DNA methylation haplotype block signatures responding to Staphylococcus aureus subclinical mastitis and association with production and health traits.

BACKGROUND: DNA methylation has been documented to play vital roles in diseases and biological processes. In bovine, little is known about the regulatory roles of DNA methylation alterations on production and health traits, including mastitis. RESULTS: Here, we employed whole-genome DNA methylation sequencing to profile the DNA methylation patterns of milk somatic cells from sixteen cows with naturally occurring Staphylococcus aureus (S. aureus) subclinical mastitis and ten healthy control cows. We observed abundant DNA methylation alterations, including 3,356,456 differentially methylated cytosines and 153,783 differential methylation haplotype blocks (dMHBs). The DNA methylation in regulatory regions, including promoters, first exons and first introns, showed global significant negative correlations with gene expression status. We identified 6435 dMHBs located in the regulatory regions of differentially expressed genes and significantly correlated with their corresponding genes, revealing their potential effects on transcriptional activities. Genes harboring DNA methylation alterations were significantly enriched in multiple immune- and disease-related pathways, suggesting the involvement of DNA methylation in regulating host responses to S. aureus subclinical mastitis. In addition, we found nine discriminant signatures (differentiates cows with S. aureus subclinical mastitis from healthy cows) representing the majority of the DNA methylation variations related to S. aureus subclinical mastitis. Validation of seven dMHBs in 200 cows indicated significant associations with mammary gland health (SCC and SCS) and milk production performance (milk yield). CONCLUSIONS: In conclusion, our findings revealed abundant DNA methylation alterations in milk somatic cells that may be involved in regulating mammary gland defense against S. aureus infection. Particularly noteworthy is the identification of seven dMHBs showing significant associations with mammary gland health, underscoring their potential as promising epigenetic biomarkers. Overall, our findings on DNA methylation alterations offer novel insights into the regulatory mechanisms of bovine subclinical mastitis, providing further avenues for the development of effective control measures.

IgA nephropathy in children with minimal proteinuria: to biopsy or not to biopsy?

BACKGROUND: Tubulointerstitial lesions and glomerular inflammation severity have been shown to correlate with proteinuria in children with IgA nephropathy (cIgAN). However, there is a lack of data regarding severity of histopathologic findings in cIgAN in patients with minimal to absent proteinuria since kidney biopsy indications are not well defined in these cases. METHODS: Twenty-eight cIgAN patients with kidney biopsy from 4 different centers in Paris (France) and Montreal (Canada) with a urine protein/creatinine ratio (UPCr) ≤ 0.03 g/mmol and a normal estimated glomerular filtration rate (eGFR > 90 ml/min/1.73 m2) on the day of kidney biopsy prior to treatment were included. RESULTS: Median age was 11.82 (9.32-13.45) years, and median follow-up was 4 years (2.87-6.53). At time of biopsy, median eGFR was 116 (102.3-139.7) ml/min/1.73 m2, and median UPCr was 0.02 (0.011-0.03) g/mmol. Microscopic or macroscopic hematuria was present in 35.7% and 64.3% of cases, respectively. Kidney biopsy microscopy analysis showed mesangial (M1), endocapillary (E1), or extracapillary (C1) hypercellularity in 53.5%, 32.1%, and 7.1% of patients, respectively. Chronic histological lesions were also present: glomerulosclerosis (S1) in 42.8% and tubular atrophy/interstitial fibrosis in 7.1%. Podocytopathic features were detected in 21.4%. An ACE inhibitor or immunosuppressive therapy (IS) was prescribed in 42.8% and 21.4% of these patients respectively. One-third (35.7%) received no treatment. At last follow-up, median eGFR was 111.9 (90.47-136.1) ml/min/1.73 m2, and median UPCr was 0.028 (0.01-0.03) g/mmol. CONCLUSION: cIgAN with minimal proteinuria at time of biopsy might be linked with acute and chronic glomerular lesions.

Dairy farmer's income, working time, and antimicrobial use under different dry cow therapy protocols.

Mastitis is one of the most common diseases of dairy cattle. It has a high impact on farm economy, farmers' working time, and antimicrobial usage (AMU). Selective dry cow therapy (SDCT) is an effective means of reducing AMU without negatively affecting udder health. The objective of our study was to evaluate the impact of SDCT implementation on farmer's income, working time, and AMU, using a bioeconomic model. A stochastic dairy simulation model (DairyHealthSim) based on a weekly model was used to simulate herd dynamics, reproduction, milk production, culling decisions, health outcomes, and the management of health events. A specific module was developed for the simulation of quarter-level intramammary infection (IMI) acquisition and elimination during the lactation and dry-off periods, and 25 different farm settings were defined to represent herds with various udder health situations. We then defined 20 scenarios of SDCT by combining both the use of different thresholds of somatic cell count and milk bacteriology for treatment allocation and the use of internal teat sealant (ITS). All SDCT protocols had a low impact on farmer's income, and we identified some protocols with a positive farm gross margin (up to 15.83 CA$/dried- cow). We also found that adding an ITS to all cows led to greater economic gain. The application of SDCT had a low impact on farmers' working time, except when milk bacteriology was used for decision-making. Antimicrobial treatment to all cows above 200,000 cells/mL at last control, with the use of ITS on all cows, seems a good choice in most dairy farms. These findings could be used to convince farmers to adopt this strategy at dry-off.

Redefining On-Farm Practices: The Perceived Impact of a Responsible Antimicrobial Use Regulation on Dairy Farmers.

The global food animal industry faces a growing concern regarding antimicrobial resistance (AMR), primarily driven by the use of antimicrobials (AMs) for the treatment, control, and prevention of diseases. Addressing this challenge requires promoting responsible antimicrobial use (AMU) practices. In 2019, the province of Québec, Canada, took a significant step by implementing a regulation that limits the use of AMs of very high importance for human medicine (category I AMs as defined by Health Canada) in the food animal industry. However, the implementation of such regulation can significantly influence behavioral shifts among producers, contributing to the wider effort against AMR. Therefore, the objective of this observational study was to describe the perceived changes in knowledge of dairy producers and on-farm practices following the implementation of this regulation, using a cohort design. Data collection involved administering questionnaires to 87 dairy producers from 3 regions of the province of Québec (Estrie, Montérégie, Centre-Du-Québec) before (2017-2018) and after (2020-2021) the implementation of the regulation. The questionnaires explored the descriptive characteristics of farms, the knowledge of producers about the categorization of AMs, their on-farm treatment practices, and the perceived impacts of the regulation. Statistical analysis included t-tests and McNemar tests to compare the paired data obtained using the 2 questionnaires. The results indicated an increase in the knowledge score (the number of AMs correctly categorized by the producers by their importance for human medicine) after the implementation of the regulation, suggesting an improved understanding of the categorization of AMs based on their importance for human medicine. Trends in AMU practices for treating clinical mastitis and reproductive diseases suggested that category I AMs were less likely to be reported as the primary treatment after the regulation, while category II AMs were more often reported as primary treatment. Adoption of the selective dry cow therapy method significantly increased, while the use of teat sealants remained unchanged. Moreover, producers had divergent perceptions regarding the effect of the regulation on the cure rates and disease frequencies. This disparity emphasizes the need for comprehensive data collection to discern the risks associated with such regulatory shifts. The study acknowledges several limitations, including the potential for recall bias, confirmation bias, and desirability bias. Despite these limitations, this study shows that implementing regulations to encourage responsible AMU drives positive transformations in producers' knowledge and on-farm practices. This underscores the pivotal impact of proactive interventions in combating the escalating threat of AMR within the global food animal industry.

Adoption and decision factors regarding selective treatment of clinical mastitis on Canadian dairy farms.

As clinical mastitis (CM) treatments are responsible for a large portion of antimicrobial use on dairy farms, many selective CM treatment protocols have been developed and evaluated against a blanket treatment approach of CM cases. Selective treatment protocols use outcomes of diagnostic tests to exclude CM cases from antimicrobial treatment when they are unlikely to benefit. To tailor interventions to increase uptake of selective treatment strategies, a comprehension of current on-farm treatment practices and factors affecting treatment decisions is vital. Two questionnaires were conducted among 142 farms across 5 provinces participating in the Canadian Dairy Network for Antimicrobial Stewardship and Resistance in this cross-sectional study. Self-reported adoption of selective CM treatments by dairy farmers was 64%, with median of 82% of cows treated in those herds using selective treatment. Using logistic regression models, the odds to implement a selective CM treatment protocol increased with a decreasing average cow somatic cell count. No other associations were identified between use of a selective CM treatment protocol and farm characteristics (herd size, CM incidence, province, milking system, and housing system). Three subsets of farmers making cow-level CM treatment decisions were identified using a cluster analysis approach: those who based decisions almost exclusively on severity of clinical signs, those who used various udder health indicators, and farmers who also incorporated more general cow information such as production, age, and genetics. When somatic cell count was considered, the median threshold used for treating was >300,000 cells/mL at the last Dairy Herd Improvement test. Various thresholds were present among those considering CM case history. Veterinary laboratories were most frequently used for bacteriological testing. Test results were used to start, change, and stop treatments. Regardless of protocol, reasons for antimicrobial treatment withheld included cow being on a cull list, having a chronic intramammary infection, or being at end of lactation (i.e., close to dry off). If clinical signs persisted after treatment, farmers indicated that they would ask veterinarians for advice, stop treatment, or continue with the same or different antibiotics. Results of this study can be used to design interventions targeting judicious mastitis-related antimicrobial use, and aid discussions between veterinarians and dairy producers regarding CM-related antimicrobial use.

Frequency of isolation and phenotypic antimicrobial resistance of fecal Salmonella enterica recovered from dairy cattle in Canada.

Salmonellosis is one of the leading causes of gastrointestinal infections in humans. In Canada, it is estimated that approximately 87,500 cases of salmonellosis occur every year in humans, resulting in 17 deaths. In the United States, it is estimated that 26,500 hospitalizations and 420 deaths occur every year. In dairy cattle, infections caused by nontyphoidal Salmonella enterica can cause mild to severe disease, including enteritis, pneumonia, and septicemia. Our study objectives were to determine the proportion of fecal samples positive for Salmonella in dairy cattle in Canada and determine the resistance pattern of these isolates. We used data collected through the Canadian Dairy Network for Antimicrobial Stewardship and Resistance (CaDNetASR). Pooled fecal samples from preweaning calves, postweaning heifers, lactating cows, and manure storage were cultured for Salmonella, and the isolates were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined using the minimum inhibitory concentration test, and resistance interpretation was made according to the Clinical and Laboratory Standards Institute. A 2-level, multivariable logistic regression model was built to determine the probability of recovering Salmonella from a sample, accounting for province, year, and sample source. The proportion of farms with at least one positive sample were 12% (17/140), 19% (28/144), and 17% (24/144) for the sampling years 2019, 2020, and 2021, respectively. Out of the 113 Salmonella isolates, 23 different serovars were identified. The occurrence of Salmonella appeared to be clustered by farms and provinces. The most common serovars identified were Infantis (14%) and Typhimurium (14%). Overall, 21% (24/113) of the Salmonella isolates were resistant to at least one antimicrobial. Resistance to tetracycline was commonly observed (17%); however, very limited resistance to category I antimicrobials (categorization according to Health Canada that includes third-generation cephalosporins, fluoroquinolones, polymyxins, and carbapenems) was observed, with one isolate resistant to amoxicillin and clavulanic acid. The proportion of Salmonella isolates resistant to 2 and 3 antimicrobial classes was 3.5% and 8.8%, respectively. Our study provided valuable information on the proportion of fecal samples positive for Salmonella, the serovars identified, and the associated resistance patterns across CaDNetASR herds, at regional and national levels.

Do therapeutic exercises impact supraspinatus tendon thickness? Secondary analyses of the combined dataset from two randomised controlled trials in patients with rotator cuff-related shoulder pain.

BACKGROUND: The mechanistic response of rotator cuff tendons to exercises within the context of rotator cuff-related shoulder pain (RCRSP) remains a significant gap in current research. A greater understanding of this response can shed light on why individuals exhibit varying responses to exercise interventions. It can also provide information on the influence of certain types of exercise on tendons. The primary aim of this article is to explore if changes in supraspinatus tendon thickness (SSTT) ratio differ between exercise interventions (high load vs. low load). The secondary aims are to explore if changes in SSTT ratio differ between ultrasonographic tendinopathy subgroups (reactive vs. degenerative) and if there are associations between tendinopathy subgroups, changes in tendon thickness ratio, and clinical outcomes (disability). METHODS: This study comprises secondary analyses of the combined dataset from two randomized controlled trials that compared high and low-load exercises in patients with RCRSP. In those trials, different exercise interventions were compared: 1) progressive high-load strengthening exercises, and 2) low-load strengthening with or without motor control exercises. In one trial, there was also a third group that was not allocated to exercises (education only). Ultrasound-assessed SSTT ratio, derived from comparing symptomatic and asymptomatic sides, served as the primary measure in categorizing participants into tendinopathy subgroups (reactive, normal and degenerative) at baseline. RESULTS: Data from 159 participants were analyzed. Two-way repeated measures ANOVAs revealed significant Group (p<0.001) and Group X Time interaction (p<0.001) effects for the SSTT ratio in different tendinopathy subgroups, but no Time effect (p=0.63). Following the interventions, SSTT ratio increased in the "Degenerative" subgroup (0.14 [95% CI: 0.09 to 0.19]), decreased in the "Reactive" subgroup (-0.11 [95% CI: -0.16 to -0.06]), and remained unchanged in the "Normal" subgroup (-0.01 [95% CI: -0.04 to 0.02]). There was no Time (p=0.21), Group (p=0.61), or Group X Time interaction (p=0.66) effect for the SSTT ratio based on intervention allocation. Results of the linear regression did not highlight any significant association between the tendinopathy subgroup (p=0.25) or change in SSTT ratio (p=0.40) and change in disability score. CONCLUSION: Findings from this study suggest that, over time, SSTT in individuals with RCRSP tends to normalize, compared to the contralateral side, regardless of the exercise intervention. Different subgroups of symptomatic tendons behave differently, emphasizing the need to potentially consider tendinopathy subtypes in RCRSP research. Future adequately powered studies should investigate how those different tendinopathy subgroups may predict long-term clinical outcomes.

Assessing the Impact of COVID-19 on Amateur Runners' Performance: An Analysis through Monitoring Devices.

This retrospective study aimed to analyze the return to running of non-professional runners after experiencing asymptomatic or mild COVID-19. Participants aged 18-55 years who maintained a training load of ≥10 km/week for at least three months prior to diagnosis and utilized Garmin/Polar apps were included. From these devices, parameters such as pace, distance, total running time, cadence, and heart rate were collected at three intervals: pre-COVID, immediately post-COVID, and three months after diagnosis. The Wilcoxon signed rank test was used for analysis (significance was set at ≤0.05). Twenty-one participants (57.1% male; mean age 35.0 ± 9.8 years) were included. The results revealed a significant decrease in running duration and distance two weeks after diagnosis, without significant changes in other parameters. Three months after infection, no differences were observed compared to pre-infection data, indicating a return to the pre-disease training load. These findings underscore the transient impact of COVID-19 on training performance among non-professional runners with mild or asymptomatic symptoms, highlighting the importance of tailored strategies for resuming running after infection.

Relationship between pain and proprioception among individuals with rotator cuff-related shoulder pain.

BACKGROUND: Individuals with rotator cuff-related shoulder pain (RCRSP) have altered proprioception. The relationship between shoulder pain and proprioception is not well understood. PURPOSE: This study aimed to investigate the relationship between shoulder pain and proprioception. STUDY DESIGN: This was a cross-sectional comparative study. METHODS: Twenty-two participants with RCRSP (mean age 27.6 ± 4.8 years) and 22 matched pain-free participants (23.4 ± 2.5 years) performed two upper limb active joint position sense tests: (1) the Upper Limb Proprioception Reaching Test (PRO-Reach; reaching toward seven targets) in centimeters and (2) Biodex System at 90% of maximum internal rotation in degrees. Participants performed three memorization and three reproduction trials blindfolded. The proprioception error (PE) is the difference between the memorized and estimation trials. Pain levels were captured pre- and post-evaluation (11-point Likert Numerical Pain Rating Scale). Relationships between PE and pain were investigated using independent t-tests and Spearman rank correlations. RESULTS: Overall, 22.7% RCRSP participants indicated an increase in pain following the PRO-Reach (X̅ increase of 1.4 ± 1.5 points), while 59% did so with the Biodex (X̅ increase of 2.3 ± 1.8 points), reflecting a clinically important increase in pain. Weak-to-moderate correlations between pain and PEs were found with the Biodex (r = 0.39-0.53) and weak correlations with the PRO-Reach (r = -0.26 to 0.38). Concerning PEs, no significant differences were found between groups with the Biodex (p = 0.32, effect size d = -0.31 [-0.90 to 0.29]). The RCRSP participants demonstrated lower PEs with the PRO-Reach in elevation compared to pain-free participants (global X̅ = 4.6 ± 1.2 cm vs 5.5 ± 1.5 cm; superior 3.8 ± 2.1 cm vs 5.7 ± 2.9 cm; superior-lateral nondominant targets 4.3 ± 2.2 cm vs 6.1 ± 2.8 cm; p = 0.02-0.05, effect size d = 0.72-0.74 [0.12-1.3]). CONCLUSIONS: Individuals with RCRSP demonstrated better upper limb proprioception in elevation, suggesting a change to interoception (sensory reweighting) in the presence of pain.

Connectivity patterns of the core resting-state networks associated with apathy in late-life depression.

BACKGROUND: Apathy is associated with reduced antidepressant response and dementia in late-life depression (LLD). However, the functional cerebral basis of apathy is understudied in LLD. We investigated the functional connectivity of 5 resting-state networks (RSN) hypothesized to underlie apathy in LLD. METHODS: Resting-state functional MRI data were collected from individuals with LLD who did not have dementia as well as healthy older adults between October 2019 and April 2022. Apathy was evaluated using the diagnostic criteria for apathy (DCA), the Apathy Evaluation Scale (AES) and the Apathy Motivation Index (AMI). Subnetworks whose connectivity was significantly associated with each apathy measure were identified via the threshold-free network-based statistics. Regions that were consistently associated with apathy across the measures were reported as robust findings. RESULTS: Our sample included 39 individuals with LLD who did not have dementia and 26 healthy older adults. Compared with healthy controls, individuals with LLD had an altered intra-RSN and inter-RNS connectivity in the default mode, the cingulo-opercular and the frontoparietal networks. All 3 apathy measurements showed associations with modified intra-RSN connectivity in these networks, except for the DCA in the cingulo-opercular network. The AMI scores showed stronger associations with the cingulo-opercular and frontoparietal networks, whereas the AES had stronger associations with the default mode network and the goal-oriented behaviour network. LIMITATIONS: The study was limited by the small number of participants without apathy according to the DCA, which may have reduced the statistical power of between-group comparisons. Additionally, the reliance on specific apathy measures may have influenced the observed overlap in brain regions. CONCLUSION: Our findings indicate that apathy in LLD is consistently associated with changes in both intra-RSN and inter-RSN connectivity of brain regions implicated in goal-oriented behaviours. These results corroborate previous findings of altered functional RSN connectivity in severe LLD.

"I wanted to know what was hurting so much": a qualitative study exploring patients' expectations and experiences with primary care management.

BACKGROUND: The management of shoulder pain is challenging for primary care clinicians considering that 40% of affected individuals remain symptomatic one year after initial consultation. Developing tailored knowledge mobilization interventions founded on evidence-based recommendations while also considering patients' expectations could improve primary care for shoulder pain. The aim of this qualitative study is to explore patients' expectations and experiences of their primary care consultation for shoulder pain. METHODS: In this qualitative study, participants with shoulder pain and having consulted a primary care clinician in the past year were interviewed. All the semi-structured interviews were transcribed verbatim, and inductive thematic analysis was performed to identify themes related to the participants' expectations and experiences of primary care consultations for shoulder pain. RESULTS: Thirteen participants with shoulder pain were interviewed (8 women, 5 men; mean age 50 ± 12 years). Eleven of them initially consulted a family physician or an emergency physician, and two participants initially consulted a physiotherapist. Four overarching themes related to patients' expectations and experiences were identified from our thematic analysis: 1) I can't sleep because of my shoulder; 2) I need to know what is happening with my shoulder; 3) But… we need to really see what is going on to help me!; and 4) Please take some time with me so I can understand what to do!. Several participants waited until they experienced a high level of shoulder pain before making an appointment since they were not confident about what their family physician could do to manage their condition. Although some participants felt that their physician took the time to listen to their concerns, many were dissatisfied with the limited assessment and education provided by the clinician. CONCLUSIONS: Implementing evidence-based recommendations while considering patients' expectations is important as it may improve patients' satisfaction with healthcare. Several participants reported that their expectations were not met, especially when it came to the explanations provided. One unexpected finding that emerged from this study was the waiting period between the onset of shoulder pain and when patients decided to consult their primary care clinician.

Selective dry-cow therapy can be implemented successfully in cows of all milk production levels.

Antibiotic stewardship on dairy farms can be heightened through the implementation of selective dry-cow therapy (SDCT). However, some producers are concerned that this practice may be related to poor udder health outcomes in cows with high milk production at the time of dry-off. The objective of this study was to evaluate if the effect of culture-guided SDCT (Cult-SDCT) and algorithm-guided SDCT (Alg-SDCT) on dry-period intramammary infection (IMI) dynamics and postcalving udder health and performance [when compared with blanket dry-cow therapy (BDCT)] varied according to milk production level before dry-off. Data were compiled from clinical trials conducted in the United States and Canada that compared Cult-SDCT and Alg-SDCT to a positive control, i.e., BDCT. In those trials, cows were enrolled 1-2 d before dry-off, randomized to their dry-cow therapy strategy and followed until 120 d in milk of the subsequent lactation. The number of cows and quarters in the final data set were 1,485 and 5,097, respectively. Measured outcomes included quarter-level antibiotic use at dry-off, quarter-level IMI prevalence after calving, quarter-level dry-period IMI cure risk, quarter-level dry-period new IMI risk, cow-level clinical mastitis and removal from the herd during 1-120 d in milk, and somatic cell count and milk yield during 1-120 DIM. The primary objective of analysis was to investigate if the effect of Cult-SDCT and Alg-SDCT on these outcomes, when compared with BDCT, varied according to milk production level before dry-off. To do this, each cow was classified as having low, mid or high production, based on her milk yield tertile group at the most recent herd test before enrollment (low: <23.7 kg/d, mid: 23.7 to 30.4 kg/d, and high >30.4 kg/d). Multivariable generalized estimating equations were used to estimate risk differences and differences in means, and Cox regression was used to estimate hazard ratios. For Cult-SDCT, the proportion of quarters treated with dry-cow antibiotics within each milk production level were 40.7% (low), 41.7% (mid) and 47.2% (high). For Alg-SDCT, the proportions were 60.6% (low), 38.7% (mid), and 35.1% (high). Measures of udder health were not markedly different when comparing Cult-SDCT to BDCT and Alg-SDCT to BDCT. This was consistently observed in low, mid and high producing cows. In conclusion, the findings from this study indicate that Cult-SDCT and Alg-SDCT can be successfully implemented in cows of all milk production levels.

Does the addition of motor control or strengthening exercises to education result in better outcomes for rotator cuff-related shoulder pain? A multiarm randomised controlled trial.

OBJECTIVE: To compare the short-term, mid-term and long-term effects between three interventions (education only, education and strengthening exercises, education and motor control exercises) for rotator cuff-related shoulder pain (RCRSP) on symptoms and function. METHODS: 123 adults presenting with RCRSP took part in a 12-week intervention. They were randomly assigned to 1 of 3 intervention groups. Symptoms and function were evaluated at baseline and at 3 weeks, 6 weeks, 12 weeks and 24 weeks using the Disability of Arm, Shoulder and Hand Questionnaire (QuickDASH) (primary outcome) and Western Ontario Rotator Cuff Index (WORC). Linear mixed modelling was used to compare the effects of the three programmes on the outcomes. RESULTS: After 24 weeks, between-group differences were -2.1 (-7.7 to 3.5) (motor control vs education), 1.2 (-4.9 to 7.4) (strengthening vs education) and -3.3 (-9.5 to 2.8) (motor control vs strengthening) for the QuickDASH and 9.3 (1.5 to 17.1) (motor control vs education), 1.3 (-7.6 to 10.2) (strengthening vs education) and 8.0 (-0.5 to 16.5) (motor control vs strengthening) for the WORC. There was a significant group-by-time interaction (p=0.04) with QuickDASH, but follow-up analyses did not reveal any clinically meaningful between-group differences. There was no significant group-by-time interaction (p=0.39) for the WORC. Between-group differences never exceeded the minimal clinically important difference of QuickDASH or WORC. CONCLUSION: In people with RCRSP, the addition of motor control or strengthening exercises to education did not lead to larger improvements in symptoms and function compared with education alone. Further research should investigate the value of providing stepped care by identifying individuals who may only need education and those who would benefit from the addition of motor control or strengthening exercises. TRIAL REGISTRATION NUMBER: NCT03892603.

Gene co-expression in response to Staphylococcus aureus infection reveals networks of genes with specific functions during bovine subclinical mastitis.

Staphylococcus aureus is one of the most prevalent contagious bacterial pathogen of bovine mastitis. The subclinical mastitis it causes has long-term economic implications and it is difficult to control. To further understanding of the genetic basis of mammary gland defense against S. aureus infection, the transcriptomes of milk somatic cells from 15 cows with persistent natural S. aureus infection (S. aureus-positive, SAP) and 10 healthy control cows (HC) were studied by deep RNA-sequencing technology. Comparing the transcriptomes of SAP to HC group revealed 4,077 differentially expressed genes (DEG; 1,616 up- and 2,461 downregulated). Functional annotation indicated enrichment of DEG in 94 Gene Ontology (GO) and 47 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Terms related to the immune response and disease processes were mostly enriched for by upregulated DEG, whereas biological process terms related to cell adhesion, cell movement and localization, and tissue development were mostly enriched for by downregulated DEG. Weighted gene co-expression network analysis grouped DEG into 7 modules, the most important module (colored turquoise by software and here referred to as Turquoise module) was positively significantly correlated with S. aureus subclinical mastitis. The 1,546 genes in the Turquoise module were significantly enriched in 48 GO terms and 72 KEGG pathways, with 80% of them being disease- and immune-related terms [e.g., immune system process (GO:0002376), cytokine-cytokine receptor interaction (bta04060) and S. aureus infection (bta05150)]. Some DEG such as IFNG, IL18, IL1B, NFKB1, CXCL8, and IL12B were enriched in immune and disease pathways suggesting their possible involvement in the regulation of the host response to S. aureus infection. Four modules (Yellow, Brown, Blue, and Red) were negatively correlated (significantly) with S. aureus subclinical mastitis, and were enriched in functional annotations involved in the regulation of cell migration, cell communication, metabolic process, and blood circulatory system development, respectively. Application of sparse partial least squares discriminant analysis to genes of the Turquoise module identified 5 genes (NR2F6, PDLIM5, RAB11FIP5, ACOT4, and TMEM53) capable of explaining the majority of the differences in the expression patterns between SAP and HC cows. In conclusion, this study has furthered understanding of the genetic changes in the mammary gland and the molecular mechanisms underlying S. aureus mastitis, as well as revealed a list of candidate discriminant genes with potential regulatory roles in response to S. aureus infection.

Reducing Noise, Artifacts and Interference in Single-Channel EMG Signals: A Review.

Electromyography (EMG) is gaining importance in many research and clinical applications, including muscle fatigue detection, control of robotic mechanisms and prostheses, clinical diagnosis of neuromuscular diseases and quantification of force. However, EMG signals can be contaminated by various types of noise, interference and artifacts, leading to potential data misinterpretation. Even assuming best practices, the acquired signal may still contain contaminants. The aim of this paper is to review methods employed to reduce the contamination of single channel EMG signals. Specifically, we focus on methods which enable a full reconstruction of the EMG signal without loss of information. This includes subtraction methods used in the time domain, denoising methods performed after the signal decomposition and hybrid approaches that combine multiple methods. Finally, this paper provides a discussion on the suitability of the individual methods based on the type of contaminant(s) present in the signal and the specific requirements of the application.

Electromyographic Activity of the Pelvic Floor Muscles and Internal Oblique Muscles in Women during Running with Traditional and Minimalist Shoes: A Cross-Over Clinical Trial.

The study aimed to investigate the effects of footwear on the electromyographic (EMG) activity of pelvic floor muscles (PFMs) and internal oblique (IO) muscles during running at different speeds. The study also aimed to explore the correlation between EMG activity of PFMs and IO muscles and participants' morphological characteristics. Ten nulliparous female runners were included in the study. The participants ran for 90 s at speeds of 9, 11, and 13 km/h wearing both traditional and minimalist shoes. EMG outcomes were presented as a percentage of maximum voluntary contraction (%MVC). Comparative analysis was conducted using the Wilcoxon rank test. Correlational analysis was performed using the Rho-Spearman correlation coefficient. The %MVC for the IO muscles was significantly lower when using minimalist shoes compared to traditional shoes (p = 0.04). No statistically significant differences were found for the PFMs (p > 0.05). The study also observed large correlations between age and %MVC of the PFMs and IO muscles (rho = -0.64; p = 0.04). Minimalist shoes decreased the activity of IO muscles in female runners. However, no significant differences in EMG activity of PFMs were found when comparing traditional and minimalist footwear. The long-term effects of minimalist footwear on EMG activity of PFMs and IO muscles, as well as their relationship to morphological characteristics, require further investigation.

Genome-Wide DNA Methylation and Transcriptome Integration Associates DNA Methylation Changes with Bovine Subclinical Mastitis Caused by Staphylococcus chromogenes.

Staphylococcus chromogenes (SC) is a common coagulase-negative staphylococcus described as an emerging mastitis pathogen and commonly found in dairy farms. This study investigated the potential involvement of DNA methylation in subclinical mastitis caused by SC. The whole-genome DNA methylation patterns and transcriptome profiles of milk somatic cells from four cows with naturally occurring SC subclinical mastitis (SCM) and four healthy cows were characterized by next-generation sequencing, bioinformatics, and integration analyses. Comparisons revealed abundant DNA methylation changes related to SCM, including differentially methylated cytosine sites (DMCs, n = 2,163,976), regions (DMRs, n = 58,965), and methylation haplotype blocks (dMHBs, n = 53,098). Integration of methylome and transcriptome data indicated a negative global association between DNA methylation at regulatory regions (promoters, first exons, and first introns) and gene expression. A total of 1486 genes with significant changes in the methylation levels of their regulatory regions and corresponding gene expression showed significant enrichment in biological processes and pathways related to immune functions. Sixteen dMHBs were identified as candidate discriminant signatures, and validation of two signatures in more samples further revealed the association of dMHBs with mammary gland health and production. This study demonstrated abundant DNA methylation changes with possible involvement in regulating host responses and potential as biomarkers for SCM.

French Version of the Musculoskeletal Pain Intensity and Interference Questionnaire for Professional Orchestra Musicians (MPIIQM-F): Cross-Cultural Adaptation and Preliminary Validation.

BACKGROUND: The Musculoskeletal Pain Intensity and Interference Questionnaire for Professional Orchestra Musicians (MPIIQM) is a prominent patient-reported outcome measure (PROM) in the musicians' health literature. It has been published in at least four languages, but not in French. AIMS: To cross-culturally adapt the MPIIQM into French and establish the preliminary psychometric properties (validity, reliability, and responsiveness) of the MPIIQM-F. METHODS: Standardized cross-cultural adaptation methods included forward translations, an expert committee, and verbal field tests in the target population. Psychometric properties were assessed in a population of French-speaking professional orchestra musicians who participated in three evaluation sessions. Evaluated properties include content, face, structural and construct validity, reliability (internal consistency, test-retest reliability, minimal detectable change [MDC], measurement error), and responsiveness (effect size and standardized response means [SRM]). RESULTS: Sixty-one French-speaking orchestra musicians participated in the psychometric validation. Exploratory factor analysis revealed a two-factor solution equivalent to previous versions, confirming the Pain Intensity and Interference subscales. Spearman correlations for construct validity were as hypothesized for four of six hypotheses (minor deviances for the other two hypotheses) using the Brief Pain Inventory, Disability of the Arm, Shoulder and Hand Performing Arts Module, and PROMIS Global Health Scale as comparators. Reliability results demonstrated high internal consistency (Cronbach's a=0.84-0.89), excellent test-retest reliability (intraclass correlation coefficient = 0.91-0.97), and small measurement error with MDC for the overall scale <10%. Responsiveness resulted in moderate to large effect sizes and SRM (0.54-0.87). CONCLUSIONS: Preliminary validation of the MPIIQM-F suggests good validity, reliability, and responsiveness, indicating its suitability for use in French-speaking orchestra musicians.

Patient-reported outcome measures of musculoskeletal symptoms and psychosocial factors in musicians: a systematic review of psychometric properties.

PURPOSE: To systematically review patient-reported outcome measures (PROMs) of musicians' musculoskeletal symptoms (MSS) and psychosocial factors and their psychometric properties. METHODS: Six databases were searched. Studies evaluating at least one psychometric property of a PROM developed for or adapted to adult musicians and measuring MSS or occupational psychosocial factors were included. Study quality was evaluated using mainly the COSMIN checklist. RESULTS: Twenty-eight studies were included, yielding 27 PROMs. Most COSMIN scores are Doubtful or Inadequate. Validity and internal consistency are the most evaluated psychometric properties. Test-retest reliability was evaluated in five studies (all inadequate sample sizes), measurement error in one, and responsiveness in none. The English, German and Polish Musculoskeletal Pain Intensity and Interference Questionnaire for professional orchestra Musicians (MPIIQM), the 40-item English and Peruvian Spanish Kenny Music Performance Anxiety Inventory (KMPAI) and the Psychosocial Risks Questionnaire for Musicians (PRQM, Polish) are the most robust scales for their constructs. Their internal consistency is sufficient (Cronbach's α ≥ 0.70). Test-retest reliability and construct validity are only sufficient for the German MPIIQM (intraclass correlation coefficients ≥ 0.70). However, results are based on one study per PROM; all require further validation before validity, reliability and responsiveness can be confirmed. CONCLUSION: Due to generally poor methodological quality and one study per PROM on average, none can be confirmed valid, reliable and responsive. Yet, preliminary validation recommends prudent use of some PROMs pending further validation. Robust PROM studies are needed to fill the important literature gap regarding musician-specific, validated PROMs.

Does musculoskeletal pain interfere with motor learning in a gait adaptation task? A proof-of-concept study.

BACKGROUND: Experimental pain during gait has been shown to interfere with learning a new locomotor task. However, very few studies have investigated the impact of clinical pain on motor learning due to the challenges associated with clinical populations. OBJECTIVE: The first objective of this proof-of-concept study was to determine the feasibility to obtain two groups of participants with chronic ankle pathology with or without residual pain while walking. The second objective was to evaluate the impact of clinical musculoskeletal pain on motor learning during gait. METHODS: Participants with chronic isolated ankle pathology were recruited and their personal and clinical characteristics were collected (functional performance, dorsiflexion maximal strength, range of motion). To assess motor acquisition (Day 1) and retention (Day 2), participants performed an adaptation task on two consecutive days that consisted of walking while experiencing a perturbing force applied to the ankle. The level of pain during the task was measured, and participants who reported pain were attributed to the Pain group and participants without pain to the No Pain group. Learning performance was assessed by measuring ankle kinematics (Mean plantarflexion absolute error) and learning strategy was assessed by measuring the Relative timing of error and the tibialis anterior (TA) electromyographic activity. RESULTS: Twenty-five participants took part in the experiment. Eight (32%) were excluded because they could not be included in either the Pain or No Pain group due to the intermittent pain, leaving eight participants in the Pain group and nine in the No Pain group. Both groups were similar in terms of baseline characteristics. Musculoskeletal pain had no influence on learning performance, but the learning strategy were different between the two groups. The No Pain group showed a TA activity reduction before perturbation between the days, while the Pain group did not. CONCLUSION: Some barriers were identified in studying musculoskeletal pain including the high rates of participants' exclusion, leading to a small sample size. However, we showed that it is feasible to investigate clinical pain and motor learning. From the results of this study, musculoskeletal pain has no influence on motor learning performance but influences the learning strategy.