searched, adhering to PRISMA guidelines, for articles relating to electrical stimulation and thromboprophylaxis. Articles were screened according to a priori inclusion and exclusion criteria. Results The search strategy identified 10 randomised controlled trials, which were used in three separate meta-analyses: five trials compared neuromuscular electrical stimulation to control, favouring neuromuscular electrical stimulation (odds ratio of deep vein thrombosis 0.29, 95% confidence interval 0.13–0.65; P = .003); three trials compared neuromuscular electrical stimulation to heparin, favouring heparin (odds ratio of deep vein thrombosis 2.00, 95% confidence interval 1.13–3.52; P = .02); three trials compared neuromuscular electrical stimulation as an adjunct to heparin versus heparin only, demonstrating no significant difference (odds ratio of deep vein thrombosis 0.33, 95% confidence interval 0.10–1.14; P = .08). Conclusion Neuromuscular electrical stimulation significantly reduces the risk of deep vein thrombosis compared to no prophylaxis. It is inferior to heparin in preventing deep vein thrombosis and there is no evidence for its use as an adjunct to heparin. [ABSTRACT FROM AUTHOR]

Many cancer patients receive combination treatments with radiation and chemotherapy. Available mathematical models for cellular pharmacodynamics have limited ability to represent observed in vitro responses to radiochemotherapy. Here, a family of additive damage models is proposed to describe cell kill resulting from radiochemotherapy with fixed schedule and variable doses. The pathways by which the agents produce cellular damage are assumed to converge in a single cell death process, so that survival depends on total damage, which can be represented as a sum of contributions from the various damage pathways. Heterogeneity in response across the cell population is ascribed to variations in the damage threshold for cell kill. The family of proposed models includes effects of one or two pathways of damage for each agent, saturation in drug responses, and cooperative or antagonistic interactions between agents. Models from this family with 4-7 unknown parameters are tested for their ability to fit 218 in vitro literature data sets for a range of drugs and cell lines. Overall, the additive damage models are found to outperform models based on the existing concept of independent cell kill, according to the corrected Akaike Information Criterion. The results are used to assess the importance of the various effects included in the models. These additive damage models have potential applications to the optimization of treatment and to the analysis and interpretation of in vitro screening data for new drug-radiation combinations. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents has shown great promise in visualising and quantifying active vascular density. Most existing approaches for vascular density quantification using CEUS are calculated based on image intensity and are susceptible to confounding factors and imaging artefact. Poor reproducibility is a key challenge to clinical translation. In this study, a new automated temporal and spatial signal analysis approach is developed for reproducible microbubble segmentation and quantification of contrast enhancement in human lower limbs. The approach is evaluated in vitro on phantoms and in vivo in lower limbs of healthy volunteers before and after physical exercise. In this approach, vascular density is quantified based on the relative areas microbubbles occupy instead of their image intensity. Temporal features of the CEUS image sequences are used to identify pixels that contain microbubble signals. A microbubble track density (MTD) measure, the ratio of the segmented microbubble area to the whole tissue area, is calculated as a surrogate for active capillary density. In vitro results reveal a good correlation (r2 = 0.89) between the calculated MTD measure and the known bubble concentration. For in vivo results, a significant increase (129% in average) in the MTD measure is found in lower limbs of healthy volunteers after exercise, with excellent repeatability over a series of days (intra-class correlation coefficient = 0.96). This compares to the existing state-of-the-art approach of destruction and replenishment analysis on the same patients (intra-class correlation coefficient ≤0.78). The proposed new approach shows great potential as an accurate and highly reproducible clinical tool for quantification of active vascular density. [ABSTRACT FROM AUTHOR]

The biosynthesis of the herbicide cornexistin in the fungus Paecilomyces variotii was investigated by full sequencing of its genome, knockout of key genes within its biosynthetic gene cluster and isolation and identification of intermediate compounds. The general biosynthetic pathway resembles that of byssochlamic acid and other nonadrides in the early stages, but differs in requiring fewer enzymes in the key nonadride dimerisation step, and in the removal of one maleic anhydride moiety. [ABSTRACT FROM AUTHOR]

Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY. [ABSTRACT FROM AUTHOR]

Introduction: Veteran's Affairs Office of Specialty Care (OSC) launched four national initiatives (Electronic-Consults [e-Consults], Specialty Care Access Networks-Extension for Community Healthcare Outcomes [SCAN-ECHO], Mini-Residencies, and Specialty Care Neighborhood) to improve specialty care delivery and funded a center to evaluate the initiatives. Methods: The evaluation, guided by two implementation frameworks, provides formative (administrator/provider interviews and surveys) and summative data (quantitative data on patterns of use) about the initiatives to OSC. Results: Evaluation of initiative implementation is assessed through CFIR (Consolidated Framework for Implementation Research)-grounded qualitative interviews to identify barriers/facilitators. Depending on high or low implementation, factors such as receiving workload credit, protected time, existing workflow/systems compatibility, leadership engagement, and access to information/resources were considered implementation barriers or facilitators. Findings were shared with OSC and used to further refine implementation at additional sites. Evaluation of other initiatives is ongoing. Conclusions: The mixed-methods approach has provided timely information to OSC about initiative effect and impacted OSC policies on implementation at additional sites. [ABSTRACT FROM AUTHOR]

Food contact materials containing antibacterial properties are progressively appearing in the market. Items intended to provide antimicrobial effects such as increased shelf life and food safety are incorporating silver materials during the manufacture of such products. This study examined the total silver content, release capacity, and antibacterial activity of three different silver-containing food contact materials: plastic food storage containers, a plastic cutting board, and food wrapping paper. Silver content and release were determined by Inductively Coupled Plasma Mass Spectrometry, and the results showed that, although the amount of silver in each product was similar, migration varied considerably with kind of material and simulant choice. Antimicrobial effect was tested by measuring the growth of Salmonella Typhimurium during or after exposure to the different food contact materials. The results showed that the food storage containers and wrapping paper delayed the growth of S . Typhimurium under certain conditions, but that these effects were short-lived. The strain of S . Typhimurium used in this study was found to be negative for the presence of tested silver resistance genes. The results of this study suggest that a thorough investigation should be required to show/claim the efficacy of silver-containing food contact materials for food safety purposes. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory infections (ARI) are a leading cause of morbidity and mortality globally, and are often linked to seasonal and/or meteorological conditions. Globally, Indigenous peoples may experience a different burden of ARI compared to non-Indigenous peoples. This protocol outlines our process for conducting a systematic review to investigate whether associations between ARI and seasonal or meteorological parameters differ between Indigenous and non-Indigenous groups residing in the same geographical region. Methodology: A search string will be used to search PubMed®, CAB Abstracts/CAB Direct©, and Science Citation Index® aggregator databases. Articles will be screened using inclusion/exclusion criteria applied first at the title and abstract level, and then at the full article level by two independent reviewers. Articles maintained after full article screening will undergo risk of bias assessment and data will be extracted. Heterogeneity tests, meta-analysis, and forest and funnel plots will be used to synthesize the results of eligible studies. Discussion and registration: This protocol paper describes our systematic review methods to identify and analyze relevant ARI, season, and meteorological literature with robust reporting. The results are intended to improve our understanding of potential associations between seasonal and meteorological parameters and ARI and, if identified, whether this association varies by place, population, or other characteristics. The protocol is registered in the PROSPERO database (#38051). [ABSTRACT FROM AUTHOR]

Background: The antimicrobial activity of silver nanoparticles (AgNP) has led to interest in their use in consumer products such as food contact materials, utensils, and storage containers. Incorporation of these materials into items intended for food processing and storage suggests that consumer use of these products could result in gastrointestinal exposure to AgNP, should the nanoparticles migrate from the product. The health impact of AgNP exposure is unknown, especially effects related to intestinal epithelial permeability and barrier function. This study examined the effects of AgNP exposure of different sizes (10, 20, 75 and 110 nm) and doses (20 and 100 μg/mL) on the permeability of T84 human colonic epithelial cells, which serve as an in vitro model of the human gut epithelium. Results: Results showed that effects of AgNP on the T84 epithelial cells were size- and dose-dependent, with the 10 nm AgNP causing the most significant changes. Changes in permeability of the epithelial cell monolayer, as measured by transepithelial electrical resistance, after exposure to 10 nm AgNP were most dramatic at the highest dose (100 μg/mL), but also observed at the lower dose (20 μg/mL). AgNP could be visualized inside cells using transmission electron microscopy and silver was detected in basal wells using inductively coupled plasma-mass spectrometry. Exposure to AgNP significantly affected the expression of genes involved in anchoring tight junctions, cellular proliferation and signaling, endocytosis, and cell-cell adhesion, with the 10 nm AgNP having the greatest effect. Conclusions: The results of this study show that small-size AgNP have significant effects on intestinal permeability in an in vitro model of the human gastrointestinal epithelium. Such effects have the potential to compromise the integrity of the intestinal epithelium and this disruption of barrier function could have health consequences for the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background: Red blood cell (RBC) transfusion thresholds have yet to be examined in large randomized trials in hematologic malignancies. This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy.Study Design and Methods: A randomized (2:1) study was conducted of restrictive (LOW) hemoglobin (Hb) trigger (7 g/dL) compared to higher (HIGH) Hb trigger (8 g/dL). The primary outcome was feasibility of conducting a larger trial. The four requirements for success required that more than 50% of the eligible patients could be consented, more than 75% of the patients randomized to the LOW arm tolerated the transfusion trigger, fewer than 15% of patients crossed over from the LOW arm to the HIGH arm, and no indication for the need to pause the study for safety concerns. Secondary outcomes included fatigue, bleeding, and RBCs and platelets transfused.Results: Ninety patients were consented and randomly assigned to LOW to HIGH. The four criteria for the primary objective of feasibility were met. When the number of units transfused was compared, adjusting for baseline Hb, the LOW arm was transfused on average 8.0 (95% confidence interval [CI], 6.9-9.1) units/patient while the HIGH arm received 11.7 (95% CI, 10.1-13.2) units (p = 0.0003). There was no significant difference in bleeding events or neutropenic fevers between study arms.Conclusion: This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile. This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting. [ABSTRACT FROM AUTHOR]

Climate change has increased the occurrence of heat waves, causing heat stress among humans and livestock, with potentially fatal consequences. Heat stress maps provide information about related health risks and insight for control strategies. Weather data were collected throughout Southern Ontario, and the heat stress index (HSI) was estimated for 2010–2012. Geostatistical kriging was applied to map heat stress, heat waves, and control periods. Average HSI for each period ranged from 55 to 78 during control periods, and from 65 to 84 during heat waves, surpassing levels where morbidity is known to increase substantially. Heat stress followed a temporally consistent geographic pattern. HSI maps indicate high-risk areas for heat-related illness and indicate areas where agriculture and human health may be at increased risk in future. [ABSTRACT FROM PUBLISHER]

Summary HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at ∼1 year post-infection, including one with cross-clade breadth. The nAbs bind to envelope trimer from the transmitted virus, suggesting that this interaction may have initiated development of the infant nAbs. The infant cross-clade bnAb targets the N332 supersite on envelope but, unlike adult bnAbs targeting this site, lacks indels and has low SHM. The identification of this infant bnAb illustrates that HIV-1-specific neutralization breadth can develop without prolonged affinity maturation and extensive SHM. [ABSTRACT FROM AUTHOR]

Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9-membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate-processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine-binding proteins. [ABSTRACT FROM AUTHOR]

Die von Pilzen produzierten Maleidride sind eine wichtige Klasse bioaktiver Sekundärmetaboliten, die aus sieben ‐ , acht ‐ oder neungliedrigen Carbocyclen bestehen. Jeder Cyclus ist mit einem oder zwei anellierten Maleinsäureanhydridresten substituiert. Durch Gen ‐ Knockouts und heterologe Expressionsexperimente wurde die Biosynthese von Byssochlaminsäure (ein Nonadrid) und Agnestadrid A (ein Heptadrid) untersucht. Unsere Experimente zeigen, dass der Vorläufer der Cyclisierung von einer iterativen, vollständig reduzierenden, pilzlichen Polyketidsynthase erzeugt wird, die durch eine Hydrolase und zwei Citrat ‐ verarbeitende Enzyme unterstützt wird. Die ungewöhnliche Cyclisierung wird zum einen von zwei Proteinen katalysiert, die Homologien zu Ketosteroidisomerasen aufweisen, und zum anderen von zwei weiteren Proteinen mit Homologien zu Phosphatidylethanolamin ‐ bindenden Proteinen. Rätselhafter Ringschluss: Die an der bisher unaufgeklärten Cyclisierung der biologisch aktiven, pilzlichen Naturstoffe der Maleidridfamilie – unter anderem Agnestatrid A (2) und Byssochlaminsäure (1) – beteiligten Enzyme wurden identifiziert. Die vorher unbekannten Proteine sind homolog zu Ketosteroidisomerasen (KI ‐ ähnlich) und Phosphatidylethanolamin ‐ bindenden Proteinen (PEBP ‐ ähnlich). [ABSTRACT FROM AUTHOR]

Common environmental contaminants such as bisphenols and phthalates and persistent contaminants such as polychlorinated biphenyls are thought to influence tissue homeostasis and carcinogenesis by acting as disrupters of endocrine function. In this study we investigated the direct effects of exposure to bisphenol A (BPA), mono-n-butyl phthalate (Pht), and polychlorinated biphenyl 153 (PCB153) on the proteome of primary organotypic cultures of the mouse mammary gland. At low-nanomolar doses each of these agents induced distinct effects on the proteomes of these cultures. Although BPA treatment produced effects that were similar to those induced by estradiol, there were some notable differences, including a reduction in the abundance of retinoblastomaassociated protein and increases in the Rho GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle protein CDC42. Both Pht and PCB153 induced changes that were distinct from those induced by estrogen, including decreased levels of the transcriptional corepressor C-terminal binding protein 1. Interestingly, the three chemicals appeared to alter the abundance of distinct splice forms of many proteins as well as the abundance of several proteins that regulate RNA splicing. Our combined results indicate that the three classes of chemical have distinct effects on the proteome of normal mouse mammary cultures, some estrogen-like but most estrogen independent, that influence diverse biological processes including apoptosis, cell adhesion, and proliferation. [ABSTRACT FROM AUTHOR]