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The effectiveness of wrist guards and modifying elbow posture for reducing impact-induced accelerations at the wrist and elbow, for the purpose of decreasing upper extremity injury risk during forward fall arrest, has not yet been documented in living people. A seated human pendulum was used to simulate the impact conditions consistent with landing on outstretched arms during a forward fall. Accelerometers measured the wrist and elbow response characteristics of 28 subjects following impacts with and without a wrist guard, and with elbows straight or slightly bent. Overall, the wrist guard was very effective, with significant reductions in peak accelerations at the elbow in the axial and off-axis directions, and in the off-axis direction at the wrist by almost 50%. The effect of elbow posture as an intervention strategy was mixed; a change in magnitude and direction of the acceleration response was documented at the elbow, while there was little effect at the wrist. Unique evidence was presented in support of wrist guard use in activities like in-line skating where impacts to the hands are common. The elbow response clearly shows that more proximal anatomical structures also need to be monitored when assessing the effectiveness of injury prevention strategies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to quantify decision time and classification errors made during trunk posture assessment tasks using a computerised sampling approach. Ninety (45 male, 45 female) university-aged participants, who had varying expertise with body posture evaluation, were asked to accurately classify a series of static images of the trunk using a computer interface by selecting the posture category or 'bin', within which the presented posture fell. Images were presented randomly in either a flexion/extension or lateral bending view at various distances from the boundary lines of each posture bin. Subjects with the least experience performed the tasks in the shortest amount of time; however, they also made the most errors. Expert participants reduced the number of classification errors by increasing the time of each posture classification decision. The flexion/extension task proved to take more time and resulted in more errors than the lateral bend task. The closer the presented images were to the bin boundaries, the greater was the time taken and errors made during posture classification. These data have implications for the design of posture classification biomechanical software interfaces and the training of operators who utilise the software. [ABSTRACT FROM AUTHOR]

The trunk posture misclassification errors made by novice and experienced operators were quantified as a function of the angular distance from posture bin boundaries, similar to those used in observation-based posture assessment tools such as 3DMatch. The effect that these misclassification errors had on cumulative and peak low back loads was also determined in three simulated lifting scenarios. Ninety subjects in 3 experience groups were randomly presented with images of known trunk angle via a monitor. Subjects were instructed to make quick and accurate bin selections using standardized pictures included below the images on the monitor. Mean % bin misclassification errors were approximately 32% and 22% for the flexion/extension and lateral bend views, respectively. More bin classification errors were made the closer a viewed image was to a posture bin boundary, regardless of expertise level, and the number of errors made decreased as operator experience increased. Approximately 99% of bin selections were made either in the correct bin or in the bins immediately adjacent to the correct bin in both views. Misclassification errors made in the 3 simulated lifting scenarios induced errors in peak and cumulative loads in 66% of the cases assessed, with an average absolute difference of 13.5% across all load variables. Future work is aimed at determining the effect of training and bin size on the error misclassification rate for all body segments and views. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the ability of subjects to detect a visual difference between trunk postures. Three groups of participants, ranging from novices to experts, were required to make perceptual discriminations between two trunk postures from a series of image pairs on a computer screen. Images were presented for flexion and lateral bending motions from three different reference postures in both ascending and descending directions. Overall, direction played the largest role, interacting with all other variables. Subjects were most sensitive to changes in the ascending direction, where differences were detected at an average of 2°. In the descending direction, subjects detected differences at an average of 7° between postures. These data have implications for the usability and design of posture matching-based biomechanical software interfaces and the accuracy of peak and cumulative load estimates from models that utilize such interfaces to acquire segment posture inputs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to predict 3D cumulative L4/L5 spine loads and moments incurred during non-occupational tasks, from heart rate determined physical activity level (HR-PAL). Twelve subjects were videotaped while performing activities in their own homes. HR was continuously recorded during video collection and was subsequently used to calculate the PAL over the course of the 2-hour collection session. Simple regression revealed that between 76% and 82% of the variance in 3 of the 13 cumulative load measures studied (cumulative compression force and cumulative flexion and right axial twist moments) was accounted for by HR-PAL. Four additional cumulative output variables approached statistical significance. Cumulative compression force was the best predicted of all measures studied. Predicted and actual loads were not different from each other for all significant load measures. This initial study suggests that the use of heart rate for predicting cumulative compression shows potential as a simple method to track extended periods of cumulative exposure. Future work is planned to test this method in a number of industrial settings. [ABSTRACT FROM AUTHOR]

The aim of this research was to examine the repeatability of task cycle loading to assess the feasibility of data extrapolation approaches for calculating a shift cumulative exposure. The number of trials of a lifting task that would be necessary to provide a stable estimate of the cumulative low back loads sustained during manual material handling tasks throughout a normal working day was examined. Both a lab-based experiment (n=10 males) with a highly constrained task, and an externally paced industrial sample performing their regular workday task (n=8 males), were studied. Both study groups were videotaped while performing lifting trials and 10 consecutive trials were chosen for biomechanical analysis. Cumulative loading variables were determined for each lift and accumulating means were calculated for comparison with the gold standard, or criterion measure, which was the average of all 10 trials. It was found that a minimum of 4 trials was required to provide a stable estimate of cumulative loading in the lab-based task. The lab data were tightly clustered with an overall average coefficient of variation of 5.7%. Data obtained in the industrial setting were more variable with an average coefficient of variation of 24.8%. When individual lifting cycles were extrapolated to an 8 hour shift exposure, cumulative compression for the industrial task varied by 6.3 MN x s (range=15.2 to 21.5 MN x s) for one subject and for the constrained laboratory task it varied by 5.0 MN x s (range=32.0 to 37.0 MN·s). These results highlight the importance of using multiple cycle samples to establish a stable estimate of cumulative loading prior to extrapolating for a shift exposure. [ABSTRACT FROM AUTHOR]

Background: At the beginning of the COVID-19 pandemic, some workers had the opportunity to work from home, while others remained in on-site work. The aim of the present study was to compare the psychosocial work aspects, work ability, mental health conditions and SARS-CoV-2 infection rates of Brazilian workers in remote and on-site work through a longitudinal study with quarterly follow-up assessments over a 12-month period., Method: A convenience sample of 1,211 workers from different economic sectors participated in the study, 897 of whom (74.1%) worked from home and 314 (25.9%) remained in on-site work. Psychosocial work aspects were assessed using the Copenhagen Psychosocial Questionnaire (COPSOQ). Work ability was assessed using the Work Ability Index (WAI) and the Work Ability Score (WAS). Mental health conditions and SARS-CoV-2 infection rate were recorded based on self-reported medical diagnoses. Online questionnaires were answered from June 2020 to September 2021, involving two waves of the COVID-19 pandemic. The groups were compared using chi-square tests, t-tests, and two-way ANOVA., Results: In the first wave of the pandemic, remote workers reported more quantitative demands and work-family conflicts, whereas on-site workers reported more emotional demands, low development of new skills, low commitment, low predictability, low recognition, and low satisfaction. They also reported greater occurrences of unwanted sexual attention, threats of violence, and physical violence. In the second wave, the remote group continued to report high work-family conflicts, whereas the on-site group reported - in addition to the results of the 1st wave - low influence at work, low quality of leadership, and burnout. No significant difference was found between groups with regards to the WAI in either wave. A significant difference was found for the WAS between the 3rd and 12th months (P < 0.01) in both groups. No significant differences were found between groups for the prevalence of anxiety, depression, burnout/stress, insomnia, panic syndrome, and eating disorders, except for the prevalence of insomnia at the 12-month follow-up, with higher rates in the remote group (P = 0.03). SARS-CoV-2 infection was significantly lower in the remote group (11.3%) compared to the on- site (16.9%) group (P < 0.01)., Conclusions: Psychosocial work aspects differed between remote and on-site workers. Work ability and mental health conditions were similar between groups. Remote work might have played a role in limiting the spread of the virus in Brazil had it been more widely available., (© 2024. The Author(s).)

Various species of campylobacters cause significant disease problems in both humans and animals. The continuing development of tools and methods for genetic and molecular manipulation of campylobacters enables the detailed study of bacterial virulence and disease pathogenesis. Campylobacter hepaticus is an emerging pathogen that causes spotty liver disease (SLD) in poultry. SLD has a significant economic and animal welfare impact as the disease results in elevated mortalities and significant decreases in egg production. Although potential virulence genes of C. hepaticus have been identified, they have not been further studied and characterized, as appropriate genetic tools and methods to transform and perform mutagenesis studies in C. hepaticus have not been available. In this study, the genetic manipulation of C. hepaticus is reported, with the development of novel plasmid vectors, methods for transformation, site-specific mutagenesis, and mutant complementation. These tools were used to delete the pglB gene , an oligosaccharyltransferase, a central enzyme of the N- glycosylation pathway, by allelic exchange. In the mutant strain, N -glycosylation was completely abolished. The tools and methods developed in this study represent innovative approaches that can be applied to further explore important virulence factors of C. hepaticus and other closely related Campylobacter species., Importance: Spotty liver disease (SLD) of layer chickens, caused by infection with Campylobacter hepaticus , is a significant economic and animal welfare burden on an important food production industry. Currently, SLD is controlled using antibiotics; however, alternative intervention methods are needed due to increased concerns associated with environmental contamination with antibiotics, and the development of antimicrobial resistance in many bacterial pathogens of humans and animals. This study has developed methods that have enabled the genetic manipulation of C. hepaticus . To validate the methods, the pglB gene was inactivated by allelic exchange to produce a C. hepaticus strain that could no longer N -glycosylate proteins. Subsequently, the mutation was complemented by reintroduction of the gene in trans , on a plasmid vector, to demonstrate that the phenotypic changes noted were caused by the mutation of the targeted gene. The tools developed enable ongoing studies to understand other virulence mechanisms of this important emerging pathogen., Competing Interests: D.M.A. is an employee of Bioproperties Pty Ltd, a veterinary vaccine business that manufactures and sells live vaccines for production animals. Therefore, he has a commercial interest in understanding the biology of veterinary pathogens such as Campylobacter hepaticus. All other authors declare no conflict of interest.

Background: Pickleball has grown tremendously in recent years, yet little evidence exists regarding pickleball-related injuries. This scoping review extends current work on pickleball participation by identifying positive and negative health effects associated with the sport. We summarize how pickleball impacts the health and well-being of adult participants., Methods: Searches were conducted on MEDLINE, CINAHL, ProQuest Nursing, ERIC, SPORTDiscus, PsycINFO, Scopus, CBCA Complete, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ProQuest Dissertations and Theses. Selected studies considered aspects of health and/or well-being of adult pickleball participants. Using the population/concept/context framework, participants were healthy, able-bodied adults 18 years of age or over, who had played pickleball at least once. The positive and negative outcomes of pickleball on participants' health and well-being (concept) within the context of pickleball participation were examined. Full-text articles written in English since 2013 were included. Extracted data were tabulated, and a descriptive summary with thematic analysis was completed., Results: This scoping review comprised 27 articles that met the inclusion criteria. Pickleball is promising as an exercise intervention for all adults, and there is evidence of positive social and psychological effects, and health and fitness benefits to participating in pickleball by older adults., Conclusions: Although we are still in the early stages of studying pickleball, there have been some documented health benefits of using the sport as a physical exercise intervention for adults. More research is needed on the types, prevalence, and severity of pickleball injuries and the sport's impact on younger players.

Role of dust in Salmonella transmission on chicken farms is not well characterised. Salmonella Typhimurium (ST) infection of commercial layer chickens was investigated using a novel sprinkling method of chicken dust spiked with ST and the uptake compared to a conventional oral infection. While both inoculation methods resulted in colonisation of the intestines, the Salmonella load in liver samples was significantly higher at 7 dpi after exposing chicks to sprinkled dust compared to the oral infection group. Infection of chickens using the sprinkling method at a range of doses showed a threshold for colonisation of the gut and organs as low as 1000 CFU/g of dust. Caecal content microbiota analysis post-challenge showed that the profiles of chickens infected by the sprinkling and oral routes were not significantly different; however, both challenges induced differences when compared to the uninfected negative controls. Overall, the study showed that dust sprinkling was an effective way to experimentally colonise chickens with Salmonella and alter the gut microbiota than oral gavage at levels as low as 1000 CFU/g dust. This infection model mimics the field scenario of Salmonella infection in poultry sheds. The model can be used for future challenge studies for effective Salmonella control., (© 2024 The Authors. Environmental Microbiology Reports published by John Wiley & Sons Ltd.)

Among the Salmonella reduction strategies in poultry production, one option is to use a Salmonella vaccine. The aim of vaccinating layer flocks is to reduce the shedding of wild-type Salmonella in the poultry environment, thereby reducing the contamination of poultry products (eggs and meat). Nutritive diluent and a higher dose of vaccine may enhance its colonization potential in the gut of chickens. In this study, a commercially available live attenuated vaccine (Vaxsafe ® ST) was reconstituted in different media and delivered orally to day-old chicks at three different doses (10 7 , 10 8 , and 10 9 CFU/chick). Gut colonization of the vaccine strain and the effects of vaccination on gut microbiota were assessed in commercial-layer chickens. The vaccine diluent and dosage minimally affected microbiota alpha diversity. Microbiota beta diversity was significantly different (P < 0.05) based on the vaccine diluent and dose, which indicated that the vaccinated and unvaccinated chickens had different gut microbial communities. Differences were noted in the abundance of several genera, including Blautia, Colidextribacter, Dickeya, Enterococcus, Lactobacillus, Pediococcus , and Sellimonas . The abundance of Colidextribacter was significantly lower in chickens that received vaccine reconstituted in Marek's and water diluents, while Lactobacillus abundance was significantly lower in the water group. The highest vaccine dose (10 9 CFU/chick) did not significantly alter ( P > 0.05) the abundance of microbial genera. Chicken age affected the microbiota composition more significantly than the vaccine dose and diluent. The abundance of Lactobacillus, Blautia, Caproiciproducens, Pediococcus , and Colidextribacter was significantly higher on day 14 compared with day 7 post-vaccination. The Salmonella Typhimurium vaccine load in the caeca was not significantly affected by diluent and vaccine dose; however, it was significantly lower ( P < 0.0001) on day 14 compared with day 7 post-vaccination. Overall, the S . Typhimurium vaccine minimally affected the gut microbiota structure of layer chicks, whereas changes in microbiota were more significant with chicken age., Competing Interests: The authors declare that this study received funding from Bioproperties Pty Ltd. Bioproperties Pty Ltd. was involved in study design, interpretation of data and reviewing this article, and supplied the vaccine and Marek's diluent used in this research project. GU and DA are employees of Bioproperties Pty Ltd, a commercial veterinary vaccine business that manufactures and sells the Vaxsafe ST vaccine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Khan, McWhorter, Andrews, Underwood, Moore, Van, Gast and Chousalkar.)

Synthetic biology applications would benefit from protein modules of reduced complexity that function orthogonally to cellular components. As many subcellular processes depend on peptide-protein or protein-protein interactions, de novo designed polypeptides that can bring together other proteins controllably are particularly useful. Thanks to established sequence-to-structure relationships, helical bundles provide good starting points for such designs. Typically, however, such designs are tested in vitro and function in cells is not guaranteed. Here, we describe the design, characterization, and application of de novo helical hairpins that heterodimerize to form 4-helix bundles in cells. Starting from a rationally designed homodimer, we construct a library of helical hairpins and identify complementary pairs using bimolecular fluorescence complementation in E. coli . We characterize some of the pairs using biophysics and X-ray crystallography to confirm heterodimeric 4-helix bundles. Finally, we demonstrate the function of an exemplar pair in regulating transcription in both E. coli and mammalian cells.

The live attenuated temperature sensitive vaccine strain MS-H (Vaxsafe® MS, Bioproperties Pty. Ltd., Australia) is widely used to control disease associated with M. synoviae infection in commercial poultry. MS-H was derived from a field strain (86079/7NS) through N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-induced mutagenesis. Whole genomic sequence analysis of the MS-H and comparison with that of the 86079/7NS have found that MS-H contains 32 single nucleotide polymorphisms (SNPs). Three of these SNPs, found in the obgE, oppF and gapdh genes, have been shown to be prone to reversion under field condition, albeit at a low frequency. Three MS-H reisolates containing the 86079/7NS genotype in obgE (AS2), obgE and oppF (AB1), and obgE, oppF and gapdh (TS4), appeared to be more immunogenic and transmissible compared to MS-H in chickens. To investigate the influence of these reversions in the in vitro fitness of M. synoviae, the growth kinetics and steady state metabolite profiles of the MS-H reisolates, AS2, AB1 and TS4, were compared to those of the vaccine strain. Steady state metabolite profiling of the reisolates showed that changes in ObgE did not significantly influence the metabolism, while changes in OppF was associated with significant alterations in uptake of peptides and/or amino acids into the M. synoviae cell. It was also found that GAPDH plays a role in metabolism of the glycerophospholipids as well as an arginine deiminase (ADI) pathway. This study underscores the role of ObgE, OppF and GAPDH in M. synoviae metabolism, and suggests that the impaired fitness arising from variations in ObgE, OppF and GAPDH contributes to attenuation of MS-H., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was funded by the Australian Research Council and Bioproperties Pty. Ltd., Australia through the ARC Linkage Project grant LP180100762. The MS-H vaccine is produced by Bioproperties Pty. Ltd., Australia., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Poultry vaccines are often administered using water as a suspension media and applied using an oral or coarse spray method. Gel-based vaccine diluents have been developed as an alternative vaccine delivery method. Gels are more viscous, and droplets adhere more effectively to feathers giving the vaccine a longer time to be ingested (through preening). Application of gel diluents with live bacterial vaccines, however, is limited. The present study tested a gel diluent prepared in various media, using a live, attenuated Salmonella Typhimurium vaccine, Vaxsafe ST. Reconstitution in gel diluent did not negatively affect vaccine viability or motility. The invasive capacity of vaccine suspended in gel diluent into cultured intestinal epithelial cells was also tested. Results demonstrated that vaccine suspended in gel diluent retained invasiveness. Day old chicks were orally administered with Vaxsafe ST suspended in gel diluent to characterize in vivo colonization capacity of the vaccine. The results revealed that the VaxSafe ST suspended in gel diluent could efficiently colonize the caeca of chicks, which is needed for the development of effective immunity., Competing Interests: Conflict of Interest GJU and DMA are employees of Bioproperties Pty Ltd, a veterinary vaccine business that manufactures and sells live vaccines for production animals. Therefore, they have a commercial interest in understanding the biology of veterinary pathogens such as Salmonella Typhimurium. All other authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Soft tissues overlying the hip play a critical role in protecting against fractures during fall-related hip impacts. Consequently, the development of an efficient and cost-effective method for estimating hip soft tissue thicknesses in living people may prove to be valuable for assessing an individual's injury risk and need to adopt preventative measures. The present study used multiple linear stepwise regression to generate prediction equations from participant characteristics (i.e., height, sex) and anthropometric measurements of the pelvis, trunk, and thigh to estimate soft tissue thickness at the iliac crests (IC) and greater trochanters (GT) in younger (16-35 years of age: 37 males, 37 females) and older (36-65 years of age: 38 males, 38 females) adults. Equations were validated against soft tissue thicknesses measured from full body Dual-energy X-ray Absorptiometry scans of independent samples (younger: 13 males, 13 females; older: 13 males, 12 females). Younger adult prediction equations exhibited adjusted R2 values ranging from 0.704 to 0.791, with more explained variance for soft tissue thicknesses at the GT than the IC; corresponding values for the older adult equations were higher overall and ranged from 0.819 to 0.852. Predicted and actual soft tissue thicknesses were significantly correlated for both the younger (R2 = 0.466 to 0.738) and older (R2 = 0.842 to 0.848) adults, averaging ≤ 0.75cm of error. This research demonstrates that soft tissue thicknesses overlying the GT and IC can be accurately predicted from equations using anthropometric measurements. These equations can be used by clinicians to identify individuals at higher risk of hip fractures who may benefit from the use of preventative measures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Town et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Over the course of the COVID-19 pandemic, SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and immune escape capabilities, such as Delta and Omicron, have triggered waves of new COVID-19 infections worldwide, and Omicron subvariants continue to represent a global health concern. Tracking the prevalence and dynamics of VOCs has clinical and epidemiological significance and is essential for modeling the progression and evolution of the COVID-19 pandemic. Next generation sequencing (NGS) is recognized as the gold standard for genomic characterization of SARS-CoV-2 variants, but it is labor and cost intensive and not amenable to rapid lineage identification. Here we describe a two-pronged approach for rapid, cost-effective surveillance of SARS-CoV-2 VOCs by combining reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) and periodic NGS with the ARTIC sequencing method. Variant surveillance by RT-qPCR included the commercially available TaqPath COVID-19 Combo Kit to track S-gene target failure (SGTF) associated with the spike protein deletion H69-V70, as well as two internally designed and validated RT-qPCR assays targeting two N-terminal-domain (NTD) spike gene deletions, NTD156-7 and NTD25-7. The NTD156-7 RT-qPCR assay facilitated tracking of the Delta variant, while the NTD25-7 RT-qPCR assay was used for tracking Omicron variants, including the BA.2, BA.4, and BA.5 lineages. In silico validation of the NTD156-7 and NTD25-7 primers and probes compared with publicly available SARS-CoV-2 genome databases showed low variability in regions corresponding to oligonucleotide binding sites. Similarly, in vitro validation with NGS-confirmed samples showed excellent correlation. RT-qPCR assays allow for near-real-time monitoring of circulating and emerging variants allowing for ongoing surveillance of variant dynamics in a local population. By performing periodic sequencing of variant surveillance by RT-qPCR methods, we were able to provide ongoing validation of the results obtained by RT-qPCR screening. Rapid SARS-CoV-2 variant identification and surveillance by this combined approach served to inform clinical decisions in a timely manner and permitted better utilization of sequencing resources.

Campylobacter hepaticus is an important pathogen which causes Spotty Liver Disease (SLD) in layer chickens. SLD results in an increase in mortality and a significant decrease in egg production and therefore is an important economic concern of the global poultry industry. The human pathogen Campylobacter jejuni encodes an N-linked glycosylation system that plays fundamental roles in host colonization and pathogenicity. While N-linked glycosylation has been extensively studied in C. jejuni and is now known to occur in a range of Campylobacter species, little is known about C. hepaticus glycosylation. In this study glycoproteomic analysis was used to confirm the functionality of the C. hepaticus N-glycosylation system. It was shown that C. hepaticus HV10 T modifies > 35 proteins with an N-linked heptasaccharide glycan. C. hepaticus shares highly conserved glycoproteins with C. jejuni that are involved in host colonisation and also possesses unique glycoproteins which may contribute to its ability to survive in challenging host environments. C. hepaticus N-glycosylation may function as an important virulence factor, providing an opportunity to investigate and develop a better understanding the system's role in poultry infection., (© 2023. The Author(s).)

Prophylactic use of antimicrobials after administration of live vaccines is a common practice in the poultry industry, but the impact of this on the efficacy and duration of protection induced by the vaccines is unknown. The effect of treatment with tylosin on the efficacy of vaccination with the live attenuated M. gallisepticum strain, Vaxsafe MG ts-304, was examined. This vaccine has previously been shown to provide protection for at least 57 weeks. Ten-week-old specific-pathogen-free chickens were vaccinated with Vaxsafe MG ts-304 and then treated with tylosin at a therapeutic dose in drinking water from 6 weeks after vaccination. Tylosin was withdrawn 5 days before challenge with M. gallisepticum strain Ap3AS at 6, 10, 14, 18 or 22 weeks after vaccination. Air sac lesions, tracheal mucosal thickening and the concentrations of serum antibodies against M. gallisepticum were assessed at 2 weeks after challenge. The protection induced by the vaccine in the 6 weeks before initiation of tylosin treatment persisted for 18 weeks after vaccination, with lesions only observed in the air sacs of vaccinated birds that had been treated with tylosin after challenge at 22 weeks after vaccination. Concentrations of serum antibodies against M. gallisepticum began to decrease in vaccinated birds that had been treated with tylosin from 16 weeks after vaccination. This study has suggested that treatment of chickens with tylosin after vaccination with a live attenuated mycoplasma vaccine reduces the duration of protective immunity afforded by the vaccine., Competing Interests: Declaration of Competing Interest Chris J. Morrow, Gregory J. Underwood and Daniel M. Andrews are employees of Bioproperties Pty. Ltd. The other authors have no potential conflicts of interest (financial, professional or personal) related to the research reported here. The University of Melbourne licenses the M. gallisepticum ts-11 and Vaxsafe MG ts-304 vaccines to Bioproperties Pty. Ltd. and, as employees of the university involved in the creation of Vaxsafe MG ts-304, A.KC, P.K.S, P.F.M and G.F.B are entitled to a share of any royalties generated from this license., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The Mycoplasma synoviae live attenuated vaccine strain MS-H (Vaxsafe MS; Bioproperties Pty., Ltd., Australia) is commonly used around the world to prevent chronic infections caused by M. synoviae in birds and to minimize economic losses in the poultry industry. MS-H is a temperature-sensitive strain that is generated via the chemical mutagenesis of a virulent M. synoviae isolate, 86079/7NS. 32 single nucleotide polymorphisms have been found in the genome of MS-H compared to that of 86079/7NS, including 25 in predicted coding sequences (CDSs). There is limited information on the stability of these mutations in MS-H in vitro during the propagation of the vaccine manufacturing process or in vivo after the vaccination of chickens. Here, we performed a comparative analysis of MS-H genomes after in vitro and in vivo passages under different circumstances. Studying the dynamics of the MS-H population can provide insights into the factors that potentially affect the health of vaccinated birds. The genomes of 11 in vitro laboratory passages and 138 MS-H bird reisolates contained a total of 254 sequence variations. Of these, 39 variations associated with CDSs were detected in more than one genome (range = 2 to 62, median = 2.5), suggesting that these sequences are particularly prone to mutations. From the 25 CDSs containing previously characterized variations between MS-H and 86079/7NS, 7 were identified in the MS-H reisolates and progenies examined here. In conclusion, the MS-H genome contains individual regions that are prone to mutations that enable the restoration of the genotype or the phenotype of wild-type 86079/7NS in those regions. However, accumulated mutations in these regions are rare. IMPORTANCE Preventative measures, such as vaccination, are commonly used for the control of mycoplasmal infections in poultry. A live attenuated vaccine strain (Vaxsafe MS; MS-H; Bioproperties Pty. Ltd., Australia) is used for the prevention of disease caused by M. synoviae in many countries. However, information on the stability of previously characterized mutations in the MS-H genome is limited. In this study, we performed a comparative analysis of the whole-genome sequences of MS-H seeds used for vaccine manufacturing, commercial batches of the vaccine, cultures minimally passaged under small-scale laboratory and large-scale manufacturing conditions, MS-H reisolated from specific-pathogen-free (SPF) chickens that were vaccinated under controlled conditions, and MS-H reisolated from vaccinated commercial poultry flocks around the world. This study provides a comprehensive assessment of genome stability in MS-H after in vitro and in vivo passages under different circumstances and suggests that most of the mutations in the attenuated MS-H vaccine strain are stable.

Mycoplasma gallisepticum is the primary causative agent of chronic respiratory disease in poultry, and vaccination is the measure most commonly used for its control. Pathological changes caused by M. gallisepticum are mainly observed in the trachea and air sacs, but assessment of air sac lesions is subjective. Standardized parameters for evaluation of pathological changes, and their reproducibility and discrimination in uninfected and infected groups, are critical when assessing the efficacy of M. gallisepticum vaccination. This study reviewed and critically appraised the published literature on evaluation of vaccine efficacy against pathological changes caused by M. gallisepticum in poultry in the trachea and air sacs. A search of four electronic databases, with subsequent manual filtering, identified 23 eligible papers published since 1962 describing the assessment of histopathological changes in the trachea using tracheal lesion scores and/or measurement of tracheal mucosal thicknesses and assessment of gross air sac lesions using lesion scores. Measurement of tracheal lesions proved a more reliable and robust method of assessing disease induced by M. gallisepticum when compared to assessment of air sac lesions, highlighting the importance of including assessment of tracheal lesions as the primary outcome variable in vaccine efficacy studies. In addition, this study also identified the necessity for use of a standardized model for evaluation and reporting on M. gallisepticum vaccines to minimize variations between vaccine efficacy studies and to allow direct comparisons between them. RESEARCH HIGHLIGHTS Tracheal and air sac lesions have been used to assess M. gallisepticum vaccine efficacy.The specific parameters and statistical tests used to compare tracheal and air sac lesions vary greatly.Measures of tracheal lesions are more discriminatory than measures of air sac lesions.A standardized model is needed to evaluate vaccines against infection with M. gallisepticum .

Infections caused by Mycoplasma synoviae are major welfare and economic concerns in poultry industries worldwide. These infections cause chronic respiratory disease and/or synovitis in chickens and turkeys leading to reduced production and increased mortality rates. The live attenuated vaccine strain MS-H (Vaxsafe ® MS), commonly used for protection against M. synoviae infection in many countries, contains 32 single nucleotide variations compared to its wildtype parent strain, 86079/7NS. Genomic analysis of vaccine strains reisolated from flocks following the administration of MS-H has identified reversions to the original 86079/7NS sequence in the obgE , oppF and gapdh genes. Here, three MS-H field reisolates containing the 86079/7NS genotype in obgE (AS2), obgE and oppF (AB1), and obgE , oppF and gapdh (TS4), as well as the vaccine MS-H and the parental strain 86079/7NS were experimentally inoculated to chickens. The strains were assessed for their ability to infect and elicit immune responses in the recipient chickens, as well as in naïve in-contact chickens. Despite the loss of temperature sensitivity phenotype and colonization of the reisolates in the lower respiratory tract, there was no significant differences detected in the microscopic mucosal thickness of the middle or lower trachea of the inoculated chickens. Concurrent reversions in ObgE, OppF and GAPDH proteins were associated with higher gross air sac lesion scores and increased microscopic upper-tracheal mucosal thickness in chickens directly inoculated with the reisolates following intratracheal administration of a virulent strain of infectious bronchitis virus. The gross air sac lesions of the chickens in-contact with those inoculated with reisolates were not significantly different to those of chickens in-contact with MS-H inoculated chickens, suggesting that horizontal transmission of the reisolates in the poultry flock will not lead to higher pathogenicity or clinical signs. These results suggest a significant role of GAPDH and/or cumulative effect of ObgE, OppF and GAPDH on M. synoviae pathogenicity. Future experiments will be required to investigate the effect of single mutations in gapdh or oppF gene on pathogenicity of M. synoviae ., Competing Interests: This study was funded by the Australian Research Council and Bioproperties Pty. Ltd. through the ARC Linkage Project grant LP180100762. The MS-H vaccine is produced by the Bioproperties Pty. Ltd., Australia. The authors declare that this study received funding from Bioproperties Pty. Ltd. The funder had the following involvement in the study: study design, decision to publish, and reviewing the manuscript., (Copyright © 2022 Klose, Omotainse, Zare, Vaz, Armat, Shil, Wawegama, Kanci Condello, O'Rourke, Disint, Andrews, Underwood, Morrow, Marenda and Noormohammadi.)

The role of B-cell-activating factor (BAFF) in B-lymphocyte biology has been comprehensively studied, but its contributions to innate immunity remain unclear. Natural killer (NK) cells form the first line of defense against viruses and tumors, and have been shown to be defective in patients with systemic lupus erythematosus (SLE). The link between BAFF and NK cells in the development and progression of SLE remains unstudied. By assessing NK cell numbers in wild-type (WT), BAFF -/- (BAFF deficient), BAFF-R -/- (BAFF receptor deficient), TACI -/- (transmembrane activator and calcium modulator and cyclophilin ligand interactor deficient), BCMA -/- (B-cell maturation antigen deficient) and BAFF transgenic (Tg) mice, we observed that BAFF signaling through BAFF-R was essential for sustaining NK cell numbers in the spleen. However, according to the cell surface expression of CD27 and CD11b on NK cells, we found that BAFF was dispensable for NK cell maturation. Ex vivo and in vivo models showed that NK cells from BAFF -/- and BAFF Tg mice produced interferon-γ and killed tumor cells at a level similar to that in WT mice. Finally, we established that NK cells do not express receptors that interact with BAFF in the steady state or in the BAFF Tg mouse model of SLE. Our findings demonstrate that BAFF has an indirect effect on NK cell homeostasis and no effect on NK cell function., (© 2022 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

The design of completely synthetic proteins from first principles- de novo protein design-is challenging. This is because, despite recent advances in computational protein-structure prediction and design, we do not understand fully the sequence-to-structure relationships for protein folding, assembly, and stabilization. Antiparallel 4-helix bundles are amongst the most studied scaffolds for de novo protein design. We set out to re-examine this target, and to determine clear sequence-to-structure relationships, or design rules, for the structure. Our aim was to determine a common and robust sequence background for designing multiple de novo 4-helix bundles. In turn, this could be used in chemical and synthetic biology to direct protein-protein interactions and as scaffolds for functional protein design. Our approach starts by analyzing known antiparallel 4-helix coiled-coil structures to deduce design rules. In terms of the heptad repeat, abcdefg - i.e. , the sequence signature of many helical bundles-the key features that we identify are: a = Leu, d = Ile, e = Ala, g = Gln, and the use of complementary charged residues at b and c. Next, we implement these rules in the rational design of synthetic peptides to form antiparallel homo- and heterotetramers. Finally, we use the sequence of the homotetramer to derive in one step a single-chain 4-helix-bundle protein for recombinant production in E. coli . All of the assembled designs are confirmed in aqueous solution using biophysical methods, and ultimately by determining high-resolution X-ray crystal structures. Our route from peptides to proteins provides an understanding of the role of each residue in each design., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Most ergonomics studies on office workstations evaluate the effects of an intervention only by subjective measures such as musculoskeletal pain and discomfort. Limited evidence has been provided regarding risk factor reduction in office environments through standardized methods assessments. The Rapid Office Strain Assessment (ROSA) tool can provide an estimation of risk factor exposure for office workers as a means by which the outcome of interventions can be quantified., Purpose: The aim of the study was to evaluate if ROSA scores reflect changes in risk factors after an ergonomics intervention among office workers., Methods: Office workers (n = 60) were divided into two groups. The experimental group received a workstation intervention and the control group received no intervention. Changes in ROSA scores were compared before and after the intervention in both groups., Results: Statistically significant reductions in the ROSA final and section scores occurred after the intervention in the experimental group with (mean reduction of 2.9, 0.8 and 1.6 points for sections A, B and C, respectively). In contrast, no differences were detected in the control group (mean increase of 0.1 point for sections A and C and mean reduction of 0.1 point for Section B)., Conclusions: These findings show that ROSA scores reflect changes in risk factors after an ergonomics intervention in an office environment. Consequently, this tool can be used for identifying and controlling risk factors among computer workers, before and after interventions., (© 2022. The Author(s).)

Due to rises in antibiotic resistance, fate and transport of antibiotics in soil systems requires greater understanding to determine potential risks to human and animal health. Adsorption coefficients (K d and K f ) are standard measures for determining sorption capacity and partitioning behavior of organic contaminants in solid matrices. Frequently, sorption studies use higher antibiotic concentrations (mg L -1 ) and larger spiked water volume to mass of soil (>5:1), which may not reflect sorption behaviors of antibiotics at low concentrations (ng L -1 - μg L -1 ) in natural soils. The aim of this study was to determine sorption and desorption behaviors of four antibiotics commonly found in soils due to wastewater reuse using parameters replicating typical soil conditions. Concentrations (μg L -1 ) of sulfamethoxazole (SMX), trimethoprim (TMP), lincomycin (LIN) and ofloxacin (OFL) were equilibrated with four soil types at a 2:1 ratio of spiked water volume to mass of soil, which better represents field conditions. Log K f and log K foc value ranges in this study were 1.88-1.95 and 3.2-4.7 for TMP, 0.43-1.4 and 2.7-3.2 for SMX, and 0.65-1.4 and 2.0-4.1 for LIN, respectively. Ofloxacin adsorbed tightly to soil particles, and adsorption coefficients could not be calculated. Sorption values were higher than previous studies that used similar soil types but had higher ratios of spiking solution to mass of soil (>5:1). Overall, OFL and TMP are expected to strongly interact with soil particles and be less mobile, while SMX and LIN are expected to be more mobile due to weaker sorption interactions., (Published by Elsevier Ltd.)

Phosphatidyl inositol (4,5)-bisphosphate (PI(4,5)P 2 ) plays several key roles in human biology and the lipid kinase that produces PI(4,5)P 2 , PIP5K, has been hypothesized to provide a potential therapeutic target of interest in the treatment of cancers. To better understand and explore the role of PIP5K in human cancers there remains an urgent need for potent and specific PIP5K inhibitor molecules. Following a high throughput screen of the AstraZeneca collection, a novel, moderately potent and selective inhibitor of PIP5K, 1, was discovered. Detailed exploration of the SAR for this novel scaffold resulted in the considerable optimization of both potency for PIP5K, and selectivity over the closely related kinase PI3Kα, as well as identifying several opportunities for the continued optimization of drug-like properties. As a result, several high quality in vitro tool compounds were identified (8, 20 and 25) that demonstrate the desired biochemical and cellular profiles required to aid better understanding of this complex area of biology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The emerging field of artificial intelligence (AI) will probably affect the practice for the next generation of doctors. However, the students' views on AI have not been largely investigated. Methods: An anonymous electronic survey on AI was designed for medical and dental students to explore: (1) sources of information about AI, (2) AI applications and concerns, (3) AI status as a topic in medicine, and (4) students' feelings and attitudes. The questionnaire was advertised on social media platforms in 2020. Security measures were employed to prevent fraudulent responses. Mann-Whitney U -test was employed for all comparisons. A sensitivity analysis was also performed by binarizing responses to express disagreement and agreement using the Chi-squared test. Results: Three thousand one hundred thirty-three respondents from 63 countries from all continents were included. Most respondents reported having at least a moderate understanding of the technologies underpinning AI and of their current application, with higher agreement associated with being male ( p < 0.0001), tech-savvy ( p < 0.0001), pre-clinical student ( p < 0.006), and from a developed country ( p < 0.04). Students perceive AI as a partner rather than a competitor (72.2%) with a higher agreement for medical students ( p = 0.002). The belief that AI will revolutionize medicine and dentistry (83.9%) with greater agreement for students from a developed country ( p = 0.0004) was noted. Most students agree that the AI developments will make medicine and dentistry more exciting (69.9%), that AI shall be part of the medical training (85.6%) and they are eager to incorporate AI in their future practice (99%). Conclusion: Currently, AI is a hot topic in medicine and dentistry. Students have a basic understanding of AI principles, a positive attitude toward AI and would like to have it incorporated into their training., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bisdas, Topriceanu, Zakrzewska, Irimia, Shakallis, Subhash, Casapu, Leon-Rojas, Pinto dos Santos, Andrews, Zeicu, Bouhuwaish, Lestari, Abu-Ismail, Sadiq, Khamees, Mohammed, Williams, Omran, Ismail and Ebrahim.)

Purpose of Review Given the rapid development of diagnostic approaches to test for and diagnose infection with SARS-CoV-2 and its associated variants including Omicron (B.1.1.529), many options are available to diagnose infection. Multiple established diagnostic companies are now providing testing platforms whereas initially, testing was being performed with simple PCR-based tests using standard laboratory reagents. Recent Findings Additional testing platforms continue to be developed, including those to detect specific variants, but challenges with testing, including obtaining testing reagents and other related supplies, are frequently encountered. With time, the testing supply chain has improved, and more established companies are providing materials to support these testing efforts. In the United States (U.S.), the need for rapid assay development and subsequent approval through the attainment of emergency use authorization (EUA) has superseded the traditional arduous diagnostic testing approval workflow mandated by the FDA. Through these efforts, the U.S. has been able to continue to significantly increase its testing capabilities to address this pandemic; however, challenges still remain due to the diversity of the performance characteristics of tests being utilized and newly discovered viral variants. Summary This review provides an overview of the current diagnostic testing landscape, with pertinent information related to SARS-CoV-2 virology, variants and antibody responses that are available to diagnose infection in the U.S.

The CD8αβ heterodimer plays a crucial role in the stabilization between major histocompatibility complex class I molecules (MHC-I) and the T cell receptor (TCR). The interaction between CD8 and MHC-I can be regulated by posttranslational modifications, which are proposed to play an important role in the development of CD8 T cells. One modification that has been proposed to control CD8 coreceptor function is ribosylation. Utilizing NAD + , the ecto-enzyme adenosine diphosphate (ADP) ribosyl transferase 2.2 (ART2.2) catalyzes the addition of ADP-ribosyl groups onto arginine residues of CD8α or β chains and alters the interaction between the MHC and TCR complexes. To date, only interactions between modified CD8 and classical MHC-I (MHC-Ia), have been investigated and the interaction with non-classical MHC (MHC-Ib) has not been explored. Here, we show that ADP-ribosylation of CD8 facilitates the binding of the liver-restricted nonclassical MHC, H2-Q10, independent of the associated TCR or presented peptide, and propose that this highly regulated binding imposes an additional inhibitory leash on the activation of CD8-expressing cells in the presence of NAD + . These findings highlight additional important roles for nonclassical MHC-I in the regulation of immune responses., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The synthetic cadaver is a high-fidelity model intended to replace or supplement other anatomy learning modalities. Academic attainment and student perceptions were examined in an undergraduate human anatomy course using a combination of plastic models and synthetic cadavers to learn lower body anatomy ("Experimental group"), compared to a Historical group who used only plastic models. Grades on an upper body test, for which both groups used only plastic models, were compared to ensure that no academic differences existed between groups (P = 0.7653). Students in the Experimental group performed better on the lower body test for which they used both plastic models and synthetic cadavers (median = 73.8% (95% CI: 72.0%-75.0%) compared to the Historical group (70.1% (95% CI: 68.3%-70.7%), P < 0.0001); however, less than half of students (49%) attributed this to the synthetic cadavers. Students' perception of laboratory resources (P < 0.0001) and learning experience (P < 0.0001) both improved with the addition of synthetic cadavers compared to using only plastic models, and 60% of students in the Experimental group agreed that the synthetic cadavers would be a key reason that they would choose that institution for undergraduate studies. This investigation showed improved student grades when plastic models and synthetic cadavers were combined, in addition to improved student perceptions of the learning experience. Results of the student questionnaires also suggested that although synthetic cadavers carry a notable up-front cost, they may be a useful recruitment tool for institutions., (© 2020 American Association for Anatomy.)